Sex Differences in Schizophrenia

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World Health Organisation defines schizophrenia as “a severe mental disorder, characterized by profound disruptions in thinking, affecting language, perception, and the sense of self. It often includes psychotic experiences, such as hearing voices or delusions. It can impair functioning through the loss of an acquired capability to earn a livelihood or the disruption of studies.”

Evident and persisting sex differences have been described in many areas of schizophrenia research. The objective of this study is to extend our empirical knowledge and theoretical understanding by elucidating sex differences in schizophrenia. Evidence from other areas of psychopathology states that methodical examination of gender differences can help formulate etiological theories. (Cloninger, Christiansen, Reich, & Gottesman, 1978; Weissman & Klerman, 1977). Furthermore, sex is not a vague variable, like intelligence or socioeconomic status, therefore, it isn’t affected by cause-effect ambiguity.

This paper illustrates sex differences in the following areas: age, social and cognitive functioning, prognosis, and response to treatment. Moreover, the study tries to discern the reasons behind the presence of these differences. Finally, it is questioned whether these differences prevail in the Indian context.

Age

The most replicated findings in studies about sex differences in schizophrenia are about age-of-onset. Typically, but not always, the age-of-onset for men has been stated to be less than that of women. Studies have observed a later age-of-onset as well as older age at first admission in hospitals for females with schizophrenia. The ICD-10 and the DSM-IV-TR also mark that females have a later age-of-onset of schizophrenia. In addition, the onset distribution curves for males and females are not isomorphic. There appear to be two peaks in the age-of-onset of disease when it comes to women: the ﬁrst after menarche and the second once they are over 40.

Social and Cognitive Functioning

It has been seen that when it comes to social and cognitive functioning, women show better performance. Chaves et al.(1993) found that women were better adapted and presented less disability than men.

Work record: Affleck et al. (1976) reported women's superior work record following a schizophrenic illness.
Marriage: Women are more capable to form intimate relationships that culminate in marriage. It is well-known that more schizophrenic women than men are married. Still, this could probably be a reflection of later onset of illness.
Sociability: Social adjustment (post-hospital) is superior in women as judged by work records and the ability to live with others. One study found differences in sociability in favor of schizophrenic women who were currently hospitalized as well.
Suicide: Although mortality rates from disease, accident, and suicide are high for both men and women in schizophrenia and as high for schizophrenic women in contrast to their female age peers as to their male age peers, suicide, in schizophrenia, as in the general public, remains a decidedly male option.

It appears that in order to trigger a psychotic disorder, women undergo a lack of basic and functional needs and more exposure to stressful life events than men. Though gender differences in cognitive functioning are controversial, the studies that found gender diﬀerences indicate higher levels of functioning in women especially in the language, executive, and memory domains. Goldstein et al., 1994; Seidman et al. 1997; Goldstein et al., 1998; Hoﬀ et al., 1998; Vaskinn, 2011)

Prognosis

Male schizophrenics have been observed to have more negative symptoms. It is more likely for them to exhibit 'typical' schizophrenic symptomatology. They have a tendency towards withdrawal and passivity. Females, on the other hand, more often demonstrate 'atypical' features, including a strong affective component (see Lewine, 1981; Goldstein & Link, 1988). Galderisi et al. (2012) found that men scored higher in disorganization and negative symptoms. In a large sample of patients, Morgan et al. (2008) conducted a study that revealed that there was a higher prevalence of depressive symptoms and a lower prevalence of negative symptoms in women. Previous literature concurs that there exists a higher prevalence of depression and anxiety symptoms.

Response to treatment

Studies concur that schizophrenic women respond somewhat better than men to the various modalities of treatment. Due to the response to the treatment being multi-varied, this finding isn’t as well established as the age-of-onset data. It has been found that schizophrenic women experienced significantly fewer re-hospitalizations and shorter stays at the hospital five and ten year periods as compared to schizophrenic men.

