童年期创伤通过免疫炎症途径影响精神分裂症快感缺失的研究进展

doi:10.3969/j.issn.1674-8115.2026.02.013

摘要/Abstract

摘要：

童年期创伤是精神分裂症发病的重要环境风险因素，通过复杂的生物学编程机制增加个体神经发育异常易感性。快感缺失作为精神分裂症的核心阴性症状之一，表现为对愉悦刺激反应能力的持续减退，严重影响患者的社会功能及长期预后。研究发现，免疫炎症通路的异常激活可能是连接童年期创伤暴露与精神分裂症快感缺失病理过程的关键桥梁。童年期创伤通过持续激活应激与代谢相关生理通路，可导致全身性低度慢性炎症状态，进而引起促炎因子升高、抗炎功能受抑制及神经免疫细胞异常活化等一系列免疫紊乱。这些变化可能进一步通过影响神经功能与环路，介导快感缺失的发生与发展。该文总结现有研究进展，系统阐述童年期创伤对免疫系统的影响及精神分裂症快感缺失的潜在机制，重点分析两者的关联性以及免疫炎症因子在其中所起的介导作用。

关键词: 童年期创伤, 免疫炎症, 精神分裂症, 快感缺失

Abstract:

Childhood trauma serves as a significant environmental risk factor for the onset of schizophrenia, and through complex biological programming mechanisms, it increases the susceptibility of individuals to neurodevelopmental abnormalities. Anhedonia, as one of the core negative symptoms of schizophrenia, is characterized by a persistent decline in the ability to respond to pleasurable stimuli, severely affecting the social functions and long-term prognosis of patients. Recent studies have revealed that the abnormal activation of immune-inflammatory pathways may serve as a crucial intermediary link connecting childhood trauma exposure with the pathophysiological process of anhedonia in schizophrenia. Childhood trauma can lead to a systemic low-grade chronic inflammatory state by continuously activating stress- and metabolism-related physiological pathways, which in turn causes a series of immune disorders, such as elevated pro-inflammatory factors, suppressed anti-inflammatory functions, and abnormal activation of neuroimmune cells. These changes may further mediate the occurrence and development of anhedonia by affecting neural functions and circuits. This review summarizes and analyzes current research progress, systematically elaborates the impact of childhood trauma on the immune system and the potential mechanisms of anhedonia in schizophrenia, and focuses on analyzing the correlation between the two and the mediating role of immune-inflammatory factors.

Key words: childhood trauma, immune inflammation, schizophrenia, anhedonia

中图分类号:

R749.3

刘文霞, 张晨. 童年期创伤通过免疫炎症途径影响精神分裂症快感缺失的研究进展[J]. 上海交通大学学报（医学版）, 2026, 46(2): 235-240.

Liu Wenxia, Zhang Chen. Research advances in the impact of childhood trauma on anhedonia in schizophrenia via immune-inflammatory pathways[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(2): 235-240.

