Sensory gating endophenotype based on its neural oscillatory pattern and heritability estimate.

Context: The auditory sensory gating deficit has been considered a leading endophenotype in schizophrenia. However, the commonly used index of sensory gating, P50, has low heritability in families of people with schizophrenia, raising questions about its utility in genetic studies. We hypothesized that the sensory gating deficit may occur in a specific neuronal oscillatory frequency that reflects the underlying biological process of sensory gating. Frequency-specific sensory gating may be less complex than the P50 response, and therefore closer to the direct genetic effects, and thus a more valid endophenotype.

Objectives: To compare the gating of frequency-specific oscillatory responses with the gating of P50 and to compare their heritabilities.

Design: We explored single trial-based oscillatory gating responses in people with schizophrenia, their relatives, and control participants from the community.

Setting: Outpatient clinics.

Participants: Persons with schizophrenia (n = 102), their first-degree relatives (n = 74), and control participants from the community (n = 70).

Main Outcome Measures: Gating of frequency-specific oscillatory responses, gating of the P50 wave, and their heritability estimates.

Results: Gating of the theta-alpha-band responses of the control participants were significantly different from those with schizophrenia (P < .001) and their first-degree relatives (P = .04 to .009). The heritability of theta-alpha-band gating was estimated to be between 0.49 and 0.83 and was at least 4-fold higher than the P50 heritability estimate.

Conclusions: Gating of the theta-alpha-frequency oscillatory signal in the paired-click paradigm is more strongly associated with schizophrenia and has significantly higher heritability compared with the traditional P50 gating. This measure may be better suited for genetic studies of the gating deficit in schizophrenia.