Tassapa tata

GENDER DIFFERENCES IN SCHIZOPHRENIA OBSERVATIONS FROM NORTHERN FINLAND

 

SAMI

RÄSÄNEN

 

Departments of Psychiatry and Public

Health Science and General Practice

 

( tässä osia em. tekijän tutkimuksesta, Jk)

(URL: http://herkules.oulu.fi/issn03553221/)

 

 

 

Abstract

 

 

Using three different schizophrenic populations from Northern Finland , gender differences in some socio demographic variables, age at onset, incidence, treatment, outcome and deinstitutionalization of schizophrenia were examined. The first study population comprises the Northern Finland 1966 Birth Cohort, which is an unselected, general population birth cohort. We followed prospectively 11017 subjects from 16 to28 years of age by means of the Finnish Hospital Discharge Register. From this study population gender differences at the age of onset and incidence of schizophrenia were calculated. The second study population was formed of 1525 patients who had their first treatment episodes at the closed therapeutic community ward situated at the Department of Psychiatry, University of Oulu during 1977 - 1993. Gender differences were assessed in relation to age at first admission, some sociodemographic variables, degree of active participation of the patients in individual, group, and milieu therapy and institutional outcome of the patients with schizophrenia. The third study population consisted of all the 253 long-stay psychiatric inpatients treated for at least six months without a break during 1992 in the Department of Psychiatry, Oulu University Hospital . From this study population gender differences at the age of onset and in relation to some sociodemographic and clinical variables were studied. The placements after the last discharge and at the end of the follow-up and factors predicting hospitalization after the follow-up were also monitored. There were no statistically significant gender differences regarding age at onset in any of these three different study populations. The time lag between the first psychotic symptoms and the first psychiatric hospitalization was minimal. In the Northern Finland 1966 Birth Cohort study the annual incidence rate of DSM-III-R schizophrenia was relatively high, 7.9 per 10 000 in men and 4.4 in women by the age of 28. In men it was highest in the age group of the 20-24 year-olds while in women the peak occurred earlier in the age group of the 16-19 year-olds. In the Therapeutic community study there were no statistically significant gender differences in the sociodemographic variables, in the length of stay and in the number of treatment episodes in this ward in any of the diagnostic groups. Differences with regard to male and female participation in individual, group and milieu therapy and the institutional outcome were minimal, some trends, however, favoring females. In the long-stay patients study almost two-thirds of these patients were men. Very few gender differences were found in relation to sociodemographic and clinical characteristics or regarding the utilization of psychiatric hospital care. About 70% of the long-stay patients were discharged during the four year follow-up period and only 15% were able to live without continuous support. Marital status (being not married), dwelling place (living in city), absence of negative symptoms and severity of the illness were associated with hospitalization at the end of the follow-up. Gender did not predict hospitalization at the end of the follow-up period. The results of this study indicate that there are probably different subgroups of schizophrenia in which there are no gender differences regarding age at onset and in the clinical picture of the disturbance or there are regional differences in the manifestation of the illness. In Finland patients are hospitalized earlier after the onset of the first psychotic symptoms than in many other countries. According to the Northern Finland 1966 Birth Cohort study the incidence of schizophrenia is higher among young men than women and the total life-time incidence of schizophrenia may be smaller in women. The results from the Therapeutic community study suggest that therapeutic community treatment may level out the gender differences in the treatment process and outcome. The long-stay patient study showed that long-term patients are dependent on considerable support and that the most seriously ill patients are in fact in hospital. Alternative residential facilities have been a presupposition to the deinstitutionalization of the long-stay patients.

 

Keywords: age at onset, incidence, long-stay patients, deinstitutionalization

 

4.3. Statistical methods

4.3.1. Methods in the Northern Finland 1966 Birth Cohort study (II)

Gender differences with regard to continuous and normally distributed variables were assessed with Student’s t-test (Altman 1991). The ordinary chi-square test was chosen to test for the statistical significance of differences in frequency distributions in case of categorial variables. Finally, male to female rate ratios with 95% confidence limits were calculated for each age group (Ingelfinger et al. 1994). The statistical software used was SPSS for Windows version 6.1 (Norusis 1994).

 

4.3.2. Methods in the therapeutic community study (III)

 

The readmission period (the number of days from discharge following the first admission to rehospitalization) was evaluated in all diagnostic groups. The groups of schizophrenia, schizophreniform and schizoaffective were combined, and the readmission period of this combined group was presented graphically. The data were analyzed using the SPSS for Windows software. Cross-tabulation was used as the main tool for data presentation and analysis. The statistical significance of factors associated with gender was evaluated using the Chi-square test and the Mann- Whitney U-test. The gender differences were evaluated by diagnostic groups. The Kaplan-Meier method, as operationalized in the Kaplan-Meier survival analysis procedure of the SPSS for Windows software (Norusis 1994), was used to obtain the estimated time to readmission of patients. These curves (III: Figure 1) represent the proportion of readmitted patients at a certain time point after discharge and are expressions of the time elapsed before rehospitalization. The curves were approximations for male and female patients in different diagnostic groups. The statistical significance of the differences between gender groups was determined by log-rank statistic.

 

4.3.3. Methods in the long-stay patients study (IV,V)

 

In the original paper IV, the Chi-square and Fisher’s exact test were used to test statistical significances of differences in frequency distribution between genders. For continuous variables, statistical significance of gender differences were assessed with Student’s t-test or the non-parametric Mann-Whitney U-test if the variables were not normally distributed. A two-group discriminant function analysis was performed to determine the most essential variables that discriminated male and female long-stay psychiatric patients. In the original paper V, cross-tabulation was used as the main tool for data presentation. Statistical significance of differences between two independent groups were assessed with the Chi-square test, Fisher’s exact test or Student’s t-test, whichever appropriate. The logistic regression analysis was used to assess the probability of 38 hospitalization at the end of the follow-up after the most essential clinical and sociodemographic variables were adjusted. In the original papers IV and V the primary software used to analyze the data were SPSS and SAS for Windows (Norusis 1994). The level of significance was set at P0.05 in all statistical analyses.

