Denise Napoli

Parkinson’s disease patients with mild cognitive impairment have dysfunctional circuitry in brain networks involving the right dorsal caudate nucleus and the bilateral anterior cingulate cortex, compared with unaffected Parkinson’s patients, according to a prospective cohort study.

"The cognitive dysfunctions associated with Parkinson’s disease are gaining clinical importance because of the relative success of therapeutic approaches in the treatment of motor symptoms, but knowledge of the neuropathology underlying cognitive impairment remains insufficient," wrote first author Urban Ekman and his colleagues at Umeå University, Sweden.

The investigators looked at all patients in the Umeå University catchment area who were newly diagnosed with idiopathic Parkinson’s disease between Jan. 1, 2004, and April 30, 2009, in what they called the first study to evaluate mild cognitive impairment with functional MRI (fMRI) (Lancet Neurol. 2012;11:679-87).

In total, 77 Parkinson’s patients were included in the analysis (60% male, mean age 68 years); they were compared with 24 controls (50% male, mean age 68 years).

All patients were drug naive for dopaminergic medication. Patients were excluded from the study if they had dementia, major depression, or if they answered fewer than 55% of questions in the working memory task correctly.

Mild cognitive impairment (MCI) was diagnosed according to Movement Disorder Society criteria (Mov. Disord. 2012;27:349-56). In short, participants were tested in several cognitive domains: executive function, attention and working memory, episodic memory, language, and visuospatial function. Participants who scored 1.5 standard deviations or more below the mean for at least two domains were diagnosed with MCI.

Mr. Ekman and his colleagues found that 33 (43%) of the 77 Parkinson’s patients had MCI, according to the criteria. Thirty were included in the analysis after three patients were excluded because their impairment was primarily visuospatial or language contingent.

The researchers then conducted a verbal "two-back" working memory task while patients and controls underwent fMRI scans. Upon hearing a series of nouns, patients were asked to respond "yes" when the word matched the one presented two items earlier, and "no" when it was different, using MRI-compatible keypads.

On this test, in general, patients with Parkinson’s had fewer correct answers than did controls (P = .024), and patients with Parkinson’s and MCI had fewer correct answers compared with both controls (P = .02) and Parkinson’s patients without MCI (P = .04).

"Compared with controls, patients with Parkinson’s disease had significant underrecruitment of the right dorsolateral prefrontal cortex, the bilateral primary and premotor cortices, the occipital cortex, and the cerebellum when undertaking the two-back task," the authors wrote regarding the fMRI results.

Moreover, "A lower BOLD [blood-oxygen-level-dependent] signal was noted for the Parkinson’s disease group in bilateral striatal regions compared with the control group," they added.

The authors then looked at Parkinson’s patients with and without MCI in a whole-brain analysis.

They found that "the anterior cingulate cortex region was significantly recruited in both control individuals and patients with Parkinson’s disease without MCI [P less than .001], but weakly and nonsignificantly recruited in patients with Parkinson’s disease with MCI."

Finally, in region of interest analysis, "there was underrecruitment of the right dorsal caudate in patients with Parkinson’s disease with MCI compared with those without MCI [P = .005]," wrote the authors.

Indeed, a plot of the effect revealed a "stepwise" response, "such that the right caudate response was maximum in control individuals, intermediate in patients with Parkinson’s disease without MCI, and lowest and nonsignificant in those with Parkinson’s disease and MCI," they wrote.

In seeking to verify that these results were due to cognition and were not motor related, the researchers compared groups matched according to motor scores.

"The results persisted" in the right caudate and anterior cingulate cortex, they wrote.

The authors declared that they had no conflicts of interest. The study was funded by nonprofit organizations, including the Swedish Medical Research Council and the Swedish Parkinson Foundation.

Parkinson’s disease patients with mild cognitive impairment have dysfunctional circuitry in brain networks involving the right dorsal caudate nucleus and the bilateral anterior cingulate cortex, compared with unaffected Parkinson’s patients, according to a prospective cohort study.

"The cognitive dysfunctions associated with Parkinson’s disease are gaining clinical importance because of the relative success of therapeutic approaches in the treatment of motor symptoms, but knowledge of the neuropathology underlying cognitive impairment remains insufficient," wrote first author Urban Ekman and his colleagues at Umeå University, Sweden.

The investigators looked at all patients in the Umeå University catchment area who were newly diagnosed with idiopathic Parkinson’s disease between Jan. 1, 2004, and April 30, 2009, in what they called the first study to evaluate mild cognitive impairment with functional MRI (fMRI) (Lancet Neurol. 2012;11:679-87).

In total, 77 Parkinson’s patients were included in the analysis (60% male, mean age 68 years); they were compared with 24 controls (50% male, mean age 68 years).

All patients were drug naive for dopaminergic medication. Patients were excluded from the study if they had dementia, major depression, or if they answered fewer than 55% of questions in the working memory task correctly.

Mild cognitive impairment (MCI) was diagnosed according to Movement Disorder Society criteria (Mov. Disord. 2012;27:349-56). In short, participants were tested in several cognitive domains: executive function, attention and working memory, episodic memory, language, and visuospatial function. Participants who scored 1.5 standard deviations or more below the mean for at least two domains were diagnosed with MCI.

Mr. Ekman and his colleagues found that 33 (43%) of the 77 Parkinson’s patients had MCI, according to the criteria. Thirty were included in the analysis after three patients were excluded because their impairment was primarily visuospatial or language contingent.

The researchers then conducted a verbal "two-back" working memory task while patients and controls underwent fMRI scans. Upon hearing a series of nouns, patients were asked to respond "yes" when the word matched the one presented two items earlier, and "no" when it was different, using MRI-compatible keypads.

On this test, in general, patients with Parkinson’s had fewer correct answers than did controls (P = .024), and patients with Parkinson’s and MCI had fewer correct answers compared with both controls (P = .02) and Parkinson’s patients without MCI (P = .04).

"Compared with controls, patients with Parkinson’s disease had significant underrecruitment of the right dorsolateral prefrontal cortex, the bilateral primary and premotor cortices, the occipital cortex, and the cerebellum when undertaking the two-back task," the authors wrote regarding the fMRI results.

Moreover, "A lower BOLD [blood-oxygen-level-dependent] signal was noted for the Parkinson’s disease group in bilateral striatal regions compared with the control group," they added.

The authors then looked at Parkinson’s patients with and without MCI in a whole-brain analysis.

They found that "the anterior cingulate cortex region was significantly recruited in both control individuals and patients with Parkinson’s disease without MCI [P less than .001], but weakly and nonsignificantly recruited in patients with Parkinson’s disease with MCI."

Finally, in region of interest analysis, "there was underrecruitment of the right dorsal caudate in patients with Parkinson’s disease with MCI compared with those without MCI [P = .005]," wrote the authors.

Indeed, a plot of the effect revealed a "stepwise" response, "such that the right caudate response was maximum in control individuals, intermediate in patients with Parkinson’s disease without MCI, and lowest and nonsignificant in those with Parkinson’s disease and MCI," they wrote.

In seeking to verify that these results were due to cognition and were not motor related, the researchers compared groups matched according to motor scores.

"The results persisted" in the right caudate and anterior cingulate cortex, they wrote.

The authors declared that they had no conflicts of interest. The study was funded by nonprofit organizations, including the Swedish Medical Research Council and the Swedish Parkinson Foundation.

Parkinson’s disease patients with mild cognitive impairment have dysfunctional circuitry in brain networks involving the right dorsal caudate nucleus and the bilateral anterior cingulate cortex, compared with unaffected Parkinson’s patients, according to a prospective cohort study.

"The cognitive dysfunctions associated with Parkinson’s disease are gaining clinical importance because of the relative success of therapeutic approaches in the treatment of motor symptoms, but knowledge of the neuropathology underlying cognitive impairment remains insufficient," wrote first author Urban Ekman and his colleagues at Umeå University, Sweden.

The investigators looked at all patients in the Umeå University catchment area who were newly diagnosed with idiopathic Parkinson’s disease between Jan. 1, 2004, and April 30, 2009, in what they called the first study to evaluate mild cognitive impairment with functional MRI (fMRI) (Lancet Neurol. 2012;11:679-87).

In total, 77 Parkinson’s patients were included in the analysis (60% male, mean age 68 years); they were compared with 24 controls (50% male, mean age 68 years).

All patients were drug naive for dopaminergic medication. Patients were excluded from the study if they had dementia, major depression, or if they answered fewer than 55% of questions in the working memory task correctly.

Mild cognitive impairment (MCI) was diagnosed according to Movement Disorder Society criteria (Mov. Disord. 2012;27:349-56). In short, participants were tested in several cognitive domains: executive function, attention and working memory, episodic memory, language, and visuospatial function. Participants who scored 1.5 standard deviations or more below the mean for at least two domains were diagnosed with MCI.

Mr. Ekman and his colleagues found that 33 (43%) of the 77 Parkinson’s patients had MCI, according to the criteria. Thirty were included in the analysis after three patients were excluded because their impairment was primarily visuospatial or language contingent.

The researchers then conducted a verbal "two-back" working memory task while patients and controls underwent fMRI scans. Upon hearing a series of nouns, patients were asked to respond "yes" when the word matched the one presented two items earlier, and "no" when it was different, using MRI-compatible keypads.

On this test, in general, patients with Parkinson’s had fewer correct answers than did controls (P = .024), and patients with Parkinson’s and MCI had fewer correct answers compared with both controls (P = .02) and Parkinson’s patients without MCI (P = .04).

"Compared with controls, patients with Parkinson’s disease had significant underrecruitment of the right dorsolateral prefrontal cortex, the bilateral primary and premotor cortices, the occipital cortex, and the cerebellum when undertaking the two-back task," the authors wrote regarding the fMRI results.

Moreover, "A lower BOLD [blood-oxygen-level-dependent] signal was noted for the Parkinson’s disease group in bilateral striatal regions compared with the control group," they added.

The authors then looked at Parkinson’s patients with and without MCI in a whole-brain analysis.

