Within the sample of UHR patients, males appeared to have more severe negative symptoms and lower functioning than females, when data from all three time points was examined. The absence of differences between males and females at baseline suggests that differences in negative symptoms and functioning in UHR patients may be subtle but remain stable over time. Although the sample size was very small, incorporating data from follow-up time points decreased measurement error, thus providing a more stable and reliable means of detecting gender differences. Furthermore, differences in symptoms and functioning may be detectable at baseline with a large enough sample size.
Although the observed differences in symptoms and functioning did not remain significant after Bonferroni correction for multiple comparisons, they were exactly as predicted a priori, and they support the large literature in the field indicating that there are differences in the clinical presentation of male and female participants with psychotic disorders (Angermeyer, Kühn, & Goldstein, 1990
; Bardenstein & McGlashan, 1990
; DeLisi et al., 1989
; Goldstein & Link, 1988
; Grossman et al., 2006
; Hambrecht et al., 1992
; Lindamer et al., 2003
; Shtasel et al., 1992
; Usall et al., 2003
). These findings suggest that underlying differences may predate the onset of psychosis. This could reflect the fact that males and females are vulnerable to different “types” of psychotic disorders or that psychosis develops differently in men and women.
Differences in gonadal hormones may explain why men and women with schizophrenia have different symptom presentation and functional outcomes. Findings that secondary-sex characteristics and other markers of hormonal activity may be disrupted in adult schizophrenia patients have supported the role of estrogen in the psychotic process (DeLisi et al., 1989
; Maric et al., 2005
). While antipsychotic medications are known to effect prolactin levels in patients (Riecher-Rossler et al., 1994
), it has been shown that disruptions in estrogen levels in female patients with schizophrenia spectrum disorders cannot be fully explained by the effects of antipsychotic medications alone (Canuso et al., 2002
). Furthermore, recent work by Goldstein et al. (2007)
indicates that hippocampal abnormalities, which may be caused by abnormal levels of gonadal hormones, are present in both patients and their healthy relatives. This suggests that endocrine imbalances are associated with disease risk and are not a product of disease state. Furthermore, these differences appear to be more pronounced in females (Goldstein et al., 2007
), indicating that these hormonal effects may be more related to disease risk for female patients than males.
Estrogen and other gonadal hormones alter many important neuronal processes (Cameron, 2004
; Meethal & Atwood, 2005
), have effects on cognitive and psychological functioning (Cameron, 2004
) and may affect symptoms presentation in schizophrenia (Halbreich & Kahn, 2003
; Riechler-Rossler & Hafner, 2000; Salem & Kring, 1998
). Estrogen may also protect against the effects of glutamate toxicity, ischemia, and amyloid β exposure and may act as an antioxidant and as a general protector against inflammation in the central nervous system (Meethal & Atwood, 2005
; Sribnic et al., 2004). There is even evidence that estrogen may facilitate the effects of antipsychotic medications, causing women to have a better treatment response than men and thus a better course of illness (Goldstein et al., 2002
). However, more research is necessary in order to fully understand the relative contribution of gonadal hormones or any other sex-specific developmental influences towards symptoms and functioning in psychosis.
Differences in other psychosocial factors may also be contributing to better functioning and lower levels of negative symptoms in female UHR patients. Among the sample of UHR participants, males reported less positive social support than their female counterparts and felt they received marginally more criticism than females. This is of interest because among patients with psychosis, the level of hostility or criticism expressed by family members regarding an ill relative has been found to predict relapse in over a dozen studies (Butzlaff & Hooley, 1998
) and the quality of social networks around an individual patient has been shown to correlate with that person’s level of functioning (Erikson et al, 1998). Additionally, recent work conducted on UHR patients found that family involvement, support, and warmth predict improvement in negative symptoms and social functioning (O’Brien et al., 2006
). Social support remains an important link to follow in UHR studies. Variations in social support among UHR patients may not be unique to psychosis but may instead reflect “normal” differences between males and females. It is also likely that a bidirectional relationship exists between symptoms and social support among UHR patients. However, if relationships between social support and functioning for UHR patients hold true in later analyses, then that would lend credence to the importance of psychosocial interventions for this population.
Male and female participants did not vary significantly in any relevant demographic variables, including age. The absence of an age difference in our clinical population could be explained by a variety of reasons. It may be that female participants have a longer prodromal period than males (i.e.
males may experience a faster deterioration once subthreshold psychotic symptoms arise). Additionally, some recent studies have suggested that the age of onset differences may only exist in certain kinds of psychosis, namely among those patients who develop paranoid schizophrenia (Salokangas et al., 2003
). This study would be not be appropriately powered to detect any potential differences in populations who are only susceptible to specific kinds of psychotic illnesses. Follow-up studies pooling from a larger number of participants and with greater conversion data available may be better equipped to answer these questions in the future.
In our sample, differences in negative symptoms were found to mediate differences in functioning between male and female patients. The link between negative symptoms and functioning has been well established in research examining outcomes in chronic schizophrenic patients (Brier et al., 1991; Velligan et al., 1997
) however this is the first study to-date, that the authors are aware of, to show an association between negative symptoms and functioning in UHR patients. This has large implications both for future research and also for the treatment of UHR patients. The results of this study suggest that male and female UHR patients may experience different combinations of symptoms during the psychosis prodrome, and that these differences in symptoms may contribute to different functional outcomes. Due to a large attrition rate, long-term differences in symptoms and functioning could only be assessed in a small number of participants. Future replication of these findings with a larger sample size will be necessary to fully understand whether differences in symptoms and functioning predate conversion to psychosis. However, this observed association between negative symptoms and functioning highlights the importance of developing targeted interventions to decrease the severity of negative symptoms, in order to increase the general functioning and quality of life for patients.