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American College of Psychiatrists: Annual Meeting
Dimensional aspects of DSM-5 personality disorder criteria discussed
HUNTINGTON BEACH, CALIF. – In the opinion of Dr. John M. Oldham, clinicians who deem the alternative personality disorder model of the DSM-5 as too confusing are misguided.
“If you’re going to compare DSM-5 alternative personality disorder model with the DSM-IV model, you have to do a fair comparison,” Dr. Oldham told attendees at the annual meeting of the American College of Psychiatrists. ”In fact, we reduced the number of items that you have to measure by 43%.”
So when people describe the DSM-5’s personality disorders criteria as more complicated, he continued, “what they really mean is, ‘it’s more complicated than what I do,’ not that it’s more complicated than [the] DSM-IV.”
Along with Dr. Andrew E. Skodol, Dr. Oldham cochaired a work group of experts convened by the American Psychiatric Association to update diagnostic criteria related to personality and personality disorders for the DSM-5. “We took our work and our charge seriously,” recalled Dr. Oldham, senior vice president and chief of staff at the Menninger Clinic, Houston. “It was not easy. We had many challenges. A great deal of research has been done in the factor analytic research psychology world around things like the five-factor model of personality. Such terms are not always terribly familiar in clinical medicine, so there was a problem with the lack of familiarity. Then there were vested interests different groups had that were influential in some ways.”
Ultimately, the alternative personality disorder model was placed in section III of the DSM-5. The model enables clinicians “to individually portray the dimensions of the patient’s pathology in a thorough and broad way,” Dr. Oldham explained. “We emphasize impairment in functioning. That’s an important new requirement. So you have to determine, by using the level of functioning scale, whether the person does or doesn’t have moderate or greater impairment. If you have a patient with mild impairment, you can describe what you’re concerned about, but you’re not putting that patient into a diagnostic box of pathology. There is a dimensional scope that enables you to capture many types of patients.”
An empirical study of 337 clinicians demonstrated that in 14 of 18 comparisons, respondents deemed the DSM-5 pathological personality traits as more clinical useful, compared with the DSM-IV, with respect to ease of use, communication of clinical information to other professionals, communication of clinical information to patients, comprehensiveness in describing pathology, and treatment planning (J. Abnorm. Psychol. 2013;122:836-41). “In fact, this was a preference to the new model, which was unfamiliar, compared to the model that these clinicians had been using for 20 years,” Dr. Oldham said.
The study also found that the new DSM-5 personality disorder model was more strongly related to clinical decision making in areas of global functioning, risk assessment, recommended treatment type and intensity, and prognosis.
According to unpublished data from the DSM-5 field trials conducted in the United States and Canada, more than 80% of clinicians in academic and routine clinical practice fields found the new personality disorder criteria “moderately” to “extremely” useful, compared with the DSM-IV. In fact, the respondents rated the new criteria as more useful than other changes to the DSM-5, including those related to bipolar and related disorders, schizophrenia spectrum and other psychotic disorders, and other conditions.
In addition, a test-retest reliability study conducted at 11 academic medical centers found that the new model for borderline personality disorder had a good test-retest reliability (.054), in the same ballpark as that for bipolar I disorder (0.56) and schizophrenia (.50) (Am. J. Psychiatry 2013;170:43-58). “This surprised a lot of people,” Dr. Oldham said.
About 1 year after the DSM-5’s release, Medscape Psychiatry surveyed almost 3,000 clinicians about their impressions of the new guidelines. Of the 2,828 respondents, nearly one-third (28%) were psychiatrists, 22% were psychologists, 13% were family medicine clinicians, and the rest were from other medical fields. The researchers found that 39% of survey respondents were considering the dimensional approaches offered in the new personality disorder criteria of the DSM-5.
“That’s not bad,” Dr. Oldham said.
He reported having no relevant financial conflicts.
On Twitter @dougbrunk
HUNTINGTON BEACH, CALIF. – In the opinion of Dr. John M. Oldham, clinicians who deem the alternative personality disorder model of the DSM-5 as too confusing are misguided.
“If you’re going to compare DSM-5 alternative personality disorder model with the DSM-IV model, you have to do a fair comparison,” Dr. Oldham told attendees at the annual meeting of the American College of Psychiatrists. ”In fact, we reduced the number of items that you have to measure by 43%.”
So when people describe the DSM-5’s personality disorders criteria as more complicated, he continued, “what they really mean is, ‘it’s more complicated than what I do,’ not that it’s more complicated than [the] DSM-IV.”
Along with Dr. Andrew E. Skodol, Dr. Oldham cochaired a work group of experts convened by the American Psychiatric Association to update diagnostic criteria related to personality and personality disorders for the DSM-5. “We took our work and our charge seriously,” recalled Dr. Oldham, senior vice president and chief of staff at the Menninger Clinic, Houston. “It was not easy. We had many challenges. A great deal of research has been done in the factor analytic research psychology world around things like the five-factor model of personality. Such terms are not always terribly familiar in clinical medicine, so there was a problem with the lack of familiarity. Then there were vested interests different groups had that were influential in some ways.”
Ultimately, the alternative personality disorder model was placed in section III of the DSM-5. The model enables clinicians “to individually portray the dimensions of the patient’s pathology in a thorough and broad way,” Dr. Oldham explained. “We emphasize impairment in functioning. That’s an important new requirement. So you have to determine, by using the level of functioning scale, whether the person does or doesn’t have moderate or greater impairment. If you have a patient with mild impairment, you can describe what you’re concerned about, but you’re not putting that patient into a diagnostic box of pathology. There is a dimensional scope that enables you to capture many types of patients.”
An empirical study of 337 clinicians demonstrated that in 14 of 18 comparisons, respondents deemed the DSM-5 pathological personality traits as more clinical useful, compared with the DSM-IV, with respect to ease of use, communication of clinical information to other professionals, communication of clinical information to patients, comprehensiveness in describing pathology, and treatment planning (J. Abnorm. Psychol. 2013;122:836-41). “In fact, this was a preference to the new model, which was unfamiliar, compared to the model that these clinicians had been using for 20 years,” Dr. Oldham said.
The study also found that the new DSM-5 personality disorder model was more strongly related to clinical decision making in areas of global functioning, risk assessment, recommended treatment type and intensity, and prognosis.
According to unpublished data from the DSM-5 field trials conducted in the United States and Canada, more than 80% of clinicians in academic and routine clinical practice fields found the new personality disorder criteria “moderately” to “extremely” useful, compared with the DSM-IV. In fact, the respondents rated the new criteria as more useful than other changes to the DSM-5, including those related to bipolar and related disorders, schizophrenia spectrum and other psychotic disorders, and other conditions.
In addition, a test-retest reliability study conducted at 11 academic medical centers found that the new model for borderline personality disorder had a good test-retest reliability (.054), in the same ballpark as that for bipolar I disorder (0.56) and schizophrenia (.50) (Am. J. Psychiatry 2013;170:43-58). “This surprised a lot of people,” Dr. Oldham said.
About 1 year after the DSM-5’s release, Medscape Psychiatry surveyed almost 3,000 clinicians about their impressions of the new guidelines. Of the 2,828 respondents, nearly one-third (28%) were psychiatrists, 22% were psychologists, 13% were family medicine clinicians, and the rest were from other medical fields. The researchers found that 39% of survey respondents were considering the dimensional approaches offered in the new personality disorder criteria of the DSM-5.
“That’s not bad,” Dr. Oldham said.
He reported having no relevant financial conflicts.
On Twitter @dougbrunk
HUNTINGTON BEACH, CALIF. – In the opinion of Dr. John M. Oldham, clinicians who deem the alternative personality disorder model of the DSM-5 as too confusing are misguided.
“If you’re going to compare DSM-5 alternative personality disorder model with the DSM-IV model, you have to do a fair comparison,” Dr. Oldham told attendees at the annual meeting of the American College of Psychiatrists. ”In fact, we reduced the number of items that you have to measure by 43%.”
So when people describe the DSM-5’s personality disorders criteria as more complicated, he continued, “what they really mean is, ‘it’s more complicated than what I do,’ not that it’s more complicated than [the] DSM-IV.”
Along with Dr. Andrew E. Skodol, Dr. Oldham cochaired a work group of experts convened by the American Psychiatric Association to update diagnostic criteria related to personality and personality disorders for the DSM-5. “We took our work and our charge seriously,” recalled Dr. Oldham, senior vice president and chief of staff at the Menninger Clinic, Houston. “It was not easy. We had many challenges. A great deal of research has been done in the factor analytic research psychology world around things like the five-factor model of personality. Such terms are not always terribly familiar in clinical medicine, so there was a problem with the lack of familiarity. Then there were vested interests different groups had that were influential in some ways.”
Ultimately, the alternative personality disorder model was placed in section III of the DSM-5. The model enables clinicians “to individually portray the dimensions of the patient’s pathology in a thorough and broad way,” Dr. Oldham explained. “We emphasize impairment in functioning. That’s an important new requirement. So you have to determine, by using the level of functioning scale, whether the person does or doesn’t have moderate or greater impairment. If you have a patient with mild impairment, you can describe what you’re concerned about, but you’re not putting that patient into a diagnostic box of pathology. There is a dimensional scope that enables you to capture many types of patients.”
An empirical study of 337 clinicians demonstrated that in 14 of 18 comparisons, respondents deemed the DSM-5 pathological personality traits as more clinical useful, compared with the DSM-IV, with respect to ease of use, communication of clinical information to other professionals, communication of clinical information to patients, comprehensiveness in describing pathology, and treatment planning (J. Abnorm. Psychol. 2013;122:836-41). “In fact, this was a preference to the new model, which was unfamiliar, compared to the model that these clinicians had been using for 20 years,” Dr. Oldham said.
The study also found that the new DSM-5 personality disorder model was more strongly related to clinical decision making in areas of global functioning, risk assessment, recommended treatment type and intensity, and prognosis.
