Mood-incongruent psychotic features in bipolar disorder: familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33.
Mood-incongruent psychotic features in bipolar disorder: familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33.
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DOI：
10.1176/ajp.2007.164.2.236
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发表时间：
2007-02
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通讯作者：
F. Goes;P. Zandi;Kuangyi Miao;F. McMahon;Jo Steele;V. Willour;D. MacKinnon;Francis M. Mondimore;Barbara W. Schweizer;J. Nurnberger;J. Rice;W. Scheftner;W. Coryell;W. Berrettini;J. Kelsoe;W. Byerley;D. Murphy;E. Gershon;Bipolar Disorder Phenome Group;J. R. DePaulo;M. McInnis;J. Potash
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文献类型：
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作者：
F. Goes;P. Zandi;Kuangyi Miao;F. McMahon;Jo Steele;V. Willour;D. MacKinnon;Francis M. Mondimore;Barbara W. Schweizer;J. Nurnberger;J. Rice;W. Scheftner;W. Coryell;W. Berrettini;J. Kelsoe;W. Byerley;D. Murphy;E. Gershon;Bipolar Disorder Phenome Group;J. R. DePaulo;M. McInnis;J. Potash
目的双相情感障碍的心境不一致精神病性特征可能意味着更严重的疾病形式，并可能代表与精神分裂症共有的易感基因的表型表现。本研究试图描述具有这些特征的受试者的临床相关性、家族聚集性和遗传连锁。方法受试者来自美国国家精神卫生研究所（NIMH）遗传学倡议双相情感障碍协作队列，包括708个家庭在10个学术医疗中心招募。受试者的情绪不一致和情绪一致的精神病特征进行了比较的临床变量。使用先证者预测模型和广义估计方程对家族聚集性进行了检验。一个全基因组连锁扫描纳入情绪不一致协变量进行。结果：情绪不一致的精神病特征与住院率和自杀未遂率的增加相关。与所有其他受试者相比，以及与情绪一致性精神病受试者相比，情绪不一致的先证者预测双相I型障碍亲属的情绪不一致。情绪不一致的精神病特征的存在增加了染色体13 q21 -33和2 p11-q14上连锁的证据。这些比值比（LOD）评分的对数及其较基线的增加符合经验性全基因组显著性提示标准。结论：情绪不一致的精神病特征表现出更严重的病程、家族聚集性，并提示与先前与主要精神疾病易感性有关的两个染色体区域存在关联。13 q21 -33的发现支持了双相情感障碍/精神分裂症在该区域重叠的先前证据，而2 p11-q14的发现，据作者所知，首次表明该精神分裂症连锁区域也可能含有双相情感障碍易感基因。
OBJECTIVE Mood-incongruent psychotic features in bipolar disorder may signify a more severe form of the illness and might represent phenotypic manifestations of susceptibility genes shared with schizophrenia. This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features. METHOD Subjects were drawn from The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative cohort, consisting of 708 families recruited at 10 academic medical centers. Subjects with mood-incongruent and mood-congruent psychotic features were compared on clinical variables. Familial aggregation was tested using a proband-predictive model and generalized estimating equations. A genome-wide linkage scan incorporating a mood-incongruence covariate was performed. RESULTS Mood-incongruent psychotic features were associated with an increased rate of hospitalization and attempted suicide. A proband with mood-incongruence predicted mood-incongruence in relatives with bipolar I disorder when compared with all other subjects and when compared with subjects with mood-congruent psychosis. The presence of mood-incongruent psychotic features increased evidence for linkage on chromosomes 13q21-33 and 2p11-q14. These logarithm of the odds ratio (LOD) scores and their increase from baseline met empirical genome-wide suggestive criteria for significance. CONCLUSIONS Mood-incongruent psychotic features showed evidence of a more severe course, familial aggregation, and suggestive linkage to two chromosomal regions previously implicated in major mental illness susceptibility. The 13q21-33 finding supports prior evidence of bipolar disorder/schizophrenia overlap in this region, while the 2p11-q14 finding is, to the authors' knowledge, the first to suggest that this schizophrenia linkage region might also harbor a bipolar disorder susceptibility gene.