Scott Julia A, Goodrich-Hunsaker Naomi, Kalish Kristopher, Lee Aaron, Hunsaker Michael R, Schumann Cynthia M, Carmichael Owen T, Simon Tony J
From the Department of Neurology, University of California, Davis (Scott); Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California, Davis (Goodrich-Hunsaker, Kalish, Lee, Hunsaker, Schumann, Simon); and Pennington Biomedical Research Center, Louisiana State University (Carmichael).
J Psychiatry Neurosci. 2016 Apr;41(3):203-13. doi: 10.1503/jpn.140299.
Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an elevated risk for schizophrenia, which increases with history of childhood anxiety. Altered hippocampal morphology is a common neuroanatomical feature of 22q11.2DS and idiopathic schizophrenia. Relating hippocampal structure in children with 22q11.2DS to anxiety and impaired cognitive ability could lead to hippocampus-based characterization of psychosis-proneness in this at-risk population.
We measured hippocampal volume using a semiautomated approach on MRIs collected from typically developing children and children with 22q11.2DS. We then analyzed hippocampal morphology with Localized Components Analysis. We tested the modulating roles of diagnostic group, hippocampal volume, sex and age on local hippocampal shape components. Lastly, volume and shape components were tested as covariates of IQ and anxiety.
We included 48 typically developing children and 69 children with 22q11.2DS in our study. Hippocampal volume was reduced bilaterally in children with 22q11.2DS, and these children showed greater variation in the shape of the anterior hippocampus than typically developing children. Children with 22q11.2DS had greater inward deformation of the anterior hippocampus than typically developing children. Greater inward deformation of the anterior hippocampus was associated with greater severity of anxiety, specifically fear of physical injury, within the 22q11.2DS group.
Shape alterations are not specific to hippocampal subfields.
Alterations in the structure of the anterior hippocampus likely affect function and may impact limbic circuitry. We suggest these alterations potentially contribute to anxiety symptoms in individuals with 22q11.2DS through modulatory pathways. Altered hippocampal morphology may be uniquely linked to anxiety risk factors for schizophrenia, which could be a powerful neuroanatomical marker of schizophrenia risk and hence protection.
患有22q11.2缺失综合征（22q11.2DS）的个体患精神分裂症的风险升高，且随着童年焦虑史而增加。海马形态改变是22q11.2DS和特发性精神分裂症常见的神经解剖学特征。将22q11.2DS儿童的海马结构与焦虑及认知能力受损联系起来，可能会在这一高危人群中基于海马对精神病易感性进行特征描述。
我们采用半自动方法，对从正常发育儿童和22q11.2DS儿童收集的磁共振成像（MRI）测量海马体积。然后，我们用局部成分分析法分析海马形态。我们测试了诊断组、海马体积、性别和年龄对局部海马形状成分的调节作用。最后，将体积和形状成分作为智商和焦虑的协变量进行测试。
我们的研究纳入了48名正常发育儿童和69名22q11.2DS儿童。22q11.2DS儿童双侧海马体积减小，且这些儿童海马前部形状的变异比正常发育儿童更大。22q11.2DS儿童海马前部的向内变形比正常发育儿童更明显。在22q11.2DS组中，海马前部更大的向内变形与更严重的焦虑相关，尤其是对身体受伤的恐惧。
形状改变并非海马亚区所特有。
海马前部结构的改变可能影响功能，并可能影响边缘回路。我们认为这些改变可能通过调节途径导致22q11.2DS个体出现焦虑症状。海马形态改变可能与精神分裂症的焦虑风险因素有独特联系，这可能是精神分裂症风险及预防的一个有力神经解剖学标志物。