 

5. Results

 

5.1. Age at onset of schizophrenia by gender (II, III, IV)

5.1.1. Age at onset in the Northern Finland 1966 Birth Cohort study (II)

 

There were 89 DSM-III-R schizophrenia cases (58 men = 65.2% and 31 women = 34.8%) of which one man and one woman were traced through outpatient search. Mean age at onset (first psychotic symptoms) in men was 21.4 (SD 3.4) and in women 21.2 (SD 3.5) (Student’s t-test with equal variances p = 0.756). The peak of onset in men lay in the 20-24 year age group whereas in women it occurred in the 16-19 year age group. There were no statistically significant gender difference in age at onset. Table 1 in the original paper II presents the distributions of age at onset (first psychotic symptoms) in male and female schizophrenia patients in three age groups. The mean age at first hospitalization due to any psychiatric disorder in men (n=57) was 21.5 (SD 4.0) and in women (n=30) 21.4 (SD 3.9) (Student’s t-test p=0.874). The first psychotic symptoms appeared slightly earlier than the first hospitalization. The mean time difference between first psychotic symptoms and first psychiatric hospital admission was 0.05 years (SD 2.4) for men and 0.20 (1.5) for women (Student’s t-test p=0.757).

 

5.1.2. Age at first treatment in the therapeutic community study (III)

 

The mean age for males at the time of their first treatment episode in this ward was 30.4 years (SD 10.4) and for females it was 31.2 (SD 10.6). The mean age of patients with schizophrenia was lower, being 27.4 years in men (SD 7.4) and 27.8 in women (SD 7.5) and in patients with diagnoses of schizophreniform/schizoaffective disorders 26.5 years in men (SD 7.2) and 27.4 in women (SD 7.7). Of the men with schizophrenia 34 %, and of the women 31%, were under 23 years of age at the onset of the illness. In the group of men with schizophreniform/schizoaffective disorders 38% and in the women 37% were 40 under 23 years old. There were no statistically significant differences between men and women in age distribution in the groups of schizophrenia and schizophreniform/schizoaffective disorders.

 

5.1.3. Age at onset in the long-stay patients study (IV)

 

The mean and median ages as well as standard deviations of long-stay patients at five different points in time are presented in Table 3. There were no statistically significant differences between men and women in any of these age variables.

 

Table 3. Mean and median ages as well as standard deviations of long-stay patients at five different points in time .Definition of age at onset Males Females All mean median SD mean median SD mean median SD First sign of the psychiatric symptoms

22.2 20.0 10.1 24.3 21.0 11.8 23.0 20.0 10.8

 

Manifestation of the first psychotic symptoms

24.0 21.0 9.7 25.4 22.0 11.8 24.5 21.0 10.5

 

First contact with health care for the psychiatric reasons

23.5 21.0 10.2 24.7 21.0 11.4 24.0 21.0 10.6

 

First contact with specialist care

23.9 21.0 10.4 25.3 22.0 11.9 24.4 21.0 11.0

 

First psychiatric hospital admission

24.6 21.9 10.0 26.5 22.3 13.0 25.3 22.1 11.3

 

Mean/median time lag in years between the first sign of psychiatric symptoms and the first psychiatric hospitalization was 2.5/1.0 (SD 5.1) overall, 2.6/1.0 (SD 4.4) for males and 2.2/1.0 (SD 6.0) for females. Statistically significant gender differences were not found. Mean/median time lag in years between the first psychotic symptoms and the first psychiatric hospitalization was 0.06/0.0 (SD 3.5) overall, 0.04/0.0 (SD 3.3 ) in males and 0.09/0.0 (SD 3.7) in females. Again, no statistically significant differences were observed. There were 32 patients (13.2% in all, of which 20=13.1% were male and 12=13.5% were female) whose first psychotic symptoms appeared after the first hospitalization. 41

 

5.2. Incidence of schizophrenia by gender in the Northern Finland 1966 Birth Cohort (II)

 

The cumulative incidence was two times as high among men as among women until the age of 28. Fig. 1 displays the cumulative incidence (%) of DSM-III-R schizophrenia in males and females.

 

Fig. 1. The cumulative incidence (%) of DSM-III-R schizophrenia by gender up to

the age of 28 in the Northern Finland 1966 Birth Cohort.

 

The annual incidence in men was highest in the age group of the 20-24 year-olds while in women the peak occurred in the age group of the 16-19 year-olds (II: Table 1). Until the end of the follow-up period (at the age of 28) there was a decreasing trend in the incidence rates for women. Male to female rate ratios differed statistically significantly only in the age group of the 20-24 year-olds.

0,0

0,2

0,4

0,6

0,8

1,0

1,2

16 17 18 19 20 21 22 23 24 25 26 27 28

Age at onset of schizophrenia Cumulative incidence % Males Females 42

 

 

 

5.3. Treatment and outcome of schizophrenia by gender in the therapeutic community study (III)

 

There were no statistically significant (p < 0.05) differences between men and women regarding age distribution, education, dwelling place and way of admission of any diagnostic group. In the group with schizophrenia, however, the general trend was that the men’s educational levels were lower than those of the women and that most of the men were living in small localities (under 10 000 inhabitants). Distribution of some first episode (at the ward under study) patient variables in the therapeutic community ward are presented in the original paper III:

 

Table 1. Women participated more actively than men in individual therapy of the diagnostic group of mood disorders (very active males 60.2% and females 72.7%, p = 0.033), as well as in group therapy in the patient group of schizophreniform/schizoaffective disorders (very active males 34.8% and females 46.7%, p = 0.037). There were no statistically significant differences regarding the participation in milieu therapy of any diagnostic group. In the groups of schizophrenia and psychosis generally, there was a trend towards women participating more actively in milieu therapy than men. A difference in the institutional outcome was established between men and women in the group of schizophreniform/schizoaffective disorders (p = 0.038). A positive outcome was more common among women and a negative outcome among men. A conflicting outcome (limitations in goal attainment) was equally common in both gender groups. A similar trend was observed also in the group with schizophrenia, but not in other diagnostic groups. Data on the distributions of men and women in the participation of psychosocial therapies, length of stay and outcome according to the five diagnostic groups are presented in the original paper III:

 

