抑郁症神经生理机制研究进展
Progress in Neurophysiological Mechanisms of Depression
DOI: 10.12677/AP.2021.117196, PDF,    科研立项经费支持
作者: 卢 玺, 吴 燕:成都医学院,四川 成都
关键词: 抑郁症神经生理机制下丘脑HPADepression Neurophysiological Mechanisms Hypothalamic HPA
摘要: 抑郁症是一种常见的精神障碍疾病,是以显著而持久的情绪低落为主要特征的精神障碍。其主要表现是以情感低落、思维迟缓和精神运动性抑制三大症状为基本特征。部分抑郁症患者伴有严重的焦虑症状,出现自杀观念及行为,给全球带来沉重的疾病负担。抑郁症的病因十分复杂,迄今仍未完全阐明。近年来,国内外对抑郁症的研究从未停止,在抑郁症发病机制的研究上取得了重要进展。文本文通过对以往基因遗传学研究,脑结构和功能研究,神经炎症以及神经内分泌的研究进行阐述,以拓展对抑郁症的认识。
Abstract: Depression is a common mental disorder that is characterized by significant and persistent de-pressed mood. It is characterized by low emotion, slow thinking and psychomotor inhibition. Some patients with depression have serious anxiety symptoms, suicidal ideas and behaviors, which bring heavy disease burden to the world. The etiology of depression is very complex and has not yet been fully elucidated. In recent years, the research on depression has never stopped at home and abroad, and important progress has been made in the pathogenesis of depression. In this paper, the past genetic studies, brain structure and function studies, neuroinflammation and neuroendocrine studies are briefly described in order to expand the understanding of depression.
文章引用:卢玺, 吴燕 (2021). 抑郁症神经生理机制研究进展. 心理学进展, 11(7), 1759-1767. https://doi.org/10.12677/AP.2021.117196

参考文献

[1] 龚绍麟(2010). 抑郁症(pp. 158-160). 北京: 人民卫生出版社.
[2] 聂容荣, 莫碧文, 曾伟星, 等(2017). 针灸对脑卒中后抑郁症患者血清5-HT、NE和BDNF水平的影响. 西部医学, 29(6), 808-812+816.
[3] 汪道文, 何健(2010). 唾液皮质醇检测在抑郁症诊断中的应用探讨. 硕士学位论文, 北京: 北京协和医学院.
[4] 于璟(2013). 甲状腺功能与抑郁障碍关系的研究. 博士学位论文, 大连: 大连理工大学.
[5] 郁仁强, 张志伟, 吕发金, 等(2019). 静息态功能磁共振研究未治疗首次发作重症抑郁症患者默认网络功能连接. 西部医学, 31(4), 608-613.
[6] Amin, N., Belonogova, N. M., Jovanova, O. et al. (2017a). Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations. Biological Psychiatry, 81, 702-707.[CrossRef] [PubMed]
[7] Amin, N., Jovanova, O., Adams, H. H. et al. (2017b). Exome-Sequencing in a Large Population-Based Study Reveals a Rare Asn396ser Variant in the LIPG Gene Associated with Depressive Symptoms. Molecular Psychiatry, 22, 537-543.[CrossRef] [PubMed]
[8] Amore, M., Innamorati, M., Costi, S., Sher, L., Girardi, P., & Pompili, M. (2012). Partial Androgen Deficiency, Depression, and Testosterone Supplementation in Aging Men. International Journal of Endocrinology, 2012, Article ID: 280724.[CrossRef] [PubMed]
[9] Arnone, D. (2019). Functional MRI Findings, Pharmacological Treatment in Major Depression and Clinical Response. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 91, 28-37.[CrossRef] [PubMed]
[10] Azadmarzabadi, E., Haghighatfard, A., & Mohammadi, A. (2018). Low Resilience to Stress Is Associated with Candidate Gene Expression Alterations in the Dopaminergic Signaling Pathway. Psychogeriatrics, 18, 190-201.[CrossRef] [PubMed]
[11] Barden, N. (2004). Implication of the Hypothalamic-Pituitary-Adrenal Axis in the Physiopathology of Depression. Journal of Psychiatry and Neuroscience, 29, 185-193.