They found that "the anterior cingulate cortex region was significantly recruited in both control individuals and patients with Parkinson’s disease without MCI [P less than .001], but weakly and nonsignificantly recruited in patients with Parkinson’s disease with MCI."

Finally, in region of interest analysis, "there was underrecruitment of the right dorsal caudate in patients with Parkinson’s disease with MCI compared with those without MCI [P = .005]," wrote the authors.

Indeed, a plot of the effect revealed a "stepwise" response, "such that the right caudate response was maximum in control individuals, intermediate in patients with Parkinson’s disease without MCI, and lowest and nonsignificant in those with Parkinson’s disease and MCI," they wrote.

In seeking to verify that these results were due to cognition and were not motor related, the researchers compared groups matched according to motor scores.

"The results persisted" in the right caudate and anterior cingulate cortex, they wrote.

The authors declared that they had no conflicts of interest. The study was funded by nonprofit organizations, including the Swedish Medical Research Council and the Swedish Parkinson Foundation.

HIV-infected adults should start antiretroviral therapy as soon as possible, regardless of CD4 count, according to a recommendation from the International Antiviral Society–USA presented at the AIDS 2012 meeting in Washington.

The recommendation represents a major change from the last set of guidelines, issued in 2010. Those earlier guidelines recommended starting antiretrovirals when CD4 counts fell beneath 500 cells/mL, and "considering" treatment in patients with higher counts.

In writing the new guidelines, which also appear in the July 25 issue of JAMA (2012;308:387-402), Dr. Melanie A. Thompson and a panel convened by the International Antiviral Society–USA (IAS-USA) conducted a literature review of all new published data and data presented at scientific conferences between July 2010 and May 2012.

All recommendations were applicable only to HIV-infected adults in resource-rich settings, and dealt with antiretroviral therapies that were either already approved or in late-stage development.

The field of HIV prophylaxis has also seen significant progress since the 2010 update, and the new guidelines reflect those advances.

"Recently, antiretroviral therapy used as oral pre-exposure prophylaxis (PrEP) has been shown to be effective in three large trials using daily tenofovir/emtricitabine or tenofovir in gay and bisexual men and transgender women (iPrEx), heterosexual HIV-serodiscordant couples (Partners PrEP), and heterosexual men and women (TDF2)," wrote Dr. Thompson of the AIDS Research Consortium of Atlanta.

Indeed, following the iPrEx results, the Centers for Disease Control and Prevention issued interim guidance (MMWR 2011;60:65-8) for HIV-negative homosexual men who elect to take tenofovir/emtricitabine for prophylaxis.

And July 16, the Food and Drug Administration approved the use of an oral once-daily combination antiviral medication, Truvada (tenofovir and emtricitabine), for prevention in uninfected people at high risk for acquiring HIV.

While efficacy in PrEP has been positively correlated with medication adherence (as measured by serum drug levels), "pharmacokinetic and pharmacodynamic variability and the presence of vaginal or rectal inflammation also may affect outcome."

As in the 2010 recommendations (JAMA 2010;304:321-33), the initial choice of prophylactic therapy "continues to be based on a combination of two nucleos(t)ide reverse transcriptase inhibitors and a potent third agent," the authors noted, with the once-daily fixed-dose combination of tenofovir plus emtricitabine remaining the first choice.

Although tenofovir is well tolerated, its use has been linked with kidney injury, "which appears to increase in incidence with long-term administration and concurrent [protease inhibitor, ritonavir-boosted] use," the authors cautioned.

Tenofovir is also associated with decreased bone mineral density of the spine and hip. Thus, given the increased risk of fragility fractures in postmenopausal women, ‘it may be prudent to consider avoiding tenofovir as part of initial therapy in this group," the authors wrote.

Another choice, the once-daily abacavir/lamivudine fixed-dose combination, is now a recommended initial therapy. In 2010, it was considered only a possible alternative.

"Screening for [the HLA-B*5701 gene] markedly reduces the risk of potentially life-threatening hypersensitivity reaction to abacavir," the guideline authors wrote.

In addition, some studies have found abacavir to be associated with a higher risk of acute myocardial infarction.

Dr. Thompson and her colleagues disclosed multiple financial and professional relationships with several pharmaceutical companies, including the makers of antiretroviral therapies. They stated that members of the panel who developed the recommendations did not participate in industry promotional activities such as speakers bureaus or lectures during their membership, and that members with previous conflicts recused themselves from evaluating evidence when a conflict was present.

The development of the recommendations was sponsored by the IAS-USA, according to the authors.

HIV-infected adults should start antiretroviral therapy as soon as possible, regardless of CD4 count, according to a recommendation from the International Antiviral Society–USA presented at the AIDS 2012 meeting in Washington.

The recommendation represents a major change from the last set of guidelines, issued in 2010. Those earlier guidelines recommended starting antiretrovirals when CD4 counts fell beneath 500 cells/mL, and "considering" treatment in patients with higher counts.

In writing the new guidelines, which also appear in the July 25 issue of JAMA (2012;308:387-402), Dr. Melanie A. Thompson and a panel convened by the International Antiviral Society–USA (IAS-USA) conducted a literature review of all new published data and data presented at scientific conferences between July 2010 and May 2012.

All recommendations were applicable only to HIV-infected adults in resource-rich settings, and dealt with antiretroviral therapies that were either already approved or in late-stage development.

The field of HIV prophylaxis has also seen significant progress since the 2010 update, and the new guidelines reflect those advances.

"Recently, antiretroviral therapy used as oral pre-exposure prophylaxis (PrEP) has been shown to be effective in three large trials using daily tenofovir/emtricitabine or tenofovir in gay and bisexual men and transgender women (iPrEx), heterosexual HIV-serodiscordant couples (Partners PrEP), and heterosexual men and women (TDF2)," wrote Dr. Thompson of the AIDS Research Consortium of Atlanta.

Indeed, following the iPrEx results, the Centers for Disease Control and Prevention issued interim guidance (MMWR 2011;60:65-8) for HIV-negative homosexual men who elect to take tenofovir/emtricitabine for prophylaxis.

And July 16, the Food and Drug Administration approved the use of an oral once-daily combination antiviral medication, Truvada (tenofovir and emtricitabine), for prevention in uninfected people at high risk for acquiring HIV.

While efficacy in PrEP has been positively correlated with medication adherence (as measured by serum drug levels), "pharmacokinetic and pharmacodynamic variability and the presence of vaginal or rectal inflammation also may affect outcome."

As in the 2010 recommendations (JAMA 2010;304:321-33), the initial choice of prophylactic therapy "continues to be based on a combination of two nucleos(t)ide reverse transcriptase inhibitors and a potent third agent," the authors noted, with the once-daily fixed-dose combination of tenofovir plus emtricitabine remaining the first choice.

Although tenofovir is well tolerated, its use has been linked with kidney injury, "which appears to increase in incidence with long-term administration and concurrent [protease inhibitor, ritonavir-boosted] use," the authors cautioned.

Tenofovir is also associated with decreased bone mineral density of the spine and hip. Thus, given the increased risk of fragility fractures in postmenopausal women, ‘it may be prudent to consider avoiding tenofovir as part of initial therapy in this group," the authors wrote.

Another choice, the once-daily abacavir/lamivudine fixed-dose combination, is now a recommended initial therapy. In 2010, it was considered only a possible alternative.

"Screening for [the HLA-B*5701 gene] markedly reduces the risk of potentially life-threatening hypersensitivity reaction to abacavir," the guideline authors wrote.

In addition, some studies have found abacavir to be associated with a higher risk of acute myocardial infarction.

Dr. Thompson and her colleagues disclosed multiple financial and professional relationships with several pharmaceutical companies, including the makers of antiretroviral therapies. They stated that members of the panel who developed the recommendations did not participate in industry promotional activities such as speakers bureaus or lectures during their membership, and that members with previous conflicts recused themselves from evaluating evidence when a conflict was present.

The development of the recommendations was sponsored by the IAS-USA, according to the authors.

HIV-infected adults should start antiretroviral therapy as soon as possible, regardless of CD4 count, according to a recommendation from the International Antiviral Society–USA presented at the AIDS 2012 meeting in Washington.

The recommendation represents a major change from the last set of guidelines, issued in 2010. Those earlier guidelines recommended starting antiretrovirals when CD4 counts fell beneath 500 cells/mL, and "considering" treatment in patients with higher counts.

In writing the new guidelines, which also appear in the July 25 issue of JAMA (2012;308:387-402), Dr. Melanie A. Thompson and a panel convened by the International Antiviral Society–USA (IAS-USA) conducted a literature review of all new published data and data presented at scientific conferences between July 2010 and May 2012.

All recommendations were applicable only to HIV-infected adults in resource-rich settings, and dealt with antiretroviral therapies that were either already approved or in late-stage development.

The field of HIV prophylaxis has also seen significant progress since the 2010 update, and the new guidelines reflect those advances.

"Recently, antiretroviral therapy used as oral pre-exposure prophylaxis (PrEP) has been shown to be effective in three large trials using daily tenofovir/emtricitabine or tenofovir in gay and bisexual men and transgender women (iPrEx), heterosexual HIV-serodiscordant couples (Partners PrEP), and heterosexual men and women (TDF2)," wrote Dr. Thompson of the AIDS Research Consortium of Atlanta.

Indeed, following the iPrEx results, the Centers for Disease Control and Prevention issued interim guidance (MMWR 2011;60:65-8) for HIV-negative homosexual men who elect to take tenofovir/emtricitabine for prophylaxis.

And July 16, the Food and Drug Administration approved the use of an oral once-daily combination antiviral medication, Truvada (tenofovir and emtricitabine), for prevention in uninfected people at high risk for acquiring HIV.

While efficacy in PrEP has been positively correlated with medication adherence (as measured by serum drug levels), "pharmacokinetic and pharmacodynamic variability and the presence of vaginal or rectal inflammation also may affect outcome."