Duration of stay in hospital: Findings from first-admission studies showed that schizophrenic women experienced fewer re-hospitalizations, shorter hospital stays, better social and work functioning, better response to neuroleptics, lower relapse rates, and less severe psychopathological outcomes. Many of the studies found that schizophrenic women experienced fewer re-hospitalizations and shorter hospital stays than schizophrenic men. However, Haro et al. (2008) reported in the SOHO study that women exhibited a higher risk of hospitalization than men.
Quality of remission: Schwartz et al. (1975) assert that the mental status aspect of remission is determined by treatment variables such as time and treatment and time on neuroleptics, but that the social adjustment aspect of remission is related to greater extent socio-demographic variables. In their follow-up study, Affleck et al. (1976) found "present status" worse for males. However, he was discussing employment and hospitalization status instead of mental status.
Neuroleptic Resistance: The patients who were resistant to neuroleptics had a pointedly younger age-at-onset as compared to the neuroleptic-responsive patients. The gender difference in age-at-onset in neuroleptic-resistant schizophrenic patients was not significant. Yet, the expected gender difference in age-at-onset was confirmed in neuroleptic-responsive patients. (Meltzer et al., 1997) In neuroleptic-responsive patients (in some subgroups of schizophrenic patients, especially the paranoid type) gender difference in age-at-onset was significant. Meltzer et al. (1997) confirmed that there was an earlier onset in male schizophrenic patients as a group. The age-at-onset was not significantly different in neuroleptic-resistant men and women. The interval between age at onset and age at first hospitalization is found to be significantly shorter in neuroleptic-resistant patients than in neuroleptic-responsive patients. Thus, it can be inferred that both neuroleptic responsivity and subtype of schizophrenia are influencing the gender effect on age at onset. The neuroleptic-responsive females with the paranoid subtype having onsets 5 to 7 years later, on average than their male counterparts. Younger age-at-onset, particularly for women, is associated with resistance to typical neuroleptic treatment. The onset of neuroleptic-resistant schizophrenia was found to be earlier than that of neuroleptic-responsive schizophrenia. This relationship was most evident in the female patients but was also apparent in the men as well.
Recurrence Rates: In a study by Hogarty et al. (1974), it was observed that men relapsed twice as frequently as women. Female superiority in avoiding re-hospitalization was also supported by Affleck et al. (1976)

Why do these differences exist?

Previous work has also demonstrated a bivariate relationship between gender and premorbid functioning and between premorbid functioning and outcome. That is, schizophrenic men have been found to have poorer premorbid histories than schizophrenic women, and poor premorbid history has been found to lead to a poorer outcome.
Non-specific accumulating stress factors could selectively affect the male, which results in reaching demonstrable illness at a relatively earlier age.
The presence of specific biological protective factors in the female.
1. Laterality. Cerebral laterality refers to the anatomic and functional differences between the two halves of the brain. Women and men end up with a consistently different pattern of lateralized functions. The left hemisphere has less adequate circulation than the right one in both sexes, thereby, making it more vulnerable to disease. Several linguistic, articulatory disturbances of childhood, disturbances of functions develop because of the presence of this vulnerability. Infantile autism, childhood dyslexia, and stuttering are thought to be left hemisphere dysfunctions. In each of these dysfunctions, the male has four to five times increased incidence over the female. This may be a consequence of the female’s bilateral representation of language functions. There is some evidence that schizophrenia is also a left hemisphere disorder. Therefore, it has similar sex differences.
2. Neurotransmitters. The reason for later onset in neuroleptic-responsive female patients with paranoid subtype maybe the existence of differences in neurotransmitters related to psychosis (e.g., dopamine, serotonin, glutamate), sex steroids (estrogens, progesterone, testosterone), glucocorticoids. Further, other complex processes related to psychosis (synaptic pruning) may operate differently than in other patients with schizophrenia. Thus, sex differences in brain organization, vulnerability to birth trauma, rate of postnatal maturation, and effects of sex steroids on various biological processes during the premorbid period may contribute to the manifestation of neuroleptic resistance.
  1. Estrogen differences in Dopamine. Studies show that estrogen produces an anti-dopaminergic effect. Estrogen acts as neuroleptic which explains clinical observations like later onset of the illness in women and improved prognosis. This happens because the estrogen enhances the vulnerability threshold for schizophrenia, resulting in the first manifestation in females. From puberty on, this structural effect is reinforced by a functional effect. It also gives an explanation about postpartum schizophrenia which occurs after estrogen drop. Both effects disappear when estrogen secretion reduces around menopause leading to late-onset of those genetically predisposed women who had been protected by the effect of estrogens.

