Athina R Aruldass, Manfred Kitzbichler, Tsen Vei Lim, Jonathan Cavanagh, Philip Cowen, Carmine Pariante, Edward Bullmore, Neil Harrison
{"title":"Reward-related activation of fronto-striatal regions scaled negatively with C-reactive protein.","authors":"Athina R Aruldass, Manfred Kitzbichler, Tsen Vei Lim, Jonathan Cavanagh, Philip Cowen, Carmine Pariante, Edward Bullmore, Neil Harrison","doi":"10.1017/S0033291725102031","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Depression is characterized by divergent changes in positive and negative affect. Emerging roles of inflammation in depression portend avenues for novel immunomodulator-based monotherapy, targeting mechanistically distinct symptoms such as anhedonia and pessimism.</p><p><strong>Methods: </strong>To investigate links between these divergent affective components and inflammation, we used a probabilistic reinforcement-learning fMRI paradigm, testing for evidence of hyposensitivity to reward, and hypersensitivity to punishment in low-inflammation depression cases (loCRP depression; CRP ≤ 3 mg/L; <i>N</i> = 48), high-inflammation depression cases (hiCRP depression; CRP > 3 mg/L; <i>N</i> = 31), and healthy controls (HC; CRP ≤ 3 mg/L; <i>N</i> = 45). We aimed to (i) determine whether depression cases with high and low inflammation showed aberrant neural activation to monetary gains and losses compared to controls, and (ii) examine if these alterations correlated with a continuous measure of C-reactive protein (CRP) in depression, as well as indices of anhedonia and pessimism derived from behavioral instruments in depression.</p><p><strong>Results: </strong>Voxel-wise activation was observed in key brain regions sensitive to monetary reward (ventromedial prefrontal cortex, vmPFC; nucleus accumbens, NAc) and punishment (insula) outcomes across all three groups. However, there was no significant difference in activation between groups. Within depression cases, increasing CRP scaled negatively with activation in the right vmPFC and left NAc but not insula cortex. However, there was no significant association between regional activation and severity of anhedonia or pessimism.</p><p><strong>Conclusions: </strong>Our results support the previously reported association between CRP and striatal reward reactivity in depression but do not extend this to processing of negatively valenced information.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e308"},"PeriodicalIF":5.5000,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychological Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1017/S0033291725102031","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Depression is characterized by divergent changes in positive and negative affect. Emerging roles of inflammation in depression portend avenues for novel immunomodulator-based monotherapy, targeting mechanistically distinct symptoms such as anhedonia and pessimism.
Methods: To investigate links between these divergent affective components and inflammation, we used a probabilistic reinforcement-learning fMRI paradigm, testing for evidence of hyposensitivity to reward, and hypersensitivity to punishment in low-inflammation depression cases (loCRP depression; CRP ≤ 3 mg/L; N = 48), high-inflammation depression cases (hiCRP depression; CRP > 3 mg/L; N = 31), and healthy controls (HC; CRP ≤ 3 mg/L; N = 45). We aimed to (i) determine whether depression cases with high and low inflammation showed aberrant neural activation to monetary gains and losses compared to controls, and (ii) examine if these alterations correlated with a continuous measure of C-reactive protein (CRP) in depression, as well as indices of anhedonia and pessimism derived from behavioral instruments in depression.
Results: Voxel-wise activation was observed in key brain regions sensitive to monetary reward (ventromedial prefrontal cortex, vmPFC; nucleus accumbens, NAc) and punishment (insula) outcomes across all three groups. However, there was no significant difference in activation between groups. Within depression cases, increasing CRP scaled negatively with activation in the right vmPFC and left NAc but not insula cortex. However, there was no significant association between regional activation and severity of anhedonia or pessimism.
Conclusions: Our results support the previously reported association between CRP and striatal reward reactivity in depression but do not extend this to processing of negatively valenced information.
背景:抑郁症以积极情绪和消极情绪的发散变化为特征。炎症在抑郁症中的新作用预示着新的基于免疫调节剂的单一疗法,针对机制不同的症状,如快感缺乏和悲观。方法:为了研究这些不同的情感成分与炎症之间的联系,我们使用了概率强化学习功能磁共振成像范式,测试了低炎症抑郁患者(loCRP抑郁,CRP≤3mg /L, N = 48)、高炎症抑郁患者(hiCRP抑郁,CRP >≤3mg /L, N = 31)和健康对照组(HC, CRP≤3mg /L, N = 45)对奖励低敏感性和惩罚超敏感性的证据。我们的目的是(1)确定与对照组相比,患有高炎症和低炎症的抑郁症患者是否表现出对金钱收益和损失的异常神经激活,以及(2)检查这些改变是否与抑郁症中c反应蛋白(CRP)的持续测量相关,以及抑郁症中行为工具得出的快乐缺乏和悲观指数。结果:在所有三组中,对金钱奖励敏感的关键大脑区域(腹内侧前额叶皮层,vmPFC;伏隔核,NAc)和惩罚(脑岛)结果均观察到体素激活。然而,两组之间的激活没有显著差异。在抑郁症患者中,CRP的升高与右侧vmPFC和左侧NAc的激活呈负相关,但与脑岛皮层无关。然而,在区域激活和快感缺乏或悲观的严重程度之间没有显著的联系。结论:我们的研究结果支持先前报道的CRP与抑郁症纹状体奖励反应之间的关联,但并未将其扩展到负价值信息的处理。
期刊介绍:
Now in its fifth decade of publication, Psychological Medicine is a leading international journal in the fields of psychiatry, related aspects of psychology and basic sciences. From 2014, there are 16 issues a year, each featuring original articles reporting key research being undertaken worldwide, together with shorter editorials by distinguished scholars and an important book review section. The journal''s success is clearly demonstrated by a consistently high impact factor.