Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
DTU Compute, Cognitive Systems, Technical University of Denmark, Lyngby, Denmark.
Schizophr Bull. 2018 Feb 15;44(2):388-397. doi: 10.1093/schbul/sbx058.
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.
22q11.2 缺失综合征显著增加了精神分裂症的风险。没有明显精神病的 22q11.2 缺失携带者提供了识别临床发病前功能异常的可能性。由于精神分裂症与听觉刺激 40Hz 时皮质伽马反应减少有关，我们假设 22q11.2 缺失的非精神病个体的 40Hz 听觉稳态反应（ASSR）可能会减弱。
18 名年轻的非精神病 22q11.2 缺失携带者和一组年龄范围（12-25 岁）和性别比例相当的 27 名非携带者接受了 128 通道 EEG 检查。我们记录了皮质 ASSR 对 40Hz 点击串的反应，以 25ms 的规则间隔或 11-37ms 的不规则间隔给予刺激。
健康的非携带者对规则的但不规则的 40Hz 点击刺激表达了稳定的 ASSR。22q11.2 缺失组的 ASSR 伽马功率和试验间相位相干性均显著降低。皮质伽马活动对规则听觉 40Hz 刺激的相位锁定能力与缺失携带者的阴性症状个体表达相关（ρ=-0.487，P=0.041）。
非精神病 22q11.2 缺失携带者缺乏对规则 40Hz 听觉刺激的诱发伽马活动的有效相位锁定。这种异常表明伽马频带内快速皮质内振荡处理的功能障碍。由于非精神病缺失携带者的 ASSR 减弱，ASSR 缺陷可能构成精神分裂症的前驱风险标志物。