Table 2. No statistically significant gender differences were found with regard to the length of stay in the different diagnostic groups when assessed as quartiles or when evaluating the means, medians and maxima (III: Table 3). In the groups with schizophrenia, the lowest number of patients who had a short length of stay were encountered. Correspondingly, in those same groups there were the largest number of patients with very long lengths of stay when compared with other diagnostic groups. There were no significant gender differences in the number of treatment episodes at the ward under study in any of the diagnostic groups. The number of episodes was highest in the group of schizophrenia. Original paper III: Table 3 presents also the means, medians and maxima of the number of episodes at the ward in all diagnostic groups. The rate of readmission was evaluated in all diagnostic groups. There were no significant gender differences in any of these groups. Among the combined group of schizophrenia, schizophreniform and schizoaffective patients, no gender differences were detected at the time to readmission (III: Fig. 1). In the diagnostic groups of schizophrenia, the proportion of male and female patients did not change during the second and third treatment periods, but the gender differences diminished. During the second treatment period, the gender difference came out as a more negative outcome among males with schizophreniform/schizoaffective disorders: positive outcome male 32 / female 34 (61.5 % / 85.0 %), controversial 12/6 (23.1 % / 15.0 %), negative 8/0 (15.4 % / 0.0 %) (p=0.013). During the third treatment period, there was a gender difference with regard to the activity in milieu therapy in the group of 43 schizophreniform/schizoaffective disorders, women being more active than men: very active male 6 / female 12 (23.1 % / 57.1 %), moderately active 12/4 (46.2 % / 19.0 %), passive 8/5 (30.8 % / 23.8 %) (p=0.044).

 

5.4. Gender differences of long-stay patients (IV)

 

About 62% of the patients were males and 38% females. The mean/median age (standard deviation) of all subjects at the end of the index hospitalization was 47.0/46.0 (15.5). The age of the men was 45.6/45.0 (14.4) and that of the women 49.4/47.5 (16.9), resulting in a statistically marginal difference between men and women with regard to age (P=0.069). Compared to women, men were living more commonly outside the City of Oulu . Men were also more commonly single, had fewer children, and lived more commonly in a primary family than did women. In original paper IV: Table 1 presents the sociodemographic characteristics of the patients by gender before the index hospitalization. Of the patients 97% were on disability pension at the end of the index hospitalization. Three of the patients were so young (under 16 years) that they did not have the right to collect a disability pension.

About 40% of the patients had most of the time (≥75%) been in inpatient care since their first admission to the psychiatric hospital. There were no statistically significant gender differences in the number of admissions, in the number of involuntary hospitalizations and in the proportion of treatment days under psychiatric hospital care before the index hospitalization (IV: Table 2). The diagnostic distribution did not differ significantly between genders. There was a trend that women had more other functional psychoses and mood disorders than men and men had more organic disorders than women. There were no significant gender differences in CGI- and GAS-scores. Men had more DSM-III-R negative symptoms than women. The mean of the total Strauss-Carpenter score in men was lower (10.3, sd 4.7) than in women (11.6, sd 5.0) (t-test, P=0.039). There was no statistically significant gender difference in the doses of the antipsychotic medication as determined by analyses in the seven categories and in the mean/median quantities of equivalents of chlorpromazine (men 755/460, women 723/500) (IV: Table 3). A total of 51 patients had depot-injection medication; 39 of them were men (24.8% of all men) and 12 of them were women (12.5% of the women) (P=0.018). A discriminant analysis between male and female long-stay psychiatric patients revealed that a higher number of children (F=17,619, P<0.001), fewer negative symptoms (F=5.402, P=0.021) and being married (F=6.305, P=0.013) were more typical for females and served as the only significant factors for discriminating the genders. The patients were homogeneous with regard to diagnoses. To ensure the comparability with the previous studies concerning schizophrenia patients, all analyses were repeated in the group of schizophrenic patients (n=203). The results, however, remained unchanged. 44

 

5.5. Deinstitutionalization of long-stay patients by gender (V)

 

During the follow-up, about 90 % of all patients had had at least one hospitalization. About one third of both men and women were less than 25% of the follow-up period in hospital care and one third over 75% of the time. There was no difference between men and women in the utilization of hospital care. The placements after the last discharge and at the end of the follow-up as well as the change of the placements between the last discharge and at the end of the follow-up are presented graphically in Fig. 2. During the follow-up there were only minor changes in the placements of the patients. About 90% of the patients placed in residential facilities or at home did not change the placement. If the patients were discharged to other institutions, 72% of them stayed there and 25% of the patients died

 

 

 

a Before index hospitalization

b At the end of index hospitalization

c Proportion of days in inpatient care between the first psychiatric hospitalization and

the beginning of index hospitalization

All other variables (gender, number of children, way of living, age, positive and

depressive symptoms, social functioning measured with the Strauss-Carpenter scale,

number of involuntary hospitalizations, number of psychiatric hospitalization) remained

non-significant.

 

6. Discussion

6.1. Main findings of the study (I, II, III, IV, V)

 

The main findings in a review of gender differences in schizophrenia (I) were that most studies have accepted that the lifetime risk of schizophrenia has been equally common in both sexes, with men developing schizophrenia 3 - 4 years earlier than women and women having more often a favorable course of the disease than men. Males with schizophrenia furthermore tend to have more central nervous system abnormalities than females. However, there were also opposite findings, and thus the final conclusions at this point in time, are difficult to formulate. In the Northern Finland 1966 Birth Cohort study (II) there were no significant gender differences in age at the onset of schizophrenia. However, the peak of onset occurred earlier in females than in males. The incidence rates of schizophrenia were relatively high compared to earlier incidence studies and incidence among men was about two times higher than in women. In the Therapeutic Community Study (III) only minimal gender differences were observed in the sociodemographic variables, with regard to participation in psychosocial therapies (individual, group and milieu therapy) and in the institutional outcome of the schizophrenia patients. In the long-stay patients study (IV,V) almost twothirds of the long-stay patients were men. Some gender differences were found in sociodemographic and clinical characteristics or in the utilization of psychiatric hospital care. Long-term patients were dependent on considerable support, but only the most seriously ill patients were left in hospital at the end of the follow-up. Most of the patients were placed in alternative residential facilities. Gender was not associated with hospitalization at the end of the follow-up period. 51

