王薇,聂昭雯,刘忠纯

• 1:武汉大学人民医院精神卫生中心
• 2:武汉大学泰康生命医学中心

摘要(Abstract)：

快感缺失是抑郁症的核心症状之一，也是抑郁症治疗中的难点，是抑郁症患者出现病程长、生活质量大幅下降、社会功能严重受损的重要预测因子之一。当前国内外对抑郁症快感缺失表型的研究为探索其发生发展机制提供了重要信息，但仍未建立一个完整可靠的病因网络，这使得研发针对性的靶向治疗方案受到局限。因此，探索抑郁症快感缺失表型的病因对临床治疗具有重要的意义。现对既往有关抑郁症快感缺失的文献进行总结，从社会心理因素、生理生化因素、脑影像及神经环路与基因遗传等方面介绍抑郁症快感缺失的发病机制研究进展。

关键词(KeyWords)： 抑郁症;快感缺失;发病机制;神经环路;基因遗传

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金联合基金重点项目（No.U21A20364）;; 国家重点研发计划（No.2018YFC1314600)

作者(Author): 王薇,聂昭雯,刘忠纯

DOI: 10.16780/j.cnki.sjssgncj.20221120

参考文献(References)：

• [1]孙思琦,陈国鹏,周恩奇,等.衰老对应激前后小鼠抑郁及焦虑样行为的影响[J].神经损伤与功能重建, 2022, 17(1):4-8.
• [2] Banica I, Schell SE, Racine SE, et al. Associations between different facets of anhedonia and neural response to monetary, social, and food reward in emerging adults[J]. Biol Psychol, 2022, 172:108363.
• [3] Lu S, Wu C, Jia L, et al. Increased plasma levels of IL-6 are associated with striatal structural atrophy in major depressive disorder patients with anhedonia[J]. Front Psychiatry, 2022, 13:1016735.
• [4] H?flich A, Michenthaler P, Kasper S, et al. Circuit Mechanisms of Reward, Anhedonia, and Depression[J]. Int J Neuropsychopharmacol,2019, 22(2):105-118.
• [5] Watanabe K, Fujimoto S, Marumoto T, et al. Therapeutic Potential of Vortioxetine for Anhedonia-Like Symptoms in Depression:A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan[J].Neuropsychiatr Dis Treat, 2022, 18:363-373.
• [6] Costi S, Morris L S, Collins A, et al. Peripheral immune cell reactivity and neural response to reward in patients with depression and anhedonia[J]. Transl Psychiatry, 2021, 11(1):565.
• [7] Langlois LD, Berman RY, Shepard RD, et al. Potentiation of glutamatergic synaptic transmission onto lateral habenula neurons following early life stress and intravenous morphine self-administration in rats[J]. Addict Biol, 2022, 27(1);e13064.
• [8] Bolton J L, Molet J, Regev L, et al. Anhedonia Following Early-Life Adversity Involves Aberrant Interaction of Reward and Anxiety Circuits and Is Reversed by Partial Silencing of Amygdala Corticotropin-Releasing Hormone Gene[J]. Biol Psychiatry, 2018, 83(2):137-147.
• [9] Novick AM, Levandowski ML, Laumann LE, et al. The effects of early life stress on reward processing[J]. J Psychiatr Res, 2018, 101:80-103.
• [10] Dodell-Feder D, Shovestul B, Woodyatt J, et al. Social anhedonia,social networks, and psychotic-like experiences:A test of social deafferentation[J]. Psychiatry Res, 2020, 284:112682.
• [11] Jawad MY, Di Vincenzo JD, Badulescu S, et al. The therapeutic role of ketamine and esketamine in treating psychopathological domains of depression[J]. Neuropharmacology, 2023, 223:109299.
• [12] Bloomfield-Clagett B, Greenstein DK, Kush JM, et al. Predictors of suicidal ideation trajectories in the Sequenced Treatment Alternatives to Relieve Depression(STAR*D)study[J]. J Psychiatr Res, 2022, 148:9-13.
• [13] Ducasse D, Loas G, Dassa D, et al. Anhedonia is associated with suicidal ideation independently of depression:A meta-analysis[J]. Depress Anxiety, 2018, 35(5):382-392.
• [14] Fleshner M, Frank M, Maier SF. Danger Signals and Inflammasomes:Stress-Evoked Sterile Inflammation in Mood Disorders[J].Neuropsychopharmacology, 2017, 42(1):36-45.
