Sex differences in schizophrenia

Sex differences in schizophrenia are widely reported.[1][2][3] Men and women exhibit different rates of incidence and prevalence, age at onset, symptom expression, course of illness, and response to treatment.[2][3] [4] Reviews of the literature suggest that understanding the implications of sex differences on schizophrenia may help inform individualized treatment and positively affect outcomes.[2][5]

Incidence and prevalence

For both men and women, incidence of schizophrenia onset peaks at multiple points across the lifespan.[3] For men, the highest frequency of incidence onset occurs in the early twenties and there is evidence of a second peak in the mid-thirties. For women, there is a similar pattern with peaks in the early twenties and middle age.[6] Studies have also demonstrated a tertiary peak for women in the early sixties. Men have higher frequency rates of onset than women from the early twenties to middle age, and women have higher frequency rates of onset starting in late middle age. [7]

2005 and 2008 studies of prevalence rates of schizophrenia estimate that the lifetime likelihood of developing the disorder is 0.3%–0.7%, and did not find evidence of sex differences.[8][9] However, other studies have found a higher prevalence and severity in males than females.[10][11][12]

Clinical presentation

Symptom expression systematically differs between men and women. Women are more likely to experience high levels of depressive symptoms (i.e., low mood, anhedonia, fatigue) at illness onset and over the course of illness.[3][6] Men are more likely to experience more negative symptoms than women at illness onset. There is conflicting evidence related to sex differences in the expression of positive symptoms.[3][6] Some studies have found that women are more likely to experience positive symptoms.[13][14] Other studies have found no significant sex differences in the expression of positive symptoms.[15] Younger age of onset is also related to earlier hospitalizations in men and more acute symptom severity in women.[16][17]

Ties have been found between schizophrenic women's estrogen levels and their level of schizophrenia symptoms.[18] Such women have sometimes been found to benefit from hormonal treatment. Menstrual psychosis and postpartum psychosis may in some cases be linked to an underlying schizophrenic condition.[19]

Differences course of illness and treatment outcomes

Course of illness and treatment outcomes

Longitudinal studies have found evidence of sex differences in presence of psychosis, global outcome, and recovery across periods of 15-20 years.[20][21][22] Several studies have demonstrated that women with schizophrenia are more likely to exhibit significantly greater reduction in psychotic symptoms, as well as better cognitive and global functioning relative to men.[20][22] Additionally, studies have found that women are more likely to experience a period of recovery across the lifespan than men.[20] Further, there is consistent evidence of higher mortality rates, suicide attempts and completions, homelessness, poorer family and social support in men compared to women.[21] It is currently unclear the extent to which these observed differences can be attributed to age of onset.

Some studies demonstrate that age at illness onset likely contributes to observed sex differences in course of illness and treatment outcomes.[23] Increased negative and cognitive symptoms and poorer overall treatment outcomes are both related to younger age at onset, while fewer negative and cognitive symptoms are associated with older age at onset.[24][25] These findings are consistent with the patterns of symptom expression observed in men and women and the relative age of onset for each gender. It is possible that men are more likely to experience poorer overall outcomes than women because of the relationship between younger age at onset and symptom severity.[26] However, some longitudinal studies have found that sex is a unique predictor of functional outcome over and above the effects of age.[20]

Differences in response to antipsychotic medications

Clinical trials examining sex differences in the efficacy of atypical antipsychotic medications found greater rates of symptom reduction in women compared to men.[27] However, women are at a greater risk for experiencing weight gain and developing metabolic syndrome as a result of antipsychotic medication use.[28] It is possible, however, that these differences in treatment response may be confounded by sex differences in clinical symptom severity and age at illness onset described above.[3]

Factors contributing to sex differences

Biological factors

The steroids and hormones associated with sex differentiation during fetal development have critical effects on neuronal development in humans, and there is evidence that these hormones have implications for sex differences in brain abnormalities observed in adults with schizophrenia.[3] MRI studies have revealed more severe brain damage in men diagnosed with schizophrenia than women.[29] Specifically, larger lateral and third ventricles and reduced volumes of critical regions such as the hippocampus, amygdala, and prefrontal cortical regions have been observed in men.[29] These brain abnormalities likely contribute to the observed short-term and long-term memory deficits in men diagnosed with schizophrenia.[30] It has been hypothesized that estrogen may serve a protective role in female development, buffering against the development of pervasive damage to this region.[31][27] Further support for this hypothesis derives from the observation of a third peak of onset for women after menopause, which is associated with a reduction of estrogen, and the increased response to treatment in pre-menopausal women compared to post-menopausal women.[27][32][33] Additionally, there is evidence that estradiol may be an effective adjunct to antipsychotic medication in reducing psychotic symptoms.[34]