This means that women who develop schizophrenia ought to display greater genetic vulnerability, greater cumulative and precipitating stress factors, “male” cerebral hemisphere organization, and low estrogen levels. There haven’t been biological explanations for sex-related clinical differences that can successfully persuade one to believe them. This may be because such justifications do not take into account diverse influences, including social variables.

Sex differences in Schizophrenia: In the Indian Context

This study conducted by Venkatesh et al. (2008) indicates that there is no significant difference between the sexes in the age of onset of schizophrenia in India. It actually shows a completely reverse result. Among early-onset patients, females have an earlier age-of-onset than males. Among late-onset patients, they have a later age of onset. A significant finding is the lack of association between age of onset and sex, which has been one of the most vigorously researched areas in gender-based work.

Although nearly all Western studies have unmistakeably found a later age-of-onset in women, studies from Ghana (Sikanartey & Eaton, 1984) and Southeast Asia (Tsoi & Cheng, 1979; Buhrich & Haq, 1980) reported a similar trend. A reversed pattern was reported to form the Philippines (Weiner & Marvit, 1977). The three center sample of the same study (Verghese et al, 1985) found no gender differences in the age of onset.

The results of the study show that similar to the literature from Western countries, “women have an earlier, higher peak in age-of-onset in the early twenties and a later, lower peak in their late thirties. However, unlike Western countries, men had a fairly later peak in the age of onset in the early thirties, followed by a steep decline through the older age ranges. It may be reasoned that this is because of the lesser number of men with very early age-of-onset in the sample.”

As a measure of abundant caution, it would be good to bear in mind that many Indian studies may not have absolutely accurate age measurements, since a large section of the population tend to be more approximate than truly accurate as far as age estimation is conceded. This is especially true of a rural sample and a lower income group urban population. The final word on age-of-onset in India can be said only after a study that carefully eliminates even the slightest of errors in the recording of age is conducted.

Conclusion

This paper discusses gender differences in schizophrenia. Most studies hold that males have a younger age-of-onset. There are two peaks for the onset of the illness in women: menarche and menopause. A review of previous literature confirmed that though gender differences in social and cognitive functioning aren’t as well-established, according to most studies, women tend to fare better in these areas as compared to men. Males were found to be more disabled and less well-adjusted, socially and occupationally, than their female counterparts. It has also been observed that men with schizophrenia have a somewhat inferior response to treatment and a generally poorer prognosis than women. Male schizophrenics are disposed to a more severe form of schizophrenia than females. In addition, relapses are more frequent and more severe, and response to neuroleptic medication less favorable. Males are more likely to exhibit negative symptoms characterized by withdrawal and passiveness while women display more affective symptoms. The occurrence of these differences can be attributed to the presence of biological protective factors in women: bilateral representation of language functions, and the anti-dopaminergic effect of estrogen. Finally, in the Indian context, significant sex differences haven’t been observed. Still, it appears that among early-onset patients, women have an earlier age-of-onset but among later-onset patients, they have been reported to have a later age of onset. Further studies are required to examine the influence of confounding factors, such as the family history of schizophrenia, pre-morbid personality, and obstetric complications on gender differences in age at onset of schizophrenia.