Background The 40-Hz auditory steady state response (ASSR) is reduced in patients with schizophrenia and bipolar disorder. Recent evidence suggests that ASSR may be altered in clinical high risk and familial high-risk populations. Here, we hypothesize that children aged 11-12 years with familial high risk for schizophrenia and bipolar disorder exhibit impairments in 40-Hz ASSR compared to population-based controls (PBC).

Methods The cross-sectional study included 196 participants aged 11-12 years: 76 at familial high risk for schizophrenia (FHR-SZ), 50 at familial high risk for bipolar disorder (FHR-BP) and 70 PBC. ASSR power and inter-trial phase coherence (ITPC) were measured with 128-channel electroencephalography during regular and irregular 40-Hz auditory stimulation. Group differences in power and ITPC of the ASSR were assessed with independent linear mixed models for both the early and late ASSR component. Statistical analyses are reported with both frequentist p-values and Bayes factors.

Results Both PBC and participants with FHR demonstrated stable ASSRs during regular 40 Hz click stimulation, but not during irregular. Bayes analyses showed moderate and anecdotal evidence against a difference in ASSR power or ITPC among the three groups in the early-latency and the late-latency component of the ASSR. Results remained unchanged after controlling for the presence of an Axis I disorder.

Conclusions While reductions of 40-Hz ASSR are well-documented across psychiatric disorders and stages, our results show that these deficits are not evident in 11–12-year-old children at familial high risk for these disorders.

HRS has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, and as senior editor (NeuroImage) and editor-in-chief (Neuroimage Clinical) from Elsevier Publishers, Amsterdam, The Netherlands. HRS has also received royalties as book editor from Springer Publishers, Stuttgart, Germany, Oxford University Press, Oxford, England, and Gyldendahl Publishers, Copenhagen, Denmark. All disclosures are independent of the work published here. All other authors report no financial disclosures.

The current study received funding from the Research Fund in the Capital Region of Denmark, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH R102-A9118), the Mental Health Services of the Capital Region of Denmark and Innovation Fund Denmark (6152-00002B). KML received funding from The Lundbeck Foundation (R322-2019-2311). Hartwig Roman Siebner received funding from Innovation Fund Denmark (9068-00025B) and from The Lundbeck Foundation (R336-2020-1035).

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