Emma M Devenney1, Rebekah M Ahmed2, Glenda Halliday2, Olivier Piguet2, Matthew C Kiernan2, John R Hodges2. 1. From the Brain and Mind Centre (E.M.D., R.M.A., G.H., O.P., M.C.K., J.R.H.), University of Sydney; Central Clinical School (E.M.D., R.M.A., M.C.K., J.R.H.), University of Sydney; and ARC Centre of Excellence in Cognition and its Disorders (E.M.D., R.M.A., O.P., J.R.H.), Sydney, Australia. Emma.devenney@sydney.edu.au. 2. From the Brain and Mind Centre (E.M.D., R.M.A., G.H., O.P., M.C.K., J.R.H.), University of Sydney; Central Clinical School (E.M.D., R.M.A., M.C.K., J.R.H.), University of Sydney; and ARC Centre of Excellence in Cognition and its Disorders (E.M.D., R.M.A., O.P., J.R.H.), Sydney, Australia.
Abstract
OBJECTIVE: The aim of this study was 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 semistructured 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 used both the hazard ratio (HR) and the relative risk ratio to determine the risk profiles within families. RESULTS: A significant HR of 4.9 (95% confidence interval [CI]: 1.9-13.9, p = 0.003) confirmed a higher probability of developing schizophrenia for relatives of C9orf72 carriers compared with noncarriers. In addition, 8 relatives of C9orf72 carriers experienced an episode of late-onset psychosis unrelated to schizophrenia, in comparison to one noncarrier (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). An HR of 2.7 (95% CI: 1.1-6.9, p = 0.03) indicated a higher probability of 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 of psychiatric disorders in C9orf72 kindreds to aid in clinical decision making, particularly regarding genetic counseling, through collaborations between neurology and psychiatry.
OBJECTIVE: The aim of this study was 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 semistructured 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 used both the hazard ratio (HR) and the relative risk ratio to determine the risk profiles within families. RESULTS: A significant HR of 4.9 (95% confidence interval [CI]: 1.9-13.9, p = 0.003) confirmed a higher probability of developing schizophrenia for relatives of C9orf72 carriers compared with noncarriers. In addition, 8 relatives of C9orf72 carriers experienced an episode of late-onset psychosis unrelated to schizophrenia, in comparison to one noncarrier (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). An HR of 2.7 (95% CI: 1.1-6.9, p = 0.03) indicated a higher probability of 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 of psychiatric disorders in C9orf72 kindreds to aid in clinical decision making, particularly regarding genetic counseling, through collaborations between neurology and psychiatry.
Authors: Stacey Li Hi Shing; Mary Clare McKenna; We Fong Siah; Rangariroyashe H Chipika; Orla Hardiman; Peter Bede Journal: Brain Imaging Behav Date: 2021-01-05 Impact factor: 3.978
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Authors: Simon Ducharme; Annemiek Dols; Robert Laforce; Emma Devenney; Fiona Kumfor; Jan van den Stock; Caroline Dallaire-Théroux; Harro Seelaar; Flora Gossink; Everard Vijverberg; Edward Huey; Mathieu Vandenbulcke; Mario Masellis; Calvin Trieu; Chiadi Onyike; Paulo Caramelli; Leonardo Cruz de Souza; Alexander Santillo; Maria Landqvist Waldö; Ramon Landin-Romero; Olivier Piguet; Wendy Kelso; Dhamidhu Eratne; Dennis Velakoulis; Manabu Ikeda; David Perry; Peter Pressman; Bradley Boeve; Rik Vandenberghe; Mario Mendez; Carole Azuar; Richard Levy; Isabelle Le Ber; Sandra Baez; Alan Lerner; Ratnavalli Ellajosyula; Florence Pasquier; Daniela Galimberti; Elio Scarpini; John van Swieten; Michael Hornberger; Howard Rosen; John Hodges; Janine Diehl-Schmid; Yolande Pijnenburg Journal: Brain Date: 2020-06-01 Impact factor: 13.501
Authors: Nga Yan Tse; Sicong Tu; Yu Chen; Jashelle Caga; Carol Dobson-Stone; John B Kwok; Glenda M Halliday; Rebekah M Ahmed; John R Hodges; Olivier Piguet; Matthew C Kiernan; Emma M Devenney Journal: J Neurol Date: 2022-03-13 Impact factor: 6.682