 

6.2. Age at onset (II,III,IV)

 

The Northern Finland 1966 Birth Cohort study and the Therapeutic Community study did not detect any gender difference with regard to age at onset of schizophrenia, which was contradictory to findings in the numerous earlier studies (Angermeyer & Kuhn 1988, Goldstein et al. 1989, Evenson et al. 1993, Häfner et al. 1993, Susser & Wanderling 1994, Maurer & Häfner 1995). In the long-stay patient study, the mean age at the onset of the illness, using five different criteria, was between 22.2-24.0 years in men and 24.3-25.4 years in women. The results remained practically the same when only the schizophrenia group was analysed. Age at onset in men was lower than that of women, but the difference was about two years smaller than that found in earlier studies on schizophrenia patients. This can be explained by the selected study sample. Our study population represented the most chronic schizophrenia patient group, which is probably more homogeneous with regard to the course of the illness than the schizophrenia patient group in the broader hospital population. In the Northern Finland 1966 Birth Cohort study, the probands were 28 years old at the end of the present follow-up. This means that if there are more females in new schizophrenia cases of the older age groups (Angermeyer et al. 1989, Goldstein et al. 1989, Jablensky 1993) and a second peak of onset in women appears, as reported earlier (Häfner et al. 1991, Castle et al. 1993), the gender difference with regard to age at onset will probably appear in the future. Naturally, the extent of the possible age difference will depend on the number of men and women in the new schizophrenia cases of the older age groups. In the Therapeutic Community study, the same age of males and females at their first admissions to the ward can be explained by the selected study sample. It is also possible that men and women were selected in different ways. Most of the patients were selected for therapeutic community treatment by personal interview or by discussing a patient’s medical records in a team before the patient’s admission to the ward. For example, extensive age gaps and gender disproportions were avoided, if possible, although different adult age groups were admitted. Also, it was considered in the selection of the patients that the patients benefit from the therapeutic community treatment (Isohanni 1983). In this study group there were also some patients who were not real first timers in the psychiatric hospital, although the treatment period under study was their first at this particular therapeutic community ward. Thus, the findings of this study may not be generalisable and applicable to other schizophrenic populations. In the Northern Finland 1966 Birth Cohort study the schizophrenia patients were divided into three age groups according to the onset age at the first psychotic symptoms (16-19 years, 20-24 years and 25-28 years). This kind of grouping facilitated comparisons with earlier studies. In our study a remarkable proportion (42%) of the female schizophrenia patients had become schizophrenic before the age of 20. This finding challenges earlier studies in which the peak of onset in women has been reported to occur after 25 years of age (Eaton et al. 1988, Goldstein et al. 1989, Häfner et al. 1991). The finding may even indicate that the main peak of onset could be earlier in women than in men. The peak of onset in men occurred in the age group of the under 24 year-olds, which concurs with earlier studies (Eaton et al. 1988, Goldstein et al. 1989). Naturally, this finding may be a chance phenomenon and requires replication. 52 The onset age of schizophrenia has been defined in several ways - from the first sign of mental disorder to the first hospital admission with a diagnosis of schizophrenia (Häfner et al. 1993). In spite of the different definitions, a significant gender difference in age at onset has been found to exist (Häfner et al. 1993, Maurer and Häfner 1995). In the Northern Finland 1966 Birth Cohort study, the age at onset was defined in two ways and in the long-stay patient study in five different ways. In the Northern Finland 1966 Birth Cohort study and in the long-stay patient study, there was practically no time lag between the age at which the first psychotic symptoms appeared according to the patients’ case notes and the age at first hospitalization due to any psychiatric disorder. It was much smaller than in some other studies where the first psychotic symptomatology had been found to appear on average two years prior to the first hospitalization with a diagnosis of schizophrenia (Häfner et al. 1993a, McGorry et al. 1996). The small difference noticed in this study may be due to incomplete information, because our data for symptoms were collected from case records retrospectively and some information may have been missing from the case notes. In addition, the first psychiatric hospitalization may not necessarily have been critical for the diagnosis of schizophrenia. It is also possible that in Finland the patients are hospitalized earlier than in many other countries after the manifestation of the first psychotic symptoms. In Finland good social security and relatively small localities (people know each other) have led to the welldeveloped practice of taking care of the patients and, therefore, this time lag may be smaller than in many other countries.

 

6.3. Incidence (II)

 