According to unpublished data from the DSM-5 field trials conducted in the United States and Canada, more than 80% of clinicians in academic and routine clinical practice fields found the new personality disorder criteria “moderately” to “extremely” useful, compared with the DSM-IV. In fact, the respondents rated the new criteria as more useful than other changes to the DSM-5, including those related to bipolar and related disorders, schizophrenia spectrum and other psychotic disorders, and other conditions.
In addition, a test-retest reliability study conducted at 11 academic medical centers found that the new model for borderline personality disorder had a good test-retest reliability (.054), in the same ballpark as that for bipolar I disorder (0.56) and schizophrenia (.50) (Am. J. Psychiatry 2013;170:43-58). “This surprised a lot of people,” Dr. Oldham said.
About 1 year after the DSM-5’s release, Medscape Psychiatry surveyed almost 3,000 clinicians about their impressions of the new guidelines. Of the 2,828 respondents, nearly one-third (28%) were psychiatrists, 22% were psychologists, 13% were family medicine clinicians, and the rest were from other medical fields. The researchers found that 39% of survey respondents were considering the dimensional approaches offered in the new personality disorder criteria of the DSM-5.
“That’s not bad,” Dr. Oldham said.
He reported having no relevant financial conflicts.
On Twitter @dougbrunk
EXPERT ANALYSIS FROM THE ANNUAL MEETING OF THE AMERICAN COLLEGE OF PSYCHIATRISTS
Early intervention key in food addiction
HUNTINGTON BEACH, CALIF. – The way pioneering researcher Dr. Mark S. Gold sees it, food addiction is akin to dependence on alcohol, nicotine, and other drugs, and the earlier clinicians intervene and treat, the better.
“The evidence that sugar and other constituents of food can be an addiction is quite good, especially if you think about binging, craving, withdrawal, cross-sensitization, increased consumption, and drive for the ‘drug’ in a classic manner,” Dr. Gold said at the annual meeting of the American College of Psychiatrists. “If you focus on dopamine, sugar and food would be a drug. There’s anticipatory dopamine release if you’re presented with dessert, even after a huge meal, for example.”
Just as gambling, sex, and work can be addicting and result in a pathologic attachment, one’s drive for certain foods can lead to loss of control and/or continued use despite serious consequences such as the development of type 2 diabetes or knee and joint disease tied to weight gain. In the case of sugar, for example, “not only does it stimulate its own taking [in the form of] self-administration, loss of self-control, and binging, it can produce withdrawal as if the person is taking opiates,” said Dr. Gold, coauthor of “Food and Addiction: A Comprehensive Handbook” (New York: Oxford University Press, 2012) and the former chair of the department of psychiatry at the University of Florida, Jacksonville. “There’s an indirect opiate effect if naloxone (Narcan) produces withdrawal after sugar self-administration.”
And while obesity is currently the nation’s No. 2 health problem behind tobacco and secondhand smoke, it will be No. 1 soon, predicted Dr. Gold, a psychiatrist who has spent more than 40 years developing models for understanding the effects of tobacco, opiates, cocaine, other drugs, and food on the brain and behavior (Physiol. Behav. 2011;104:157-61).He pointed to a recent comparison of data from the Medical Expenditure Panel Survey between 2000 and 2010, which suggests that obesity “is going to bankrupt the health system because, as compared to tobacco, where death and disability tend to occur in the last 7 years of a person’s life, obesity is an unwanted gift to the health system that keeps on giving, with type 2 diabetes and other complications,” he said. “Now, bariatric surgery is the fastest-growing operation in the United States, and it’s been successful in treating teenagers. Two-thirds of Americans now qualify for obesity treatment.”
He went on to note that Americans are “conditioned by fast food,” and cited potential addictive factors as a nutritionally imbalanced prenatal diet, child rearing, genetics, and lack of exercise. “We [Americans] eat abnormally fast,” Dr. Gold added. “Our group has shown in functional imaging that it takes about 12 minutes for a thin person’s brain to get the food signal. It takes 25 minutes for an obese person to get the signal. So if the obese person goes into a fast food restaurant” and starts eating, that person gets back in line because he’s still hungry.
When first meeting a patient with a suspected food addiction, he advises clinicians to measure the person’s body mass index and to administer the Yale Food Addiction Scale, “which is easy to use,” he said. “Think about intervening and treating people when they have a BMI of 25 or greater, rather than just when they have a pre–bariatric surgery evaluation. One size doesn’t fit all when it comes to treatment.
“It’s important to have a careful look [at what’s causing their obesity]. It could be due to a thyroid condition or to a medication they’re taking.”
In addition to early intervention, “you want cognitive-behavioral treatment, new psychopharmacologic treatment where relevant, and group treatment rather than individualized treatment alone. The food addiction model is leading to a new way of thinking and new pharmacological treatment based on addiction research.”
Dr. Gold reported having no relevant financial conflicts.
On Twitter @dougbrunk
HUNTINGTON BEACH, CALIF. – The way pioneering researcher Dr. Mark S. Gold sees it, food addiction is akin to dependence on alcohol, nicotine, and other drugs, and the earlier clinicians intervene and treat, the better.
“The evidence that sugar and other constituents of food can be an addiction is quite good, especially if you think about binging, craving, withdrawal, cross-sensitization, increased consumption, and drive for the ‘drug’ in a classic manner,” Dr. Gold said at the annual meeting of the American College of Psychiatrists. “If you focus on dopamine, sugar and food would be a drug. There’s anticipatory dopamine release if you’re presented with dessert, even after a huge meal, for example.”
Just as gambling, sex, and work can be addicting and result in a pathologic attachment, one’s drive for certain foods can lead to loss of control and/or continued use despite serious consequences such as the development of type 2 diabetes or knee and joint disease tied to weight gain. In the case of sugar, for example, “not only does it stimulate its own taking [in the form of] self-administration, loss of self-control, and binging, it can produce withdrawal as if the person is taking opiates,” said Dr. Gold, coauthor of “Food and Addiction: A Comprehensive Handbook” (New York: Oxford University Press, 2012) and the former chair of the department of psychiatry at the University of Florida, Jacksonville. “There’s an indirect opiate effect if naloxone (Narcan) produces withdrawal after sugar self-administration.”
And while obesity is currently the nation’s No. 2 health problem behind tobacco and secondhand smoke, it will be No. 1 soon, predicted Dr. Gold, a psychiatrist who has spent more than 40 years developing models for understanding the effects of tobacco, opiates, cocaine, other drugs, and food on the brain and behavior (Physiol. Behav. 2011;104:157-61).He pointed to a recent comparison of data from the Medical Expenditure Panel Survey between 2000 and 2010, which suggests that obesity “is going to bankrupt the health system because, as compared to tobacco, where death and disability tend to occur in the last 7 years of a person’s life, obesity is an unwanted gift to the health system that keeps on giving, with type 2 diabetes and other complications,” he said. “Now, bariatric surgery is the fastest-growing operation in the United States, and it’s been successful in treating teenagers. Two-thirds of Americans now qualify for obesity treatment.”
He went on to note that Americans are “conditioned by fast food,” and cited potential addictive factors as a nutritionally imbalanced prenatal diet, child rearing, genetics, and lack of exercise. “We [Americans] eat abnormally fast,” Dr. Gold added. “Our group has shown in functional imaging that it takes about 12 minutes for a thin person’s brain to get the food signal. It takes 25 minutes for an obese person to get the signal. So if the obese person goes into a fast food restaurant” and starts eating, that person gets back in line because he’s still hungry.
When first meeting a patient with a suspected food addiction, he advises clinicians to measure the person’s body mass index and to administer the Yale Food Addiction Scale, “which is easy to use,” he said. “Think about intervening and treating people when they have a BMI of 25 or greater, rather than just when they have a pre–bariatric surgery evaluation. One size doesn’t fit all when it comes to treatment.
“It’s important to have a careful look [at what’s causing their obesity]. It could be due to a thyroid condition or to a medication they’re taking.”
In addition to early intervention, “you want cognitive-behavioral treatment, new psychopharmacologic treatment where relevant, and group treatment rather than individualized treatment alone. The food addiction model is leading to a new way of thinking and new pharmacological treatment based on addiction research.”
Dr. Gold reported having no relevant financial conflicts.
On Twitter @dougbrunk
HUNTINGTON BEACH, CALIF. – The way pioneering researcher Dr. Mark S. Gold sees it, food addiction is akin to dependence on alcohol, nicotine, and other drugs, and the earlier clinicians intervene and treat, the better.
“The evidence that sugar and other constituents of food can be an addiction is quite good, especially if you think about binging, craving, withdrawal, cross-sensitization, increased consumption, and drive for the ‘drug’ in a classic manner,” Dr. Gold said at the annual meeting of the American College of Psychiatrists. “If you focus on dopamine, sugar and food would be a drug. There’s anticipatory dopamine release if you’re presented with dessert, even after a huge meal, for example.”
Just as gambling, sex, and work can be addicting and result in a pathologic attachment, one’s drive for certain foods can lead to loss of control and/or continued use despite serious consequences such as the development of type 2 diabetes or knee and joint disease tied to weight gain. In the case of sugar, for example, “not only does it stimulate its own taking [in the form of] self-administration, loss of self-control, and binging, it can produce withdrawal as if the person is taking opiates,” said Dr. Gold, coauthor of “Food and Addiction: A Comprehensive Handbook” (New York: Oxford University Press, 2012) and the former chair of the department of psychiatry at the University of Florida, Jacksonville. “There’s an indirect opiate effect if naloxone (Narcan) produces withdrawal after sugar self-administration.”
