Schizophrenia is a severe mental disorder with established gender differencesReference Abel, Drake and Goldstein1 in the biological, psychological, and social presentation of the disorder.Reference Falkenburg and Tracy2 The risk of developing schizophrenia and having a more severe course of the disorder is higher among males compared with females,Reference Abel, Drake and Goldstein1,Reference Levine and Rabinowitz3 with females having fewer and shorter hospital admissions.Reference Häfner4–Reference Rabinowitz, Levine and Häfner6 The better course for females has been attributed to later onset, allowing increased social and occupational status.Reference Riecher-Rössler, Pflueger, Borgwardt and Kohen7 However, occasionally, females with schizophrenia present worse outcome data than males, as is the case with quality of life. Females report lower quality of life than males,Reference Dubreucq, Plasse, Gabayet, Blanc, Chereau and Cervello8 including in global circumstances, health status and financial resources.Reference Huppert, Weiss, Lim, Pratt and Smith9
The interplay between quality of life and the course of schizophrenia has been studied in the past. Higher quality of life is associated with lower levels of general psychopathology,Reference Packer, Husted, Cohen and Tomlinson10 less severe psychiatric symptomsReference Desalegn, Girma and Abdeta11 and lower rates of psychiatric admissions.Reference Boyer, Baumstarck, Boucekine, Blanc, Lançon and Auquier12–Reference Voruganti, Heslegrave, Awad and Seeman14 However, no single study to date has directly considered gender differences in the association between quality of life and the course of schizophrenia. The current study aims to examine gender differences in the association between quality of life and the risk of subsequent psychiatric admissions in a national sample with schizophrenia.
Method
Participants
The current study data were derived from the Psychiatric Rehabilitation Routine Outcome Measurement Project described elsewhere.Reference Roe, Gelkopf, Gornemann, Baloush-Kleinman and Shadmi15 All procedures contributing to this study were approved by and comply with the ethical standards of the Helsinki Committee at the Israeli Ministry of Health and the Institutional Review Board at the University of Haifa. Written informed consent was obtained from all participants. The study cohort comprised of participants with a last ICD-10 diagnosis of schizophrenia disorder (n = 1624), of whom 60.90% (n = 989) were males and 39.10% (n = 635) were females. This cohort received national psychiatric rehabilitation services in Israel. Participants with illicit drug addiction, violent behaviour or a lack of monitoring by a psychiatrist were not included in the study. Quality of life was assessed from 1 January 2013 to 19 August 2015.
Additional data sources
Demographic data (i.e. gender), information on psychiatric hospital admissions (i.e. dates) and psychiatric diagnosis (i.e. ICD-10 diagnoses) were obtained from the Israeli National Psychiatric Case Registry. This registry contains lifelong listings of psychiatric admissions in Israel from 1950 onwards, with the accompanying updated ICD-10 diagnoses given by an Israeli medical board-certified psychiatrist. The diagnoses in this registry cover over 90% of persons with schizophrenia,Reference Weiser, Werbeloff, Dohrenwend, Levav, Yoffe and Davidson16 are reported to be unchanged over timeReference Rabinowitz, Slyuzberg, Ritsner, Mark, Popper and Ginath17 and have acceptable sensitivity compared with research diagnostic criteria.Reference Weiser, Kanyas, Malaspina, Harvey, Glick and Goetz18 The National Psychiatric Case Registry identifies all patients admitted for broadly defined schizophrenia. The registry has been used in various studies.Reference Levine, Levav, Goldberg, Pugachova, Becher and Yoffe19–Reference Ullman, Levine, Reichenberg and Rabinowitz21
Quality of life
Quality of life was measured using a translated version of the Manchester Short Assessment of Quality of Life, an abbreviation of the Lancashire Quality of Life Profile.Reference Priebe, Huxley, Knight and Evans22 Eight items measured satisfaction with physical and mental health, work or volunteering projects, social status, financial situation, family ties, leisure activities and residential status. The items were self-rated on a 5-point Likert scale. Higher scores marked higher quality of life. Research has shown that this measure has acceptable psychometric properties.Reference Roe, Gelkopf, Gornemann, Baloush-Kleinman and Shadmi15
Analytic approach
Quality of life scores were summed based on the individual item scores. The course of schizophrenia was assessed based on subsequent psychiatric hospital admissions, meaning that admissions were analysed only if they occurred after the date that the quality of life questionnaire was completed. Participants were followed up for the risk of psychiatric admissions for 18 months or until their last psychiatric admission, whichever came first (as in prior studiesReference Levine and Rabinowitz23). To characterise the sample, descriptive statistics were computed. Next, the association between quality of life and the risk of psychiatric admissions was quantified using hazard ratios (HR) from Cox proportional hazards regression models.Reference Cox, Kotz and Johnson24 These models were computed for males and females separately, as well as for the entire cohort. All variables included in the regression models were checked for multicollinearity via the variance inflation factor for the entire cohort and the male and female subpopulations. Models were then computed unadjusted and adjusted for birth year and age at onset. Gender was an additional covariate in the model computed for the entire cohort. The proportional hazard assumption of the Cox regression models was tested by visualising Schoenfeld residual plots.Reference Schoenfeld25
All analyses were computed in R version 3.4.3 for windows using the ‘survival’ libraryReference Therneau and Lumley26 for Cox proportional hazards regression models.
