Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Schizophr Res. 2013 Aug;148(1-3):67-73. doi: 10.1016/j.schres.2013.06.014. Epub 2013 Jun 22.
Siblings of patients diagnosed with schizophrenia are at elevated risk for developing this disorder. The nature of such risk associated with brain abnormalities, and whether such abnormalities are similar to those observed in schizophrenia, remain unclear. Deficits in language processing are frequently reported in increased risk populations. Interestingly, white matter pathology involving fronto-temporal language pathways, including arcuate fasciculus (AF), uncinate fasciculus (UF), and inferior occipitofrontal fasciculus (IOFF), are frequently reported in schizophrenia. In this study, high spatial and directional resolution diffusion MRI data was obtained on a 3T magnet from 33 subjects with increased familial risk for developing schizophrenia, and 28 control subjects. Diffusion tractography was performed to measure white matter integrity within AF, UF, and IOFF. To understand these abnormalities, Fractional Anisotropy (FA, a measure of tract integrity) and Trace (a measure of overall diffusion), were combined with more specific measures of axial diffusivity (AX, a putative measure of axonal integrity) and radial diffusivity (RD, a putative measure of myelin integrity). Results revealed a significant decrease in Trace within IOFF, and a significant decrease in AX in all tracts. FA and RD anomalies, frequently reported in schizophrenia, were not observed. Moreover, AX group effect was modulated by age, with increased risk subjects demonstrating a deviation from normal maturation trajectory. Findings suggest that familial risk for schizophrenia may be associated with abnormalities in axonal rather than myelin integrity, and possibly associated with disruptions in normal brain maturation. AX should be considered a possible biomarker of risk for developing schizophrenia.
精神分裂症患者的兄弟姐妹患该病的风险增加。与脑异常相关的这种风险的性质，以及这种异常是否与精神分裂症中观察到的异常相似，尚不清楚。在高风险人群中，语言处理缺陷经常被报道。有趣的是，涉及额颞语言通路的白质病变，包括弓状束（AF）、钩束（UF）和下额枕额束（IOFF），在精神分裂症中经常被报道。在这项研究中，对 33 名有精神分裂症发病高家族风险的受试者和 28 名对照受试者，在 3T 磁体上获得了具有高空间和方向分辨率的弥散 MRI 数据。进行弥散轨迹追踪以测量 AF、UF 和 IOFF 内的白质完整性。为了理解这些异常，分数各向异性（FA，一种束完整性的度量）和轨迹（一种整体扩散的度量）与轴向弥散度（AX，一种轴突完整性的推测度量）和径向弥散度（RD，一种推测的髓鞘完整性的度量）的更具体度量相结合。结果显示，IOFF 内的轨迹明显减少，所有束中的 AX 明显减少。未观察到精神分裂症中经常报道的 FA 和 RD 异常。此外，AX 组效应受年龄调制，高风险受试者表现出偏离正常成熟轨迹的现象。研究结果表明，精神分裂症的家族风险可能与轴突完整性异常而不是髓鞘完整性异常有关，并且可能与正常大脑成熟过程中断有关。AX 应被视为精神分裂症发病风险的一个可能的生物标志物。
