Aberrant structural-functional connectivity coupling in patients with psychotic major depression

Patients with psychotic major depression (PMD) experience significant distress and require specific therapy strategies. While previous studies have identified differences in brain structure and function between PMD and non-psychotic major depression (NPMD), the distinct neural mechanisms underlying PMD from an integrated structure-function perspective, along with their microscopic biological basis, remain unclear.

We recruited 40 PMD patients, 80 NPMD patients, and 123 healthy controls (HCs), and then assessed group differences in their structural-functional connectivity (SC-FC) coupling. Subsequently, we further correlated these differences with underlying genetic/neurotransmitter profiles and clinical variables.

Compared with HCs and NPMD group, patients with PMD showed significantly increased SC-FC coupling in the right ventrolateral inferior temporal gyrus and bilateral dorsal posterior cingulate cortex, as well as within the ventral attention network. The SC-FC coupling in these regions was positively correlated with psychotic symptoms, while its correlation with childhood trauma was observed only in the right dorsal posterior cingulate cortex. In the PMD group, regional SC-FC coupling alterations correlated with the spatial distributions of the 5-HT2a, GABA, and glutamate systems and with specific gene expression maps, but not with the dopamine system.

These results provide new evidence supporting distinct neurobiological mechanisms in PMD compared to NPMD, as characterized by altered SC-FC coupling patterns. Elucidating these mechanisms may promote the development of more precise, tailored therapeutic strategies for patients with PMD.