As in the 2010 recommendations (JAMA 2010;304:321-33), the initial choice of prophylactic therapy "continues to be based on a combination of two nucleos(t)ide reverse transcriptase inhibitors and a potent third agent," the authors noted, with the once-daily fixed-dose combination of tenofovir plus emtricitabine remaining the first choice.

Although tenofovir is well tolerated, its use has been linked with kidney injury, "which appears to increase in incidence with long-term administration and concurrent [protease inhibitor, ritonavir-boosted] use," the authors cautioned.

Tenofovir is also associated with decreased bone mineral density of the spine and hip. Thus, given the increased risk of fragility fractures in postmenopausal women, ‘it may be prudent to consider avoiding tenofovir as part of initial therapy in this group," the authors wrote.

Another choice, the once-daily abacavir/lamivudine fixed-dose combination, is now a recommended initial therapy. In 2010, it was considered only a possible alternative.

"Screening for [the HLA-B*5701 gene] markedly reduces the risk of potentially life-threatening hypersensitivity reaction to abacavir," the guideline authors wrote.

In addition, some studies have found abacavir to be associated with a higher risk of acute myocardial infarction.

Dr. Thompson and her colleagues disclosed multiple financial and professional relationships with several pharmaceutical companies, including the makers of antiretroviral therapies. They stated that members of the panel who developed the recommendations did not participate in industry promotional activities such as speakers bureaus or lectures during their membership, and that members with previous conflicts recused themselves from evaluating evidence when a conflict was present.

The development of the recommendations was sponsored by the IAS-USA, according to the authors.

Adalimumab safely induced and maintained remission in about one-third of pediatric patients with treatment-resistant Crohn’s disease, reported Dr. Jeffrey S. Hyams and his colleagues in the August issue of Gastroenterology.

In a phase III, multicenter, randomized trial consisting of an open-label induction followed by double-blind maintenance therapy (IMAgINE 1), Dr. Hyams of the Connecticut Children’s Medical Center, Hartford, studied 188 patients aged 6-17 years with a recent diagnosis of Crohn’s disease confirmed by endoscopy or radiology.

All patients were classified as having moderate to severe disease, with a Pediatric Crohn’s Disease Activity Index (PCDAI) of greater than 30 despite concurrent treatment with an oral corticosteroid and/or an immunomodulator such as azathioprine, 6-mercaptopurine, or methotrexate. The 45 sites were located in Canada, Europe, and the United States.

Patients received induction therapy for 4 weeks, and then were randomly assigned to high-dose or low-dose adalimumab as double-blind maintenance therapy for 48 weeks thereafter.

High-dose patients whose body weight was 40 kg or greater received 40 mg of the drug every other week; patients weighing less than 40 kg received 20 mg every other week. Low-dose patients with a body weight of 40 kg or greater received 20 mg every other week. Patients weighing less than 40 kg received 10 mg every other week (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.04.046]).

At week 12, patients who were nonresponders, defined as a change in PCDAI of less than 15 points, or who had a flare were switched to weekly dosing at the same dose. If at 8 weeks after increasing the frequency, patients were still nonresponders, they transitioned to open-label, high-dose therapy according to their weight.

Overall, 155 patients (82.4%) responded to induction (a PCDAI decrease of 15 or more points from baseline), and 52 patients (27.7%) were in clinical remission at the end of the 4-week induction period. At week 26, 33.5% of patients were in clinical remission, wrote the authors.

"A numerically higher proportion of patients in the high-dose adalimumab group were in clinical remission and clinical response compared with the low-dose group, but the differences did not achieve statistical significance," they added.

Looking at safety, the authors noted that 124 patients (66.0%) completed the entire 26-week study. The most common reasons for dropping out of the study were lack of efficacy and adverse events.

"In the open-label induction period, 101/192 (52.6%) of patients reported treatment-emergent adverse events, including two serious infections (one Yersinia infection and one viral infection; both events resolved and the patients completed the study)," wrote the authors. Eight serious infections were observed during the double-blind period.

"There were no cases of malignancy, congestive heart failure, demyelinating disease, lupus-like syndrome, or tuberculosis, and no deaths," they added. "No new safety signals were identified in this study."

Dr. Hyams pointed out that the lack of a placebo in this study is a potential limitation. However, "The design was considered appropriate for a pediatric trial because of ethical considerations after the principal evidence of efficacy had been established in adult patients with moderate to severe CD," he wrote.

The study was funded by Abbott Laboratories, maker of adalimumab. Several authors were also employees of Abbott, and several (including Dr. Hyams) disclosed financial relationships with Abbott as well as other pharmaceutical companies, including the makers of biologics.

Adalimumab safely induced and maintained remission in about one-third of pediatric patients with treatment-resistant Crohn’s disease, reported Dr. Jeffrey S. Hyams and his colleagues in the August issue of Gastroenterology.

In a phase III, multicenter, randomized trial consisting of an open-label induction followed by double-blind maintenance therapy (IMAgINE 1), Dr. Hyams of the Connecticut Children’s Medical Center, Hartford, studied 188 patients aged 6-17 years with a recent diagnosis of Crohn’s disease confirmed by endoscopy or radiology.

All patients were classified as having moderate to severe disease, with a Pediatric Crohn’s Disease Activity Index (PCDAI) of greater than 30 despite concurrent treatment with an oral corticosteroid and/or an immunomodulator such as azathioprine, 6-mercaptopurine, or methotrexate. The 45 sites were located in Canada, Europe, and the United States.

Patients received induction therapy for 4 weeks, and then were randomly assigned to high-dose or low-dose adalimumab as double-blind maintenance therapy for 48 weeks thereafter.

High-dose patients whose body weight was 40 kg or greater received 40 mg of the drug every other week; patients weighing less than 40 kg received 20 mg every other week. Low-dose patients with a body weight of 40 kg or greater received 20 mg every other week. Patients weighing less than 40 kg received 10 mg every other week (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.04.046]).

At week 12, patients who were nonresponders, defined as a change in PCDAI of less than 15 points, or who had a flare were switched to weekly dosing at the same dose. If at 8 weeks after increasing the frequency, patients were still nonresponders, they transitioned to open-label, high-dose therapy according to their weight.

Overall, 155 patients (82.4%) responded to induction (a PCDAI decrease of 15 or more points from baseline), and 52 patients (27.7%) were in clinical remission at the end of the 4-week induction period. At week 26, 33.5% of patients were in clinical remission, wrote the authors.

"A numerically higher proportion of patients in the high-dose adalimumab group were in clinical remission and clinical response compared with the low-dose group, but the differences did not achieve statistical significance," they added.

Looking at safety, the authors noted that 124 patients (66.0%) completed the entire 26-week study. The most common reasons for dropping out of the study were lack of efficacy and adverse events.

"In the open-label induction period, 101/192 (52.6%) of patients reported treatment-emergent adverse events, including two serious infections (one Yersinia infection and one viral infection; both events resolved and the patients completed the study)," wrote the authors. Eight serious infections were observed during the double-blind period.

"There were no cases of malignancy, congestive heart failure, demyelinating disease, lupus-like syndrome, or tuberculosis, and no deaths," they added. "No new safety signals were identified in this study."

Dr. Hyams pointed out that the lack of a placebo in this study is a potential limitation. However, "The design was considered appropriate for a pediatric trial because of ethical considerations after the principal evidence of efficacy had been established in adult patients with moderate to severe CD," he wrote.

The study was funded by Abbott Laboratories, maker of adalimumab. Several authors were also employees of Abbott, and several (including Dr. Hyams) disclosed financial relationships with Abbott as well as other pharmaceutical companies, including the makers of biologics.

Adalimumab safely induced and maintained remission in about one-third of pediatric patients with treatment-resistant Crohn’s disease, reported Dr. Jeffrey S. Hyams and his colleagues in the August issue of Gastroenterology.

In a phase III, multicenter, randomized trial consisting of an open-label induction followed by double-blind maintenance therapy (IMAgINE 1), Dr. Hyams of the Connecticut Children’s Medical Center, Hartford, studied 188 patients aged 6-17 years with a recent diagnosis of Crohn’s disease confirmed by endoscopy or radiology.

All patients were classified as having moderate to severe disease, with a Pediatric Crohn’s Disease Activity Index (PCDAI) of greater than 30 despite concurrent treatment with an oral corticosteroid and/or an immunomodulator such as azathioprine, 6-mercaptopurine, or methotrexate. The 45 sites were located in Canada, Europe, and the United States.

Patients received induction therapy for 4 weeks, and then were randomly assigned to high-dose or low-dose adalimumab as double-blind maintenance therapy for 48 weeks thereafter.

High-dose patients whose body weight was 40 kg or greater received 40 mg of the drug every other week; patients weighing less than 40 kg received 20 mg every other week. Low-dose patients with a body weight of 40 kg or greater received 20 mg every other week. Patients weighing less than 40 kg received 10 mg every other week (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.04.046]).

At week 12, patients who were nonresponders, defined as a change in PCDAI of less than 15 points, or who had a flare were switched to weekly dosing at the same dose. If at 8 weeks after increasing the frequency, patients were still nonresponders, they transitioned to open-label, high-dose therapy according to their weight.

Overall, 155 patients (82.4%) responded to induction (a PCDAI decrease of 15 or more points from baseline), and 52 patients (27.7%) were in clinical remission at the end of the 4-week induction period. At week 26, 33.5% of patients were in clinical remission, wrote the authors.

"A numerically higher proportion of patients in the high-dose adalimumab group were in clinical remission and clinical response compared with the low-dose group, but the differences did not achieve statistical significance," they added.

Looking at safety, the authors noted that 124 patients (66.0%) completed the entire 26-week study. The most common reasons for dropping out of the study were lack of efficacy and adverse events.

"In the open-label induction period, 101/192 (52.6%) of patients reported treatment-emergent adverse events, including two serious infections (one Yersinia infection and one viral infection; both events resolved and the patients completed the study)," wrote the authors. Eight serious infections were observed during the double-blind period.

