Effects of the brain-derived neurotrophic growth factor val66met variation on hippocampus morphology in bipolar disorder.
Effects of the brain-derived neurotrophic growth factor val66met variation on hippocampus morphology in bipolar disorder.
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DOI：
10.1038/npp.2008.107
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发表时间：
2009-03
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--
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双相情感障碍（BD）的组织学和行为学研究表明海马体存在结构异常。脑源性神经营养生长因子（BDNF）蛋白与海马体的发育和可塑性以及情绪障碍的病理生理学有关。我们检验了以下假设：BDNF val66met多态性和BD诊断都与海马体体积减小有关，并且与无BD的个体和val/val纯合子相比，携带met等位基因的BD患者海马体体积最小。我们进一步探究了在与met等位基因相关的BD中，海马体内形态差异的定位。20名BD患者和18名健康对照（HC）受试者参与了高分辨率磁共振成像扫描，据此对海马体体积进行了定义和测量。我们使用线性混合模型分析来研究诊断和BDNF基因型对海马体体积的影响。然后我们采用三维映射来定位在BD中与BDNF met等位基因相关的海马体内的变化区域。我们发现与HC受试者相比，BD患者的海马体体积明显更小，并且在两个诊断组中，BDNF met等位基因的存在都与海马体体积更小有关。携带BDNF met等位基因的BD亚组海马体体积最小，并且三维映射确定这些减小在左侧海马前部最为显著。这些结果支持了BD诊断和BDNF基因型对海马体结构的影响，并表明在BD中存在一个遗传亚组，该亚组可能最易出现海马体缺陷，并且可能从影响BDNF介导的信号传导的干预措施中获益最大。
Histological and behavioral research in bipolar disorder (BD) implicates structural abnormalities in the hippocampus. Brain-derived neurotrophic growth factor (BDNF) protein is associated with hippocampal development and plasticity, and in mood disorder pathophysiology. We tested the hypotheses both the BDNF val66met polymorphism and BD diagnosis are associated with decreased hippocampus volume, and individuals with BD who carry the met allele have the smallest hippocampus volumes compared to individuals without BD and val/val homozygotes. We further explored localization of morphological differences within hippocampus in BD associated with the met allele. Twenty individuals with BD and 18 healthy comparison (HC) subjects participated in high resolution magnetic resonance imaging scans from which hippocampus volumes were defined and measured. We used linear mixed model analysis to study effects of diagnosis and BDNF genotype on hippocampus volumes. We then employed three-dimensional mapping to localize areas of change within hippocampus associated with the BDNF met allele in BD. We found hippocampus volumes were significantly smaller in BD compared to HC subjects, and presence of the BDNF met allele was associated with smaller hippocampus volume in both diagnostic groups. The BD subgroup who carried the BDNF met allele had the smallest hippocampus volumes, and three-dimensional mapping identified these decreases were most prominent in left anterior hippocampus. These results support effects of BD diagnosis and BDNF genotype on hippocampus structure and suggest a genetic subgroup within BD who may be most vulnerable to deficits in hippocampus and may most benefit from interventions that influence BDNF-mediated signaling.
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影响因子：
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