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Original Investigation
October 12, 2016

The 40-Hz Auditory Steady-State Response in Patients With SchizophreniaA Meta-analysis

Author Affiliations
  • 1Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, Scotland

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Psychiatry. Published online October 12, 2016. doi:10.1001/jamapsychiatry.2016.2619
Key Points

Question  How robust are 40-Hz auditory steady-state response (ASSR) impairments in schizophrenia across different patient samples and paradigm designs?

Findings  In this meta-analysis of the 40-Hz ASSR in schizophrenia, including 20 studies and a total of 606 patients with schizophrenia and 590 healthy controls, 26 of 29 reported effects showed a reduction in ASSR measures in patients with schizophrenia compared with healthy controls.

Meaning  The 40-Hz ASSR spectral power and phase-locking deficits are robust in schizophrenia, suggesting that these measures could be useful probes for assessing circuit dysfunctions in the disorder.


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.