• [15] Felger JC. Imaging the Role of Inflammation in Mood and Anxiety-related Disorders[J]. Curr Neuropharmacol, 2018, 16(5):533-558.
• [16] Bekhbat M, Treadway MT, Felger JC. Inflammation as a Pathophysiologic Pathway to Anhedonia:Mechanisms and Therapeutic Implications[J]. Curr Top Behav Neurosci, 2022, 58:397-419.
• [17] Lee CH, Giuliani F. The Role of Inflammation in Depression and Fatigue[J]. Front Immunol, 2019, 10:1696.
• [18] Duque-Wilckens N, Teis R, Sarno E, et al. Early life adversity drives sex-specific anhedonia and meningeal immune gene expression through mast cell activation[J]. Brain Behav Immun, 2022, 103:73-84.
• [19] Cuomo-Haymour N, Sigrist H, Ineichen C, et al. Evidence for Effects of Extracellular Vesicles on Physical, Inflammatory, Transcriptome and Reward Behaviour Status in Mice[J]. Int J Mol Sci, 2022, 23(3):1028.
• [20] Lucido MJ, Bekhbat M, Goldsmith DR, et al. Aiding and Abetting Anhedonia:Impact of Inflammation on the Brain and Pharmacological Implications[J]. Pharmacol Rev, 2021, 73(3):1084-1117.
• [21] Bekhbat M, Li Z, Mehta ND, et al. 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):4113-4121.
• [22] Stanton CH, Holmes AJ, Chang SWC, et al. From Stress to Anhedonia:Molecular Processes through Functional Circuits[J]. Trends Neurosci, 2019, 42(1):23-42.
• [23] Ducasse D, Dubois J, Jaussent I, et al. Association between anhedonia and suicidal events in patients with mood disorders:A 3-year prospective study[J]. Depress Anxiety, 2021, 38(1):17-27.
• [24] Buchel C, Miedl S, Sprenger C. Hedonic processing in humans is mediated by an opioidergic mechanism in a mesocorticolimbic system[J].Elife, 2018, 7:e39648.
• [25] Eikemo M, Lobmaier PP, Pedersen ML, et al. Intact responses to non-drug rewards in long-term opioid maintenance treatment[J].Neuropsychopharmacology, 2019, 44(8):1456-1463.
• [26] Krystal AD, Pizzagalli DA, Smoski M, et al. A randomized proof-of-mechanism trial applying the‘fast-fail’approach to evaluatingκ-opioid antagonism as a treatment for anhedonia[J]. Nat Med, 2020, 26(5):760-768.
• [27] Grigsby KB, Childs TE, Booth FW. The role of nucleus accumbens CREB attenuation in rescuing low voluntary running behavior in female rats[J]. J Neurosci Res, 2020, 98(11):2302-2316.
• [28] Arnsten AFT, Joyce MKP, Roberts AC. The Aversive Lens:Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion[J]. Neurosci Biobehav Rev, 2023, 145:105000.
• [29] Husain M, Roiser JP. Neuroscience of apathy and anhedonia:a transdiagnostic approach[J]. Nat Rev Neurosci, 2018, 19(8):470-484.
• [30] Schaub A-C, Kirschner M, Schweinfurth N, et al. Neural mapping of anhedonia across psychiatric diagnoses:A transdiagnostic neuroimaging analysis[J]. Neuroimage Clin, 2021, 32:102825.
• [31] Zhu X, Ward J, Cullen B, et al. Phenotypic and genetic associations between anhedonia and brain structure in UK Biobank[J]. Transl Psychiatry, 2021, 11(1):395.
• [32] Coloigner J, Batail J-M, Commowick O, et al. White matter abnormalities in depression:A categorical and phenotypic diffusion MRI study[J]. Neuroimage Clin, 2019, 22:101710.
• [33] Petrie DJ, Knapp KS, Freet CS, et al. Prefrontal cortical response to natural rewards and self-reported anhedonia are associated with greater craving among recently withdrawn patients in residential treatment for opioid use disorder[J]. Brain Res Bull, 2022, 190:32-41.
