Polne razlike u terapijskom odgovoru na antidepresive: biološka osnova i kliničke implikacije
Sažetak
Depresija predstavlja ozbiljan zdravstveni problem na globalnom nivou koji pogađa milione ljudi i ograničava ih u obavljanju dnevnih poslovnih i privatnih obaveza. Istraživanja ukazuju na značajnu ulogu polnog dimorfizma u patogenezi i terapiji depresivnih poremećaja. Naime, pokazano je da između muškaraca i žena postoje značajne razlike u prevalenci, simptomatologiji i terapijskom odgovoru prilikom tretmana različitim grupama antidepresiva. Žene češće oboljevaju od depresivnih poremećaja, što se može pripisati hormonalnim uticajima i specifičnim mehanizmima suočavanja sa psihosocijalnim i drugim oblicima stresa. S druge strane, kod muškaraca je depresivna simptomatologija okarakterisana eksternalizovanim ponašanjem i višim stopama samoubistava u odnosu na žensku populaciju. Neurobiološke studije ukazuju na postojanje jasnih razlika u strukturi i funkciji određenih moždanih regija koje su specifične za pol. Takođe, između muškaraca i žena postoji razlika u aktivnosti neurotransmiterskih sistema, što može ispoljiti uticaj na efikasnost lečenja i dovesti do varijabilnosti u odgovoru na terapiju u zavisnosti od pola. Uz farmakoterapiju koja je osnova terapije depresivnih poremećaja, poslednjih godina se akcenat stavlja na personalizovan pristup u lečenju, koji integriše psihoterapijske modalitete poput kognitivno-bihejvioralne terapije i meditacije. Međutim, prisustvo razlika u ishodima lečenja u zavisnosti od pola naglašava potrebu za novim kliničkim strategijama. U prikazanom preglednom radu razmatrani su dostupni literaturni podaci u cilju isticanja važnosti personalizovanog pristupa u tretmanu depresivnih poremećaja kako bi klinički ishodi lečenja bili optimalni.
Reference
World Health Organization. Depression and other common mental disorders: global health estimates. World Health Organization; 2017.
Kessler RC, Aguilar-Gaxiola S, Alonso J, Chatterji S, Lee S, Ormel J, et al. Global and local burden of depression: findings from the World Mental Health Surveys. Epidemiol Psichiatr Soc. 2009;18(1):23-33.
Brody DJ, Pratt LA, Hughes JP. Prevalence of depression among adults aged 20 and over: United States, 2013–2016. NCHS data brief; 2018.
Marcus SM, Young EA, Kerber KB, Kornstein S, Farabaugh AH, Mitchell J, et al. Gender differences in depression: findings from the STAR*D study. J Affect Disord. 2005;87:141–50.
Cavanagh A, Wilson CJ, Kavanagh DJ, Caputi P. Differences in the expression of symptoms in men versus women with depression: a systematic review and Meta-analysis. Harv Rev Psychiatry. 2017;25:29–38.
Albert K, Pruessner J, Newhouse P. Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle. Psychoneuroendocrinology. 2015;59:14–24.
Barth C, Villringer A, Sacher J. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods. Front Neurosci. 2015;9:37.
Barth C, Steele JC, Mueller K, Rekkas PV, Arélin K. In-vivo Dynamics of the Human Hippocampus across the Menstrual Cycle. Sci Rep. 2016;6:32833.
Dubol M, Epperson CN, Sacher J, Pletzer B, Derntl B, Lanzenberger R, et al. Neuroimaging the menstrual cycle: A multimodal systematic review. Front Neuroendocrinol. 2021;60:100878.
Lisofsky N, Mårtensson J, Eckert A, Lindenberger U, Gallinat J, Kühn S. Hippocampal volume and functional connectivity changes during the female menstrual cycle. Neuroimage. 2015;118:154–62.
Bigos KL, Pollock BG, Stankevich BA, Bies RR. Sex differences in the pharmacokinetics and pharmacodynamics of antidepressants: an updated review. Gend Med. 2009;6:522–43.