And while obesity is currently the nation’s No. 2 health problem behind tobacco and secondhand smoke, it will be No. 1 soon, predicted Dr. Gold, a psychiatrist who has spent more than 40 years developing models for understanding the effects of tobacco, opiates, cocaine, other drugs, and food on the brain and behavior (Physiol. Behav. 2011;104:157-61).He pointed to a recent comparison of data from the Medical Expenditure Panel Survey between 2000 and 2010, which suggests that obesity “is going to bankrupt the health system because, as compared to tobacco, where death and disability tend to occur in the last 7 years of a person’s life, obesity is an unwanted gift to the health system that keeps on giving, with type 2 diabetes and other complications,” he said. “Now, bariatric surgery is the fastest-growing operation in the United States, and it’s been successful in treating teenagers. Two-thirds of Americans now qualify for obesity treatment.”
He went on to note that Americans are “conditioned by fast food,” and cited potential addictive factors as a nutritionally imbalanced prenatal diet, child rearing, genetics, and lack of exercise. “We [Americans] eat abnormally fast,” Dr. Gold added. “Our group has shown in functional imaging that it takes about 12 minutes for a thin person’s brain to get the food signal. It takes 25 minutes for an obese person to get the signal. So if the obese person goes into a fast food restaurant” and starts eating, that person gets back in line because he’s still hungry.
When first meeting a patient with a suspected food addiction, he advises clinicians to measure the person’s body mass index and to administer the Yale Food Addiction Scale, “which is easy to use,” he said. “Think about intervening and treating people when they have a BMI of 25 or greater, rather than just when they have a pre–bariatric surgery evaluation. One size doesn’t fit all when it comes to treatment.
“It’s important to have a careful look [at what’s causing their obesity]. It could be due to a thyroid condition or to a medication they’re taking.”
In addition to early intervention, “you want cognitive-behavioral treatment, new psychopharmacologic treatment where relevant, and group treatment rather than individualized treatment alone. The food addiction model is leading to a new way of thinking and new pharmacological treatment based on addiction research.”
Dr. Gold reported having no relevant financial conflicts.
On Twitter @dougbrunk
EXPERT ANALYSIS FROM THE AMERICAN COLLEGE OF PSYCHIATRISTS MEETING
Headway being made in developing biomarkers for PTSD
HUNTINGTON BEACH, CALIF. – Researchers are making significant headway in developing objective, reliable, and valid biomarkers to discriminate individuals with warzone post traumatic stress disorder from healthy controls, according to Dr. Charles R. Marmar.
“It’s clear that over the next four or five years we will identify very clear biological, psychological, and other behavioral risk and resilience profiles,” Dr. Marmar told attendees at the annual meeting of the American College of Psychiatrists.
Currently, clinicians largely rely on patient self-reports and clinical observations to diagnose PTSD in military personnel, said Dr. Marmar, professor and chair of the department of psychiatry at NYU Langone Medical Center and director of NYU’s Steven and Alexandra Cohen Veterans Center.
“The problem from the military and law enforcement perspective is that the majority of war fighters experience tremendous stigma in acknowledging their symptoms, particularly active duty military personnel,” he said. “A minority will exaggerate to avoid service or for compensation. Given that we’ve had nearly three million men and women serve in Iraq and Afghanistan, and the fact that we have no objective way yet of determining which ones continue to be fit for redeployment, which ones are in urgent need of help, and which ones deserve compensation, we need to develop better ways to determine if treatments are effective, to inform new treatment selection, and to define new targets for treatment.”
The scope of the problem is underscored in an analysis of data from 289,328 veterans entering VA Healthcare for the first time beginning on April 1, 2002 through March 31, 2006 (Am J. Pub. Health 2009;99[9]:1651-8). Prior to the invasion of Iraq, the distribution of mental health problems was very similar among veterans as in the general population: depression being most common, and low rates of PTSD and alcohol and drug abuse. However, “with each quarter since the invasion of Iraq, there’s been an incubative growth in the prevalence of PTSD, which has now eclipsed depression,” Dr. Marmar said. “We have a toll, a generational effect which looks similar in magnitude with the Vietnam War, both in the number of men and women who serve and in the prevalence of PTSD, depression and alcohol- and drug-related disorders.”
In the general population, risk factors include female sex, child abuse, genetics, which in twin studies account for 30-40% of the risk, lower IQ and lower educational attainment, stressful life events in the prior and following year, and panic reaction at the time of event, such as racing heart, shaking, and sweating.
According to findings from the National Vietnam Veterans Readjustment Study, risk factors for chronic warzone PTSD include high school dropout rate, history of child abuse, high warzone exposure, serious warzone injury, killing combatants, prisoners, and civilians, peritraumatic dissociation, hostile homecoming, post-discharge trauma, and genetics. “These are the risk profiles, and they should give us some clues about where to look for biological factors,” Dr. Marmar said.
The risks of service are not limited to stress, anxiety, depression, alcohol and drug abuse, or traumatic brain injury (TBI). “If you compare men and women returning from Iraq and Afghanistan with no mental health issues to those who have a diagnosis of either PTSD, depression, or the combination, the [diagnosed] cases have 2.5 times the risk of tobacco use, hypertension, dyslipidemia, obesity, and type 2 diabetes,” he said. “These are people in their late 20s and early 30s. So the costs of warzone-related stress and depression are enormous on general health.”
Dr. Marmar presented preliminary findings from the ongoing PTSD Systems Biology Consortium, an effort by researchers at seven universities to establish biomarkers for PTSD. Funded by the Department of Defense, the National Institutes of Health, and other sources, the consortium is comprised of integrated cores including neurocognition, genetics, structural and functional brain imaging, endocrinology, metabolism, genomics, proteomics, metabolomics, and bioinformatics.
To date, the researchers have screened 2,215 veterans from service in Iraq and Afghanistan, all of whom have been deployed to war at least once. Cases were PTSD positive and had a CAPS (Clinician-Administered PTSD scale) score of 20 or greater. Controls were PTSD negative and had a CAPS score of less than 20. They excluded subjects with lifetime psychosis, bipolar disorder, or OCD, as well as alcohol dependence in the past eight months, and drug abuse in the past year. They also excluded veterans with TBI “because we’re trying to be very careful to see if we can get a biological signal comparing combat PTSD cases with controls,” Dr. Marmar noted.
Dr. Marmar presented preliminary findings from 52 PTSD cases and 52 controls that were matched for sex, ethnicity, and age. The sample was entirely men, their mean age was 34 years, and they had a mean of 14.8 years of education. The researchers covaried for depression and other known confounders. “It’s very difficult to disentangle the effects of PTSD and depression because 50% of the cases of warzone PTSD also meet criteria for current major depression, and over 80% meet criteria for lifetime depression,” he said.
In results from the clinical diagnostic evaluation, PTSD cases, compared with controls, were significantly more likely to have current anxiety (7% vs. 0%, respectively; P = .041); lifetime anxiety (9.6% vs. 0%; P = .022); current major depressive disorder (51.5% vs. 1.9%; P<.001); lifetime MDD (84.6% vs. 23.1%; P<.001); and lifetime alcohol abuse dependence (63.5% vs. 25%; P = .001). There was also a non-signficant trend toward lifetime substance abuse/dependence (13.5% vs. 3.9%; P = .081).
Results from the neurocognitive assessments revealed that PTSD positive men had a significantly lower estimated IQ, compared with their PTSD negative counterparts (a mean of 99.3 vs. 107.9, respectively; P = .031). Other significant differences between the two groups were observed in tests of auditory and working memory, specifically digit span (8.67 vs. 10.04; P = .02), and the visual memory sum (9.1 vs. 10.67; P = .01).
One of the consortium collaborators developed a test to compare reward and punishment learning. For the test, “the subject is required to understand what the meaning of a symbol is in a task, and they have no prior knowledge [of the meaning],” Dr. Marmar explained. “They’re either rewarded for guessing correctly or punished for guessing incorrectly.” So far, the healthy controls “are performing much better in identifying the symbols when they’re rewarded, compared with the PTSD cases, and there’s no difference in punishment,” he said. “So there’s impaired reward learning and intact punishment learning in PTSD cases compared to controls, which likely reflects underlying disturbances in dopamine reward circuitry.”
Investigators in the neurogenetics core hypothesized that DNA variants in stress-response genes identified from previous medical studies will be associated with PTSD. These included FKBP5, COMT, APOE, BDNF, PACAP/PAC1R, and OPRL1. Initial analysis revealed that there were a greater number of BDNF allele frequencies among cases, compared with controls (P = .008). “It would appear that BDNF variants confer resilience for combat-related PTSD,” Dr. Marmar said.
The researchers also found a single nucleotide polymorphism never previously described on Chromosome 4. “It’s in a region between genes, probably a micro-RNA regulatory gene on the 4th chromosome,” he said. “That gene in our sample was associated with higher levels of PTSD. In addition, fMRI studies found that carrying this allele was associated with weaker activation of prefrontal cortical areas in the brain to empirical faces tasks.”
The endocrine core found that PTSD cases had lower ambient cortisol levels, compared with controls (P = .051). They also had significantly greater cortisol suppression following dexamethasone administration, compared with controls (P = .013). “This is evidence that there is increased glucocorticoid receptor sensitivity in PTSD expressing as elevated cortisol suppression,” Dr. Marmar said.
Investigators from the structural imaging core found no significant differences in overall hippocampal volume or in the five major hippocampal subfields between PTSD cases and controls, nor in difference in the volume of other brain structures previously implicated in PTSD, such as the amygdala and the thalamus. However, the researchers are finding some differences between cases and controls on functional imaging, including increased spontaneous activity in the amygdala and the insula, and decreased spontaneous activity in the precuneus. “The overall findings on fMRI are that there’s increased activity in the regions [of the brain] associated with fear and decreased connectivity between the frontal cortex and the amygdala,” he said. “This is consistent with the model of dysregulated fear activity in PTSD.”
Researchers have also observed that many markers of metabolic syndrome are significantly elevated between PTSD cases and controls, including fasting glucose (P = .001), weight (P = .03), and resting pulse (P = .003). “When you covary for depression, these findings remain,” Dr. Marmar said. “It’s important to note that these are men mostly in their early 30s recently returned from war and recently in military training, physically fit to be deployed to war.”
