The 40-Hz auditory steady-state response in bipolar disorder: A meta-analysis

Objective: Bipolar disorder is characterized by aberrant neurophysiological responses as measured with electroencephalography (EEG) and magnetoencephalography (MEG), including the 40-Hz auditory steady-state response (ASSR). 40-Hz ASSR deficits are also found in patients with schizophrenia and may represent a transdiagnostic biomarker of neuronal circuit dysfunction. In this systematic review and meta-analysis, we summarize and evaluate the evidence for 40-Hz ASSR deficits in patients with bipolar disorder.

Methods: We identified studies from PubMed, EMBASE, and SCOPUS. We assessed the risk of bias, calculated Hedges' g meta-level effect sizes, and investigated small-study effects using funnel plots and Egger regression.

Results: Seven studies, comprising 396 patients with bipolar disorder and 404 healthy controls, were included in the meta-analysis. Studies displayed methodological heterogeneity and an overall high risk of bias. Patients with bipolar disorder showed consistent reductions in 40-Hz ASSR evoked power (Hedges' g = -0.49; 95% confidence intervals [-0.67, -0.31]) and inter-trial phase coherence (ITPC) (Hedges' g = -0.43; 95 %CI [-0.58, -0.29]) compared with healthy controls.

Conclusions: Our meta-analysis provides evidence that 40-Hz ASSRs are reduced in patients with bipolar disorder compared with healthy controls.

Significance: Future large-scale studies are warranted to link 40-Hz ASSR deficits to clinical features and developmental trajectories.