Sampogna G, Toni C, Catapano P, Rocca BD, Di Vincenzo M, Luciano M, Fiorillo A. New trends in personalized treatment of depression. Curr Opin Psychiatry. 2024;37(1):3-8.
Maj M, Stein JD, Parker G, Zimmerman M, Fava AG. The clinical characterization of the adult patient with depression aimed at personalization of management. World Psychiatry. 2020 Oct;19(3):269–293.
Hofmann SG, Gómez AF. Mindfulness-Based Interventions for Anxiety and Depression. Psychiatr Clin North Am. 2017;40(4):739–749.
Watson HJ, Nathan PR. Role of gender in depressive disorder outcome for individual and group cognitive-behavioral treatment. J Clin Psychol 2008;64(12):1323–1337.
Markowitz JC, Weissman MM. Interpersonal psychotherapy: principles and applications. World Psychiatry. 2004;3(3):136–139.
Kirshner LA, Genack, Hauser S.T. Effects of gender on short-term psychotherapy. Psychother: Theo Res Prac. 1978:15(2):158–167.
Sherbourne CD, Weiss R, Duan N, Bird CE, Wells KB. Do the Effects of Quality Improvement for Depression Care Differ for Men and Women? Medical Care. 2004;42(12):1186–1193.
Schoenbaum M, Sherbourne C, Wells K. Gender patterns in cost effectiveness of quality improvement for depression: Results of a randomized, controlled trial. J Affect Disord. 2005;87(2-3):319–325.
Duman RS, Aghajanian GK, Sanacora G, Krystal JH. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med. 2016;22:238–249.
Penner-Goeke S, Binder EB. Epigenetics and depression. Dialogues Clin Neurosci. 2019;21:397– 405.
Lee EH, Han PL. Reciprocal interactions across and within multiple levels of monoamine and corticolimbic systems in stress-induced depression: A systematic review. Neurosci Biobehav Rev. 2019;101:13–31.
Masi G, Brovedani P. The hippocampus, neurotrophic factors and depression: possible implications for the pharmacotherapy of depression. CNS Drugs. 2011;25:913–31.
Hammen C. Stress and depression. Annu Rev Clin Psychol. 2005;1:293–319.
Beurel E, Toups M, Nemeroff CB. The Bidirectional Relationship of Depression and Inflammation: Double Trouble. Neuron. 2020;107:234–56.
Himmerich H, Patsalos O, Lichtblau N, Ibrahim MAA, Dalton B. Cytokine Research in Depression: Principles, Challenges, and Open Questions. Front Psychiatry. 2019;10:30.
Wainwright SR, Galea LA. The Neural Plasticity Theory of Depression: Assessing the Roles of Adult Neurogenesis and PSA-NCAM within the Hippocampus. Neural Plast. 2013;2013:805497.
Liu W, Ge T, Leng Y, Pan Z, Fan J, Yang W, Cui R. The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex. Neural Plast. 2017;2017:6871089.
Murphy DD, Cole NB, Greenberger V, Segal M. Estradiol increases dendritic spine density by reducing GABA neurotransmission in hippocampal neurons. J Neurosci. 1998;18:2550–9.
Sun Q, Li G, Zhao F, Dong M, Xie W, Liu Q, et al. Role of estrogen in treatment of female depression. Aging. 2024;16(3):3021–3042.
Nestler JE, Barrot M, DiLeone JR, Eisch JA, Gold JS, Monteggia ML. Neurobiology of depression. Neuron. 2002;34:13–25 .
Mohammadi S, Seyedmirzaei H, Salehi MA, Jahanshahi A, Zakavi SS, Dehghani Firouzabadi F, et al. Brain-based Sex Differences in Depression: A Systematic Review of Neuroimaging Studies. Brain Imaging Behav. 2023;17(5):541-569.
Knol JM, Twisk JWR, Beekman ATF, Heine RJ, Snoek FJ, Pouwer F. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia. 2006;49:837–845.