He closed his presentation by noting that mounting evidence from animal and human studies suggests evidence of mitochondrial dysfunction in PTSD. In the current analysis, researchers observed a reduced abundance of citrate and other mitochondrial metabolites in PTSD cases compared with controls, as well as an increased abundance of “premitochondrial” metabolites such as pyruvate and lactate. “These findings stand when you covary for depression and for metabolic syndrome,” Dr. Marmar said.
“We believe that these may be very important potential future candidate biomarkers to differentiate PTSD cases from controls.”
The next step in this effort, he added, is to replicate the consortium’s overall findings in a cross-validation sample of 50 male cases and 50 male controls. “We also have a sample of 40 female cases and 40 controls to see if the markers are the same or different,” he said. The researchers are also conducting a prospective study of 1,200 active duty military personnel, who will be evaluated before and after deployment.
For now, some clinicians wonder what should be done for men and women who carry the PTSD risk alleles, or carry the endocrine or metabolism vulnerability to develop complications from combat exposure. “That’s a very sensitive national question,” Dr. Marmar said. “People want to serve their country. The answer may be to allow service but to have a more nuanced approach to what people’s roles should be within the military, to match individuals’ stress resilience with the responsibilities they have.”
Dr. Marmar reported that he had no relevant financial conflicts.
On Twitter @dougbrunk
HUNTINGTON BEACH, CALIF. – Researchers are making significant headway in developing objective, reliable, and valid biomarkers to discriminate individuals with warzone post traumatic stress disorder from healthy controls, according to Dr. Charles R. Marmar.
“It’s clear that over the next four or five years we will identify very clear biological, psychological, and other behavioral risk and resilience profiles,” Dr. Marmar told attendees at the annual meeting of the American College of Psychiatrists.
Currently, clinicians largely rely on patient self-reports and clinical observations to diagnose PTSD in military personnel, said Dr. Marmar, professor and chair of the department of psychiatry at NYU Langone Medical Center and director of NYU’s Steven and Alexandra Cohen Veterans Center.
“The problem from the military and law enforcement perspective is that the majority of war fighters experience tremendous stigma in acknowledging their symptoms, particularly active duty military personnel,” he said. “A minority will exaggerate to avoid service or for compensation. Given that we’ve had nearly three million men and women serve in Iraq and Afghanistan, and the fact that we have no objective way yet of determining which ones continue to be fit for redeployment, which ones are in urgent need of help, and which ones deserve compensation, we need to develop better ways to determine if treatments are effective, to inform new treatment selection, and to define new targets for treatment.”
The scope of the problem is underscored in an analysis of data from 289,328 veterans entering VA Healthcare for the first time beginning on April 1, 2002 through March 31, 2006 (Am J. Pub. Health 2009;99[9]:1651-8). Prior to the invasion of Iraq, the distribution of mental health problems was very similar among veterans as in the general population: depression being most common, and low rates of PTSD and alcohol and drug abuse. However, “with each quarter since the invasion of Iraq, there’s been an incubative growth in the prevalence of PTSD, which has now eclipsed depression,” Dr. Marmar said. “We have a toll, a generational effect which looks similar in magnitude with the Vietnam War, both in the number of men and women who serve and in the prevalence of PTSD, depression and alcohol- and drug-related disorders.”
In the general population, risk factors include female sex, child abuse, genetics, which in twin studies account for 30-40% of the risk, lower IQ and lower educational attainment, stressful life events in the prior and following year, and panic reaction at the time of event, such as racing heart, shaking, and sweating.
According to findings from the National Vietnam Veterans Readjustment Study, risk factors for chronic warzone PTSD include high school dropout rate, history of child abuse, high warzone exposure, serious warzone injury, killing combatants, prisoners, and civilians, peritraumatic dissociation, hostile homecoming, post-discharge trauma, and genetics. “These are the risk profiles, and they should give us some clues about where to look for biological factors,” Dr. Marmar said.
The risks of service are not limited to stress, anxiety, depression, alcohol and drug abuse, or traumatic brain injury (TBI). “If you compare men and women returning from Iraq and Afghanistan with no mental health issues to those who have a diagnosis of either PTSD, depression, or the combination, the [diagnosed] cases have 2.5 times the risk of tobacco use, hypertension, dyslipidemia, obesity, and type 2 diabetes,” he said. “These are people in their late 20s and early 30s. So the costs of warzone-related stress and depression are enormous on general health.”
Dr. Marmar presented preliminary findings from the ongoing PTSD Systems Biology Consortium, an effort by researchers at seven universities to establish biomarkers for PTSD. Funded by the Department of Defense, the National Institutes of Health, and other sources, the consortium is comprised of integrated cores including neurocognition, genetics, structural and functional brain imaging, endocrinology, metabolism, genomics, proteomics, metabolomics, and bioinformatics.
To date, the researchers have screened 2,215 veterans from service in Iraq and Afghanistan, all of whom have been deployed to war at least once. Cases were PTSD positive and had a CAPS (Clinician-Administered PTSD scale) score of 20 or greater. Controls were PTSD negative and had a CAPS score of less than 20. They excluded subjects with lifetime psychosis, bipolar disorder, or OCD, as well as alcohol dependence in the past eight months, and drug abuse in the past year. They also excluded veterans with TBI “because we’re trying to be very careful to see if we can get a biological signal comparing combat PTSD cases with controls,” Dr. Marmar noted.
Dr. Marmar presented preliminary findings from 52 PTSD cases and 52 controls that were matched for sex, ethnicity, and age. The sample was entirely men, their mean age was 34 years, and they had a mean of 14.8 years of education. The researchers covaried for depression and other known confounders. “It’s very difficult to disentangle the effects of PTSD and depression because 50% of the cases of warzone PTSD also meet criteria for current major depression, and over 80% meet criteria for lifetime depression,” he said.
In results from the clinical diagnostic evaluation, PTSD cases, compared with controls, were significantly more likely to have current anxiety (7% vs. 0%, respectively; P = .041); lifetime anxiety (9.6% vs. 0%; P = .022); current major depressive disorder (51.5% vs. 1.9%; P<.001); lifetime MDD (84.6% vs. 23.1%; P<.001); and lifetime alcohol abuse dependence (63.5% vs. 25%; P = .001). There was also a non-signficant trend toward lifetime substance abuse/dependence (13.5% vs. 3.9%; P = .081).
Results from the neurocognitive assessments revealed that PTSD positive men had a significantly lower estimated IQ, compared with their PTSD negative counterparts (a mean of 99.3 vs. 107.9, respectively; P = .031). Other significant differences between the two groups were observed in tests of auditory and working memory, specifically digit span (8.67 vs. 10.04; P = .02), and the visual memory sum (9.1 vs. 10.67; P = .01).
One of the consortium collaborators developed a test to compare reward and punishment learning. For the test, “the subject is required to understand what the meaning of a symbol is in a task, and they have no prior knowledge [of the meaning],” Dr. Marmar explained. “They’re either rewarded for guessing correctly or punished for guessing incorrectly.” So far, the healthy controls “are performing much better in identifying the symbols when they’re rewarded, compared with the PTSD cases, and there’s no difference in punishment,” he said. “So there’s impaired reward learning and intact punishment learning in PTSD cases compared to controls, which likely reflects underlying disturbances in dopamine reward circuitry.”
Investigators in the neurogenetics core hypothesized that DNA variants in stress-response genes identified from previous medical studies will be associated with PTSD. These included FKBP5, COMT, APOE, BDNF, PACAP/PAC1R, and OPRL1. Initial analysis revealed that there were a greater number of BDNF allele frequencies among cases, compared with controls (P = .008). “It would appear that BDNF variants confer resilience for combat-related PTSD,” Dr. Marmar said.
The researchers also found a single nucleotide polymorphism never previously described on Chromosome 4. “It’s in a region between genes, probably a micro-RNA regulatory gene on the 4th chromosome,” he said. “That gene in our sample was associated with higher levels of PTSD. In addition, fMRI studies found that carrying this allele was associated with weaker activation of prefrontal cortical areas in the brain to empirical faces tasks.”
The endocrine core found that PTSD cases had lower ambient cortisol levels, compared with controls (P = .051). They also had significantly greater cortisol suppression following dexamethasone administration, compared with controls (P = .013). “This is evidence that there is increased glucocorticoid receptor sensitivity in PTSD expressing as elevated cortisol suppression,” Dr. Marmar said.
Investigators from the structural imaging core found no significant differences in overall hippocampal volume or in the five major hippocampal subfields between PTSD cases and controls, nor in difference in the volume of other brain structures previously implicated in PTSD, such as the amygdala and the thalamus. However, the researchers are finding some differences between cases and controls on functional imaging, including increased spontaneous activity in the amygdala and the insula, and decreased spontaneous activity in the precuneus. “The overall findings on fMRI are that there’s increased activity in the regions [of the brain] associated with fear and decreased connectivity between the frontal cortex and the amygdala,” he said. “This is consistent with the model of dysregulated fear activity in PTSD.”
Researchers have also observed that many markers of metabolic syndrome are significantly elevated between PTSD cases and controls, including fasting glucose (P = .001), weight (P = .03), and resting pulse (P = .003). “When you covary for depression, these findings remain,” Dr. Marmar said. “It’s important to note that these are men mostly in their early 30s recently returned from war and recently in military training, physically fit to be deployed to war.”
He closed his presentation by noting that mounting evidence from animal and human studies suggests evidence of mitochondrial dysfunction in PTSD. In the current analysis, researchers observed a reduced abundance of citrate and other mitochondrial metabolites in PTSD cases compared with controls, as well as an increased abundance of “premitochondrial” metabolites such as pyruvate and lactate. “These findings stand when you covary for depression and for metabolic syndrome,” Dr. Marmar said.
