Commentary

There is a need to connect mental and physical symptoms in the diagnosis and treatment of psychiatric disorders. Obviously, we are not yet equipped to clearly recognize which neurotransmitters cause which symptoms. The science of defining the underlying mechanisms is lagging behind the clinical needs. However, in this article, we present a few hypothetical clinical cases to emphasize a possible way of analyzing symptoms in order to identify underlying pathology and guide more effective treatment. Our descriptions do not reflect the entire set of symptoms caused by these neurotransmitters; we created them based on what is presently known (or suspected). Additional research is needed to confirm or disprove the hypotheses we present.

In Part 1 (Current Psychiatry, May 2022), we argued that for depression, anxiety, psychosis, and bipolar disorder, development and approval of medications is currently based on descriptive diagnoses, with disregard to the various underlying causes of those conditions. Similar to how the many types of pneumonia are treated differently based on the specific infective agent, we suggested there are various types of depression or chronic pain based on the underlying neuro­transmitter pathology. Such an approach may be extrapolated to anxiety, psychosis, or bipolar disorder, although those conditions are outside the scope of this article. In Part 1, we described serotonin- and dopamine-associated mental and physical symptoms that suggest distinctly different types of depression or chronic pain, and we suggested specific ways of treating those described conditions. Part 2 reflects on pathology that is possibly connected to endorphin and norepinephrine dysfunction. Table 1 outlines medical and psychiatric symptoms that likely reflect endorphin excess^1-16 and deficiency,^1,16-24 and Table 2 lists symptoms that likely reflect norepinephrine excess^16,25-30and deficiency.^16,26,31-39 It is worth noting that both the quantity of neurotransmitters as well as the quality of the transmission (as in receptors, cellular pumps, and distribution mechanisms) are important.

Endorphin excess (Table 1^1-16)

Ms. R is a frustrated chronic pain patient who bitterly complains that despite having seen more than 20 physicians, she does not have an answer to what causes her “all over” pain and headache.^4,5,11 She does not believe that all her laboratory test are normal, and insists that “something is missing.” She aches all over but says she can actually tolerate more pain than others and experiences only a little discomfort during an electromyogram or dental interventions. Though Ms. R is not very susceptible to acute pain,^4,5,9,16 pain all over without an identifiable cause is part of her life.^4,5,11 She says that listening to music and social interactions help decrease her pain.^4,5,10 Ms. R states that opioid medications do not help her pain, though she has a history of opioid overuse and opioid-induced hyperalgesia.^6,11,16

Ms. R tends to overdo pleasureful activities to achieve satisfaction.² She says exercise is particularly satisfying, to the point that she experiences euphoria and a loss of time.⁹ She is angry that her neurologist suggested she see a psychiatrist. Her depression bothers her more than her anxiety.^2,5,7

Ms. R clearly has a self-image problem, alternating between high and low self-esteem. She has a low appetite^1,12,14-16 and sleeps excessively.^2,4,7,9,10 Her mother privately tells you that Ms. R has a history of childhood sexual abuse and lagged in life due to a lack of motivation. Ms. R used to self-mutilate “to feel normal.”¹² Her primary care physician chronically addresses Ms. R’s poorly explained cholestasis and pruritus⁸ as well as dysregulation of blood pressure and heart rate, both of which tend to be low.^12,13,16

Impression. Ms. R shows multiple symptoms associated with endorphin excess. A trial of an opioid antagonist may be reasonable. Dopamine blockade helps with endorphin suppression and also may be used for this patient. Using a low starting dose and a slow titration of such medications would be beneficial due to frequent intolerance issues, especially nausea. Gamma aminobutyric acid-ergic medications modulate the opioid system and may be considered. A serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine may help patients such as Ms. R to control mood and pain through norepinephrine’s influence on endorphins.

Endorphin deficiency (Table 1^1,16-24)

Mr. J complains of low back pain, diffuse body pain, depression, and moodiness.^19,20,24 He is sluggish and plagued by psychomotor retardation.²⁴ All his life, a heightened perception of pain has caused him problems,^19,20 but has not stopped him from engaging in self-mutilation.²⁴ His “unexplained” pain and general body aches seem to be associated with objectively verifiable pain generators (such as bruises and surgical procedures) but this pain is in excess of what would generally be expected. Mr. J describes his low back pain as mild degenerative disc disease and is eager to explain that his wife’s spine is more diseased, yet she has no back pain.

Continue to: Mr. J responds to treatment...

Mr. J responds to treatment with opioids^16,20 but comments that his mood, and not necessarily his pain, improves when he takes these medications.²⁰ He tends to overuse his pain medications, and had run into trouble with his previous pain management physician. Nitrous oxide is remarkably effective during dental procedures.¹⁹ Acupuncture helps to control his pain and mood.¹⁷ Exercise is also rewarding.¹⁸

Mr. J has difficulty achieving orgasm, a decreased sexual drive, and emotional sensitivity.²⁴ He is impulsive.^19,20,24 His baseline mood is low-grade; anxiety bothers him more than depression.^23,24 Mr. J is thin, has a poor appetite,^1,16 and sleeps poorly.²⁴ His primary care physician struggles to help Mr. J to control dysregulation of his heart rate, blood pressure,²¹ and urinary retention,^16,22 as well as episodes of hypoglycemia.^1,16 He reluctantly admits to abusing alcohol, but explains that it helps with his mood and pain better than his prescribed medications.^18,23

Impression. Mr. J exhibits multiple symptoms associated with endorphin deficiency. Short-term use of opioids is warranted, but he should avoid long-term opioid use, and he and his physician should work together to establish strict control of their intake. Buprenorphine would be the opioid of choice for such a patient. Psychiatric treatment, including for alcohol use disorder, should be a mandatory part of his treatment regimen. Behavioral therapy with a focus on finding healthy ways to achieve gratification would be effective. Alternative treatments such as acupuncture may be of value.

Norepinephrine excess (Table 2^16,25-30)

Mr. G comes to the office irritable and angry^28,30 because no one can help him with his intractable headaches.^16,25 He is pale, his breathing is noisy, and he licks his dry lips while sweating.^16,25 His wife is shy and seems to be afraid of her husband, who is easily irritated and edgy.^28,30 His heart rate and blood pressure are high; he has a history of palpitations and chest pain.^16,25 When unhappy, he gets pale, sweaty, tremulous, and nauseous.^16,25 He masks his anxiety with aggression and has impaired concentration, restless sleep, muscle tension, muscle cramps, and abdominal cramps.^27,28,30 Mr. G suffers from frequent nausea.^16,25 His neck is stiff and pupils are dilated; he clenches his teeth and uses a mouth guard for correction of temporomandibular joint disorder.^16,25 His sleep apnea is poorly controlled because he feels entrapped when he uses a continuous positive airway pressure machine.²⁹ He blames his wife for his premature ejaculation and says that she gives him goosebumps.²⁵ His hypervigilance and hyperarousal are torturous to his wife.^27,30 Despite his overall angry state, Mr. G is also constantly fearful.^28,30 He is almost never hungry, does not like crowds, hates your waiting area, and is vocal about his dislike of doctors being late “all the time.”^26,28,30

Comment. Norepinephrine and dopamine functions are connected through common neuronal and glial uptake mechanisms. This is a foundation of norepinephrine excess symptoms crossing over with symptoms of dopamine deficiency.

Continue to: Impression

Impression. Mr. G shows multiple symptoms associated with norepinephrine excess. It is important to avoid caffeine intake in patients with clinical signs of excessive norepinephrine. Beta-blockers and alpha-2 agonists work well in patients such as Mr. G. Benzodiazepines indirectly decrease norepinephrine activity, but need to be used carefully due to the potential for misuse and addiction. In particular, short-acting benzodiazepines such as alprazolam and lorazepam must be avoided due to the induction of CNS instability with rapidly changing medication blood levels. Chlordiazepoxide may be a good choice for a patient such as Mr. G because it has the fewest adverse effects and the lowest abuse potential compared with other benzodiazepines. Avoid SNRIs in such a patient. Using mood-stabilizing antipsychotic medications may be especially warranted in treating Mr. G’s depression and pain.

Norepinephrine deficiency (Table 2^16,26,31-39)

Two years ago, Ms. A was diagnosed with chronic fatigue³¹ and fibromyalgia. She also had been diagnosed with depression and attention-deficit/hyperactivity disorder (ADHD). She presents with concerns of “brain fog,” no energy, low sex drive, and daytime sleepiness.^33,35 Allodynia is widespread.^16,36,37 Ms. A suffers from bulimia; she eats once a day but is still overweight.²⁶ She has orthostatic hypotension in addition to baseline low blood pressure and bradycardia.^16,38,39 Her pupils are almost pinpoint, even when she does not take opioid medications.¹⁶ Her skin is dry and her hair is brittle; deep tendon reflexes are weakened, and her muscle tone is decreased.¹⁶ Ms. A’s constant low mood drives her to drink excessive amounts of caffeine, which she says “helps with daytime sleepiness but does not last”^32,33 and causes heart rhythm problems³⁸ and dyspepsia.¹⁶ She sees that her headaches and body pain are associated with her caffeine intake, but refuses to stop taking caffeine. Her low interest in life and general passivity have caused her many problems, though the problems themselves do not make her feel much.^31,32,39 She is rather indifferent to pleasurable activities, including sex.³¹ Her response to exciting experiences is blunted,³² but she is still frequently tearful.³⁴ Ms. A’s mood does not improve with selective serotonin reuptake inhibitors; she has tried many. She says that she would not come to see a physician, but “my mom told me to.” She resents that her family thinks she is lazy^31,32,39 and blames her ADHD for underperformance in life.^32,33 Ms. A has a family history of chronic pain and Alzheimer disease, and the longer she experiences pain, the worse her memory.³⁵

Comment. As mentioned earlier, because of the norepinephrine/dopamine relationship, symptoms of excess dopamine overlap with symptoms of norepinephrine deficiency.

Impression. Ms. A shows multiple symptoms associated with norepinephrine deficiency. The use of noradrenergic antidepressants (such as SNRIs and mirtazapine)²⁶ and stimulants may be warranted. Physical exercise, participating in social activities, massage, acupuncture, and family support may help with Ms. A’s pain as well as her depression, as might vasopressors.

In Part 3, we will address gamma aminobutyric acid and glutamate.

Bottom Line

Both high and low levels of endorphins and norepinephrine may be associated with certain psychiatric and medical symptoms and disorders. An astute clinician may judge which neurotransmitter is dysfunctional based on the patient’s presentation, and tailor treatment accordingly.

Related Resources

• Arbuck DM, Salmerón JM, Mueller R. Neurotransmitter-based diagnosis and treatment: a hypothesis (Part 1). Current Psychiatry. 2022;21(5):30-36. doi:10.12788/cp.0242

Drug Brand Names

Alprazolam • Xanax
Chlordiazepoxide • Librium
Lorazepam • Ativan
Mirtazapine • Remeron

There is a need to connect mental and physical symptoms in the diagnosis and treatment of psychiatric disorders. Obviously, we are not yet equipped to clearly recognize which neurotransmitters cause which symptoms. The science of defining the underlying mechanisms is lagging behind the clinical needs. However, in this article, we present a few hypothetical clinical cases to emphasize a possible way of analyzing symptoms in order to identify underlying pathology and guide more effective treatment. Our descriptions do not reflect the entire set of symptoms caused by these neurotransmitters; we created them based on what is presently known (or suspected). Additional research is needed to confirm or disprove the hypotheses we present.

In Part 1 (Current Psychiatry, May 2022), we argued that for depression, anxiety, psychosis, and bipolar disorder, development and approval of medications is currently based on descriptive diagnoses, with disregard to the various underlying causes of those conditions. Similar to how the many types of pneumonia are treated differently based on the specific infective agent, we suggested there are various types of depression or chronic pain based on the underlying neuro­transmitter pathology. Such an approach may be extrapolated to anxiety, psychosis, or bipolar disorder, although those conditions are outside the scope of this article. In Part 1, we described serotonin- and dopamine-associated mental and physical symptoms that suggest distinctly different types of depression or chronic pain, and we suggested specific ways of treating those described conditions. Part 2 reflects on pathology that is possibly connected to endorphin and norepinephrine dysfunction. Table 1 outlines medical and psychiatric symptoms that likely reflect endorphin excess^1-16 and deficiency,^1,16-24 and Table 2 lists symptoms that likely reflect norepinephrine excess^16,25-30and deficiency.^16,26,31-39 It is worth noting that both the quantity of neurotransmitters as well as the quality of the transmission (as in receptors, cellular pumps, and distribution mechanisms) are important.

Endorphin excess (Table 1^1-16)

Ms. R is a frustrated chronic pain patient who bitterly complains that despite having seen more than 20 physicians, she does not have an answer to what causes her “all over” pain and headache.^4,5,11 She does not believe that all her laboratory test are normal, and insists that “something is missing.” She aches all over but says she can actually tolerate more pain than others and experiences only a little discomfort during an electromyogram or dental interventions. Though Ms. R is not very susceptible to acute pain,^4,5,9,16 pain all over without an identifiable cause is part of her life.^4,5,11 She says that listening to music and social interactions help decrease her pain.^4,5,10 Ms. R states that opioid medications do not help her pain, though she has a history of opioid overuse and opioid-induced hyperalgesia.^6,11,16

Ms. R tends to overdo pleasureful activities to achieve satisfaction.² She says exercise is particularly satisfying, to the point that she experiences euphoria and a loss of time.⁹ She is angry that her neurologist suggested she see a psychiatrist. Her depression bothers her more than her anxiety.^2,5,7

Ms. R clearly has a self-image problem, alternating between high and low self-esteem. She has a low appetite^1,12,14-16 and sleeps excessively.^2,4,7,9,10 Her mother privately tells you that Ms. R has a history of childhood sexual abuse and lagged in life due to a lack of motivation. Ms. R used to self-mutilate “to feel normal.”¹² Her primary care physician chronically addresses Ms. R’s poorly explained cholestasis and pruritus⁸ as well as dysregulation of blood pressure and heart rate, both of which tend to be low.^12,13,16

Impression. Ms. R shows multiple symptoms associated with endorphin excess. A trial of an opioid antagonist may be reasonable. Dopamine blockade helps with endorphin suppression and also may be used for this patient. Using a low starting dose and a slow titration of such medications would be beneficial due to frequent intolerance issues, especially nausea. Gamma aminobutyric acid-ergic medications modulate the opioid system and may be considered. A serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine may help patients such as Ms. R to control mood and pain through norepinephrine’s influence on endorphins.

Endorphin deficiency (Table 1^1,16-24)

Mr. J complains of low back pain, diffuse body pain, depression, and moodiness.^19,20,24 He is sluggish and plagued by psychomotor retardation.²⁴ All his life, a heightened perception of pain has caused him problems,^19,20 but has not stopped him from engaging in self-mutilation.²⁴ His “unexplained” pain and general body aches seem to be associated with objectively verifiable pain generators (such as bruises and surgical procedures) but this pain is in excess of what would generally be expected. Mr. J describes his low back pain as mild degenerative disc disease and is eager to explain that his wife’s spine is more diseased, yet she has no back pain.

Continue to: Mr. J responds to treatment...

Mr. J responds to treatment with opioids^16,20 but comments that his mood, and not necessarily his pain, improves when he takes these medications.²⁰ He tends to overuse his pain medications, and had run into trouble with his previous pain management physician. Nitrous oxide is remarkably effective during dental procedures.¹⁹ Acupuncture helps to control his pain and mood.¹⁷ Exercise is also rewarding.¹⁸

Mr. J has difficulty achieving orgasm, a decreased sexual drive, and emotional sensitivity.²⁴ He is impulsive.^19,20,24 His baseline mood is low-grade; anxiety bothers him more than depression.^23,24 Mr. J is thin, has a poor appetite,^1,16 and sleeps poorly.²⁴ His primary care physician struggles to help Mr. J to control dysregulation of his heart rate, blood pressure,²¹ and urinary retention,^16,22 as well as episodes of hypoglycemia.^1,16 He reluctantly admits to abusing alcohol, but explains that it helps with his mood and pain better than his prescribed medications.^18,23

Impression. Mr. J exhibits multiple symptoms associated with endorphin deficiency. Short-term use of opioids is warranted, but he should avoid long-term opioid use, and he and his physician should work together to establish strict control of their intake. Buprenorphine would be the opioid of choice for such a patient. Psychiatric treatment, including for alcohol use disorder, should be a mandatory part of his treatment regimen. Behavioral therapy with a focus on finding healthy ways to achieve gratification would be effective. Alternative treatments such as acupuncture may be of value.

Norepinephrine excess (Table 2^16,25-30)

Mr. G comes to the office irritable and angry^28,30 because no one can help him with his intractable headaches.^16,25 He is pale, his breathing is noisy, and he licks his dry lips while sweating.^16,25 His wife is shy and seems to be afraid of her husband, who is easily irritated and edgy.^28,30 His heart rate and blood pressure are high; he has a history of palpitations and chest pain.^16,25 When unhappy, he gets pale, sweaty, tremulous, and nauseous.^16,25 He masks his anxiety with aggression and has impaired concentration, restless sleep, muscle tension, muscle cramps, and abdominal cramps.^27,28,30 Mr. G suffers from frequent nausea.^16,25 His neck is stiff and pupils are dilated; he clenches his teeth and uses a mouth guard for correction of temporomandibular joint disorder.^16,25 His sleep apnea is poorly controlled because he feels entrapped when he uses a continuous positive airway pressure machine.²⁹ He blames his wife for his premature ejaculation and says that she gives him goosebumps.²⁵ His hypervigilance and hyperarousal are torturous to his wife.^27,30 Despite his overall angry state, Mr. G is also constantly fearful.^28,30 He is almost never hungry, does not like crowds, hates your waiting area, and is vocal about his dislike of doctors being late “all the time.”^26,28,30

Comment. Norepinephrine and dopamine functions are connected through common neuronal and glial uptake mechanisms. This is a foundation of norepinephrine excess symptoms crossing over with symptoms of dopamine deficiency.