"There were no cases of malignancy, congestive heart failure, demyelinating disease, lupus-like syndrome, or tuberculosis, and no deaths," they added. "No new safety signals were identified in this study."

Dr. Hyams pointed out that the lack of a placebo in this study is a potential limitation. However, "The design was considered appropriate for a pediatric trial because of ethical considerations after the principal evidence of efficacy had been established in adult patients with moderate to severe CD," he wrote.

The study was funded by Abbott Laboratories, maker of adalimumab. Several authors were also employees of Abbott, and several (including Dr. Hyams) disclosed financial relationships with Abbott as well as other pharmaceutical companies, including the makers of biologics.

Regular celiac disease follow-up often is lacking, according to a report by Dr. Margot L. Herman and Dr. Alberto Rubio-Tapia to be published in the August issue of Clinical Gastroenterology and Hepatology.

Moreover, when follow-up visits do occur, they are likely to be insufficient, without assessment of serology or dietary compliance, added the investigators.

Dr. Herman and Dr. Rubio-Tapia, both of the Mayo Clinic in Rochester, Minn., and their colleagues looked at 5 years of medical records of doctor visits from 122 patients with celiac disease recruited through the Rochester Epidemiology Project database, which links to medical records at the Mayo Clinic and the Olmsted Medical Center. Of the 122 patients, 70% were women. The median age was 42 years.

Cases with any degree of villous atrophy, associated crypt hyperplasia, and an increased number of intraepithelial lymphocytes were confirmed by intestinal biopsy, plus clinical or histologic improvement after the introduction of a gluten-free diet, as well as positive endomysial or tissue transglutaminase antibodies.

"Celiac disease visits" were defined as visits with a primary care physician or gastroenterologist that addressed the disease, or with any other physician or midlevel provider (for example, a dietitian) who documented assessment of celiac symptoms and compliance with a gluten-free diet, and/or tested relevant celiac disease serologies.

Patients were classed as having either no follow-up or "regular" follow-up, meaning two or more celiac disease follow-up visits and two or more serologies at least 6 months apart during the 5-year study period, beginning 6 months after diagnosis. A third category, "irregular" follow-up, was defined as some follow-up visits or serologies not meeting the minimal criteria of the previous definition.

Overall, there were 314 celiac disease visits for the 122 patients during the 5-year follow-up period, mostly with primary care providers (n = 175; 56%) and gastroenterologists (n = 122; 39%).

Among patients with at least 4 years of follow-up after diagnosis (n = 113), the authors calculated that just 40 (35%) had "regular" follow-up (Clin. Gastro. Hepatol. 2012 [doi:10.1016/j.cgh.2012.05.007]).

A greater number (n = 65; 58%) had "irregular" follow-up, and eight patients (7%) had no celiac disease follow-up.

A complete blood count was assessed in 62% of all follow-up visits, and tissue transglutaminase antibodies, transaminases, thyroid stimulating hormone, and ferritin were each assessed in about one out of every two to three visits, wrote the authors.

In general, some form of serology was tested in 147 (47%) of 314 follow-up visits.

Moreover, 42 patients (37%) had at least one celiac disease visit without any documentation of gluten-free diet compliance.

Having diarrhea at time of diagnosis was significantly associated with regular follow-up (P =.02), wrote the authors, while having family history of disease was nonsignificantly associated with irregular or no follow-up (P = .11).

"Age, sex, and indication of a dietitian consult and other gastrointestinal symptoms at diagnosis (for example, bloating, nausea/vomiting, weight loss, abdominal pain) were not significantly associated with follow-up categories," they added.

And while the researchers conceded that the review was limited to patients in a distinct geographical area, "Olmsted County is a unique population in that there is tremendous access to medical care, fewer uninsured, and overall higher degrees of education and wealth," they wrote.

"These factors would likely enhance a patient’s probability of receiving follow-up medical care, implying that our estimates are an overstatement of follow-up, compared to other locations."

According to the authors, the National Institutes of Health and the American Gastroenterology Association recommend that patients be evaluated at "regular intervals" by a "physician and a dietitian," but "practice guidelines vary greatly, and many specific recommendations are not evidence based."

Neither is there consensus on whether and how often serology should be assessed, nor when or if intestinal biopsy is warranted.

Indeed, "The considerable incongruency of guidelines posed a challenge in defining the categories of follow-up."

Nevertheless, "very few patients had medical follow-up that would be in keeping with even the most lax interpretation of current guidelines."

The authors stated that there were no conflicts of interest associated with this study.

Regular celiac disease follow-up often is lacking, according to a report by Dr. Margot L. Herman and Dr. Alberto Rubio-Tapia to be published in the August issue of Clinical Gastroenterology and Hepatology.

Moreover, when follow-up visits do occur, they are likely to be insufficient, without assessment of serology or dietary compliance, added the investigators.

Dr. Herman and Dr. Rubio-Tapia, both of the Mayo Clinic in Rochester, Minn., and their colleagues looked at 5 years of medical records of doctor visits from 122 patients with celiac disease recruited through the Rochester Epidemiology Project database, which links to medical records at the Mayo Clinic and the Olmsted Medical Center. Of the 122 patients, 70% were women. The median age was 42 years.

Cases with any degree of villous atrophy, associated crypt hyperplasia, and an increased number of intraepithelial lymphocytes were confirmed by intestinal biopsy, plus clinical or histologic improvement after the introduction of a gluten-free diet, as well as positive endomysial or tissue transglutaminase antibodies.

"Celiac disease visits" were defined as visits with a primary care physician or gastroenterologist that addressed the disease, or with any other physician or midlevel provider (for example, a dietitian) who documented assessment of celiac symptoms and compliance with a gluten-free diet, and/or tested relevant celiac disease serologies.

Patients were classed as having either no follow-up or "regular" follow-up, meaning two or more celiac disease follow-up visits and two or more serologies at least 6 months apart during the 5-year study period, beginning 6 months after diagnosis. A third category, "irregular" follow-up, was defined as some follow-up visits or serologies not meeting the minimal criteria of the previous definition.

Overall, there were 314 celiac disease visits for the 122 patients during the 5-year follow-up period, mostly with primary care providers (n = 175; 56%) and gastroenterologists (n = 122; 39%).

Among patients with at least 4 years of follow-up after diagnosis (n = 113), the authors calculated that just 40 (35%) had "regular" follow-up (Clin. Gastro. Hepatol. 2012 [doi:10.1016/j.cgh.2012.05.007]).

A greater number (n = 65; 58%) had "irregular" follow-up, and eight patients (7%) had no celiac disease follow-up.

A complete blood count was assessed in 62% of all follow-up visits, and tissue transglutaminase antibodies, transaminases, thyroid stimulating hormone, and ferritin were each assessed in about one out of every two to three visits, wrote the authors.

In general, some form of serology was tested in 147 (47%) of 314 follow-up visits.

Moreover, 42 patients (37%) had at least one celiac disease visit without any documentation of gluten-free diet compliance.

Having diarrhea at time of diagnosis was significantly associated with regular follow-up (P =.02), wrote the authors, while having family history of disease was nonsignificantly associated with irregular or no follow-up (P = .11).

"Age, sex, and indication of a dietitian consult and other gastrointestinal symptoms at diagnosis (for example, bloating, nausea/vomiting, weight loss, abdominal pain) were not significantly associated with follow-up categories," they added.

And while the researchers conceded that the review was limited to patients in a distinct geographical area, "Olmsted County is a unique population in that there is tremendous access to medical care, fewer uninsured, and overall higher degrees of education and wealth," they wrote.

"These factors would likely enhance a patient’s probability of receiving follow-up medical care, implying that our estimates are an overstatement of follow-up, compared to other locations."

According to the authors, the National Institutes of Health and the American Gastroenterology Association recommend that patients be evaluated at "regular intervals" by a "physician and a dietitian," but "practice guidelines vary greatly, and many specific recommendations are not evidence based."

Neither is there consensus on whether and how often serology should be assessed, nor when or if intestinal biopsy is warranted.

Indeed, "The considerable incongruency of guidelines posed a challenge in defining the categories of follow-up."

Nevertheless, "very few patients had medical follow-up that would be in keeping with even the most lax interpretation of current guidelines."

The authors stated that there were no conflicts of interest associated with this study.

Regular celiac disease follow-up often is lacking, according to a report by Dr. Margot L. Herman and Dr. Alberto Rubio-Tapia to be published in the August issue of Clinical Gastroenterology and Hepatology.

Moreover, when follow-up visits do occur, they are likely to be insufficient, without assessment of serology or dietary compliance, added the investigators.

Dr. Herman and Dr. Rubio-Tapia, both of the Mayo Clinic in Rochester, Minn., and their colleagues looked at 5 years of medical records of doctor visits from 122 patients with celiac disease recruited through the Rochester Epidemiology Project database, which links to medical records at the Mayo Clinic and the Olmsted Medical Center. Of the 122 patients, 70% were women. The median age was 42 years.

Cases with any degree of villous atrophy, associated crypt hyperplasia, and an increased number of intraepithelial lymphocytes were confirmed by intestinal biopsy, plus clinical or histologic improvement after the introduction of a gluten-free diet, as well as positive endomysial or tissue transglutaminase antibodies.

"Celiac disease visits" were defined as visits with a primary care physician or gastroenterologist that addressed the disease, or with any other physician or midlevel provider (for example, a dietitian) who documented assessment of celiac symptoms and compliance with a gluten-free diet, and/or tested relevant celiac disease serologies.

Patients were classed as having either no follow-up or "regular" follow-up, meaning two or more celiac disease follow-up visits and two or more serologies at least 6 months apart during the 5-year study period, beginning 6 months after diagnosis. A third category, "irregular" follow-up, was defined as some follow-up visits or serologies not meeting the minimal criteria of the previous definition.

Overall, there were 314 celiac disease visits for the 122 patients during the 5-year follow-up period, mostly with primary care providers (n = 175; 56%) and gastroenterologists (n = 122; 39%).