“We believe that these may be very important potential future candidate biomarkers to differentiate PTSD cases from controls.”
The next step in this effort, he added, is to replicate the consortium’s overall findings in a cross-validation sample of 50 male cases and 50 male controls. “We also have a sample of 40 female cases and 40 controls to see if the markers are the same or different,” he said. The researchers are also conducting a prospective study of 1,200 active duty military personnel, who will be evaluated before and after deployment.
For now, some clinicians wonder what should be done for men and women who carry the PTSD risk alleles, or carry the endocrine or metabolism vulnerability to develop complications from combat exposure. “That’s a very sensitive national question,” Dr. Marmar said. “People want to serve their country. The answer may be to allow service but to have a more nuanced approach to what people’s roles should be within the military, to match individuals’ stress resilience with the responsibilities they have.”
Dr. Marmar reported that he had no relevant financial conflicts.
On Twitter @dougbrunk
HUNTINGTON BEACH, CALIF. – Researchers are making significant headway in developing objective, reliable, and valid biomarkers to discriminate individuals with warzone post traumatic stress disorder from healthy controls, according to Dr. Charles R. Marmar.
“It’s clear that over the next four or five years we will identify very clear biological, psychological, and other behavioral risk and resilience profiles,” Dr. Marmar told attendees at the annual meeting of the American College of Psychiatrists.
Currently, clinicians largely rely on patient self-reports and clinical observations to diagnose PTSD in military personnel, said Dr. Marmar, professor and chair of the department of psychiatry at NYU Langone Medical Center and director of NYU’s Steven and Alexandra Cohen Veterans Center.
“The problem from the military and law enforcement perspective is that the majority of war fighters experience tremendous stigma in acknowledging their symptoms, particularly active duty military personnel,” he said. “A minority will exaggerate to avoid service or for compensation. Given that we’ve had nearly three million men and women serve in Iraq and Afghanistan, and the fact that we have no objective way yet of determining which ones continue to be fit for redeployment, which ones are in urgent need of help, and which ones deserve compensation, we need to develop better ways to determine if treatments are effective, to inform new treatment selection, and to define new targets for treatment.”
The scope of the problem is underscored in an analysis of data from 289,328 veterans entering VA Healthcare for the first time beginning on April 1, 2002 through March 31, 2006 (Am J. Pub. Health 2009;99[9]:1651-8). Prior to the invasion of Iraq, the distribution of mental health problems was very similar among veterans as in the general population: depression being most common, and low rates of PTSD and alcohol and drug abuse. However, “with each quarter since the invasion of Iraq, there’s been an incubative growth in the prevalence of PTSD, which has now eclipsed depression,” Dr. Marmar said. “We have a toll, a generational effect which looks similar in magnitude with the Vietnam War, both in the number of men and women who serve and in the prevalence of PTSD, depression and alcohol- and drug-related disorders.”
In the general population, risk factors include female sex, child abuse, genetics, which in twin studies account for 30-40% of the risk, lower IQ and lower educational attainment, stressful life events in the prior and following year, and panic reaction at the time of event, such as racing heart, shaking, and sweating.
According to findings from the National Vietnam Veterans Readjustment Study, risk factors for chronic warzone PTSD include high school dropout rate, history of child abuse, high warzone exposure, serious warzone injury, killing combatants, prisoners, and civilians, peritraumatic dissociation, hostile homecoming, post-discharge trauma, and genetics. “These are the risk profiles, and they should give us some clues about where to look for biological factors,” Dr. Marmar said.
The risks of service are not limited to stress, anxiety, depression, alcohol and drug abuse, or traumatic brain injury (TBI). “If you compare men and women returning from Iraq and Afghanistan with no mental health issues to those who have a diagnosis of either PTSD, depression, or the combination, the [diagnosed] cases have 2.5 times the risk of tobacco use, hypertension, dyslipidemia, obesity, and type 2 diabetes,” he said. “These are people in their late 20s and early 30s. So the costs of warzone-related stress and depression are enormous on general health.”
Dr. Marmar presented preliminary findings from the ongoing PTSD Systems Biology Consortium, an effort by researchers at seven universities to establish biomarkers for PTSD. Funded by the Department of Defense, the National Institutes of Health, and other sources, the consortium is comprised of integrated cores including neurocognition, genetics, structural and functional brain imaging, endocrinology, metabolism, genomics, proteomics, metabolomics, and bioinformatics.
To date, the researchers have screened 2,215 veterans from service in Iraq and Afghanistan, all of whom have been deployed to war at least once. Cases were PTSD positive and had a CAPS (Clinician-Administered PTSD scale) score of 20 or greater. Controls were PTSD negative and had a CAPS score of less than 20. They excluded subjects with lifetime psychosis, bipolar disorder, or OCD, as well as alcohol dependence in the past eight months, and drug abuse in the past year. They also excluded veterans with TBI “because we’re trying to be very careful to see if we can get a biological signal comparing combat PTSD cases with controls,” Dr. Marmar noted.
Dr. Marmar presented preliminary findings from 52 PTSD cases and 52 controls that were matched for sex, ethnicity, and age. The sample was entirely men, their mean age was 34 years, and they had a mean of 14.8 years of education. The researchers covaried for depression and other known confounders. “It’s very difficult to disentangle the effects of PTSD and depression because 50% of the cases of warzone PTSD also meet criteria for current major depression, and over 80% meet criteria for lifetime depression,” he said.
In results from the clinical diagnostic evaluation, PTSD cases, compared with controls, were significantly more likely to have current anxiety (7% vs. 0%, respectively; P = .041); lifetime anxiety (9.6% vs. 0%; P = .022); current major depressive disorder (51.5% vs. 1.9%; P<.001); lifetime MDD (84.6% vs. 23.1%; P<.001); and lifetime alcohol abuse dependence (63.5% vs. 25%; P = .001). There was also a non-signficant trend toward lifetime substance abuse/dependence (13.5% vs. 3.9%; P = .081).
Results from the neurocognitive assessments revealed that PTSD positive men had a significantly lower estimated IQ, compared with their PTSD negative counterparts (a mean of 99.3 vs. 107.9, respectively; P = .031). Other significant differences between the two groups were observed in tests of auditory and working memory, specifically digit span (8.67 vs. 10.04; P = .02), and the visual memory sum (9.1 vs. 10.67; P = .01).
One of the consortium collaborators developed a test to compare reward and punishment learning. For the test, “the subject is required to understand what the meaning of a symbol is in a task, and they have no prior knowledge [of the meaning],” Dr. Marmar explained. “They’re either rewarded for guessing correctly or punished for guessing incorrectly.” So far, the healthy controls “are performing much better in identifying the symbols when they’re rewarded, compared with the PTSD cases, and there’s no difference in punishment,” he said. “So there’s impaired reward learning and intact punishment learning in PTSD cases compared to controls, which likely reflects underlying disturbances in dopamine reward circuitry.”
Investigators in the neurogenetics core hypothesized that DNA variants in stress-response genes identified from previous medical studies will be associated with PTSD. These included FKBP5, COMT, APOE, BDNF, PACAP/PAC1R, and OPRL1. Initial analysis revealed that there were a greater number of BDNF allele frequencies among cases, compared with controls (P = .008). “It would appear that BDNF variants confer resilience for combat-related PTSD,” Dr. Marmar said.
The researchers also found a single nucleotide polymorphism never previously described on Chromosome 4. “It’s in a region between genes, probably a micro-RNA regulatory gene on the 4th chromosome,” he said. “That gene in our sample was associated with higher levels of PTSD. In addition, fMRI studies found that carrying this allele was associated with weaker activation of prefrontal cortical areas in the brain to empirical faces tasks.”
The endocrine core found that PTSD cases had lower ambient cortisol levels, compared with controls (P = .051). They also had significantly greater cortisol suppression following dexamethasone administration, compared with controls (P = .013). “This is evidence that there is increased glucocorticoid receptor sensitivity in PTSD expressing as elevated cortisol suppression,” Dr. Marmar said.
Investigators from the structural imaging core found no significant differences in overall hippocampal volume or in the five major hippocampal subfields between PTSD cases and controls, nor in difference in the volume of other brain structures previously implicated in PTSD, such as the amygdala and the thalamus. However, the researchers are finding some differences between cases and controls on functional imaging, including increased spontaneous activity in the amygdala and the insula, and decreased spontaneous activity in the precuneus. “The overall findings on fMRI are that there’s increased activity in the regions [of the brain] associated with fear and decreased connectivity between the frontal cortex and the amygdala,” he said. “This is consistent with the model of dysregulated fear activity in PTSD.”
Researchers have also observed that many markers of metabolic syndrome are significantly elevated between PTSD cases and controls, including fasting glucose (P = .001), weight (P = .03), and resting pulse (P = .003). “When you covary for depression, these findings remain,” Dr. Marmar said. “It’s important to note that these are men mostly in their early 30s recently returned from war and recently in military training, physically fit to be deployed to war.”
He closed his presentation by noting that mounting evidence from animal and human studies suggests evidence of mitochondrial dysfunction in PTSD. In the current analysis, researchers observed a reduced abundance of citrate and other mitochondrial metabolites in PTSD cases compared with controls, as well as an increased abundance of “premitochondrial” metabolites such as pyruvate and lactate. “These findings stand when you covary for depression and for metabolic syndrome,” Dr. Marmar said.
“We believe that these may be very important potential future candidate biomarkers to differentiate PTSD cases from controls.”
The next step in this effort, he added, is to replicate the consortium’s overall findings in a cross-validation sample of 50 male cases and 50 male controls. “We also have a sample of 40 female cases and 40 controls to see if the markers are the same or different,” he said. The researchers are also conducting a prospective study of 1,200 active duty military personnel, who will be evaluated before and after deployment.