Continue to: Impression

Impression. Mr. G shows multiple symptoms associated with norepinephrine excess. It is important to avoid caffeine intake in patients with clinical signs of excessive norepinephrine. Beta-blockers and alpha-2 agonists work well in patients such as Mr. G. Benzodiazepines indirectly decrease norepinephrine activity, but need to be used carefully due to the potential for misuse and addiction. In particular, short-acting benzodiazepines such as alprazolam and lorazepam must be avoided due to the induction of CNS instability with rapidly changing medication blood levels. Chlordiazepoxide may be a good choice for a patient such as Mr. G because it has the fewest adverse effects and the lowest abuse potential compared with other benzodiazepines. Avoid SNRIs in such a patient. Using mood-stabilizing antipsychotic medications may be especially warranted in treating Mr. G’s depression and pain.

Norepinephrine deficiency (Table 2^16,26,31-39)

Two years ago, Ms. A was diagnosed with chronic fatigue³¹ and fibromyalgia. She also had been diagnosed with depression and attention-deficit/hyperactivity disorder (ADHD). She presents with concerns of “brain fog,” no energy, low sex drive, and daytime sleepiness.^33,35 Allodynia is widespread.^16,36,37 Ms. A suffers from bulimia; she eats once a day but is still overweight.²⁶ She has orthostatic hypotension in addition to baseline low blood pressure and bradycardia.^16,38,39 Her pupils are almost pinpoint, even when she does not take opioid medications.¹⁶ Her skin is dry and her hair is brittle; deep tendon reflexes are weakened, and her muscle tone is decreased.¹⁶ Ms. A’s constant low mood drives her to drink excessive amounts of caffeine, which she says “helps with daytime sleepiness but does not last”^32,33 and causes heart rhythm problems³⁸ and dyspepsia.¹⁶ She sees that her headaches and body pain are associated with her caffeine intake, but refuses to stop taking caffeine. Her low interest in life and general passivity have caused her many problems, though the problems themselves do not make her feel much.^31,32,39 She is rather indifferent to pleasurable activities, including sex.³¹ Her response to exciting experiences is blunted,³² but she is still frequently tearful.³⁴ Ms. A’s mood does not improve with selective serotonin reuptake inhibitors; she has tried many. She says that she would not come to see a physician, but “my mom told me to.” She resents that her family thinks she is lazy^31,32,39 and blames her ADHD for underperformance in life.^32,33 Ms. A has a family history of chronic pain and Alzheimer disease, and the longer she experiences pain, the worse her memory.³⁵

Comment. As mentioned earlier, because of the norepinephrine/dopamine relationship, symptoms of excess dopamine overlap with symptoms of norepinephrine deficiency.

Impression. Ms. A shows multiple symptoms associated with norepinephrine deficiency. The use of noradrenergic antidepressants (such as SNRIs and mirtazapine)²⁶ and stimulants may be warranted. Physical exercise, participating in social activities, massage, acupuncture, and family support may help with Ms. A’s pain as well as her depression, as might vasopressors.

In Part 3, we will address gamma aminobutyric acid and glutamate.

Bottom Line

Both high and low levels of endorphins and norepinephrine may be associated with certain psychiatric and medical symptoms and disorders. An astute clinician may judge which neurotransmitter is dysfunctional based on the patient’s presentation, and tailor treatment accordingly.

Related Resources

• Arbuck DM, Salmerón JM, Mueller R. Neurotransmitter-based diagnosis and treatment: a hypothesis (Part 1). Current Psychiatry. 2022;21(5):30-36. doi:10.12788/cp.0242

Drug Brand Names

Alprazolam • Xanax
Chlordiazepoxide • Librium
Lorazepam • Ativan
Mirtazapine • Remeron

There is a need to connect mental and physical symptoms in the diagnosis and treatment of psychiatric disorders. Obviously, we are not yet equipped to clearly recognize which neurotransmitters cause which symptoms. The science of defining the underlying mechanisms is lagging behind the clinical needs. However, in this article, we present a few hypothetical clinical cases to emphasize a possible way of analyzing symptoms in order to identify underlying pathology and guide more effective treatment. Our descriptions do not reflect the entire set of symptoms caused by these neurotransmitters; we created them based on what is presently known (or suspected). Additional research is needed to confirm or disprove the hypotheses we present.

In Part 1 (Current Psychiatry, May 2022), we argued that for depression, anxiety, psychosis, and bipolar disorder, development and approval of medications is currently based on descriptive diagnoses, with disregard to the various underlying causes of those conditions. Similar to how the many types of pneumonia are treated differently based on the specific infective agent, we suggested there are various types of depression or chronic pain based on the underlying neuro­transmitter pathology. Such an approach may be extrapolated to anxiety, psychosis, or bipolar disorder, although those conditions are outside the scope of this article. In Part 1, we described serotonin- and dopamine-associated mental and physical symptoms that suggest distinctly different types of depression or chronic pain, and we suggested specific ways of treating those described conditions. Part 2 reflects on pathology that is possibly connected to endorphin and norepinephrine dysfunction. Table 1 outlines medical and psychiatric symptoms that likely reflect endorphin excess^1-16 and deficiency,^1,16-24 and Table 2 lists symptoms that likely reflect norepinephrine excess^16,25-30and deficiency.^16,26,31-39 It is worth noting that both the quantity of neurotransmitters as well as the quality of the transmission (as in receptors, cellular pumps, and distribution mechanisms) are important.

Endorphin excess (Table 1^1-16)

Ms. R is a frustrated chronic pain patient who bitterly complains that despite having seen more than 20 physicians, she does not have an answer to what causes her “all over” pain and headache.^4,5,11 She does not believe that all her laboratory test are normal, and insists that “something is missing.” She aches all over but says she can actually tolerate more pain than others and experiences only a little discomfort during an electromyogram or dental interventions. Though Ms. R is not very susceptible to acute pain,^4,5,9,16 pain all over without an identifiable cause is part of her life.^4,5,11 She says that listening to music and social interactions help decrease her pain.^4,5,10 Ms. R states that opioid medications do not help her pain, though she has a history of opioid overuse and opioid-induced hyperalgesia.^6,11,16

Ms. R tends to overdo pleasureful activities to achieve satisfaction.² She says exercise is particularly satisfying, to the point that she experiences euphoria and a loss of time.⁹ She is angry that her neurologist suggested she see a psychiatrist. Her depression bothers her more than her anxiety.^2,5,7

Ms. R clearly has a self-image problem, alternating between high and low self-esteem. She has a low appetite^1,12,14-16 and sleeps excessively.^2,4,7,9,10 Her mother privately tells you that Ms. R has a history of childhood sexual abuse and lagged in life due to a lack of motivation. Ms. R used to self-mutilate “to feel normal.”¹² Her primary care physician chronically addresses Ms. R’s poorly explained cholestasis and pruritus⁸ as well as dysregulation of blood pressure and heart rate, both of which tend to be low.^12,13,16

Impression. Ms. R shows multiple symptoms associated with endorphin excess. A trial of an opioid antagonist may be reasonable. Dopamine blockade helps with endorphin suppression and also may be used for this patient. Using a low starting dose and a slow titration of such medications would be beneficial due to frequent intolerance issues, especially nausea. Gamma aminobutyric acid-ergic medications modulate the opioid system and may be considered. A serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine may help patients such as Ms. R to control mood and pain through norepinephrine’s influence on endorphins.

Endorphin deficiency (Table 1^1,16-24)

Mr. J complains of low back pain, diffuse body pain, depression, and moodiness.^19,20,24 He is sluggish and plagued by psychomotor retardation.²⁴ All his life, a heightened perception of pain has caused him problems,^19,20 but has not stopped him from engaging in self-mutilation.²⁴ His “unexplained” pain and general body aches seem to be associated with objectively verifiable pain generators (such as bruises and surgical procedures) but this pain is in excess of what would generally be expected. Mr. J describes his low back pain as mild degenerative disc disease and is eager to explain that his wife’s spine is more diseased, yet she has no back pain.

Continue to: Mr. J responds to treatment...

Mr. J responds to treatment with opioids^16,20 but comments that his mood, and not necessarily his pain, improves when he takes these medications.²⁰ He tends to overuse his pain medications, and had run into trouble with his previous pain management physician. Nitrous oxide is remarkably effective during dental procedures.¹⁹ Acupuncture helps to control his pain and mood.¹⁷ Exercise is also rewarding.¹⁸

Mr. J has difficulty achieving orgasm, a decreased sexual drive, and emotional sensitivity.²⁴ He is impulsive.^19,20,24 His baseline mood is low-grade; anxiety bothers him more than depression.^23,24 Mr. J is thin, has a poor appetite,^1,16 and sleeps poorly.²⁴ His primary care physician struggles to help Mr. J to control dysregulation of his heart rate, blood pressure,²¹ and urinary retention,^16,22 as well as episodes of hypoglycemia.^1,16 He reluctantly admits to abusing alcohol, but explains that it helps with his mood and pain better than his prescribed medications.^18,23

Impression. Mr. J exhibits multiple symptoms associated with endorphin deficiency. Short-term use of opioids is warranted, but he should avoid long-term opioid use, and he and his physician should work together to establish strict control of their intake. Buprenorphine would be the opioid of choice for such a patient. Psychiatric treatment, including for alcohol use disorder, should be a mandatory part of his treatment regimen. Behavioral therapy with a focus on finding healthy ways to achieve gratification would be effective. Alternative treatments such as acupuncture may be of value.

Norepinephrine excess (Table 2^16,25-30)

Mr. G comes to the office irritable and angry^28,30 because no one can help him with his intractable headaches.^16,25 He is pale, his breathing is noisy, and he licks his dry lips while sweating.^16,25 His wife is shy and seems to be afraid of her husband, who is easily irritated and edgy.^28,30 His heart rate and blood pressure are high; he has a history of palpitations and chest pain.^16,25 When unhappy, he gets pale, sweaty, tremulous, and nauseous.^16,25 He masks his anxiety with aggression and has impaired concentration, restless sleep, muscle tension, muscle cramps, and abdominal cramps.^27,28,30 Mr. G suffers from frequent nausea.^16,25 His neck is stiff and pupils are dilated; he clenches his teeth and uses a mouth guard for correction of temporomandibular joint disorder.^16,25 His sleep apnea is poorly controlled because he feels entrapped when he uses a continuous positive airway pressure machine.²⁹ He blames his wife for his premature ejaculation and says that she gives him goosebumps.²⁵ His hypervigilance and hyperarousal are torturous to his wife.^27,30 Despite his overall angry state, Mr. G is also constantly fearful.^28,30 He is almost never hungry, does not like crowds, hates your waiting area, and is vocal about his dislike of doctors being late “all the time.”^26,28,30

Comment. Norepinephrine and dopamine functions are connected through common neuronal and glial uptake mechanisms. This is a foundation of norepinephrine excess symptoms crossing over with symptoms of dopamine deficiency.

Continue to: Impression

Impression. Mr. G shows multiple symptoms associated with norepinephrine excess. It is important to avoid caffeine intake in patients with clinical signs of excessive norepinephrine. Beta-blockers and alpha-2 agonists work well in patients such as Mr. G. Benzodiazepines indirectly decrease norepinephrine activity, but need to be used carefully due to the potential for misuse and addiction. In particular, short-acting benzodiazepines such as alprazolam and lorazepam must be avoided due to the induction of CNS instability with rapidly changing medication blood levels. Chlordiazepoxide may be a good choice for a patient such as Mr. G because it has the fewest adverse effects and the lowest abuse potential compared with other benzodiazepines. Avoid SNRIs in such a patient. Using mood-stabilizing antipsychotic medications may be especially warranted in treating Mr. G’s depression and pain.

Norepinephrine deficiency (Table 2^16,26,31-39)

Two years ago, Ms. A was diagnosed with chronic fatigue³¹ and fibromyalgia. She also had been diagnosed with depression and attention-deficit/hyperactivity disorder (ADHD). She presents with concerns of “brain fog,” no energy, low sex drive, and daytime sleepiness.^33,35 Allodynia is widespread.^16,36,37 Ms. A suffers from bulimia; she eats once a day but is still overweight.²⁶ She has orthostatic hypotension in addition to baseline low blood pressure and bradycardia.^16,38,39 Her pupils are almost pinpoint, even when she does not take opioid medications.¹⁶ Her skin is dry and her hair is brittle; deep tendon reflexes are weakened, and her muscle tone is decreased.¹⁶ Ms. A’s constant low mood drives her to drink excessive amounts of caffeine, which she says “helps with daytime sleepiness but does not last”^32,33 and causes heart rhythm problems³⁸ and dyspepsia.¹⁶ She sees that her headaches and body pain are associated with her caffeine intake, but refuses to stop taking caffeine. Her low interest in life and general passivity have caused her many problems, though the problems themselves do not make her feel much.^31,32,39 She is rather indifferent to pleasurable activities, including sex.³¹ Her response to exciting experiences is blunted,³² but she is still frequently tearful.³⁴ Ms. A’s mood does not improve with selective serotonin reuptake inhibitors; she has tried many. She says that she would not come to see a physician, but “my mom told me to.” She resents that her family thinks she is lazy^31,32,39 and blames her ADHD for underperformance in life.^32,33 Ms. A has a family history of chronic pain and Alzheimer disease, and the longer she experiences pain, the worse her memory.³⁵

Comment. As mentioned earlier, because of the norepinephrine/dopamine relationship, symptoms of excess dopamine overlap with symptoms of norepinephrine deficiency.

Impression. Ms. A shows multiple symptoms associated with norepinephrine deficiency. The use of noradrenergic antidepressants (such as SNRIs and mirtazapine)²⁶ and stimulants may be warranted. Physical exercise, participating in social activities, massage, acupuncture, and family support may help with Ms. A’s pain as well as her depression, as might vasopressors.

In Part 3, we will address gamma aminobutyric acid and glutamate.

Bottom Line

Both high and low levels of endorphins and norepinephrine may be associated with certain psychiatric and medical symptoms and disorders. An astute clinician may judge which neurotransmitter is dysfunctional based on the patient’s presentation, and tailor treatment accordingly.

Related Resources

• Arbuck DM, Salmerón JM, Mueller R. Neurotransmitter-based diagnosis and treatment: a hypothesis (Part 1). Current Psychiatry. 2022;21(5):30-36. doi:10.12788/cp.0242

Drug Brand Names

Alprazolam • Xanax
Chlordiazepoxide • Librium
Lorazepam • Ativan
Mirtazapine • Remeron

Having witnessed the devastating impact of stigma on patients with mental illness throughout my psychiatric career, I am fed up and disgusted with this malevolent scourge.

I regard the stigma that engulfs neuropsychiatric disorders as a malignancy that mutilates patients’ souls and hastens their mortality.

Stigma is hate speech

How would you feel if you had a serious medical illness, a disabling brain disorder such as schizophrenia, depression, or anxiety, and people refer to you with pejorative and insulting terms such as crazy, deranged, lunatic, unhinged, nutty, insane, wacky, berserk, cuckoo, bonkers, flaky, screwball, or unglued? This is hate speech generated by stigma against people with mental illness. Individuals with heart disease, cancer, or diabetes never get called such disgraceful and stigmatizing terms that shame, stain, besmirch, and scar them, which happens daily to persons with psychiatric brain disorders.

The damage and harm of the discriminatory stigma on our patients is multifaceted. It is painful, detrimental, pernicious, and deleterious. It is corrosive to their spirits, crippling to their self-image, and subversive to their self-confidence. Hate speech is not simply words, but a menacing weapon that assaults the core humanity of medically ill psychiatric patients.

Although hate speech is punishable by law, there are rarely any legal actions against those who hurl hate speech at psychiatric patients every day. Society has institutionalized the stigma of mental illness and takes it in stride instead of recognizing it as an illegal, harmful act.

Long before the stresses of the COVID-19 pandemic, 43% of the population had been shown to experience a diagnosable psychiatric disorder over the course of their life.¹ Thus, tens of millions of people are burdened by stigma and the hate speech associated with it. This is directly related to massive ignorance about mental illness being the result of a neurobiological condition due to either genetic or intrauterine adverse events that disrupt brain development. Delusions and hallucinations are symptoms of a malfunctioning brain, depression is not a sign of personal weakness, anxiety is the most prevalent mental disorder in the world, and obsessive-compulsive disorder (OCD) is not odd behavior but the result of dysfunction of neural circuits. Correcting public misperceptions about psychiatric brain disorders can mitigate stigma, but it has yet to happen.

Stigma is a hate crime

Stigma can accelerate physical death and premature mortality. Many studies have confirmed that persons with schizophrenia do not receive basic primary care treatments for the life-shortening medical conditions that often afflict them, such as diabetes, dyslipidemia, and hypertension.² Stigma is responsible for a significant disparity of medical^3-5 and intensive care⁶ among individuals with mental illness compared to the general population. It’s no wonder most psychiatric disorders are associated with accelerated mortality.⁷ A recent study during the pandemic by Balasuriya et al⁸ reported that patients with depression had poor access to care. Stigma interferes with or delays necessary medical care, leading to clinical deterioration and unnecessary, preventable death. Stigma shortens life and is a hate crime.

