Phase delay and neural dyssynchrony of the 40-Hz auditory steady-state response in mood and psychotic disorders

Impaired gamma-band neural synchrony has emerged as a promising biomarker for precision psychiatry; however, clinically scalable methods for individual-level assessment remain limited. Widely available evoked response audiometry (ERA) systems offer a pragmatic and accessible platform for measuring the 40-Hz auditory steady-state response (ASSR), and their utility has been demonstrated in patients with schizophrenia. This study investigated whether ERA-based profiling could be extended to mood disorders, which are believed to share underlying biological mechanisms with schizophrenia.

Using a conventional ERA system, phase delay and phase-locking status of the 40-Hz ASSR were assessed in 107 participants, including individuals with schizophrenia (n = 29), bipolar disorder (n = 24), major depressive disorder (n = 25), and healthy controls (n = 29). Phase locking status was classified as either a phase-locked response or a nonphase-locked response (NPLR).

Compared with the healthy control group, all clinical groups exhibited significant phase delays in the 40-Hz ASSR. Phase-locking analysis identified NPLR not only in individuals with schizophrenia but also in a subset of participants with bipolar disorder and major depressive disorder.

These findings extend previous evidence of 40-Hz ASSR phase delay and demonstrate that individual-level NPLR assessment using a conventional ERA system applies beyond schizophrenia to bipolar disorder and major depressive disorder. ERA-based evaluation of the 40-Hz ASSR may represent a practical and scalable approach for biomarker development in mood and psychotic disorders.