A distinctive subcortical functional connectivity pattern linking negative affect and treatment outcome in major depressive disorder

Abstract

Abstract Major depressive disorder (MDD) is associated with functional disturbances in subcortical regions. However, little is known about how the subcortical functional network relates to depressive symptom profile and treatment outcome. In this study, we aimed to investigate associations among subcortical connectivity, clinical symptoms and antidepressant response in MDD using multivariate methods. Data for the present study were derived from the Towards Neurobiology-based Diagnosis and Treatment of Affective Disorders (TNDTAD), which is a naturalistic prospective study of mood disorders (NCT03294525). Medication-free participants with MDD (n = 135) underwent a functional magnetic resonance imaging scan at baseline and completed posttreatment clinical assessment after 8 weeks of antidepressant monotherapy. We used partial least squares (PLS) analysis to explore associations between subcortical connectivity and symptom profile. Replication was undertaken in an independent sample (n = 74). We also investigated the association between the observed subcortical connectivity pattern and treatment outcome in the discovery sample. A distinctive subcortical connectivity pattern, critically involving dorsal striatum and thalamus, was associated with negative affect. This association was partly replicated in the independent sample. Lower composite functional connectivity score (reflecting the connectivity pattern) at baseline predicted greater symptom improvement after 8 weeks of antidepressant treatment. The emphasis here on the role of dorsal striatum and thalamus consolidates prior work of subcortical connectivity in MDD. The findings provide insight into the pathogenesis of MDD, linking subcortical functional connectivity with negative affect. However, while connectivity pattern significantly predicted treatment outcome, the low odds ratio suggests that finding predictive biomarkers for depression remains an aspiration.