Faculty Bibliography

OBJECTIVE: Advanced paternal age is consistently associated with an increased risk for schizophrenia, accounting for up to a quarter of cases in some populations. If paternal age-related schizophrenia (PARS) involves a distinct etiopathology, then PARS cases may show specific characteristics, vis-a-vis other schizophrenia cases. This study examined if PARS exhibits the symptom profile and sex differences that are consistently observed for schizophrenia in general, wherein males have an earlier onset age and more severe negative symptoms than females. METHOD: Symptoms were assessed at baseline (admission) and during medication-free and treatment phases for 153 inpatients on a schizophrenia research unit, 38 of whom fulfilled operationally defined criteria for PARS (sporadic cases with paternal age > or = 35). RESULTS: Males and females with PARS had the same age at onset and a similar preponderance of negative symptoms, whereas the other (non-PARS) cases showed the typical earlier onset age and more severe negative symptoms in males. When medications were withdrawn, PARS cases showed significantly worse symptoms than non-PARS cases (higher total PANSS scores and positive, activation, and autistic preoccupation scores). However these symptoms globally improved with antipsychotic treatment, such that the differences between the PARS and other schizophrenia cases receded. CONCLUSION: The lack of sex differences in the age at onset and the greater severity of medication-free symptoms bolster the hypothesis that PARS has a distinct etiopathology. It also suggests that female sex does not exert a protective effect on the course of PARS, as it may in other forms of schizophrenia

This paper describes the process by which child mental health researchers partnered with paraprofessionals called peer family advisors to create a stress-reducing intervention for caregivers of children and adolescents with mental health challenges. The issues that arose as the team strove to develop an intervention that was both relevant to the issues that these caregivers grapple with, as well as palatable and feasible for peers to deliver, are discussed.

BACKGROUND: This review evaluates the DSM-IV criteria of social anxiety disorder (SAD), with a focus on the generalized specifier and alternative specifiers, the considerable overlap between the DSM-IV diagnostic criteria for SAD and avoidant personality disorder, and developmental issues. METHOD: A literature review was conducted, using the validators provided by the DSM-V Spectrum Study Group. This review presents a number of options and preliminary recommendations to be considered for DSM-V. RESULTS/CONCLUSIONS: Little supporting evidence was found for the current specifier, generalized SAD. Rather, the symptoms of individuals with SAD appear to fall along a continuum of severity based on the number of fears. Available evidence suggested the utility of a specifier indicating a "predominantly performance" variety of SAD. A specifier based on "fear of showing anxiety symptoms" (e.g., blushing) was considered. However, a tendency to show anxiety symptoms is a core fear in SAD, similar to acting or appearing in a certain way. More research is needed before considering subtyping SAD based on core fears. SAD was found to be a valid diagnosis in children and adolescents. Selective mutism could be considered in part as a young child's avoidance response to social fears. Pervasive test anxiety may belong not only to SAD, but also to generalized anxiety disorder. The data are equivocal regarding whether to consider avoidant personality disorder simply a severe form of SAD. Secondary data analyses, field trials, and validity tests are needed to investigate the recommendations and options.

Improving outcomes for children and adolescents with mental health needs demands a broad meta-systemic orientation to overcome persistent problems in current service systems. Improving outcomes necessitates inclusion of current and emerging evidence about effective practices for the diverse population of youth and their families. Key components of the meta-system for children with emotional or behavioral needs include families, cultural norms and values, and service sectors such as schools, pediatric health centers, specialty mental health systems, juvenile justice systems, child protection services, and substance use treatment systems. We describe each component of the meta-system, noting challenges to the provision of evidence-based practice (EBP) and highlighting ways to optimize outcomes. Our focus is on the inclusion of evidence-based assessment and interventions, including prevention, within a developmentally driven and culturally responsive contextual model. Recommendations for addressing disparities in research funding and essential steps to foster communication and coordination of EBP across settings are provided.

OBJECTIVE: To determine the effect of serotonin transporter polymorphism promoter region (5-HTTPLR) genotypic variation (low, intermediate, and high expression groups) on response to escitalopram treatment of children and adolescents with autism spectrum disorders (ASDs). METHOD: The study used a forced titration, open label design, with genotype blind until study completion. Participants were children and adolescents aged 4-17 years of age with a confirmed ASD (autistic disorder, Asperger's disorder, or pervasive developmental disorder, not otherwise specified). RESULTS: There was an interaction between genotype group and time on the Aberrant Behavior Checklist (ABC) Irritability Subscale (primary outcome variable) (linear maximum marginal likelihood estimation=-4.84, Z=-2.89, SE=1.67, P=0.004). Examination of baseline to last visit revealed that a genotype grouping based on a previous study of platelet 5-HT uptake revealed less response in the genotype group that had S/S genotype for 5-HTTLPR and did not have a diplotype in intron 1 previously shown to be associated with increased platelet 5-HT uptake. CONCLUSION: This genotype-blind, prospective pharmacogenetic study found the group of subjects with associated with the lowest platelet 5-HT uptake from previous study had the smallest reduction in ABC-Irritability scores after open label treatment with escitalopram. Replication is necessary to confirm these findings

Treatment-resistant depression may be related to polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) or dysregulation of noradrenergic systems. To examine 5-HTTLPR genotypes and responses to treatment, adult patients (N=261) with current major depression and a symptom severity rating > or =8 on the 17-item Hamilton Depression Rating Scale (HAMD(17)) were treated for 8 weeks with open-label sertraline (100-200 mg/d). Patients remaining symptomatic (total score >4, or >1 on any item of the HAMD(17) Maier-Philipp subscale) were randomly assigned to double-blind therapy with sertraline plus either atomoxetine (40-120 mg/d) or placebo for 8 additional weeks. 5-HTTLPR genotype did not predict responses to sertraline monotherapy or discontinuation rates. Among the 138 patients remaining symptomatic after sertraline monotherapy (L/L = 21%, S/L = 50%, S/S = 29%), significantly more S/S-genotype patients achieved remission under combined sertraline/atomoxetine treatment relative to the other genotypes (S/S = 81.8%; non-S/S = 32.7%), but not under sertraline/placebo treatment (S/S = 35.7%; non-S/S = 37.7%). Minor genotypic differences were noted in adverse event profiles. In patients with poor responses to sertraline monotherapy for depression, addition of atomoxetine may improve responses to treatment of depression in S/S-genotyped patients. Although this study is speculative, it represents a pharmacologically and genotypically well-defined patient population