抑郁症性别差异的生物学机制研究进展
Research Progress on the Biological Mechanisms of Gender Differences in Depression
DOI: 10.12677/ijpn.2026.151001, PDF,   
作者: 储琳娜, 贾艳滨:暨南大学附属第一医院精神医学科,广东 广州
关键词: 抑郁障碍性别差异遗传性激素脑神经环路Major Depressive Disorder Sex Difference Genetics Sex Hormones Brain Neural Circuit
摘要: 抑郁症是一种以情绪低落为主要临床特征的精神疾病,具有高发病率、高自杀率和高致残率的临床特点。抑郁症的患病率、症状表现和治疗反应存在着显著的性别差异,因此揭示其中的生理病理机制对于抑郁症的预防和治疗意义重大。本文从遗传、性激素和脑神经环路等角度综述了抑郁症在发病、治疗及预后中性别差异的生物学机制,并加以探讨。
Abstract: Major depressive disorder (MDD) is a group of mental diseases with low mood as the main clinical feature, which is characterized by high morbidity, high suicide rate, and high disability rate. There are marked sex differences in the prevalence, symptom manifestations and treatment response for major depression, and it is of great significance to reveal the mechanism of gender differences in MDD. This review aims to summarize the neurobiological mechanism of gender difference in MDD from the aspects of genetics, sex hormones and brain neural circuits, so as to provide ideas for the pathogenesis and treatment of MDD.
文章引用:储琳娜, 贾艳滨. 抑郁症性别差异的生物学机制研究进展[J]. 国际神经精神科学杂志, 2026, 15(1): 1-9. https://doi.org/10.12677/ijpn.2026.151001

参考文献

[1] Shorey, S., Ng, E.D. and Wong, C.H.J. (2022) Global Prevalence of Depression and Elevated Depressive Symptoms among Adolescents: A Systematic Review and Meta‐Analysis. British Journal of Clinical Psychology, 61, 287-305. [Google Scholar] [CrossRef] [PubMed]
[2] Estrela, M., Herdeiro, M.T., Ferreira, P.L. and Roque, F. (2020) The Use of Antidepressants, Anxiolytics, Sedatives and Hypnotics in Europe: Focusing on Mental Health Care in Portugal and Prescribing in Older Patients. International Journal of Environmental Research and Public Health, 17, Article 8612. [Google Scholar] [CrossRef] [PubMed]
[3] Salk, R.H., Hyde, J.S. and Abramson, L.Y. (2017) Gender Differences in Depression in Representative National Samples: Meta-Analyses of Diagnoses and Symptoms. Psychological Bulletin, 143, 783-822. [Google Scholar] [CrossRef] [PubMed]
[4] Sramek, J.J., Murphy, M.F. and Cutler, N.R. (2016) Sex Differences in the Psychopharmacological Treatment of Depression. Dialogues in Clinical Neuroscience, 18, 447-457. [Google Scholar] [CrossRef
[5] Kornstein, S.G., Schatzberg, A.F., Thase, M.E., Yonkers, K.A., McCullough, J.P., Keitner, G.I., et al. (2000) Gender Differences in Treatment Response to Sertraline versus Imipramine in Chronic Depression. American Journal of Psychiatry, 157, 1445-1452. [Google Scholar] [CrossRef] [PubMed]
[6] Sullivan, P.F., Neale, M.C. and Kendler, K.S. (2000) Genetic Epidemiology of Major Depression: Review and Meta-Analysis. American Journal of Psychiatry, 157, 1552-1562. [Google Scholar] [CrossRef] [PubMed]
[7] Kendler, K.S., Gatz, M., Gardner, C.O. and Pedersen, N.L. (2006) A Swedish National Twin Study of Lifetime Major Depression. American Journal of Psychiatry, 163, 109-114. [Google Scholar] [CrossRef] [PubMed]
[8] Kendler, K.S., Gardner, C.O., Neale, M.C. and Prescott, C.A. (2001) Genetic Risk Factors for Major Depression in Men and Women: Similar or Different Heritabilities and Same or Partly Distinct Genes? Psychological Medicine, 31, 605-616. [Google Scholar] [CrossRef] [PubMed]
[9] Singer, J.B. (2009) Candidate Gene Association Analysis. In: DiPetrillo, K., Ed., Methods in Molecular Biology, Humana Press, 223-230. [Google Scholar] [CrossRef] [PubMed]