Social and environmental factors

Social cognition and social functioning

Premorbid social functioning and social cognition, robust predictors of relapse in this population, differ significantly between men and women.[15][35] Men have poorer overall premorbid social functioning and social cognition, which is associated with higher rates of isolation, loneliness, and lower quality of life.[35][36] Social cognitive and functional deficits are also related to the increased expression of negative symptoms observed in men.[15][37] Additionally, these factors are also associated with reduced social network size and lower marriage rates in men with schizophrenia compared to women.[4] Younger age at onset in men may also negatively impact community reintegration following the illness onset by delaying the development of life skills necessary to develop strong social support networks and foster self-perceptions of efficacy and agency.[36]

Substance abuse and dependence

Sex-related differences in substance use and dependence have been observed in individuals with schizophrenia and those at risk for developing the illness. In early adolescence, sex-related differences in cannabis use have been observed, with males using more heavily than females in the general population and in those at risk for developing schizophrenia.[38] There is evidence that these differences could in part be attributed to the predictive relationship between levels of testosterone in early adolescence and later cannabis use and dependence.[39] Frequent cannabis use in early adolescence may be a risk factor for developing schizophrenia in men.[40] There is some evidence that heavy, early cannabis use may be associated with impeded cortical maturation in males at a high risk for developing schizophrenia, potentially accelerating the course of illness in these individuals.[38]

Substance abuse is also highly correlated with poorer functional outcomes and can significantly influence the course of illness. Current research estimates that 36% of men have a history of illicit substance use versus 16% of women.[3][41] Nicotine dependence is also highly prevalent in individuals with schizophrenia. An estimated 80% of individuals with schizophrenia smoke cigarettes compared to 20% of the general population.[42] Men with schizophrenia are more likely to start smoking than women, but social factors associated with mental illness contributing to increased rate of smoking in both genders.[43]

