Prasad K M R, Shirts B H, Yolken R H, Keshavan M S, Nimgaonkar V L
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Mol Psychiatry. 2007 Jan;12(1):105-13, 1. doi: 10.1038/sj.mp.4001915. Epub 2006 Oct 10.
Infectious agents have been proposed as one of the risk factors for schizophrenia. However, the data on the association of infectious agents with in vivo brain changes are scant. We evaluated the association of serological evidence of exposure to herpes simplex virus 1 (HSV1) with in vivo brain structural variations among first-episode antipsychotic-naive schizophrenia/schizoaffective disorder patients and control subjects. We assayed HSV1 immunoglobulin G (IgG) antibody in serum samples from 30 patients and 44 healthy subjects and obtained structural magnetic resonance imaging scans from the same individuals. There were proportionately more patients with elevated HSV1 antibody ratios than healthy comparison subjects (chi2=3.98, 1 df, P=0.046) and patients had significantly higher HSV1 IgG antibody ratios compared with healthy subjects. Using optimized voxel-based morphometry, we examined diagnosis by HSV1 serological status interaction followed by within- and between-group comparison across the serological status. We observed a diagnosis by HSV1 serological status interaction and a significant main effect of HSV1 serological status in the prefrontal gray matter. Patients exposed to HSV1 had decreased gray matter in Brodmann area 9 (dorsolateral prefrontal cortex) and 32 (anterior cingulate cortex) compared with patients without serological evidence of exposure to HSV1. HSV1-associated differences in brain structure were not detected among healthy subjects. These findings suggest that HSV1 exposure in schizophrenia is associated with specific regional gray matter differences that may not be attributable to medications, illness chronicity or comorbid substance use. This study provides suggestive evidence for a link between HSV1 exposure and some of the cerebral morphological changes often reported in schizophrenia.
感染源已被认为是精神分裂症的风险因素之一。然而，关于感染源与活体脑变化之间关联的数据却很少。我们评估了单纯疱疹病毒1型（HSV1）暴露的血清学证据与首发未服用抗精神病药物的精神分裂症/分裂情感性障碍患者及对照者活体脑结构变异之间的关联。我们检测了30例患者和44例健康受试者血清样本中的HSV1免疫球蛋白G（IgG）抗体，并对同一批个体进行了结构磁共振成像扫描。与健康对照受试者相比，HSV1抗体比率升高的患者比例更高（卡方=3.98，自由度=1，P=0.046），且患者的HSV1 IgG抗体比率显著高于健康受试者。我们采用优化的基于体素的形态学测量方法，通过HSV1血清学状态交互作用进行诊断，然后在血清学状态内和组间进行比较。我们观察到HSV1血清学状态交互作用的诊断结果以及HSV1血清学状态在前额叶灰质中的显著主效应。与没有HSV1暴露血清学证据的患者相比，暴露于HSV1的患者在布罗德曼区9（背外侧前额叶皮质）和32（前扣带回皮质）的灰质减少。在健康受试者中未检测到与HSV1相关的脑结构差异。这些发现表明，精神分裂症患者中HSV1暴露与特定区域的灰质差异有关，这些差异可能并非由药物、疾病慢性化或合并物质使用所致。本研究为HSV1暴露与精神分裂症中经常报道的一些脑形态学变化之间的联系提供了提示性证据。
