Faculty Bibliography

Although antidepressants are moderately effective in treating major depressive disorder (MDD), concerns have arisen that selective serotonin-reuptake inhibitors (SSRIs) are associated with suicidal thinking and behavior, especially in children, adolescents and young adults. Almost no experimental research in model systems has considered the mechanisms by which SSRIs might be associated with this potential side effect in some susceptible individuals. Suicide is a complex behavior and impossible to fully reproduce in an animal model. However, by investigating traits that show strong cross-species parallels in addition to associations with suicide in humans, animal models might elucidate the mechanisms by which SSRIs are associated with suicidal thinking and behavior. Traits linked with suicide in humans that can be successfully modeled in rodents include aggression, impulsivity, irritability and hopelessness/helplessness. Modeling these relevant traits in animals can help to clarify the impact of SSRIs on these traits, suggesting avenues for reducing suicide risk in this vulnerable population.

There has been growing interest in the use of complementary and alternative treatments in pediatric bipolar disorder (BPD). There are limited data, however, regarding the safety and efficacy of these treatments. This article discusses select complementary and alternative treatments that have been considered for use in pediatric BPD and/or depression, including omega-3-fatty acids, inositol, St. John's wort, SAMe, melatonin, lecithin, and acupuncture. Background information, reference to available adult and pediatric data, proposed mechanisms of action, dosing, side effects, and precautions of these treatments are included. Across the board, more research is necessary and warranted regarding the long-term safety and efficacy of available complementary and alternative treatments for the management of pediatric BPD.

OBJECTIVE: To report results of the clinical reappraisal study of lifetime DSM-IV diagnoses based on the fully structured lay-administered World Health Organization Composite International Diagnostic Interview (CIDI) Version 3.0 in the U.S. National Comorbidity Survey Replication Adolescent Supplement (NCS-A). METHOD: Blinded clinical reappraisal interviews with a probability subsample of 347 NCS-A respondents were administered using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) as the gold standard. The DSM-IV/CIDI cases were oversampled, and the clinical reappraisal sample was weighted to adjust for this oversampling. RESULTS: Good aggregate consistency was found between CIDI and K-SADS prevalence estimates, although CIDI estimates were meaningfully higher than K-SADS estimates for specific phobia (51.2%) and oppositional defiant disorder (38.7%). Estimated prevalence of any disorder, in comparison, was only slightly higher in the CIDI than K-SADS (8.3%). Strong individual-level CIDI versus K-SADS concordance was found for most diagnoses. Area under the receiver operating characteristic curve, a measure of classification accuracy not influenced by prevalence, was 0.88 for any anxiety disorder, 0.89 for any mood disorder, 0.84 for any disruptive behavior disorder, 0.94 for any substance disorder, and 0.87 for any disorder. Although area under the receiver operating characteristic curve was unacceptably low for alcohol dependence and bipolar I and II disorders, these problems were resolved by aggregation with alcohol abuse and bipolar I disorder, respectively. Logistic regression analysis documented that consideration of CIDI symptom-level data significantly improved prediction of some K-SADS diagnoses. CONCLUSIONS: These results document that the diagnoses made in the NCS-A based on the CIDI have generally good concordance with blinded clinical diagnoses

Although it is known that schizophrenia is associated with social class, controversy exists as to the nature of this association. The authors studied the incidence of schizophrenia in relation to social class at birth in a population-based cohort of 88,829 offspring born in Jerusalem in 1964-1976. They constructed a six-point scale to index social class, based on paternal occupation at the time of birth, with each of 108 occupations being ranked by mean education. Cox proportional hazards methods were used in adjusting for sex, parents' ages, duration of marriage and birth order. Linkage with Israel's Psychiatric Registry identified 637 people admitted to psychiatric care facilities with schizophrenia-related diagnoses, before 1998. There was no gradient of risk for schizophrenia associated with social class at birth; however, offspring of fathers in the lowest social class showed a modest increase in risk (adjusted Relative Risk = 1.4; 95% Confidence interval = 1.1-1.8, P = 0.002). These data suggest that in contrast to many other health outcomes, there is not a continuous gradient for increasing schizophrenia with decreasing social class of origin. Instead, a modest increase in risk for schizophrenia was observed only for those born at the bottom of the social ladder

OBJECTIVE: The aim of this study was to assess the effectiveness and tolerability of a long-acting methylphenidate (MPH) formulation, beaded MPH (B-MPH), for treatment of attention-deficit/hyperactivity disorder (ADHD) in 4- and 5-year-old children. METHOD: Eleven children (9 boys and 2 girls) with ADHD received 4 weeks of B-MPH treatment in a single-site, open-label pilot study. Medication dosing was flexible, with titration to a maximum of 30 mg/day. A brief education session on behavior management was offered to parents at each treatment visit. RESULTS: Subjects experienced a mean decrease of 1.09 (standard deviation [SD]=0.73, p<0.01) on the Swanson, Nolan, and Pelham Questionnaire (SNAP-IV) ADHD composite score to an end point of 1.18 (SD=0.64). Subjects demonstrated mean decreases in scores of inattention of 1.01 (SD=0.85, p<0.01) and in hyperactivity/impulsivity of 1.17 (SD=0.74, p<0.01), with end point scores of 1.10 (SD=0.61) and 1.26 (SD=0.77), respectively. The Clinical Global Impressions-Severity (CGI-S) scale showed a statistically significant improvement from a baseline mean of 5 to the final visit mean of 3.36 (p<0.01). At the final visit, the mean daily B-MPH dose was 17.73 mg. Subjects did not experience any statistically significant changes in weight, blood pressure, or pulse during the study. The most common adverse event was decreased appetite. CONCLUSION: B-MPH was safe and effective for the treatment of ADHD in the 4- and 5-year-olds participating in this study

Frontolimbic structures involved in fear conditioning have also been associated with hypothalamic-pituitary-adrenal (HPA)-axis modulation, including amygdaloid, hippocampal, and ventromedial prefrontal cortex regions. Although HPA-axis function and endocrine changes have been investigated in the context of stress provocation, much research has not been conducted using functional neuroimaging in the study of the HPA axis and frontolimbic function in response to emotional stimuli. Using functional magnetic resonance imaging, the association of blood-oxygen-level dependent signal with salivary cortisol in response to an emotional visual scene paradigm was investigated, with prescan and postscan salivary cortisol analyzed as a covariate of interest during specific conditions. Cortisol reactivity to the paradigm was positively associated with amygdalar and hippocampal activity and negatively associated with ventromedial prefrontal cortex activity in conditions involving emotional imagery

The authors examined racial/ethnic disparities in mental health service use based on problem type (internalizing/externalizing). A diverse sample of youth in contact with public sectors of care and their families provided reports of youth's symptoms and functional impairment during an initial interview. Specialty and school-based mental health service use during the subsequent 2 years was assessed prospectively. Greater disparities in mental health service receipt were evident for internalizing problems, with non-Hispanic White youth more likely to receive services in response to internalizing symptoms than minority youth. Fewer disparities in rates of unmet need emerged for externalizing problems, but minority youth were more likely to have need for externalizing problems met and African American youth were particularly likely to receive services in response to such problems. Findings highlight the importance of considering problem type when examining racial disparities in mental health services and underscore concerns about the responsiveness of mental health services for minority youth with internalizing disorders.