In the Northern Finland 1966 Birth Cohort study, the incidence of schizophrenia was higher in men than in women. The male to female rate ratio ranged from 1.3 to 2.3 in three different age groups. These ratios were similar to ratios observed in previous studies and thus supported the findings that incidence among young men was higher than in young women (Sartorius et al. 1986, McCovern & Cope 1987, Goldstein et al. 1989, Castle et al. 1993). Opposite to our hypothesis and also to earlier studies, the male to female rate ratio remained relatively high in the oldest age group, that of the 25-28 year-olds. There was also a trend that, regarding women, the number of new schizophrenia cases decreased with age. Based on earlier studies we expected a smaller difference of the ratios as well as an increase in the incidence of schizophrenia in women over time, because women have been found to exhibit a peak of onset after an age of 25 and men before the age of 24 (Eaton et al. 1988, Goldstein et al. 1989, Häfner et al. 1991). This study does not cover the incidence of schizophrenia in age groups older than 28 years of age and therefore a final conclusion of the total life-time incidence can not yet be formulated. However, the results of this study suggest that the number of female schizophrenia cases may not reach the number of male cases. Such a conclusion would support the finding of a higher prevalence of schizophrenia in males (2.4%) than in females (1.8%) in Northern Finland , reported in the Mini-Finland Health Survey (Lehtinen et al. 1991). The same life-time incidence in men and women of this study population would require a remarkable second peak of onset 53 in women. Such a big second peak does not seem to be probable, because until the age of 28 only 35% of all schizophrenia cases involved women. As far as we know, prospective age cohort studies like this study of the incidence of schizophrenia have not previously been performed and a comparison of the incidence rates of this study with earlier studies may be difficult. Sampling differences may lead to misleading conclusions concerning the differences in incidence rates between different studies. For example, hospital first-admission rates, which have been used in many earlier incidence studies may be unreliable, because not all patients with schizophrenia are so diagnosed at the time of their first hospital admission and some patients recorded as first admissions can be re-admissions. Diagnostic procedures and methods of calculation of incidence statistics may also vary between studies. For example, diagnostic criteria may have been changed during the study period or different diagnostic criteria were used in different studies. (Kendell et al. 1993). The diagnostic criteria used have been found to be related to the incidence rates and to the apparent gender differences in incidence (Regier et al. 1998). It has been suggested that the more stringent the diagnostic criteria for schizophrenia are, the more females are excluded (Lewine et al. 1984, Lewis 1992, Castle et al. 1993, Navarro et al. 1996, Haas & Castle 1997). Especially the age criteria are important, because late onset cases are more common in women. In this study, diagnoses were based on DSM-III-R schizophrenia criteria, which are rather stringent, but not as stringent as, for example, DSM-III criteria used in some earlier reports. Furthermore, there is a tendency to diagnose women with schizophrenia at a later age than men (Bardenstein & McGlashan 1990), but in this study the careful validation process has led to a reduction of this potential bias. However, compared with many other incidence studies, the annual incidence rates of DSM-III-R schizophrenia in this study over the whole 13 year follow-up period were relatively high (7.9 per 10 000 in men and 4.4 in women). Cooper et al. (1987) reported incidence rates of DSM-III schizophrenia in men of 1.7 per 10 000 and in women of 0.7 per 10 000, while Iacono and Beiser (1992) provided respective figures of 0.7 and 0.2. In the study of Nicole et al. (1992), the incidence of DSM-III-R schizophrenia was 4 per 10 000 in men and 2.2 per 10 000 in women. The main reason for the rather high incidence rates of schizophrenia observed in the present study may be the young age of the study population. Thus far, the cohort has been followed through the high risk years for the morbidity to schizophrenia. Presumably the annual incidence rates will decrease as time goes on and the follow-up continues. One explanation for the high rates may also be the earlier finding of a higher prevalence of schizophrenia in Northern Finland rather than in other parts of Finland (Lehtinen et al. 1990, Hovatta et al. 1997). A sizeable reduction of first admissions with schizophrenia has been demonstrated in Scotland , England , Wales , Denmark , and New Zealand (Geddes et al. 1993, Kendell et al. 1993) and it has been discussed whether the incidence of schizophrenia has, indeed, been decreasing (Kendell et al. 1993). The incidence of schizophrenia has also been reported to decline in Finland (Suvisaari et al. 1999). In Finland there are only few studies reporting incidence rates of schizophrenia and methodological discrepancies make it difficult to compare the incidence rates of different studies with each other (Kendell et al. 1993). However, in spite of the major differences between the studies, the high annual incidence rates in our study compared with earlier DSM-III schizophrenia findings of incidences in Finland (1.6-2.8 per 10 000 population) (National Board of Health in Finland 1988; 54 Pakaslahti 1992) and all psychotic disorders (20 per 10 000) (Lehtinen 1996) do not support the view that the incidence of schizophrenia is actually decreasing in Finland.

 

6.4. Treatment and outcome (III)

 

In the therapeutic community study, there were no statistically significant differences between men and women regarding the sociodemographic factors (age, education, dwelling place). However, in the schizophrenia group the educational level of men was somewhat lower than that of women. A higher proportion of the men with a diagnosis of schizophrenia and schizophreniform/schizoaffective disorders were living in sparsely inhabited localities, compared with the women. These two trends may indicate a poorer social functioning of male patients. Men with a psychiatric illness are commonly staying in their home districts with their parents. Involuntary admissions into a mental hospital were equally common for both genders. A similar finding has been described earlier in another Finnish sample (Kaltiala-Heino 1995), but it does not support the expectation often presented that women would be more inclined to apply for psychiatric help than men (Seeman 1986). The same rates of involuntary admission in men and women into this acute, closed, therapeutic community ward can be explained by the selected study sample. Besides, there were equal proportions of male and female nurses amongst the staff, which in practice made it impossible to treat the violent male patients who were difficult to treat. During the day shift, three out of five staff members were women and two were men. The hospital attendants and the ward secretary were all women. During the night shift there were two nurses, one of them was always a man. There were no major gender differences among patients with a diagnosis of schizophrenia regarding participation in psychosocial therapies. This group of patients had the most severe clinical profile; their clinical pictures were very uniform and they participated in their treatments in the same way. The women in the group of schizophreniform/schizoaffective disorders participated significantly more actively in group therapy and, to some extent, also in milieu therapy. On the other hand, there were no statistically significant differences in the level of activity in individual therapy between men and women in any other diagnostic group apart from mood disorders. However, this shows that women are more actively involved in their treatment than men. Statistically significant gender differences regarding the length of stay, number of episodes and readmission rates were not found in this study. These findings are at odds with various other studies suggesting that female patients with schizophrenia have shorter and fewer hospital treatment stays than men (Salokangas 1983, Seeman 1986). The finding of this study can be explained by the selection of the patients, a process that probably homogenized the study population. It was also very clearly shown that the more severe the diagnosed disorder which the patient had (non psychotic vs. psychotic), the longer was the stay in hospital. The same result has also been obtained previously in a study on the same sample (Nieminen et al. 1994). The women with schizophreniform/schizoaffective disorders had better institutional outcomes than the men, but this was not seen in the case of schizophrenia or in the other 55 diagnostic groups. Previous studies have shown that there are gender differences in outcome especially among the patients with schizophrenic disorders (Bardenstein & McGlashan 1990, McGlashan & Bardenstein 1990, Mueser et al. 1990). At least in part, the better outcome of women may be due to women having more remissions and their psychosocial functioning being better than that of men (Pakaslahti 1992). The better outcome in the diagnostic group of schizophreniform/schizoaffective disorders can also be partly explained by the finding that women were more seriously committed to their treatment in this diagnostic group than men. However, the minor gender differences are indicative of the realization of the treatment goals of a milieu-therapy-oriented ward in the treatment of severe disorders. The gender differences of the patients in this study sample were found to be very minor also during the second and third treatment periods. This is due to the even more stringent selection of the patients at the beginning of the second and third treatment periods than at the first. The patients who had responded positively to the therapeutic community treatment during their first treatment period were admitted to the same ward at rehospitalization and the patients who did not respond at all were more probably admitted to another ward. On the other hand, the clinical picture of the patients with several treatment periods was probably more severe. Thus, the patients with several treatment periods formed the more homogenous group of the patients with a severe clinical picture.

