Lee Jiwon, Costa-Dookhan Kenya, Panganiban Kristoffer, MacKenzie Nicole, Treen Quinn Casuccio, Chintoh Araba, Remington Gary, Müller Daniel J, Sockalingam Sanjeev, Gerretsen Philip, Sanches Marcos, Karnovsky Alla, Stringer Kathleen A, Ellingrod Vicki L, Tso Ivy F, Taylor Stephan F, Agarwal Sri Mahavir, Hahn Margaret K, Ward Kristen M
Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Front Psychiatry. 2023 Apr 24;14:1169787. doi: 10.3389/fpsyt.2023.1169787. eCollection 2023.
Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data ( = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs.
精神病性谱系障碍（PSD）以及其他可能存在精神病性特征的严重精神疾病，如双相情感障碍，都与内在代谢异常有关。抗精神病药物（AP）是PSD治疗的基石，但会引发额外的代谢问题，包括体重增加。目前，在理解精神病性疾病生物标志物以及AP所致体重增加的危险因素和机制方面存在重大差距。代谢组学谱可能会识别生物标志物，并深入了解PSD和抗精神病药物所致体重增加的机制基础。在这项为期12周的前瞻性自然主义研究中，我们将25例开始服用AP后约1周内的患者血清代谢组学谱与6名基线时的健康对照进行比较，以检查PSD中内在代谢功能障碍的生物标志物。然后，在17例有基线和第12周样本的病例参与者中，我们检查了AP治疗12周内代谢组学谱的变化，以确定可能与AP所致体重增加相关的代谢物。在有前后数据的队列（n = 17）中，我们还比较了体重增加≥5%基线体重的参与者与体重增加<5%的参与者的基线代谢组，以确定抗精神病药物所致体重增加的潜在生物标志物。在基线时比较，最少接触AP的病例与对照在六种脂肪酸上存在差异，即棕榈油酸、月桂酸和二十一烷酸水平降低，以及山嵛酸、花生四烯酸和肉豆蔻油酸水平升高（错误发现率<0.05）。与未出现体重增加的个体相比，11例在接受12周AP暴露后出现临床显著体重增加（≥5%）的个体中，脂肪酸肾上腺酸的基线水平升高（错误发现率 = 0.0408）。脂肪酸可能代表PSD的疾病生物标志物以及AP所致体重增加的早期预测指标。这些发现可能对早期识别那些可从预防策略中受益以降低未来心脏代谢风险的个体具有重要的临床意义，并可能导致新的、有针对性的治疗方法来对抗PSD中的代谢功能障碍。
