Faculty Bibliography

BACKGROUND: We sought to test the hypothesis that deficits in grey matter volume are characteristic of psychotic youth with early-onset schizophrenia-spectrum disorders (EOSS) but not of psychotic youth with early-onset mood disorders (EOMD). METHODS: We used magnetic resonance imaging to examine brain volume in 24 psychotic youth (13 male, 11 female) with EOSS (n = 12) or EOMD (n = 12) and 17 healthy controls (10 male, 7 female). We measured the volume of grey and white matter using an automated segmentation program. RESULTS: After adjustment for age and intracranial volume, whole brain volume was lower in the EOSS patients than in the healthy controls (p = 0.001) and EOMD patients (p = 0.002). The EOSS patients had a deficit in grey matter volume (p = 0.005), especially in the frontal (p = 0.003) and parietal (p = 0.006) lobes, with no significant differences in white matter volume. LIMITATIONS: The main limitations of our study were its small sample size and the inclusion of patients with depression and mania in the affective group. CONCLUSION: Adolescents with EOSS have grey matter deficits compared with healthy controls and psychotic adolescents with EOMD. Our results suggest that grey matter deficits are not generally associated with psychosis but may be specifically associated with schizophrenia. Larger studies with consistent methods are needed to reconcile the contradictory findings among imaging studies involving psychotic youth.

OBJECTIVE: It is still a matter of debate whether estrogen can have a protective effect on brain integrity and against age- and Alzheimer-related assaults. Evidence points toward selective sparing of gray matter (GM) in postmenopausal women using hormone therapy. In the current study, the effect of sex and estrogen therapy (ET) exposure on GM density using voxel-based morphometry was assessed. METHODS: High-resolution structural magnetic resonance imaging scans of 46 healthy participants were analyzed using voxel-based morphometry. A total of 15 men and 31 healthy postmenopausal women were included: 15 ET-naive women (never users) and 16 current ET users with an average duration of use of 11 years. RESULTS: Sex differences were found in fronto-temporo-parietal areas, with postmenopausal women having greater GM concentration in the medial prefrontal cortex, temporal cortices, angular gyrus, and precuneus, whereas the men had greater GM density in the superior frontal, inferior temporal gyri, and inferior parietal lobules. ET users compared with never users had greater GM density in the superior frontal gyrus and less GM density in the posterior part of the hippocampus and parahippocampal gyrus, posterior cingulate, and angular gyri. In the group of ET users, a negative association was found between duration of ET use and posterior hippocampus and parahippocampal GM density, whereas a positive association was found in the hypothalamus, striatum, precunei, and inferior parietal lobules. CONCLUSIONS: These results point toward a potential regional- and duration-dependent estrogen exposure effect on cerebral areas known to be involved in age-related cognitive functions and Alzheimer and Parkinson diseases

As the population of the United States becomes more ethnically diverse, clinicians are faced with treating patients from a variety of different cultures with various customs, beliefs, and practices. This case report describes the presentation of a 55-year-old Somali refugee suffering from depression and posttraumatic stress disorder, in the context of his culture. The discussion suggests ways in which clinicians may respond to and work with Somali patients, in order to promote their well-being in a culturally competent manner.

BACKGROUND: A common polymorphism in the serotonin transporter gene (SLC6A4, 5HTT) has been repeatedly shown to moderate the influence of childhood adversity and stressful life events on the development of psychopathology. Using data from the English and Romanian Adoptee Study, a prospective-longitudinal study of individuals (n = 125) exposed to severe early institutional deprivation (ID), we tested whether the effect of ID on adolescent emotional problems is moderated by 5HTT genotype and stressful life events in adolescence. METHODS: Emotional problems were assessed using questionnaire data (age 11), and on the basis of the CAPA diagnostic interview (age 15). Additionally, the number of stressful life events was measured. RESULTS: There was a significant effect for genotype (p = .003) and a gene x environment interaction (p = .008) that was independent of age at testing. Carriers of the s/l and s/s genotype who experienced severe ID showed the highest emotional problem scores, while l/l homozygotes in the severe ID group showed the lowest overall levels. Furthermore, s/s carriers in the severe ID group who experienced a high number of stressful life events between 11 and 15 years had the largest increases in emotional problem scores, while a low number of stressful life events was associated with the largest decrease (4-way interaction: p = .05). CONCLUSIONS: The effects of severe early ID on emotional problems in adolescence are moderated by 5HTT genotype, and influenced by stressful life events in adolescence

OBJECTIVE: The aims of this paper are as follows: to present past-year prevalence data for DSM-IV disorders in the early elementary school years; to examine the impact of impairment criteria on prevalence estimates; to examine the relation of sociodemographic and psychosocial risk factors to disorders; and to explore associations between "internalizing" and "externalizing" disorders and social competence and family burden as further validation of the impairing nature of these disorders. METHOD: As part of a longitudinal representative population study of children born healthy between July 1995 and September 1997 in the New Haven-Meriden Standard Metropolitan Statistical Area of the 1990 Census (n = 1,329), parents of a subsample enriched for child psychopathology (n = 442; 77.6% response rate, 69.5% of eligible sample) were interviewed in the child's kindergarten or first-grade year with the Diagnostic Interview Schedule for Children, Version IV (DISC-IV). Parents were surveyed about sociodemographic and psychosocial characteristics, and both parents and teachers were surveyed about social competence. RESULTS: Approximately one in five (21.6 %) children met criteria for psychiatric disorder(s) with impairment. Sociodemographic and psychosocial correlates included persistent poverty beginning in early childhood, limited parental education, low family expressiveness, stressful life events, and violence exposure. Finally, diagnostic status was significantly associated with poorer social competence and family burden. CONCLUSIONS: That approximately one in five children evidenced a psychiatric disorder with impairment during the transition to formal schooling highlights the importance of integrating psychiatric epidemiological and developmental approaches to inform conversations about school readiness and intervention planning.

