Narayanan B, Soh P, Calhoun V D, Ruaño G, Kocherla M, Windemuth A, Clementz B A, Tamminga C A, Sweeney J A, Keshavan M S, Pearlson G D
Olin Neuropsychiatry Research Center, Hartford Hospital, Institute of Living, Hartford, CT, USA.
1] Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA [2] The Mind Research Network, Albuquerque, NM, USA.
Transl Psychiatry. 2015 Jun 23;5(6):e588. doi: 10.1038/tp.2015.76.
Schizophrenia (SZ) and psychotic bipolar disorder (PBP) are disabling psychiatric illnesses with complex and unclear etiologies. Electroencephalogram (EEG) oscillatory abnormalities in SZ and PBP probands are heritable and expressed in their relatives, but the neurobiology and genetic factors mediating these abnormalities in the psychosis dimension of either disorder are less explored. We examined the polygenic architecture of eyes-open resting state EEG frequency activity (intrinsic frequency) from 64 channels in 105 SZ, 145 PBP probands and 56 healthy controls (HCs) from the multisite BSNIP (Bipolar-Schizophrenia Network on Intermediate Phenotypes) study. One million single-nucleotide polymorphisms (SNPs) were derived from DNA. We assessed eight data-driven EEG frequency activity derived from group-independent component analysis (ICA) in conjunction with a reduced subset of 10,422 SNPs through novel multivariate association using parallel ICA (para-ICA). Genes contributing to the association were examined collectively using pathway analysis tools. Para-ICA extracted five frequency and nine SNP components, of which theta and delta activities were significantly correlated with two different gene components, comprising genes participating extensively in brain development, neurogenesis and synaptogenesis. Delta and theta abnormality was present in both SZ and PBP, while theta differed between the two disorders. Theta abnormalities were also mediated by gene clusters involved in glutamic acid pathways, cadherin and synaptic contact-based cell adhesion processes. Our data suggest plausible multifactorial genetic networks, including novel and several previously identified (DISC1) candidate risk genes, mediating low frequency delta and theta abnormalities in psychoses. The gene clusters were enriched for biological properties affecting neural circuitry and involved in brain function and/or development.
精神分裂症（SZ）和精神病性双相情感障碍（PBP）是致残性精神疾病，其病因复杂且尚不明确。SZ和PBP先证者的脑电图（EEG）振荡异常具有遗传性，并在其亲属中表现出来，但在这两种疾病的精神病维度中，介导这些异常的神经生物学和遗传因素的研究较少。我们在多中心的双相情感障碍-精神分裂症中间表型网络（BSNIP）研究中，对105名SZ患者、145名PBP先证者和56名健康对照（HCs）的64个通道睁眼静息状态EEG频率活动（固有频率）的多基因结构进行了研究。从DNA中获取了100万个单核苷酸多态性（SNP）。我们通过使用并行独立成分分析（para-ICA）的新型多变量关联，评估了从独立成分分析（ICA）得出的8种数据驱动的EEG频率活动，并结合10422个SNP的简化子集。使用通路分析工具对促成该关联的基因进行了综合检查。Para-ICA提取了5个频率和9个SNP成分，其中θ波和δ波活动与两个不同的基因成分显著相关，这些基因广泛参与大脑发育、神经发生和突触形成。SZ和PBP中均存在δ波和θ波异常，而两种疾病中的θ波有所不同。θ波异常还由参与谷氨酸途径、钙黏蛋白和基于突触接触的细胞黏附过程的基因簇介导。我们的数据表明存在合理的多因素遗传网络，包括新发现的以及一些先前已确定的（DISC1）候选风险基因，介导了精神病中低频δ波和θ波异常。这些基因簇富含影响神经回路的生物学特性，并参与大脑功能和/或发育。
Zotero 插件
