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

Area of Science:

• Neurogenetics
• Psychiatry
• Cognitive Science

Background:

• Women with the FMR1 premutation (PM) have an increased risk of fragile X-associated conditions (FXPAC), including fragile X-associated neuropsychiatric disorders (FXAND).
• Systematic investigation of cognitive and psychiatric features in Italian female premutation carriers (PCs) is lacking.

Purpose of the Study:

• To systematically investigate cognitive and psychiatric features in Italian women with the FMR1 premutation.
• To stratify findings by age groups and assess the prevalence of FXAND.

Main Methods:

• One hundred Italian female PCs were divided into four age groups.
• Cognitive function was assessed using Raven's Standard Progressive Matrices (RSPM) and the Telephone Montreal Cognitive Assessment (T-MoCA).
• Psychiatric diagnoses were determined using the Structured Clinical Interview for DSM-5 (SCID-5), supplemented by self-report questionnaires.

Main Results:

• Cognitive scores were generally normal, but participants aged ≥65 years showed significantly lower performance on RSPM and T-MoCA.
• 51% of participants met criteria for at least one current psychiatric disorder, with generalized anxiety (37%) and major depression (18%) being most common.
• Early-life neurodevelopmental difficulties were frequently reported, and self-report measures often underestimated clinical severity compared to interview findings.

Conclusions:

• Female FMR1 premutation carriers exhibit significant psychiatric vulnerability.
• Routine psychiatric assessment is crucial for early detection and intervention in this population.
• Age is a factor in cognitive decline among older female carriers.