Psychiatric and Cognitive Features in Italian Women With the FMR1 Premutation: A Comprehensive Assessment Using...

Women with the FMR1 premutation (PM) are at increased risk for fragile X-associated conditions (FXPAC), including cognitive and psychiatric features collectively termed fragile X-associated neuropsychiatric disorders (FXAND). This study is the first to systematically investigate cognitive and psychiatric features in Italian female premutation carriers (PCs). One hundred Italian women with the PM were stratified into four age-groups (≤ 40, 41-50, 51-64, and ≥ 65 years). Cognitive performance was assessed using Raven's Standard Progressive Matrices (RSPM) and the Telephone Montreal Cognitive Assessment (T-MoCA). Psychological symptoms were measured with standardized self-report questionnaires, and psychiatric diagnoses were determined through the Structured Clinical Interview for DSM-5 (SCID-5) disorders. Cognitive scores were generally within the normal range; however, participants aged ≥ 65 years performed significantly worse on both RSPM and T-MoCA. SCID-5 interviews showed that 51% met criteria for at least one current psychiatric disorder, most commonly generalized anxiety (37%) and major depression (18%). Early-life neurodevelopmental difficulties were frequently reported. Self-report measures often underestimated clinical severity relative to interview findings. These findings underline significant psychiatric vulnerability in female PCs and emphasize the need for prevention and timely intervention, including routine psychiatric assessment in clinical care.