The 40-Hz Auditory Steady-State Response in Patients With Schizophrenia: A Meta-analysis.

Importance: The neurobiological mechanisms underlying circuit dysfunctions in schizophrenia remain poorly understood. The 40-Hz auditory steady-state response (ASSR) has been suggested as a potential biomarker for schizophrenia.

Objectives: To provide a meta-analytical insight into the presence of 40-Hz ASSR impairments in patients with schizophrenia and to examine the effects of the participant group, stimulus parameters, and analysis and recording techniques.

Data Sources: Searches were conducted in PubMed and reference lists of appropriate publications to identify relevant studies published from November 1999 to March 2016. Initial literature searches were performed with combinations of the following search terms: (1) auditory steady state response, (2) schizophrenia, (3) 40 Hz, (4) EEG, (5) MEG, and (6) steady state response.

Study Selection: Original articles reporting 40-Hz ASSR data on patients with schizophrenia (chronic or first episode) compared with healthy controls using electroencephalographic (EEG) and magnetoencephalographic (MEG) recordings.

Data Extraction and Synthesis: Hedges g effect sizes were calculated using sample sizes, P values, and/or Cohen d effect sizes from 20 studies. Effect size data were pooled using random-effects models. Publication bias was corrected for using funnel plots, the Egger regression test, and a trim and fill test. The contributions of study design parameters and participant characteristics were assessed using a mixed linear model approach and subsequent post hoc t tests. The present analysis was performed during the period from November 2015 to March 2016.

Main Outcomes and Measures: Random model Hedges g effect sizes for auditory steady-state amplitude and phase-locking measures from sensor/electrode and sources-space responses in EEG and MEG studies.

Results: Of the 20 studies analyzed (representing a total of 590 healthy controls and 606 patients with schizophrenia), 17 reported significant reductions in 40-Hz ASSR spectral power and/or phase locking in patients with schizophrenia compared with healthy controls (Hedges g effect: -0.58 [power] and -0.46 [phase]). Effect sizes from spectral power and phase-locking measures did not differ significantly (95% CI, -0.49 to 0.22; t = -0.80; P = .43). Stimulus characteristics and analysis methods were not associated with the findings of 40-Hz ASSR impairment in schizophrenia.

Conclusions and Relevance: The 40-Hz ASSR spectral power and phase-locking deficits are robust in schizophrenia, which suggests that these measures could be useful probes for assessing circuit dysfunctions in the disorder. Moreover, these findings should motivate large-scale studies of the longitudinal expression in patients with schizophrenia and at-risk populations, to further validate the 40-Hz ASSR as a potential biomarker.