Schifani Christin, Hafizi Sina, Tseng Huai-Hsuan, Gerritsen Cory, Kenk Miran, Wilson Alan A, Houle Sylvain, Rusjan Pablo M, Mizrahi Romina
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Schizophr Res. 2019 Nov;213:80-86. doi: 10.1016/j.schres.2018.10.008. Epub 2018 Nov 6.
Prolonged stress can cause neuronal loss in the hippocampus resulting in disinhibition of glutamatergic neurons proposed to enhance dopaminergic firing in subcortical regions including striatal areas. Supporting this, imaging studies show increased striatal dopamine release in response to psychosocial stress in healthy individuals with low childhood maternal care, individuals at clinical high risk for psychosis (CHR) and patients with schizophrenia. The prefrontal cortex (PFC) is connected to the hippocampus and a key region to control neurochemical responses to stressful stimuli. We recently reported a disrupted PFC dopamine-stress regulation in schizophrenia, which was intact in CHR. Given the available evidence on the link between psychosocial stress, PFC dopamine release and hippocampal immune activation in psychosis, we explored, for the first time in vivo, whether stress-induced PFC dopamine release is associated with hippocampal TSPO expression (a neuroimmune marker) in the psychosis spectrum. We used an overlapping sample of antipsychotic-naïve subjects with CHR (n = 6) and antipsychotic-free schizophrenia patients (n = 9) from our previously published studies, measuring PFC dopamine release induced by a psychosocial stress task with [C]FLB457 positron emission tomography (PET) and TSPO expression with [F]FEPPA PET. We observed that participants on the psychosis spectrum with lower stress-induced dopamine release in PFC had significantly higher TSPO expression in hippocampus (β = -2.39, SE = 0.96, F(1,11) = 6.17, p = 0.030). Additionally, we report a positive association between stress-induced PFC dopamine release, controlled for hippocampal TSPO expression, and Global Assessment of Functioning. This is the first exploration of the relationship between PFC dopamine release and hippocampal TSPO expression in vivo in humans.
长期应激可导致海马体神经元丢失，致使谷氨酸能神经元去抑制，进而增强包括纹状体区域在内的皮质下区域的多巴胺能神经元放电。对此的支持证据是，成像研究表明，童年期母亲照料较少的健康个体、临床精神病高风险个体（CHR）以及精神分裂症患者在面对心理社会应激时，纹状体多巴胺释放会增加。前额叶皮质（PFC）与海马体相连，是控制对应激刺激的神经化学反应的关键区域。我们最近报告称，精神分裂症患者的PFC多巴胺-应激调节存在破坏，而CHR患者的这种调节是完整的。鉴于现有证据表明心理社会应激、PFC多巴胺释放与精神病中海马体免疫激活之间存在联系，我们首次在体内探究了应激诱导的PFC多巴胺释放是否与精神病谱系中海马体TSPO表达（一种神经免疫标志物）相关。我们使用了来自我们之前发表的研究中的未服用抗精神病药物的CHR受试者（n = 6）和未服用抗精神病药物的精神分裂症患者（n = 9）的重叠样本，通过[C]FLB457正电子发射断层扫描（PET）测量心理社会应激任务诱导的PFC多巴胺释放，并通过[F]FEPPA PET测量TSPO表达。我们观察到，在精神病谱系中，PFC中应激诱导多巴胺释放较低的参与者海马体中的TSPO表达显著更高（β = -2.39，标准误 = 0.96，F(1,11) = 6.17，p = 0.030）。此外，我们报告了在控制海马体TSPO表达的情况下，应激诱导的PFC多巴胺释放与总体功能评估之间存在正相关。这是首次在人体体内探索PFC多巴胺释放与海马体TSPO表达之间的关系。