Continue to: The extremely high suicide rates...

The extremely high suicide rates among individuals with serious mental illness, who live under the oppressiveness of stigma, is another example of how stigma is a hate crime that can cause patients with psychiatric disorders to give up and end their lives. Zaheer et al⁹ found that young patients with schizophrenia had an astronomical suicide rate compared to the general population (1 in 52 in individuals with schizophrenia, compared to 12 in 100,000 in the general population, roughly a 200-fold increase!). This is clearly a consequence of stigma and discrimination,¹⁰ which leads to demoralization, shame, loneliness, distress, and hopelessness. Stigma can be fatal, and that makes it a hate crime.

Stigma also limits vocational opportunities for individuals with mental illness. They are either not hired, or quickly fired. Even highly educated professionals such as physicians, nurses, lawyers, or teachers can lose their jobs if they divulge a history of a psychiatric disorder or alcohol or substance abuse, regardless of whether they are receiving treatment and are medically in remission. Even highly qualified politicians have been deemed “ineligible” for higher office if they disclose a history of psychiatric treatment. Stigma is loaded with outrageous discrimination that deprives our patients of “the pursuit of happiness,” a fundamental constitutional right.

Stigma surrounding the mental health professions

Stigma also engulfs mental health professionals, simply because they deal with psychiatric patients every day. In a classic article titled “The Enigma of Stigma,”¹¹ Dr. Paul Fink, past president of the American Psychiatric Association (1988-1989), described how psychiatrists are perceived as “different” from other physicians by the public and by the media. He said psychiatrists are tarred by the same brush as their patients as “undesirables” in society. And movies such as Psycho and One Flew Over the Cuckoo’s Nest reinforce the stigma against both psychiatric patients and the psychiatrists and nurses who treat them. The health care system that carves out “behavioral health” from the umbrella of “medical care” further accentuates the stigma by portraying the “separateness” of psychiatry, a genuine medical specialty, from its fellow medical disciplines. This becomes fodder for the antipsychiatry movement at every turn and can even lead to questioning the existence of mental illness, as Thomas Szasz¹² did by declaring that mental illness is a myth and describing psychiatry as “the science of lies.” No other medical specialty endures abuse and insults like psychiatry, and that’s a direct result of stigma.

Extinguishing stigma is a societal imperative

So what can be done to squelch stigma and defeat it once and for all, so that psychiatric patients can be treated with dignity and compassion, like people with cancer, heart attacks, diabetes, or brain tumors? The pandemic, terrible as it has been for the entire world, did have the silver lining of raising awareness about the ubiquity of psychiatric symptoms, such as anxiety and depression, across all ages, genders, educational and religious backgrounds, and socioeconomic classes. But there should also be a robust legal battle against the damaging effects of stigma. There are laws to sanction and penalize hate speech and hate crimes that must be implemented when stigma is documented. There are also parity laws, but they have no teeth and have not ameliorated the insurance discrepancies and economic burden of psychiatric disorders. A bold step would be to reclassify serious psychiatric brain disorders (schizophrenia, bipolar disorder, major depressive disorder, OCD, attention-deficit/hyperactivity disorder, generalized anxiety disorder/panic attacks, and borderline personality disorder) as neurologic disorders, which would automatically give patients with these disorders broad access to medical care, which happened when autism was reclassified as a neurologic disorder. Finally, a much more intensive public education must be disseminated about the neurobiological etiologies, brain structure, and function in psychiatric disorders, and the psychiatric symptoms associated with all neurologic disorders. Regrettably, empathy can be difficult to teach.

Stigma is hate speech and a hate crime. It must be permanently eliminated by effective laws and by erasing the widespread ignorance about the medical and neurologic roots of mental disorders, and by emphasizing the fact that they are as treatable as other general medical conditions.

Having witnessed the devastating impact of stigma on patients with mental illness throughout my psychiatric career, I am fed up and disgusted with this malevolent scourge.

I regard the stigma that engulfs neuropsychiatric disorders as a malignancy that mutilates patients’ souls and hastens their mortality.

Stigma is hate speech

How would you feel if you had a serious medical illness, a disabling brain disorder such as schizophrenia, depression, or anxiety, and people refer to you with pejorative and insulting terms such as crazy, deranged, lunatic, unhinged, nutty, insane, wacky, berserk, cuckoo, bonkers, flaky, screwball, or unglued? This is hate speech generated by stigma against people with mental illness. Individuals with heart disease, cancer, or diabetes never get called such disgraceful and stigmatizing terms that shame, stain, besmirch, and scar them, which happens daily to persons with psychiatric brain disorders.

The damage and harm of the discriminatory stigma on our patients is multifaceted. It is painful, detrimental, pernicious, and deleterious. It is corrosive to their spirits, crippling to their self-image, and subversive to their self-confidence. Hate speech is not simply words, but a menacing weapon that assaults the core humanity of medically ill psychiatric patients.

Although hate speech is punishable by law, there are rarely any legal actions against those who hurl hate speech at psychiatric patients every day. Society has institutionalized the stigma of mental illness and takes it in stride instead of recognizing it as an illegal, harmful act.

Long before the stresses of the COVID-19 pandemic, 43% of the population had been shown to experience a diagnosable psychiatric disorder over the course of their life.¹ Thus, tens of millions of people are burdened by stigma and the hate speech associated with it. This is directly related to massive ignorance about mental illness being the result of a neurobiological condition due to either genetic or intrauterine adverse events that disrupt brain development. Delusions and hallucinations are symptoms of a malfunctioning brain, depression is not a sign of personal weakness, anxiety is the most prevalent mental disorder in the world, and obsessive-compulsive disorder (OCD) is not odd behavior but the result of dysfunction of neural circuits. Correcting public misperceptions about psychiatric brain disorders can mitigate stigma, but it has yet to happen.

Stigma is a hate crime

Stigma can accelerate physical death and premature mortality. Many studies have confirmed that persons with schizophrenia do not receive basic primary care treatments for the life-shortening medical conditions that often afflict them, such as diabetes, dyslipidemia, and hypertension.² Stigma is responsible for a significant disparity of medical^3-5 and intensive care⁶ among individuals with mental illness compared to the general population. It’s no wonder most psychiatric disorders are associated with accelerated mortality.⁷ A recent study during the pandemic by Balasuriya et al⁸ reported that patients with depression had poor access to care. Stigma interferes with or delays necessary medical care, leading to clinical deterioration and unnecessary, preventable death. Stigma shortens life and is a hate crime.

Continue to: The extremely high suicide rates...

The extremely high suicide rates among individuals with serious mental illness, who live under the oppressiveness of stigma, is another example of how stigma is a hate crime that can cause patients with psychiatric disorders to give up and end their lives. Zaheer et al⁹ found that young patients with schizophrenia had an astronomical suicide rate compared to the general population (1 in 52 in individuals with schizophrenia, compared to 12 in 100,000 in the general population, roughly a 200-fold increase!). This is clearly a consequence of stigma and discrimination,¹⁰ which leads to demoralization, shame, loneliness, distress, and hopelessness. Stigma can be fatal, and that makes it a hate crime.

Stigma also limits vocational opportunities for individuals with mental illness. They are either not hired, or quickly fired. Even highly educated professionals such as physicians, nurses, lawyers, or teachers can lose their jobs if they divulge a history of a psychiatric disorder or alcohol or substance abuse, regardless of whether they are receiving treatment and are medically in remission. Even highly qualified politicians have been deemed “ineligible” for higher office if they disclose a history of psychiatric treatment. Stigma is loaded with outrageous discrimination that deprives our patients of “the pursuit of happiness,” a fundamental constitutional right.

Stigma surrounding the mental health professions

Stigma also engulfs mental health professionals, simply because they deal with psychiatric patients every day. In a classic article titled “The Enigma of Stigma,”¹¹ Dr. Paul Fink, past president of the American Psychiatric Association (1988-1989), described how psychiatrists are perceived as “different” from other physicians by the public and by the media. He said psychiatrists are tarred by the same brush as their patients as “undesirables” in society. And movies such as Psycho and One Flew Over the Cuckoo’s Nest reinforce the stigma against both psychiatric patients and the psychiatrists and nurses who treat them. The health care system that carves out “behavioral health” from the umbrella of “medical care” further accentuates the stigma by portraying the “separateness” of psychiatry, a genuine medical specialty, from its fellow medical disciplines. This becomes fodder for the antipsychiatry movement at every turn and can even lead to questioning the existence of mental illness, as Thomas Szasz¹² did by declaring that mental illness is a myth and describing psychiatry as “the science of lies.” No other medical specialty endures abuse and insults like psychiatry, and that’s a direct result of stigma.

Extinguishing stigma is a societal imperative

So what can be done to squelch stigma and defeat it once and for all, so that psychiatric patients can be treated with dignity and compassion, like people with cancer, heart attacks, diabetes, or brain tumors? The pandemic, terrible as it has been for the entire world, did have the silver lining of raising awareness about the ubiquity of psychiatric symptoms, such as anxiety and depression, across all ages, genders, educational and religious backgrounds, and socioeconomic classes. But there should also be a robust legal battle against the damaging effects of stigma. There are laws to sanction and penalize hate speech and hate crimes that must be implemented when stigma is documented. There are also parity laws, but they have no teeth and have not ameliorated the insurance discrepancies and economic burden of psychiatric disorders. A bold step would be to reclassify serious psychiatric brain disorders (schizophrenia, bipolar disorder, major depressive disorder, OCD, attention-deficit/hyperactivity disorder, generalized anxiety disorder/panic attacks, and borderline personality disorder) as neurologic disorders, which would automatically give patients with these disorders broad access to medical care, which happened when autism was reclassified as a neurologic disorder. Finally, a much more intensive public education must be disseminated about the neurobiological etiologies, brain structure, and function in psychiatric disorders, and the psychiatric symptoms associated with all neurologic disorders. Regrettably, empathy can be difficult to teach.

Stigma is hate speech and a hate crime. It must be permanently eliminated by effective laws and by erasing the widespread ignorance about the medical and neurologic roots of mental disorders, and by emphasizing the fact that they are as treatable as other general medical conditions.

Having witnessed the devastating impact of stigma on patients with mental illness throughout my psychiatric career, I am fed up and disgusted with this malevolent scourge.

I regard the stigma that engulfs neuropsychiatric disorders as a malignancy that mutilates patients’ souls and hastens their mortality.

Stigma is hate speech

How would you feel if you had a serious medical illness, a disabling brain disorder such as schizophrenia, depression, or anxiety, and people refer to you with pejorative and insulting terms such as crazy, deranged, lunatic, unhinged, nutty, insane, wacky, berserk, cuckoo, bonkers, flaky, screwball, or unglued? This is hate speech generated by stigma against people with mental illness. Individuals with heart disease, cancer, or diabetes never get called such disgraceful and stigmatizing terms that shame, stain, besmirch, and scar them, which happens daily to persons with psychiatric brain disorders.

The damage and harm of the discriminatory stigma on our patients is multifaceted. It is painful, detrimental, pernicious, and deleterious. It is corrosive to their spirits, crippling to their self-image, and subversive to their self-confidence. Hate speech is not simply words, but a menacing weapon that assaults the core humanity of medically ill psychiatric patients.

Although hate speech is punishable by law, there are rarely any legal actions against those who hurl hate speech at psychiatric patients every day. Society has institutionalized the stigma of mental illness and takes it in stride instead of recognizing it as an illegal, harmful act.

Long before the stresses of the COVID-19 pandemic, 43% of the population had been shown to experience a diagnosable psychiatric disorder over the course of their life.¹ Thus, tens of millions of people are burdened by stigma and the hate speech associated with it. This is directly related to massive ignorance about mental illness being the result of a neurobiological condition due to either genetic or intrauterine adverse events that disrupt brain development. Delusions and hallucinations are symptoms of a malfunctioning brain, depression is not a sign of personal weakness, anxiety is the most prevalent mental disorder in the world, and obsessive-compulsive disorder (OCD) is not odd behavior but the result of dysfunction of neural circuits. Correcting public misperceptions about psychiatric brain disorders can mitigate stigma, but it has yet to happen.

Stigma is a hate crime

Stigma can accelerate physical death and premature mortality. Many studies have confirmed that persons with schizophrenia do not receive basic primary care treatments for the life-shortening medical conditions that often afflict them, such as diabetes, dyslipidemia, and hypertension.² Stigma is responsible for a significant disparity of medical^3-5 and intensive care⁶ among individuals with mental illness compared to the general population. It’s no wonder most psychiatric disorders are associated with accelerated mortality.⁷ A recent study during the pandemic by Balasuriya et al⁸ reported that patients with depression had poor access to care. Stigma interferes with or delays necessary medical care, leading to clinical deterioration and unnecessary, preventable death. Stigma shortens life and is a hate crime.

Continue to: The extremely high suicide rates...

The extremely high suicide rates among individuals with serious mental illness, who live under the oppressiveness of stigma, is another example of how stigma is a hate crime that can cause patients with psychiatric disorders to give up and end their lives. Zaheer et al⁹ found that young patients with schizophrenia had an astronomical suicide rate compared to the general population (1 in 52 in individuals with schizophrenia, compared to 12 in 100,000 in the general population, roughly a 200-fold increase!). This is clearly a consequence of stigma and discrimination,¹⁰ which leads to demoralization, shame, loneliness, distress, and hopelessness. Stigma can be fatal, and that makes it a hate crime.

Stigma also limits vocational opportunities for individuals with mental illness. They are either not hired, or quickly fired. Even highly educated professionals such as physicians, nurses, lawyers, or teachers can lose their jobs if they divulge a history of a psychiatric disorder or alcohol or substance abuse, regardless of whether they are receiving treatment and are medically in remission. Even highly qualified politicians have been deemed “ineligible” for higher office if they disclose a history of psychiatric treatment. Stigma is loaded with outrageous discrimination that deprives our patients of “the pursuit of happiness,” a fundamental constitutional right.

Stigma surrounding the mental health professions

Stigma also engulfs mental health professionals, simply because they deal with psychiatric patients every day. In a classic article titled “The Enigma of Stigma,”¹¹ Dr. Paul Fink, past president of the American Psychiatric Association (1988-1989), described how psychiatrists are perceived as “different” from other physicians by the public and by the media. He said psychiatrists are tarred by the same brush as their patients as “undesirables” in society. And movies such as Psycho and One Flew Over the Cuckoo’s Nest reinforce the stigma against both psychiatric patients and the psychiatrists and nurses who treat them. The health care system that carves out “behavioral health” from the umbrella of “medical care” further accentuates the stigma by portraying the “separateness” of psychiatry, a genuine medical specialty, from its fellow medical disciplines. This becomes fodder for the antipsychiatry movement at every turn and can even lead to questioning the existence of mental illness, as Thomas Szasz¹² did by declaring that mental illness is a myth and describing psychiatry as “the science of lies.” No other medical specialty endures abuse and insults like psychiatry, and that’s a direct result of stigma.

Extinguishing stigma is a societal imperative

So what can be done to squelch stigma and defeat it once and for all, so that psychiatric patients can be treated with dignity and compassion, like people with cancer, heart attacks, diabetes, or brain tumors? The pandemic, terrible as it has been for the entire world, did have the silver lining of raising awareness about the ubiquity of psychiatric symptoms, such as anxiety and depression, across all ages, genders, educational and religious backgrounds, and socioeconomic classes. But there should also be a robust legal battle against the damaging effects of stigma. There are laws to sanction and penalize hate speech and hate crimes that must be implemented when stigma is documented. There are also parity laws, but they have no teeth and have not ameliorated the insurance discrepancies and economic burden of psychiatric disorders. A bold step would be to reclassify serious psychiatric brain disorders (schizophrenia, bipolar disorder, major depressive disorder, OCD, attention-deficit/hyperactivity disorder, generalized anxiety disorder/panic attacks, and borderline personality disorder) as neurologic disorders, which would automatically give patients with these disorders broad access to medical care, which happened when autism was reclassified as a neurologic disorder. Finally, a much more intensive public education must be disseminated about the neurobiological etiologies, brain structure, and function in psychiatric disorders, and the psychiatric symptoms associated with all neurologic disorders. Regrettably, empathy can be difficult to teach.

Stigma is hate speech and a hate crime. It must be permanently eliminated by effective laws and by erasing the widespread ignorance about the medical and neurologic roots of mental disorders, and by emphasizing the fact that they are as treatable as other general medical conditions.

Ramadan is one of the obligatory pillars in Islam during which healthy Muslims are required to fast from dawn until sunset every day for 1 month. There are an estimated 3.45 million Muslims in the United States, and this population will continue to grow by 100,000 per year.¹ With the increased growth of the Muslim population, it is important for clinicians to be aware of how patients of Muslim faith are affected during Ramadan. In this article, we explore the potential risks, as well as the benefits, the month of Ramadan brings to patients. We will also explain how being religiously aware is necessary to provide optimal care for these individuals.

For some patients, fasting may pose risks

Similar to other communities in the United States, individuals who are Muslim experience mood disorders, anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, schizophrenia, substance use disorders, and other psychiatric illnesses.² During the month of Ramadan, Muslims are to abstain completely from eating and drinking from dawn until sunset. This includes medications as well as food and drink.

