Taken together, the findings show consistent neural aberrations during reward processing in depression, namely, reduced striatal signal during feedback and blunted FRN. These aberrations may underlie the pathogenesis of depression and have important implications for development of new treatments.

Drs. Towbin and Vidal-Ribas contributed equally to this research. Objective: Despite the clinical importance of chronic and severe irritability, there is a paucity of controlled trials for its pharmacological treatment. Here, we examine the effects of adding citalopram (CTP) to methylphenidate (MPH) in the treatment of chronic severe irritability in youth using a double-blind randomized placebo-controlled design. Method: After a lead-in phase of open treatment with stimulant, 53 youth meeting criteria for severe mood dysregulation (SMD) were randomly assigned to receive CTP or placebo (PBO) for 8 weeks. A total of 49 participants, 48 of them (98%) meeting disruptive mood dysregulation disorder (DMDD) criteria, were included in the intent-to-treat analysis. The primary outcome measure was the proportion of response based on improvements of irritability at the week 8 of the trial. Results: At the end of the trial, a significantly higher proportion of response was seen in those participants randomly assigned to CTPþMPH compared to PBOþMPH (35% CTPþMPH versus 6% PBOþMPH; odds ratio ¼ 11.70, 95% CI ¼ 2.00À68.16, p ¼ 0.006). However, there were no differences in functional impairment between groups at the end of the trial. No differences were found in any adverse effect between treatment groups, and no trial participant exhibited hypomanic or manic symptoms. Conclusion: Adjunctive CTP might be efficacious in the treatment of chronic severe irritability in youth resistant to stimulant treatment alone. Clinical trial registration information: A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation; https://clinicaltrials.gov; NCT00794040.

Background The network theory suggests that psychopathology may reflect causal relationships between individual symptoms. Several studies have examined cross‐sectional relationships between individual symptoms in youth. However, these studies cannot address the directionality of the temporal relationships hypothesized by the network theory. Therefore, we estimated the longitudinal relationships between individual internalizing, externalizing, and attention symptoms in youth. Methods Data from 4,093 youth participants in the Adolescent Brain Cognitive Development (ABCD) study were used. Symptoms were assessed using the Brief Problem Monitor, which was administered at three time points spaced six months apart. Unique longitudinal relationships between symptoms at T1 and T2 were estimated using cross‐lagged panel network modeling. Network replicability was assessed by comparing this network to an identically estimated replication network of symptoms at T2 predicting symptoms at T3. Results After controlling for all other symptoms and demographic covariates, depressed mood, inattention, and worry at T1 were most predictive of other symptoms at T2. In contrast, threats of violence and destructiveness at T2 were most prospectively predicted by other symptoms at T1. The reciprocal associations between depressed mood and worthlessness were among the strongest bivariate relationships in the network. Comparisons between the original network and the replication network (correlation between edge lists = .61; individual edge replicability = 64%–84%) suggested moderate replicability. Conclusions Although causal inferences are precluded by the observational design and methodological considerations, these findings demonstrate the directionality of relationships between individual symptoms in youth and highlight depressed mood, inattention, and worry as potential influencers of other symptoms.