Aberrant functional connectivity of the dorsolateral prefrontal cortex-nucleus accumbens during naturalistic stimulation in adolescent major depressive disorder.

Objective: This study aimed to examine alterations in the functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC) and the nucleus accumbens (NAc) in adolescents with major depressive disorder (MDD) during naturalistic stimulation, and to determine the symptom specificity of this pathway. Methods: A total of 152 participants were enrolled, including 87 MDD patients and 65 matched healthy controls (HCs). Functional magnetic resonance imaging (fMRI) was conducted during naturalistic video stimulation, and seed-based functional connectivity analysis was performed with the NAc as the seed region. To explore symptom specificity, four factors were derived from the 17-item Hamilton Depression Rating Scale (HAMD-17)-anxiety, depression, insomnia, and somatization- and their associations with DLPFC-NAc functional connectivity were tested in the MDD group. Results: Our findings demonstrate that adolescents with MDD exhibit significantly higher DLPFC-NAc functional connectivity compared to HCs (PFWE = 0.038). This alteration was positively associated with overall depressive severity, and more specifically with anxiety and somatization dimensions, but not with core depressive or insomnia symptoms. Conclusion: These findings suggest that DLPFC-NAc hyperconnectivity is a neural substrate of MDD in adolescents and may preferentially contribute to anxiety-related or somatization-related symptomatology rather than depressive mood or sleep disturbance.