22q11.2 Deletion Syndrome Is Associated With Impaired Auditory Steady-State Gamma Response

The 22q11.2 deletion syndrome confers a markedly increased risk for schizophrenia. 22q11.2 deletion carriers without manifest psychotic disorder offer the possibility to identify functional abnormalities that precede clinical onset. Since schizophrenia is associated with a reduced cortical gamma response to auditory stimulation at 40 Hz, we hypothesized that the 40 Hz auditory steady-state response (ASSR) may be attenuated in nonpsychotic individuals with a 22q11.2 deletion. Eighteen young nonpsychotic 22q11.2 deletion carriers and a control group of 27 noncarriers with comparable age range (12-25 years) and sex ratio underwent 128-channel EEG. We recorded the cortical ASSR to a 40 Hz train of clicks, given either at a regular inter-stimulus interval of 25 ms or at irregular intervals jittered between 11 and 37 ms. Healthy noncarriers expressed a stable ASSR to regular but not in the irregular 40 Hz click stimulation. Both gamma power and inter-trial phase coherence of the ASSR were markedly reduced in the 22q11.2 deletion group. The ability to phase lock cortical gamma activity to regular auditory 40 Hz stimulation correlated with the individual expression of negative symptoms in deletion carriers (ρ = -0.487, P = .041). Nonpsychotic 22q11.2 deletion carriers lack efficient phase locking of evoked gamma activity to regular 40 Hz auditory stimulation. This abnormality indicates a dysfunction of fast intracortical oscillatory processing in the gamma-band. Since ASSR was attenuated in nonpsychotic deletion carriers, ASSR deficiency may constitute a premorbid risk marker of schizophrenia.