Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Neurobiology of male sexual dysfunctions in psychiatric disorders: the cases of depression, anxiety, mania and schizophrenia

Abstract

While the pathophysiology of several psychiatric disorders has become modestly elucidated in the last decade, comorbid sexual dysfunctions in such patients are frequently left apart from clinical and research interest. We aimed to address the malfunctioning neurocircuitry underlying sexual dysfunctions in depression, anxiety, schizophrenia and mania. We performed a comprehensive literature review, addressing any combination of the topics of “neurobiology”/“neural”, “sexual”/“desire”/“arousal”/“orgasm”/“ejaculation” and “depression”/“anxiety”/“schizophrenia”/“mania”/“bipolar”. Altered neurotransmitter levels or connectivity in patients are reported in sexual dysfunctions (either desire, arousal, orgasm and ejaculation) and main psychiatric disorders (depression, anxiety, mania and schizophrenia). Neuronal pathways responsible for the occurrence of sexual dysfunctions in psychiatric disorders can be  figured out by overlap  of their acknowledged pathophysiology. However, specific research in that group is scant, so future tailored studies are warranted to elucidate actual mechanisms.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Waldinger MD. Psychiatric disorders and sexual dysfunction. Handb Clin Neurol. 2015;130:469–89.

    PubMed  Google Scholar 

  2. Waldinger MD. Not medical solutions, but overmedicalization by pharmaceutical company policies endanger both sexological care, science, and sexual medicine. A commentary. J Sex Marital Ther. 2008;34:179–83.

    PubMed  Google Scholar 

  3. Freud S, Haute Pv, Westerink H, Freud S, Freud S. Three essays on the theory of sexuality: the1905 edition. London; New York: Verso; 2016. xc, p. 111.

  4. Tharoor H, Kaliappan A, Gopal S. Sexual dysfunctions in schizophrenia: professionals and patients perspectives. Indian J Psychiatry. 2015;57:85–7.

    PubMed  PubMed Central  Google Scholar 

  5. Atlantis E, Sullivan T. Bidirectional association between depression and sexual dysfunction: a systematic review and meta-analysis. J Sex Med. 2012;9:1497–507.

    PubMed  Google Scholar 

  6. Shabsigh R, Zakaria L, Anastasiadis AG, Seidman AS. Sexual dysfunction and depression: etiology, prevalence, and treatment. Curr Urol Rep. 2001;2:463–7.

    CAS  PubMed  Google Scholar 

  7. Labbate LA, Lare SB. Sexual dysfunction in male psychiatric outpatients: validity of the Massachusetts General Hospital Sexual Functioning Questionnaire. Psychother Psychosom. 2001;70:221–5.

    CAS  PubMed  Google Scholar 

  8. Harley EW, Boardman J, Craig T. Sexual problems in schizophrenia: prevalence and characteristics. A cross sectional survey. Soc Psychiatry Psychiatr Epidemiol. 2010;45:759–66.

    PubMed  Google Scholar 

  9. Jonusiene G, Griffioen, T. Psychiatric disorders and sexual dysfunctions. In: Kirana PS, Tripodi, F, Reisman, Y, Porst, H, editors. The EFS and ESSM Syllabus of Clinical Sexology. Amsterdam: Medix; 2013.

  10. Basson R. A model of women’s sexual arousal. J Sex Marital Ther. 2002;28:1–10.

    PubMed  Google Scholar 

  11. McKenna KE. Neural circuitry involved in sexual function. J Spinal Cord Med. 2001;24:148–54.

    CAS  PubMed  Google Scholar 

  12. Chapelle PA, Durand J, Lacert P. Penile erection following complete spinal cord injury in man. Br J Urol. 1980;52:216–9.

    CAS  PubMed  Google Scholar 

  13. Dean RC, Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am. 2005;32:379–95.

    PubMed  PubMed Central  Google Scholar 

  14. Argiolas A, Melis MR. Central control of penile erection: role of the paraventricular nucleus of the hypothalamus. Prog Neurobiol. 2005;76:1–21.