Due to these circumstances, patients will often change the timing, frequency, and dosing of their medications to allow them to fast. One study found 60% of Muslims made medication adjustments during Ramadan without seeking medical advice.³ It is possible that such alterations may be detrimental. During Ramadan, some Muslims wake up early in the morning to eat a pre-dawn meal, and often go back to sleep. This has been reported to cause a delay in sleep-wake times and to reduce rapid eye movement sleep.⁴ These circadian rhythm changes can be detrimental to patients with bipolar disorder. One study found higher rates of relapse to depression and mania in patients with bipolar disorder who were fasting during Ramadan.⁵ Circadian rhythm disturbances also may worsen depression.⁶ Another point of concern is patients with eating disorders. One small case series (N = 6) found that fasting during Ramadan exacerbated symptoms in patients with eating disorders.⁷

Another concern is that dehydration while fasting can lead to lithium toxicity. However, one study found lithium levels remained stable while fasting for 10 to 12 hours.⁵ Another showed that changing lithium dosing from twice a day to once a day allowed for easier administration without causing a subtherapeutic change in blood lithium levels.⁸

The practice also may have benefits for mental health

For many Muslims, Ramadan is the best time of the year, where they reconnect with their religion and experience the utmost spiritual growth. Studies have shown that the incidence of suicide is lowest during Ramadan compared to other months.⁹ A study of older men found that intermittent fasting and calorie restriction (not during Ramadan) resulted in decreases in tension, confusion, anger, and mood disturbance.¹⁰ Another study found that fasting during Ramadan had a positive impact on depression, anxiety, stress, and cognitive function.¹¹

Clinical considerations

To provide the best care for Muslim patients during Ramadan, clinicians should take a holistic approach and take all factors into consideration. It is common for circadian rhythm disruptions to exacerbate mood disorders, so encourage patients to maintain healthy sleep hygiene to their best ability during this month. Another important consideration is medication timing and dosing.¹² For patients prescribed a medication that typically is taken twice a day, determine if this dosing can be changed to once a day, or if both doses can be taken when it is permissible to eat (sunset to dawn). For medications that are absorbed with food, consider how these medications might be adjusted and maintained while a patient is fasting. Some medications may be sedating or activating, so the timing of administration may need to be adjusted to meet the patient’s needs. Lastly, keep in mind that certain medications can have withdrawal effects, and the likelihood of this occurring while a patient is fasting.

One vital point is that if a patient is at high risk of clinically decompensating due to fasting or medication adjustments or discontinuation, advise them to not fast. Muslims with physical or mental illnesses are excused from fasting. Bear in mind that because Ramadan is meant to be a month of heightened spirituality, many Muslims will prefer to fast.

Ramadan is one of the obligatory pillars in Islam during which healthy Muslims are required to fast from dawn until sunset every day for 1 month. There are an estimated 3.45 million Muslims in the United States, and this population will continue to grow by 100,000 per year.¹ With the increased growth of the Muslim population, it is important for clinicians to be aware of how patients of Muslim faith are affected during Ramadan. In this article, we explore the potential risks, as well as the benefits, the month of Ramadan brings to patients. We will also explain how being religiously aware is necessary to provide optimal care for these individuals.

For some patients, fasting may pose risks

Similar to other communities in the United States, individuals who are Muslim experience mood disorders, anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, schizophrenia, substance use disorders, and other psychiatric illnesses.² During the month of Ramadan, Muslims are to abstain completely from eating and drinking from dawn until sunset. This includes medications as well as food and drink.

Due to these circumstances, patients will often change the timing, frequency, and dosing of their medications to allow them to fast. One study found 60% of Muslims made medication adjustments during Ramadan without seeking medical advice.³ It is possible that such alterations may be detrimental. During Ramadan, some Muslims wake up early in the morning to eat a pre-dawn meal, and often go back to sleep. This has been reported to cause a delay in sleep-wake times and to reduce rapid eye movement sleep.⁴ These circadian rhythm changes can be detrimental to patients with bipolar disorder. One study found higher rates of relapse to depression and mania in patients with bipolar disorder who were fasting during Ramadan.⁵ Circadian rhythm disturbances also may worsen depression.⁶ Another point of concern is patients with eating disorders. One small case series (N = 6) found that fasting during Ramadan exacerbated symptoms in patients with eating disorders.⁷

Another concern is that dehydration while fasting can lead to lithium toxicity. However, one study found lithium levels remained stable while fasting for 10 to 12 hours.⁵ Another showed that changing lithium dosing from twice a day to once a day allowed for easier administration without causing a subtherapeutic change in blood lithium levels.⁸

The practice also may have benefits for mental health

For many Muslims, Ramadan is the best time of the year, where they reconnect with their religion and experience the utmost spiritual growth. Studies have shown that the incidence of suicide is lowest during Ramadan compared to other months.⁹ A study of older men found that intermittent fasting and calorie restriction (not during Ramadan) resulted in decreases in tension, confusion, anger, and mood disturbance.¹⁰ Another study found that fasting during Ramadan had a positive impact on depression, anxiety, stress, and cognitive function.¹¹

Clinical considerations

To provide the best care for Muslim patients during Ramadan, clinicians should take a holistic approach and take all factors into consideration. It is common for circadian rhythm disruptions to exacerbate mood disorders, so encourage patients to maintain healthy sleep hygiene to their best ability during this month. Another important consideration is medication timing and dosing.¹² For patients prescribed a medication that typically is taken twice a day, determine if this dosing can be changed to once a day, or if both doses can be taken when it is permissible to eat (sunset to dawn). For medications that are absorbed with food, consider how these medications might be adjusted and maintained while a patient is fasting. Some medications may be sedating or activating, so the timing of administration may need to be adjusted to meet the patient’s needs. Lastly, keep in mind that certain medications can have withdrawal effects, and the likelihood of this occurring while a patient is fasting.

One vital point is that if a patient is at high risk of clinically decompensating due to fasting or medication adjustments or discontinuation, advise them to not fast. Muslims with physical or mental illnesses are excused from fasting. Bear in mind that because Ramadan is meant to be a month of heightened spirituality, many Muslims will prefer to fast.

Ramadan is one of the obligatory pillars in Islam during which healthy Muslims are required to fast from dawn until sunset every day for 1 month. There are an estimated 3.45 million Muslims in the United States, and this population will continue to grow by 100,000 per year.¹ With the increased growth of the Muslim population, it is important for clinicians to be aware of how patients of Muslim faith are affected during Ramadan. In this article, we explore the potential risks, as well as the benefits, the month of Ramadan brings to patients. We will also explain how being religiously aware is necessary to provide optimal care for these individuals.

For some patients, fasting may pose risks

Similar to other communities in the United States, individuals who are Muslim experience mood disorders, anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, schizophrenia, substance use disorders, and other psychiatric illnesses.² During the month of Ramadan, Muslims are to abstain completely from eating and drinking from dawn until sunset. This includes medications as well as food and drink.

Due to these circumstances, patients will often change the timing, frequency, and dosing of their medications to allow them to fast. One study found 60% of Muslims made medication adjustments during Ramadan without seeking medical advice.³ It is possible that such alterations may be detrimental. During Ramadan, some Muslims wake up early in the morning to eat a pre-dawn meal, and often go back to sleep. This has been reported to cause a delay in sleep-wake times and to reduce rapid eye movement sleep.⁴ These circadian rhythm changes can be detrimental to patients with bipolar disorder. One study found higher rates of relapse to depression and mania in patients with bipolar disorder who were fasting during Ramadan.⁵ Circadian rhythm disturbances also may worsen depression.⁶ Another point of concern is patients with eating disorders. One small case series (N = 6) found that fasting during Ramadan exacerbated symptoms in patients with eating disorders.⁷

Another concern is that dehydration while fasting can lead to lithium toxicity. However, one study found lithium levels remained stable while fasting for 10 to 12 hours.⁵ Another showed that changing lithium dosing from twice a day to once a day allowed for easier administration without causing a subtherapeutic change in blood lithium levels.⁸

The practice also may have benefits for mental health

For many Muslims, Ramadan is the best time of the year, where they reconnect with their religion and experience the utmost spiritual growth. Studies have shown that the incidence of suicide is lowest during Ramadan compared to other months.⁹ A study of older men found that intermittent fasting and calorie restriction (not during Ramadan) resulted in decreases in tension, confusion, anger, and mood disturbance.¹⁰ Another study found that fasting during Ramadan had a positive impact on depression, anxiety, stress, and cognitive function.¹¹

Clinical considerations

To provide the best care for Muslim patients during Ramadan, clinicians should take a holistic approach and take all factors into consideration. It is common for circadian rhythm disruptions to exacerbate mood disorders, so encourage patients to maintain healthy sleep hygiene to their best ability during this month. Another important consideration is medication timing and dosing.¹² For patients prescribed a medication that typically is taken twice a day, determine if this dosing can be changed to once a day, or if both doses can be taken when it is permissible to eat (sunset to dawn). For medications that are absorbed with food, consider how these medications might be adjusted and maintained while a patient is fasting. Some medications may be sedating or activating, so the timing of administration may need to be adjusted to meet the patient’s needs. Lastly, keep in mind that certain medications can have withdrawal effects, and the likelihood of this occurring while a patient is fasting.

One vital point is that if a patient is at high risk of clinically decompensating due to fasting or medication adjustments or discontinuation, advise them to not fast. Muslims with physical or mental illnesses are excused from fasting. Bear in mind that because Ramadan is meant to be a month of heightened spirituality, many Muslims will prefer to fast.

The inaugural issue of GI & Hepatology News was published in January 2007, and the newspaper has gone on to become part of the fabric of the AGA. This year, we celebrate the newspaper’s 15th year with a special 15th Anniversary Series that will run from June through December 2022. We will feature reflections from GIHN’s three former editors-in-chief, Dr. Charles J. Lightdale, Dr. Colin Howden, and Dr. John Allen, on the evolution of the newspaper (and the field of GI) over the past 15 years. We also will present a series of Then and Now columns, highlighting high-impact areas of GI and hepatology covered in past GIHN issues, and reflecting on how the field has changed since that time.

In this month’s issue, we are pleased to kick off the 15th Anniversary Series with reflections by Dr. Lightdale, GIHN’s inaugural editor-in-chief, as well as a Then and Now column written by Dr. Kimberly M. Persley (GIHN associate editor and longstanding AGA member) reflecting on how the demographics of gastroenterology and of the AGA as an organization have changed over the past 15 years. I hope you will find these special contributions to be engaging and thought-provoking. Other issue highlights include a lead article describing impacts of social determinants of health in driving disparities in IBD care and offering recommendations for achieving IBD health equity, a new AGA Clinical Practice Update on dietary options for our many patients with irritable bowel syndrome, and new data on the safety of anti-TNF medications prior to surgery in patients with inflammatory bowel disease.

As summer vacation season commences, I hope you will join me in taking some well-deserved time away from work demands, spending some quality time with friends and family, and seizing the opportunity to rest and recharge.

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

The inaugural issue of GI & Hepatology News was published in January 2007, and the newspaper has gone on to become part of the fabric of the AGA. This year, we celebrate the newspaper’s 15th year with a special 15th Anniversary Series that will run from June through December 2022. We will feature reflections from GIHN’s three former editors-in-chief, Dr. Charles J. Lightdale, Dr. Colin Howden, and Dr. John Allen, on the evolution of the newspaper (and the field of GI) over the past 15 years. We also will present a series of Then and Now columns, highlighting high-impact areas of GI and hepatology covered in past GIHN issues, and reflecting on how the field has changed since that time.

In this month’s issue, we are pleased to kick off the 15th Anniversary Series with reflections by Dr. Lightdale, GIHN’s inaugural editor-in-chief, as well as a Then and Now column written by Dr. Kimberly M. Persley (GIHN associate editor and longstanding AGA member) reflecting on how the demographics of gastroenterology and of the AGA as an organization have changed over the past 15 years. I hope you will find these special contributions to be engaging and thought-provoking. Other issue highlights include a lead article describing impacts of social determinants of health in driving disparities in IBD care and offering recommendations for achieving IBD health equity, a new AGA Clinical Practice Update on dietary options for our many patients with irritable bowel syndrome, and new data on the safety of anti-TNF medications prior to surgery in patients with inflammatory bowel disease.

As summer vacation season commences, I hope you will join me in taking some well-deserved time away from work demands, spending some quality time with friends and family, and seizing the opportunity to rest and recharge.

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

The inaugural issue of GI & Hepatology News was published in January 2007, and the newspaper has gone on to become part of the fabric of the AGA. This year, we celebrate the newspaper’s 15th year with a special 15th Anniversary Series that will run from June through December 2022. We will feature reflections from GIHN’s three former editors-in-chief, Dr. Charles J. Lightdale, Dr. Colin Howden, and Dr. John Allen, on the evolution of the newspaper (and the field of GI) over the past 15 years. We also will present a series of Then and Now columns, highlighting high-impact areas of GI and hepatology covered in past GIHN issues, and reflecting on how the field has changed since that time.

In this month’s issue, we are pleased to kick off the 15th Anniversary Series with reflections by Dr. Lightdale, GIHN’s inaugural editor-in-chief, as well as a Then and Now column written by Dr. Kimberly M. Persley (GIHN associate editor and longstanding AGA member) reflecting on how the demographics of gastroenterology and of the AGA as an organization have changed over the past 15 years. I hope you will find these special contributions to be engaging and thought-provoking. Other issue highlights include a lead article describing impacts of social determinants of health in driving disparities in IBD care and offering recommendations for achieving IBD health equity, a new AGA Clinical Practice Update on dietary options for our many patients with irritable bowel syndrome, and new data on the safety of anti-TNF medications prior to surgery in patients with inflammatory bowel disease.

As summer vacation season commences, I hope you will join me in taking some well-deserved time away from work demands, spending some quality time with friends and family, and seizing the opportunity to rest and recharge.

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

Here we go again, and again, and again.

There just aren’t enough tears, and before the bodies of 19 small children are identified, the political noise starts up. Mass shootings are a part of the American landscape, but when they happen at schools, we all feel a distinct sense of violation and gaping grief. Those children are so innocent, so deserving of a right to live their lives, hold their place with their families, create their own legacies, and die of natural causes at a ripe old age. And those children could have been our children. There was nothing special about them; they were just sent to school that day like every child who is sent to school every day.

Here is how the politics goes: The Republicans will blame the Democrats and the Democrats will blame the Republicans. Is Rachel Maddow at fault, or is it Tucker Carlson? Social media accounts blamed both of them for the racially motivated mass murder in a Buffalo grocery store on May 14.

Mass murders were previously defined as a shooting where four or more victims are killed, excluding the shooter, in a public place that is not related to the commission of another crime. In 2012, the definition was changed to include events with three victims. This definition excludes gang violence and the murder of family members.

When it comes to explaining mass murder, the camps divide: They are the result of some combination of mental illness, easy access to firearms, and terrorism and hate. For psychiatry, there is a unique place in the argument – half of all mass shooters have exhibited signs or symptoms of psychiatric illness, and for those who want to deflect the issue away from issues related to the regulation of firearms, it becomes easy to blame “mental illness,” as though that explains it all. Either the gunman “snapped” in such a way that no one could have predicted, or the mental health system is at fault for not preventing it.

There are many ways to be emotionally disturbed; mental illness is only one of them, and there is no psychiatric diagnosis that includes the symptom of shooting strangers, or shooting children. The vast majority of people, including nearly all psychiatrists, will never know someone who perpetrates a mass shooting. 

Can mental illness give us any insight into these senseless killings? Sometimes, but rarely. Take John Hinckley Jr., who shot President Ronald Reagan as a means to impress actress Jodie Foster. Sometimes these killings are motivated by delusional beliefs. But the planning and preparation that goes into most mass shootings involves a degree of organization and forethought that we don’t typically see in those with severe psychotic disorders.

The other psychological explanation that satisfies some of a nonmedical population is that these killers “just snap.” This, too, is a term that is not included in our diagnostic vocabulary, but it remains a way for some to explain that which can’t be explained. If mental illness, however, is the cause of mass murders, then more stringent gun control is unnecessary. Every state already has a mechanism to prevent those with criminal and specified psychiatric histories from buying legal firearms, and it may be inevitable that these screens are not perfect. 

The next line of political thinking moves to the psychiatric “if only.” If only there were more state hospital beds and if only it were easier to compel people with psychiatric disorders to get treatment against their will, then we could eliminate these crimes. The Virginia tech shooter was mandated to get outpatient psychiatric treatment after a brief hospitalization, yet he never went and there was no mechanism in place to track him.

In cases where a person with a psychotic illness has a history of repeated violent episodes after stopping medications, it does make sense to mandate treatment, not because they are likely to shoot strangers, but because some people do become violent when they are ill and mental illness is believed to play a role in 10% of murders.

Mass murders remain rare, and while advocates for legislation that would make it easier to mandate involuntary care have cited violence prevention as a reason, it is hard to imagine that we would force people to get care because they “might” commit such a crime – unless there was convincing evidence that someone was at risk of committing such a heinous act.

For those who oppose stronger gun control laws, the “what if” may circulate around the need for even more firearms. What if teachers carried guns? What if schools were more heavily policed? What if the criminals were made to be afraid?

We are left with the fact that other countries do not see these numbers of mass shooting events, yet mental illness is ubiquitous. While the presence of psychiatric disorders does little to explain school shootings, we still have no understanding of what motivated the Sandy Hook killer, and it remains to be seen what we will come to understand about the gunman in Uvalde, Texas.

Mental illness is not unique to the United States; however, the number of available firearms is. In a country of 323 million people (including children and people who live in institutions where they have no access to firearms), there are estimated to be over 400 million guns in the United States, 98% of which are owned by civilians. 

Hate crimes and terrorism are another explanation for mass murders. In these instances, the gunman makes his motive obvious: There are social media announcements, or the site of the shooting is a synagogue, a mosque, or a location where the victims are of a specific race or religion. But hate may come out of a psychotic illness, and easy access to firearms allows for these crimes to continue. 