[10] Spinelli, S., Schwandt, M.L., Lindell, S.G., Heilig, M., Suomi, S.J., Higley, J.D., et al. (2012) The Serotonin Transporter Gene Linked Polymorphic Region Is Associated with the Behavioral Response to Repeated Stress Exposure in Infant Rhesus Macaques. Development and Psychopathology, 24, 157-165. [Google Scholar] [CrossRef] [PubMed]
[11] Beaver, K.M., Vaughn, M.G., Wright, J.P. and DeLisi, M. (2012) An Interaction between Perceived Stress and 5HTTLPR Genotype in the Prediction of Stable Depressive Symptomatology. American Journal of Orthopsychiatry, 82, 260-266. [Google Scholar] [CrossRef] [PubMed]
[12] Sjöberg, R.L., Nilsson, K.W., Nordquist, N., Öhrvik, J., Leppert, J., Lindström, L., et al. (2006) Development of Depression: Sex and the Interaction between Environment and a Promoter Polymorphism of the Serotonin Transporter Gene. The International Journal of Neuropsychopharmacology, 9, 443-449. [Google Scholar] [CrossRef] [PubMed]
[13] Wüst, S., Kumsta, R., Treutlein, J., Frank, J., Entringer, S., Schulze, T.G., et al. (2009) Sex-Specific Association between the 5-HTT Gene-Linked Polymorphic Region and Basal Cortisol Secretion. Psychoneuroendocrinology, 34, 972-982. [Google Scholar] [CrossRef] [PubMed]
[14] Sesack, S.R. and Grace, A.A. (2010) Cortico-Basal Ganglia Reward Network: Microcircuitry. Neuropsychopharmacology, 35, 27-47. [Google Scholar] [CrossRef] [PubMed]
[15] Beninger, R.J. and Beninger, R. (1998) Dopamine D1-Like Receptors and Reward-Related Incentive Learning. Neuroscience & Biobehavioral Reviews, 22, 335-345. [Google Scholar] [CrossRef] [PubMed]
[16] Beaulieu, J. and Gainetdinov, R.R. (2011) The Physiology, Signaling, and Pharmacology of Dopamine Receptors. Pharmacological Reviews, 63, 182-217. [Google Scholar] [CrossRef] [PubMed]
[17] Wang, M., Lee, F.J.S. and Liu, F. (2008) Dopamine Receptor Interacting Proteins (Drips) of Dopamine D1-Like Receptors in the Central Nervous System. Molecules and Cells, 25, 149-157. [Google Scholar] [CrossRef] [PubMed]
[18] Pei, L., Li, S., Wang, M., Diwan, M., Anisman, H., Fletcher, P.J., et al. (2010) Uncoupling the Dopamine D1-D2 Receptor Complex Exerts Antidepressant-Like Effects. Nature Medicine, 16, 1393-1395. [Google Scholar] [CrossRef] [PubMed]
[19] Hasbi, A., Nguyen, T., Rahal, H., Manduca, J.D., Miksys, S., Tyndale, R.F., et al. (2020) Sex Difference in Dopamine D1-D2 Receptor Complex Expression and Signaling Affects Depression-and Anxiety-Like Behaviors. Biology of Sex Differences, 11, Article No. 8. [Google Scholar] [CrossRef] [PubMed]
[20] Gray, A.L., Hyde, T.M., Deep-Soboslay, A., Kleinman, J.E. and Sodhi, M.S. (2015) Sex Differences in Glutamate Receptor Gene Expression in Major Depression and Suicide. Molecular Psychiatry, 20, 1057-1068. [Google Scholar] [CrossRef] [PubMed]
[21] Ritter, C., Buchmann, A., Müller, S.T., Volleberg, M., Haynes, M., Ghisleni, C., et al. (2022) Evaluation of Prefrontal Γ-Aminobutyric Acid and Glutamate Levels in Individuals with Major Depressive Disorder Using Proton Magnetic Resonance Spectroscopy. JAMA Psychiatry, 79, 1209-1216. [Google Scholar] [CrossRef] [PubMed]
[22] Hall, L.S., Adams, M.J., Arnau-Soler, A., Clarke, T., Howard, D.M., Zeng, Y., et al. (2018) Genome-Wide Meta-Analyses of Stratified Depression in Generation Scotland and UK Biobank. Translational Psychiatry, 8, Article No. 9. [Google Scholar] [CrossRef] [PubMed]
[23] Dunn, E.C., Sofer, T., Wang, M., Soare, T.W., Gallo, L.C., Gogarten, S.M., et al. (2018) Genome-Wide Association Study of Depressive Symptoms in the Hispanic Community Health Study/Study of Latinos. Journal of Psychiatric Research, 99, 167-176. [Google Scholar] [CrossRef] [PubMed]
