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

Area of Science:

• Neuroscience
• Psychiatry
• Brain Imaging

Background:

• Psychotic major depression (PMD) presents unique challenges and requires distinct therapeutic approaches.
• While structural and functional brain differences exist between PMD and non-psychotic major depression (NPMD), integrated structure-function insights and their biological underpinnings are lacking.

Purpose of the Study:

• To investigate the integrated structural-functional connectivity (SC-FC) coupling differences between PMD, NPMD, and healthy controls (HCs).
• To explore the relationship between SC-FC coupling alterations and genetic/neurotransmitter profiles, as well as clinical variables in PMD.

Main Methods:

• Recruited 40 PMD patients, 80 NPMD patients, and 123 HCs.
• Assessed group differences in SC-FC coupling.
• Correlated SC-FC coupling differences with genetic/neurotransmitter profiles and clinical data.

Main Results:

• PMD patients exhibited significantly increased SC-FC coupling in specific brain regions (right ventrolateral inferior temporal gyrus, bilateral dorsal posterior cingulate cortex) and the ventral attention network compared to NPMD and HCs.
• Increased SC-FC coupling correlated with psychotic symptom severity and, in one region, childhood trauma.
• Alterations in PMD were linked to serotonin (5-HT2a), GABA, and glutamate systems, but not the dopamine system.

Conclusions:

• Altered SC-FC coupling patterns represent distinct neurobiological mechanisms in PMD versus NPMD.
• Understanding these mechanisms can guide the development of precise therapeutic strategies for PMD.