Evans DL, Charney DS, Lewis L, Golden RN, Gorman JM, Krishnan KR, et al. Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry. 2005;58:175–189.
Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature. 2008;455(7215):894–902.
Beery AK, Zucker I. Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev. 2011;35(3):565–572.
Clayton JA, Collins FS. NIH to balance sex in cell and animal studies. Nature. 2014;509(7500):282-3.
Will TR, Proaño SB, Thomas AM, Kunz LM, Thompson KC, Ginnari LA, et al. Problems and Progress regarding Sex Bias and Omission in Neuroscience Research. eNeuro. 2017;4(6):0278-17.
Rechlin RK, Splinter TFL, Hodges TE, Albert AY, Galea LAM. An analysis of neuroscience and psychiatry papers published from 2009 and 2019 outlines opportunities for increasing discovery of sex differences. Nat Commun. 2022;13(1):2137.
Weissman MM, Klerman GL. Sex differences and the epidemiology of depression. Arch Gen Psychiatry. 1977;34(1):98-111.
Weissman MM, Bland R, Joyce PR, Newman S, Wells JE, Wittchen HU. Sex differences in rates of depression: cross-national perspectives. J Affect Disord. 1993;29(2-3):77-84.
Kundakovic M, Tickerhoof M. Epigenetic Mechanisms Underlying Sex Differences in the Brain and Behavior. Trends Neurosci. 2024;47(1):18–35.
Amin Z, Canli T, Epperson CN. Effect of estrogen-serotonin interactions on mood and cognition. Behav Cogn Neurosci Rev. 2005;4(1):43-58.
Moreno FA, McGahuey CA, Freeman MP, Delgado PL. Sex differences in depressive response during monoamine depletions in remitted depressive subjects. J Clin Psychiatry. 2006;67(10):1618-1623.
Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, de Montigny C, et al. Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A. 1997;94(10):5308-5313.
Liiver K, Imbeault S, Školnaja M, Kaart T, Kanarik M, Laugus K, et al. Active vs passive novelty-related strategies: Sex differences in exploratory behaviour and monoaminergic systems. Behav Brain Res. 2023;441:114297.
Cahill L. Why sex matters for neuroscience. Nat Rev Neurosci. 2006;7(6):477-84.
Koss WA, Frick KM. Sex differences in hippocampal function. J Neurosci Res. 2017;95:539–562.
Altemus M, Sarvaiya N, Epperson CN. Sex differences in anxiety and depression clinical perspectives. Front Neuroendocrinol. 2014;35:320–330.
Becker JB, Chartoff E. Sex differences in neural mechanisms mediating reward and addiction. Neuropsychopharmacology. 2019;44:166–183.
Marrocco J, McEwen BS. Sex in the brain: hormones and sex differences. Dialogues Clin Neurosci. 2016;18:373–383.
Gogos A, Ney JL, Seymour N, Rheenen ET, Felmingham KL. Sex differences in schizophrenia, bipolar disorder, and post-traumatic stress disorder: Are gonadal hormones the link? Br J Pharmacol. 2019;176:4119–4135.
Kundakovic M, Rocks D. Sex hormone fluctuation and increased female risk for depression and anxiety disorders: From clinical evidence to molecular mechanisms. Front Neuroendocrinol. 2022;66:101010.
Galea LAM, Frick KM, Hampson E, Sohrabji F, Choleris E. Why estrogens matter for behavior and brain health. Neurosci Biobehav Rev. 2017;76(Pt B):363-379.
Oliva M, Muñoz-Aguirre M, Kim-Hellmuth S, Wucher V, Gewirtz ADH, Cotter DJ, et al. The impact of sex on gene expression across human tissues. Science. 2020;369(6509):eaba3066.
Jaric I, Rocks D, Greally JM, Suzuki M, Kundakovic M. Chromatin organization in the female mouse brain fluctuates across the oestrous cycle. Nat Commun. 2019;10:2851.
