Altered Cortical Network Dynamics A Potential Intermediate Phenotype for Schizophrenia and Association With ZNF804A

被引:137
|
作者
Rasetti, Roberta [1 ]
Sambataro, Fabio [1 ]
Chen, Qiang [1 ]
Callicott, Joseph H. [1 ]
Mattay, Venkata S. [1 ]
Weinberger, Daniel R. [1 ]
机构
[1] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
CATECHOL-O-METHYLTRANSFERASE; GENOME-WIDE ASSOCIATION; WORKING-MEMORY; FUNCTIONAL CONNECTIVITY; NEURAL MECHANISMS; GENETIC-VARIATION; ALLELIC VARIATION; VERBAL FLUENCY; GRAY-MATTER; BRAIN;
D O I
10.1001/archgenpsychiatry.2011.103
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Context: Studies have shown patterns of abnormal dorsolateral prefrontal cortex (DLPFC) functional connectivity with other brain areas in schizophrenia and association of these patterns with a putative susceptibility gene (ZNF804A). However, whether these patterns are trait phenomena linked to genetic risk for illness is unclear. Objective: To test the hypotheses that altered DLPFC connectivity is (1) a familial, likely heritable feature of genetic risk for schizophrenia, (2) a novel intermediate phenotype independent of altered DLPFC engagement, and (3) selectively modulated by a polymorphism in ZNF804A. Design: Cross-sectional case-control study using blood oxygen level-dependent functional magnetic resonance imaging during a working memory task and genotyping of rs1344706 in ZNF804A. Setting: Research center. Participants: A total of 402 subjects (153 cognitively normal controls, 171 healthy siblings of patients with schizophrenia, and 78 patients). Main Outcome Measures: Task-independent and task-dependent physiologic coupling between the DLPFC and other brain "target" regions investigated with (1) seeded connectivity and (2) psychophysiological interaction analysis. Results: Siblings and patients showed greater DLPFC" in-efficiency" than controls. Abnormal DLPFC functional coupling with the hippocampus and, to a lesser degree, the rest of the prefrontal cortex, was observed in patients and siblings when compared with controls using both connectivity analyses. Prefrontal activation and connectivity measures within siblings did not correlate, implying that they were independent phenomena. The ZNF804A genotype significantly modulated DLPFC coupling with the hippocampus and prefrontal cortex but not DLPF Cactivity in the control group. Similarly, ZNF804A genotype modulated right DLPFC-hippocampal formation coupling in siblings and patients. Conclusions: Coupling between the DLPFC and hippocampus is compromised in siblings of patients with schizophrenia and is independent of DLPFC engagement. The selective association with a single-nucleotide polymorphism in ZNF804A suggests that this intermediate phenotype proxies a distinct neural system mechanism related to genetic risk for schizophrenia and the biology of this gene.
引用
收藏
页码:1207 / 1217
页数:11
相关论文
共 50 条
  • [41] Influence of ZNF804a on Brain Structure Volumes and Symptom Severity in Individuals With Schizophrenia
    Wassink, Thomas H.
    Epping, Eric A.
    Rudd, Danielle
    Axelsen, Michael
    Ziebell, Stephen
    Fleming, Frank W.
    Monson, Eric
    Ho, Beng Choon
    Andreasen, Nancy C.
    ARCHIVES OF GENERAL PSYCHIATRY, 2012, 69 (09) : 885 - 892
  • [42] A schizophrenia risk gene, ZNF804A, is associated with brain white matter microstructure
    Ikuta, T.
    Peters, B. D.
    Guha, S.
    John, M.
    Karlsgodt, K. H.
    Lencz, T.
    Szeszko, P. R.
    Malhotra, A. K.
    SCHIZOPHRENIA RESEARCH, 2014, 155 (1-3) : 15 - 20
  • [43] Associations between the schizophrenia susceptibility gene ZNF804A and clinical outcomes in psychosis
    Wickramasinghe, A.
    Tulloch, A. D.
    Hayes, R. D.
    Chang, C-K
    Broadbent, M.
    Di Forti, M.
    Murray, R. M.
    Iyegbe, C.
    Stewart, R.
    TRANSLATIONAL PSYCHIATRY, 2015, 5 : e698 - e698
  • [44] Associations between the schizophrenia susceptibility gene ZNF804A and clinical outcomes in psychosis
    A Wickramasinghe
    A D Tulloch
    R D Hayes
    C-K Chang
    M Broadbent
    M Di Forti
    R M Murray
    C Iyegbe
    R Stewart
    Translational Psychiatry, 2015, 5 : e698 - e698
  • [45] Evidence of IQ-Modulated Association Between ZNF804A Gene Polymorphism and Cognitive Function in Schizophrenia Patients
    Min Chen
    Zhansheng Xu
    Jinguo Zhai
    Xin Bao
    Qiumei Zhang
    Huang Gu
    Qiuge Shen
    Lina Cheng
    Xiongying Chen
    Keqin Wang
    Xiaoxiang Deng
    Feng Ji
    Chuanxin Liu
    Jun Li
    Qi Dong
    Chuansheng Chen
    Neuropsychopharmacology, 2012, 37 : 1572 - 1578
  • [46] No association between ZNF804A rs1344706 and schizophrenia in a case-control study of Han Chinese
    Wang, Jun
    Zhao, Shuidi
    Shugart, Yin Yao
    Zhou, Zhenhe
    Jin, Chunhui
    Yuan, Jianmin
    Wang, Guoqiang
    Wang, Dong
    Cheng, Zaohuo
    Zhang, Fuquan
    NEUROSCIENCE LETTERS, 2016, 618 : 14 - 18
  • [47] Evidence of IQ-Modulated Association Between ZNF804A Gene Polymorphism and Cognitive Function in Schizophrenia Patients
    Chen, Min
    Xu, Zhansheng
    Zhai, Jinguo
    Bao, Xin
    Zhang, Qiumei
    Gu, Huang
    Shen, Qiuge
    Cheng, Lina
    Chen, Xiongying
    Wang, Keqin
    Deng, Xiaoxiang
    Ji, Feng
    Liu, Chuanxin
    Li, Jun
    Dong, Qi
    Chen, Chuansheng
    NEUROPSYCHOPHARMACOLOGY, 2012, 37 (07) : 1572 - 1578
  • [48] Data on association of the variation (rs1344706) in the ZNF804A gene with schizophrenia and its symptoms in the Russian population
    Lezheiko, T. V.
    Romanov, D. V.
    Kolesina, N. Yu.
    Golimbet, V. E.
    DATA IN BRIEF, 2019, 24
  • [49] ANK3 and ZNF804A intronic variants increase risk of schizophrenia in Iranian population: An association study
    Dashtban, Shayesteh
    Haj-Nasrolah-Fard, Fatemeh
    Kosari, Zeinab
    Ghamari, Rana
    Forouzesh, Flora
    Alizadeh, Fatemeh
    GENE REPORTS, 2022, 26
  • [50] Schizophrenia-associated variation at ZNF804A correlates with altered experience-dependent dynamics of sleep slow waves and spindles in healthy young adults
    Bartsch, Ullrich
    Corbin, Laura J.
    Hellmich, Charlotte
    Taylor, Michelle
    Easey, Kayleigh E.
    Durant, Claire
    Marston, Hugh M.
    Timpson, Nicholas J.
    Jones, Matthew W.
    SLEEP, 2021, 44 (12)