    CAS  PubMed  Google Scholar 

  15. Rubio-Aurioles E, Bivalacqua TJ. Standard operational procedures for low sexual desire in men. J Sex Med. 2013;10:94–107.

    PubMed  Google Scholar 

  16. Cacioppo S, Bianchi-Demicheli F, Frum C, Pfaus JG, Lewis JW. The common neural bases between sexual desire and love: a multilevel kernel density fMRI analysis. J Sex Med. 2012;9:1048–54.

    PubMed  Google Scholar 

  17. Seok JW, Sohn JH, Cheong C. Neural substrates of sexual arousal in heterosexual males: event-related fMRI investigation. J Physiol Anthropol. 2016;35:8.

    PubMed  PubMed Central  Google Scholar 

  18. Cheng JC, Secondary J, Burke WH, Fedoroff JP, Dwyer RG. Neuroimaging and sexual behavior: identification of regional and functional differences. Curr Psychiatry Rep. 2015;17:55.

    PubMed  Google Scholar 

  19. Poeppl TB, Langguth B, Laird AR, Eickhoff SB. The functional neuroanatomy of male psychosexual and physiosexual arousal: a quantitative meta-analysis. Hum Brain Mapp. 2014;35:1404–21.

    PubMed  Google Scholar 

  20. Georgiadis JR, Kringelbach ML. The human sexual response cycle: brain imaging evidence linking sex to other pleasures. Prog Neurobiol. 2012;98:49–81.

    CAS  PubMed  Google Scholar 

  21. Georgiadis JR. Functional neuroanatomy of human cortex cerebri in relation to wanting sex and having it. Clin Anat. 2015;28:314–23.

    PubMed  Google Scholar 

  22. Pfaus JG. Pathways of sexual desire. J Sex Med. 2009;6:1506–33.

    CAS  PubMed  Google Scholar 

  23. Graf H, Walter M, Metzger CD, Abler B. Antidepressant-related sexual dysfunction—perspectives from neuroimaging. Pharmacol Biochem Behav. 2014;121:138–45.

    CAS  PubMed  Google Scholar 

  24. Veening JG, de Jong TR, Waldinger MD, Korte SM, Olivier B. The role of oxytocin in male and female reproductive behavior. Eur J Pharmacol. 2015;753:209–28.

    CAS  PubMed  Google Scholar 

  25. Rowland DL. Neurobiology of sexual response in men and women. CNS Spectr. 2006;11(8 Suppl 9):6–12.

    PubMed  Google Scholar 

  26. Lorrain DS, Riolo JV, Matuszewich L, Hull EM. Lateral hypothalamic serotonin inhibits nucleus accumbens dopamine: implications for sexual satiety. J Neurosci. 1999;19:7648–52.

    CAS  PubMed  Google Scholar 

  27. Argiolas A, Melis MR. Neuropeptides and central control of sexual behaviour from the past to the present: a review. Prog Neurobiol. 2013;108:80–107.

    CAS  PubMed  Google Scholar 

  28. Jesulola E, Micalos P, Baguley IJ. Understanding the pathophysiology of depression: From monoamines to the neurogenesis hypothesis model—are we there yet? Behav Brain Res. 2018;341:79–90.

    CAS  PubMed  Google Scholar 

  29. Laurent SM, Simons AD. Sexual dysfunction in depression and anxiety: conceptualizing sexual dysfunction as part of an internalizing dimension. Clin Psychol Rev. 2009;29:573–85.

    PubMed  Google Scholar 

  30. Friedman A, Deri I, Friedman Y, Dremencov E, Goutkin S, Kravchinsky E, et al. Decoding of dopaminergic mesolimbic activity and depressive behavior. J Mol Neurosci. 2007;32:72–9.

    CAS  PubMed  Google Scholar 

  31. Nestler EJ, Carlezon WA Jr.. The mesolimbic dopamine reward circuit in depression. Biol Psychiatry. 2006;59:1151–9.

    CAS  PubMed  Google Scholar 

  32. Fitzgerald PB, Srithiran A, Benitez J, Daskalakis ZZ, Oxley TJ, Kulkarni J, et al. An fMRI study of prefrontal brain activation during multiple tasks in patients with major depressive disorder. Hum Brain Mapp. 2008;29:490–501.

