Prospective Volumetric Changes in the Thalamus in Adolescent First Episode of Mania and Cannabis Use: A Preliminary Study

BACKGROUND: Aberrant thalamic structure has been documented in youth with bipolar disorder (BD) and linked with cannabis use, which commonly co-occurs with BD. However, the timeline of when these associations evolve remains unclear. This study aimed to longitudinally compare thalamic volume among youth with and without first episode mania who do or do not use cannabis and other substances. METHODS: Demographic and magnetic resonance imaging (MRI) data from youth (13-18 years old) with BD (n = 22) were compared to similarly aged healthy youth (n = 23) at baseline and 12-month follow-up. Clinical group status, including BD and substance misuse and dependence, was evaluated using semistructured interviews. Multivariate analyses accounting for total brain volume and baseline age were conducted to evaluate baseline and longitudinal group differences in thalamic volume. RESULTS: At 12 months, BD youth had significantly smaller left thalamus volumes compared to healthy youth (p = 0.009). Lifetime cannabis use was associated with smaller left thalamus volumes for all youth (p < 0.001) and for youth with BD compared to healthy controls (p < 0.001) across time. Among BD youth, co-occurring lifetime substance use was associated with significant volumetric reductions in the left thalamus from baseline to follow-up (p = 0.004), but not among healthy youth (p = 0.517). No significant group differences or changes were observed in the right thalamus. CONCLUSIONS: BD is associated with smaller left thalamic volume after the first manic episode. Cannabis use may compound thalamic volume reductions in youth with BD. Investigations with larger sample sizes are needed to replicate these findings and examine clinical correlates of cannabis use alongside long-term thalamic trajectories.