January 1988

Psychiatric Disability in Female Carriers of the Fragile X Chromosome

Author Affiliations

From the Division of Child Psychiatry and Kennedy Institute, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore (Dr Reiss); the Department of Pediatrics, University of Colorado Health Sciences Center, and the Child Development Unit, Children's Hospital, Denver (Dr Hagerman); and the Department of Psychiatry and Behavioral Sciences, Stanford (Calif) University School of Medicine (Drs Vinogradov and King and Mr Abrams).

Arch Gen Psychiatry. 1988;45(1):25-30. doi:10.1001/archpsyc.1988.01800250029005

• Fragile X syndrome, an X-linked genetic condition, is an important genetic cause of mental retardation in males. In addition to mental retardation, hemizygous males with fragile X syndrome appear to have a greater likelihood of displaying behaviors classified under the diagnostic category of pervasive developmental disorder than would be expected on the basis of mental retardation alone. Although the majority of female heterozygotes with the fragile X genetic defect are of normal intelligence, our clinical work with this population and a recent case report have suggested that females with fragile X syndrome have an increased rate of schizophrenia spectrum and affective disorders. In this study, the relationship of the fragile X genetic defect to psychopathology in female heterozygotes is investigated by psychiatric evaluation of 35 obligate female carriers of the fragile X chromosome and a comparison group of 24 fragile X—negative controls. Female fragile X carriers were found to have a greater frequency of psychopathology associated with schizophrenia spectrum diagnoses, particularly schizotypal features. A weaker association between the fragile X genetic defect and chronic affective disorders was detected. The specificity of the neuropsychiatric phenotype occurring in particular genetic conditions such as the fragile X syndrome adds a potentially valuable tool to the study of psychopathology in the general population.