Attenuated frontotemporal brain activation during cognitive tasks is associated with lower succinate dehydrogenase protein levels in patients with major depressive disorder.

Background: Previous studies have shown a lower hemodynamic response in patients with major depressive disorder (MDD) during cognitive tasks. However, the mechanism underlying impaired hemodynamic and neural responses to cognitive tasks in MDD patients remains unclear. Succinate dehydrogenase (SDH) is a key biomarker of mitochondrial energy generation, and it can affect the hemodynamic response via the neurovascular coupling effect. In the current study, cerebral hemodynamic responses were detected during verbal fluency tasks (VFTs) via functional near-infrared spectroscopy (fNIRS) and SDH protein levels were examined in serum from MDD patients to quickly identify whether these hemodynamic alterations were related to mitochondrial energy metabolism.

Methods: Fifty patients with first-episode drug-naïve MDD and 42 healthy controls (HCs) were recruited according to inclusion and exclusion criteria. The 17-item Hamilton Depression Rating Scale (17-HDRS), Hamilton Anxiety Rating Scale (HAMA) and Inventory of Depressive Symptomatology-Self Report (IDS-SR) were used to assess the clinical symptoms of the patients. All participants underwent fNIRS measurements to evaluate cerebral hemodynamic responses in the frontal and temporal cortex during VFTs; moreover, SDH protein levels were measured using an enzyme-linked immunosorbent assay.

Results: Activation in the frontal-temporal brain region during the VFTs was lower in patients with MDD than in HCs. The SDH level in the serum of MDD patients was also significantly lower than that in HCs (p = 0.003), which significantly affected right lateral frontal (p = 0.025) and right temporal (p = 0.022) lobe activation. Both attenuated frontal-temporal activation during the VFTs (OR = 1.531) and lower SDH levels (OR = 1.038) were risk factors for MDD.

Conclusions: MDD patients had lower cerebral hemodynamic responses to VFTs; this was associated with mitochondrial dysfunction, as indicated by SDH protein levels. Furthermore, attenuated hemodynamic responses in frontotemporal regions and lower SDH levels increased the risk for MDD.

Limitations: The sample size is relatively small. SDH protein levels in peripheral blood may not necessarily reflect mitochondrial energy generation in the central nervous system.