Firearms are now the No. 1 cause of mortality in children. Very few of these deaths are the result of mass murders. Many more are from accidental deaths, targeted crime, or suicide. Still, school shootings rip at our hearts. Neither the victims nor their grieving families have any role in the act, and suffering leaves its mark on families, communities, and all of us.
 

Are there answers?

In many states, physicians can now request emergency removal of firearms from the home of someone who is both mentally ill and threatening either suicide or homicide. During the era when high-capacity firearms were banned, from 1994 to 2004, mass murders decreased in our country. While most gunmen use legal firearms they have purchased, I would contend that “smart guns” – firearms that allow only the legal owner to operate them based on biometrics – would prevent some mass shootings and many accidents, crimes, and suicides. Universal background checks and tracking gun purchases in the way we monitor controlled medications, or even Sudafed, might allow authorities to predict who might be at risk of committing these heinous acts.

In his newly released book, Trigger Points: Inside the Mission to Stop Mass Murders in America, journalist Mark Follman argues for a proactive community approach using threat assessment methods and providing wraparound services to those who are deemed to be at risk for violent acts. Mr. Follman’s voice is one of the few out there saying that these events are not random and are, in fact, preventable.

In psychiatry, we struggle with school shootings such as the one we just saw in Uvalde. Our own hearts ache as we hold our children close and empathize with the loss of strangers who have been through the unthinkable. We help our patients as they process their emotions. And we wonder whether any of our patients might ever do anything so horrific. The feelings get complicated, the sadness and anger intermingle while the frustration builds, and we are left with our fears and the hope that if that very rare person were to walk through our office door, we would know what to do.

Dr. Miller is a coauthor of Committed: The Battle Over Involuntary Psychiatric Care (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. A version of this article first appeared on Medscape.com.

Here we go again, and again, and again.

There just aren’t enough tears, and before the bodies of 19 small children are identified, the political noise starts up. Mass shootings are a part of the American landscape, but when they happen at schools, we all feel a distinct sense of violation and gaping grief. Those children are so innocent, so deserving of a right to live their lives, hold their place with their families, create their own legacies, and die of natural causes at a ripe old age. And those children could have been our children. There was nothing special about them; they were just sent to school that day like every child who is sent to school every day.

Here is how the politics goes: The Republicans will blame the Democrats and the Democrats will blame the Republicans. Is Rachel Maddow at fault, or is it Tucker Carlson? Social media accounts blamed both of them for the racially motivated mass murder in a Buffalo grocery store on May 14.

Mass murders were previously defined as a shooting where four or more victims are killed, excluding the shooter, in a public place that is not related to the commission of another crime. In 2012, the definition was changed to include events with three victims. This definition excludes gang violence and the murder of family members.

When it comes to explaining mass murder, the camps divide: They are the result of some combination of mental illness, easy access to firearms, and terrorism and hate. For psychiatry, there is a unique place in the argument – half of all mass shooters have exhibited signs or symptoms of psychiatric illness, and for those who want to deflect the issue away from issues related to the regulation of firearms, it becomes easy to blame “mental illness,” as though that explains it all. Either the gunman “snapped” in such a way that no one could have predicted, or the mental health system is at fault for not preventing it.

There are many ways to be emotionally disturbed; mental illness is only one of them, and there is no psychiatric diagnosis that includes the symptom of shooting strangers, or shooting children. The vast majority of people, including nearly all psychiatrists, will never know someone who perpetrates a mass shooting. 

Can mental illness give us any insight into these senseless killings? Sometimes, but rarely. Take John Hinckley Jr., who shot President Ronald Reagan as a means to impress actress Jodie Foster. Sometimes these killings are motivated by delusional beliefs. But the planning and preparation that goes into most mass shootings involves a degree of organization and forethought that we don’t typically see in those with severe psychotic disorders.

The other psychological explanation that satisfies some of a nonmedical population is that these killers “just snap.” This, too, is a term that is not included in our diagnostic vocabulary, but it remains a way for some to explain that which can’t be explained. If mental illness, however, is the cause of mass murders, then more stringent gun control is unnecessary. Every state already has a mechanism to prevent those with criminal and specified psychiatric histories from buying legal firearms, and it may be inevitable that these screens are not perfect. 

The next line of political thinking moves to the psychiatric “if only.” If only there were more state hospital beds and if only it were easier to compel people with psychiatric disorders to get treatment against their will, then we could eliminate these crimes. The Virginia tech shooter was mandated to get outpatient psychiatric treatment after a brief hospitalization, yet he never went and there was no mechanism in place to track him.

In cases where a person with a psychotic illness has a history of repeated violent episodes after stopping medications, it does make sense to mandate treatment, not because they are likely to shoot strangers, but because some people do become violent when they are ill and mental illness is believed to play a role in 10% of murders.

Mass murders remain rare, and while advocates for legislation that would make it easier to mandate involuntary care have cited violence prevention as a reason, it is hard to imagine that we would force people to get care because they “might” commit such a crime – unless there was convincing evidence that someone was at risk of committing such a heinous act.

For those who oppose stronger gun control laws, the “what if” may circulate around the need for even more firearms. What if teachers carried guns? What if schools were more heavily policed? What if the criminals were made to be afraid?

We are left with the fact that other countries do not see these numbers of mass shooting events, yet mental illness is ubiquitous. While the presence of psychiatric disorders does little to explain school shootings, we still have no understanding of what motivated the Sandy Hook killer, and it remains to be seen what we will come to understand about the gunman in Uvalde, Texas.

Mental illness is not unique to the United States; however, the number of available firearms is. In a country of 323 million people (including children and people who live in institutions where they have no access to firearms), there are estimated to be over 400 million guns in the United States, 98% of which are owned by civilians. 

Hate crimes and terrorism are another explanation for mass murders. In these instances, the gunman makes his motive obvious: There are social media announcements, or the site of the shooting is a synagogue, a mosque, or a location where the victims are of a specific race or religion. But hate may come out of a psychotic illness, and easy access to firearms allows for these crimes to continue. 

Firearms are now the No. 1 cause of mortality in children. Very few of these deaths are the result of mass murders. Many more are from accidental deaths, targeted crime, or suicide. Still, school shootings rip at our hearts. Neither the victims nor their grieving families have any role in the act, and suffering leaves its mark on families, communities, and all of us.
 

Are there answers?

In many states, physicians can now request emergency removal of firearms from the home of someone who is both mentally ill and threatening either suicide or homicide. During the era when high-capacity firearms were banned, from 1994 to 2004, mass murders decreased in our country. While most gunmen use legal firearms they have purchased, I would contend that “smart guns” – firearms that allow only the legal owner to operate them based on biometrics – would prevent some mass shootings and many accidents, crimes, and suicides. Universal background checks and tracking gun purchases in the way we monitor controlled medications, or even Sudafed, might allow authorities to predict who might be at risk of committing these heinous acts.

In his newly released book, Trigger Points: Inside the Mission to Stop Mass Murders in America, journalist Mark Follman argues for a proactive community approach using threat assessment methods and providing wraparound services to those who are deemed to be at risk for violent acts. Mr. Follman’s voice is one of the few out there saying that these events are not random and are, in fact, preventable.

In psychiatry, we struggle with school shootings such as the one we just saw in Uvalde. Our own hearts ache as we hold our children close and empathize with the loss of strangers who have been through the unthinkable. We help our patients as they process their emotions. And we wonder whether any of our patients might ever do anything so horrific. The feelings get complicated, the sadness and anger intermingle while the frustration builds, and we are left with our fears and the hope that if that very rare person were to walk through our office door, we would know what to do.

Dr. Miller is a coauthor of Committed: The Battle Over Involuntary Psychiatric Care (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. A version of this article first appeared on Medscape.com.

Here we go again, and again, and again.

There just aren’t enough tears, and before the bodies of 19 small children are identified, the political noise starts up. Mass shootings are a part of the American landscape, but when they happen at schools, we all feel a distinct sense of violation and gaping grief. Those children are so innocent, so deserving of a right to live their lives, hold their place with their families, create their own legacies, and die of natural causes at a ripe old age. And those children could have been our children. There was nothing special about them; they were just sent to school that day like every child who is sent to school every day.

Here is how the politics goes: The Republicans will blame the Democrats and the Democrats will blame the Republicans. Is Rachel Maddow at fault, or is it Tucker Carlson? Social media accounts blamed both of them for the racially motivated mass murder in a Buffalo grocery store on May 14.

Mass murders were previously defined as a shooting where four or more victims are killed, excluding the shooter, in a public place that is not related to the commission of another crime. In 2012, the definition was changed to include events with three victims. This definition excludes gang violence and the murder of family members.

When it comes to explaining mass murder, the camps divide: They are the result of some combination of mental illness, easy access to firearms, and terrorism and hate. For psychiatry, there is a unique place in the argument – half of all mass shooters have exhibited signs or symptoms of psychiatric illness, and for those who want to deflect the issue away from issues related to the regulation of firearms, it becomes easy to blame “mental illness,” as though that explains it all. Either the gunman “snapped” in such a way that no one could have predicted, or the mental health system is at fault for not preventing it.

There are many ways to be emotionally disturbed; mental illness is only one of them, and there is no psychiatric diagnosis that includes the symptom of shooting strangers, or shooting children. The vast majority of people, including nearly all psychiatrists, will never know someone who perpetrates a mass shooting. 

Can mental illness give us any insight into these senseless killings? Sometimes, but rarely. Take John Hinckley Jr., who shot President Ronald Reagan as a means to impress actress Jodie Foster. Sometimes these killings are motivated by delusional beliefs. But the planning and preparation that goes into most mass shootings involves a degree of organization and forethought that we don’t typically see in those with severe psychotic disorders.

The other psychological explanation that satisfies some of a nonmedical population is that these killers “just snap.” This, too, is a term that is not included in our diagnostic vocabulary, but it remains a way for some to explain that which can’t be explained. If mental illness, however, is the cause of mass murders, then more stringent gun control is unnecessary. Every state already has a mechanism to prevent those with criminal and specified psychiatric histories from buying legal firearms, and it may be inevitable that these screens are not perfect. 

The next line of political thinking moves to the psychiatric “if only.” If only there were more state hospital beds and if only it were easier to compel people with psychiatric disorders to get treatment against their will, then we could eliminate these crimes. The Virginia tech shooter was mandated to get outpatient psychiatric treatment after a brief hospitalization, yet he never went and there was no mechanism in place to track him.

In cases where a person with a psychotic illness has a history of repeated violent episodes after stopping medications, it does make sense to mandate treatment, not because they are likely to shoot strangers, but because some people do become violent when they are ill and mental illness is believed to play a role in 10% of murders.

Mass murders remain rare, and while advocates for legislation that would make it easier to mandate involuntary care have cited violence prevention as a reason, it is hard to imagine that we would force people to get care because they “might” commit such a crime – unless there was convincing evidence that someone was at risk of committing such a heinous act.

For those who oppose stronger gun control laws, the “what if” may circulate around the need for even more firearms. What if teachers carried guns? What if schools were more heavily policed? What if the criminals were made to be afraid?

We are left with the fact that other countries do not see these numbers of mass shooting events, yet mental illness is ubiquitous. While the presence of psychiatric disorders does little to explain school shootings, we still have no understanding of what motivated the Sandy Hook killer, and it remains to be seen what we will come to understand about the gunman in Uvalde, Texas.

Mental illness is not unique to the United States; however, the number of available firearms is. In a country of 323 million people (including children and people who live in institutions where they have no access to firearms), there are estimated to be over 400 million guns in the United States, 98% of which are owned by civilians. 

Hate crimes and terrorism are another explanation for mass murders. In these instances, the gunman makes his motive obvious: There are social media announcements, or the site of the shooting is a synagogue, a mosque, or a location where the victims are of a specific race or religion. But hate may come out of a psychotic illness, and easy access to firearms allows for these crimes to continue. 

Firearms are now the No. 1 cause of mortality in children. Very few of these deaths are the result of mass murders. Many more are from accidental deaths, targeted crime, or suicide. Still, school shootings rip at our hearts. Neither the victims nor their grieving families have any role in the act, and suffering leaves its mark on families, communities, and all of us.
 

Are there answers?

In many states, physicians can now request emergency removal of firearms from the home of someone who is both mentally ill and threatening either suicide or homicide. During the era when high-capacity firearms were banned, from 1994 to 2004, mass murders decreased in our country. While most gunmen use legal firearms they have purchased, I would contend that “smart guns” – firearms that allow only the legal owner to operate them based on biometrics – would prevent some mass shootings and many accidents, crimes, and suicides. Universal background checks and tracking gun purchases in the way we monitor controlled medications, or even Sudafed, might allow authorities to predict who might be at risk of committing these heinous acts.

In his newly released book, Trigger Points: Inside the Mission to Stop Mass Murders in America, journalist Mark Follman argues for a proactive community approach using threat assessment methods and providing wraparound services to those who are deemed to be at risk for violent acts. Mr. Follman’s voice is one of the few out there saying that these events are not random and are, in fact, preventable.

In psychiatry, we struggle with school shootings such as the one we just saw in Uvalde. Our own hearts ache as we hold our children close and empathize with the loss of strangers who have been through the unthinkable. We help our patients as they process their emotions. And we wonder whether any of our patients might ever do anything so horrific. The feelings get complicated, the sadness and anger intermingle while the frustration builds, and we are left with our fears and the hope that if that very rare person were to walk through our office door, we would know what to do.

Dr. Miller is a coauthor of Committed: The Battle Over Involuntary Psychiatric Care (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. A version of this article first appeared on Medscape.com.

“It must be mental illness. My mind cannot possibly conceive of an alternative. A rational healthy mind cannot be capable of this, Doc.”

These were the opening words of one of many discussions that I had with patients in the wake of yet another gut-wrenching tragedy where we saw innocent children and their teachers murdered in school.

Courtesy of Mena Mirhom

Do any mass shooters have untreated mental illness?

There are data to suggest that of 14,785 murders studied in a database to track death by guns, 1,315 mass shootings were identified. Of these mass shootings, 11% of the shooters had serious mental illness. Could we have diagnosed those cases earlier? Intervened sooner? Offered more effective treatment? Certainly. Would that have explain away the rest of the cases? Unfortunately, no.

What is it, then?

The scary answer is that the people who are capable of doing this are not so far away. They are not the folks that we would image locking up in a “psych ward” and throwing away the key. They are, rather, people who are lonely, neglected, rejected, bullied, and broken down by life. Anger, hatred, racism, and evil may be ailments of the soul, but they are not mental illnesses. The carnage they produce is just as tangible. As a psychiatrist, I must admit to you that I do not have a good medication to treat these manifestations of the human condition.

What do we do as a society?

Gun reform is the first obvious and essential answer, without which little else is truly as impactful. We must advocate for it and fight tirelessly.

But at the time you will read this article, your disgruntled coworker will be able to walk into a local store in a moment of despair, anguish, and hopelessness and purchase a semiautomatic weapon of war.

What if we were to start seeing, as a society, that our lives are interwoven? What if we saw that our health is truly interdependent? The COVID-19 pandemic shattered many things in our lives, but one element in particular is our radical individualism. We saw that the choices you make certainly affect me and vice versa. We saw that public health is just that – a public matter, not a private one. We saw that there are some areas of our lives that force us to come together for our own survival.

Perhaps politicians will not save us here. Perhaps kindness will. Empathy can be as potent as legislation, and compassion as impactful as a Twitter hashtag. We each know a lonely coworker, an isolated neighbor, a bullied student, or someone beaten down by life.

What if some of the prevention is in fact in our hands? Together.

“Darkness cannot drive out darkness. Only light can do that. Hate cannot drive out hate; only love can do that.” – Reverend Dr. Martin Luther King, Jr.

Mena Mirhom, MD, is an assistant professor of psychiatry at Columbia University and teaches writing to public psychiatry fellows. He is a board-certified psychiatrist and a consultant for the National Basketball Players Association, treating NBA players and staff.

A version of this article first appeared on Medscape.com.

“It must be mental illness. My mind cannot possibly conceive of an alternative. A rational healthy mind cannot be capable of this, Doc.”

These were the opening words of one of many discussions that I had with patients in the wake of yet another gut-wrenching tragedy where we saw innocent children and their teachers murdered in school.

Courtesy of Mena Mirhom

Do any mass shooters have untreated mental illness?

There are data to suggest that of 14,785 murders studied in a database to track death by guns, 1,315 mass shootings were identified. Of these mass shootings, 11% of the shooters had serious mental illness. Could we have diagnosed those cases earlier? Intervened sooner? Offered more effective treatment? Certainly. Would that have explain away the rest of the cases? Unfortunately, no.

What is it, then?

The scary answer is that the people who are capable of doing this are not so far away. They are not the folks that we would image locking up in a “psych ward” and throwing away the key. They are, rather, people who are lonely, neglected, rejected, bullied, and broken down by life. Anger, hatred, racism, and evil may be ailments of the soul, but they are not mental illnesses. The carnage they produce is just as tangible. As a psychiatrist, I must admit to you that I do not have a good medication to treat these manifestations of the human condition.

What do we do as a society?

Gun reform is the first obvious and essential answer, without which little else is truly as impactful. We must advocate for it and fight tirelessly.

But at the time you will read this article, your disgruntled coworker will be able to walk into a local store in a moment of despair, anguish, and hopelessness and purchase a semiautomatic weapon of war.

What if we were to start seeing, as a society, that our lives are interwoven? What if we saw that our health is truly interdependent? The COVID-19 pandemic shattered many things in our lives, but one element in particular is our radical individualism. We saw that the choices you make certainly affect me and vice versa. We saw that public health is just that – a public matter, not a private one. We saw that there are some areas of our lives that force us to come together for our own survival.