Among patients with at least 4 years of follow-up after diagnosis (n = 113), the authors calculated that just 40 (35%) had "regular" follow-up (Clin. Gastro. Hepatol. 2012 [doi:10.1016/j.cgh.2012.05.007]).

A greater number (n = 65; 58%) had "irregular" follow-up, and eight patients (7%) had no celiac disease follow-up.

A complete blood count was assessed in 62% of all follow-up visits, and tissue transglutaminase antibodies, transaminases, thyroid stimulating hormone, and ferritin were each assessed in about one out of every two to three visits, wrote the authors.

In general, some form of serology was tested in 147 (47%) of 314 follow-up visits.

Moreover, 42 patients (37%) had at least one celiac disease visit without any documentation of gluten-free diet compliance.

Having diarrhea at time of diagnosis was significantly associated with regular follow-up (P =.02), wrote the authors, while having family history of disease was nonsignificantly associated with irregular or no follow-up (P = .11).

"Age, sex, and indication of a dietitian consult and other gastrointestinal symptoms at diagnosis (for example, bloating, nausea/vomiting, weight loss, abdominal pain) were not significantly associated with follow-up categories," they added.

And while the researchers conceded that the review was limited to patients in a distinct geographical area, "Olmsted County is a unique population in that there is tremendous access to medical care, fewer uninsured, and overall higher degrees of education and wealth," they wrote.

"These factors would likely enhance a patient’s probability of receiving follow-up medical care, implying that our estimates are an overstatement of follow-up, compared to other locations."

According to the authors, the National Institutes of Health and the American Gastroenterology Association recommend that patients be evaluated at "regular intervals" by a "physician and a dietitian," but "practice guidelines vary greatly, and many specific recommendations are not evidence based."

Neither is there consensus on whether and how often serology should be assessed, nor when or if intestinal biopsy is warranted.

Indeed, "The considerable incongruency of guidelines posed a challenge in defining the categories of follow-up."

Nevertheless, "very few patients had medical follow-up that would be in keeping with even the most lax interpretation of current guidelines."

The authors stated that there were no conflicts of interest associated with this study.

A swallowed, viscous solution of topical steroids was more effective at reducing eosinophil counts than was a nebulized solution in eosinophilic esophagitis, Dr. Evan S. Dellon and his colleagues reported in the August issue of Gastroenterology.

However, in what the authors called "the first study comparing two methods of topical steroid delivery for treatment of EoE, and the first examining the use of oral viscous budesonide in adults," they also found that decreased eosinophils did not correlate with improvements in dysphagia.

Dr. Dellon and his colleagues at the University of North Carolina at Chapel Hill randomized 22 dysphagia patients to budesonide 1 mg twice daily for 8 weeks, either nebulized and then swallowed (n = 11) or in an oral viscous slurry formulation (n = 11). The patients’ mean age was 35 years; 60% were men.

At baseline, the maximum eosinophil count for the nebulizer treatment group was 101 eosinophils per high-power field; for the viscous slurry group, it was 83 (P = .62).

Following treatment, the nebulizer group had a maximum count of 89 eosinophils per high-power field, compared with a maximum of 11 in the viscous slurry group (P = .02) (Gastroenterology 2012 May 7 [doi:10.1053/j.gastro.2012.04.049]).

The authors then used nuclear scintigraphy to assess mucosal medication contact time, where higher median areas under the esophageal emptying curve (AUC) were assumed to mean greater contact time.

They found that the oral viscous preparation AUC was indeed higher for the viscous preparation than for the nebulized budesonide; however, "higher mucosal contact time correlated with the decrease in eosinophil count regardless of treatment type (P = .001)," they wrote.

The researchers also assessed dysphagia improvement, as measured on the Mayo Dysphagia Questionnaire-30 Day (which has not been validated in eosinophilic esophagitis).

"In contrast to the eosinophil counts, dysphagia symptom scores improved in both groups, and this improvement persisted after excluding patients who received esophageal dilation at baseline" they reported.

Nor did improvement in dysphagia correlate with endoscopic or histologic improvement.

Looking at side effects, Dr. Dellon and his colleagues reported that three patients had asymptomatic candidal esophagitis on posttreatment endoscopy, and that one patient in the nebulizer group withdrew because of epistaxis, but that no other side effects or adverse events occurred.

They added that no patients had adrenal insufficiency by cortisol stimulation testing, and no budesonide was detected in patients’ serum after 8 weeks, which suggested a "topical, rather than systemic activity."

The researchers did concede several limitations to this study, including its small sample size and the lack of a placebo control.

However, the study "was adequately powered for the primary outcomes, and the effect size estimates for the power calculations proved to be accurate," they noted.

"The mechanistic assessment with nuclear scintigraphy corroborated the main results and introduced new quantitative methodology to this area, which may guide future drug development," the researchers added.

While "it makes intuitive sense" that a swallowed formulation would be easier to administer than an inhaler, "the ideal medication delivery system does not yet exist," although several are currently under development, including gels, powders, and dissolving tablets, the authors noted.

They disclosed that they had no personal conflicts of interest, but the study was supported in part by AstraZeneca, maker of budesonide.

A swallowed, viscous solution of topical steroids was more effective at reducing eosinophil counts than was a nebulized solution in eosinophilic esophagitis, Dr. Evan S. Dellon and his colleagues reported in the August issue of Gastroenterology.

However, in what the authors called "the first study comparing two methods of topical steroid delivery for treatment of EoE, and the first examining the use of oral viscous budesonide in adults," they also found that decreased eosinophils did not correlate with improvements in dysphagia.

Dr. Dellon and his colleagues at the University of North Carolina at Chapel Hill randomized 22 dysphagia patients to budesonide 1 mg twice daily for 8 weeks, either nebulized and then swallowed (n = 11) or in an oral viscous slurry formulation (n = 11). The patients’ mean age was 35 years; 60% were men.

At baseline, the maximum eosinophil count for the nebulizer treatment group was 101 eosinophils per high-power field; for the viscous slurry group, it was 83 (P = .62).

Following treatment, the nebulizer group had a maximum count of 89 eosinophils per high-power field, compared with a maximum of 11 in the viscous slurry group (P = .02) (Gastroenterology 2012 May 7 [doi:10.1053/j.gastro.2012.04.049]).

The authors then used nuclear scintigraphy to assess mucosal medication contact time, where higher median areas under the esophageal emptying curve (AUC) were assumed to mean greater contact time.

They found that the oral viscous preparation AUC was indeed higher for the viscous preparation than for the nebulized budesonide; however, "higher mucosal contact time correlated with the decrease in eosinophil count regardless of treatment type (P = .001)," they wrote.

The researchers also assessed dysphagia improvement, as measured on the Mayo Dysphagia Questionnaire-30 Day (which has not been validated in eosinophilic esophagitis).

"In contrast to the eosinophil counts, dysphagia symptom scores improved in both groups, and this improvement persisted after excluding patients who received esophageal dilation at baseline" they reported.

Nor did improvement in dysphagia correlate with endoscopic or histologic improvement.

Looking at side effects, Dr. Dellon and his colleagues reported that three patients had asymptomatic candidal esophagitis on posttreatment endoscopy, and that one patient in the nebulizer group withdrew because of epistaxis, but that no other side effects or adverse events occurred.

They added that no patients had adrenal insufficiency by cortisol stimulation testing, and no budesonide was detected in patients’ serum after 8 weeks, which suggested a "topical, rather than systemic activity."

The researchers did concede several limitations to this study, including its small sample size and the lack of a placebo control.

However, the study "was adequately powered for the primary outcomes, and the effect size estimates for the power calculations proved to be accurate," they noted.

"The mechanistic assessment with nuclear scintigraphy corroborated the main results and introduced new quantitative methodology to this area, which may guide future drug development," the researchers added.

While "it makes intuitive sense" that a swallowed formulation would be easier to administer than an inhaler, "the ideal medication delivery system does not yet exist," although several are currently under development, including gels, powders, and dissolving tablets, the authors noted.

They disclosed that they had no personal conflicts of interest, but the study was supported in part by AstraZeneca, maker of budesonide.

A swallowed, viscous solution of topical steroids was more effective at reducing eosinophil counts than was a nebulized solution in eosinophilic esophagitis, Dr. Evan S. Dellon and his colleagues reported in the August issue of Gastroenterology.

However, in what the authors called "the first study comparing two methods of topical steroid delivery for treatment of EoE, and the first examining the use of oral viscous budesonide in adults," they also found that decreased eosinophils did not correlate with improvements in dysphagia.

Dr. Dellon and his colleagues at the University of North Carolina at Chapel Hill randomized 22 dysphagia patients to budesonide 1 mg twice daily for 8 weeks, either nebulized and then swallowed (n = 11) or in an oral viscous slurry formulation (n = 11). The patients’ mean age was 35 years; 60% were men.

At baseline, the maximum eosinophil count for the nebulizer treatment group was 101 eosinophils per high-power field; for the viscous slurry group, it was 83 (P = .62).

Following treatment, the nebulizer group had a maximum count of 89 eosinophils per high-power field, compared with a maximum of 11 in the viscous slurry group (P = .02) (Gastroenterology 2012 May 7 [doi:10.1053/j.gastro.2012.04.049]).

The authors then used nuclear scintigraphy to assess mucosal medication contact time, where higher median areas under the esophageal emptying curve (AUC) were assumed to mean greater contact time.

They found that the oral viscous preparation AUC was indeed higher for the viscous preparation than for the nebulized budesonide; however, "higher mucosal contact time correlated with the decrease in eosinophil count regardless of treatment type (P = .001)," they wrote.

The researchers also assessed dysphagia improvement, as measured on the Mayo Dysphagia Questionnaire-30 Day (which has not been validated in eosinophilic esophagitis).

"In contrast to the eosinophil counts, dysphagia symptom scores improved in both groups, and this improvement persisted after excluding patients who received esophageal dilation at baseline" they reported.

Nor did improvement in dysphagia correlate with endoscopic or histologic improvement.