BACKGROUND: Exaggerated amygdala activation to threatening faces has been detected in adults and children with anxiety disorders, compared to healthy comparison (HC) subjects. However, the profile of amygdala activation in response to facial expressions in obsessive-compulsive disorder (OCD) may be a distinguishing feature; a prior study found that compared with healthy adults, adults with OCD exhibited less amygdala activation to emotional and neutral faces, relative to fixation [Cannistraro et al. (2004). Biological Psychiatry 56:916-920]. METHODS: In the current event-related functional magnetic resonance imaging (fMRI) study, a pediatric OCD sample (N=12) and a HC sample (N=17) performed a gender discrimination task while viewing emotional faces (happy, fearful, disgusted) and neutral faces. RESULTS: Compared to the HC group, the OCD group showed less amygdala/hippocampus activation in all emotion and neutral conditions relative to fixation. CONCLUSIONS: Like previous reports in adult OCD, pediatric OCD may have a distinct neural profile from other anxiety disorders, with respect to amygdala activation in response to emotional stimuli that are not disorder specific.

Recent studies in rodents have suggested a role for the central endocannabinoid system in the regulation of mood and alcohol related behaviors. Alcohol use disorder is often associated with suicidal behavior. In the present study, we examined whether abnormalities in the endocannabinoid system in the ventral striatum are associated with alcohol dependence and suicide. The levels of CB1 receptors, receptor-mediated G-protein signaling, and activity and level of the fatty acid amide hydrolase (FAAH) were analyzed postmortem in the ventral striatum of alcohol-dependent nonsuicides (CA, n=9), alcohol-dependent suicides (AS, n=9) and nonpsychiatric controls (C, n=9). All subjects underwent a psychological autopsy, and toxicological and neuropathological examinations. The levels of the CB1 receptors and the CB1 receptor-mediated G-protein signaling were significantly lower in the ventral striatum of CA compared to the control group. However, these parameters were elevated in AS when compared to CA group. The activity of FAAH enzyme was lower in CA compared to the control group while it was found to be significantly higher in AS compared with CA group. These findings suggest that alcohol dependence is associated with the downregulation of the CB1 receptors, while suicide is linked to the upregulation of these receptors in the ventral striatum. Alteration in the activity of FAAH enzyme that regulates the anandamide (AEA) content might in turn explain differences in the CB1 receptor function in alcohol dependence and suicide. These findings may have etiological and therapeutic implications for the treatment of alcohol addiction and suicidal behavior

OBJECTIVE: The goal of this study was to pilot a randomized controlled trial of OROS methylphenidate (OROS-MPH) to treat attention deficit hyperactivity disorder (ADHD) plus epilepsy. METHODS: Thirty-three patients, 6-18years of age, taking antiepileptic drugs and with a last seizure 1-60months prior were assigned to a maximum daily dose of 18, 36, or 54mg of OROS-MPH in a double-blind placebo-controlled crossover trial. RESULTS: There were no serious adverse events and no carryover effects in the crossover trial. OROS-MPH reduced ADHD symptoms more than did placebo treatment. There were too few seizures during the active (5) and placebo arms (3) to confidently assess seizure risk; however, considering exposure time, we observed an increased daily risk of seizures with increasing dose of OROS-MPH, suggesting that potential safety concerns require further study. CONCLUSION: A larger study to assess the effect of OROS-MPH on seizure risk is needed. A crossover design including subjects with frequent seizures could maximize power and address high patient heterogeneity and recruitment difficulties.

BACKGROUND: Dermatomyositis is an autoimmune disease of unknown etiology characterized by inflammation of the skin and muscles. Several medications have been implicated in the development of dermatomyositis; however, the disease has rarely been linked to the use of tumor necrosis factor (TNF) inhibitors. We report 4 cases of dermatomyositis that developed or were exacerbated by exposure to the TNF inhibitors etanercept and adalimumab. Observation Four patients with symptoms of inflammatory arthritis were treated with TNF inhibitors for a duration ranging from 2 months to 2 years. All 4 patients developed symptoms consistent with dermatomyositis, including inflammatory rash and muscle weakness. Their symptoms persisted after discontinuation of the treatment with the TNF inhibitors but responded to treatment with corticosteroids and immunosuppressive medications. CONCLUSIONS: Tumor necrosis factor inhibitors have been associated with the onset of a number of autoimmune disorders, most commonly vasculitis and a lupuslike syndrome. Rarely have they been associated with dermatomyositis. The 4 cases reported herein indicate that TNF inhibitor use can be associated with either induction or exacerbation of dermatomyositis.