Neurophysiological markers of depression detection and severity prediction in first-episode major depressive disorder

Deviant γ auditory steady-state responses (γ-ASSRs) have been documented in some psychiatric disorders. Nevertheless, the role of γ-ASSR in drug-naïve first-episode major depressive disorder (FEMD) patients remains equivocal. This study aimed to examine whether γ-ASSRs are impaired in FEMD patients and predict depression severity.Cortical reactivity was assessed in a cohort of 28 FEMD patients relative to 30 healthy control (HC) subjects during an ASSR paradigm randomly presented at 40 and 60 Hz. Event-related spectral perturbation and inter-trial phase coherence (ITC) were calculated to quantify dynamic changes of the γ-ASSR. Receiver operating characteristic curve combined with binary logistic regression were then employed to summarize ASSR variables that maximally differentiated groups.FEMD patients exhibited significantly inferior 40 Hz-ASSR-ITC in the right hemisphere versus HC subjects (p = 0.007), along with attenuated θ-ITC that reflected underlying impairments in θ responses during 60 Hz clicks (p < 0.05). Moreover, the 40 Hz-ASSR-ITC and θ-ITC in the right hemisphere can be used as a combinational marker to detect FEMD patients with 84.0 % sensitivity and 81.5 % specificity (area under the curve was 0.868, 95 % CI: 0.768-0.968). Pearson's correlations between the depression severity and ASSR variables were further conducted. The symptom severity of FEMD patients was negatively correlated with 60 Hz-ASSR-ITC in the midline and right hemisphere, possibly indicating that depression severity mediated high γ neural synchrony.Our findings provide critical insight into the pathological mechanism of FEMD, suggesting first that 40 Hz-ASSR-ITC and θ-ITC in right hemisphere constitute potential neurophysiological markers for early depression detection, and second, that high γ entrainment deficits may contribute to underlying symptom severity in FEMD patients.