Sex differences in sub-clinical psychosis—Results from a community study over 30 years Wulf Rössler a, b, ⁎, Michael P. Hengartner a , Vladeta Ajdacic-Gross a , Helene Haker a , Jules Angst a a Department of General and Social Psychiatry, Psychiatric University Hospital, University of Zurich, Militärstrasse 8, 8004 Zurich, Switzerland b Collegium Helveticum, A Joint Research Institute between the University of Zurich and the Swiss Federal Institute of Technology, Zurich, Switzerland abstract article info Article history: Received 18 January 2012 Received in revised form 1 April 2012 Accepted 28 April 2012 Available online 24 May 2012 Keywords: Age of onset Course Epidemiology Sex differences Schizophrenia Schizotypy Sub-clinical psychosis Sex differences in schizophrenia have long been reported. They are found within almost all aspects of the disease, from incidence and prevalence, age of onset, symptomatology, and course to its psycho-social outcome. Many sex-related hypotheses have been developed about the biology, psychology, or sociology of that disease. A further approach to study sex differences would be to examine such differences in sub-clinical psychotic states as well. If factors related to full-blown psychosis were equally meaningful over the entire psychosis continuum, we should expect that “true” sex differences could also be identified in sub-clinical psychosis. Here, we studied sex differ- ences in sub-clinical psychosis within a community cohort in Zurich, Switzerland. This population was followed for over 30 years and included males and females between the ages of 20/21 and 49/50. We applied two different measures of sub-clinical psychosis representing schizotypal signs and schizophrenia nuclear symptoms. Using cross-sectional and longitudinal analyses, we found no significant sex differences in sub-clinical psychosis over time with respect to age of onset, symptomatology, course, or psycho-social outcome. Thus it appears that sex differences in psychosis manifest themselves at the high end of the continuum (full-blown schizophrenia) rather than within the sub-threshold range. Possibly males and females have separate thresholds for certain symptoms because they are differently vulnerable or exposed to various risk factors. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Historically, sex differences in schizophrenia cases have been associ- ated with almost all aspects of the disease, including incidence and prev- alence, age of onset, symptomatology, or time course to its psycho-social outcome (Leung and Chue, 2000; Abel et al., 2010). To obtain clues about the aetiology of this disorder, analyses of this disorder have always in- cluded sex-related hypotheses. Until recently, most researchers have believed that males and fe- males are at equal risk to develop schizophrenia. However, a review by McGrath et al. (2008) showed that men have a significantly higher incidence. Nevertheless, such differences in incidence and prevalence have depended upon diagnostic criteria, i.e., the broader the criteria the less significant the differences (Abel et al., 2010). The time of onset for schizophrenia varies between males and females, and methodologically sound studies have consistently shown that women are older than men when symptoms arise (Sartorius et al., 1986; Hafner et al., 1989, 1993a, 1993b; Salokangas and Stengard, 1990; Jablensky et al., 1992). Less routine are the findings concerning differences in symptomatology and the course of the disease, which might be due partly to methodological problems (Riecher-Rossler and Rossler, 1998). For example, symptomatology is apparently worsened with an earlier age of onset. Women seem to have a more favorable course and a better psycho- social outcome than do men (Riecher-Rossler and Rossler, 1998; Riecher-Rossler and Hafner, 2000). In particular, social adjustments are probably better for the former. However, women tend to exhibit, at times dramatically, an enhanced risk for the exacerbation of psy- chosis, such as after parturition (Kendell et al., 1987), or during peri- menopause (Riecher-Rossler, 2002). These epidemiological findings can be further investigated by ex- amining the sex differences found in sub-clinical psychotic states, a field that is gaining increased interest within schizophrenia research. Recent studies have suggested that the psychosis phenotype might also be expressed at sub-clinical levels (van Os et al., 2000; Johns and van Os, 2001; Rossler et al., 2007). That phenotype commonly entails psychotic-(like) experiences, proneness to psychosis, an at-risk mental state, or schizotypy. Sub-clinical psychosis focuses mostly on positive symptoms, which are of particular importance to detection of the early stages (Tandon et al., 2012). Current data support the notion of a continuity of psychotic symp- toms with normal experiences (van Os et al., 2009). Such symptoms typically follow an inverse Gaussian (i.e., Wald) distribution, as would be expected for continuously distributed symptoms within the general population. If sex-related factors, as identified in full-blown psychosis, Schizophrenia Research 139 (2012) 176–182 ⁎ Corresponding author at: Department of General and Social Psychiatry, Psychiatric University Hospital, University of Zurich, Militärstrasse 8, CH-8004 Zurich, Switzerland. Tel.: +41 44 296 7400; fax: +41 296 7409. E-mail address: roessler@dgsp.uzh.ch (W. Rössler). 0920-9964/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2012.04.017 Contents lists available at SciVerse ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres