SynthesisFrontiers in psychiatry2026
Psychiatric difficulties in females with fragile X syndrome: a systematic review and meta-analyses.
Synthesis in Frontiers in psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Fragile X syndrome (FXS) is the most common monogenic cause of autism, yet research has largely prioritized males. Females show more variable phenotypes and remain comparatively understudied. This paper provides the first systematic review and meta-analysis of psychiatric difficulties in females with FXS, examines associations with intellectual ability and co-occurring autism, and evaluates sex representation within the FXS psychiatric literature. Methods: Systematic searches of PsycINFO, MEDLINE, Embase, and Web of Science identified English-language, peer-reviewed studies published between 1980 and 2025 reporting psychiatric conditions or symptoms in females with FXS. Of 3,533 records screened, 37 studies met inclusion criteria. Findings were synthesized narratively, and random-effects meta-analyses estimated prevalence of psychiatric difficulties. Results: A pronounced sex imbalance was observed, with male-focused studies outnumbering female-focused studies by approximately 4:1. Anxiety, depression, attention-deficit/hyperactivity disorder (ADHD), aggression, and self-injury were most commonly reported. Meta-analyses indicated high prevalence of anxiety (57%) and depression (41%), with substantial heterogeneity partly attributable to age variability across samples. Less heterogeneous prevalence estimates were observed for ADHD (33%), aggression (20%), and self-injury (14%). Co-occurring autism was consistently associated with greater psychiatric vulnerability, whereas intellectual ability showed no consistent associations. Conclusion: Females with FXS exhibit a marked vulnerability to psychiatric difficulties. However, their ongoing underrepresentation in research suggests that the present findings likely underestimate the true level of psychiatric risk. These findings highlight the importance of developing more refined, sex-specific models of psychopathology in FXS, informed by advances in autism research, to enhance the recognition, understanding, and support for females.
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