Seidman Larry J, Thermenos Heidi W, Poldrack Russell A, Peace Nicole K, Koch Jennifer K, Faraone Stephen V, Tsuang Ming T
Harvard Medical School, Department of Psychiatry, Massachusetts Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Schizophr Res. 2006 Jul;85(1-3):58-72. doi: 10.1016/j.schres.2006.03.019. Epub 2006 Apr 24.
Adult first-degree relatives of persons with schizophrenia carry elevated genetic risk for the illness, demonstrate working memory (WM) impairments, and manifest alterations in dorsolateral prefrontal cortical (DLPFC) function during WM. Because substantially less is known about these phenotypes in adolescent subjects we sought to demonstrate that young relatives of persons with schizophrenia manifest impaired WM and altered prefrontal activation.
Participants were 21 non-psychotic, unmedicated first-degree relatives of persons with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, depressed type and 24 unmedicated controls, recruited from the community and hospitals in metropolitan Boston (ages 13-28). We compared groups on an auditory WM task with interference prior to scanning and used functional magnetic resonance imaging (fMRI) to compare groups while performing visual 2-back WM and control vigilance tasks. Blood oxygen level dependent signal change was measured using two whole-brain gradient echo EPI pulse acquisitions (21 contiguous, 5mm axial slices), acquired on a Siemens 1.5T MR scanner. Data were analyzed using Statistical Parametric Mapping-99.
The high risk subjects were significantly impaired on the auditory WM task, had significantly greater Phobic Anxiety, and marginally greater Psychoticism than controls on the Symptom Checklist-90-Revised, and showed significantly greater task-elicited activation in the right DLPFC (BA 46). Psychopathology, IQ, and in-scanner WM performance did not account for group differences in brain activation.
Data support a physiological difference (an exaggerated fMRI response) in DLPFC in adolescents at genetic risk for schizophrenia, independent of psychosis. Future work can study the relationship of these measures to possible onset of schizophrenia.
精神分裂症患者的成年一级亲属患该疾病的遗传风险升高，表现出工作记忆（WM）受损，并且在执行WM任务期间背外侧前额叶皮质（DLPFC）功能发生改变。由于对青少年受试者的这些表型了解甚少，我们试图证明精神分裂症患者的年轻亲属存在WM受损和前额叶激活改变的情况。
参与者为21名无精神病、未服药的一级亲属，他们的亲属被诊断为符合《精神疾病诊断与统计手册》第四版（DSM-IV）标准的精神分裂症或分裂情感性障碍（抑郁型），以及24名未服药的对照者，均从波士顿大都市的社区和医院招募而来（年龄在13 - 28岁之间）。我们在扫描前比较了两组在有干扰的听觉WM任务中的表现，并使用功能磁共振成像（fMRI）在执行视觉2-back WM任务和对照警觉任务时比较两组。使用西门子1.5T MR扫描仪通过两次全脑梯度回波EPI脉冲采集（21个连续的5毫米轴向切片）测量血氧水平依赖信号变化。使用统计参数映射99对数据进行分析。
高风险受试者在听觉WM任务上显著受损，在《症状自评量表-90修订版》上的恐惧焦虑得分显著高于对照组，精神病性得分略高于对照组，并且在右侧DLPFC（BA 46）中表现出显著更强的任务诱发激活。精神病理学、智商和扫描时的WM表现并不能解释两组在脑激活方面的差异。
数据支持有精神分裂症遗传风险的青少年DLPFC存在生理差异（fMRI反应过度），且与精神病无关。未来的研究可以探讨这些测量结果与精神分裂症可能发病之间的关系。