Looking at side effects, Dr. Dellon and his colleagues reported that three patients had asymptomatic candidal esophagitis on posttreatment endoscopy, and that one patient in the nebulizer group withdrew because of epistaxis, but that no other side effects or adverse events occurred.

They added that no patients had adrenal insufficiency by cortisol stimulation testing, and no budesonide was detected in patients’ serum after 8 weeks, which suggested a "topical, rather than systemic activity."

The researchers did concede several limitations to this study, including its small sample size and the lack of a placebo control.

However, the study "was adequately powered for the primary outcomes, and the effect size estimates for the power calculations proved to be accurate," they noted.

"The mechanistic assessment with nuclear scintigraphy corroborated the main results and introduced new quantitative methodology to this area, which may guide future drug development," the researchers added.

While "it makes intuitive sense" that a swallowed formulation would be easier to administer than an inhaler, "the ideal medication delivery system does not yet exist," although several are currently under development, including gels, powders, and dissolving tablets, the authors noted.

They disclosed that they had no personal conflicts of interest, but the study was supported in part by AstraZeneca, maker of budesonide.

NEW YORK – Much of the complementary and alternative medicine that is practiced by Asian and Hispanic cultures can actually do more harm than good, according to Dr. Roopal V. Kundu.

In these cultures, patients often view illness as having strong spiritual origins and consequences, she said at the seminar. Illness "can have a dramatic effect on psyche."

In the traditional Hispanic community, many individuals have seen or are concurrently seeing a local healer, said Dr. Kundu, director of the Northwestern Center for Ethnic Skin at Northwestern University, Chicago. These healers might be practitioners of curanderismo, in which they believe they are healing as a "gift from a higher power," while employing prayers, baths, and botanicals to combat illness. Another practice is espiritismo, which is a belief that good and evil spirits affect health.

Courtesy Dr. Roopal V. Kundu

Asian patients, meanwhile, have their own set of healers and practices. For example, patients may practice "cupping" for chronic pain and respiratory disease, whereby a glass or plastic cup is placed over the back to create a local vacuum, in the hopes of relieving congestion and increasing circulation.

"Wet cupping" is similar, except that a small scratch or incision is made prior to the cupping procedure.

Both cupping practices leave behind circular patterns of erythema, edema, and ecchymosis, and could be mistaken for child abuse or another skin disorder, said Dr. Kundu, who recently published a paper on this and other Asian dermatoses (Int. J. Dermatol. 2012;51:372-82).

Similarly, "coining," "spooning," or "cao gio" is a Vietnamese dermabrasion therapy, whereby skin is lubricated with oils and then rubbed firmly using the edge of a spoon or coin.

The result will be parallel lines of ecchymoses on the chest and back in a "pine tree" pattern, said Dr. Kundu.

Another Asian practice, moxibustion, or moxa, involves burning materials on the skin to combat atopic dermatitis, postherpetic neuralgia, and tinea pedis. The small, circular scars left behind approximate cigarette burns.

She also advised questioning the use of hair oils in Southeast Asian and black patients. Mustard, coconut, and amla oil are supposed to be toxic to certain dermatophytes, said Dr. Kundu. However, she warned, the theory might backfire in practice. "Are the different oils perpetuating different organisms and allowing [tinea capitas]?"

Finally, Dr. Kundu noted that among Asian and Hispanic populations, decision making by family consensus is the norm. "With almost all of my ethnic patients, I almost always have someone else in the room – a sister, brother, parent, child, uncle," she said. "You’re kind of engaging both of them in the dialogue and [the patient is] often looking toward that person for help in navigating the health care system."

Dr. Kundu stated that she had no relevant relationships with industry to disclose.

NEW YORK – Much of the complementary and alternative medicine that is practiced by Asian and Hispanic cultures can actually do more harm than good, according to Dr. Roopal V. Kundu.

In these cultures, patients often view illness as having strong spiritual origins and consequences, she said at the seminar. Illness "can have a dramatic effect on psyche."

In the traditional Hispanic community, many individuals have seen or are concurrently seeing a local healer, said Dr. Kundu, director of the Northwestern Center for Ethnic Skin at Northwestern University, Chicago. These healers might be practitioners of curanderismo, in which they believe they are healing as a "gift from a higher power," while employing prayers, baths, and botanicals to combat illness. Another practice is espiritismo, which is a belief that good and evil spirits affect health.

Courtesy Dr. Roopal V. Kundu

Asian patients, meanwhile, have their own set of healers and practices. For example, patients may practice "cupping" for chronic pain and respiratory disease, whereby a glass or plastic cup is placed over the back to create a local vacuum, in the hopes of relieving congestion and increasing circulation.

"Wet cupping" is similar, except that a small scratch or incision is made prior to the cupping procedure.

Both cupping practices leave behind circular patterns of erythema, edema, and ecchymosis, and could be mistaken for child abuse or another skin disorder, said Dr. Kundu, who recently published a paper on this and other Asian dermatoses (Int. J. Dermatol. 2012;51:372-82).

Similarly, "coining," "spooning," or "cao gio" is a Vietnamese dermabrasion therapy, whereby skin is lubricated with oils and then rubbed firmly using the edge of a spoon or coin.

The result will be parallel lines of ecchymoses on the chest and back in a "pine tree" pattern, said Dr. Kundu.

Another Asian practice, moxibustion, or moxa, involves burning materials on the skin to combat atopic dermatitis, postherpetic neuralgia, and tinea pedis. The small, circular scars left behind approximate cigarette burns.

She also advised questioning the use of hair oils in Southeast Asian and black patients. Mustard, coconut, and amla oil are supposed to be toxic to certain dermatophytes, said Dr. Kundu. However, she warned, the theory might backfire in practice. "Are the different oils perpetuating different organisms and allowing [tinea capitas]?"

Finally, Dr. Kundu noted that among Asian and Hispanic populations, decision making by family consensus is the norm. "With almost all of my ethnic patients, I almost always have someone else in the room – a sister, brother, parent, child, uncle," she said. "You’re kind of engaging both of them in the dialogue and [the patient is] often looking toward that person for help in navigating the health care system."

Dr. Kundu stated that she had no relevant relationships with industry to disclose.

NEW YORK – Much of the complementary and alternative medicine that is practiced by Asian and Hispanic cultures can actually do more harm than good, according to Dr. Roopal V. Kundu.

In these cultures, patients often view illness as having strong spiritual origins and consequences, she said at the seminar. Illness "can have a dramatic effect on psyche."

In the traditional Hispanic community, many individuals have seen or are concurrently seeing a local healer, said Dr. Kundu, director of the Northwestern Center for Ethnic Skin at Northwestern University, Chicago. These healers might be practitioners of curanderismo, in which they believe they are healing as a "gift from a higher power," while employing prayers, baths, and botanicals to combat illness. Another practice is espiritismo, which is a belief that good and evil spirits affect health.

Courtesy Dr. Roopal V. Kundu

Asian patients, meanwhile, have their own set of healers and practices. For example, patients may practice "cupping" for chronic pain and respiratory disease, whereby a glass or plastic cup is placed over the back to create a local vacuum, in the hopes of relieving congestion and increasing circulation.

"Wet cupping" is similar, except that a small scratch or incision is made prior to the cupping procedure.

Both cupping practices leave behind circular patterns of erythema, edema, and ecchymosis, and could be mistaken for child abuse or another skin disorder, said Dr. Kundu, who recently published a paper on this and other Asian dermatoses (Int. J. Dermatol. 2012;51:372-82).

Similarly, "coining," "spooning," or "cao gio" is a Vietnamese dermabrasion therapy, whereby skin is lubricated with oils and then rubbed firmly using the edge of a spoon or coin.

The result will be parallel lines of ecchymoses on the chest and back in a "pine tree" pattern, said Dr. Kundu.

Another Asian practice, moxibustion, or moxa, involves burning materials on the skin to combat atopic dermatitis, postherpetic neuralgia, and tinea pedis. The small, circular scars left behind approximate cigarette burns.

She also advised questioning the use of hair oils in Southeast Asian and black patients. Mustard, coconut, and amla oil are supposed to be toxic to certain dermatophytes, said Dr. Kundu. However, she warned, the theory might backfire in practice. "Are the different oils perpetuating different organisms and allowing [tinea capitas]?"

Finally, Dr. Kundu noted that among Asian and Hispanic populations, decision making by family consensus is the norm. "With almost all of my ethnic patients, I almost always have someone else in the room – a sister, brother, parent, child, uncle," she said. "You’re kind of engaging both of them in the dialogue and [the patient is] often looking toward that person for help in navigating the health care system."

Dr. Kundu stated that she had no relevant relationships with industry to disclose.

Many children with oppositional defiant disorder but not autism nevertheless exhibit elevated symptoms of autism spectrum disorder as well as schizophrenia spectrum disorder.

Moreover, children rated by mothers or teachers to have characteristics of anger and irritability associated with their oppositional defiant disorder (ODD) also had more severe symptoms of autism spectrum disorder and schizophrenia spectrum disorder as did children with the noncompliant aspect of ODD, according to a study in the July-August issue of Research in Developmental Disabilities.

"These results provide additional support for the notion that anger/irritability symptoms and noncompliance symptoms represent divergent phenomena in non-ASD clinically referred youth, and extend this observation to ASD (autism spectrum disorder) and SSD (schizophrenia spectrum disorder) symptoms," wrote the researchers (Res. Dev. Disabil. 2012;33:1157-68).

Dr. Kenneth D. Gadow of Stony Brook University, in Stony Brook, N.Y., and Dr. Deborah A.G. Drabick of Temple University, Philadelphia, looked at 1,160 children between the ages of 6 and 18 years who were consecutive referrals to a university hospital child psychiatry outpatient service. The researchers divided subjects who met the DSM criteria for oppositional defiant disorder into two subtypes: those with an angry/irritable symptomatology and those whose personality was primarily characterized by noncompliance.

