PDF(Pubmed)
Abstract：
One third of people with psychosis become antipsychotic treatment-resistant and the underlying mechanisms remain unclear. We investigated whether altered cognitive control function is a factor underlying development of treatment resistance. We studied 50 people with early psychosis at a baseline visit (mean < 2 years illness duration) and follow-up visit (1 year later), when 35 were categorized at treatment-responsive and 15 as treatment-resistant. Participants completed an emotion-yoked reward learning task that requires cognitive control whilst undergoing fMRI and MR spectroscopy to measure glutamate levels from Anterior Cingulate Cortex (ACC). Changes in cognitive control related activity (in prefrontal cortex and ACC) over time were compared between treatment-resistant and treatment-responsive groups and related to glutamate. Compared to treatment-responsive, treatment-resistant participants showed blunted activity in right amygdala (decision phase) and left pallidum (feedback phase) at baseline which increased over time and was accompanied by a decrease in medial Prefrontal Cortex (mPFC) activity (feedback phase) over time. Treatment-responsive participants showed a negative relationship between mPFC activity and glutamate levels at follow-up, no such relationship existed in treatment-resistant participants. Reduced activity in right amygdala and left pallidum at baseline was predictive of treatment resistance at follow-up (67% sensitivity, 94% specificity). The findings suggest that deterioration in mPFC function over time, a key cognitive control region needed to compensate for an initial dysfunction within a social-emotional network, is a factor underlying development of treatment resistance in early psychosis. An uncoupling between glutamate and cognitive control related mPFC function requires further investigation that may present a future target for interventions.
摘要：
三分之一的精神病患者成为抗精神病药物治疗抵抗者，其潜在机制仍不清楚。我们调查了认知控制功能的改变是否是治疗抵抗发展的潜在因素。我们在基线访视（平均病程<2年）和随访访视（1年后）时研究了50名早期精神病患者，当35人被归类为治疗敏感，15人被归类为治疗耐药。参与者完成了一项情感约束的奖励学习任务，该任务需要进行认知控制，同时进行fMRI和MR光谱学检查以测量前扣带回皮质（ACC）的谷氨酸水平。比较了抵抗治疗和治疗反应组之间认知控制相关活动（前额叶皮层和ACC）随时间的变化，并与谷氨酸有关。与治疗反应性相比，治疗抵抗的参与者在基线时右杏仁核(决策阶段)和左苍白球(反馈阶段)的活动减弱,随着时间的推移而增加,并伴随内侧前额叶皮质(mPFC)活动(反馈阶段)随着时间的推移而减少.对治疗有反应的参与者在随访时显示mPFC活性与谷氨酸水平之间呈负相关，在治疗耐药的参与者中不存在这种关系.基线时右杏仁核和左苍白球的活性降低是随访时治疗抵抗的预测因素(67%敏感性,94%特异性)。研究结果表明，mPFC功能随着时间的推移而恶化，一个关键的认知控制区域需要补偿社会情绪网络中的初始功能障碍，是早期精神病治疗抵抗发展的潜在因素。谷氨酸与认知控制相关的mPFC功能之间的解偶联需要进一步的研究，这可能是未来干预的目标。