    PubMed  Google Scholar 

  33. Anand A, Li Y, Wang Y, Gardner K, Lowe MJ. Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an FMRI study. J Neuropsychiatry Clin Neurosci. 2007;19:274–82.

    PubMed  PubMed Central  Google Scholar 

  34. Opel N, Redlich R, Grotegerd D, Dohm K, Zaremba D, Meinert S, et al. Prefrontal brain responsiveness to negative stimuli distinguishes familial risk for major depression from acute disorder. J Psychiatry Neurosci. 2017;42:343–52.

    PubMed  PubMed Central  Google Scholar 

  35. Stoy M, Schlagenhauf F, Sterzer P, Bermpohl F, Hagele C, Suchotzki K, et al. Hyporeactivity of ventral striatum towards incentive stimuli in unmedicated depressed patients normalizes after treatment with escitalopram. J Psychopharmacol. 2012;26:677–88.

    PubMed  Google Scholar 

  36. Yang JC. Functional neuroanatomy in depressed patients with sexual dysfunction: blood oxygenation level dependent functional MR imaging. Korean J Radiol. 2004;5:87–95.

    PubMed  PubMed Central  Google Scholar 

  37. Stoleru S, Redoute J, Costes N, Lavenne F, Bars DL, Dechaud H, et al. Brain processing of visual sexual stimuli in men with hypoactive sexual desire disorder. Psychiatry Res. 2003;124:67–86.

    PubMed  Google Scholar 

  38. Serretti A, Chiesa A. Sexual side effects of pharmacological treatment of psychiatric diseases. Clin Pharmacol Ther. 2011;89:142–7.

    CAS  PubMed  Google Scholar 

  39. Clayton AH, El Haddad S, Iluonakhamhe JP, Ponce Martinez C, Schuck AE. Sexual dysfunction associated with major depressive disorder and antidepressant treatment. Expert Opin Drug Saf. 2014;13:1361–74.

    CAS  PubMed  Google Scholar 

  40. Duval ER, Javanbakht A, Liberzon I. Neural circuits in anxiety and stress disorders: a focused review. Ther Clin Risk Manag. 2015;11:115–26.

    PubMed  PubMed Central  Google Scholar 

  41. Hilbert K, Lueken U, Beesdo-Baum K. Neural structures, functioning and connectivity in Generalized Anxiety Disorder and interaction with neuroendocrine systems: a systematic review. J Affect Disord. 2014;158:114–26.

    PubMed  Google Scholar 

  42. Pietrini F, Godini L, Lazzeretti L, Benni L, Pracucci C, Talamba GA, et al. [Neuroimaging and neurobiology of social anxiety]. Riv Psichiatr. 2010;45:349–60.

    PubMed  Google Scholar 

  43. Shackman AJ, Stockbridge MD, Tillman RM, Kaplan CM, Tromp DP, Fox AS, et al. The neurobiology of dispositional negativity and attentional biases to threat: implications for understanding anxiety disorders in adults and youth. J Exp Psychopathol. 2016;7:311–42.

    PubMed  PubMed Central  Google Scholar 

  44. Barlow DH. Causes of sexual dysfunction: the role of anxiety and cognitive interference. J Consult Clin Psychol. 1986;54:140–8.

    CAS  PubMed  Google Scholar 

  45. Beck JG, Barlow DH. The effects of anxiety and attentional focus on sexual responding—II. Cognitive and affective patterns in erectile dysfunction. Behav Res Ther. 1986;24:19–26.

    CAS  PubMed  Google Scholar 

  46. Carvalho J, Nobre P. Biopsychosocial determinants of men’s sexual desire: testing an integrative model. J Sex Med. 2011;8:754–63.