For now, some clinicians wonder what should be done for men and women who carry the PTSD risk alleles, or carry the endocrine or metabolism vulnerability to develop complications from combat exposure. “That’s a very sensitive national question,” Dr. Marmar said. “People want to serve their country. The answer may be to allow service but to have a more nuanced approach to what people’s roles should be within the military, to match individuals’ stress resilience with the responsibilities they have.”
Dr. Marmar reported that he had no relevant financial conflicts.
On Twitter @dougbrunk
EXPERT ANALYSIS AT THE ANNUAL MEETING OF THE AMERICAN COLLEGE OF PSYCHIATRISTS
AUDIO: Can you really be addicted to food?
HUNTINGTON BEACH, CALIF. – Can you really be addicted to food?
That’s the question posed by Dr. Mark S. Gold, adjunct professor of psychiatry at the Washington University School of Medicine in St. Louis.* His answer? “Maybe not in the same sense that you can be addicted to heroin – but certain foods, especially highly manufactured, sugar-rich foods, stimulate their own taking as if they’re a drug.”
In an interview at the annual meeting of the American College of Psychiatrists, Dr. Gold – a pioneer in the so-called “food addiction hypothesis” – highlighted current trends in food and process addictions.
He noted that behavioral and medical treatments commonly used for alcohol dependence, for example, are proving effective for patients coping with overeating, obesity, and binge eating. Psychiatrists will play an expanding role in caring for such patients, he predicted.
Dr. Gold reported having no relevant financial disclosures.
*Correction, 4/2/2015: An earlier version of this story misstated Dr. Gold's title.
On Twitter @dougbrunk
HUNTINGTON BEACH, CALIF. – Can you really be addicted to food?
That’s the question posed by Dr. Mark S. Gold, adjunct professor of psychiatry at the Washington University School of Medicine in St. Louis.* His answer? “Maybe not in the same sense that you can be addicted to heroin – but certain foods, especially highly manufactured, sugar-rich foods, stimulate their own taking as if they’re a drug.”
In an interview at the annual meeting of the American College of Psychiatrists, Dr. Gold – a pioneer in the so-called “food addiction hypothesis” – highlighted current trends in food and process addictions.
He noted that behavioral and medical treatments commonly used for alcohol dependence, for example, are proving effective for patients coping with overeating, obesity, and binge eating. Psychiatrists will play an expanding role in caring for such patients, he predicted.
Dr. Gold reported having no relevant financial disclosures.
*Correction, 4/2/2015: An earlier version of this story misstated Dr. Gold's title.
On Twitter @dougbrunk
HUNTINGTON BEACH, CALIF. – Can you really be addicted to food?
That’s the question posed by Dr. Mark S. Gold, adjunct professor of psychiatry at the Washington University School of Medicine in St. Louis.* His answer? “Maybe not in the same sense that you can be addicted to heroin – but certain foods, especially highly manufactured, sugar-rich foods, stimulate their own taking as if they’re a drug.”
In an interview at the annual meeting of the American College of Psychiatrists, Dr. Gold – a pioneer in the so-called “food addiction hypothesis” – highlighted current trends in food and process addictions.
He noted that behavioral and medical treatments commonly used for alcohol dependence, for example, are proving effective for patients coping with overeating, obesity, and binge eating. Psychiatrists will play an expanding role in caring for such patients, he predicted.
Dr. Gold reported having no relevant financial disclosures.
*Correction, 4/2/2015: An earlier version of this story misstated Dr. Gold's title.
On Twitter @dougbrunk
AT THE AMERICAN COLLEGE OF PSYCHIATRISTS MEETING
Neuroimaging techniques making inroads as a diagnostic tool
HUNTINGTON BEACH, CALIF. – Five years ago, Dr. Bradley S. Peterson was about to give up on the idea that advanced neuroimaging could one day be used as a diagnostic tool for clinical practice in child psychiatry.
“I thought it was completely hopeless; I really did,” Dr. Peterson told attendees at the annual meeting of the American College of Psychiatrists. “I’m extremely optimistic now.”
Thanks to advances in technology and more rigorously designed studies, imaging will aid clinical diagnoses in the foreseeable future, predicted Dr. Peterson, director of the Institute for the Developing Mind at Children’s Hospital Los Angeles.
“I sincerely believe it’s around the corner,” he said. “I think the biggest challenge may be addressing regulatory issues, as some of these computer algorithms, depending on how they are used, may constitute a medical device. Getting things through the [Food and Drug Administration] can be prohibitively expensive, time consuming, and arduous.”
Using examples from studies conducted by his lab and that of colleagues in the field, he discussed four cutting-edge new uses of imaging studies in childhood disorders psychiatry.
Identifying biological vulnerabilities
In an ongoing study conducted with Myrna M. Weissman, Ph.D., division chief of epidemiology in the department of psychiatry at Columbia University, New York, researchers are prospectively following a three-generation cohort for more than 25 years in an effort to understand families at high and low risk for major depressive disorder. A large sample of patients with chronic, severe, highly impairing depression was recruited in and around New Haven, Conn., along with a group of community controls who, according to self-report, spouses, and other family members, had never suffered from depression. Longitudinal studies of that cohort to date have demonstrated that grandchildren in families with multiple generations of major depressive disorder are at high risk for depression and anxiety disorders.
In a study that Dr. Peterson conducted with Dr. Weissman and colleagues, the brains of 131 study participants were imaged “to identify in the brain what is transmitted between these generations that place these biological offspring of depressed people at risk for depression,” he explained. He presented published brain measurement findings from 66 subjects in the high-risk group and 65 in the low-risk group (PNAS 2009;105:6273-8). The primary measurement of interest was the cortical mantle, which he described as “the gray matter at the surface of the brain, which contains most of the nerve cell bodies and synapses of the brain that carry information from one part of the brain to another. This is generally about 6 mm thick on average, but it varies slightly across the brain.”
Dr. Peterson and his associates found that subjects at high risk for depression had a 28% average reduction in cortical thickness, compared with their counterparts in the low-risk group, primarily in the right hemisphere of the brain. He characterized this as “a massive finding in two respects. It’s massive in its spatial extent, from the back of the brain to the front. It’s also massive at each point of the brain. The average reduction of 28% in offspring of the high-risk people is a massive biological effect. It’s astounding that we can find this in offspring. Even people who are offspring of depressed individuals two generations removed carry this abnormality, and it’s there even if they’ve never been sick in their lifetime. This high-risk approach is one way of identifying true biological vulnerability to illness.”
Identifying brain-based causal mechanisms
This effort involves yoking MRI or other imaging technology to randomized, controlled trials. “Instead of having a change in symptoms be an outcome measure, here it’s a change in MRI or brain-based measure,” said Dr. Peterson, who is also director of child and adolescent psychiatry at the University of Southern California, Los Angeles.
In a recent study, he and other researchers, including Dr. David J. Hellerstein and Dr. Jonathan Posner at Columbia University, conducted functional MRIs to determine whether antidepressant medication normalizes default mode network connectivity in adults with dysthymia. They imaged 25 healthy controls at one point in time and imaged 41 dysthymic adults twice: once before and once after a 10-week trial of duloxetine (JAMA Psychiatry 2013;70:373-82). They were interested in the effects of duloxetine on the default mode network of the brain, a “circuit” of brain regions that include the ventral anterior cingulate, the posterior cingulate, and the inferior parietal lobule.
“It’s called the default mode [circuit] because when you daydream or mind wander or introspect, this set of circuits is highly active,” Dr. Peterson said. “If you have to perform a task rather than let your mind wander, that system has to shut off. This region has been implicated many times in depression, because it’s been shown to be hyperactive in currently depressed people. It’s been especially related to ruminations. So the more people ruminate, the more this default system is active.”
At baseline, the researchers found that the coherence of neural activity within the brain’s default mode network was greater in persons with dysthymia than in healthy controls. Following the 10-week trial, they found that treatment with duloxetine, but not placebo, normalized default mode network connectivity (P < .03). “If they received placebo, the activity [in this brain region] didn’t change at all; it’s exactly the same as it was before the medication trial,” Dr. Peterson said. “If they received active medication, activity normalized; it reduced the cross-talk across nodes of the default mode network so that now, their [default mode network] activity is no longer discernible or different from the healthy controls. This shows that duloxetine is causing the reduction in the cross-talk between these circuits, and by doing so, it’s normalizing activity in the default mode system.”
A similar effect was observed in a study that assessed the impact of stimulant medications in children with attention-deficit/hyperactivity disorder (ADHD). Specifically, researchers including Dr. Peterson used cross-sectional MRI to examine the morphologic features of the basal ganglia nuclei in 48 children with ADHD who were off medication and 56 healthy controls (Am. J. Psychiatry 2010;167:977-86).
“Reduced volume in portions of the basal ganglia structures is important for impulse control and attention,” Dr. Peterson said. “We found that those same structures are enlarged when kids are on their medication so as not to be different from healthy controls. We think that stimulant medications in ADHD are normalizing these disturbances in the structure of the basal ganglia.”
Identifying neurometabolic dysfunction
Prior studies measured lactate in peripheral blood, muscle, or postmortem samples of people with autism spectrum disorders (ASD), “but these do not necessarily indicate the presence of metabolic dysfunction in the brain,” Dr. Peterson said. In a recent study he and other researchers used magnetic resonance spectroscopic imaging to measure lactate in the brains of people at risk for ASD. The analysis included 75 high-functioning ASD participants and 96 typically developing children and adults (JAMA Psychiatry 2014;71:665:71). Definite lactate peaks were present at a significantly higher rate in the ASD participants, compared with controls (13% vs. 1%, P = .001). In addition, the presence of lactate was significantly greater in adults, compared with children (20% vs. 6%; P = .004), ”perhaps suggesting that this could be a degenerative process that exacerbates through time,” Dr. Peterson said.