 

6.5. Gender differences of long-stay patients (IV)

 

In the long-stay patient study, women were more commonly married, more likely to have had children and lived alone or with a secondary family than men. All these factors are indicators of the women’s better ability to cope socially even when suffering from schizophrenia; this has also been shown in earlier studies (Salokangas 1996). Women lived more commonly in the city of Oulu , which reflects better social functioning in Northern Finland , because many people have to move to the city because of work, study or spouse. On the other hand, there was no gender difference in relation to social class or education. The difference between men and women regarding social functioning seemed toremain stable at the end of the index  hospitalization, as measured by the Strauss-Carpenter scale. It seems that in our study population the better social functioning of women did not protect them from long-stay hospitalization. Men exhibited significantly more negative symptoms than women, which is compatible with other studies (Salokangas & Stengård 1990, Gur et al. 1996, Salokangas et al. 1997). There were no significant gender differences with regard to positive symptoms. There were also no gender differences in the number of hospitalizations, proportion of treatment days and number of involuntary hospitalizations after the first admission to the psychiatric hospital. There were, however, differences between men and women in CGI- and GAS-scores at the end of the index hospitalization. All these variables provide a good measure of the severity of the illness. Almost all patients had had more than one hospitalization and at least one involuntary hospitalization before the index hospitalization. Over half of the patients had spent at least 50% of the days between the first psychiatric admission and the index hospitalization in inpatient care. In practice this 56 has meant years of hospitalization because the difference between mean/median age of first contact for psychiatric care as marked on the patients’ case notes and mean age at index hospitalization of all subjects was 22.6 years. The patients’ psychopathological state, assessed by CGI scores, was rated as at least moderately ill in almost every patient and severely or extremely ill in over half of the patients. The low GAS scores confirmed these results. Almost every patient displayed a remarkable deficiency in social functioning according to measurements on the Strauss- Carpenter-scale. Almost all were on a disability pension. Collectively, all these results indicated that the long-stay patients were seriously ill. Mean daily doses of antipsychotic medication were relatively high in the long-stay patient study group, also being a reflection of the severity of the illness in these patients. Doses were surprisingly high in females and, therefore, no differences between men and women were noticed. The finding is contradictory to many earlier studies in which the doses of antipsychotic medication have been reported to be lower in females (Andia et al. 1995, Baldessarini et al. 1995). On the other hand, the gender difference in medication has been found to become smaller in older patient groups and especially following menopause (Seeman 1983). In this study, the mean age of the women was close to menopause, which might explain the similarity of medication in male and female patients. Men had significantly more neuroleptic depot-injections than women, which could be a consequence of the men’s poorer ability to take care of their medication and their greater lack of compliance (Lewis 1992). Our study population represented a selected group of the most severely ill, long-stay psychiatric patients, of whom 80% were diagnosed as schizophrenic. About 10 % of our sample were patients with organic disorders, which demonstrates that these patients along with the schizophrenia patients in this catchment area are also most frequently included in the long-stay patient group (Lamb 1993). Only a few patients could be assigned to the diagnostic groups of personality disorders, mood disorders or other functional psychoses. The lack of gender differences within the various diagnoses, may be a reflection of the homogeneity of the long-stay patient group. The hospital diagnoses used can be regarded as reliable, because every patient had been in the ward for at least six months and in addition a great majority of the patients had already experienced years of earlier hospitalizations. The possibility of false positive diagnoses is very unlikely (Pakaslahti 1986, Isohanni et al. 1997).

 

JNE….

 

6.7. Methodological concerns (I, II, III, IV, V)

 

This thesis is based on three different study populations, which enabled analyses of gender differences in patients representing either different phases of the illness or different subgroups of patients with the same diagnosis. To study clinically homogenous samples has been suggested to be important in future gender research (Harding & Hall 1997). This study allows comparisons of the results from selected study populations with the results from earlier studies representing the whole spectrum of schizophrenia. There are, however, no earlier studies of gender differences in schizophrenia from the therapeutic community and, considering everyday clinical problems, the studies from the therapeutic community ward and the long-stay patients are clinically important. In a review article of gender differences in schizophrenia (I), mostly studies involving the whole schizophrenic population are reviewed. To include this article as a separate part of this thesis was legitimate because the theme of gender differences in schizophrenia is very extensive and covers practically everything under the topic of schizophrenia. This practice provided better possibilities to focus in the summary of this study on gender differences that were examined in the other original papers (II-V) and also gave a wider perspective to the differences in schizophrenia between men and women.

 

6.7.1. Strengths and limitations of the Northern Finland 1966 Birth Cohort study (II)

 

The major strength of the Northern Finland 1966 Birth Cohort is the large study population - over 12 000 individuals. The study population is an unselected epidemiologically intact general population sample, representing 96% of all births in the region in one year and thus the results can be generalized to the population in Northern Finland . The second strength is that psychiatric diagnoses in this study can be regarded as reliable (Isohanni et al. 1997). Diagnostic codes appeared to transfer reliably from case records (Keskimäki & Aro 1991, Mähönen 1993) into the FHDR and therefore probably only few, if any, of the psychiatric hospital treated cases were lost (Isohanni et al. 1997). In this study all psychotic outpatients of the age group were identified to diminish any bias. All psychiatric diagnoses were also validated carefully using the criteria of DSM-IIIR, which allows comparison of the results with the results from other methodologically valid epidemiological studies. The third strength of this study is the very reliable information of the age at first hospitalization. The first limitation of this study is that the information of the time point when the first psychotic symptoms appeared was collected from the case notes. Although it is the basic data that a physician and other staff should gather through psychiatric interviews and report them in the case notes, it is possible that in some cases this information is inexact. The amount of the documented information may vary between different physicians, hospitals and years. However, the information from the case notes may even be more reliable or at least as reliable as more retrospective interviews. The number of recalled events decreases steadily over time, which is called the ”fall-off” effect (Maurer & Häfner 61 1995). Also, several studies have reported a lower number of positive findings in the retest situation, which is called ”retest artefact” (Maurer & Häfner 1995). In the study of Maurer and Häfner (1995), different sources of information of age at onset of schizophrenic disorders were compared. There were no differences in age at onset defined as first positive symptom, age at first treatment or first admission for schizophrenia between the ratings of a research psychiatrist on the basis of medical case records and the results of structured interviews of the patients or close relatives.

