Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Brain Imaging Behav. 2011 Mar;5(1):65-75. doi: 10.1007/s11682-010-9111-2.
Patients with schizophrenia exhibit deficient response monitoring as indexed by blunted activation of the dorsal anterior cingulate cortex (dACC) and functionally related regions during error commission. This pattern may reflect heritable alterations of dACC function. We examined whether the hypofunctional 677C>T variant in MTHFR, a candidate schizophrenia risk gene, contributed to our previous findings of blunted error-related dACC activation and reduced microstructural integrity of dACC white matter. Eighteen medicated outpatients with schizophrenia underwent diffusion tensor imaging and performed an antisaccade paradigm during functional magnetic resonance imaging (fMRI). T allele carriers exhibited significantly less error-related activation than C/C patients in bilateral dACC and substantia nigra, regions that are thought to mediate dopamine-dependent error-based reinforcement learning. T carrier patients also showed significantly lower fractional anisotropy in bilateral dACC. These findings suggest that the MTHFR 677T allele blunts response monitoring in schizophrenia, presumably via effects on dopamine signaling and dACC white matter microstructural integrity.
精神分裂症患者在犯错时，背侧前扣带皮层（dACC）及其相关功能区的激活会减弱，表明其存在反应监控缺陷。这种模式可能反映了 dACC 功能的遗传性改变。我们研究了候选精神分裂症风险基因 MTHFR 的 677C>T 变异是否导致了我们之前发现的 dACC 激活减弱以及 dACC 白质微观结构完整性降低的现象。18 名接受药物治疗的精神分裂症门诊患者接受了弥散张量成像，并在功能磁共振成像（fMRI）期间执行了反扫视范式。与 C/C 患者相比，T 等位基因携带者在双侧 dACC 和黑质中显示出明显较弱的错误相关激活，这些区域被认为介导多巴胺依赖的基于错误的强化学习。T 携带者患者双侧 dACC 的各向异性分数也明显较低。这些发现表明，MTHFR 677T 等位基因通过影响多巴胺信号和 dACC 白质微观结构完整性，使精神分裂症患者的反应监控能力减弱。