• [34] Huhn AS, Brooner RK, Sweeney MM, et al. The association of prefrontal cortex response during a natural reward cue-reactivity paradigm,anhedonia, and demoralization in persons maintained on methadone[J].Addict Behav, 2021, 113:106673.
• [35] Seidemann R, Duek O, Jia R, et al. The Reward System and Post-Traumatic Stress Disorder:Does Trauma Affect the Way We Interact With Positive Stimuli[J]? Chronic Stress, 2021, 5:247054702199600.
• [36] Saha R, Shrivastava K, Jing L, et al. Perturbation of GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Induces Trans-regional Metaplasticity at the Medial Prefrontal Cortex[J]. Cereb Cortex, 2018, 28(1):395-410.
• [37] Green IW, Pizzagalli DA, Admon R, et al. Anhedonia modulates the effects of positive mood induction on reward-related brain activation[J].NeuroImage, 2019, 193:115-125.
• [38] Macoveanu J, Meluken I, Chase HW, et al. Reduced frontostriatal response to expected value and reward prediction error in remitted monozygotic twins with mood disorders and their unaffected high-risk co-twins[J]. Psychol Med, 2021, 51(10):1637-1646.
• [39] Ward J, Lyall LM, Bethlehem RAI, et al. Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders,and polygenic association with brain structure[J]. Transl Psychiatry, 2019, 9(1):327.
• [40] Ren H, Fabbri C, Uher R, et al. Genes associated with anhedonia:a new analysis in a large clinical trial(GENDEP)[J]. Transl Psychiatry,2018, 8(1):150.
• [41] Pain O, Dudbridge F, Cardno A G, et al. Genome-wide analysis of adolescent psychotic-like experiences shows genetic overlap with psychiatric disorders[J]. Am J Med Genet B Neuropsychiatr Genet, 2018,177(4):416-425.
• [42] Williams AV, Pe?a CJ, Ramos-Maciel S, et al. Comparative Transcriptional Analyses in the Nucleus Accumbens Identifies RGS2 as a Key Mediator of Depression-Related Behavior[J]. Biol Psychiatry, 2022,92(12):942-951.
• [43] Wu Y, Wei Z, Li Y, et al. Perturbation of Ephrin Receptor Signaling and Glutamatergic Transmission in the Hypothalamus in Depression Using Proteomics Integrated With Metabolomics[J]. Front Neurosci, 2019, 13:1359.
• [44] Koeppen J, Nguyen AQ, Nikolakopoulou AM, et al. Functional Consequences of Synapse Remodeling Following Astrocyte-Specific Regulation of Ephrin-B1 in the Adult Hippocampus[J]. J Neurosci, 2018,38(25):5710-5726.
• [45] Shevelkin AV, Terrillion CE, Hasegawa Y, et al. Astrocyte DISC1contributes to cognitive function in a brain region-dependent manner[J].Hum Mol Genet, 2020, 29(17):2936-2950.
• [46] Forrester SY, Jahan N. Depression Onset in Long-term Adolescent Cannabinoid Use:A Neurobiological Review[J]. Cureus, 2020, 12(4):e7759.
• [47] Rutten-Jacobs LCA, Tozer DJ, Duering M, et al. Genetic Study of White Matter Integrity in UK Biobank(N=8448)and the Overlap With Stroke, Depression, and Dementia[J]. Stroke, 2018, 49(6):1340-1347.
• [48] Kakeda S, Watanabe K, Katsuki A, et al. Genetic effects on white matter integrity in drug-naive patients with major depressive disorder:a diffusion tensor imaging study of 17 genetic loci associated with depressive symptoms[J]. Neuropsychiatr Dis Treat, 2019, 15:375-383.