 he second limitation is the possibility, that some schizophrenic cases have not yet or may never come to medical attention. This bias, however, can not be significant, because almost all the schizophrenic patients in Finland and also in many other developed countries will be admitted to a mental hospital at a relatively early phase of a disturbance (Häfner et al. 1993, Maurer & Häfner 1995, Isohanni et al. 1997). The third limitation of this study is the fact that the first psychiatric hospitalisation could have been due to any psychiatric disorder prior to manifestation of schizophrenia. The fourth limitation of this study is the relatively young age of the study population. The probands were 28 years old at the end of the follow-up, thus representing only the highrisk years for the morbidity to schizophrenia and not the whole spectrum of schizophrenia. Late-onset cases for schizophrenia are still lacking from the study population (Castle et al. 1995, Häfner et al. 1998). However, there are no other birth cohorts than the Northern Finland 1966 Birth Cohort, in which the morbidity to schizophrenia has been followed for this long. The fifth limitation of this study is the possibility that prospective cohort studies may be inapt when rare diseases are studied. Because of the low annual incidence rate it is difficult to gather enough subjects to identify the true differences, because of limited statistical power. Also, when interpreting and generalizing the results of this study one should keep in mind that the prevalence of schizophrenia may be higher in Northern Finland than in other parts of Finland (Lehtinen et al. 1990, Lehtinen et al. 1991, Hovatta et al. 1997).

 

6.7.2. Strengths and limitations of the therapeutic

community study (III)

 

The principal strength of the Therapeutic community study is the high number of subjects, 1525 patients, representing all first treatment episodes during 17 years at the therapeutic community ward. The second strength of this study is the fact that the median length of hospitalization was relatively long, 39 days in all patients and 62 days in schizophrenia patients (Nieminen et al. 1994). Long treatment periods give sufficient time to observe the patients and consider the diagnoses, the degree of active participation and the outcome properly. The third strength of this study is that the degree of active participation and the institutional outcome were assessed at the time of discharge by 3-5 team members, alwaysincluding the personal doctor as well as the nurse. Also the interrater reliability of the classifications was tested and it was shown to be satisfactory (Nieminen 1996).62 The first limitation of this study population from the therapeutic community ward is that it does not represent a random hospital population. Most of the patients in the therapeutic community unit were selected by personal interview or by discussing a patient’s medical records in the team before a patient’s admission to the ward. However, different adult age groups were admitted and at a rough estimate a total of 30-50% of the patients were admitted in emergency situations during the evening or night shift, and many of them involuntarily. This diminished to a certain degree the selectivity of the study population (Nieminen 1996). The second limitation of this study is that the diagnoses of this study were not validated. They were clinical and determined by the psychiatrists working at the ward. However, they were probably more reliable than clinical diagnoses generally, because they were mainly based on the decision made by a psychiatrist (Matti Isohanni) with long work experience (1972 - 1989) in the ward. Furthermore, he has later tested his diagnostic reliability and it was found to be very satisfactory (Tienari et al. in press, Isohanni et al. 1997). There have also been changes in the diagnostic practice during the study period. For example, at the beginning of the study period, the diagnoses were not based on the criteria-based diagnostic classification and in uncertain cases giving the diagnosis of schizophrenia was avoided. Thus, false positive schizophrenia diagnoses were not likely. 63

 

6.7.3. Strengths and limitations of the long-stay patients study (IV,V)

 

The first strength of this study is that the study population represents all long-stay psychiatric patients (n=253) in the region in 1992, because at that time there were no other psychiatric hospitals in the catchment area. Thus the study population can be considered as representative regarding similar patient groups in general. The second strength of this study is that the case records included detailed information on the patients, because the patients had been for such a long time in the ward. Also the majority of them had had several admissions, which meant practically years of hospitalization and copious written case notes. Thus, the collected data and the clinical hospital diagnoses used in this study can be regarded as reliable although the diagnoses of this study were not validated. False positive schizophrenia diagnoses are not likely, because in earlier diagnostic studies in Finland , only false negative diagnoses of schizophrenia have been found to be remarkable (Pakaslahti 1986, Isohanni et al. 1997). The third strength of this study is that the interrater reliability regarding assessments of CGI, GAS, DSM-III-R symptoms and Strauss-Carpenter scale was satisfactory between researchers. The fourth strength is that we were able to complete the data concerning the placements of the patients after the last discharge by interviewing the personnel of the last inpatient ward. The first limitation of this study is that the data of the long-stay patients, including symptoms, were collected retrospectively from case records. Due to this procedure, some information may be lacking. However, the data collection from the case records diminish the ”fall-off” effect and ”retest artefact” (Maurer & Häfner 1995) compared to more retrospective interviews. These phenomena are described and discussed in more detail earlier in chapter 6.7.1. The second limitation in this study is that the time between the last discharge and the end of the follow-up may differ in theory from one day to three years. This means that further follow-ups are needed to draw final conclusions about the success of the deinstitutionalization at this area. However, one third of the patients were less than 25% and two thirds of the patients were less than 75% of the follow-up period in hospital care.

 

8. Summary

 

8.1. Background and aims of the study

During the last decade schizophrenia research has emphasized the importance of gender differences. The purpose of the present study was to analyze gender differences with regard to some important sociodemographic variables, age at onset, incidence, treatment, outcome and deinstitutionalization in three different, mainly schizophrenic populations from Northern Finland .

