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Dylan Campbell, BS




Research Staff


Brigham and Women's Hospital




Dylan Campbell, Sinead M. Kelly, Michael J. Coleman, Nora Penzel, Elana Kotler, Nicholas Kim, Omar John, Anastasia Haidar, Simone Veale, Tashrif Billah, Ofer Pasternak, Sylvain Bouix, Yogesh Rathi, Daphne Holt, Matcheri S. Keshavan, Dost Öngür, Alan Breier, Martha E. Shenton, Marek Kubicki, Johanna Seitz-Holland

Principal Investigator


Interaction of Family History and Sex in Individuals with Psychosis


Background: While existing literature has documented sex differences in the age of onset of psychosis, emerging evidence suggests that a family history of psychosis may modulate these sex-specific effects. Furthermore, integrating sex and family history has demonstrated enhanced statistical power in Genome-wide Association Studies of psychiatric disorders. However, limited knowledge exists regarding the interactive effects of sex and family history on psychopathology in individuals with a psychotic disorder. Therefore, this study investigates whether notable differences exist in the prevalence of family history between sexes and whether sex and family history exhibit interactive effects on variables such as the age of onset, symptom severity, and hippocampal volumes in affected individuals.

Methods: We examined 220 individuals from the Human Connectome Project for Early Psychosis with a psychotic disorder and data from the Family Interview for Genetic Studies. We compared individuals with 1) a first-degree family history of psychosis (N = 30, mean age = 22.13, 50% male) and 2) only a second-degree history (N = 29, mean age = 24.02, 46.67% male) to 3) those with no family history (N = 161, mean age = 23.22, 64.60% male). Hippocampal volumes were obtained from FreeSurfer parcellations of T1 images. We used Chi-square tests to examine sex differences and ANCOVAs to examine the interactive effects of sex and family history on age of onset, symptom severity, and hippocampal volumes.

Results: Individuals with a first- or second-degree family history were more likely to be female than those with no family history (p = 0.038). However, no other interactive effects of sex and family history were significant.

Conclusions: The observed association between sex and family history underscores the importance of further investigation in clinical high-risk populations for psychosis, early psychosis, and chronic cohorts. Such findings may have implications for tailored prevention and treatment strategies.

Research Context

Having a family history of psychosis confers an approximate 10% to 12% probability of developing a psychotic disorder (Georgopoulos et al., 2019). The current findings underscore the critical need to understand if and why being female represents an additional risk for developing psychosis when paired with family history. If substantiated by further investigations across cohorts encompassing early-psychosis, clinical high-risk, and chronic populations, this observation holds promise for informing the refinement of predictive models and the development of more targeted therapeutic interventions tailored to females.