Jauhar Sameer, McCutcheon Robert A, Nour Matthew M, Veronese Mattia, Rogdaki Maria, Bonoldi Ilaria, Azis Matilda, Whitehurst Thomas, Arumuham Atheeshaan, Onwordi Ellis, Turkheimer Federico, McGuire Philip, Young Allan H, Howes Oliver D
Division of Psychiatry, Imperial College London, London, United Kingdom.
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
JAMA Psychiatry. 2025 Aug 13. doi: 10.1001/jamapsychiatry.2025.1811.
There is limited neurobiological or trial evidence guiding treatment of comorbid affective syndromes in psychotic disorders. Given the use of dopamine-blocking antipsychotics, understanding dopamine function across these mood states is warranted.
To test for differences in dopamine synthesis capacity (Kicer) between affective syndromes across psychotic disorders and for association with psychotic symptom severity.
DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study using fluorine F 18-labeled fluorodopa (18F-DOPA) positron emission tomography (PET), individuals with first-episode psychosis and comorbid affective syndromes, including a current major depressive episode (MDE) or mixed/mania syndromes, and matched controls were recruited from early intervention services in inner-city London, United Kingdom. Data were collected from March 2013 to February 2022 and analyzed from October 1, 2023, to January 1, 2025.
Striatal Kicer measured by 18F-DOPA PET.
Striatal Kicer and scores on the Positive and Negative Syndrome Scale, Hamilton Depression Rating Scale, Montgomery-Åsberg Depression Rating Scale, and Young Mania Rating Scale were determined.
The study included a total of 76 individuals (38 with first-episode psychosis and comorbid affective syndromes [25 with MDE and 13 with mixed/mania syndromes] and 38 matched controls). The mean (SD) age was 27.2 (8.9) years overall, 30.7 (12.8) years among those with MDE, 23.7 (3.1) years among those with mixed/mania syndromes, and 26.0 (6.0) years among controls. Sex distribution did not differ (MDE, 13 [52%] male; mixed/mania syndromes, 8 [62%] male; controls, 25 [66%] male; P = .56). Kicer (controlling for age and sex) was significant across groups in whole striatum (F2,71 = 4.04; P = .02; R2 = 0.13). People with psychosis and MDE had lower Kicer compared with those with psychosis and mixed/mania syndromes (β [SE], 0.014 [0.001]; P = .02), with the largest difference observed in the limbic striatum (Cohen d = 1.57; P < .001). In the overall psychosis sample, higher striatal Kicer was associated with greater positive psychotic symptoms (R2 = 0.13; β [SE], 0.000066 [0.000030]; P = .03), notably in the associative striatum (R2 = 0.15; P = .02). No significant association was found in the limbic striatum.
Kicer was lower in psychosis and comorbid MDE than mixed/mania syndromes, and transdiagnostically, greater positive psychotic symptoms were associated with higher Kicer in the associative, but not limbic, striatum. This subregion dopamine dysregulation has relevance for dopamine-modulating therapeutic agents and drug discovery.
在精神病性障碍中共病情感综合征的治疗方面，神经生物学或试验证据有限。鉴于多巴胺阻断型抗精神病药物的使用，有必要了解这些情绪状态下的多巴胺功能。
测试精神病性障碍中不同情感综合征之间多巴胺合成能力（Kicer）的差异，以及与精神病性症状严重程度的关联。
设计、设置和参与者：在这项使用氟F 18标记的氟多巴（18F-DOPA）正电子发射断层扫描（PET）的横断面研究中，从英国伦敦市中心的早期干预服务机构招募了首发精神病并伴有情感综合征的个体，包括当前的重度抑郁发作（MDE）或混合/躁狂综合征，以及匹配的对照组。数据收集时间为2013年3月至2022年2月，分析时间为2023年10月1日至2025年1月1日。
通过18F-DOPA PET测量纹状体Kicer。
测定纹状体Kicer以及阳性和阴性综合征量表、汉密尔顿抑郁量表、蒙哥马利-阿斯伯格抑郁量表和杨氏躁狂量表的得分。
该研究共纳入76名个体（38名首发精神病并伴有情感综合征[25名患有MDE，13名患有混合/躁狂综合征]和38名匹配的对照组）。总体平均（标准差）年龄为27.2（8.9）岁，MDE患者中为30.7（12.8）岁，混合/躁狂综合征患者中为23.7（3.1）岁，对照组中为26.0（6.0）岁。性别分布无差异（MDE组，13名[52%]男性；混合/躁狂综合征组，8名[62%]男性；对照组，25名[66%]男性；P = 0.56）。在整个纹状体中，校正年龄和性别后，Kicer在各组间存在显著差异（F2,71 = 4.04；P = 0.02；R2 = 0.13）。患有精神病和MDE的患者与患有精神病和混合/躁狂综合征的患者相比，Kicer较低（β[标准误]，0.014[0.001]；P = 0.02），在边缘纹状体中观察到的差异最大（Cohen d = 1.57；P < 0.001）。在总体精神病样本中，较高的纹状体Kicer与更严重的阳性精神病性症状相关（R2 = 0.13；β[标准误]，0.000066[0.000030]；P = 0.03），特别是在联合纹状体中（R2 = 0.15；P = 0.02）。在边缘纹状体中未发现显著关联。
精神病和共病MDE患者的Kicer低于混合/躁狂综合征患者，并且从跨诊断角度来看，更严重的阳性精神病性症状与联合纹状体（而非边缘纹状体）中较高的Kicer相关。这种亚区域多巴胺失调与多巴胺调节治疗药物及药物研发相关。