[24] Aragam, N., Wang, K. and Pan, Y. (2011) Genome-wide Association Analysis of Gender Differences in Major Depressive Disorder in the Netherlands NESDA and NTR Population-Based Samples. Journal of Affective Disorders, 133, 516-521. [Google Scholar] [CrossRef] [PubMed]
[25] Kang, H., Park, Y., Yoo, K., Kim, K., Kim, E., Kim, J., et al. (2020) Sex Differences in the Genetic Architecture of Depression. Scientific Reports, 10, Article No. 9927. [Google Scholar] [CrossRef] [PubMed]
[26] Grigoriadis, S. and Kennedy, S.H. (2002) Role of Estrogen in the Treatment of Depression. American Journal of Therapeutics, 9, 503-509. [Google Scholar] [CrossRef] [PubMed]
[27] Parker, G. and Brotchie, H. (2010) Gender Differences in Depression. International Review of Psychiatry, 22, 429-436. [Google Scholar] [CrossRef] [PubMed]
[28] Newhouse, P. and Dumas, J. (2015) Estrogen-Cholinergic Interactions: Implications for Cognitive Aging. Hormones and Behavior, 74, 173-185. [Google Scholar] [CrossRef] [PubMed]
[29] Parker, G.B. and Brotchie, H.L. (2004) From Diathesis to Dimorphism: The Biology of Gender Differences in Depression. Journal of Nervous & Mental Disease, 192, 210-216. [Google Scholar] [CrossRef] [PubMed]
[30] Albert, K., Pruessner, J. and Newhouse, P. (2015) Estradiol Levels Modulate Brain Activity and Negative Responses to Psychosocial Stress across the Menstrual Cycle. Psychoneuroendocrinology, 59, 14-24. [Google Scholar] [CrossRef] [PubMed]
[31] Rubinow, D.R., Johnson, S.L., Schmidt, P.J., Girdler, S. and Gaynes, B. (2015) Efficacy of Estradiol in Perimenopausal Depression: so Much Promise and So Few Answers. Depression and Anxiety, 32, 539-549. [Google Scholar] [CrossRef] [PubMed]
[32] Zarrouf, F.A., Artz, S., Griffith, J., Sirbu, C. and Kommor, M. (2009) Testosterone and Depression: Systematic Review and Meta-Analysis. Journal of Psychiatric Practice, 15, 289-305. [Google Scholar] [CrossRef] [PubMed]
[33] Diblasio, C.J., Hammett, J., Malcolm, J.B., et al. (2008) Prevalence and Predictive Factors for the Development of de Novo Psychiatric Illness in Patients Receiving Androgen Deprivation Therapy for Prostate Cancer. The Canadian Journal of Urology, 15, 4249-4256.
[34] Miller, K.K., Perlis, R.H., Papakostas, G.I., Mischoulon, D., Iosifescu, D.V., Brick, D.J., et al. (2009) Low-Dose Transdermal Testosterone Augmentation Therapy Improves Depression Severity in Women. CNS Spectrums, 14, 688-694. [Google Scholar] [CrossRef] [PubMed]
[35] Goldstat, R., Briganti, E., Tran, J., Wolfe, R. and Davis, S.R. (2003) Transdermal Testosterone Therapy Improves Well-Being, Mood, and Sexual Function in Premenopausal Women. Menopause, 10, 390-398. [Google Scholar] [CrossRef] [PubMed]
[36] Bouma, E.M.C., Ormel, J., Verhulst, F.C. and Oldehinkel, A.J. (2008) Stressful Life Events and Depressive Problems in Early Adolescent Boys and Girls: The Influence of Parental Depression, Temperament and Family Environment. Journal of Affective Disorders, 105, 185-193. [Google Scholar] [CrossRef] [PubMed]
[37] Stephens, M.A.C., Mahon, P.B., McCaul, M.E. and Wand, G.S. (2016) Hypothalamic-Pituitary-Adrenal Axis Response to Acute Psychosocial Stress: Effects of Biological Sex and Circulating Sex Hormones. Psychoneuroendocrinology, 66, 47-55. [Google Scholar] [CrossRef] [PubMed]
