Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT-1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n=25/condition), relative to typical controls (n=100). This revealed alterations in the expression of these proteins that were specific to schizophrenia. Further characterization of metabolic alterations in an extended cohort of first-onset antipsychotic drug-naïve schizophrenia patients (n=58) and controls (n=63) revealed that the relationship between insulin receptor expression in monocytes and physiological insulin sensitivity was disrupted in schizophrenia and that altered expression of the insulin receptor was associated with whole genome polygenic risk scores for schizophrenia. Finally, longitudinal follow-up of the schizophrenia patients over the course of antipsychotic drug treatment revealed that peripheral metabolic markers predicted changes in psychopathology and the principal side effect of weight gain at clinically relevant time points. These findings suggest that peripheral blood cells can provide an accessible surrogate model for metabolic alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic complications following antipsychotic therapy.

中文翻译：

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探索神经精神谱系外周血单核细胞代谢综合征的细胞标志物

最近的证据表明，神经精神疾病和代谢综合征之间的合并症可能先于甚至加剧精神药物的长期副作用，例如患 2 型糖尿病和心血管疾病的风险更高，从而导致死亡率增加。在本研究中，我们比较了关键代谢蛋白的表达，包括胰岛素受体 (CD220)、葡萄糖转运蛋白 1 (GLUT-1) 和脂肪酸转位酶 (CD36)，在来自神经精神病学谱系患者的外周血单核细胞亚型上，包括精神分裂症、双相情感障碍、重度抑郁症和自闭症谱系状况（n=25/状况），相对于典型对照（n=100）。这揭示了这些特定于精神分裂症的蛋白质表达的改变。对初发抗精神病药物初治精神分裂症患者 (n=58) 和对照 (n=63) 的扩展队列的代谢改变的进一步表征表明，单核细胞中胰岛素受体表达与生理胰岛素敏感性之间的关系在精神分裂症中被破坏，并且胰岛素受体表达的改变与精神分裂症的全基因组多基因风险评分相关。最后，在抗精神病药物治疗过程中对精神分裂症患者的纵向随访显示，外周代谢标志物可以预测临床相关时间点的精神病理学变化和体重增加的主要副作用。