Perhaps politicians will not save us here. Perhaps kindness will. Empathy can be as potent as legislation, and compassion as impactful as a Twitter hashtag. We each know a lonely coworker, an isolated neighbor, a bullied student, or someone beaten down by life.

What if some of the prevention is in fact in our hands? Together.

“Darkness cannot drive out darkness. Only light can do that. Hate cannot drive out hate; only love can do that.” – Reverend Dr. Martin Luther King, Jr.

Mena Mirhom, MD, is an assistant professor of psychiatry at Columbia University and teaches writing to public psychiatry fellows. He is a board-certified psychiatrist and a consultant for the National Basketball Players Association, treating NBA players and staff.

A version of this article first appeared on Medscape.com.

“It must be mental illness. My mind cannot possibly conceive of an alternative. A rational healthy mind cannot be capable of this, Doc.”

These were the opening words of one of many discussions that I had with patients in the wake of yet another gut-wrenching tragedy where we saw innocent children and their teachers murdered in school.

Courtesy of Mena Mirhom

Do any mass shooters have untreated mental illness?

There are data to suggest that of 14,785 murders studied in a database to track death by guns, 1,315 mass shootings were identified. Of these mass shootings, 11% of the shooters had serious mental illness. Could we have diagnosed those cases earlier? Intervened sooner? Offered more effective treatment? Certainly. Would that have explain away the rest of the cases? Unfortunately, no.

What is it, then?

The scary answer is that the people who are capable of doing this are not so far away. They are not the folks that we would image locking up in a “psych ward” and throwing away the key. They are, rather, people who are lonely, neglected, rejected, bullied, and broken down by life. Anger, hatred, racism, and evil may be ailments of the soul, but they are not mental illnesses. The carnage they produce is just as tangible. As a psychiatrist, I must admit to you that I do not have a good medication to treat these manifestations of the human condition.

What do we do as a society?

Gun reform is the first obvious and essential answer, without which little else is truly as impactful. We must advocate for it and fight tirelessly.

But at the time you will read this article, your disgruntled coworker will be able to walk into a local store in a moment of despair, anguish, and hopelessness and purchase a semiautomatic weapon of war.

What if we were to start seeing, as a society, that our lives are interwoven? What if we saw that our health is truly interdependent? The COVID-19 pandemic shattered many things in our lives, but one element in particular is our radical individualism. We saw that the choices you make certainly affect me and vice versa. We saw that public health is just that – a public matter, not a private one. We saw that there are some areas of our lives that force us to come together for our own survival.

Perhaps politicians will not save us here. Perhaps kindness will. Empathy can be as potent as legislation, and compassion as impactful as a Twitter hashtag. We each know a lonely coworker, an isolated neighbor, a bullied student, or someone beaten down by life.

What if some of the prevention is in fact in our hands? Together.

“Darkness cannot drive out darkness. Only light can do that. Hate cannot drive out hate; only love can do that.” – Reverend Dr. Martin Luther King, Jr.

Mena Mirhom, MD, is an assistant professor of psychiatry at Columbia University and teaches writing to public psychiatry fellows. He is a board-certified psychiatrist and a consultant for the National Basketball Players Association, treating NBA players and staff.

A version of this article first appeared on Medscape.com.

A 75-year-old male is seen in the emergency department for shortness of breath. D-dimer is very high, and a CT scan chest reveals bilateral pulmonary emboli without right heart strain. He is admitted and started on enoxaparin 1 mg/kg subcutaneously every 12 hours.

By the next morning, he is feeling better and wants to discuss discharge to home and follow-up plans.

Two months ago he presented with abdominal pain and evaluation revealed he had a pancreatic head mass with liver metastases. A liver biopsy was positive for adenocarcinoma consistent with pancreas primary. CA 19-9 level was 1,200 U/mL and he was started on FOLFIRINOX chemotherapy – which he has tolerated well thus far. CA 19-9 and follow-up CT scan show early response to chemotherapy.

Of course, this case raises many questions. Given how successful some directed biomarker-positive therapies are now, you would want to know his microsatellite instability (MSI)/progressive death–ligand 1 (PD-L1) and BRCA mutation status. A high PD-L1 positivity or MSI deficiency would suggest immunoantibody therapy and a BRCA mutation might suggest a poly (ADP-ribose) polymerase inhibitor could play a role.

However, let’s use this case to discuss his venous thromboembolism (VTE) .

Studies show that metastatic cancer patients on chemotherapy might experience a VTE episode of deep vein thrombosis (DVT) or pulmonary embolism (PE) or both as high as 20% of the time during their cancer course and therapy. This patient would be among those who experience the highest incidence of VTE because of the liver metastasis from the pancreatic adenocarcinoma.

So, what to do? Standard treatment of his pulmonary emboli would include either enoxaparin therapeutic dosing 1 mg/kg subcutaneously q12H or 1.5 mg/kg q24H for 3 months. At 3 months, repeat a CT chest scan to show resolution of pulmonary emboli and/or DVT or both, and repeat D-dimer, which should now be well under 1.

But then, there is a second decision to make: Can you stop anticoagulation if his clots have resolved? The answer is yes. If the clots were provoked and the provoking feature is gone you can stop anticoagulation. Patients with pregnancy, on a birth control pill, or on a long trip where immobilization occurred for a extended time (such as driving or flying) can have anticoagulation stopped because the provoking feature is gone, but this is not true in this case. This patient’s pancreas cancer and chemotherapy are ongoing and he will be at increased risk to clot once again if anticoagulation is stopped.

Should this patient have a hypercoagulable workup which might include protein C, protein S, and antithrombin levels? Remember this is quite rare and patients with these deficiencies usually present in their teens or 20s with increased clotting issues. The more common hypercoagulable workup would include checking for factor V Leiden and prothrombin G20210A mutations, as well as acquired antiphospholipid antibodies such as beta₂ glycoprotein I, anticardiolipin, and the lupus inhibitor. However, in this 75-year-old cancer patient, these are not necessary or even relevant since his VTE was clearly provoked by metastatic cancer on chemotherapy.

Unfortunately, with metastatic active cancer, anticoagulation would need to be continued at full or possibly half therapeutic dose. Of course, enoxaparin injections can get tiresome for the patient and data suggest the same result can be achieved either with initial management or by continuing anticoagulation management using either rivaroxaban or apixaban.

Wouldn’t it have been better if this patient had never experienced VTE in the first place? Is that possible?

Yes, data suggest that it is. Higher-risk patients like this one could benefit from prophylactic anticoagulation. The Khorana predictive model gives us a simple clinical means to evaluate this and decide who might be at highest VTE risk and who could benefit from low-dose preventive anticoagulation.

In summary, cancer patients undergoing treatment for metastatic disease are at increased risk for symptomatic VTE. Once diagnosed, therapy is usually very effective, but may need to be prolonged as long as the cancer is still active or else, the VTE could recur. Preventive therapy for high-risk patients would be reasonable.

Dr. Henry is a medical oncologist with the Abramson Cancer Center at the University of Pennsylvania, Philadelphia.

A 75-year-old male is seen in the emergency department for shortness of breath. D-dimer is very high, and a CT scan chest reveals bilateral pulmonary emboli without right heart strain. He is admitted and started on enoxaparin 1 mg/kg subcutaneously every 12 hours.

By the next morning, he is feeling better and wants to discuss discharge to home and follow-up plans.

Two months ago he presented with abdominal pain and evaluation revealed he had a pancreatic head mass with liver metastases. A liver biopsy was positive for adenocarcinoma consistent with pancreas primary. CA 19-9 level was 1,200 U/mL and he was started on FOLFIRINOX chemotherapy – which he has tolerated well thus far. CA 19-9 and follow-up CT scan show early response to chemotherapy.

Of course, this case raises many questions. Given how successful some directed biomarker-positive therapies are now, you would want to know his microsatellite instability (MSI)/progressive death–ligand 1 (PD-L1) and BRCA mutation status. A high PD-L1 positivity or MSI deficiency would suggest immunoantibody therapy and a BRCA mutation might suggest a poly (ADP-ribose) polymerase inhibitor could play a role.

However, let’s use this case to discuss his venous thromboembolism (VTE) .

Studies show that metastatic cancer patients on chemotherapy might experience a VTE episode of deep vein thrombosis (DVT) or pulmonary embolism (PE) or both as high as 20% of the time during their cancer course and therapy. This patient would be among those who experience the highest incidence of VTE because of the liver metastasis from the pancreatic adenocarcinoma.

So, what to do? Standard treatment of his pulmonary emboli would include either enoxaparin therapeutic dosing 1 mg/kg subcutaneously q12H or 1.5 mg/kg q24H for 3 months. At 3 months, repeat a CT chest scan to show resolution of pulmonary emboli and/or DVT or both, and repeat D-dimer, which should now be well under 1.

But then, there is a second decision to make: Can you stop anticoagulation if his clots have resolved? The answer is yes. If the clots were provoked and the provoking feature is gone you can stop anticoagulation. Patients with pregnancy, on a birth control pill, or on a long trip where immobilization occurred for a extended time (such as driving or flying) can have anticoagulation stopped because the provoking feature is gone, but this is not true in this case. This patient’s pancreas cancer and chemotherapy are ongoing and he will be at increased risk to clot once again if anticoagulation is stopped.

Should this patient have a hypercoagulable workup which might include protein C, protein S, and antithrombin levels? Remember this is quite rare and patients with these deficiencies usually present in their teens or 20s with increased clotting issues. The more common hypercoagulable workup would include checking for factor V Leiden and prothrombin G20210A mutations, as well as acquired antiphospholipid antibodies such as beta₂ glycoprotein I, anticardiolipin, and the lupus inhibitor. However, in this 75-year-old cancer patient, these are not necessary or even relevant since his VTE was clearly provoked by metastatic cancer on chemotherapy.

Unfortunately, with metastatic active cancer, anticoagulation would need to be continued at full or possibly half therapeutic dose. Of course, enoxaparin injections can get tiresome for the patient and data suggest the same result can be achieved either with initial management or by continuing anticoagulation management using either rivaroxaban or apixaban.

Wouldn’t it have been better if this patient had never experienced VTE in the first place? Is that possible?

Yes, data suggest that it is. Higher-risk patients like this one could benefit from prophylactic anticoagulation. The Khorana predictive model gives us a simple clinical means to evaluate this and decide who might be at highest VTE risk and who could benefit from low-dose preventive anticoagulation.

In summary, cancer patients undergoing treatment for metastatic disease are at increased risk for symptomatic VTE. Once diagnosed, therapy is usually very effective, but may need to be prolonged as long as the cancer is still active or else, the VTE could recur. Preventive therapy for high-risk patients would be reasonable.

Dr. Henry is a medical oncologist with the Abramson Cancer Center at the University of Pennsylvania, Philadelphia.

A 75-year-old male is seen in the emergency department for shortness of breath. D-dimer is very high, and a CT scan chest reveals bilateral pulmonary emboli without right heart strain. He is admitted and started on enoxaparin 1 mg/kg subcutaneously every 12 hours.

By the next morning, he is feeling better and wants to discuss discharge to home and follow-up plans.

Two months ago he presented with abdominal pain and evaluation revealed he had a pancreatic head mass with liver metastases. A liver biopsy was positive for adenocarcinoma consistent with pancreas primary. CA 19-9 level was 1,200 U/mL and he was started on FOLFIRINOX chemotherapy – which he has tolerated well thus far. CA 19-9 and follow-up CT scan show early response to chemotherapy.

Of course, this case raises many questions. Given how successful some directed biomarker-positive therapies are now, you would want to know his microsatellite instability (MSI)/progressive death–ligand 1 (PD-L1) and BRCA mutation status. A high PD-L1 positivity or MSI deficiency would suggest immunoantibody therapy and a BRCA mutation might suggest a poly (ADP-ribose) polymerase inhibitor could play a role.

However, let’s use this case to discuss his venous thromboembolism (VTE) .

Studies show that metastatic cancer patients on chemotherapy might experience a VTE episode of deep vein thrombosis (DVT) or pulmonary embolism (PE) or both as high as 20% of the time during their cancer course and therapy. This patient would be among those who experience the highest incidence of VTE because of the liver metastasis from the pancreatic adenocarcinoma.

So, what to do? Standard treatment of his pulmonary emboli would include either enoxaparin therapeutic dosing 1 mg/kg subcutaneously q12H or 1.5 mg/kg q24H for 3 months. At 3 months, repeat a CT chest scan to show resolution of pulmonary emboli and/or DVT or both, and repeat D-dimer, which should now be well under 1.

But then, there is a second decision to make: Can you stop anticoagulation if his clots have resolved? The answer is yes. If the clots were provoked and the provoking feature is gone you can stop anticoagulation. Patients with pregnancy, on a birth control pill, or on a long trip where immobilization occurred for a extended time (such as driving or flying) can have anticoagulation stopped because the provoking feature is gone, but this is not true in this case. This patient’s pancreas cancer and chemotherapy are ongoing and he will be at increased risk to clot once again if anticoagulation is stopped.

Should this patient have a hypercoagulable workup which might include protein C, protein S, and antithrombin levels? Remember this is quite rare and patients with these deficiencies usually present in their teens or 20s with increased clotting issues. The more common hypercoagulable workup would include checking for factor V Leiden and prothrombin G20210A mutations, as well as acquired antiphospholipid antibodies such as beta₂ glycoprotein I, anticardiolipin, and the lupus inhibitor. However, in this 75-year-old cancer patient, these are not necessary or even relevant since his VTE was clearly provoked by metastatic cancer on chemotherapy.

Unfortunately, with metastatic active cancer, anticoagulation would need to be continued at full or possibly half therapeutic dose. Of course, enoxaparin injections can get tiresome for the patient and data suggest the same result can be achieved either with initial management or by continuing anticoagulation management using either rivaroxaban or apixaban.

Wouldn’t it have been better if this patient had never experienced VTE in the first place? Is that possible?

Yes, data suggest that it is. Higher-risk patients like this one could benefit from prophylactic anticoagulation. The Khorana predictive model gives us a simple clinical means to evaluate this and decide who might be at highest VTE risk and who could benefit from low-dose preventive anticoagulation.

In summary, cancer patients undergoing treatment for metastatic disease are at increased risk for symptomatic VTE. Once diagnosed, therapy is usually very effective, but may need to be prolonged as long as the cancer is still active or else, the VTE could recur. Preventive therapy for high-risk patients would be reasonable.

Dr. Henry is a medical oncologist with the Abramson Cancer Center at the University of Pennsylvania, Philadelphia.

As Usha Lee McFarling has pointed out, the orthopedic surgeon specialty suffers from a gross underrepresentation of minorities and women, more severe than in other medical specialties. There are various reasons for this and a variety of possible paths toward improvement, but the “critical first step,” as American Academy of Orthopedic Surgeons former president Kristy Weber, MD, told Ms. McFarling, “is changing the culture.”

“Changing the culture” is a large, diffuse aspiration. The AAOS has taken a number of steps toward that end, but they have not had much success. The two of us have identified others, which may help to move the needle. But any approach to resolving this stubbornly resistant racial and gender imbalance requires, first of all, an understanding of the psychological and neurobiological roots that underlie it.

Viewed from this perspective, the cultural barriers to inclusivity are similar to those that perpetuate inequitable health care. Both are driven by ingroup/outgroup prejudices that operate below the level of consciousness and are largely unseen.In our book Seeing Patients, we examined health disparities in six “non-mainstream” groups: African Americans, Hispanic Americans, women, gays and lesbians, and the elderly. We based our work initially on the Institute of Medicine’s breakthrough 2003 compendium, Unequal Treatment, which brought together a large number of studies on health care inequities that had appeared in a variety of journals over many years, but had never generated the critical mass necessary to create a call for action or even attract serious attention.

Unequal Treatment allowed us to understand that each medical specialty, right down the line – orthopedics, cardiology, gynecology, oncology, psychiatry, to name just a few – has its own grim history of discrimination. Our sense of the medical community in the 21st century led us away from the idea that overt bias is a significant cause of these still ongoing inequities. Most physicians, we believed, consider themselves to be, and strive to be, humane, compassionate, and egalitarian caregivers. The answer then seemed to be in subconscious rather than conscious bias.

As we reviewed the literature and strove to understand the primary drivers of the discrimination that systematically affects medical care, our attention was drawn to two critical and complementary mechanisms hard-wired into our systems for parsing and responding to our environment. The first was “stereotyping,” so often used as a pejorative, but which is, in fact, a primary and essential mental function.

“We all make stereotypic judgments,” says Rice University emeritus professor of psychology David Schneider in The Psychology of Stereotyping (page 419). “It happens with race. It happens with disability. It happens ... with gender, age, and physical appearance. ... That’s just the way it is: Our mental apparatus was designed to facilitate quick decisions based on category membership.”

Differentiation – social stereotyping in our case – is a given, then; it’s innate. The content of stereotyping – of Blacks, gays, women, and others – is not innate, but it is deeply ingrained by living in a given milieu and just as impossible to ignore.

The second mechanism we focused on was the neurobiology that underlies the impact of hidden emotion on rational thought. In his seminal book Descartes’ Error, neuroscientist Antonio Damasio spells out how the mind with its cognitive functions has evolved from the body and its emotional systems, and how they function together through neuro-networks that connect the mechanisms of feeling with the brain’s decision-making centers.