The presence of lactate did not correlate with clinical symptoms based on ASD subtype, autism diagnostic observation schedule domain score, or full-scale IQ. Dr. Peterson said the presence of lactate is “definitive proof that mitochondria are dysfunctional in the brains of a substantial number of autistic people. This disturbance is found now in autism, but it will likely be true in people with other neuropsychiatric disorders as well.”
A key advantage of MR spectroscopic imaging, he continued, “is that we can determine where in the brain lactate’s being produced. These kinds of studies will help guide studies in mitochondrial genetics and dysfunction in ASD and other conditions. It also has important clinical implications, because there are novel treatment approaches now for mitochondrial dysfunction, such as dietary interventions that can reduce the metabolic dysfunction.”
Using automated, brain-based diagnostic classifications
Dr. Peterson and other researchers used an automated method to diagnose individuals as having one of various neuropsychiatric illnesses using only anatomical MRI scans. “The method employs a semisupervised learning algorithm that discovers natural groupings of brains based on the spatial patterns of variation in the morphology of the cerebral cortex and other brain regions,” they explained in their article (PLoS One 2012;7:e50698). “We used split-half and leave-one-out cross-validation analyses in large MRI datasets to assess the reproducibility and diagnostic accuracy of those groupings.”
Conceptually, “we look at the volume increases and decreases throughout the surface of the cortex,” Dr. Peterson said at the meeting. “We do the same thing at the basal ganglia, thalamus, cerebellum, amygdala, and hippocampus. What we’re trying to do is to use structural variation in the brain to identify spatial patterns in brain structure that help to identify people who have brain features in common, just as the pattern of dermatomal ridges on your finger can identify specific individuals with great accuracy.
“We use machine learning algorithms to identify a pattern of abnormality in brain structure that’s more similar among people with Tourette’s syndrome, for example, than in people who have ADHD.”
Using this automated approach to making clinical diagnoses yielded impressive results. For example, the sensitivity and specificity to differentiate ADHD subjects from healthy controls was 93.6% and 89.5%, respectively. It also was strong for diagnosis of Tourette’s syndrome, (94.6% sensitive and 79% specific) and for schizophrenia (93.1% sensitive and 94.5% specific).
Dr. Peterson disclosed that he has received research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, the National Institute of Environmental Health Sciences, the National Science Foundation, the Brain & Behavior Research Foundation (formerly NARSAD), and the Simons Foundation. He also has received investigator-initiated funding from Eli Lilly and Pfizer.
On Twitter @dougbrunk
HUNTINGTON BEACH, CALIF. – Five years ago, Dr. Bradley S. Peterson was about to give up on the idea that advanced neuroimaging could one day be used as a diagnostic tool for clinical practice in child psychiatry.
“I thought it was completely hopeless; I really did,” Dr. Peterson told attendees at the annual meeting of the American College of Psychiatrists. “I’m extremely optimistic now.”
Thanks to advances in technology and more rigorously designed studies, imaging will aid clinical diagnoses in the foreseeable future, predicted Dr. Peterson, director of the Institute for the Developing Mind at Children’s Hospital Los Angeles.
“I sincerely believe it’s around the corner,” he said. “I think the biggest challenge may be addressing regulatory issues, as some of these computer algorithms, depending on how they are used, may constitute a medical device. Getting things through the [Food and Drug Administration] can be prohibitively expensive, time consuming, and arduous.”
Using examples from studies conducted by his lab and that of colleagues in the field, he discussed four cutting-edge new uses of imaging studies in childhood disorders psychiatry.
Identifying biological vulnerabilities
In an ongoing study conducted with Myrna M. Weissman, Ph.D., division chief of epidemiology in the department of psychiatry at Columbia University, New York, researchers are prospectively following a three-generation cohort for more than 25 years in an effort to understand families at high and low risk for major depressive disorder. A large sample of patients with chronic, severe, highly impairing depression was recruited in and around New Haven, Conn., along with a group of community controls who, according to self-report, spouses, and other family members, had never suffered from depression. Longitudinal studies of that cohort to date have demonstrated that grandchildren in families with multiple generations of major depressive disorder are at high risk for depression and anxiety disorders.
In a study that Dr. Peterson conducted with Dr. Weissman and colleagues, the brains of 131 study participants were imaged “to identify in the brain what is transmitted between these generations that place these biological offspring of depressed people at risk for depression,” he explained. He presented published brain measurement findings from 66 subjects in the high-risk group and 65 in the low-risk group (PNAS 2009;105:6273-8). The primary measurement of interest was the cortical mantle, which he described as “the gray matter at the surface of the brain, which contains most of the nerve cell bodies and synapses of the brain that carry information from one part of the brain to another. This is generally about 6 mm thick on average, but it varies slightly across the brain.”
Dr. Peterson and his associates found that subjects at high risk for depression had a 28% average reduction in cortical thickness, compared with their counterparts in the low-risk group, primarily in the right hemisphere of the brain. He characterized this as “a massive finding in two respects. It’s massive in its spatial extent, from the back of the brain to the front. It’s also massive at each point of the brain. The average reduction of 28% in offspring of the high-risk people is a massive biological effect. It’s astounding that we can find this in offspring. Even people who are offspring of depressed individuals two generations removed carry this abnormality, and it’s there even if they’ve never been sick in their lifetime. This high-risk approach is one way of identifying true biological vulnerability to illness.”
Identifying brain-based causal mechanisms
This effort involves yoking MRI or other imaging technology to randomized, controlled trials. “Instead of having a change in symptoms be an outcome measure, here it’s a change in MRI or brain-based measure,” said Dr. Peterson, who is also director of child and adolescent psychiatry at the University of Southern California, Los Angeles.
In a recent study, he and other researchers, including Dr. David J. Hellerstein and Dr. Jonathan Posner at Columbia University, conducted functional MRIs to determine whether antidepressant medication normalizes default mode network connectivity in adults with dysthymia. They imaged 25 healthy controls at one point in time and imaged 41 dysthymic adults twice: once before and once after a 10-week trial of duloxetine (JAMA Psychiatry 2013;70:373-82). They were interested in the effects of duloxetine on the default mode network of the brain, a “circuit” of brain regions that include the ventral anterior cingulate, the posterior cingulate, and the inferior parietal lobule.
“It’s called the default mode [circuit] because when you daydream or mind wander or introspect, this set of circuits is highly active,” Dr. Peterson said. “If you have to perform a task rather than let your mind wander, that system has to shut off. This region has been implicated many times in depression, because it’s been shown to be hyperactive in currently depressed people. It’s been especially related to ruminations. So the more people ruminate, the more this default system is active.”
At baseline, the researchers found that the coherence of neural activity within the brain’s default mode network was greater in persons with dysthymia than in healthy controls. Following the 10-week trial, they found that treatment with duloxetine, but not placebo, normalized default mode network connectivity (P < .03). “If they received placebo, the activity [in this brain region] didn’t change at all; it’s exactly the same as it was before the medication trial,” Dr. Peterson said. “If they received active medication, activity normalized; it reduced the cross-talk across nodes of the default mode network so that now, their [default mode network] activity is no longer discernible or different from the healthy controls. This shows that duloxetine is causing the reduction in the cross-talk between these circuits, and by doing so, it’s normalizing activity in the default mode system.”
A similar effect was observed in a study that assessed the impact of stimulant medications in children with attention-deficit/hyperactivity disorder (ADHD). Specifically, researchers including Dr. Peterson used cross-sectional MRI to examine the morphologic features of the basal ganglia nuclei in 48 children with ADHD who were off medication and 56 healthy controls (Am. J. Psychiatry 2010;167:977-86).
“Reduced volume in portions of the basal ganglia structures is important for impulse control and attention,” Dr. Peterson said. “We found that those same structures are enlarged when kids are on their medication so as not to be different from healthy controls. We think that stimulant medications in ADHD are normalizing these disturbances in the structure of the basal ganglia.”
Identifying neurometabolic dysfunction
Prior studies measured lactate in peripheral blood, muscle, or postmortem samples of people with autism spectrum disorders (ASD), “but these do not necessarily indicate the presence of metabolic dysfunction in the brain,” Dr. Peterson said. In a recent study he and other researchers used magnetic resonance spectroscopic imaging to measure lactate in the brains of people at risk for ASD. The analysis included 75 high-functioning ASD participants and 96 typically developing children and adults (JAMA Psychiatry 2014;71:665:71). Definite lactate peaks were present at a significantly higher rate in the ASD participants, compared with controls (13% vs. 1%, P = .001). In addition, the presence of lactate was significantly greater in adults, compared with children (20% vs. 6%; P = .004), ”perhaps suggesting that this could be a degenerative process that exacerbates through time,” Dr. Peterson said.
The presence of lactate did not correlate with clinical symptoms based on ASD subtype, autism diagnostic observation schedule domain score, or full-scale IQ. Dr. Peterson said the presence of lactate is “definitive proof that mitochondria are dysfunctional in the brains of a substantial number of autistic people. This disturbance is found now in autism, but it will likely be true in people with other neuropsychiatric disorders as well.”
A key advantage of MR spectroscopic imaging, he continued, “is that we can determine where in the brain lactate’s being produced. These kinds of studies will help guide studies in mitochondrial genetics and dysfunction in ASD and other conditions. It also has important clinical implications, because there are novel treatment approaches now for mitochondrial dysfunction, such as dietary interventions that can reduce the metabolic dysfunction.”
Using automated, brain-based diagnostic classifications
Dr. Peterson and other researchers used an automated method to diagnose individuals as having one of various neuropsychiatric illnesses using only anatomical MRI scans. “The method employs a semisupervised learning algorithm that discovers natural groupings of brains based on the spatial patterns of variation in the morphology of the cerebral cortex and other brain regions,” they explained in their article (PLoS One 2012;7:e50698). “We used split-half and leave-one-out cross-validation analyses in large MRI datasets to assess the reproducibility and diagnostic accuracy of those groupings.”
