M. Afzal Javed, M.D., MRCPsych*

Schizophrenia is a condition that has been recognised all over the world. Similarities in its incidence, prevalence and presentation are well acknowledged in all cultures. There are, however, some dissenting voices which point out some important differences in certain aspects of this illness. Gender is one such area where recent work highlights different views. This paper summarises the said work suggesting a strong case for dissimilarities in age of onset, genetic predisposition, pre morbid functioning, morphological changes, phenomenology, course and outcome of schizophrenia in male and female schizophrenics. While discussing these differences, an attempt is made to generate some discussions whether we are having two types of schizophrenias or are we dealing with one disorder having two overlapping, but, distinct syndromes?

J Psychiatr Assoc Thailand 2000; 45(2):189-198.

Key words : schizophrenia, gender

* Consultant Psychiatrist and Visiting Senior Lecturer, University of Warwick, the Medical Centre, 2 Manor Court Avenue, Nuneaton CV11 5HX, United Kingdom

M Afzal Javed, M.D., MRCPsych*

โรคจิตเภทเป็นที่รู้จักกันทั่วโลกโดยพบอุบัติการณ์ ความชุก และลักษณะอาการที่คล้ายคลึงกันในทุกวัฒนธรรม อย่างไรก็ตามพบว่ายังมีความแตกต่างบางประการในโรคนี้ ซึ่งรวมทั้งความแตกต่างระหว่างเพศด้วย บทความนี้จึงได้สรุปและทบทวนถึงความแตกต่างระหว่างผู้ป่วยโรคจิตเภทเพศหญิง และเพศชาย ในเรื่องของอายุที่เจ็บป่วย ปัจจัยทางพันธุกรรม การทำงานเมื่อก่อนป่วย การเปลี่ยนแปลงทางกายวิภาค ปรากฏการณ์วิทยา การดำเนินโรค และผลของการรักษา ในการวิจารณ์ถึงความแตกต่างนี้ ผู้นิพนธ์ได้นำเสนอว่า อาจมีโรคจิตเภทสองชนิด หรืออาจมีเพียงชนิดเดียว แต่ทั้งสองกลุ่มนั้นมีบางส่วนที่ทับซ้อนกันอยู่

วารสารสมาคมจิตแพทย์แห่งประเทศไทย 2543; 45(2): 189-198.

* จิตแพทย์ปรึกษา และอาจารย์พิเศษอาวุโสของมหาวิทยาลัยวาร์วิค, The Medical Centre, 2 Manor Court Avenue, Nuneaton CV11 5HX, ประเทศสหราชอาณาจักร 

Introduction

Schizophrenia is one of the most disabling conditions of all mental disorders. It has been recognised all over the world and is found to affect about 1% of the adult population in all regions and cultures. This illness can begin at any age, but, as this usually starts in the young life, it often disrupts the carrier, damages relationships, causes problems in personality and leads to a number of problems of adjustment in society¹. It is generally assumed that schizophrenia is a chronic and progressive illness, leading to severe impairment in social functioning. While the prognosis and course of this disorder may vary, a poor outcome has been considered to be an almost inevitable eventual outcome in the majority of the cases².

Described at times as one distinct syndrome, schizophrenia is now generally considered as a group of syndromes which are phenomenologically heterogeneous. Although many attempts to describe its phenomenology, aetiology, prognosis and outcome have been proposed since the original description by Emil Kraepelin³, a number of diverse views still exist regarding the boundaries of this disorder.

The difference of opinion in terms of various aspects of this illness range from aetiology to treatment, manifestations to predispositions and clinical presentation to response to different management strategies. It is also interesting to note that when the issue of gender comes up for some scrutiny, it is found that schizophrenia not only affects men and women at different ages; but, it also follows a different course and displays a different gender sensitivity to outcome and treatment. This paper describes some of the updated findings and current viewpoints on the gender difference in this illness. The paper provides an overview of some of the work looking at the presentation, onset, symptomatology, genetic predisposition, treatment and outcome of this disorder with reference to male and female individuals. Based on these observations it is argued that there is a differential susceptibility of males and females to this illness and a division is suggested on the basis of gender for this disorder.

It has been consistently observed that male patients as compared to females have an earlier onset of the illness. Most of the studies find that this difference goes even up to five years. The peak age of onset in males is found to be between 21-25 years, whereas in females the peak age seems to range from 25-30 years. This difference stays consistent considering all measures of onset such as: first psychotic symptoms, earliest signs of mental disorder, contact with the mental health services and a number of hospitalisations⁴. An extensive work on schizophrenia from Central Institute of Mental Health in Mannheim, Germany, by Hafner and colleagues⁵ also concluded that males had an earlier onset. In another study of about 400 consecutive first admissions from a defined catchment area with a diagnosis of schizophrenia or paranoid disorder, Hafner et al found that males showed a single marked peak in their early 20's while females had an onset at a later age group⁶.