Results
Sample characteristics
The analytic sample was based on 1624 participants with schizophrenia, followed up for 18 months. Males constituted 60.90% of the total sample (n = 989) and females constituted 39.10% (n = 635). A subsample of 148 participants was admitted to a psychiatric hospital during the follow-up time. This subsample comprised 62.84% males (n = 93) and 37.16% females (n = 55). Both samples are characterised in Table 1.
Quality of life and the risk of subsequent psychiatric admissions
The association between quality of life scores and the risk of subsequent psychiatric hospital admissions was quantified using hazard ratios from Cox proportional hazards models. All variables included in the models were checked for multicollinearity via the variance inflation factor and were found sufficiently uncorrelated (<1.5). For males, higher quality of life scores were statistically significantly (P < 0.05) associated with a reduced likelihood of subsequent psychiatric admissions (unadjusted: HR = 0.96, 95% CI 0.93–0.99; adjusted HR = 0.96, 95% CI 0.93–0.99). For females, there was a null association. For the entire cohort, higher quality of life scores were statistically significantly (P < 0.05) associated with a reduced likelihood of subsequent psychiatric hospital admissions (unadjusted: HR = 0.97, 95% CI 0.94–0.99; adjusted HR = 0.97, 95% CI 0.94–0.99), but no significant (P = 0.38) effect was found for gender. See Table 2 for all hazard ratios.
Discussion
Based on data from a national sample with schizophrenia, the current study is the first to explore gender differences in the association between quality of life and the course of schizophrenia. Higher quality of life was associated with a lower risk of subsequent psychiatric hospital admissions among males but not among females.
The null association found for females may be explained by several tentative mechanisms, including the severity of psychiatric symptoms,Reference Eack and Newhill27 oestrogen effects,Reference Häfner28 social circumstancesReference Munk-Jørgensen, Mortensen and Machón29 and premorbid functioning.Reference Childers and Harding30 Gender differences may be explained by combined biological and psychosocial factorsReference Riecher-Rössler and Häfner31 and should be scrutinised in future research.
In schizophrenia research, gender differences are not always examined, although they are a consistently reported aspect of the disorder.Reference Leung and Chue32 Our results show that investigating gender differences in schizophrenia may identify otherwise masked patterns. The model we computed for the entire cohort did not reveal a significant effect for gender, unlike the analyses by gender separately. Furthermore, quality of life was significantly associated with hospital admissions for the entire sample, but within the female sample, the association was null. Exploration of gender differences may therefore have promising implications both in future research of schizophrenia and in clinical practice.Reference Moldin and Frank33
Limitations
The current study has notable limitations. Quality of life was assessed using the Manchester Short Assessment of Quality of Life.Reference Priebe, Huxley, Knight and Evans22 Broader measures that are tailored to schizophrenia (e.g. the Schizophrenia Quality of Life ScaleReference Wilkinson, Hesdon, Wild, Cookson, Farina and Sharma34) exist that may yield different results. However, given the large sample of our study, the Manchester Short Assessment of Quality of Life was chosen for its quick and easy administration. Moreover, the measure has been used in multiple studies (e.g.Reference Savill, Orfanos, Reininghaus, Wykes, Bentall and Priebe35).
Our follow-up time was restricted to 18 months. This period exceeds the minimum 6-month follow-up that is considered adequate and exceeds the 12-month follow-up time in most studies.Reference Leucht, Barnes, Kissling, Engel, Correll and Kane36 Nonetheless, if a longer follow-up time was used, the hospital admission rate would be greater and the results may have changed. A longer follow-up is therefore a direction for future research.
Finally, the current study did not account for all possible confounders that may influence the likelihood of psychiatric hospital admission, such as impaired global functioning, residual symptoms, adverse effects and medication non-adherence,Reference Higashi, Medic, Littlewood, Diez, Granström and De Hert37 or those that may specifically explain the null association found for females (e.g. oestrogen effectsReference Häfner28). Age at onset was included as a confounder because it is established as associated with quality of life and psychiatric admissions in the literature.Reference Rabinowitz, Levine and Häfner6,Reference DeLisi38,Reference Rotstein, Roe, Gelkopf and Levine39 Future prospective studies are warranted to examine how additional factors influence the association between quality of life and psychiatric hospital admissions in both genders.
Data availability
The data that support the findings of this study are available from the corresponding author on reasonable request.
Acknowledgement
We are grateful for the ongoing collaboration with the Mental Health Rehabilitation Department, especially Ronit Dudai and Vered Balush, and the Department of Information and Evaluation at the Ministry of Health, especially Rinat Yoffe, as well as the entire team of the Psychiatric Rehabilitation Patient Reported Outcome Measurement project, notably Aid Rohanna, Paula Garber, Adi Telem and Ronit Mirkin. We acknowledge with thanks the support of the Center for Mental Health Research, Practice and Policy at the University of Haifa.
Author contributions
A.R.: initial and subsequent manuscript drafting, statistical analysis, data management, study conceptualisation. E.S.: critical manuscript feedback. D.R.: data management, study conceptualisation, critical manuscript feedback, mentoring. M.G.: data management, critical manuscript feedback. S.Z.L.: manuscript drafting, statistical analysis, data management, study conceptualisation, mentoring.
Funding
This paper is based on the results of the Outcomes Project, which was conducted by D.R. and M.G. of the Center for Mental Health Research, Practice and Policy at the Department of Community Mental Health with joint funding from the Israeli Ministry of Health and the Laszlo N. Tauber Family Foundation.
Declaration of interest
None.
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