“Feelings,” Dr. Damasio tells us, “come first in [brain] development and retain a primacy that pervades our mental life.” The limbic system, the part of the brain that controls our emotional responses, constitutes a “frame of reference and has “a say on how the rest of the brain and cognition go about their business. [Its] influence is immense.” (Page 185)

Dr. Damasio was not focusing on medical decisions, but his insights, we felt, had great relevance for the question of unconscious bias in health care. Various studies by physicians and medical scientists do speak directly to the issue of how affective bias influences diagnosis and treatment. Pat Croskerry, director of Dalhousie University’s Clinical Research Center, argues that “cognitive and affective biases are known to compromise the decision-making” and that commonly “these are largely unconscious mistakes.”

Harvard’s Jerome Groopman, in his book How Doctors Think (page 40), writes that most incorrect diagnoses and treatments are “mistakes in thinking. And part of what causes these cognitive errors is our inner feelings, feelings we ... often don’t even recognize.” Cognition and emotion, Dr. Groopman insists, are inseparable. The emotional landscape sets the ground for decision-making.

The underlying mechanisms that enable health care prejudice are the same that enable interpersonal prejudice generally. Unseen and largely unrecognized, they affect ingroup/outgroup relations in every field of interaction, from bias in policing, to bias in housing, to bias in employment – “powerful and universal,” in Dr. Croskerry’s words, “affecting all walks of life.”

Decision-making about acceptance into orthopedic residencies is no exception. As Prof. Schneider says, “That’s just the way it is.”

What conclusions can be drawn from understanding the deep origins of subconscious bias that might improve the inclusion of minorities and women in orthopedics? A growing interest in “debiasing” in both the medical and cognitive psychology literature has identified or suggested methods of counteracting the prejudices we all harbor. (See Bhatti’s “Cognitive Bias in Clinical Practice,” Wilson and Brekke’s “Mental Contamination and Mental Correction: Unwanted Influences on Judgments and Evaluations,” and De Neys and colleagues’ “Feeling We’re Biased: Autonomic Arousal and Reasoning Conflict.”)

Many of these debiasing techniques have to do with education regarding cognitive functions, from training in decision-making processes to “time outs,” to checklists à la Atul Gawande, to other methods of metacognition.

But the two key prerequisites to all of these approaches are more or less self-evident. “For biases to be successfully addressed,” says Dr. Croskerry, “there needs to be ... awareness as well as the motivation for change.”

In a previous article we discussed the need to heighten awareness over and above current levels, and we have suggested steps toward that end. But awareness is only the first prerequisite; the second is motivation, and the depth of motivation necessary to create change in the business of orthopedic inclusion is, for all the AAOS’s efforts, simply inadequate – the result being that the culture does not change, or it changes so glacially as to be hardly noticeable.

Ms. McFarling noted in her interviews with orthopedic leaders, clinicians, residents, and medical students simmering feelings of frustration and perplexity. We would suggest that the frustration is because of the fact that, while there is a general awareness of the problem, there has simply not been the sufficiently determined motivation to fix it. “It is not neglected truths,” as religious scholar Gregory Dix put it, “but those that are at once fully acknowledged and frustrated of their proper expression, which take the most drastic psychological revenge.”

All of this leads back to the original problem posed by Prof. Weber, the former AAOS president: changing the orthopedic culture. The question of how cultures undergo transformation has been addressed by scholars across widely diverse fields (see, for example, Thomas Kuhn’s The Structure of Scientific Revolutions, Francis Fukuyama›s The End of History and the Last Man, and many others). But we are addressing here a narrow, well-defined slice of that problem. And our own explorations have led to the conclusion that the answer here lies in the issue of motivation – namely, how can a community that is aware of a problem be sufficiently motivated to fix it?

In Seeing Patients we argued that doctoring is the paradigmatic humanitarian profession, that physicians’ whole business is to care for and alleviate the suffering of other human beings. In this sense, doctors are the carriers of the humane ideal, which is congruent also with the noblest egalitarian principles of our life as a nation. We argued also that humanitarian medicine with its egalitarian mandate is a win-win-win proposition. The patient wins, the doctor wins, the society wins.

We think arguments like these should provide plenty of motivation for change. But in reality they are not sufficient. Our arguments and those of others along the same lines (see Louis Sullivan’s Breaking Ground and David McBride’s Caring for Equality) are directed for the most part at the better angels of our nature. They appeal to personal and political values: compassion, fairness, equality – powerful yet set against custom, habituation, and the daily pressures of practice, such arguments can and do easily come up short.

But when looked at straight on, with unblinking eyes, health care disparities should provoke other more forceful emotions: anger, to begin with; chagrin, consternation. Women receive fewer heart catheterizations and reperfusions than men. (See R. Di Cecco and colleagues’ “Is There a Clinically Significant Gender Bias in Post-Myocardial Infarction Pharmacological Management in the Older Population of a Primary Care Practice?” and Jneid and coworkers’ “Sex Difference in Medical Care and Early Death after Acute Myocardial Infarction.”) Because of this, more women die.

Blacks and Hispanics receive fewer analgesics for the excruciating pain of broken bones, and they are amputated more frequently than whites for identical peripheral arterial disease. (See Knox and colleagues’ “Ethnicity as a Risk Factor for Inadequate Emergency Department Analgesia,” Bonham’s “Race, Ethnicity and Pain Treatments: Striving to Understand the Causes and Solutions to the Disparities in Pain Treatments,” and Feinglass and coworkers’ “Racial Differences in Primary and Repeat Lower Extremity Amputation: Results From a Multihospital Study.”) They suffer accordingly.

The statistical accounting of these disparities masks the faces of pain and desperation – of disabilities, often of mortality. These are hard visceral truths that derive in part from the underrepresentation of minorities in various specialties, most pronounced in orthopedics. These are the truths that, when actually absorbed rather than just registered, have the capacity to transform awareness into motivation and in so doing can begin reshaping a culture that restricts minorities and women and makes orthopedics, as Ms. McFarling calls it, “the whitest specialty.”

A version of this article first appeared on Medscape.com.

As Usha Lee McFarling has pointed out, the orthopedic surgeon specialty suffers from a gross underrepresentation of minorities and women, more severe than in other medical specialties. There are various reasons for this and a variety of possible paths toward improvement, but the “critical first step,” as American Academy of Orthopedic Surgeons former president Kristy Weber, MD, told Ms. McFarling, “is changing the culture.”

“Changing the culture” is a large, diffuse aspiration. The AAOS has taken a number of steps toward that end, but they have not had much success. The two of us have identified others, which may help to move the needle. But any approach to resolving this stubbornly resistant racial and gender imbalance requires, first of all, an understanding of the psychological and neurobiological roots that underlie it.

Viewed from this perspective, the cultural barriers to inclusivity are similar to those that perpetuate inequitable health care. Both are driven by ingroup/outgroup prejudices that operate below the level of consciousness and are largely unseen.In our book Seeing Patients, we examined health disparities in six “non-mainstream” groups: African Americans, Hispanic Americans, women, gays and lesbians, and the elderly. We based our work initially on the Institute of Medicine’s breakthrough 2003 compendium, Unequal Treatment, which brought together a large number of studies on health care inequities that had appeared in a variety of journals over many years, but had never generated the critical mass necessary to create a call for action or even attract serious attention.

Unequal Treatment allowed us to understand that each medical specialty, right down the line – orthopedics, cardiology, gynecology, oncology, psychiatry, to name just a few – has its own grim history of discrimination. Our sense of the medical community in the 21st century led us away from the idea that overt bias is a significant cause of these still ongoing inequities. Most physicians, we believed, consider themselves to be, and strive to be, humane, compassionate, and egalitarian caregivers. The answer then seemed to be in subconscious rather than conscious bias.

As we reviewed the literature and strove to understand the primary drivers of the discrimination that systematically affects medical care, our attention was drawn to two critical and complementary mechanisms hard-wired into our systems for parsing and responding to our environment. The first was “stereotyping,” so often used as a pejorative, but which is, in fact, a primary and essential mental function.

“We all make stereotypic judgments,” says Rice University emeritus professor of psychology David Schneider in The Psychology of Stereotyping (page 419). “It happens with race. It happens with disability. It happens ... with gender, age, and physical appearance. ... That’s just the way it is: Our mental apparatus was designed to facilitate quick decisions based on category membership.”

Differentiation – social stereotyping in our case – is a given, then; it’s innate. The content of stereotyping – of Blacks, gays, women, and others – is not innate, but it is deeply ingrained by living in a given milieu and just as impossible to ignore.

The second mechanism we focused on was the neurobiology that underlies the impact of hidden emotion on rational thought. In his seminal book Descartes’ Error, neuroscientist Antonio Damasio spells out how the mind with its cognitive functions has evolved from the body and its emotional systems, and how they function together through neuro-networks that connect the mechanisms of feeling with the brain’s decision-making centers.

“Feelings,” Dr. Damasio tells us, “come first in [brain] development and retain a primacy that pervades our mental life.” The limbic system, the part of the brain that controls our emotional responses, constitutes a “frame of reference and has “a say on how the rest of the brain and cognition go about their business. [Its] influence is immense.” (Page 185)

Dr. Damasio was not focusing on medical decisions, but his insights, we felt, had great relevance for the question of unconscious bias in health care. Various studies by physicians and medical scientists do speak directly to the issue of how affective bias influences diagnosis and treatment. Pat Croskerry, director of Dalhousie University’s Clinical Research Center, argues that “cognitive and affective biases are known to compromise the decision-making” and that commonly “these are largely unconscious mistakes.”

Harvard’s Jerome Groopman, in his book How Doctors Think (page 40), writes that most incorrect diagnoses and treatments are “mistakes in thinking. And part of what causes these cognitive errors is our inner feelings, feelings we ... often don’t even recognize.” Cognition and emotion, Dr. Groopman insists, are inseparable. The emotional landscape sets the ground for decision-making.

The underlying mechanisms that enable health care prejudice are the same that enable interpersonal prejudice generally. Unseen and largely unrecognized, they affect ingroup/outgroup relations in every field of interaction, from bias in policing, to bias in housing, to bias in employment – “powerful and universal,” in Dr. Croskerry’s words, “affecting all walks of life.”

Decision-making about acceptance into orthopedic residencies is no exception. As Prof. Schneider says, “That’s just the way it is.”

What conclusions can be drawn from understanding the deep origins of subconscious bias that might improve the inclusion of minorities and women in orthopedics? A growing interest in “debiasing” in both the medical and cognitive psychology literature has identified or suggested methods of counteracting the prejudices we all harbor. (See Bhatti’s “Cognitive Bias in Clinical Practice,” Wilson and Brekke’s “Mental Contamination and Mental Correction: Unwanted Influences on Judgments and Evaluations,” and De Neys and colleagues’ “Feeling We’re Biased: Autonomic Arousal and Reasoning Conflict.”)

Many of these debiasing techniques have to do with education regarding cognitive functions, from training in decision-making processes to “time outs,” to checklists à la Atul Gawande, to other methods of metacognition.

But the two key prerequisites to all of these approaches are more or less self-evident. “For biases to be successfully addressed,” says Dr. Croskerry, “there needs to be ... awareness as well as the motivation for change.”

In a previous article we discussed the need to heighten awareness over and above current levels, and we have suggested steps toward that end. But awareness is only the first prerequisite; the second is motivation, and the depth of motivation necessary to create change in the business of orthopedic inclusion is, for all the AAOS’s efforts, simply inadequate – the result being that the culture does not change, or it changes so glacially as to be hardly noticeable.

Ms. McFarling noted in her interviews with orthopedic leaders, clinicians, residents, and medical students simmering feelings of frustration and perplexity. We would suggest that the frustration is because of the fact that, while there is a general awareness of the problem, there has simply not been the sufficiently determined motivation to fix it. “It is not neglected truths,” as religious scholar Gregory Dix put it, “but those that are at once fully acknowledged and frustrated of their proper expression, which take the most drastic psychological revenge.”

All of this leads back to the original problem posed by Prof. Weber, the former AAOS president: changing the orthopedic culture. The question of how cultures undergo transformation has been addressed by scholars across widely diverse fields (see, for example, Thomas Kuhn’s The Structure of Scientific Revolutions, Francis Fukuyama›s The End of History and the Last Man, and many others). But we are addressing here a narrow, well-defined slice of that problem. And our own explorations have led to the conclusion that the answer here lies in the issue of motivation – namely, how can a community that is aware of a problem be sufficiently motivated to fix it?

In Seeing Patients we argued that doctoring is the paradigmatic humanitarian profession, that physicians’ whole business is to care for and alleviate the suffering of other human beings. In this sense, doctors are the carriers of the humane ideal, which is congruent also with the noblest egalitarian principles of our life as a nation. We argued also that humanitarian medicine with its egalitarian mandate is a win-win-win proposition. The patient wins, the doctor wins, the society wins.

We think arguments like these should provide plenty of motivation for change. But in reality they are not sufficient. Our arguments and those of others along the same lines (see Louis Sullivan’s Breaking Ground and David McBride’s Caring for Equality) are directed for the most part at the better angels of our nature. They appeal to personal and political values: compassion, fairness, equality – powerful yet set against custom, habituation, and the daily pressures of practice, such arguments can and do easily come up short.

But when looked at straight on, with unblinking eyes, health care disparities should provoke other more forceful emotions: anger, to begin with; chagrin, consternation. Women receive fewer heart catheterizations and reperfusions than men. (See R. Di Cecco and colleagues’ “Is There a Clinically Significant Gender Bias in Post-Myocardial Infarction Pharmacological Management in the Older Population of a Primary Care Practice?” and Jneid and coworkers’ “Sex Difference in Medical Care and Early Death after Acute Myocardial Infarction.”) Because of this, more women die.

Blacks and Hispanics receive fewer analgesics for the excruciating pain of broken bones, and they are amputated more frequently than whites for identical peripheral arterial disease. (See Knox and colleagues’ “Ethnicity as a Risk Factor for Inadequate Emergency Department Analgesia,” Bonham’s “Race, Ethnicity and Pain Treatments: Striving to Understand the Causes and Solutions to the Disparities in Pain Treatments,” and Feinglass and coworkers’ “Racial Differences in Primary and Repeat Lower Extremity Amputation: Results From a Multihospital Study.”) They suffer accordingly.

The statistical accounting of these disparities masks the faces of pain and desperation – of disabilities, often of mortality. These are hard visceral truths that derive in part from the underrepresentation of minorities in various specialties, most pronounced in orthopedics. These are the truths that, when actually absorbed rather than just registered, have the capacity to transform awareness into motivation and in so doing can begin reshaping a culture that restricts minorities and women and makes orthopedics, as Ms. McFarling calls it, “the whitest specialty.”

A version of this article first appeared on Medscape.com.

As Usha Lee McFarling has pointed out, the orthopedic surgeon specialty suffers from a gross underrepresentation of minorities and women, more severe than in other medical specialties. There are various reasons for this and a variety of possible paths toward improvement, but the “critical first step,” as American Academy of Orthopedic Surgeons former president Kristy Weber, MD, told Ms. McFarling, “is changing the culture.”

“Changing the culture” is a large, diffuse aspiration. The AAOS has taken a number of steps toward that end, but they have not had much success. The two of us have identified others, which may help to move the needle. But any approach to resolving this stubbornly resistant racial and gender imbalance requires, first of all, an understanding of the psychological and neurobiological roots that underlie it.

Viewed from this perspective, the cultural barriers to inclusivity are similar to those that perpetuate inequitable health care. Both are driven by ingroup/outgroup prejudices that operate below the level of consciousness and are largely unseen.In our book Seeing Patients, we examined health disparities in six “non-mainstream” groups: African Americans, Hispanic Americans, women, gays and lesbians, and the elderly. We based our work initially on the Institute of Medicine’s breakthrough 2003 compendium, Unequal Treatment, which brought together a large number of studies on health care inequities that had appeared in a variety of journals over many years, but had never generated the critical mass necessary to create a call for action or even attract serious attention.

Unequal Treatment allowed us to understand that each medical specialty, right down the line – orthopedics, cardiology, gynecology, oncology, psychiatry, to name just a few – has its own grim history of discrimination. Our sense of the medical community in the 21st century led us away from the idea that overt bias is a significant cause of these still ongoing inequities. Most physicians, we believed, consider themselves to be, and strive to be, humane, compassionate, and egalitarian caregivers. The answer then seemed to be in subconscious rather than conscious bias.

As we reviewed the literature and strove to understand the primary drivers of the discrimination that systematically affects medical care, our attention was drawn to two critical and complementary mechanisms hard-wired into our systems for parsing and responding to our environment. The first was “stereotyping,” so often used as a pejorative, but which is, in fact, a primary and essential mental function.

“We all make stereotypic judgments,” says Rice University emeritus professor of psychology David Schneider in The Psychology of Stereotyping (page 419). “It happens with race. It happens with disability. It happens ... with gender, age, and physical appearance. ... That’s just the way it is: Our mental apparatus was designed to facilitate quick decisions based on category membership.”

Differentiation – social stereotyping in our case – is a given, then; it’s innate. The content of stereotyping – of Blacks, gays, women, and others – is not innate, but it is deeply ingrained by living in a given milieu and just as impossible to ignore.

The second mechanism we focused on was the neurobiology that underlies the impact of hidden emotion on rational thought. In his seminal book Descartes’ Error, neuroscientist Antonio Damasio spells out how the mind with its cognitive functions has evolved from the body and its emotional systems, and how they function together through neuro-networks that connect the mechanisms of feeling with the brain’s decision-making centers.

