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
  • [1] ZNF804A and cortical thickness in schizophrenia and bipolar disorder
    Bergmann, Orjan
    Haukvik, Unn K.
    Brown, Andrew A.
    Rirnol, Lars M.
    Hartberg, Cecilie B.
    Athanasiu, Lavinia
    Melle, Ingrid
    Djurovic, Srdjan
    Andreassen, Ole A.
    Dale, Anders M.
    Agartz, Ingrid
    PSYCHIATRY RESEARCH-NEUROIMAGING, 2013, 212 (02) : 154 - 157
  • [2] Sex-Sepcific Association of ZNF804A with Schizophrenia
    Zhang, Fengyu
    Chen, Qiang
    Ye, Tianzhang
    Lipska, Barbara K.
    Hyde, Thomas M.
    Kleinman, Joel E.
    Weinberger, Daniel R.
    BIOLOGICAL PSYCHIATRY, 2010, 67 (09) : 166S - 167S
  • [3] ZNF804A and Cortical Structure in Schizophrenia: In Vivo and Postmortem Studies
    Schultz, Carl Christoph
    Nenadic, Igor
    Riley, Brien
    Vladimirov, Vladimir I.
    Wagner, Gerd
    Koch, Kathrin
    Schachtzabel, Claudia
    Muehleisen, Thomas W.
    Basmanav, Buket
    Noethen, Markus M.
    Deufel, Thomas
    Kiehntopf, Michael
    Rietschel, Marcella
    Reichenbach, Juergen R.
    Cichon, Sven
    Schloesser, Ralf G. M.
    Sauer, Heinrich
    SCHIZOPHRENIA BULLETIN, 2014, 40 (03) : 532 - 541
  • [4] ZNF804A AND CORTICAL STRUCTURE IN SCHIZOPHRENIA - IN VIVO AND POSTMORTEM STUDIES
    Schultz, Carl C.
    Nenadic, Igor
    Riley, Brien
    Vladimirov, Vladimir
    Wagner, Gerd
    Muhleisen, Thomas
    Nothen, Markus
    Cichon, Sven
    Koch, Kathrin
    Schlosser, Ralf
    Sauer, Heinrich
    SCHIZOPHRENIA RESEARCH, 2014, 153 : S212 - S212
  • [5] Evidence of Sex-Modulated Association of ZNF804A with Schizophrenia
    Zhang, Fengyu
    Chen, Qiang
    Ye, Tianzhang
    Lipska, Barbara K.
    Straub, Richard E.
    Vakkalanka, Radhakrishna
    Rujescu, Dan
    St Clair, David
    Hyde, Thomas M.
    Bigelow, Llewellyn
    Kleinman, Joel E.
    Weinberger, Daniel R.
    BIOLOGICAL PSYCHIATRY, 2011, 69 (10) : 914 - 917
  • [6] ZNF804A and schizophrenia susceptibility in Asian populations
    Li, Ming
    Shi, Cui-Juan
    Shi, Yong-Yong
    Luo, Xiong-Jian
    Zheng, Xue-Bin
    Li, Zhi-Qiang
    Liu, Jian-Jun
    Chong, Siow-Ann
    Lee, Jimmy
    Wang, Yi
    Liu, Xing-Yan
    Yin, Li-De
    Pu, Xing-Fu
    Diao, Hong-Bo
    Xu, Qi
    Su, Bing
    AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2012, 159B (07) : 794 - 802
  • [7] ZNF804A and schizophrenia: An open peer commentary
    Sand, Philipp G.
    AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2013, 162B (01) : 71 - 72
  • [8] Replication of association between schizophrenia and ZNF804A in the Irish Case–Control Study of Schizophrenia sample
    B Riley
    D Thiselton
    B S Maher
    T Bigdeli
    B Wormley
    G O McMichael
    A H Fanous
    V Vladimirov
    F A O'Neill
    D Walsh
    K S Kendler
    Molecular Psychiatry, 2010, 15 : 29 - 37
  • [9] Reply to: ZNF804A and schizophrenia: An open peer commentary
    Li, Ming
    Su, Bing
    AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2013, 162B (01) : 73 - 74
  • [10] ASSOCIATION OF ZNF804A RS1344706 GENOTYPE AND IMPULSIVITY IN PATIENTS WITH CHRONIC SCHIZOPHRENIA
    Thanju, Amod
    Lindenmayer, Jean-Pierre
    Khan, Anzalee
    SCHIZOPHRENIA BULLETIN, 2017, 43 : S113 - S113