Department of Neurobiology, Affiliated Mental Health Centre & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310013, Zhejiang, China.
Mental Health Centre & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Psychopharmacology (Berl). 2024 Jan;241(1):97-107. doi: 10.1007/s00213-023-06466-9. Epub 2023 Sep 22.
An imbalance of the tryptophan kynurenine pathway (KP) commonly occurs in psychiatric disorders, though the neurocognitive and network-level effects of this aberration are unclear.
In this study, we examined the connection between dysfunction in the frontostriatal brain circuits, imbalances in the tryptophan kynurenine pathway (KP), and neurocognition in major psychiatric disorders.
Forty first-episode medication-naive patients with schizophrenia (SCZ), fifty patients with bipolar disorder (BD), fifty patients with major depressive disorder (MDD), and forty-two healthy controls underwent resting-state functional magnetic resonance imaging. Plasma levels of KP metabolites were measured, and neurocognitive function was evaluated. Frontostriatal connectivity and KP metabolites were compared between groups while controlling for demographic and clinical characteristics. Canonical correlation analyses were conducted to explore multidimensional relationships between frontostriatal circuits-KP and KP-cognitive features.
Patient groups shared hypoconnectivity between bilateral ventrolateral prefrontal cortex (vlPFC) and left insula, with disorder-specific dysconnectivity in SCZ related to PFC, left dorsal striatum hypoconnectivity. The BD group had higher anthranilic acid and lower xanthurenic acid levels than the other groups. KP metabolites and ratios related to disrupted frontostriatal dysconnectivity in a transdiagnostic manner. The SCZ group and MDD group separately had high-dimensional associations between KP metabolites and cognitive measures.
The findings suggest that KP may influence cognitive performance across psychiatric conditions via frontostriatal dysfunction.
在精神疾病中，色氨酸犬尿氨酸途径（KP）的失衡很常见，但这种异常的神经认知和网络水平影响尚不清楚。
本研究旨在探讨额纹状体脑回路功能障碍、色氨酸犬尿氨酸途径（KP）失衡与主要精神疾病的神经认知之间的关系。
40 名首发未用药的精神分裂症（SCZ）患者、50 名双相情感障碍（BD）患者、50 名重度抑郁症（MDD）患者和 42 名健康对照者接受了静息态功能磁共振成像。测量 KP 代谢物的血浆水平，并评估神经认知功能。在控制人口统计学和临床特征的情况下，比较组间额纹状体连接和 KP 代谢物。进行典型相关分析，以探索额纹状体回路-KP 和 KP-认知特征之间的多维关系。
患者组双侧腹外侧前额叶皮层（vlPFC）和左侧岛叶之间存在连接减少，SCZ 患者的连接障碍与 PFC、左侧背侧纹状体连接减少有关。BD 组的邻氨基苯甲酸水平高于其他组，犬尿酸水平较低。KP 代谢物及其比值以跨诊断的方式与额纹状体连接障碍有关。SCZ 组和 MDD 组分别存在 KP 代谢物与认知测量之间的高维关联。
这些发现表明，KP 可能通过额纹状体功能障碍影响各种精神疾病的认知表现。
