¹The Hong Kong Polytechnic University, Department of Rehabilitation Sciences, Hong Kong, China, ²Shanghai Yangzhi Rehabilitation Hospital, Department of Neurology and Neurological Rehabilitation, Shanghai, China, ³The Hong Kong Polytechnic University, Mental Health Research Center, Hong Kong, China

Background: Half of individuals who experience an initial major depressive episode will become depressed repeatedly over the life course. Brain functional abnormalities that could help identify individuals more vulnerable to subsequent episodes remain unclear.

Aims & Objectives: To identify brain dysfunctions that are present during remission and that are linked to relapse/recurrent MDD vulnerability.

Method: In this case-control cross-sectional study, 34 currently depressed MDD patients, 34 currently remitted MDD patients (rMDD), and 27 healthy controls received single-session intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex (dlPFC). Functional near-infrared spectroscopy data was collected 3 minutes before, during, and 3 minutes after stimulation. Oxyhaemoglobin concentration change (ΔHbO) in the left dlPFC was subjected to analysis of variance (ANOVA). We performed correlation analyses to investigate potentially confounding effects of medication and symptom severity on hemoglobin response. Hierarchical regression was then performed on the ΔHbO with the number of episodes as a regressor of interest while controlling for age, sex and education year.

Results: The ANOVA showed a significant interaction effect (F = 4.010, p = 0.022) and time effect (F = 3.445, p = 0.036), while the group effect was insignificant (F = 2.097, p = 0.129). Post hoc analysis indicated that ΔHbO was significantly increased after iTBS compared to the prestimulation period in MDD (p = 0.002, passing the Bonferroni correction at p ≤ 0.008). Neither medication load index nor symptom severity significantly correlated with ΔHbO during or after iTBS for the patient subgroups. The number of prior episodes was a significant variable (p = 0.001) to explain the variance in ΔHbO post-stimulation in the rMDD group. The predictive power (β = 0.717) indicated that more episodes were associated with pronounced ΔHbO.

Discussion & Conclusions: Our results suggest that currently depressed patients tend to be more sensitive to the neuromodulatory effects of iTBS than healthy controls. Signs of normalization are observed in a remitted state. Interestingly, ΔHbO in the left dlPFC after iTBS is especially associated with the number of episodes in rMDD patients. The direction of causality remains uncertain. A longitudinal study is needed to confirm whether the iTBS-induced ΔHbO in the presumed neuropathological DLPFC can be used as a marker of depression vulnerability.