 

8.2. Material and methods

The first study population was the Northern Finland 1966 Birth Cohort, an unselected, general population birth cohort based upon 12068 pregnant women in the provinces ofLapland and O ulu with an expected delivery date during 1966. Their 12058 live-born children represent 96.3% of all births in the region. We followed prospectively 11017 subjects (males: 5636 = 51.2%; females: 5381 = 48.8%) from the age of 16 up to the age of 28 by means of the Finnish Hospital Discharge Register. All the case notes of the 387 subjects hospitalized due to the psychiatric disorder were obtained. The diagnoses were validated for the DSM-III-R criteria resulting in 89 (males: 58 = 65.2%; females: 31 = 34.8%) DSM-III-R schizophrenia cases. From this study population gender differences with regard to age at onset and incidence of schizophrenia were calculated. The second study population was derived from the closed therapeutic community ward situated at the Department of Psychiatry, University of Oulu . A total of 1525 patients who had their first treatment episodes at the ward between 1. Jan., 1977 and 2. July 1993 formed the study population. Of them, 51 % (n = 784) were males and 49 % (n = 741) females. 85 males and 64 females had been diagnosed as schizophrenics, 112 males and 90 females had been diagnosed to suffer from schizophreniform or schizoaffective psychoses. Age at first admission, the degree of active participation of the patients in individual, group, and milieu therapy and the institutional outcome of these patients were assessed. 69

The third study population was formed of 253 long-stay psychiatric inpatients treated for at least six months without a break during 1992 (index hospitalization) in the Department of Psychiatry, Oulu University Hospital . The patients were identified from the computerized patient register and data were collected from this register and from case records at the end of the index hospitalization and at the end of the four year follow-up (1992-1995). About 80% of the patients had a diagnosis of schizophrenia and because of the homogeneity of the patients, they were analyzed as a single group with regard to the diagnosis. From this study population gender differences regarding age at onset and other sociodemographic and clinical variables were studied. Also the placement after the last discharge and at the end of the follow-up as well as factors predicting hospitalization after the follow-up were studied.

 

8.3. Results and conclusions

In the Northern Finland 1966 Birth Cohort study the mean age at onset of schizophrenia using two different criteria was between 21.4-21.5 in men and 21.2-21.4 in women. The peak of onset in men lay in the 20-24 year age group whereas in women it occurred in the 16-19 year age group. The time difference between first psychotic symptoms and first psychiatric hospital admission was minimal for men and women. In the therapeutic community study the mean age of the patients with schizophrenia at their first admission to this ward was 27.4 years in men (SD 7.4) and 27.8 in women (SD 7.5) and patients with the diagnoses of schizophreniform/schizoaffective disorders 26.5 years in men (SD 7.2) and 27.4 in women (SD 7.7). In the long-stay patients study, mean age at onset of illness using five different criteria was between 22.2-24.0 years in men and 24.3-25.4 years in women. Mean/median time lag in years between the first sign of psychiatric symptoms and the first psychiatric hospitalization was 2.5/1.0 (SD 5.1) overall, 2.6/1.0 (SD 4.4) for males and 2.2/1.0 (SD 6.0) for females. Mean/median time lag in years between the first psychotic symptoms and the first psychiatric hospitalization was minimal in both males and females. There were no gender differences regarding age at onset in any of these three different studies. However, the peak of onset of females was lower than that of men. These results are contradictory to numerous earlier clinical studies of age at onset and indicate that there is no gender difference with regard to age at onset. The cohort studied is presently about halfway through the period of risk for schizophrenia and the other study populations did not represent random hospital populations. This suggests the possibility that within the schizophrenic patient group there are homogeneous subgroups with regard to the onset of illness. The minimal time lag between the first psychotic symptoms and the first psychiatric hospitalization indicates that in Finland the patients are hospitalised earlier than in many other countries after the manifestation of their first psychotic symptoms. In the Northern Finland 1966 Birth Cohort study the annual incidence rate of DSM-IIIR schizophrenia was high: 7.9 out of 10 000 in men and 4.4 in women by the age of 28 years. In men it was highest in the age group of the 20-24 year-olds while in women the peak occurred in the age group of the 16-19 year-olds. There was a decreasing trend in the incidence rates for women of the older age groups. The higher incidence rates in men 70 support the findings of earlier studies that incidence among young men is higher than in women. The high annual incidence rates of DSM-III-R schizophrenia in this study over the whole 13 year follow-up period may be due to the fact that the cohort has been followed through the high risk years for the morbidity to schizophrenia and a final conclusion of the total life-time incidence can not yet be formulated. However, the high rates do not support the view that the incidence of schizophrenia is decreasing in Finland . Incidence among men was almost two times higher than that in women. It suggests that the number of female schizophrenia cases will never reach the number of male cases, because an identical life-time incidence in this study population of men and women would require a remarkable second peak of onset in the women. In the Therapeutic community study there were no gender differences regarding the sociodemographic variables, the length of stay and the number of treatment episodes in this ward in any diagnostic group. Differences in the degree to which males and females participated in the psychosocial therapies (individual, group and milieu therapy) and differences with regard to the institutional outcome were minimal, some trend favoring females. These minimal gender differences indicate the achievement of the treatment goals, or achieving intergender equality and balance. These goals are especially important for schizophrenic males because of their more severe clinical profile and poorer prognoses. The therapeutic community model may help psychotic male patients in approaching their age- and gender-specific life span challenges. In the long-stay patients study almost two-thirds of the long-stay patients were men. Very few gender differences were found in sociodemographic and clinical characteristics or in the utilization of psychiatric hospital care. The female patients had a better ability to adjust socially. It would seem that men are overrepresented amongst long-stay inpatients because of their poorer outcome. The observed similarity between male and female patients could be a result of the severe nature of the illness in the patient group. Patients have had to pass through several filters through health care contacts before they reach this most intensive of the health services. At each filter, clinical characteristics will become constrained and thus differences between the sexes will be attenuated. The homogeneity of men and women can also be partly iatrogenic - caused by the traditional custodial care and by the high doses of medication. About 70% of the long-stay patients were discharged during the four year follow-up and only 15% were able to live without continuous support. The discharge did not cause homelessness. Marital status, dwelling place, absence of negative symptoms and severity of the illness were associated with hospitalization at the end of the follow-up. Gender was not associated with hospitalization at the end of the follow-up period. Our study showed that long-term patients are dependent on considerable support and that the most seriously ill patients are, in fact, in hospitals. Alternative residential facilities have to be regarded as pre-requisites for the deinstitutionalization process of the long-stay patients to be successful.