Data from: Psychiatric disorders in C9orf72 kindreds: study of 1,414 family members

Objective: This study aimed to determine in a systematic manner if the
C9orf72 phenotype might extend beyond frontotemporal dementia (FTD) and
amyotrophic lateral sclerosis (ALS) to include psychiatric disease.
Methods: A validated semi-structured family history interview was
conducted in a large cohort of patients with FTD and ALS (n=89), with and
without the C9orf72 expansion (n=29 and n=60 respectively) encompassing
1,414 first and second-degree relatives. Statistical analyses employed
both the hazard ratio (HR) and relative risk ratio (RR) to determine the
risk profiles within families. Results: A significant hazard ratio (HR) of
4.9 (95% CI: 1.9 - 13.9, p=0.003), confirmed a higher probability of
developing schizophrenia for relatives of C9orf72 carriers compared to
non-carriers. In total eight relatives of C9orf72 carriers experienced an
episode of late-onset psychosis unrelated to schizophrenia, in comparison
to one non-carrier (HR=17.9, 95% CI: 2.2, 143.2, p=0.007). The probability
of suicide was also significantly higher for family members of C9orf72
carriers (HR=2.7, 95% CI 1.2,6.2, p=0.02). A HR of 2.7 (95% CI: 1.1 - 6.9,
p=0.03) indicated a higher probability for Autism Spectrum Disorder (ASD)
in family members of C9orf72 carriers, and this risk extended to FTD.
Furthermore, there was a positive association between psychosis in
probands and mental health disorders including ASD in their family members
(p=0.04). Conclusion: Overall the results from this study suggest that a
psychiatric phenotype exists within C9orf72 kindreds, Further studies
should attempt to delineate the risk for psychiatric disorders in C9orf72
kindreds, to aid in clinical decision-making particularly regarding
genetic counseling, through collaborations between neurology and
psychiatry.