Psychology Research Laboratory, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
Psychiatry Res. 2012 Dec 30;200(2-3):272-80. doi: 10.1016/j.psychres.2012.07.052. Epub 2012 Aug 24.
Historically, bipolar disorder and schizophrenia have been considered distinct disorders with different etiologies. Growing evidence suggests that overlapping genetic influences contribute to risk for these disorders and that each disease is genetically heterogeneous. Using cluster analytic methods, we empirically identified homogeneous subgroups of patients, their relatives, and controls based on distinct neurophysiologic profiles. Seven phenotypes were collected from two independent cohorts at two institutions. K-means clustering was used to identify neurophysiologic profiles. In the analysis of all participants, three distinct profiles emerged: "globally impaired", "sensory processing", and "high cognitive". In a secondary analysis, restricted to patients only, we observed a similar clustering into three profiles. The neurophysiological profiles of the Schizophrenia (SZ) and Bipolar Disorder (BPD) patients did not support the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic distinction between these two disorders. Smokers in the globally impaired group smoked significantly more cigarettes than those in the sensory processing or high cognitive groups. Our results suggest that empirical analyses of neurophysiological phenotypes can identify potentially biologically relevant homogenous subgroups independent of diagnostic boundaries. We hypothesize that each neurophysiology subgroup may share similar genotypic profiles, which may increase statistical power to detect genetic risk factors.
从历史上看，双相情感障碍和精神分裂症被认为是两种具有不同病因的不同疾病。越来越多的证据表明，重叠的遗传影响导致了这些疾病的风险，而且每种疾病在遗传上都是异质的。我们使用聚类分析方法，根据不同的神经生理特征，对患者、其亲属和对照组进行了实证性的同质亚组划分。从两个机构的两个独立队列中收集了七个表型。使用 K-均值聚类来识别神经生理特征。在对所有参与者的分析中，出现了三个不同的特征：“整体受损”、“感觉处理”和“高认知”。在仅限于患者的二次分析中，我们观察到了类似的聚类为三个特征。精神分裂症（SZ）和双相情感障碍（BPD）患者的神经生理特征并不支持《精神障碍诊断与统计手册》（DSM）对这两种疾病的诊断区分。整体受损组的吸烟者比感觉处理组或高认知组的吸烟者吸烟量明显更多。我们的研究结果表明，对神经生理表型的实证分析可以识别出潜在的生物学相关的同质亚组，而不受诊断界限的影响。我们假设，每个神经生理学亚组可能具有相似的基因型特征，这可能会增加检测遗传风险因素的统计能力。
