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

Objective: Deviant gamma auditory steady-state responses (gamma-ASSRs) have been documented in some psychiatric dis-orders. Nevertheless, the role of gamma-ASSR in drug-naive first-episode major depressive disorder (FEMD) patients remains equivocal. This study aimed to examine whether gamma-ASSRs are impaired in FEMD patients and predict depression severity.Methods: 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 gamma-ASSR. Receiver operating characteristic curve combined with binary logistic regression were then employed to summarize ASSR variables that maximally differentiated groups.Results: FEMD patients exhibited significantly inferior 40 Hz-ASSR-ITC in the right hemisphere versus HC sub-jects (p = 0.007), along with attenuated theta-ITC that reflected underlying impairments in theta responses during 60 Hz clicks (p < 0.05). Moreover, the 40 Hz-ASSR-ITC and theta-ITC in the right hemisphere can be used as a combina-tional 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 gamma neural synchrony.Conclusions: Our findings provide critical insight into the pathological mechanism of FEMD, suggesting first that 40 Hz-ASSR-ITC and theta-ITC in right hemisphere constitute potential neurophysiological markers for early depression detection, and second, that high gamma entrainment deficits may contribute to underlying symptom severity in FEMD patients.