Background: To adapt the Coping Long Term with Active Suicide Program (CLASP) for use with adolescents (CLASP-A) and to assess its feasibility and acceptability on an inpatient psychiatric unit. CLASP-A entailed three individual sessions and one family session, followed by a series of outpatient phone calls to adolescent and a designated parent/guardian over 6 months of follow-up. Methods: The open trial phase involved 17 adolescent/parent pairs, followed by a pilot randomized controlled trial (RCT) in which adolescent/parent pairs were randomized to CLASP-A ( n = 25) or enhanced treatment as usual (ETAU; n = 25). Assessments were completed at baseline, 3- and 6-month follow-ups. Results: In the open trial, average in-person session attendance was 67%, and study treatment satisfaction was high. To enhance feasibility, we adapted CLASP-A to be completed in three individual sessions for the RCT; 77% of the sessions were completed and study satisfaction remained high in adolescents (3.32/4.0) and parents (3.62/4.0). There were no significant differences between groups in number of suicide attempts or readmissions during follow-up. Conclusion: Data indicate feasibility and acceptability of CLASP-A. However, the absence of treatment effects between groups raises questions regarding CLASP’s potential efficacy with adolescents or the need for more extensive adaptations for adolescents.

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Background: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. Methods: We conducted a double-blind placebo-controlled study in which 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hour). We quantified resting-state functional connectivity via data-driven global brain connectivity, related it to individual ketamine-induced symptom variation, and compared it to cortical gene expression targets. Results: We found that: i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; ii) ketamine's data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, implicating the role of SST and PVALB interneurons in ketamine's acute effects; and iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level. Conclusions: Collectively, these findings support the possibility for developing individually precise pharmacological biomarkers for treatment selection in psychiatry.

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