    PubMed  Google Scholar 

  47. Bancroft J, Janssen E, Strong D, Carnes L, Vukadinovic Z, Long JS. The relation between mood and sexuality in heterosexual men. Arch Sex Behav. 2003;32:217–30.

    PubMed  Google Scholar 

  48. Corona G, Mannucci E, Petrone L, Ricca V, Balercia G, Giommi R, et al. Psycho-biological correlates of free-floating anxiety symptoms in male patients with sexual dysfunctions. J Androl. 2006;27:86–93.

    PubMed  Google Scholar 

  49. Dvorak RD, Wray TB, Kuvaas NJ, Kilwein TM. Mania and sexual risk: associations with behavioral self-regulation. J Affect Disord. 2013;150:1076–81.

    CAS  PubMed  Google Scholar 

  50. Dell’Osso L, Carmassi C, Carlini M, Rucci P, Torri P, Cesari D, et al. Sexual dysfunctions and suicidality in patients with bipolar disorder and unipolar depression. J Sex Med. 2009;6:3063–70.

    PubMed  Google Scholar 

  51. Kopeykina I, Kim HJ, Khatun T, Boland J, Haeri S, Cohen LJ, et al. Hypersexuality and couple relationships in bipolar disorder: a review. J Affect Disord. 2016;195:1–14.

    PubMed  Google Scholar 

  52. Strakowski SM, Eliassen JC, Lamy M, Cerullo MA, Allendorfer JB, Madore M, et al. Functional magnetic resonance imaging brain activation in bipolar mania: evidence for disruption of the ventrolateral prefrontal-amygdala emotional pathway. Biol Psychiatry. 2011;69:381–8.

    PubMed  Google Scholar 

  53. Pomarol-Clotet E, Alonso-Lana S, Moro N, Sarro S, Bonnin MC, Goikolea JM, et al. Brain functional changes across the different phases of bipolar disorder. Br J Psychiatry. 2015;206:136–44.

    PubMed  Google Scholar 

  54. Fleck DE, Eliassen JC, Durling M, Lamy M, Adler CM, DelBello MP, et al. Functional MRI of sustained attention in bipolar mania. Mol Psychiatry. 2012;17:325–36.

    CAS  PubMed  Google Scholar 

  55. Blumberg HP, Stern E, Martinez D, Ricketts S, de Asis J, White T, et al. Increased anterior cingulate and caudate activity in bipolar mania. Biol Psychiatry. 2000;48:1045–52.

    CAS  PubMed  Google Scholar 

  56. Seok JW, Sohn JH. Neural substrates of sexual desire in individuals with problematic hypersexual behavior. Front Behav Neurosci. 2015;9:321.

    PubMed  PubMed Central  Google Scholar 

  57. King R, Raese JD, Barchas JD. Catastrophe theory of dopaminergic transmission: a revised dopamine hypothesis of schizophrenia. J Theor Biol. 1981;92:373–400.

    CAS  PubMed  Google Scholar 

  58. Heilbronner U, Samara M, Leucht S, Falkai P, Schulze TG. The longitudinal course of schizophrenia across the lifespan: clinical, cognitive, and neurobiological aspects. Harv Rev Psychiatry. 2016;24:118–28.

    PubMed  PubMed Central  Google Scholar 

  59. Drake CR, Pathe M. Understanding sexual offending in schizophrenia. Crim Behav Ment Health. 2004;14:108–20.

    PubMed  Google Scholar 

  60. Phillips SL, Heads TC, Taylor PJ, Hill GM. Sexual offending and antisocial sexual behavior among patients with schizophrenia. J Clin Psychiatry. 1999;60:170–5.

    CAS  PubMed  Google Scholar 

  61. de Boer MK, Castelein S, Wiersma D, Schoevers RA, Knegtering H. The facts about sexual (dys)function in schizophrenia: an overview of clinically relevant findings. Schizophr Bull. 2015;41:674–86.

    PubMed  PubMed Central  Google Scholar 

  62. Hocaoglu C, Celik FH, Kandemir G, Guveli H, Bahceci B. Sexual dysfunction in outpatients with schizophrenia in Turkey: a cross-sectional study. Shanghai Arch Psychiatry. 2014;26:347–56.

