Why do men develop schizophrenia earlier than women?

Dr. Mary Seeman offers possible answers

Article by S. Hussain Ather

Graphic design by Sherry An

A Disease Marked by Difference 
Men develop schizophrenia earlier than women, usually by up to three to five years.1,2 Men are also more likely to show harmful symptoms and decreased social functioning, while women respond more rapidly to treatment. However, the reason for these differences is not clear. Researchers have searched for explanations for decades. They have raised potential answers from environmental, psychological, and neurobiological contexts, but the answers are far from straight-forward. Dr. Mary Seeman, Professor Emerita in the Department of Psychiatry at the University of Toronto has dedicated her career to exploring gender differences and disparities in psychiatric diseases. With over 12,000 citations, Dr. Seeman has made significant contributions to her field. In this interview, she sheds light on the complexities of gender and schizophrenia.


Dr. Mary Seeman
MDCM, FRCPC, DSc
Professor Emerita in the Department of Psychiatry.

Photo Credit: Kenneth Chou

Lost in Causes and Conjecture 

Schizophrenia affects 20 million people worldwide.3 The disease is characterized by delusions and hallucinations, paranoia, and difficulty concentrating that change the brain’s wiring to alter the way we perceive the world. This creates fundamental changes, not only in the way the nervous system reacts to the world around it, but in how patients with schizophrenia patients develop and construct their own identities. The disease results from a combination of interactions between genetic, psychosocial, and environmental factors. This means the search for the cause of the disparity between men and women depends on this complicated mix of factors. 

Dr. Seeman noted many possible reasons why men develop schizophrenia earlier than women. These can occur at any time during the life course, even as early as in utero with complications during pregnancy or delivery. Dr. Seeman noted, “all neurodevelopmental illnesses really are far more common in boys.” Early exposure to physical trauma could also expose boys to more neurobiological stressors that could cause the disease. Alongside this, in childhood, males tend to show greater communication problems than females, with a higher prevalence of speech disorders and slower language acquisition. These can contribute to difficulties with emotional expression associated with schizophrenia.4,5 

The hormone hypothesis is another explanation for sex disparities in schizophrenia. Low levels of testosterone in men have been associated with more severe symptoms of the disease. While female schizophrenia patients often have more severe symptoms in the low estrogen phase of their menstrual cycle.1

The gender disparities in schizophrenia may also stem from psychosocial causes. Adherence to traditional normative beliefs of male behaviour and masculinity, notably emotional repression and self-reliance, could be a contributing factor.6 These norms and beliefs discourage men from seeking help and treatment for mental illnesses. 

There are also important neurobiological components. Schizophrenia patients have deficits in intracortical myelin (ICM), myelin found in the gray matter of the cortex in the brain.7 Rates of myelination also differ between genders, with women showing a higher rate of increase in fiber density in associative white matter regions of the brain as they age.8 These regions consist of myelinated axons, responsible for communication between regions. The brains of patients with schizophrenia tend to have abnormalities in their white matter tracts.9 Dr. Seeman noted, these deficits could also be contributing to the gender differences. 

Finally, Dr. Seeman notes that the discrepancy between men and women could also hinge on issues of sampling, confounding variables, and the individuals studied. “There are many parts of the world where this conclusion may not apply.” In some countries, such as Croatia, no gender difference was observed.10,11 Age of onset for the disease has been observed to be the same in others, and, for families with a history of schizophrenia, the difference in age of onset is typically eliminated, Dr. Seeman noted. 

On ways to move forward

Dr. Seeman and other researchers have presented various answers to the question of why there exists a difference in expression and disease progress in men and women diagnosed with schizophrenia. The links between these answers and the disparity itself can be explored more thoroughly. It is still unclear how exactly these causes play out in the grand scheme of schizophrenia. Exploring the underlying etiology and pathophysiology of the disease through interdisciplinary research in psychiatry, epidemiology, and similar fields, could shed light on this relationship.

References:

  1. Li R, Ma X, Wang G, et al. Why sex differences in schizophrenia?. J Transl Neurosci. 2016 Sep;1(1):37.
  2. Leung MD DA, Chue MRC Psych DP. Sex differences in schizophrenia, a review of the literature. Acta Psychiatr Scand. 2000 Jan;101(401):3-8.
  3. James SL, Abate D, Abate KH, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10;392(10159):1789-858.
  4. Seeman MV. Care gaps in schizophrenia: male/female differences. The University of British Columbia: This Changed My Practice. 2013 Mar 18.
  5. Seeman MV. Does gender influence outcome in schizophrenia?. Psychiatr Q. 2019 Mar;90(1):173-84.
  6. Lanzenberger R, Kranz GS, Savic I. Sex Differences in Neurology and Psychiatry, 1st edition. Elsevier; 2020. 
  7. Tishler TA, Bartzokis G, Lu PH, et al. Abnormal trajectory of intracortical myelination in schizophrenia implicates white matter in disease pathophysiology and the therapeutic mechanism of action of antipsychotics. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 May 1;3(5):454-62.
  8. Schmithorst VJ, Holland SK, Dardzinski BJ. Developmental differences in white matter architecture between boys and girls. Hum Brain Mapp. 2008 Jun;29(6):696-710.
  9. Fields RD. White matter in learning, cognition and psychiatric disorders. Trends Neurosci. 2008 Jul 1;31(7):361-70.
  10. Folnegović Z, Folnegović-Šmalc V. Schizophrenia in Croatia: age of onset differences between males and females. Schizophrenia research. 1994 Dec 1;14(1):83-91.
  11. Jablensky A, Cole SW. Is the earlier age at onset of schizophrenia in males a confounded finding?: Results from a cross-cultural investigation. The British Journal of Psychiatry. 1997 Mar;170(3):234-40.