[38] DeSantis, S.M., Baker, N.L., Back, S.E., Spratt, E., Ciolino, J.D., Moran-Santa Maria, M., et al. (2011) Gender Differences in the Effect of Early Life Trauma on Hypothalamic-Pituitary-Adrenal Axis Functioning. Depression and Anxiety, 28, 383-392. [Google Scholar] [CrossRef] [PubMed]
[39] Kumar, R. and Thompson, E.B. (2005) Gene Regulation by the Glucocorticoid Receptor: Structure: Function Relationship. The Journal of Steroid Biochemistry and Molecular Biology, 94, 383-394. [Google Scholar] [CrossRef] [PubMed]
[40] Trapp, T. and Holsboer, F. (1996) Heterodimerization between Mineralocorticoid and Glucocorticoid Receptors Increases the Functional Diversity of Corticosteroid Action. Trends in Pharmacological Sciences, 17, 145-149. [Google Scholar] [CrossRef] [PubMed]
[41] Medina, A., Seasholtz, A.F., Sharma, V., Burke, S., Bunney, W., Myers, R.M., et al. (2013) Glucocorticoid and Mineralocorticoid Receptor Expression in the Human Hippocampus in Major Depressive Disorder. Journal of Psychiatric Research, 47, 307-314. [Google Scholar] [CrossRef] [PubMed]
[42] Bonapersona, V., Damsteegt, R., Adams, M.L., van Weert, L.T.C.M., Meijer, O.C., Joëls, M., et al. (2019) Sex-Dependent Modulation of Acute Stress Reactivity after Early Life Stress in Mice: Relevance of Mineralocorticoid Receptor Expression. Frontiers in Behavioral Neuroscience, 13, Article No. 181. [Google Scholar] [CrossRef] [PubMed]
[43] Heim, C., Newport, D.J., Mletzko, T., Miller, A.H. and Nemeroff, C.B. (2008) The Link between Childhood Trauma and Depression: Insights from HPA Axis Studies in Humans. Psychoneuroendocrinology, 33, 693-710. [Google Scholar] [CrossRef] [PubMed]
[44] Yang, X., Peng, Z., Ma, X., Meng, Y., Li, M., Zhang, J., et al. (2017) Sex Differences in the Clinical Characteristics and Brain Gray Matter Volume Alterations in Unmedicated Patients with Major Depressive Disorder. Scientific Reports, 7, Article No. 2515. [Google Scholar] [CrossRef] [PubMed]
[45] Kong, L., Chen, K., Womer, F., Jiang, W., Luo, X., Driesen, N., et al. (2013) Sex Differences of Gray Matter Morphology in Cortico-Limbic-Striatal Neural System in Major Depressive Disorder. Journal of Psychiatric Research, 47, 733-739. [Google Scholar] [CrossRef] [PubMed]
[46] Ancelin, M., Carrière, I., Artero, S., Maller, J., Meslin, C., Ritchie, K., et al. (2019) Lifetime Major Depression and Grey-Matter Volume. Journal of Psychiatry and Neuroscience, 44, 45-53. [Google Scholar] [CrossRef] [PubMed]
[47] Kronmüller, K., Schröder, J., Köhler, S., Götz, B., Victor, D., Unger, J., et al. (2009) Hippocampal Volume in First Episode and Recurrent Depression. Psychiatry Research: Neuroimaging, 174, 62-66. [Google Scholar] [CrossRef] [PubMed]
[48] Furtado, C.P., Maller, J.J. and Fitzgerald, P.B. (2008) A Magnetic Resonance Imaging Study of the Entorhinal Cortex in Treatment-Resistant Depression. Psychiatry Research: Neuroimaging, 163, 133-142. [Google Scholar] [CrossRef] [PubMed]
[49] Amiri, S., Arbabi, M., Kazemi, K., Parvaresh-Rizi, M. and Mirbagheri, M.M. (2021) Characterization of Brain Functional Connectivity in Treatment-Resistant Depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 111, Article 110346. [Google Scholar] [CrossRef] [PubMed]
[50] Talishinsky, A., Downar, J., Vértes, P.E., Seidlitz, J., Dunlop, K., Lynch, C.J., et al. (2022) Regional Gene Expression Signatures Are Associated with Sex-Specific Functional Connectivity Changes in Depression. Nature Communications, 13, Article No. 5692. [Google Scholar] [CrossRef] [PubMed]