[12] Bloch, M., Azem, F., Aharonov, I., Ben Avi, I., Yagil, Y., Schreiber, S., Weizman, A. et al. (2011). GnRH-Agonist Induced Depressive and Anxiety Symptoms during in Vitro Fertilization-Embryo Transfer Cycles. Fertility and Sterility, 95, 307-309.[CrossRef] [PubMed]
[13] Bobinska, K., Galecka, E., Szemraj, J., Galecki, P., & Talarowska, M. (2017). Is There a Link between TNF Gene Expression and Cognitive Deficits in Depression? Acta Biochimica Polonica, 64, 65-73.[CrossRef] [PubMed]
[14] Bortolato, B., Carvalho, A. F., Soczynska, J. K., Perini, G. I., & McIntyre, R. S. (2015). The Involvement of TNF-α in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments. Current Neuropharmacology, 13, 558-576.[CrossRef
[15] Bustamante, A. C., Aiello, A. E., Guffanti, G. et al. (2018). Fkbp5 DNA Methylation Does Not Mediate the Association between Childhood Maltreatment and Depression Symptom Severity in the Detroit Neighborhood Health Study. Journal of Psychiatric Research, 96, 39-48.[CrossRef] [PubMed]
[16] Cheng, Y., Desse, S., Martinez, A., Worthen, R. J., Jope, R. S., & Beurel, E. (2018). TNFα Disrupts Blood Brain Barrier Integrity to Maintain Prolonged Depressive-Like Behavior in Mice. Brain, Behavior, and Immunity, 69, 556-567.[CrossRef] [PubMed]
[17] Cobb, J. A., O’Neill, K., Milner, J., Mahajan, G. J., Lawrence, T. J., May, W. L., Miguel-Hidalgo, J., Rajkowska, G., & Stockmeier, C. A. (2016). Density of GFAP-Immunoreactive Astrocytes Is Decreased in Left Hip-Pocampi in Major Depressive Disorder. Neuroscience, 316, 209-220.[CrossRef] [PubMed]
[18] Colla, M., Kronenberg, G., Deuschle, M., Meichel, K., Hagen, T., Bohrer, M., & Heuser, I. (2007). Hippocampal Volume Reduction and HPA-System Activity in Major Depression. Journal of Psychiatric Research, 41, 553-560.[CrossRef] [PubMed]
[19] Fischer, S., Gardini, E. S., Haas, F. et al. (2018). Polymor-phisms in Genes Related to the Hypothalamic-Pituitary-Adrenal Axis and Antidepressant Response-Systematic Review. Neuroscience & Biobehavioral Reviews, 96, 182-196.[CrossRef] [PubMed]
[20] Ge, J. F., Qi, C. C., & Zhou, J. N. (2013). Imbalance of Leptin Pathway and Hypothalamus Synaptic Plasticity Markers Are Associated with Stress-Induced Depression in Rats. Behavioural Brain Research, 249, 38-43.[CrossRef] [PubMed]
[21] Gillentine, M. A., Lozoya, R., Yin, J. et al. (2018). CHRNA7 Copy Number Gains Are Enriched in Adolescents with Major Depressive and Anxiety Disorders. The Journal of Affective Disorders, 239, 247-252.[CrossRef] [PubMed]
[22] Girotti, M., Donegan, J. J., & Morilak, D. A. (2013). Influence of Hypothalamic IL-6/gp130 Receptor Signaling on the HPA Axis Response to Chronic Stress. Psychoneuroendocrinology, 38, 1158-1169.[CrossRef] [PubMed]
[23] Gong, Q., & He, Y. (2015). Depression, Neuroimaging and Connectomics: A Selective Overview. Biological Psychiatry, 77, 223-235.[CrossRef] [PubMed]
[24] Hall, L. S., Adams, M. J., Arnau-Soler, A. et al. (2018). Ge-nome-Wide Meta-Analyses of Stratified Depression in Generation Scotland and UK Biobank. Translational Psychiatry, 8, 9.[CrossRef] [PubMed]
[25] Han, K. M. et al. (2014). Cortical Thickness, Cortical and Subcortical Volume, and White Matter Integrity in Patients with Their First Episode of Major Depression. The Journal of Affective Disorders, 155, 42-48.[CrossRef] [PubMed]
[26] Holsboer, F., & Ising, M. (2008). Central CRH System in Depression and Anxiety—Evidence from Clinical Studies with CRH1 Receptor Antagonists. European Journal of Pharmacology, 583, 350-357.[CrossRef] [PubMed]
[27] Howard, D. M., Adams, M. J., Shirali, M. et al. (2018). Ge-nome-Wide Association Study of Depression Phenotypes in UK Biobank Identifies Variants in Excitatory Synaptic Pathways. Nature Communications, 9, 1470.
