Resting-State Quantitative Electroencephalography Demonstrates Differential Connectivity in Adolescents with Major Depressive Disorder.

Background: Biomarkers for psychiatric disorders in children and adolescents are urgently needed. This cross-sectional pilot study investigated quantitative electroencephalogram (qEEG), a promising intermediate biomarker, in pediatric patients with major depressive disorder (MDD) compared with healthy controls (HCs). We hypothesized that youth with MDD would have increased coherence (connectivity) and absolute alpha power in the frontal cortex compared with HC. Methods: qEEG was obtained in adolescents aged 14-17 years with MDD (n = 25) and age- and gender-matched HCs (n = 14). The primary outcome was overall coherence on qEEG in the four frequency bands (alpha, beta, theta, and delta). Other outcomes included frontal-only coherence, overall and frontal-only qEEG power, and clinician-rated measures of anhedonia and anxiety. Results: Average coherence in the theta band was significantly lower in MDD patients versus HCs, and also lower in frontal cortex among MDD patients. Seven node pairs were significantly different or trending toward significance between MDD and HC; all had lower coherence in MDD patients. Average frontal delta power was significantly higher in MDD versus HCs. Conclusions: Brain connectivity measured by qEEG differs significantly between adolescents with MDD and HCs. Compared with HCs, youth with MDD showed decreased connectivity, yet no differences in power in any frequency bands. In the frontal cortex, youth with MDD showed decreased resting connectivity in the alpha and theta frequency bands. Impaired development of a resting-state brain network (e.g., default mode network) in adolescents with MDD may represent an intermediate phenotype that can be assessed with qEEG.

A Double-Blind and Placebo-Controlled Trial of Aripiprazole in Symptomatic Youths at Genetic High Risk for Bipolar Disorder.

OBJECTIVE: To determine if acute treatment with aripiprazole (APZ) would be superior to treatment with placebo in reducing dysfunctional symptoms of elevated mood and/or irritability in symptomatic children and adolescents at familial high risk for bipolar disorder (BPD) whose mood episodes occur spontaneously. These are patients we have previously referred to as suffering from "cyclotaxia." METHODS: This was single-site, randomized, double-blind, placebo-controlled outpatient clinical trial in which youths aged 5-17 years who met diagnostic criteria for either cyclothymic disorder (CYC) or BPD not otherwise specified (BP-NOS) were randomly assigned to receive either APZ or placebo. Eligible participants had at least one parent with BPD, another first- or second-degree relative afflicted with a mood disorder, and also had not responded to psychotherapy. Treatment with APZ was initiated at a dose of approximately 0.1 mg/kg/day and could be increased by approximately 0.05 mg/kg/day at each study visit. Patients were seen weekly for 4 weeks and then every other week thereafter for 12 weeks. The primary outcome measure was mean change from baseline on Young Mania Rating Scale (YMRS) total score. RESULTS: A total of 59 patients (30 APZ, 29 placebo) aged 11.8 (SD = 2.7) years were randomized and returned for at least one postbaseline assessment. The mean total daily doses of active APZ and placebo were 7.1 mg (SD = 3.7) and 7.4 mg (SD = 4.2), respectively. At the 12-week time point, APZ was superior to placebo on the primary outcome measure (p < 0.005). Most adverse events were mild and transient in nature. There was a significant difference in weight gain from baseline between patients who received APZ (2.3 kg [SD = 3.3]) and those who received placebo (0.7 kg [SD = 1.8]). CONCLUSION: This double-blind trial found that APZ was significantly more efficacious than placebo in reducing symptoms of mania in children and adolescents with cyclotaxia.

Clinical characteristics of children receiving antipsychotic medication.

This study explored the demographic and diagnostic features of children who were currently receiving antipsychotics compared to children who were receiving other psychotropics in a cohort of children with and without elevated symptoms of mania (ESM). Participants were recruited from 10 child outpatient mental health clinics associated with four universities. Guardians with children between 6-12 years who presented for new clinical evaluations completed the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M). All children who scored ≥12 on the PGBI-10M and a select demographically matched comparison group of patients who scored ≤11 were invited to participate. Children were divided into two groups: those receiving at least one antipsychotic medication and those receiving other psychotropic medications. The groups were compared on demographics, diagnoses, psychiatric symptoms, functioning, and past hospitalizations. Of the 707 children enrolled in the Longitudinal Assessment of Manic Symptoms (LAMS) study, 443 (63%) were prescribed psychotropic medication at baseline: 157 (35%) were receiving an antipsychotic and 286 (65%) were prescribed other agents. Multivariate results indicated that being prescribed antipsychotics was related to being white, previous hospitalization, having a psychotic or bipolar 1 disorder and the site where the child was receiving services (p<0.001). In this sample, it is relatively common for a child to be prescribed an antipsychotic medication. However, the only diagnoses associated with a greater likelihood of being treated with an antipsychotic were psychotic disorders or unmodified DSM-IV bipolar 1 disorder.