参考文献 54

[1]	Jauhar S, Johnstone M, Mckenna P J. Schizophrenia[J]. Lancet, 2022, 399(10323): 473-486.
[2]	O'brien K J, Ered A, Korenic S A, et al. Childhood trauma, perceived stress and anhedonia in individuals at clinical high risk for psychosis: multigroup mediation analysis[J]. Br J Psychiatry, 2023, 223(1): 273-279.
[3]	Misiak B, Frydecka D, Piotrowski P, et al. Coping styles do not interact with the association between childhood trauma history and the immune-inflammatory phenotype of schizophrenia: findings from a cross-sectional study[J]. Psychoneuroendocrinology, 2024, 166: 107062.
[4]	Neumann E, Rixe J, Driessen M, et al. Psychosocial functioning as a mediator between childhood trauma and symptom severity in patients with schizophrenia[J]. Child Abuse Negl, 2023, 144: 106372.
[5]	Kilian S, Asmal L, Phahladira L, et al. The association between childhood trauma and treatment outcomes in schizophrenia spectrum disorders[J]. Psychiatry Res, 2020, 289: 113004.
[6]	Fan F M, Tan S P, Liu S B, et al. Subcortical structures associated with childhood trauma and perceived stress in schizophrenia[J]. Psychol Med, 2023, 53(12): 5654-5662.
[7]	Asmal L, Kilian S, du Plessis S, et al. Childhood trauma associated white matter abnormalities in first-episode schizophrenia[J]. Schizophr Bull, 2019, 45(2): 369-376.
[8]	Jenness J L, Peverill M, Miller A B, et al. Alterations in neural circuits underlying emotion regulation following child maltreatment: a mechanism underlying trauma-related psychopathology[J]. Psychol Med, 2021, 51(11): 1880-1889.
[9]	Fan J, Liu W T, Xia J, et al. Childhood trauma is associated with social anhedonia and brain gray matter volume differences in healthy subjects[J]. Brain Imag Behav, 2022, 16(5): 1964-1972.
[10]	Birnie M T, Kooiker C L, Short A K, et al. Plasticity of the reward circuitry after early-life adversity: mechanisms and significance[J]. Biol Psychiatry, 2020, 87(10): 875-884.
[11]	Holochwost S J, Gomes L A, Wylie A, et al. Resting hypothalamic-pituitary-adrenal axis activity in childhood following maltreatment: a meta-analysis[J]. Dev Psychobiol, 2025, 67(2): e70022.
[12]	Menke A, Nitschke F, Hellmuth A, et al. Stress impairs response to antidepressants via HPA axis and immune system activation[J]. Brain Behav Immun, 2021, 93: 132-140.
[13]	Quidé Y, Bortolasci C C, Spolding B, et al. Association between childhood trauma exposure and pro-inflammatory cytokines in schizophrenia and bipolar-I disorder[J]. Psychol Med, 2019, 49(16): 2736-2744.
[14]	Marques-Feixa L, Palma-Gudiel H, Romero S, et al. Childhood maltreatment disrupts HPA-axis activity under basal and stress conditions in a dose-response relationship in children and adolescents[J]. Psychol Med, 2023, 53(3): 1060-1073.
[15]	Arancibia M, Manterola M, Ríos U, et al. The rs1360780 variant of FKBP5: genetic variation, epigenetic regulation, and behavioral phenotypes[J]. Genes, 2025, 16(3): 325.
[16]	Hertzberg L, Zohar A H, Yitzhaky A. Gene expression meta-analysis of cerebellum samples supports the FKBP5 gene-environment interaction model for schizophrenia[J]. Life, 2021, 11(3): 190.
[17]	Mihaljevic M, Franic D, Soldatovic I, et al. The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls[J]. Psychoneuroendocrinology, 2021, 128: 105205.
[18]	Stramecki F, Misiak B, Gawęda Ł, et al. The moderating role of the FKBP5 gene polymorphisms in the relationship between attachment style, perceived stress and psychotic-like experiences in non-clinical young adults[J]. J Clin Med, 2022, 11(6): 1614.
[19]	Yu Z Y, Cole S, Ross K, et al. Childhood adversities and the ATTACH^TM program's influence on immune cell gene expression[J]. Int J Environ Res Public Health, 2024, 21(6): 776.