Studies carried out in different countries, also support this notion. The World Health Organisation, in one of its recent multi-cultural collaborative study, found that the age of onset was lower in male schizophrenics and this finding was consistent in all countries⁷.

Faraone et al⁸ using more specific statistical tests to correct the male and female distributions of observed age of onset for sex specific age distributions provided further support to the gender difference hypothesis and confirmed that early onset in males was not due to any confounding variables, but did exist as an important and significant factor on its own.

There has been a lot of literature suggesting an effect of seasonality on the incidence of schizophrenia. Takei and Murray⁹ while looking at the season of onset in male and female schizophrenics confirmed a significant seasonal difference for first admissions among different sexes.

The evidence about the familial predisposition and genetic vulnerability to develop schizophrenic illness has been well acknowledged¹⁰. There has been a lot of interest to find out whether this information is also evident regarding different gender. Looking at the families of schizophrenic men and women for any risk for this disorder, Goldstein et al¹¹, in 1990, reanalysed the data from the IOWA cohort of schizophrenic patients. It was interesting to note that age- corrected lifetime risk of DSM III schizophrenia in the first degrees relatives of schizophrenic men was 2.2%, as compared to 5.2% in relatives of schizophrenic females. This observation got further support from some other work by the same group which predicted that relatives of male and female patients seemed to be at different risk for this illness¹².

The neurodevelopmental model of schizophrenia is currently assuming an important aspect in the aetiology of this disorder. It has been found that individuals who develop schizophrenia at a later age, generally present with a history of pre-or peri-natal complications and abnormal neurodevelopment in the early years. Crow and his colleagues favouring this hypothesis, suggested that developmental abnormalities prior to the onset of psychosis, also, differ by gender. Girls who later develop schizophrenia are shy, reserved, insecure and participate less in pear group activity. In contrast, boys who develop this illness tend to be irritable, disagreeable and defiant of authority¹³. Castel and Murray also found that most of the studies show significance differences only for females when viewed in terms of any gender difference. In their review they state that the pace of cerebral development is slower in males and the male brain is more susceptible to environmental adversity than the female brain¹⁴.

While looking at the association between pre-natal exposure to influenza and later onset of schizophrenia, Mednick et al¹⁵ reanalysed the original data of Kendell and Kemp¹⁶ and showed positive effects for females. Takei et al¹⁷ looking at influenza epidemics over a long time period also demonstrated the significance of this causative factor for female patients than male schizophrenics.

Sex has a pervasive effect across the neocortex. The possibility that differences in clinical presentation in men and women with schizophrenia are related to morphological differences in particular structures of the brain, is an important and on-going area of investigation. It has been suggested that male and female patients do differ in the pattern of volumetric reductions and brain morphology in many areas of the brain. Reviews by Castle and Murray¹⁴, Zipursky and Kapur¹⁸ concluded that there is an evidence for this difference. MRI scanning results reveal that reduced cortical brain areas, small left hippocampal formations and enlarged lateral ventricles are found more in males than in female patients. Other workers, like Andreasen et al¹⁹, Bogerts et al²⁰ and Marsh et al²¹, also suggested that investigations using neuroimaging techniques have shown different structural brain abnormalities in schizophrenia in male and female patients. Compared to men, women have a greater ratio of grey matter in hypocampus, frontal cortex, caudate and temporal gyrus. All of which are involved in higher functions like thinking, attention, language and working memory. Johnstone and her group²² reanalysed the post-mortem data on their schizophrenic patients and like many other workers found that brains of female patients showed more gliosis and focal damage than those of males.

Oestrogen has been hypothesised to change the vulnerability threshold for schizophrenia in females as fluctuations in oestrogen level have been reported to influence the severity of psychopathology²³. Lewine and Seeman²⁴, Hallonquist et al²⁵ suggest that the difference in symptomatology among males and females coincides with the diminution in oestrogen levels in female patients. They regard "pre-menstrual, postpartum, and post menopause" exacerbation of schizophrenia, as well as, the relative freedom from schizophrenic relapse during pregnancy, (as) consistent with a protective effect of estrogens . Relatively late onset of schizophrenia in women, worsening of the symptoms with age and the second incidence peak at the time of menopause, a phenomena that does not occur in men, also support the difference in underlying endocrinological changes in both sexes.

Female patients may suffer from less EPS than males and this has also been linked to the oestrogen hypothesis, suggesting modulating effects not only on symptomatology but also on side effects.

A number of studies and reports are now available which suggest that pre-morbid deficits in personality and social functioning are more common and more prevalent in boys than girls who later on develop schizophrenia. Such deficits also predict an earlier onset of schizophrenia in male patients. An association has also been found between ‘disturbed’ behaviour, minimal brain dysfunction and an increased prevalence of antisocial and emotional problems in childhood and a severe form of the illness in male gender at a later age^{26, 27}.

