Existence of Actual Gender Difference in Schizophrenia: Analytical Essay

Schizophrenia is a mental disorder affecting 1% of the population; it is classified by multiple symptom categories, including positive psychotic symptoms, negative symptoms, disordered thoughts or speech and cognitive deficits (APA, 2013 & McGrath, Saha, Chant & Welham, 2008). A characterizing feature of the disorder is the difference in pathology between men and women, which is portrayed in almost all features (Nawka et al, 2013). However, studies examining these differences produce a number of contradictory results and are methodologically flawed (Gogos, Ney, Seymour, Rheenen & Felmingham, 2018). Therefore, the existence of a true gender difference remains contentious (Cechnicki, et al., 2018). Identifying whether and how men and women differ with schizophrenia is fundamental to understanding the epidemiology of the disease, which can further help to determine treatment regimes and responses. Therefore, this essay will argue that there are a number of profound gender differences concerning most pathologies of schizophrenia, however due to methodological inconsistencies, several of these differences are overestimated and emerge as a overall gender difference rather than from schizophrenia alone. These differences will be shown through prevalence, age of onset and symptomatology; two relevant causes will be examined; and the differences in response to antipsychotics and the use of estrogen as a treatment. The terminology ‘sex’ and ‘gender’ have been inappropriately applied throughout the literature, as they have been used inconsistently and interchangeably, resulting in a misinterpretation (Lewine, 2004). Sex denotes biologically determined characteristics, while gender indicates culturally and socially shaped differences (WHO, n.d.). However, this essay will compare and examine research on both gender and sex differences in schizophrenia.

One of the best replicated gender differences is the tendency for males to manifest the disease at an earlier age of onset compared to females whose onset is typically three to five years later (Jones, 2013). Males have a single peak, which is between the ages of 21 and 25, whereas women have two peaks, between 25 and 30 and then after age 45 (Jones, 2013). The incidence of schizophrenia in men compared to women is estimated to be 1.4:1, irrespective of confounds such as culture, socio-occupational functioning, or social role expectation (Hafner, 2003). However, after the age of 45 women predominate and twice as many women are diagnosed with schizophrenia than men (Riecher- Rossler, 2017). Research has used the term ‘age of onset’ inconsistently and involves different cut off ages; therefore findings should be interpreted with caution (Chang et al., 2011). Nonetheless, differences in age of onset and prevalence are consistently demonstrated and findings are established worldwide, resulting in a prominent gender difference (Aleman, Kahn & Selten, 2003).

The age of onset is highly related to symptom severity in men and women. An earlier age of onset predicts more negative and disorganized symptoms and a poorer symptomatic course, while a later onset represents a better outcome, which is attributed to the type of symptoms experienced (Grossman, Harrow, Rosen, Faull & Strauss, 2008). Consequently, women are believed to have a more favourable course and a better psychosocial outcome than men due to their later age of onset (Lindamer, Lohr, Harris & Jeste, 2004). However, this just demonstrates that there is a relationship between age, symptoms and gender. It may be that gender differences in symptomatology are important in determining outcomes but in themselves depend on the age of presentation. For example, paranoid symptoms may be more severe in women than in men with older onset (Hafner, Maurer, Loffler, & Riecher-Rossler, 1993). Consequently, research appears to overestimate the influence of gender, as differences are more likely to be the product of age.

Following from this, men and women differ in their expression of symptoms. Men have poorer premorbid adjustments, a higher tendency to negative symptoms, lower social functioning, and a higher co-morbidity with substance abuse (Abel, Drake & Goldstein, 2010). Nonetheless, a greater propensity for substance abuse and lower functioning is also reflective of males in the general population and therefore such differences are not schizophrenic specific (Rietschel et al. 2017). Once more, women are found to have more affective and depressive symptoms and milder cognitive deficits than men. However, such findings imitate higher levels of depression found in women in the general population and again are not the product of schizophrenia alone (Grossman et al. 2008 & Seedat et al. 2009). Thus the research is misleading as it overemphasizes the extent to which gender differences are exclusive to schizophrenia.

Further, it has been proposed that the few studies that have found a distinction in symptomatology depend on the rigidness of the diagnostic criteria applied. For example, Aleman et al. (2003) searched the Medline and Psychlit database for publications on incidence and schizophrenia that appeared during January 1980 and September 2001 and found that the broader the diagnostic criteria the less significant the gender differences in symptomatology and incidence. Therefore it appears gender differences vary more by diagnostic criteria than by actual reliable and genuine differences.

Recently the roles of gonadal steroid hormones, in particular estrogen have received a lot of attention due to their potent and widespread effects on the brain (Gogos et al. 2018). Estrogen is hypothesized to play a neuro-protective and neuro-leptic role against schizophrenic pathology in women and it is thought to do this through an involvement with dopamine (Nieratschker, Nothen & Rietschel, 2010). Animal studies provide evidence that estrogen regulates dopamine systems for example; Gattaz, Behrens, De and Hafner (1992) gave ovariectomized rats a four-week estrogen treatment and found a considerable reduction of apomorphine-stimulated dopaminergic behaviour compared with two control groups. Further the post-mortem revealed that estrogen reduced the sensitivity of the D2 receptors. Leading them to conclude that estrogen acts as a barrier to dopamine receptors. Therefore estrogen may prevent an increase in dopamine in women, something often found in patients with schizophrenia, supporting the idea that estrogen acts as a deterrent.