“Feelings,” Dr. Damasio tells us, “come first in [brain] development and retain a primacy that pervades our mental life.” The limbic system, the part of the brain that controls our emotional responses, constitutes a “frame of reference and has “a say on how the rest of the brain and cognition go about their business. [Its] influence is immense.” (Page 185)

Dr. Damasio was not focusing on medical decisions, but his insights, we felt, had great relevance for the question of unconscious bias in health care. Various studies by physicians and medical scientists do speak directly to the issue of how affective bias influences diagnosis and treatment. Pat Croskerry, director of Dalhousie University’s Clinical Research Center, argues that “cognitive and affective biases are known to compromise the decision-making” and that commonly “these are largely unconscious mistakes.”

Harvard’s Jerome Groopman, in his book How Doctors Think (page 40), writes that most incorrect diagnoses and treatments are “mistakes in thinking. And part of what causes these cognitive errors is our inner feelings, feelings we ... often don’t even recognize.” Cognition and emotion, Dr. Groopman insists, are inseparable. The emotional landscape sets the ground for decision-making.

The underlying mechanisms that enable health care prejudice are the same that enable interpersonal prejudice generally. Unseen and largely unrecognized, they affect ingroup/outgroup relations in every field of interaction, from bias in policing, to bias in housing, to bias in employment – “powerful and universal,” in Dr. Croskerry’s words, “affecting all walks of life.”

Decision-making about acceptance into orthopedic residencies is no exception. As Prof. Schneider says, “That’s just the way it is.”

What conclusions can be drawn from understanding the deep origins of subconscious bias that might improve the inclusion of minorities and women in orthopedics? A growing interest in “debiasing” in both the medical and cognitive psychology literature has identified or suggested methods of counteracting the prejudices we all harbor. (See Bhatti’s “Cognitive Bias in Clinical Practice,” Wilson and Brekke’s “Mental Contamination and Mental Correction: Unwanted Influences on Judgments and Evaluations,” and De Neys and colleagues’ “Feeling We’re Biased: Autonomic Arousal and Reasoning Conflict.”)

Many of these debiasing techniques have to do with education regarding cognitive functions, from training in decision-making processes to “time outs,” to checklists à la Atul Gawande, to other methods of metacognition.

But the two key prerequisites to all of these approaches are more or less self-evident. “For biases to be successfully addressed,” says Dr. Croskerry, “there needs to be ... awareness as well as the motivation for change.”

In a previous article we discussed the need to heighten awareness over and above current levels, and we have suggested steps toward that end. But awareness is only the first prerequisite; the second is motivation, and the depth of motivation necessary to create change in the business of orthopedic inclusion is, for all the AAOS’s efforts, simply inadequate – the result being that the culture does not change, or it changes so glacially as to be hardly noticeable.

Ms. McFarling noted in her interviews with orthopedic leaders, clinicians, residents, and medical students simmering feelings of frustration and perplexity. We would suggest that the frustration is because of the fact that, while there is a general awareness of the problem, there has simply not been the sufficiently determined motivation to fix it. “It is not neglected truths,” as religious scholar Gregory Dix put it, “but those that are at once fully acknowledged and frustrated of their proper expression, which take the most drastic psychological revenge.”

All of this leads back to the original problem posed by Prof. Weber, the former AAOS president: changing the orthopedic culture. The question of how cultures undergo transformation has been addressed by scholars across widely diverse fields (see, for example, Thomas Kuhn’s The Structure of Scientific Revolutions, Francis Fukuyama›s The End of History and the Last Man, and many others). But we are addressing here a narrow, well-defined slice of that problem. And our own explorations have led to the conclusion that the answer here lies in the issue of motivation – namely, how can a community that is aware of a problem be sufficiently motivated to fix it?

In Seeing Patients we argued that doctoring is the paradigmatic humanitarian profession, that physicians’ whole business is to care for and alleviate the suffering of other human beings. In this sense, doctors are the carriers of the humane ideal, which is congruent also with the noblest egalitarian principles of our life as a nation. We argued also that humanitarian medicine with its egalitarian mandate is a win-win-win proposition. The patient wins, the doctor wins, the society wins.

We think arguments like these should provide plenty of motivation for change. But in reality they are not sufficient. Our arguments and those of others along the same lines (see Louis Sullivan’s Breaking Ground and David McBride’s Caring for Equality) are directed for the most part at the better angels of our nature. They appeal to personal and political values: compassion, fairness, equality – powerful yet set against custom, habituation, and the daily pressures of practice, such arguments can and do easily come up short.

But when looked at straight on, with unblinking eyes, health care disparities should provoke other more forceful emotions: anger, to begin with; chagrin, consternation. Women receive fewer heart catheterizations and reperfusions than men. (See R. Di Cecco and colleagues’ “Is There a Clinically Significant Gender Bias in Post-Myocardial Infarction Pharmacological Management in the Older Population of a Primary Care Practice?” and Jneid and coworkers’ “Sex Difference in Medical Care and Early Death after Acute Myocardial Infarction.”) Because of this, more women die.

Blacks and Hispanics receive fewer analgesics for the excruciating pain of broken bones, and they are amputated more frequently than whites for identical peripheral arterial disease. (See Knox and colleagues’ “Ethnicity as a Risk Factor for Inadequate Emergency Department Analgesia,” Bonham’s “Race, Ethnicity and Pain Treatments: Striving to Understand the Causes and Solutions to the Disparities in Pain Treatments,” and Feinglass and coworkers’ “Racial Differences in Primary and Repeat Lower Extremity Amputation: Results From a Multihospital Study.”) They suffer accordingly.

The statistical accounting of these disparities masks the faces of pain and desperation – of disabilities, often of mortality. These are hard visceral truths that derive in part from the underrepresentation of minorities in various specialties, most pronounced in orthopedics. These are the truths that, when actually absorbed rather than just registered, have the capacity to transform awareness into motivation and in so doing can begin reshaping a culture that restricts minorities and women and makes orthopedics, as Ms. McFarling calls it, “the whitest specialty.”

A version of this article first appeared on Medscape.com.

Air pollution is a well-established cause of morbidity and mortality. It largely comes from manmade sources such as particulate matter that arises from burning fossil fuels, which is a major contributor of greenhouse gas emissions.

Acute exposure to fine inhalable particles of as little as 2.5 mcm (PM2.5) in diameter can cause a decrease in lung function leading to respiratory and cardiovascular diseases and even death because of cardiopulmonary conditions and lung cancer.

The 2015 Global Burden of Disease study lists air pollution as the fourth highest–ranking global mortality risk factor. The World Health Organization estimated that 4.2 million deaths were caused by outdoor air pollution in 2016, and another 2.3 million from indoor air pollution.

Not all oncologists believe that air pollution is a cancer problem, but air pollution and particulate matters are carcinogens and in fact, they have been deemed level 1 carcinogens by the International Association of Research on Cancer.

The research on the link between air pollution, PM2.5 and lung cancer is robust. Numerous epidemiological studies have shown that people living in highly polluted areas are more likely to die of lung cancer than those who do not. For example, Turner and colleagues in CA: A Cancer Journal for Clinicians performed a Cox proportional hazard regression model adjusting for numerous variables – smoking, passive smoking, occupational exposures (asbestos, coal dust, diesel engine exhaust, etc.), an occupational “dirtiness” index, radon exposure, among others – and found a dose-response relationship between PM2.5 concentration and lung cancer mortality (each 10-mg/m increase in PM2.5 concentrations was associated with a 15%-27% increase in lung cancer mortality).

A similar analysis by Coleman and colleagues in Cancer Causes and Control found lung cancer mortality was adversely associated with increases in PM2.5 not only in the overall population that was studied, but also in a never-smoker cohort. A study reported in Environmental Health Perspectives also showed that exposure to air pollution increases the incidence and mortality from lung cancer, with lung cancer risk associated with PM2.5 exposure being greatest for former smokers (hazard ratio, 1.44; 95% CI, 1.04-2.01), followed by never-smokers (HR, 1.18; 95% CI, 1.00-1.39), and then current smokers (HR, 1.06; 95% CI, 0.97-1.15).

A 2020 study reported in Thorax that patients with COPD who have never smoked were more likely to get lung cancer, compared with never-smokers without COPD (HR, 2.67, 95% CI, 2.09-3.40). Other studies (The Lancet Oncology and The Lancet) confirm these findings. A meta-analysis published in Environmental Research of a large number of cohort studies over the past 25 years reported that the estimated HR, adjusted for age, sex, and smoking status, was 1.13 (95% CI, 1.07-1.20) per 10 mcg/m elevation in PM2.5.

Air pollution also affects patients who already have lung cancer. Air pollution exposures after the diagnosis of lung cancer shortens survival. For example, a 2016 study published in the journal Thorax found the median survival for patients with early-stage lung cancer at diagnosis was 2.4 years for those with high PM2.5 exposure (≥ 16 mcg/m³) and 5.7 years for those with low PM2.5 exposure (< 10 mcg/m³).

What does air pollution have to do with climate change? They both come from the burning of fossil fuels

Although the topic of climate change is generally seen through an environmental (and political) lens, it should also be seen through a health lens. In 2021, the New England Journal of Medicine and 229 other publications simultaneously published an editorial calling climate change a health emergency.

The increase in the earth’s temperature causes extreme weather events, such as heat waves, droughts, floods, and rising sea levels, all of which results in multiple health effects. These include conditions associated with water and food contamination, and increased susceptibility to allergens. There are also changes in vector ecology which leads to expanding areas of vector-borne diseases, such as Lyme disease, West Nile, and Zika.

Extreme weather events also have major impacts on the ability of cancer patients to access care and their medication. For example, a recent study published in JAMA found that poorer survival was associated with patients with non–small cell lung cancer receiving definitive radiation therapy during hurricane disasters, compared with a matched cohort of patients who underwent treatment in the absence of a hurricane disaster.

Reducing our dependence on fossil fuels will have two important health benefits: mitigating climate change and its associated effects on health, and decreasing air pollution and its subsequent oncologic consequences.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Air pollution is a well-established cause of morbidity and mortality. It largely comes from manmade sources such as particulate matter that arises from burning fossil fuels, which is a major contributor of greenhouse gas emissions.

Acute exposure to fine inhalable particles of as little as 2.5 mcm (PM2.5) in diameter can cause a decrease in lung function leading to respiratory and cardiovascular diseases and even death because of cardiopulmonary conditions and lung cancer.

The 2015 Global Burden of Disease study lists air pollution as the fourth highest–ranking global mortality risk factor. The World Health Organization estimated that 4.2 million deaths were caused by outdoor air pollution in 2016, and another 2.3 million from indoor air pollution.

Not all oncologists believe that air pollution is a cancer problem, but air pollution and particulate matters are carcinogens and in fact, they have been deemed level 1 carcinogens by the International Association of Research on Cancer.

The research on the link between air pollution, PM2.5 and lung cancer is robust. Numerous epidemiological studies have shown that people living in highly polluted areas are more likely to die of lung cancer than those who do not. For example, Turner and colleagues in CA: A Cancer Journal for Clinicians performed a Cox proportional hazard regression model adjusting for numerous variables – smoking, passive smoking, occupational exposures (asbestos, coal dust, diesel engine exhaust, etc.), an occupational “dirtiness” index, radon exposure, among others – and found a dose-response relationship between PM2.5 concentration and lung cancer mortality (each 10-mg/m increase in PM2.5 concentrations was associated with a 15%-27% increase in lung cancer mortality).

A similar analysis by Coleman and colleagues in Cancer Causes and Control found lung cancer mortality was adversely associated with increases in PM2.5 not only in the overall population that was studied, but also in a never-smoker cohort. A study reported in Environmental Health Perspectives also showed that exposure to air pollution increases the incidence and mortality from lung cancer, with lung cancer risk associated with PM2.5 exposure being greatest for former smokers (hazard ratio, 1.44; 95% CI, 1.04-2.01), followed by never-smokers (HR, 1.18; 95% CI, 1.00-1.39), and then current smokers (HR, 1.06; 95% CI, 0.97-1.15).

A 2020 study reported in Thorax that patients with COPD who have never smoked were more likely to get lung cancer, compared with never-smokers without COPD (HR, 2.67, 95% CI, 2.09-3.40). Other studies (The Lancet Oncology and The Lancet) confirm these findings. A meta-analysis published in Environmental Research of a large number of cohort studies over the past 25 years reported that the estimated HR, adjusted for age, sex, and smoking status, was 1.13 (95% CI, 1.07-1.20) per 10 mcg/m elevation in PM2.5.

Air pollution also affects patients who already have lung cancer. Air pollution exposures after the diagnosis of lung cancer shortens survival. For example, a 2016 study published in the journal Thorax found the median survival for patients with early-stage lung cancer at diagnosis was 2.4 years for those with high PM2.5 exposure (≥ 16 mcg/m³) and 5.7 years for those with low PM2.5 exposure (< 10 mcg/m³).

What does air pollution have to do with climate change? They both come from the burning of fossil fuels

Although the topic of climate change is generally seen through an environmental (and political) lens, it should also be seen through a health lens. In 2021, the New England Journal of Medicine and 229 other publications simultaneously published an editorial calling climate change a health emergency.

The increase in the earth’s temperature causes extreme weather events, such as heat waves, droughts, floods, and rising sea levels, all of which results in multiple health effects. These include conditions associated with water and food contamination, and increased susceptibility to allergens. There are also changes in vector ecology which leads to expanding areas of vector-borne diseases, such as Lyme disease, West Nile, and Zika.

Extreme weather events also have major impacts on the ability of cancer patients to access care and their medication. For example, a recent study published in JAMA found that poorer survival was associated with patients with non–small cell lung cancer receiving definitive radiation therapy during hurricane disasters, compared with a matched cohort of patients who underwent treatment in the absence of a hurricane disaster.

Reducing our dependence on fossil fuels will have two important health benefits: mitigating climate change and its associated effects on health, and decreasing air pollution and its subsequent oncologic consequences.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Air pollution is a well-established cause of morbidity and mortality. It largely comes from manmade sources such as particulate matter that arises from burning fossil fuels, which is a major contributor of greenhouse gas emissions.

Acute exposure to fine inhalable particles of as little as 2.5 mcm (PM2.5) in diameter can cause a decrease in lung function leading to respiratory and cardiovascular diseases and even death because of cardiopulmonary conditions and lung cancer.

The 2015 Global Burden of Disease study lists air pollution as the fourth highest–ranking global mortality risk factor. The World Health Organization estimated that 4.2 million deaths were caused by outdoor air pollution in 2016, and another 2.3 million from indoor air pollution.

Not all oncologists believe that air pollution is a cancer problem, but air pollution and particulate matters are carcinogens and in fact, they have been deemed level 1 carcinogens by the International Association of Research on Cancer.

The research on the link between air pollution, PM2.5 and lung cancer is robust. Numerous epidemiological studies have shown that people living in highly polluted areas are more likely to die of lung cancer than those who do not. For example, Turner and colleagues in CA: A Cancer Journal for Clinicians performed a Cox proportional hazard regression model adjusting for numerous variables – smoking, passive smoking, occupational exposures (asbestos, coal dust, diesel engine exhaust, etc.), an occupational “dirtiness” index, radon exposure, among others – and found a dose-response relationship between PM2.5 concentration and lung cancer mortality (each 10-mg/m increase in PM2.5 concentrations was associated with a 15%-27% increase in lung cancer mortality).

A similar analysis by Coleman and colleagues in Cancer Causes and Control found lung cancer mortality was adversely associated with increases in PM2.5 not only in the overall population that was studied, but also in a never-smoker cohort. A study reported in Environmental Health Perspectives also showed that exposure to air pollution increases the incidence and mortality from lung cancer, with lung cancer risk associated with PM2.5 exposure being greatest for former smokers (hazard ratio, 1.44; 95% CI, 1.04-2.01), followed by never-smokers (HR, 1.18; 95% CI, 1.00-1.39), and then current smokers (HR, 1.06; 95% CI, 0.97-1.15).

A 2020 study reported in Thorax that patients with COPD who have never smoked were more likely to get lung cancer, compared with never-smokers without COPD (HR, 2.67, 95% CI, 2.09-3.40). Other studies (The Lancet Oncology and The Lancet) confirm these findings. A meta-analysis published in Environmental Research of a large number of cohort studies over the past 25 years reported that the estimated HR, adjusted for age, sex, and smoking status, was 1.13 (95% CI, 1.07-1.20) per 10 mcg/m elevation in PM2.5.

Air pollution also affects patients who already have lung cancer. Air pollution exposures after the diagnosis of lung cancer shortens survival. For example, a 2016 study published in the journal Thorax found the median survival for patients with early-stage lung cancer at diagnosis was 2.4 years for those with high PM2.5 exposure (≥ 16 mcg/m³) and 5.7 years for those with low PM2.5 exposure (< 10 mcg/m³).

What does air pollution have to do with climate change? They both come from the burning of fossil fuels

Although the topic of climate change is generally seen through an environmental (and political) lens, it should also be seen through a health lens. In 2021, the New England Journal of Medicine and 229 other publications simultaneously published an editorial calling climate change a health emergency.

The increase in the earth’s temperature causes extreme weather events, such as heat waves, droughts, floods, and rising sea levels, all of which results in multiple health effects. These include conditions associated with water and food contamination, and increased susceptibility to allergens. There are also changes in vector ecology which leads to expanding areas of vector-borne diseases, such as Lyme disease, West Nile, and Zika.

Extreme weather events also have major impacts on the ability of cancer patients to access care and their medication. For example, a recent study published in JAMA found that poorer survival was associated with patients with non–small cell lung cancer receiving definitive radiation therapy during hurricane disasters, compared with a matched cohort of patients who underwent treatment in the absence of a hurricane disaster.

Reducing our dependence on fossil fuels will have two important health benefits: mitigating climate change and its associated effects on health, and decreasing air pollution and its subsequent oncologic consequences.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.