Objective Toevaluate feasibility and estimate effect sizes of omega-3 fatty acids (Ω3), individual-family psychoeducational psychotherapy (PEP), their combination, and moderating effects of maternal depression and psychosocial stressors in youth with depression. Method In a pilot 2X2 randomized controlled trial, 72 youth (ages 7-14; 57% Caucasian, 57% male) with major depression, dysthymia, or depression not-otherwise-specified were randomized to 12 weeks of Ω3, PEP+placebo, Ω3+PEP, or placebo. Ω3 vs. placebo was double-masked. Evaluators masked to condition assessed depressive severity at baseline (randomization), and 2, 4, 6, 9, and 12 weeks using the Children’s Depression Rating Scale-Revised. Results Side effects were either absent or mild. PEP was administered with 74% fidelity. Remission was: 77%, Ω3+PEP; 61%,PEP+placebo;44%,Ω3; 56%, placebo. Intent-to-treat analyses found small-to medium effects of combined treatment (d = .29) and Ω3 monotherapy (d =.42),but negligible effect for PEP+placebo (d<.10), all comparedto placebo alone. Relative to placebo, youth with fewer social stressors responded better to Ω3 (p=.04), PEP (p=.028), and their combination (p = .035), and those with maternal depression responded better to PEP (p=.020) than did those without maternal depression. Conclusion Remission rates were favorable compared to other studies of psychotherapy and comparable to an existing RCT of Ω3; results warrant further evaluation in a larger sample.Ω3 was well-tolerated. Active treatments show significantly more placebo-controlled depression improvement in the context of maternal depression and fewer stressors, suggesting they may benefit depression with a more endogenous than environmental origin.

Objective: This pilot study evaluates efficacy of omega-3 fatty acid supplementation (O3), individual family psychoeducational psychotherapy (IF-PEP), and their combination in youth with subsyndromal bipolar disorders (bipolar disorder not otherwise specified [BP-NOS], cyclothymic disorder [CYC]). Methods: This study was a 12 week, randomized trial of O3 versus placebo and IF-PEP versus active monitoring (AM) using a 2 · 2 design (O3 + PEP: n = 5; O3 + AM: n = 5; placebo + PEP: n = 7; placebo + AM: n = 6). Twenty-three youth ages 7-14 with BP-NOS or CYC were recruited via community advertisements and clinician referrals. Participants could be taking stable medication for attention-deficit/hyperactivity disorder and sleep aids, but no other psychotropics. Independent evaluators assessed participants at screen, baseline, and 2, 4, 6, 9, and 12 weeks. Primary outcome measures were the Kiddie Schedule for Affective Disorders (K-SADS) Depression (KDRS) and Mania (KMRS) Rating Scales, Children's Depression Rating ScaleRevised (CDRS-R), and Young Mania Rating Scale (YMRS). O3/placebo conditions were double-blind; independent evaluators were blind to psychotherapy condition.

Ω3 supplementation at 2 g/day increases blood levels substantially, more so in smaller children. A possible U-shaped response curve should be explored.

Objective: The purpose of this study was to examine similarities and differences between disruptive mood dysregulation disorder (DMDD) and bipolar disorder not otherwise specified (BP-NOS) in baseline sociodemographic and clinical characteristics and 36 month course of irritability in children 6-12.9 years of age. Methods: A total of 140 children with DMDD and 77 children with BP-NOS from the Longitudinal Assessment of Manic Symptoms cohort were assessed at baseline, then reassessed every 6 months for 36 months. Results: Groups were similar on most sociodemographic and baseline clinical variables other than most unfiltered (i.e., interviewer-rated regardless of occurrence during a mood episode) Young Mania Rating Scale (YMRS) and parent-reported General Behavior Inventory-10 Item Mania (PGBI-10M) items. Children with DMDD received lower scores on every item (including irritability) except impaired insight; differences were significant except for sexual interest and disruptiveaggressive behavior. Children with DMDD received lower scores on eight of 10 PGBI-10M items, the other two items rated irritability. Youth with DMDD were significantly less likely to have a biological parent with a bipolar diagnosis than were youth with BP-NOS. Children with DMDD were more likely to be male and older than children with BP-NOS, both small effect sizes, but had nearly double the rate of disruptive behavior disorders (large effect). Caregiver ratings of irritability based on the Child and Adolescent Symptom Inventory-4R (CASI-4R) were comparable at baseline; the DMDD group had a small but significantly steeper decline in scores over 36 months relative to the BP-NOS group (b = -0.24, SE = 0.12, 95% CI -0.48 to -0.0004). Trajectories for both groups were fairly stable, in the midrange of possible scores. Conclusions: In a sample selected for elevated symptoms of mania, twice as many children were diagnosed with DMDD than with BP-NOS. Children with DMDD and BP-NOS are similar on most characteristics other than manic symptoms, per se, and parental history of bipolar disorder. Chronic irritability is common in both groups. Comprehensive evaluations are needed to diagnose appropriately. Clinicians should not assume that chronic irritability leads exclusively to a DMDD diagnosis.

This pilot randomized controlled trial (RCT) investigated benefits of omega-3 fatty acid supplementation and Individual-Family Psychoeducational Psychotherapy (PEP; a family-focused, cognitive-behavioral therapy) for behavior problems among youth with depression. Participants aged 7–14 with DSM-IV-TR depressive disorders (N = 72; 56.9% male) were randomized to 1 of 4 treatment conditions: PEP + omega-3, PEP monotherapy (with pill placebo), omega-3 monotherapy, or placebo (without active intervention). At screen, baseline, and 2, 4, 6, 9, and 12 weeks post-baseline, parents completed the SNAP-IV, which assesses attention-deficit/hyperactivity disorder symptoms, oppositional defiant disorder symptoms, and overall behavior problems. At screen, baseline (randomization), 6 and 12 weeks, parents completed the Eyberg Child Behavior Inventory (ECBI), which includes Intensity and Problem scales for child behavior problems. Youth who had a completed SNAP-IV or ECBI for at least two assessments during treatment (n=48 and 38, respectively) were included in analyses of the respective outcome. ClinicalTrials.gov:NCT01341925. Linear mixed effects models indicated a significant effect of combined PEP + omega-3 on SNAP-IV Total (p = .022, d = 0.80) and Hyperactivity/Impulsivity trajectories (p = .008, d=0.80), such that youth in the combined group saw greater behavioral improvement than those receiving only placebo. Similarly, youth in combined treatment had more favorable ECBI Intensity trajectories than youth who received no active treatment (p = .012, d = 1.07). Results from this pilot RCT suggest that combined PEP + omega-3 is a promising treatment for co-occurring behavior symptoms in youth with depression.