References

  1. ↑ McGrath, John; Saha, Sukanta; Chant, David; Welham, Joy (2008). "Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality" (PDF). Epidemiologic Reviews. 30: 67–76. doi:10.1093/epirev/mxn001. PMID 18480098. S2CID 2448141. Archived from the original (PDF) on 2017-04-09.
  2. 1 2 3 Aleman; Kahn; Selten (2003). "Sex differences in the risk of schizophrenia: evidence from meta-analysis". Archives of General Psychiatry. 60 (6): 565–71. doi:10.1001/archpsyc.60.6.565. PMID 12796219.
  3. 1 2 3 4 5 6 7 8 Abel, Kathryn; Drake, Richard; Goldstein, Jill (2010). "Sex differences in schizophrenia". International Review of Psychiatry. 22 (5): 417–428. doi:10.3109/09540261.2010.515205. PMID 21047156. S2CID 44933381.
  4. 1 2 Diagnostic and Statistical Manual of Mental Disorders. Arlington Virginia: American Psychological Association. 2013. ISBN 9780890425596.
  5. ↑ Lewine, Richard; Martin, Morgan; Hart, Mara (2017). "Sex versus gender differences in schizophrenia: The case for normal personality differences". Schizophrenia Research. 189: 57–60. doi:10.1016/j.schres.2017.02.015. PMC 5559345. PMID 28215470.
  6. 1 2 3 Drake, Richard J.; Addington, Jean; Viswanathan, Ananth C.; Lewis, Shôn W.; Cotter, Jack; Yung, Alison R.; Abel, Kathryn M. (2016-02-16). "How Age and Gender Predict Illness Course in a First-Episode Nonaffective Psychosis Cohort". The Journal of Clinical Psychiatry. 77 (3): e283–e289. doi:10.4088/jcp.14m09369. ISSN 0160-6689. PMID 26890690.
  7. ↑ Castle, David J.; Wessely, Simon; Murray, Robin M. (May 1993). "Sex and Schizophrenia: Effects of Diagnostic Stringency, and Associations with Premorbid Variables". British Journal of Psychiatry. 162 (5): 658–664. doi:10.1192/bjp.162.5.658. ISSN 0007-1250. PMID 8149118.
  8. ↑ McGrath, J.; Saha, S.; Chant, D.; Welham, J. (2008-05-14). "Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality". Epidemiologic Reviews. 30 (1): 67–76. doi:10.1093/epirev/mxn001. ISSN 0193-936X. PMID 18480098.
  9. ↑ Saha, Sukanta; Chant, David; Welham, Joy; McGrath, John (2005-05-31). "A Systematic Review of the Prevalence of Schizophrenia". PLOS Medicine. 2 (5): e141. doi:10.1371/journal.pmed.0020141. ISSN 1549-1676. PMC 1140952. PMID 15916472.
  10. ↑ McGrath, John; Saha, Sukanta; Chant, David; Welham, Joy (2008). "Schizophrenia: A Concise Overview of Incidence, Prevalence, and Mortality" (PDF). Epidemiologic Reviews. 30: 67–76. doi:10.1093/epirev/mxn001. PMID 18480098. S2CID 2448141. Archived from the original (PDF) on 2017-04-09.
  11. ↑ Aleman; Kahn; Selten (2003). "Sex differences in the risk of schizophrenia: evidence from meta-analysis". Archives of General Psychiatry. 60 (6): 565–71. doi:10.1001/archpsyc.60.6.565. PMID 12796219.
  12. ↑ Abel, Kathryn; Drake, Richard; Goldstein, Jill (2010). "Sex differences in schizophrenia". International Review of Psychiatry. 22 (5): 417–428. doi:10.3109/09540261.2010.515205. PMID 21047156. S2CID 44933381.
  13. ↑ Goldstein, Jill M.; Link, Bruce G. (January 1988). "Gender and the expression of schizophrenia". Journal of Psychiatric Research. 22 (2): 141–155. doi:10.1016/0022-3956(88)90078-7. ISSN 0022-3956. PMID 3404482.
  14. ↑ Cheng, C.Z.; Wu Qianjin (February 1994). "Popula tion Aging in China: The Demographic Implications". China Report. 30 (1): 29–51. doi:10.1177/000944559403000103. ISSN 0009-4455. S2CID 153662106.
  15. 1 2 3 Morgan, Vera A.; Castle, David J.; Jablensky, Assen V. (January 2008). "Do Women Express and Experience Psychosis Differently from Men? Epidemiological Evidence from the Australian National Study of Low Prevalence (Psychotic) Disorders". Australian & New Zealand Journal of Psychiatry. 42 (1): 74–82. doi:10.1080/00048670701732699. ISSN 0004-8674. PMID 18058447. S2CID 23224974.