Subjects rated as "often" or "very often" losing temper, becoming angry and resentful, or being touchy and easily annoyed by others were placed in the angry/irritable subgroup. The noncompliant subgroup consisted of youths who met ODD criteria, but who had two or fewer angry/irritable criteria. Both groups were compared to similar students without symptoms.

Mothers and teachers of the referred children rated the subject’s autism and schizophrenia symptoms using the Child and Adolescent Symptom Inventory-4R. The responses were summed to create symptom severity scores for autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD).

The authors then conducted two separate analyses. The first looked at youth classified as having the angry/irritable subtype based on either a mother’s or a teacher’s report, but not both. These children were compared with noncompliant subtype youths and controls.

Youths in the angry/irritable subtype as well as those in the noncompliant subtype were rated as having more severe ASD and SSD symptoms than did controls. However, especially among younger patients, angry/irritable subtypes scored higher on the ASD and SSD scales as did the oppositional subtype and controls.

Next, the researchers compared youth rated as the angry/irritable subtype by both mothers’ and teachers’ ratings and youth who met the angry/irritable criteria according to just one source, but not the other.

The angry/irritable and noncompliant dichotomy is sometimes referred to as the affective and behavioral aspects of ODD, respectively. These symptom groups may pertain to different types of affect with unique neurobiologic substrates and phylogenetic histories, the researchers said. For example, noncompliance may be more likely to be associated with novelty-seeking and exploratory behaviors.

Regarding the second analysis and its finding that ODD youth may vary based on informer (teacher vs. mother) and environment (school vs. home), the researchers cautioned that "different strategies for defining clinical phenotypes may lead to very different conclusions about similarities and differences between diagnoses and inferences about the magnitude of therapeutic improvement," they added.

The emotion dysregulation and interpersonal conflicts that define ODD may share similarities with the communication and social skills deficits of ASD and SSD, the researchers said. Social interactions are challenging for these youth, "and thus generate a range of intense emotional reactions. It is also possible that ASD and SSD represent divergent extremes of similar processes. Our expectation that source–specific symptom groups based on teachers’ vs. mothers’ ratings would reveal more pronounced group differentiation was not supported."

Differences between anger/irritability symptoms and noncompliant symptoms were observed more frequently among mother-defined groups (anger/irritability symptoms exceeded noncompliant symptoms for 7 of 10 comparisons) than among teacher-defined groups (anger/irritability symptoms exceeded noncompliant symptoms for 1 of 10 comparisons).

Dr. Gadow disclosed being a shareholder in Checkmate Plus, the publisher of the Child and Adolescent Symptom Inventory-4R. Dr. Drabick reported having no conflict of interest.

Many children with oppositional defiant disorder but not autism nevertheless exhibit elevated symptoms of autism spectrum disorder as well as schizophrenia spectrum disorder.

Moreover, children rated by mothers or teachers to have characteristics of anger and irritability associated with their oppositional defiant disorder (ODD) also had more severe symptoms of autism spectrum disorder and schizophrenia spectrum disorder as did children with the noncompliant aspect of ODD, according to a study in the July-August issue of Research in Developmental Disabilities.

"These results provide additional support for the notion that anger/irritability symptoms and noncompliance symptoms represent divergent phenomena in non-ASD clinically referred youth, and extend this observation to ASD (autism spectrum disorder) and SSD (schizophrenia spectrum disorder) symptoms," wrote the researchers (Res. Dev. Disabil. 2012;33:1157-68).

Dr. Kenneth D. Gadow of Stony Brook University, in Stony Brook, N.Y., and Dr. Deborah A.G. Drabick of Temple University, Philadelphia, looked at 1,160 children between the ages of 6 and 18 years who were consecutive referrals to a university hospital child psychiatry outpatient service. The researchers divided subjects who met the DSM criteria for oppositional defiant disorder into two subtypes: those with an angry/irritable symptomatology and those whose personality was primarily characterized by noncompliance.

Subjects rated as "often" or "very often" losing temper, becoming angry and resentful, or being touchy and easily annoyed by others were placed in the angry/irritable subgroup. The noncompliant subgroup consisted of youths who met ODD criteria, but who had two or fewer angry/irritable criteria. Both groups were compared to similar students without symptoms.

Mothers and teachers of the referred children rated the subject’s autism and schizophrenia symptoms using the Child and Adolescent Symptom Inventory-4R. The responses were summed to create symptom severity scores for autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD).

The authors then conducted two separate analyses. The first looked at youth classified as having the angry/irritable subtype based on either a mother’s or a teacher’s report, but not both. These children were compared with noncompliant subtype youths and controls.

Youths in the angry/irritable subtype as well as those in the noncompliant subtype were rated as having more severe ASD and SSD symptoms than did controls. However, especially among younger patients, angry/irritable subtypes scored higher on the ASD and SSD scales as did the oppositional subtype and controls.

Next, the researchers compared youth rated as the angry/irritable subtype by both mothers’ and teachers’ ratings and youth who met the angry/irritable criteria according to just one source, but not the other.

The angry/irritable and noncompliant dichotomy is sometimes referred to as the affective and behavioral aspects of ODD, respectively. These symptom groups may pertain to different types of affect with unique neurobiologic substrates and phylogenetic histories, the researchers said. For example, noncompliance may be more likely to be associated with novelty-seeking and exploratory behaviors.

Regarding the second analysis and its finding that ODD youth may vary based on informer (teacher vs. mother) and environment (school vs. home), the researchers cautioned that "different strategies for defining clinical phenotypes may lead to very different conclusions about similarities and differences between diagnoses and inferences about the magnitude of therapeutic improvement," they added.

The emotion dysregulation and interpersonal conflicts that define ODD may share similarities with the communication and social skills deficits of ASD and SSD, the researchers said. Social interactions are challenging for these youth, "and thus generate a range of intense emotional reactions. It is also possible that ASD and SSD represent divergent extremes of similar processes. Our expectation that source–specific symptom groups based on teachers’ vs. mothers’ ratings would reveal more pronounced group differentiation was not supported."

Differences between anger/irritability symptoms and noncompliant symptoms were observed more frequently among mother-defined groups (anger/irritability symptoms exceeded noncompliant symptoms for 7 of 10 comparisons) than among teacher-defined groups (anger/irritability symptoms exceeded noncompliant symptoms for 1 of 10 comparisons).

Dr. Gadow disclosed being a shareholder in Checkmate Plus, the publisher of the Child and Adolescent Symptom Inventory-4R. Dr. Drabick reported having no conflict of interest.

Many children with oppositional defiant disorder but not autism nevertheless exhibit elevated symptoms of autism spectrum disorder as well as schizophrenia spectrum disorder.

Moreover, children rated by mothers or teachers to have characteristics of anger and irritability associated with their oppositional defiant disorder (ODD) also had more severe symptoms of autism spectrum disorder and schizophrenia spectrum disorder as did children with the noncompliant aspect of ODD, according to a study in the July-August issue of Research in Developmental Disabilities.

"These results provide additional support for the notion that anger/irritability symptoms and noncompliance symptoms represent divergent phenomena in non-ASD clinically referred youth, and extend this observation to ASD (autism spectrum disorder) and SSD (schizophrenia spectrum disorder) symptoms," wrote the researchers (Res. Dev. Disabil. 2012;33:1157-68).

Dr. Kenneth D. Gadow of Stony Brook University, in Stony Brook, N.Y., and Dr. Deborah A.G. Drabick of Temple University, Philadelphia, looked at 1,160 children between the ages of 6 and 18 years who were consecutive referrals to a university hospital child psychiatry outpatient service. The researchers divided subjects who met the DSM criteria for oppositional defiant disorder into two subtypes: those with an angry/irritable symptomatology and those whose personality was primarily characterized by noncompliance.

Subjects rated as "often" or "very often" losing temper, becoming angry and resentful, or being touchy and easily annoyed by others were placed in the angry/irritable subgroup. The noncompliant subgroup consisted of youths who met ODD criteria, but who had two or fewer angry/irritable criteria. Both groups were compared to similar students without symptoms.

Mothers and teachers of the referred children rated the subject’s autism and schizophrenia symptoms using the Child and Adolescent Symptom Inventory-4R. The responses were summed to create symptom severity scores for autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD).

The authors then conducted two separate analyses. The first looked at youth classified as having the angry/irritable subtype based on either a mother’s or a teacher’s report, but not both. These children were compared with noncompliant subtype youths and controls.

Youths in the angry/irritable subtype as well as those in the noncompliant subtype were rated as having more severe ASD and SSD symptoms than did controls. However, especially among younger patients, angry/irritable subtypes scored higher on the ASD and SSD scales as did the oppositional subtype and controls.

Next, the researchers compared youth rated as the angry/irritable subtype by both mothers’ and teachers’ ratings and youth who met the angry/irritable criteria according to just one source, but not the other.

The angry/irritable and noncompliant dichotomy is sometimes referred to as the affective and behavioral aspects of ODD, respectively. These symptom groups may pertain to different types of affect with unique neurobiologic substrates and phylogenetic histories, the researchers said. For example, noncompliance may be more likely to be associated with novelty-seeking and exploratory behaviors.

Regarding the second analysis and its finding that ODD youth may vary based on informer (teacher vs. mother) and environment (school vs. home), the researchers cautioned that "different strategies for defining clinical phenotypes may lead to very different conclusions about similarities and differences between diagnoses and inferences about the magnitude of therapeutic improvement," they added.

The emotion dysregulation and interpersonal conflicts that define ODD may share similarities with the communication and social skills deficits of ASD and SSD, the researchers said. Social interactions are challenging for these youth, "and thus generate a range of intense emotional reactions. It is also possible that ASD and SSD represent divergent extremes of similar processes. Our expectation that source–specific symptom groups based on teachers’ vs. mothers’ ratings would reveal more pronounced group differentiation was not supported."

Differences between anger/irritability symptoms and noncompliant symptoms were observed more frequently among mother-defined groups (anger/irritability symptoms exceeded noncompliant symptoms for 7 of 10 comparisons) than among teacher-defined groups (anger/irritability symptoms exceeded noncompliant symptoms for 1 of 10 comparisons).

