J Affect Disord. 2025 May 9:S0165-0327(25)00805-5. doi: 10.1016/j.jad.2025.05.040. Online ahead of print.
ABSTRACT
BACKGROUND: Heart rate variability (HRV), a well-established indicator of autonomic nervous system function, has been proposed as a clinical biomarker for psychiatric disorders. However, its potential is limited compared to electroencephalography (EEG) markers, possibly due to the influence of confounding factors such as cardiovascular functions. This suggests a need for autonomic metrics more specific to the central nervous system. This study investigated central autonomic control by applying 40 Hz auditory stimulation, which can transmit information beyond the auditory pathway to deep brain structures.
METHODS: A total of 165 participants, including individuals with major depressive disorder (MDD), bipolar disorder, schizophrenia spectrum disorders, and healthy controls, underwent HRV and EEG measurements during resting state and 20-Hz and 40-Hz auditory stimulation.
RESULTS: The 40-Hz stimulation led to a noticeable rise in the standard deviation of normal-to-normal intervals in HRV. There was a significant difference in low-, but not high-, frequency HRV among the diagnostic groups. Further exploratory analyses showed that during 40-Hz stimulation, patients with MDD experienced a larger decrease in low-frequency HRV compared to healthy individuals. In line with previous findings, patients with schizophrenia spectrum disorders showed a significant reduction in 40-Hz auditory steady-state response and significantly reduced resting theta.
CONCLUSIONS: These findings propose a novel metric, gamma (40-Hz) stimulated HRV, as a potential biomarker for impaired autonomic activation in MDD. Beyond the conventional framework, the combined approach of HRV and EEG using 40-Hz auditory stimulation may yield a series of biomarkers indicative of divergent brain functions between mood and psychotic disorders.
PMID:40350094 | DOI:10.1016/j.jad.2025.05.040
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