  16. ↑ Häfner, H.; Riecher, A.; Maurer, K.; Löffler, W.; Munk-Jørgensen, P.; Strömgren, E. (2009). "How does gender influence age at first hospitalization for schizophrenia? A transnational case register study". Psychological Medicine. 19 (4): 903–918. doi:10.1017/S0033291700005626. PMID 2594886.
  17. ↑ Angermeyer, M. C.; Kühn, L. (1988). "Gender differences in age at onset of schizophrenia. An overview". European Archives of Psychiatry and Neurological Sciences. 237 (6): 351–364. doi:10.1007/BF00380979. PMID 3053193. S2CID 1001928.
  18. ↑ Grigoriadis, Sophie; Seeman, Mary V. (2002). "The Role of Estrogen in Schizophrenia: Implications for Schizophrenia Practice Guidelines for Women". The Canadian Journal of Psychiatry. 47 (5): 437–442. doi:10.1177/070674370204700504. PMID 12085678.
  19. ↑ Gogos, Andrea; Sbisa, Alyssa M.; Sun, Jeehae; Gibbons, Andrew; Udawela, Madhara; Dean, Brian (2015). "A Role for Estrogen in Schizophrenia: Clinical and Preclinical Findings". International Journal of Endocrinology. 2015: 1–16. doi:10.1155/2015/615356. PMC 4600562. PMID 26491441.
  20. 1 2 3 4 Grossman, Linda S.; Harrow, Martin; Rosen, Cherise; Faull, Robert; Strauss, Gregory P. (November 2008). "Sex differences in schizophrenia and other psychotic disorders: a 20-year longitudinal study of psychosis and recovery". Comprehensive Psychiatry. 49 (6): 523–529. doi:10.1016/j.comppsych.2008.03.004. ISSN 0010-440X. PMC 2592560. PMID 18970899.
  21. 1 2 Conwell, Yeates; Chen, Eric Yu-Hai; Chan, Cecilia Lai-Wan; Mao, Wen-Jun; Ran, Mao-Sheng (April 2015). "Gender differences in outcomes in people with schizophrenia in rural China: 14-year follow-up study". The British Journal of Psychiatry. 206 (4): 283–288. doi:10.1192/bjp.bp.113.139733. ISSN 1472-1465. PMC 4381189. PMID 25573398.
  22. 1 2 Bergh, Sara; Hjorthøj, Carsten; Sørensen, Holger J.; Fagerlund, Birgitte; Austin, Stephen; Secher, Rikke Gry; Jepsen, Jens Richardt; Nordentoft, Merete (August 2016). "Predictors and longitudinal course of cognitive functioning in schizophrenia spectrum disorders, 10 years after baseline: The OPUS study". Schizophrenia Research. 175 (1–3): 57–63. doi:10.1016/j.schres.2016.03.025. ISSN 0920-9964. PMID 27050475. S2CID 3151870.
  23. ↑ Castle, David J.; Wessely, Simon; Murray, Robin M. (May 1993). "Sex and Schizophrenia: Effects of Diagnostic Stringency, and Associations with Premorbid Variables". British Journal of Psychiatry. 162 (5): 658–664. doi:10.1192/bjp.162.5.658. ISSN 0007-1250. PMID 8149118.
  24. ↑ Morgan, Vera A.; Castle, David J.; Jablensky, Assen V. (January 2008). "Do Women Express and Experience Psychosis Differently from Men? Epidemiological Evidence from the Australian National Study of Low Prevalence (Psychotic) Disorders". Australian & New Zealand Journal of Psychiatry. 42 (1): 74–82. doi:10.1080/00048670701732699. ISSN 0004-8674. PMID 18058447. S2CID 23224974.
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  26. ↑ Abel, Kathryn; Drake, Richard; Goldstein, Jill (2010). "Sex differences in schizophrenia". International Review of Psychiatry. 22 (5): 417–428. doi:10.3109/09540261.2010.515205. PMID 21047156. S2CID 44933381.
  27. 1 2 3 Goldstein, Jill M.; Cohen, Lee S.; Horton, Nicholas J.; Lee, Hang; Andersen, Scott; Tohen, Mauricio; Crawford, Ann-Marie K.; Tollefson, Gary (May 2002). "Sex differences in clinical response to olanzapine compared with haloperidol". Psychiatry Research. 110 (1): 27–37. doi:10.1016/s0165-1781(02)00028-8. ISSN 0165-1781. PMID 12007591. S2CID 25470846.
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  29. 1 2 Flaum, M.; Swayze Vw, 2nd; O'Leary, D. S.; Yuh, W. T.; Ehrhardt, J. C.; Arndt, S. V.; Andreasen, N. C. (May 1995). "Effects of diagnosis, laterality, and gender on brain morphology in schizophrenia". American Journal of Psychiatry. 152 (5): 704–714. doi:10.1176/ajp.152.5.704. ISSN 0002-953X. PMID 7726310.
