To systematically review and meta-analyze psychiatric difficulties in females with Fragile X Syndrome (FXS), examining associations with intellectual ability and co-occurring autism, and evaluating sex representation in FXS psychiatric literature.
Approach:
Systematic Review: Conducted systematic searches of PsycINFO, MEDLINE, Embase, and Web of Science for studies published between 1980 and 2025 on psychiatric conditions in females with FXS.
Meta-Analysis: Performed random-effects meta-analyses to estimate prevalence of psychiatric difficulties among females with FXS.
Key Findings:
A pronounced sex imbalance was observed, with male-focused studies outnumbering female-focused studies by approximately 4:1.
Meta-analyses indicated high prevalence of anxiety (57%) and depression (41%).
Prevalence rates for ADHD (33%), aggression (20%), and self-injury (14%) were also reported.
Co-occurring autism was consistently associated with greater psychiatric vulnerability.
Intellectual ability showed no consistent associations with psychiatric difficulties.
Interpretation:
Females with FXS exhibit vulnerability to psychiatric difficulties, but their underrepresentation in research may lead to an underestimation of psychiatric risk.
Limitations:
Significant sex imbalance in existing research, with a predominance of male-focused studies.
Variability in age across samples contributed to heterogeneity in prevalence estimates.
Methodological challenges in assessing psychiatric conditions in females with varying intellectual abilities, including the lack of validated assessment tools.
Conclusion:
The findings highlight the importance of developing more refined, sex-specific models of psychopathology in FXS.