[28] Jiang, J. et al. (2017). Microstructural Brain Abnormalities in Medication-Free Patients with Major Depressive Disorder: A Systematic Review and Meta-Analysis of Diffusion Tensor Imaging. Journal of Psychiatry & Neuroscience, 42, 150-163.[CrossRef] [PubMed]
[29] Jie, N. F. et al. (2015). Discriminating Bipolar Disorder from Major Depression Based on SVM-FoBa: Efficient Feature Selection with Multimodal Brain Imaging Data. IEEE Transactions on Autonomous Mental Development, 7, 320-331.[CrossRef
[30] Juarez-Orozco, L. E., Kurtys, E., Dierckx, R. A., Morigu-chi-Jeckel, C. M., Doorduin, J., Li, H., Sagar, A. P., & Keri, S. (2018). Translocator Protein (18 kDa TSPO) Binding, a Marker of Microglia, Is Reduced in Major Depression during Cognitive-Behavioral Therapy. The Journal of Cerebral Blood Flow & Metabolism, 83, 1-7.[CrossRef] [PubMed]
[31] Kakeda, S., Watanabe, K., Katsuki, A., Sugimoto, K., Igata, N., Ueda, I., Igata, R., Abe, O., Yoshimura, R., & Korogi, Y. (2018). Relationship between Interleukin (IL)-6 and Brain Morphology in Drug-Naive, First-Episode Major Depressive Disorder Using Surface-Based Morphometry. Scientific Reports, 8, Article No. 10054.[CrossRef] [PubMed]
[32] Kambeitz, J. et al. (2017). Detecting Neuroimaging Biomarkers for Depression: A Meta-Analysis of Multivariate Pattern Recognition Studies. Biological Psychiatry, 82, 330-338.[CrossRef] [PubMed]
[33] Kvetny, J., Ellervik, C., & Bech, P. (2015). Is Suppressed Thyroid-Stimulating Hormone (TSH) Associated with Subclinical Depression in the Danish General Suburban Population Study? Nordic Journal of Psychiatry, 69, 282-286.[CrossRef] [PubMed]
[34] Leng, L., Zhuang, K., Liu, Z., Huang, C., Gao, Y., Chen, G., Lin, H., Hu, Y., Wu, D., Shi, M., Xie, W., Sun, H., Shao, Z., Li, H., Zhang, K., Mo, W., Huang, T. Y., Xue, M., Yuan, Z., Zhang, X., Bu, G., Xu, H., Xu, Q., & Zhang, J. (2018). Menin Deficiency Leads to Depressive-Like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation. Neuron, 100, 551-563.E7.[CrossRef] [PubMed]
[35] Li, M., Li, C., Yu, H., Cai, X., Shen, X., Sun, X., Wang, J., Zhang, Y., & Wang, C. (2017). Lentivirus-Mediated Interleukin-1beta (IL-1beta) Knock-Down in the Hippocampus Alleviates Lipopolysac-Charide (LPS)-Induced Memory Deficits and Anxiety- and Depression-Like Behaviors in Mice. Journal of Neuroinflammation, 14, 190.[CrossRef] [PubMed]
[36] Li, X., Luo, Z., Gu, C. et al. (2018). Common Variants on 6q16.2, 12q24.31 and 16p13.3 Are Associated with Major Depressive Disorder. Neuropsychopharmacology, 43, 2146-2153.[CrossRef] [PubMed]
[37] Mao, R., Zhang, C., Chen, J., Zhao, G., Zhou, R., Wang, F. et al. (2018). Different Levels of Pro- and Anti-Inflammatory Cytokines in Patients with Unipolar and Bipolar Depression. Journal of Affective Disorders, 237, 65-72.[CrossRef] [PubMed]
[38] Marchand, W. R. (2010). Cortico-Basal Ganglia Circuitry: A Review of Key Research and Implications for Functional Connectivity Studies of Mood and Anxiety Disorders. Brain Structure and Function, 215, 73-96.[CrossRef] [PubMed]
[39] McGuffin, P., Cohen, S., & Knight, J. (2007). Homing in on Depression Genes. The American Journal of Psychiatry, 164, 195-197.[CrossRef] [PubMed]
[40] Monai, H., & Hirase, H. (2018). Astrocytes as a Target of Transcranial Direct Current Stimulation (tDCS) to Treat Depression. Neuroscience Research, 126, 15-21.[CrossRef] [PubMed]
[41] Nemeroff, C. B., & Vale, W. W. (2005). The Neurobiology of Depression: Inroads to Treatment and New Drug Discovery. Journal of Clinical Psychiatry, 66, 5-13.