As the phenomenology of schizophrenia is hetrogeneous, it includes various forms of delusions, hallucinations, thought disorders, abnormalities in volition, drive, emotional expression and social interaction. A number of studies and reviews have found that differences in phenomenology do exist between the different sexes^28-30. Female schizophrenics generally appear to have a less severe clinical presentation. They are more likely to present with mood disturbances, depressive symptoms, dysphoria and atypical affective features. Male patients on the other hand, present with severe positive as well as negative symptoms. Ring et al³¹ while describing the results of their catchment area study strongly suggested that negative symptoms such as affective flattening, poverty of speech and social withdrawal were more prevalent among males than females. Anti social behaviours, substance abuse and features suggesting of anti-social activities have also been increasingly found in male schizophrenic patients^32,33.

Schizophrenia and affective disorders often overlap in psychopathology. Looking at the gender difference in this regard, many researchers suggest that female schizophrenics are more likely to receive differential diagnoses of affective, atypical or manic psychosis and are also overrepresented among patients with a diagnosis of schizoaffective disorder and acute reactive psychosis^34,35.

WHO's recent multicultural study⁷ which was completed in seven research centres revealed that females did differ from males on a number of variables. They present with a late onset and have more non-specific symptoms like variations in mood, irritability and tiredness than male patients. Males were reported to have more maladaptive behaviour like alcohol abuse and antisocial tendencies, and suffered from a comparatively more severe type of illness.

Review of the data in this aspect again show that treatment response is faster in women, the duration of psychosis is reduced and the outcome is favourable in female schizophrenics. Szymanski and co-workers⁴ while using the standard therapeutic doses of antipsychotic drugs in men and women admitted to the hospital with the first episode of schizophrenia, observed rapid and better effective response for women. Overall 95% of women attained full remission from their first episode as compared to 70% of men. Haas et al³⁶ also reported that female patients who have intensive family intervention in conjunction with psychopharmacological treatment continue to improve significantly than male patients even after their discharge from the hospital.

Schizophrenia runs a chronic course and its outcome is generally considered as variable. It is interesting to note that the course and outcome of this illness in terms of gender are again suggestive of a difference. Angermeyer³⁷ looked at more than one hundred published studies about the effects of gender on the course of schizophrenia. Regardless of the outcome measures, like clinical improvement, time spent in hospital, number of relapses, symptoms at follow up, or social adjustment in the community, more than half of these studies showed a statistically significant difference in terms of gender. The conclusions were drawn that the outcome was better in female patients. Males were at greater risk of readmission and they used to spend almost twice as long in hospitals as compared to the females. Ten years follow up study of first episode schizophrenic patients fulfilling ICD-9 criteria by Thara et al³⁸ also found that male gender was a poor predictor of outcome for this illness and there were strong indications of better drug response in females and of their less liability to develop long term effects of neuroleptic treatment.

Looking specifically at readjustment of schizophrenic patients in the community it has been observed that female patients enjoy a better quality of life than male patients and had less disability in social functioning on different measures of quality of life^39,40.

The evidence presented in this paper points towards a number of differences among male and female schizophrenic patients. There are some studies suggesting that there is no difference in this regard^41-43, but despite these reports, majority of the work consistently show that schizophrenic males are different when compared to schizophrenics females. Males are more likely to show an earlier onset, present with more frequent negative symptoms, exhibit severe psychopathology, reveal more structural brain abnormalities and show a less promising response to neuroleptic medication. The gender differences are also observed in pre-morbid personality, aetiological predisposition, social demographic attributes and the overall outcome and course of the illness.

Keeping in view the above mentioned facts it may be postulated that there are two types of schizophrenias : one male schizophrenia and the other female schizophrenia (Figure 1). In many cases we may, however, encounter two distinct but overlapping syndromes that retain the individual characteristics of each illness (Figure 2).

These concepts certainly require more work and merit careful attention. It is imperative to know the gender based difference as these may entail a number of practical implications. The current classifications in psychiatry prefer sub-typing of different disorders. Based on the above mentioned observations, it can be argued that there is an advantage of using gender as the sub-dividing variable for schizophrenic illness. This attempt can be completely reliable and valid in many ways as compared to the other subdivisions like positive versus negative types, acute versus chronic types or early onset verses late onset types. In addition to getting new directions by this division, we may also be able to get more insight into the understanding of this illness. Such findings will also have implications for treatment and management of the schizophrenic patients. While looking at different symptomatology and response to the medication, perhaps there will be some hope to develop some sex specific medication that will alter neurotransmissions differently in different genders.

The above mentioned findings need to be taken as further lines of guidance and require critical appraisal, especially in terms of offering new hypothesis for understanding of this illness. It is hoped that this topic will get more attention from the clinicians and the researchers and the evidence of gender specificity in the clinical presentation, phenomenology, treatment response and course of schizophrenia will be considered relevant for more examination and further research.

The author is thankful to Tracey Rylance for her untiring efforts to type different drafts of this paper and to Dr. Pichet Udomratn for writing the Thai abstract and preparing the manuscript.

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