2024 Theses Doctoral
Two hypotheses for gender differences in the onset and outcome of schizophrenia spectrum disorders: Estrogen protection & psychosocial development
Gender has long been considered an important factor in uncovering the etiology of schizophrenia. There is now strong evidence that gender is related to the age at onset of psychotic symptoms and somewhat weaker evidence of gender differences in other aspects of schizophrenia, such as clinical and functional outcomes. Simultaneously, there is growing evidence that age at onset itself is an important prognostic factor.
This dissertation seeks to investigate the complex relationship between gender, age at onset, and outcomes of schizophrenia spectrum disorders, in light of two main mechanisms, estrogen protection and psychosocial development. The estrogen protection hypothesis posits that estrogen has antipsychotic effects that result in a later age at onset and more favorable outcomes for pre-menopausal women compared with men with onset at the same age. When women lose estrogen protection around menopause, they may develop a more severe illness. The psychosocial development hypothesis posits that women who have later onset due to estrogen protection have more time to develop psychosocial resources that improve their role functioning later in life.
In Chapter 2, a systematic literature review was conducted on the relationship between gender and age at onset of schizophrenia spectrum disorders in determining functional outcomes. There was some support for the psychosocial development hypothesis where age at onset mediates the relationship between gender and functional outcomes. Three studies were identified that conducted formal mediation analyses and used minimum criteria to detect mediation in the remaining studies. Together, these findings suggest that women have better functioning outcomes than men, by virtue of having later illness onset.
Chapters 3 & 4 utilized a nationally representative sample of people with schizophrenia spectrum disorders in China to further examine the relationship between gender, age at onset, and other illness outcomes. Unlike many studies in the current literature, this dataset included people who had never sought formal treatment, providing a unique opportunity to explore the possibility of selection bias in other studies that primarily recruit participants from treatment settings. Furthermore, the majority of schizophrenia research has been conducted in high-income countries, and these data from China could provide some important insights from a low- to middle-income country.
In Chapter 3, finite mixture techniques were used to model the entire distribution of age at onset as a function of gender and family history, taking into account any clustering patterns of observations. The analysis identified an early-onset group characterized by men and those with a family history, a mid-onset group characterized by both men and women without a family history, and a late-onset group characterized by women without a family history. Distinguishing between these groups showed that gender and family history are indeed robust predictors of age at onset.
Chapter 4 investigated a) the interaction between gender and age at onset in producing clinical outcomes and b) the mediating effect of age at onset in the relationship between gender and role functioning outcomes. This study did not find evidence of interaction between gender and age at onset in producing clinical outcomes. It did find that women’s increased probability of marrying was mediated by a later age at onset.
Overall, the results of this dissertation provide even further support of the well-established relationship between gender and age at onset. However, applying the estrogen protection hypothesis to schizophrenia spectrum outcomes requires further study. This dissertation also suggests that the psychosocial development hypothesis, which is not well-studied, may provide a promising new perspective on whether and why women appear to have better outcomes.
This research also expands our knowledge of gender differences in schizophrenia spectrum disorders in China and highlights the importance of further research in other low- to middle-income countries. While the estrogen protection and psychosocial development hypotheses are surely important in our understanding of women with schizophrenia spectrum disorders, conducting this study using a dataset from China called attention to other social, political, and economic issues that women face that affect all aspects of their illness. These issues and their impact on women are likely different in high-income countries. Ultimately, the estrogen protection and psychosocial development hypotheses can only be understood within the complex context of women’s lived experience with schizophrenia spectrum disorders.
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- WonPatBorja_columbia_0054D_18205.pdf application/pdf 1.73 MB Download File
More About This Work
- Academic Units
- Epidemiology
- Thesis Advisors
- Yang, Lawrence
- Degree
- Ph.D., Columbia University
- Published Here
- January 17, 2024