This further explains why declining levels of estrogen are associated with deteriorating symptoms in female patients and why symptoms vary with their menstrual cycles, where symptoms worsen in low estrogen phases, due to a loss of protection from estrogen (Grigoriadis & Seeman 2002). Lastly, it clarifies why women have a second peak in onset of schizophrenia in their late forties since at this time estrogen levels drop due to menopause. Not only does the neuro-protective role of estrogen explain the cause behind the later age of onset in women but also it helps to understand reasoning behind differences in symptom severity. However, there are a number of biological differences between rats and humans and animal models often do not translate into replications in human trials reducing external validity, therefore research should focus on human research (Roberts, Kwan, Evans & Haig, 2002). Even so, the role of estrogen in women with schizophrenia accounts for a robust gender difference in understanding the different causes. Future research should further understand the biochemical nature of the hormone.

The stress vulnerability model, explains how schizophrenia develops and evolves over time. It proposes that schizophrenia develops from a vulnerability that is combined with sufficient stress (Rudnick & Lundberg, 2012). Vulnerability is determined by a person’s genetic makeup and early life experiences. Traumatic events in early life such as sexual, physical and emotional abuse increase a person’s vulnerability of developing schizophrenia (Rudnick et al. 2012). Men and women differ in responses to these events and are affected differently (Ammari, Heinrich & Miles, 2010). Women are more likely to have a history and be affected by sexual abuse (Riecher-Rossler, Pfluger & Borgwardt, 2010), compared to men who are more affected by lower family support and negative family attitudes (Leung & Cheu, 2000). Thereby demonstrating a difference between what determines vulnerability. However it may be that this represents a gender difference in the likelihood of encountering a particular situation rather than an actual gender difference in shaping vulnerability to schizophrenia. Vulnerability is further affected by substance use; this is particularly prevalent in men (Rudnick et al. 2012). The Australian low prevalence study recorded that 36% of men with a psychotic disorder had a history of illicit substance abuse or dependence compare to 16% of women (Carr, Neil, Halpin, Holmes & Lewin, 2003). Cannabis is linked to triggering psychoses and is used significantly more in men. Experimental administration of the active ingredient tetrahydocannabionol in cannabis induced transient psychosis in normal subjects (Murray, Quigley, Quattrone, Englund & Di Forti, 2016). Additionally, it has a profound effect on course of illness in men such as a stronger severity of symptoms, considerable impairment of global functioning and a elevated risk of relapse, in part explaining men’s more detrimental course of illness and earlier age of onset (Crocker & Tibbo, 2017). The stress vulnerability model is a useful framework for understanding how risk factors act differently in men and women.

There are a number of treatments for schizophrenia; antipsychotics are the most common form of medication and men and women differ in their responses to them. Women show better treatment compliance and a better outcome than men, for example they show 50% less hospitalizations (Morken, Widen & Grawe, 2008). Though, they experience more side effects for example, hypotension and weight gain (Seeman, 2004 & Russel & Mackell, 2001).

There are two classes of antipsychotics, typical and atypical and they work on different symptoms. Accordingly the prescription of them differs between men and women. For example, Clozapine, an atypical antipsychotic is more appropriate for negative symptoms, which are more likely to be found in men or on affective symptoms, which are more likely to be found in women (Goldestein & Link, 1988). However, this is only found in atypical antipsychotics, consequently gender emerges as a predictor of clinical responses to antipsychotic treatment but its influence is not the same for all antipsychotics (Usall, Suarez & Haro, 2007). Additionally research is methodologically flawed due to a lack of double-blindness, little control for dose and subjects weight and absence of adequate matching of women and men. Taking these factors into account it is unclear whether there are actually any gender differences (Abel et al. 2010).

However, a difference consistently found is that men often require higher dosages of antipsychotic drugs, attributed to male patients higher levels of cigarette smoking and caffeine consumption, leading to better liver enzymatic clearance (Smith, 2010). Nevertheless this is not the case for post-menopausal women due to the decline in levels of estrogen. At this stage women respond poorly to anti-psychotic drugs, leading to the support of estrogen as a treatment (AFOTU, 2010). Arad and Weiner, (2009) found that when female rats with no ovaries were given estrogen schizophrenic symptoms decreased. Whereas treating rats with the anti-psychotic haloperidol resulted in no difference. Estrogen has been used as an adjunctive therapy to antipsychotics and it increases the effectiveness of anti-psychotic drugs not only in females but also in males (Kulkarni et al. 2011). This highlights the potential to use estrogen as a therapy in women and provides further support that it plays a neuro-protective role in women. However it is still largely unknown how exactly estrogen helps alleviate schizophrenic symptoms. Short term it has shown positive effects but researchers are unsure of its reliability in the long term and side effects are unknown. Therefore future research should focus on longitudinal studies and further investigate its affect in men.

In summary the existence of actual gender difference in schizophrenia remains a contentious issue (Cechnicki, et al., 2018). Ultimately this essay argues that there are a number of profound gender differences concerning most pathologies of schizophrenia. However due to methodological inconsistencies, several of these differences are overestimated and emerge as an overall gender difference rather than from schizophrenia alone. It has done this by discussing differences in prevalence, age of onset and symptomatology; the role of estrogen and a stress vulnerability model; the differences in response to antipsychotics and estrogen as a treatment. Therefore determine whether a true gender difference really exists future research and clinical practice needs to examine the sex and gender aspects of the disorder more intensely through more methodologically sound, longitudinal and interdisciplinary research.