  30. ↑ Han, M.; Huang, X. F.; Chen, D. C.; Xiu, M. H.; Hui, L.; Liu, H.; Kosten, T. R.; Zhang, X. Y. (2012). "Gender differences in cognitive function of patients with chronic schizophrenia". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 39 (2): 358–363. doi:10.1016/j.pnpbp.2012.07.010. PMID 22820676. S2CID 6021327.
  31. ↑ Häfner, H (2003). "Gender differences in schizophrenia". Psychoneuroendocrinology. 28: 17–54. doi:10.1016/s0306-4530(02)00125-7. PMID 12650680. S2CID 9307284.
  32. ↑ Castle D, Sham P, Murray R. (1998). "Differences in distribution of ages of onset in males and females with schizophrenia". Schizophrenia Research. 33 (3): 179–183. doi:10.1016/s0920-9964(98)00070-x. PMID 9789910. S2CID 22355423.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  33. ↑ Castle D, Sham P, Murray R. (1998). "Differences in distribution of ages of onset in males and females with schizophrenia". Schizophrenia Research. 33 (3): 179–183. doi:10.1016/s0920-9964(98)00070-x. PMID 9789910. S2CID 22355423.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  34. ↑ Kulkarni J, Riedel A, de Castella AR; et al. (2001). "Estrogen – A potential treatment for schizophrenia". Schizophrenia Research. 48 (1): 137–144. doi:10.1016/s0920-9964(00)00088-8. PMID 11278160. S2CID 42146691.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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  37. ↑ Grossman, Linda S.; Harrow, Martin; Rosen, Cherise; Faull, Robert; Strauss, Gregory P. (November 2008). "Sex differences in schizophrenia and other psychotic disorders: a 20-year longitudinal study of psychosis and recovery". Comprehensive Psychiatry. 49 (6): 523–529. doi:10.1016/j.comppsych.2008.03.004. ISSN 0010-440X. PMC 2592560. PMID 18970899.
  38. 1 2 Paus, Tomáš; Pausova, Zdenka; Smith, George Davey; Schumann, Gunter; Timpson, Nic J.; Whelan, Robert; Walter, Henrik; Smolka, Michael N.; Rietschel, Marcella (2015-10-01). "Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation in Adolescence". JAMA Psychiatry. 72 (10): 1002–1011. doi:10.1001/jamapsychiatry.2015.1131. ISSN 2168-622X. PMC 5075969. PMID 26308966.
  39. ↑ Tarter, Ralph E.; Kirisci, Levent; Gavaler, Judith S.; Reynolds, Maureen; Kirillova, Galina; Clark, Duncan B.; Wu, Jionglin; Moss, Howard B.; Vanyukov, Michael (January 2009). "Prospective Study of the Association Between Abandoned Dwellings and Testosterone Level on the Development of Behaviors Leading to Cannabis Use Disorder in Boys". Biological Psychiatry. 65 (2): 116–121. doi:10.1016/j.biopsych.2008.08.032. ISSN 0006-3223. PMC 2643094. PMID 18930183.
  40. ↑ Manrique-Garcia, E.; Zammit, S.; Dalman, C.; Hemmingsson, T.; Andreasson, S.; Allebeck, P. (2011-10-17). "Cannabis, schizophrenia and other non-affective psychoses: 35 years of follow-up of a population-based cohort". Psychological Medicine. 42 (6): 1321–1328. doi:10.1017/s0033291711002078. ISSN 0033-2917. PMID 21999906. S2CID 34537539.
  41. ↑ Jablensky, Assen; McGrath, John; Herrman, Helen; Castle, David; Gureje, Oye; Evans, Mandy; Carr, Vaughan; Morgan, Vera; Korten, Ailsa (April 2000). "Psychotic Disorders in Urban Areas: An Overview of the Study on Low Prevalence Disorders". Australian & New Zealand Journal of Psychiatry. 34 (2): 221–236. doi:10.1080/j.1440-1614.2000.00728.x. ISSN 0004-8674. PMID 10789527. S2CID 41541983.
  42. ↑ Keltner, N. L.; Grant, J. S. (2006). "Smoke, Smoke, Smoke That Cigarette". Perspectives in Psychiatric Care. 42 (4): 256–261. doi:10.1111/j.1744-6163.2006.00085.x. PMID 17107571.
  43. ↑ Johnson, J.; Ratner, P.; Malchy, L.; Okoli, C.; Procyshyn, R.; Bottorff, J.; Groening, M.; Schultz, A.; Osborne, M. (2010). "Gender-specific profiles of tobacco use among non-institutionalized people with serious mental illness". BMC Psychiatry. 10: 101. doi:10.1186/1471-244X-10-101. PMC 3002315. PMID 21118563.
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