    PubMed  PubMed Central  Google Scholar 

  63. Dembler-Stamm T, Fiebig J, Heinz A, Gallinat J. Sexual dysfunction in unmedicated patients with schizophrenia and in healthy controls. Pharmacopsychiatry. 2018. https://doi.org/10.1055/s-0044-100627.

    PubMed  Google Scholar 

  64. Baggaley M. Sexual dysfunction in schizophrenia: focus on recent evidence. Hum Psychopharmacol. 2008;23:201–9.

    CAS  PubMed  Google Scholar 

  65. Kirino E. Serum prolactin levels and sexual dysfunction in patients with schizophrenia treated with antipsychotics: comparison between aripiprazole and other atypical antipsychotics. Ann Gen Psychiatry. 2017;16:43.

    PubMed  PubMed Central  Google Scholar 

  66. Zhang XR, Zhang ZJ, Zhu RX, Yuan YG, Jenkins TA, Reynolds GP. Sexual dysfunction in male schizophrenia: influence of antipsychotic drugs, prolactin and polymorphisms of the dopamine D2 receptor genes. Pharmacogenomics. 2011;12:1127–36.

    CAS  PubMed  Google Scholar 

  67. Mete D, Dafreville C, Paitel V, Wind P. [Aripiprazole, gambling disorder and compulsive sexuality]. Encephale. 2016;42:281–3.

    CAS  PubMed  Google Scholar 

  68. Cheon E, Koo BH, Seo SS, Lee JY. Two cases of hypersexuality probably associated with aripiprazole. Psychiatry Investig. 2013;10:200–2.

    PubMed  PubMed Central  Google Scholar 

  69. Ucok A, Incesu C, Aker T, Erkoc S. Do psychiatrists examine sexual dysfunction in schizophrenia patients? J Sex Med. 2008;5:2000–1.

    PubMed  Google Scholar 

  70. Rademacher L, Schulte-Ruther M, Hanewald B, Lammertz S. Reward: from basic reinforcers to anticipation of social cues. Curr Top Behav Neurosci. 2017;30:207–21.

    PubMed  Google Scholar 

  71. Williams DR, Burkner PC. Effects of intranasal oxytocin on symptoms of schizophrenia: a multivariate Bayesian meta-analysis. Psychoneuroendocrinology. 2017;75:141–51.

    CAS  PubMed  Google Scholar 

  72. Peeters M, Giuliano F. Central neurophysiology and dopaminergic control of ejaculation. Neurosci Biobehav Rev. 2008;32:438–53.

    CAS  PubMed  Google Scholar 

  73. Veening JG, Coolen LM. Neural mechanisms of sexual behavior in the male rat: emphasis on ejaculation-related circuits. Pharmacol Biochem Behav. 2014;121:170–83.

    CAS  PubMed  Google Scholar 

  74. Alwaal A, Breyer BN, Lue TF. Normal male sexual function: emphasis on orgasm and ejaculation. Fertil Steril. 2015;104:1051–60.

    PubMed  PubMed Central  Google Scholar 

  75. Clement P, Giuliano F. Physiology and pharmacology of ejaculation. Basic Clin Pharmacol Toxicol. 2016;119(Suppl 3):18–25.

    CAS  PubMed  Google Scholar 

  76. Stoneham MD, Everitt BJ, Hansen S, Lightman SL, Todd K. Oxytocin and sexual behaviour in the male rat and rabbit. J Endocrinol. 1985;107:97–106.

    CAS  PubMed  Google Scholar 

  77. Waldinger MD. Ejaculatio praecox, erectio praecox, and detumescentia praecox as symptoms of a hypertonic state in lifelong premature ejaculation: a new hypothesis. Pharmacol Biochem Behav. 2014;121:189–94.

    CAS  PubMed  Google Scholar 

  78. Agmo A, Berenfeld R. Reinforcing properties of ejaculation in the male rat: role of opioids and dopamine. Behav Neurosci. 1990;104:177–82.