Dr. Gadow disclosed being a shareholder in Checkmate Plus, the publisher of the Child and Adolescent Symptom Inventory-4R. Dr. Drabick reported having no conflict of interest.

Deficits in memory generalization are present among schizophrenia patients, their relatives, and bipolar patients, compared with healthy controls, reported Dr. Elena I. Ivleva and her colleagues in the June issue of Schizophrenia Research.

The finding "suggests a specific deficit in memory-guided generalizations common to the psychosis probands that is independent of learning or memory for previously learned associations," wrote the authors (Schizophrenia Research 2012;138:74-80).

Dr. Ivleva of the University of Texas Southwestern Medical Center, Dallas, looked at a combination of probands with DSM-IV diagnoses of schizophrenia (n = 33) and bipolar disorder (n = 20), as well as 21 first-degree relatives of schizophrenia patients (who may or may not have had a psychiatric history) and 26 healthy controls. The groups were demographically similar, except for a slightly higher percentage of males in the schizophrenia patient group.

Most probands and three of the schizophrenia relatives underwent treatment with a combination of psychotropic agents during the study period, wrote the authors, including mood stabilizers and antipsychotics.

"Since the proband groups were comparable with respect to active medication status, cognitive outcomes were not adjusted for medication use," they wrote—a possible study limitation, conceded Dr. Ivleva.

All subjects underwent a modified version of the computer-based Acquired Equivalence paradigm (J. Cogn. Neurosci. 2003;15:185-93), which assesses associative learning, memory for learned associations, and memory generalization.

The authors found that there were no differences in overall learning and memory retrieval in either psychosis probands or the relatives of the schizophrenia patients, compared with controls, "although [schizophrenia probands] demonstrated slower initial learning, consistent with prior reports."

However, when it came to the memory generalization portion of the test, "All probands ... showed lower memory generalization performance, compared with healthy controls," wrote the authors, with P = .026.

Separately, there was a statistically significant difference between schizophrenia patients and controls (P = .038) and a trend-level difference between bipolar patients and controls (P = .069), with no differences found between proband groups.

Looking at the schizophrenia relatives, the researchers found that their performance on the memory generalization component of the test was intermediate between that of the schizophrenia patients and the controls, although more similar to the performance of the controls. Their score was not statistically different from either group (vs. probands, P = .09; vs. controls, P = .85).

"No correlations were found between memory generalization and learning across all stages; memory recall; any of the declarative memory tests; Wechsler Test of Adult Reading general intelligence estimate; age; education; total, psychosis and affective Brief Psychiatric Rating Scale scores; Global Assessment of Functioning Scale scores; age of psychosis onset, age at the first psychiatric hospitalization, or lifetime number of hospitalizations in either schizophrenia or bipolar disorder."

Dr. Ivleva wrote that while the specific mechanisms underlying how generalization deficits link to psychosis remain unknown, at least one recent report (Am. J. Psychiatry 2010;167:1178-93) offers a possible model.

That study "suggests that a hypoglutamatergic lesion in [the] dentate gyrus possibly generates alterations in synaptic plasticity in CA3, specifically, a compensatory increase in sensitivity to incoming stimuli in CA3 excitatory synapses, and results in altered memory generalization, associational mistakes and, possibly, psychotic productions," she wrote.

"This model ... is currently being tested."

The authors disclosed that the study was funded by grants from the National Institutes of Mental Health, the Brain and Behavior Research, and the American Psychiatric Foundation. They stated that they had no personal financial conflicts of interest to disclose.

Deficits in memory generalization are present among schizophrenia patients, their relatives, and bipolar patients, compared with healthy controls, reported Dr. Elena I. Ivleva and her colleagues in the June issue of Schizophrenia Research.

The finding "suggests a specific deficit in memory-guided generalizations common to the psychosis probands that is independent of learning or memory for previously learned associations," wrote the authors (Schizophrenia Research 2012;138:74-80).

Dr. Ivleva of the University of Texas Southwestern Medical Center, Dallas, looked at a combination of probands with DSM-IV diagnoses of schizophrenia (n = 33) and bipolar disorder (n = 20), as well as 21 first-degree relatives of schizophrenia patients (who may or may not have had a psychiatric history) and 26 healthy controls. The groups were demographically similar, except for a slightly higher percentage of males in the schizophrenia patient group.

Most probands and three of the schizophrenia relatives underwent treatment with a combination of psychotropic agents during the study period, wrote the authors, including mood stabilizers and antipsychotics.

"Since the proband groups were comparable with respect to active medication status, cognitive outcomes were not adjusted for medication use," they wrote—a possible study limitation, conceded Dr. Ivleva.

All subjects underwent a modified version of the computer-based Acquired Equivalence paradigm (J. Cogn. Neurosci. 2003;15:185-93), which assesses associative learning, memory for learned associations, and memory generalization.

The authors found that there were no differences in overall learning and memory retrieval in either psychosis probands or the relatives of the schizophrenia patients, compared with controls, "although [schizophrenia probands] demonstrated slower initial learning, consistent with prior reports."

However, when it came to the memory generalization portion of the test, "All probands ... showed lower memory generalization performance, compared with healthy controls," wrote the authors, with P = .026.

Separately, there was a statistically significant difference between schizophrenia patients and controls (P = .038) and a trend-level difference between bipolar patients and controls (P = .069), with no differences found between proband groups.

Looking at the schizophrenia relatives, the researchers found that their performance on the memory generalization component of the test was intermediate between that of the schizophrenia patients and the controls, although more similar to the performance of the controls. Their score was not statistically different from either group (vs. probands, P = .09; vs. controls, P = .85).

"No correlations were found between memory generalization and learning across all stages; memory recall; any of the declarative memory tests; Wechsler Test of Adult Reading general intelligence estimate; age; education; total, psychosis and affective Brief Psychiatric Rating Scale scores; Global Assessment of Functioning Scale scores; age of psychosis onset, age at the first psychiatric hospitalization, or lifetime number of hospitalizations in either schizophrenia or bipolar disorder."

Dr. Ivleva wrote that while the specific mechanisms underlying how generalization deficits link to psychosis remain unknown, at least one recent report (Am. J. Psychiatry 2010;167:1178-93) offers a possible model.

That study "suggests that a hypoglutamatergic lesion in [the] dentate gyrus possibly generates alterations in synaptic plasticity in CA3, specifically, a compensatory increase in sensitivity to incoming stimuli in CA3 excitatory synapses, and results in altered memory generalization, associational mistakes and, possibly, psychotic productions," she wrote.

"This model ... is currently being tested."

The authors disclosed that the study was funded by grants from the National Institutes of Mental Health, the Brain and Behavior Research, and the American Psychiatric Foundation. They stated that they had no personal financial conflicts of interest to disclose.

Deficits in memory generalization are present among schizophrenia patients, their relatives, and bipolar patients, compared with healthy controls, reported Dr. Elena I. Ivleva and her colleagues in the June issue of Schizophrenia Research.

The finding "suggests a specific deficit in memory-guided generalizations common to the psychosis probands that is independent of learning or memory for previously learned associations," wrote the authors (Schizophrenia Research 2012;138:74-80).

Dr. Ivleva of the University of Texas Southwestern Medical Center, Dallas, looked at a combination of probands with DSM-IV diagnoses of schizophrenia (n = 33) and bipolar disorder (n = 20), as well as 21 first-degree relatives of schizophrenia patients (who may or may not have had a psychiatric history) and 26 healthy controls. The groups were demographically similar, except for a slightly higher percentage of males in the schizophrenia patient group.

Most probands and three of the schizophrenia relatives underwent treatment with a combination of psychotropic agents during the study period, wrote the authors, including mood stabilizers and antipsychotics.

"Since the proband groups were comparable with respect to active medication status, cognitive outcomes were not adjusted for medication use," they wrote—a possible study limitation, conceded Dr. Ivleva.

All subjects underwent a modified version of the computer-based Acquired Equivalence paradigm (J. Cogn. Neurosci. 2003;15:185-93), which assesses associative learning, memory for learned associations, and memory generalization.

The authors found that there were no differences in overall learning and memory retrieval in either psychosis probands or the relatives of the schizophrenia patients, compared with controls, "although [schizophrenia probands] demonstrated slower initial learning, consistent with prior reports."

However, when it came to the memory generalization portion of the test, "All probands ... showed lower memory generalization performance, compared with healthy controls," wrote the authors, with P = .026.

Separately, there was a statistically significant difference between schizophrenia patients and controls (P = .038) and a trend-level difference between bipolar patients and controls (P = .069), with no differences found between proband groups.

Looking at the schizophrenia relatives, the researchers found that their performance on the memory generalization component of the test was intermediate between that of the schizophrenia patients and the controls, although more similar to the performance of the controls. Their score was not statistically different from either group (vs. probands, P = .09; vs. controls, P = .85).

"No correlations were found between memory generalization and learning across all stages; memory recall; any of the declarative memory tests; Wechsler Test of Adult Reading general intelligence estimate; age; education; total, psychosis and affective Brief Psychiatric Rating Scale scores; Global Assessment of Functioning Scale scores; age of psychosis onset, age at the first psychiatric hospitalization, or lifetime number of hospitalizations in either schizophrenia or bipolar disorder."

Dr. Ivleva wrote that while the specific mechanisms underlying how generalization deficits link to psychosis remain unknown, at least one recent report (Am. J. Psychiatry 2010;167:1178-93) offers a possible model.

That study "suggests that a hypoglutamatergic lesion in [the] dentate gyrus possibly generates alterations in synaptic plasticity in CA3, specifically, a compensatory increase in sensitivity to incoming stimuli in CA3 excitatory synapses, and results in altered memory generalization, associational mistakes and, possibly, psychotic productions," she wrote.

"This model ... is currently being tested."

The authors disclosed that the study was funded by grants from the National Institutes of Mental Health, the Brain and Behavior Research, and the American Psychiatric Foundation. They stated that they had no personal financial conflicts of interest to disclose.