Aripiprazole has demonstrated efficacy for the treatment of paediatric patients (10–17 years) with a manic or mixed episode associated with bipolar I disorder in a clinical trial that utilised the Young Mania Rating Scale (YMRS) Total score as the primary outcome measure.

This analysis evaluated the profile of discrete symptom response using the YMRS and other measures.

Post-hoc analysis of individual items of the YMRS and the parent or subject version of the General Behaviour Inventory (GBI) Mania and Depression scales using data from a 4-week, double-blind, randomised trial that compared aripiprazole (10 or 30 mg/day, n = 197) with placebo (n = 99).

In total, 296 patients were randomised; 80% completed the study. Significant decreases at Week 4 (p < 0.05) were seen in eight YMRS items: elevated mood, increased motor activity/energy, need for sleep, irritability, speech (rate and amount), language/thought disorder, abnormal thought content and disruptive/aggressive behaviour. For the GBI, effect sizes for parent-reported mania items were medium to large (for example, 0.41 for ‘depressed but high energy’ to 0.78 for ‘rage combined with unusually happy’) but were consistently small on subject self-reported items of mania and depression and, for the overall scale, had the poorest agreement with clinician ratings.

Aripiprazole demonstrated improvements in some of the more troublesome symptoms of paediatric patients with bipolar I disorder experiencing an acute manic or mixed episode. Of note, irritability and aggression showed large treatment effects on both clinician and parent-reported measures, but less so for subject-reported measures.

Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth.

LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables.

Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%.

These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.

Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging.

A total of 61 youth (9–17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy.

There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n = 22) and low and decreasing (LowD; n = 39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p < 0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's < 0.001, corrected).

Patterns of function in lateral prefrontal cortical–amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.