[42] Ng, A., Tam, W. W., Zhang, M. W., Ho, C. S., Husain, S. F., McIntyre, R. S., & Ho, R. C. (2018). IL-1beta, IL-6, TNF-Alpha and CRP in Elderly Patients with Depression or Alzheimer’s Disease: Systematic Review and Meta-Analysis. Scientific Reports, 8, Article No. 12050.[CrossRef] [PubMed]
[43] Ostergaard, S. D., Jensen, S. O., & Bech, P. (2011). The Heterogeneity of the Depressive Syndrome: When Numbers Get Serious. Acta Psychiatrica Scandinavica, 124, 495-496.[CrossRef] [PubMed]
[44] Park, H. J., Shim, H. S., An, K., Starkweather, A., Kim, K. S., & Shim, I. (2015). IL-4 Inhibits IL-1beta-Induced Depressive-Like Behavior and Central Neurotransmitter Alterations. Mediators of Inflammation, 2015, Article ID: 941413.[CrossRef] [PubMed]
[45] Park, H. S., Han, A., Yeo, H. L., Park, M. J., You, M. J., Choi, H. J., Hong, C. W., Lee, S. H., Kim, S. H., Kim, B., & Kwon, M. S. (2017). Chronic High Dose of Captopril Induces Depressive-Like Behaviors in Mice: Possible Mechanism of Regulatory T Cell in Depression. Oncotarget, 8, 72528-72543.[CrossRef] [PubMed]
[46] Peterson, R. E., Cai, N., Bigdeli, T. B. et al. (2017). The Genetic Architecture of Major Depressive Disorder in Han Chinese Women. JAMA Psychiatry, 74, 162-168.[CrossRef] [PubMed]
[47] Pirnia, T. et al. (2016). Electroconvulsive Therapy and Structural Neuroplasticity in Neocortical, Limbic and Paralimbic Cortex. Translational Psychiatry, 6, e832.[CrossRef] [PubMed]
[48] Pirooznia, M., Wang, T., Avramopoulos, D. et al. (2016). High-Throughput Sequencing of the Synaptome in Major Depressive Disorder. Molecular Psychiatry, 21, 650-655.[CrossRef] [PubMed]
[49] Plaza, A., Garcia-Esteve, L., Ascaso, C., Navarro, P., Gelabert, E., Halperin, I. et al. (2010). Childhood Sexual Abuse and Hypothalamus-Pituitary-Thyroid Axis in Postpartum Major Depression. Journal of Affective Disorders, 122, 159-163.[CrossRef] [PubMed]
[50] Qiu, M. et al. (2018). Aberrant Neural Activity in Patients with Bipolar Depressive Disorder Distinguishing to the Unipolar Depressive Disorder: A Resting-State Functional Magnetic Resonance Imaging Study. Frontiers in Psychiatry, 9, 238.[CrossRef] [PubMed]
[51] Rasgon, N. L., Altshuler, L. L., & Fairbanks, L. (2001). Estrogen-Replacement Therapy for Depression. American Journal of Psychiatry, 158, 1738-1738.[CrossRef] [PubMed]
[52] Schatzberg, A. F. (2015). Anna-Monika Award Lecture, DGPPN Kongress, 2013: The Role of the Hypothalamic-Pituitary- Adrenal (HPA) Axis in the Pathogenesis of Psychotic Major Depression. The World Journal of Biological Psychiatry, 16, 2-11.[CrossRef] [PubMed]
[53] Sheline, Y. I. et al. (2010). Resting-State Functional MRI in Depression Unmasks Increased Connectivity between Networks via the Dorsal Nexus. Proceedings of the National Academy of Sciences of the United States of America, 107, 11020-11025.[CrossRef] [PubMed]
[54] Sokero, T. P., Melartin, T. K., Rytsala, H. J. et al. (2005). Prospective Study of Risk Factors for Attempted Suicide among Patients with DSM-IV Major Depressive Disorder. British Journal of Psychiatry, 186, 314-318.[CrossRef] [PubMed]
[55] Su, K. P. (2015). Nutrition, Psychoneuroimmunology and Depression: The Therapeutic Implications of Omega-3 Fatty Acids in Interferon-Alpha-Induced Depression. BioMedicine, 5, 21.[CrossRef] [PubMed]
[56] Su, K. P., Lai, H. C., Peng, C. Y., Su, W. P., Chang, J. P., & Pariante, C. M. (2019). Interferon-Alpha-Induced Depression: Comparisons between Early- and Late-Onset Subgroups and with Patients with Major Depressive Disorder. Brain, Behavior, and Immunity, 80, 512-518.[CrossRef] [PubMed]