Conceptually, “we look at the volume increases and decreases throughout the surface of the cortex,” Dr. Peterson said at the meeting. “We do the same thing at the basal ganglia, thalamus, cerebellum, amygdala, and hippocampus. What we’re trying to do is to use structural variation in the brain to identify spatial patterns in brain structure that help to identify people who have brain features in common, just as the pattern of dermatomal ridges on your finger can identify specific individuals with great accuracy.
“We use machine learning algorithms to identify a pattern of abnormality in brain structure that’s more similar among people with Tourette’s syndrome, for example, than in people who have ADHD.”
Using this automated approach to making clinical diagnoses yielded impressive results. For example, the sensitivity and specificity to differentiate ADHD subjects from healthy controls was 93.6% and 89.5%, respectively. It also was strong for diagnosis of Tourette’s syndrome, (94.6% sensitive and 79% specific) and for schizophrenia (93.1% sensitive and 94.5% specific).
Dr. Peterson disclosed that he has received research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, the National Institute of Environmental Health Sciences, the National Science Foundation, the Brain & Behavior Research Foundation (formerly NARSAD), and the Simons Foundation. He also has received investigator-initiated funding from Eli Lilly and Pfizer.
On Twitter @dougbrunk
HUNTINGTON BEACH, CALIF. – Five years ago, Dr. Bradley S. Peterson was about to give up on the idea that advanced neuroimaging could one day be used as a diagnostic tool for clinical practice in child psychiatry.
“I thought it was completely hopeless; I really did,” Dr. Peterson told attendees at the annual meeting of the American College of Psychiatrists. “I’m extremely optimistic now.”
Thanks to advances in technology and more rigorously designed studies, imaging will aid clinical diagnoses in the foreseeable future, predicted Dr. Peterson, director of the Institute for the Developing Mind at Children’s Hospital Los Angeles.
“I sincerely believe it’s around the corner,” he said. “I think the biggest challenge may be addressing regulatory issues, as some of these computer algorithms, depending on how they are used, may constitute a medical device. Getting things through the [Food and Drug Administration] can be prohibitively expensive, time consuming, and arduous.”
Using examples from studies conducted by his lab and that of colleagues in the field, he discussed four cutting-edge new uses of imaging studies in childhood disorders psychiatry.
Identifying biological vulnerabilities
In an ongoing study conducted with Myrna M. Weissman, Ph.D., division chief of epidemiology in the department of psychiatry at Columbia University, New York, researchers are prospectively following a three-generation cohort for more than 25 years in an effort to understand families at high and low risk for major depressive disorder. A large sample of patients with chronic, severe, highly impairing depression was recruited in and around New Haven, Conn., along with a group of community controls who, according to self-report, spouses, and other family members, had never suffered from depression. Longitudinal studies of that cohort to date have demonstrated that grandchildren in families with multiple generations of major depressive disorder are at high risk for depression and anxiety disorders.
In a study that Dr. Peterson conducted with Dr. Weissman and colleagues, the brains of 131 study participants were imaged “to identify in the brain what is transmitted between these generations that place these biological offspring of depressed people at risk for depression,” he explained. He presented published brain measurement findings from 66 subjects in the high-risk group and 65 in the low-risk group (PNAS 2009;105:6273-8). The primary measurement of interest was the cortical mantle, which he described as “the gray matter at the surface of the brain, which contains most of the nerve cell bodies and synapses of the brain that carry information from one part of the brain to another. This is generally about 6 mm thick on average, but it varies slightly across the brain.”
Dr. Peterson and his associates found that subjects at high risk for depression had a 28% average reduction in cortical thickness, compared with their counterparts in the low-risk group, primarily in the right hemisphere of the brain. He characterized this as “a massive finding in two respects. It’s massive in its spatial extent, from the back of the brain to the front. It’s also massive at each point of the brain. The average reduction of 28% in offspring of the high-risk people is a massive biological effect. It’s astounding that we can find this in offspring. Even people who are offspring of depressed individuals two generations removed carry this abnormality, and it’s there even if they’ve never been sick in their lifetime. This high-risk approach is one way of identifying true biological vulnerability to illness.”
Identifying brain-based causal mechanisms
This effort involves yoking MRI or other imaging technology to randomized, controlled trials. “Instead of having a change in symptoms be an outcome measure, here it’s a change in MRI or brain-based measure,” said Dr. Peterson, who is also director of child and adolescent psychiatry at the University of Southern California, Los Angeles.
In a recent study, he and other researchers, including Dr. David J. Hellerstein and Dr. Jonathan Posner at Columbia University, conducted functional MRIs to determine whether antidepressant medication normalizes default mode network connectivity in adults with dysthymia. They imaged 25 healthy controls at one point in time and imaged 41 dysthymic adults twice: once before and once after a 10-week trial of duloxetine (JAMA Psychiatry 2013;70:373-82). They were interested in the effects of duloxetine on the default mode network of the brain, a “circuit” of brain regions that include the ventral anterior cingulate, the posterior cingulate, and the inferior parietal lobule.
“It’s called the default mode [circuit] because when you daydream or mind wander or introspect, this set of circuits is highly active,” Dr. Peterson said. “If you have to perform a task rather than let your mind wander, that system has to shut off. This region has been implicated many times in depression, because it’s been shown to be hyperactive in currently depressed people. It’s been especially related to ruminations. So the more people ruminate, the more this default system is active.”
At baseline, the researchers found that the coherence of neural activity within the brain’s default mode network was greater in persons with dysthymia than in healthy controls. Following the 10-week trial, they found that treatment with duloxetine, but not placebo, normalized default mode network connectivity (P < .03). “If they received placebo, the activity [in this brain region] didn’t change at all; it’s exactly the same as it was before the medication trial,” Dr. Peterson said. “If they received active medication, activity normalized; it reduced the cross-talk across nodes of the default mode network so that now, their [default mode network] activity is no longer discernible or different from the healthy controls. This shows that duloxetine is causing the reduction in the cross-talk between these circuits, and by doing so, it’s normalizing activity in the default mode system.”
A similar effect was observed in a study that assessed the impact of stimulant medications in children with attention-deficit/hyperactivity disorder (ADHD). Specifically, researchers including Dr. Peterson used cross-sectional MRI to examine the morphologic features of the basal ganglia nuclei in 48 children with ADHD who were off medication and 56 healthy controls (Am. J. Psychiatry 2010;167:977-86).
“Reduced volume in portions of the basal ganglia structures is important for impulse control and attention,” Dr. Peterson said. “We found that those same structures are enlarged when kids are on their medication so as not to be different from healthy controls. We think that stimulant medications in ADHD are normalizing these disturbances in the structure of the basal ganglia.”
Identifying neurometabolic dysfunction
Prior studies measured lactate in peripheral blood, muscle, or postmortem samples of people with autism spectrum disorders (ASD), “but these do not necessarily indicate the presence of metabolic dysfunction in the brain,” Dr. Peterson said. In a recent study he and other researchers used magnetic resonance spectroscopic imaging to measure lactate in the brains of people at risk for ASD. The analysis included 75 high-functioning ASD participants and 96 typically developing children and adults (JAMA Psychiatry 2014;71:665:71). Definite lactate peaks were present at a significantly higher rate in the ASD participants, compared with controls (13% vs. 1%, P = .001). In addition, the presence of lactate was significantly greater in adults, compared with children (20% vs. 6%; P = .004), ”perhaps suggesting that this could be a degenerative process that exacerbates through time,” Dr. Peterson said.
The presence of lactate did not correlate with clinical symptoms based on ASD subtype, autism diagnostic observation schedule domain score, or full-scale IQ. Dr. Peterson said the presence of lactate is “definitive proof that mitochondria are dysfunctional in the brains of a substantial number of autistic people. This disturbance is found now in autism, but it will likely be true in people with other neuropsychiatric disorders as well.”
A key advantage of MR spectroscopic imaging, he continued, “is that we can determine where in the brain lactate’s being produced. These kinds of studies will help guide studies in mitochondrial genetics and dysfunction in ASD and other conditions. It also has important clinical implications, because there are novel treatment approaches now for mitochondrial dysfunction, such as dietary interventions that can reduce the metabolic dysfunction.”
Using automated, brain-based diagnostic classifications
Dr. Peterson and other researchers used an automated method to diagnose individuals as having one of various neuropsychiatric illnesses using only anatomical MRI scans. “The method employs a semisupervised learning algorithm that discovers natural groupings of brains based on the spatial patterns of variation in the morphology of the cerebral cortex and other brain regions,” they explained in their article (PLoS One 2012;7:e50698). “We used split-half and leave-one-out cross-validation analyses in large MRI datasets to assess the reproducibility and diagnostic accuracy of those groupings.”
Conceptually, “we look at the volume increases and decreases throughout the surface of the cortex,” Dr. Peterson said at the meeting. “We do the same thing at the basal ganglia, thalamus, cerebellum, amygdala, and hippocampus. What we’re trying to do is to use structural variation in the brain to identify spatial patterns in brain structure that help to identify people who have brain features in common, just as the pattern of dermatomal ridges on your finger can identify specific individuals with great accuracy.
“We use machine learning algorithms to identify a pattern of abnormality in brain structure that’s more similar among people with Tourette’s syndrome, for example, than in people who have ADHD.”
Using this automated approach to making clinical diagnoses yielded impressive results. For example, the sensitivity and specificity to differentiate ADHD subjects from healthy controls was 93.6% and 89.5%, respectively. It also was strong for diagnosis of Tourette’s syndrome, (94.6% sensitive and 79% specific) and for schizophrenia (93.1% sensitive and 94.5% specific).
Dr. Peterson disclosed that he has received research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, the National Institute of Environmental Health Sciences, the National Science Foundation, the Brain & Behavior Research Foundation (formerly NARSAD), and the Simons Foundation. He also has received investigator-initiated funding from Eli Lilly and Pfizer.
On Twitter @dougbrunk