McCarthy MM, Arnold AP. Reframing sexual differentiation of the brain. Nat Neurosci. 2011;14:677–683.
McCarthy MM. Sex differences in the brain: Focus on developmental mechanisms. In: Legato MJ, editor. Principles of Gender-Specific Medicine (Fourth Edition). Elsevier/Academic Press; 2023; p. 159-180.
Nugent BM, Wright CL, Shetty AC, Hodes GE, Lenz KM, Mahurkar A, et al. Brain feminization requires active repression of masculinization via DNA methylation. Nat Neurosci. 2015;18(5):690-7.
Manotas MC, González DM, Céspedes C, Forero C, Moreno APR. Genetic and Epigenetic Control of Puberty. Sex Dev. 2022;16:1–10.
Jett S, Malviya N, Schelbaum E, Jang G, Jahan E, Clancy K, et al. Endogenous and Exogenous Estrogen Exposures: How Women’s Reproductive Health Can Drive Brain Aging and Inform Alzheimer’s Prevention. Front Aging Neurosci. 2022;14:831807.
Streifer M, Gore AC. Epigenetics, estrogenic endocrine-disrupting chemicals (EDCs), and the brain. Adv Pharmacol. 2021;92:73–99.
Lu DH, Zhou SY, Xu LZ. Association between hormone replacement therapy and sex hormones in postmenopausal women: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2023 Jun;27(11):5264-5279.
Hoekzema E, Barba-Müller E, Pozzobon C, Picado M, Lucco F, García-García D, et al. Pregnancy leads to long-lasting changes in human brain structure. Nat Neurosci. 2017;20:287–296.
Mosconi L, Berti V, Dyke J, Schelbaum E, Jett S, Loughlin L, et al. Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition. Sci Rep. 2021;11:10867.
Archer T, Oscar-Berman M, Blum K, Gold M. Neurogenetics and Epigenetics in Impulsive Behaviour: Impact on Reward Circuitry. J Genet Syndr Gene Ther. 2012;3(3):1000115.
Cui L, Li S, Wang S, Wu X, Liu Y, Yu W, et al. Major depressive disorder: hypothesis, mechanism, prevention and treatment. Signal Transduct Target Ther. 2024;9(1):30.
LeGates TA, Kvarta MD, Thompson SM. Sex differences in antidepressant efficacy. Neuropsychopharmacology. 2019;44(1):140-154.
Sramek JJ, Murphy MF, Cutler NR. Sex differences in the psychopharmacological treatment of depression Dialogues Clin Neurosci. 2016;18(4):447-457.
Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI et al. Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry. 2000;157(9):1445-1452.
Berlanga C, Flores-Ramos M. Different gender response to serotonergic and noradrenergic antidepressants. A comparative study of the efficacy of citalopram and reboxetine. J Affect Disord. 2006;95(1-3):119-123.
Naito S, Sato K, Yoshida K, Higuchi H, Takahashi H, Kamata M, et al. Gender differences in the clinical effects of fluvoxamine and milnacipran in Japanese major depressive patients. Psychiatry Clin Neurosci. 2007;61(4):421-427.
Young EA, Kornstein SG, Marcus SM, Harvey AT, Warden D, Wisniewski SR, et al. Sex differences in response to citalopram: a STAR*D report. J Psychiatr Res. 2009;43(5):503-511.
Khan A, Brodhead AE, Schwartz KA, Kolts RL, Brown WA. Sex differences in antidepressant response in recent antidepressant clinical trials. J Clin Psychopharmacol. 2005;25(4):318-324.
Vermeiden M, van den Broek WW, Mulder PG, Birkenhager TK. Influence of gender and menopausal status on antidepressant treatment response in depressed inpatients. J Psychopharmacol. 2010;24(4):497-502.
Davidson J, Pelton S. Forms of atypical depression and their response to antidepressant drugs. Psychiatry Res. 1986;17(2):87-95.
Moderie C, Nuñez N, Fielding A, Comai S, Gobbi G. Sex Differences in Responses to Antidepressant Augmentations in Treatment-Resistant Depression. Int J Neuropsychopharmacol. 2022;25(6):479-488.
