Striatal and cortical midline circuits in major depression: Implications for suicide and symptom expression

BACKGROUND In major depression, the neural mechanisms underlying suicide related thoughts and behaviors as well as the expression of other depressive symptoms are incompletely characterized. Evidence indicates that both the striatum and cortical midline structures (CMS) may be involved with both suicide and emotional dysregulation in unipolar illness. The aim of this study was to identify striatal-CMS circuits associated with current depression severity and suicidal ideation (SI) as well as a history of self-harm. METHODS Twenty-two male subjects with recurrent unipolar depression were studied using functional MRI. All subjects were unmedicated and without current psychiatric comorbidity. Correlational analyses were used to determine whether striatal-CMS functional connectivity was associated with any of the three clinical variables. RESULTS A network involving the bilateral striatum and anterior CMS was found to be associated with depressive symptom severity. Current SI was associated with a similar but less extensive circuit in the left hemisphere. A distinct striatal motor/sensory network was associated with self-harm behaviors, but not current SI or depression severity. CONCLUSIONS The striatal-anterior CMS circuit likely plays a significant role in the expression of depressive symptoms and SI. In contrast, a striatum-motor/sensory cortex network may be a trait marker of suicide-related behaviors. If replicated, this result might eventually lead to the development of a biomarker that would be useful for studies of pharmacologic and/or psychotherapeutic suicide prevention interventions.