[57] Suh, J. S. et al. (2019). Cortical Thickness in Major Depressive Disorder: A Systematic Review and Meta-Analysis. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 88, 287-302.[CrossRef] [PubMed]
[58] Sullivan, P. F., Neale, M. C., & Kendler, K. S. (2000). Genetic Epidemiology of Major Depression: Review and Meta-Analysis. The American Journal of Psychiatry, 157, 1552-1562.[CrossRef] [PubMed]
[59] Tang, S. et al. (2018). Abnormal Amygdala Resting-State Functional Connectivity in Adults and Adolescents with Major Depressive Disorder: A Comparative Meta-Analysis. EBioMedicine, 36, 436-445.[CrossRef] [PubMed]
[60] Tekin, S., & Cummings, J. L. (2002). Frontal-Subcortical Neuronal Circuits and Clinical Neuropsychiatry: An Update. Journal of Psychosomatic Research, 53, 647-654.[CrossRef
[61] Toben, C., & Baune, B. T. (2015). An Act of Balance between Adaptive and Maladaptive Immunity in Depression: A Role for T Lymphocytes. Journal of Neuroimmune Pharmacology, 10, 595-609.[CrossRef] [PubMed]
[62] Tong, L., Gong, Y., Wang, P., Hu, W., Wang, J., Chen, Z., Zhang, W., & Huang, C. (2017). Microglia Loss Contributes to the Development of Major Depression Induced by Different Types of Chronic Stresses. Neurochemical Research, 42, 2698-2711.[CrossRef] [PubMed]
[63] Van de Ven, A. C., Muntjewerff, J. W., Netea-Maier, R. T., de Vegt, F., Ross, H. A., Sweep, F. C. G. J., Janzing, J. G. E. et al. (2012). Association between Thyroid Function, Thyroid Autoimmunity, and State and Trait Factors of Depression. Acta Psychiatrica Scandinavica, 126, 377-384.[CrossRef] [PubMed]
[64] Van Der Auwera, S., Peyrot, W. J., Milaneschi, Y. et al. (2018). Genome-Wide Gene-Environment Interaction in Depression: A Systematic Evaluation of Candidate Genes: The Childhood Trauma Working-Group of PGC-MDD. Neuropsychiatric Genetics, Part B of the American Journal of Medical Genetics, 177, 40-49.[CrossRef] [PubMed]
[65] Wegener, I. et al. (2015). Changes of Explicitly and Implicitly Measured Self-Esteem in the Treatment of Major Depression: Evidence for Implicit Self-Esteem Compensation. Comprehensive Psychiatry, 58, 57-67.[CrossRef] [PubMed]
[66] Wise, T. et al. (2016). Voxel-Based Meta-Analytical Evidence of Structural Disconnectivity in Major Depression and Bipolar Disorder. Biological Psychiatry, 79, 293-302.[CrossRef] [PubMed]
[67] Wohleb, E. S., Terwilliger, R., Duman, C. H., & Duman, R. S. (2018). Stress-Induced Neuronal Colony Stimulating Factor 1 Provokes Microglia-Mediated Neuronal Remodeling and Depressive-Like Behavior. Biological Psychiatry, 83, 38-49.[CrossRef] [PubMed]
[68] Wray, N. R., Ripke, S., Mattheisen, M. et al. (2018). Genome-Wide Association Analyses Identify 44 Risk Variants and Refine the Genetic Architecture of Major Depression. Nature Genetics, 50, 668-681.[CrossRef] [PubMed]
[69] Yu, C., Baune, B. T., Wong, M. L. et al. (2017). Investigation of Copy Number Variation in Subjects with Major Depression Based on Whole-Genome Sequencing Data. The Journal of Affective Disorders, 220, 38-42.[CrossRef] [PubMed]
[70] Yu, C., Baune, B. T., Wong, M. L. et al. (2018). Investigation of Short Tandem Repeats in Major Depression Using Whole-Genome Sequencing Data. The Journal of Affective Disorders, 232, 305-309.[CrossRef] [PubMed]
[71] Zhang, F. F. et al. (2018). Brain Structure Alterations in Depression: Psychoradiological Evidence. CNS Neuroscience & Therapeutics, 24, 994-1003.[CrossRef] [PubMed]
[72] Zhang, H. et al. (2019). Intrinsic Gray-Matter Connectivity of the Brain in Major Depressive Disorder. The Journal of Affective Disorders, 251, 78-85.[CrossRef] [PubMed]
[73] Zhang, K. et al. (2016). Molecular, Functional, and Structural Imaging of Major Depressive Disorder. Neuroscience Bulletin, 32, 273-285.[CrossRef] [PubMed]