Pinto-Meza A, Usall J, Serrano-Blanco A, Suarez D, Haro JM. Gender differences in response to antidepressant treatment prescribed in primary care. Does menopause make a difference? J Affect Disord. 2006;93(1-3):53-60.
Kornstein SG, Clayton AH, Soares CN, Padmanabhan SK, Guico-Pabia CJ. Analysis by age and sex of efficacy data from placebo-controlled trials of desvenlafaxine in outpatients with major depressive disorder. J Clin Psychopharmacol. 2010;30(3):294-299.
Kornstein SG, Pedersen RD, Holland PJ, Nemeroff CB, Rothschild AJ, Thase ME, et al. Influence of sex and menopausal status on response, remission, and recurrence in patients with recurrent major depressive disorder treated with venlafaxine extended release or fluoxetine: analysis of data from the PREVENT study. J Clin Psychiatry. 2014;75(1):62-68.
Quitkin FM, Stewart JW, McGrath PJ, Taylor BP, Tisminetzky MS, Petkova E, et al. Are there differences between women’s and men’s antidepressant responses? Am J Psychiatry. 2002;159(11):1848-1854.
Hildebrandt MG, Steyerberg EW, Stage KB, Passchier J, Kragh-Soerensen P, Danish University Antidepressant Group. Are gender differences important for the clinical effects of antidepressants? Am J Psychiatry. 2003;160(9):1643-1650.
Parker G, Parker K, Austin MP, Mitchell P, Brotchie H. Gender differences in response to differing antidepressant drug classes: two negative studies. Psychol Med. 2003;33(8):1473-1477.
Wohlfarth T, Storosum JG, Elferink AJ, van Zwieten BJ, Fouwels A, van den Brink W. Response to tricyclic antidepressants: independent of gender? Am J Psychiatry. 2004;161(2):370-372.
Thiels C, Linden M, Grieger F, Leonard J. Gender differences in routine treatment of depressed outpatients with the selective serotonin reuptake inhibitor sertraline. Int Clin Psychopharmacol. 2005;20(1):1-7.
Entsuah AR, Huang H, Thase ME. Response and remission rates in dif ferent subpopulations with major depressive disorder administered ven lafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry. 2001;62(11):869-877.
Schneider LS, Small GW, Hamilton SH, Bystritsky A, Nemeroff CB, Meyers BS. Estrogen replacement and response to fluoxetine in a multicenter geriatric depression trial. Fluoxetine Collaborative Study Group. Am J Geriatr Psychiatry. 1997;5(2):97-106.
Yonkers KA, Kando JC, Cole JO, Blumenthal S. Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication. Am J Psychiatry. 1992;149(5):587-595
Pae CU, Mandelli L, Kim TS, Han C, Masand PS, Marks DM, et al. Effectiveness of antidepressant treatments in pre-menopausal versus post-menopausal women: a pilot study on differential effects of sex hormones on antidepressant effects. Biomed Pharmacother. 2009;63(3):228-235.
Holsboer F, Barden N. Antidepressants and hypothalamic-pituitary-adrenocortical regulation. Endocr Rev. 1996;17(2):187-205.
Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology. 2000;23(5):477-501.
Kokras N, Dalla C, Papadopoulou-Daifoti Z. Sex differences in pharmacokinetics of antidepressants. Expert Opin Drug Metab Toxicol. 2011;7(2):213-226.
Marazziti D, Baroni S, Picchetti M, Piccinni A, Carlini M, Vatteroni E et al. Pharmacokinetics and pharmacodynamics of psychotropic drugs: effect of sex. CNS Spectr. 2013;18(3):118-27.
Damoiseaux VA, Proost JH, Jiawan VC, Melgert BN. Sex differences in the pharmacokinetics of antidepressants: influence of female sex hormones and oral contraceptives. Clin Pharmacokinet. 2014;53(6)509–19.
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