    CAS  PubMed  Google Scholar 

  79. Kennedy SH, Rizvi S. Sexual dysfunction, depression, and the impact of antidepressants. J Clin Psychopharmacol. 2009;29:157–64.

    CAS  PubMed  Google Scholar 

  80. Fabre LF, Clayton AH, Smith LC, Goldstein IM, Derogatis LR. Association of major depression with sexual dysfunction in men. J Neuropsychiatry Clin Neurosci. 2013;25:308–18.

    PubMed  Google Scholar 

  81. Waldinger MD. Pharmacotherapy for premature ejaculation. Expert Opin Pharmacother. 2015;16:2615–24.

    CAS  PubMed  Google Scholar 

  82. Bijlsma EY, Chan JS, Olivier B, Veening JG, Millan MJ, Waldinger MD, et al. Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release? Pharmacol Biochem Behav. 2014;121:88–101.

    CAS  PubMed  Google Scholar 

  83. Waldinger MD, Berendsen HH, Blok BF, Olivier B, Holstege G. Premature ejaculation and serotonergic antidepressants-induced delayed ejaculation: the involvement of the serotonergic system. Behav Brain Res. 1998;92:111–8.

    CAS  PubMed  Google Scholar 

  84. Corona G, Petrone L, Mannucci E, Jannini EA, Mansani R, Magini A, et al. Psycho-biological correlates of rapid ejaculation in patients attending an andrologic unit for sexual dysfunctions. Eur Urol. 2004;46:615–22.

    CAS  PubMed  Google Scholar 

  85. Mourikis I, Antoniou M, Matsouka E, Vousoura E, Tzavara C, Ekizoglou C, et al. Anxiety and depression among Greek men with primary erectile dysfunction and premature ejaculation. Ann Gen Psychiatry. 2015;14:34.

    PubMed  PubMed Central  Google Scholar 

  86. Rajkumar RP, Kumaran AK. The association of anxiety with the subtypes of premature ejaculation: a chart review. Prim Care Companion CNS Disord. 2014;16:4.

    Google Scholar 

  87. McMahon CG, Jannini EA, Serefoglu EC, Hellstrom WJ. The pathophysiology of acquired premature ejaculation. Transl Androl Urol. 2016;5:434–49.

    PubMed  PubMed Central  Google Scholar 

  88. Xia J, Chen T, Chen J, Han Y, Xu Z, Zhou L, et al. The sympathetic skin response located in the penis as a predictor of the response to sertraline treatment in patients with primary premature ejaculation. J Sex Med. 2014;11:2801–8.

    CAS  PubMed  Google Scholar 

  89. Kempeneers P, Andrianne R, Cuddy M, Blairy S. Sexual cognitions, trait anxiety, sexual anxiety and distress in men with different subtypes of premature ejaculation and in their partners. J Sex Marital Ther. 2017;44:319–32.

    Google Scholar 

  90. Lyketsos GC, Sakka P, Mailis A. The sexual adjustment of chronic schizophrenics: a preliminary study. Br J Psychiatry. 1983;143:376–82.

    CAS  PubMed  Google Scholar 

  91. Fan X, Henderson DC, Chiang E, Briggs LB, Freudenreich O, Evins AE, et al. Sexual functioning, psychopathology and quality of life in patients with schizophrenia. Schizophr Res. 2007;94:119–27.

    PubMed  Google Scholar 

  92. Malik P, Kemmler G, Hummer M, Riecher-Roessler A, Kahn RS, Fleischhacker WW, et al. Sexual dysfunction in first-episode schizophrenia patients: results from European First Episode Schizophrenia Trial. J Clin Psychopharmacol. 2011;31:274–80.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ege Can Serefoglu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Trovão, J.N., Serefoglu, E.C. Neurobiology of male sexual dysfunctions in psychiatric disorders: the cases of depression, anxiety, mania and schizophrenia. Int J Impot Res 30, 279–286 (2018). https://doi.org/10.1038/s41443-018-0077-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41443-018-0077-8

This article is cited by

Search

Quick links