[20]	Ullah H, Arbab S, Tian Y L, et al. Crosstalk between gut microbiota and host immune system and its response to traumatic injury[J]. Front Immunol, 2024, 15: 1413485.
[21]	Counotte J, Drexhage H A, Wijkhuijs J M, et al. Th17/T regulator cell balance and NK cell numbers in relation to psychosis liability and social stress reactivity[J]. Brain Behav Immun, 2018, 69: 408-417.
[22]	Lucido M J, Bekhbat M, Goldsmith D R, et al. Aiding and abetting anhedonia: impact of inflammation on the brain and pharmacological implications[J]. Pharmacol Rev, 2021, 73(3): 1084-1117.
[23]	Sapienza J, Agostoni G, Repaci F, et al. Metabolic syndrome and schizophrenia: adding a piece to the interplay between the kynurenine pathway and inflammation[J]. Metabolites, 2025, 15(3): 176.
[24]	Erhardt S, Schwieler L, Imbeault S, et al. The kynurenine pathway in schizophrenia and bipolar disorder[J]. Neuropharmacology, 2017, 112: 297-306.
[25]	Rodrigues F T S, de Souza M R M, de Carvalho Lima C N, et al. Major depression model induced by repeated and intermittent lipopolysaccharide administration: long-lasting behavioral, neuroimmune and neuroprogressive alterations[J]. J Psychiatr Res, 2018, 107: 57-67.
[26]	Laumet G, Zhou W J, Dantzer R, et al. Upregulation of neuronal kynurenine 3-monooxygenase mediates depression-like behavior in a mouse model of neuropathic pain[J]. Brain Behav Immun, 2017, 66: 94-102.
[27]	Zhang Y, Shi H, Yang G, et al. Associations between expression of indoleamine 2,3-dioxygenase enzyme and inflammatory cytokines in patients with first-episode drug-naive schizophrenia[J]. Transl Psychiatry, 2021, 11: 595.
[28]	吴则南, 张晨. 快感缺失的炎症机制研究进展[J]. 上海交通大学学报(医学版), 2021, 41(2): 241-245.
	Wu Z N, Zhang C. Research advances in inflammatory mechanism of anhedonia[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021, 41(2): 241-245.
[29]	Zhilyaeva T V, Kasyanov E D, Rukavishnikov G V, et al. Pterin metabolism, inflammation and oxidative stress biochemical markers in schizophrenia: factor analysis and assessment of clinical symptoms associations[J]. Prog Neuro Psychopharmacol Biol Psychiatry, 2023, 127: 110823.
[30]	Feng Y, Feng Y H, Gu L M, et al. The critical role of tetrahydrobiopterin (BH4) metabolism in modulating radiosensitivity: BH4/NOS axis as an angel or a devil[J]. Front Oncol, 2021, 11: 720632.
[31]	Cao B, Chen Y, Ren Z Y, et al. Dysregulation of kynurenine pathway and potential dynamic changes of kynurenine in schizophrenia: a systematic review and meta-analysis[J]. Neurosci Biobehav Rev, 2021, 123: 203-214.
[32]	Park J H, Hong J S, Kim S M, et al. Effects of amisulpride adjunctive therapy on working memory and brain metabolism in the frontal cortex of patients with schizophrenia: a preliminary positron emission tomography/computerized tomography investigation[J]. Clin Psychopharmacol Neurosci, 2019, 17(2): 250-260.
[33]	Felger J C, Treadway M T. Inflammation effects on motivation and motor activity: role of dopamine[J]. Neuropsychopharmacology, 2017, 42(1): 216-241.
[34]	Bekhbat M, Li Z H, Mehta N D, et al. Correction to: functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: evidence from a dopamine challenge study[J]. Mol Psychiatry, 2022, 27(10): 4122.
[35]	Goldsmith D R, Ning C S, Strauss G P, et al. Inflammation is associated with avolition and reduced resting state functional connectivity in corticostriatal reward circuitry in patients with schizophrenia[J]. Neuropsychopharmacology, 2025, 50(11): 1706-1714.
[36]	范建华, 张程赪, 许明胜, 等. 补体因子H与精神分裂症快感缺失的关系研究[J]. 中国实用医药, 2021, 16(13): 84-87.
	Fan J H, Zhang C C, Xu M S, et al. Correlation between complement factor H and anhedonia in schizophrenia[J]. China Practical Medicine, 2021, 16(13): 84-87.
[37]	Zhang Y, Tang W, Wang W P, et al. Effects of olanzapine on anhedonia in schizophrenia: mediated by complement factor H[J]. Front Psychiatry, 2023, 14: 1146714.
[38]	Cornman J C, Witt J, Glei D A, et al. Exposure to childhood maltreatment predicts adult physiological dysregulation, particularly inflammation[J]. PLoS One, 2023, 18(11): e0294667.
[39]	Mehta N D, Stevens J S, Li Z H, et al. Inflammation, reward circuitry and symptoms of anhedonia and PTSD in trauma-exposed women[J]. Soc Cogn Affect Neurosci, 2020, 15(10): 1046-1055.
[40]	Çiftci H, Aşut G, Kaya H S, et al. Neutrophil gelatinase-associated lipocalin (NGAL) and inflammatory markers in schizophrenia: a comparative analysis of drug-naive schizophrenia patients, remitted patients, and healthy controls[J]. J Psychiatr Res, 2024, 169: 14-21.
[41]	Gül Çakıl A, Kaya H, Sakallı Nural A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) and tumor necrosis factor-α (TNF-α) levels in patients with schizophrenia[J]. Psychopharmacology, 2023, 240(5): 1091-1101.
[42]	Kristóf Z, Baranyi M, Tod P, et al. Elevated serum purine levels in schizophrenia: a reverse translational study to identify novel inflammatory biomarkers[J]. Int J Neuropsychopharmacol, 2022, 25(8): 645-659.
[43]	Quidé Y, Bortolasci C C, Spolding B, et al. Systemic inflammation and grey matter volume in schizophrenia and bipolar disorder: moderation by childhood trauma severity[J]. Prog Neuro Psychopharmacol Biol Psychiatry, 2021, 105: 110013.
[44]	Brown M, Worrell C, Pariante C M. Inflammation and early life stress: an updated review of childhood trauma and inflammatory markers in adulthood[J]. Pharmacol Biochem Behav, 2021, 211: 173291.
[45]	Yi L, Tang J X, Yang S, et al. Childhood trauma and the plasma levels of IL-6, TNF-α are risk factors for major depressive disorder and schizophrenia in adolescents: a cross-sectional and case-control study[J]. J Affect Disord, 2022, 305: 227-232.
[46]	Corsi-Zuelli F, Deakin B. Impaired regulatory T cell control of astroglial overdrive and microglial pruning in schizophrenia[J]. Neurosci Biobehav Rev, 2021, 125: 637-653.
[47]	Klawonn A M, Fritz M, Castany S, et al. Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons[J]. Immunity, 2021, 54(2): 225-234.e6.
[48]	Komori T, Okamura K, Ikehara M, et al. Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior[J]. Mol Psychiatry, 2024, 29(5): 1338-1349.
[49]	Tian T, Li J, Zhang G L, et al. Effects of childhood trauma experience and BDNF Val66Met polymorphism on brain plasticity relate to emotion regulation[J]. Behav Brain Res, 2021, 398: 112949.
[50]	Moreno I, Stojanovic-Pérez A, Bulduk B, et al. High blood levels of brain-derived neurotrophic factor (BDNF) mRNA in early psychosis are associated with inflammatory markers[J]. J Psychiatr Res, 2023, 164: 440-446.
[51]	Parrott J M, Porter G A, Redus L, et al. Brain derived neurotrophic factor deficiency exacerbates inflammation-induced anhedonia in mice[J]. Psychoneuroendocrinology, 2021, 134: 105404.
[52]	Zhao T, Piao L H, Li D P, et al. BDNF gene hydroxymethylation in hippocampus related to neuroinflammation-induced depression-like behaviors in mice[J]. J Affect Disord, 2023, 323: 723-730.
[53]	Vallée A. Neuroinflammation in schizophrenia: the key role of the WNT/β-catenin pathway[J]. Int J Mol Sci, 2022, 23(5): 2810.
[54]	Sebo D J, Ali I, Fetsko A R, et al. Activation of Wnt/β-catenin in neural progenitor cells regulates blood-brain barrier development and promotes neuroinflammation[J]. Sci Rep, 2025, 15: 3496.