Ammar Albanna1, Zia Choudhry2, Philippe-Olivier Harvey3, Ferid Fathalli4, Clifford Cassidy3, Sarojini M Sengupta3, Srividya N Iyer1, Aldanie Rho3, Martin Lepage4, Ashok Malla4, Ridha Joober5. 1. Department of Psychiatry, McGill University, Canada. 2. Douglas Mental Health University Institute, Canada; Department of Human Genetics, McGill University, Canada. 3. Douglas Mental Health University Institute, Canada. 4. Douglas Mental Health University Institute, Canada; Department of Psychiatry, McGill University, Canada. 5. Douglas Mental Health University Institute, Canada; Department of Human Genetics, McGill University, Canada; Department of Psychiatry, McGill University, Canada; Integrated Program in Neuroscience, McGill University, Canada. Electronic address: ridha.joober@douglas.mcgill.ca.
Abstract
BACKGROUND: Single nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767. However, its exact role in modulating the schizophrenia phenotype is not known. AIMS: To comprehensively investigate the relationship between rs9960767 risk allele (C) of TCF4 and cognitive performance in patients with first episode psychosis (FEP). METHODS: 173 patients with FEP received a comprehensive neurocognitive evaluation and were genotyped for rs9960767. Carriers of the risk allele (CA/CC) were compared to non-carriers (AA) using Multivariate Analysis of Covariance MANCOVA. Ethnicity, negative symptoms and substance abuse were included as covariates. RESULTS: Carriers of the risk allele had a statistically significant lower performance in the cognitive domain of Reasoning/Problem-Solving compared to non-carriers (F1,172=4.4, p=.038). There were no significant genotype effects on the other cognitive domains or general cognition. This effect on the Reasoning/Problem-Solving domain remained significant even when controlling for IQ (F1,172=4.3, p=.039). CONCLUSIONS: rs9960767 (C) of TCF4 appears to be associated with neurocognitive deficits in the Reasoning/Problem-Solving cognitive domain, in patients with FEP. A confirmation of this finding in a larger sample and including other TCF4 polymorphisms will be needed to gain further validity of this result.
BACKGROUND: Single nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767. However, its exact role in modulating the schizophrenia phenotype is not known. AIMS: To comprehensively investigate the relationship between rs9960767 risk allele (C) of TCF4 and cognitive performance in patients with first episode psychosis (FEP). METHODS: 173 patients with FEP received a comprehensive neurocognitive evaluation and were genotyped for rs9960767. Carriers of the risk allele (CA/CC) were compared to non-carriers (AA) using Multivariate Analysis of Covariance MANCOVA. Ethnicity, negative symptoms and substance abuse were included as covariates. RESULTS: Carriers of the risk allele had a statistically significant lower performance in the cognitive domain of Reasoning/Problem-Solving compared to non-carriers (F1,172=4.4, p=.038). There were no significant genotype effects on the other cognitive domains or general cognition. This effect on the Reasoning/Problem-Solving domain remained significant even when controlling for IQ (F1,172=4.3, p=.039). CONCLUSIONS:rs9960767 (C) of TCF4 appears to be associated with neurocognitive deficits in the Reasoning/Problem-Solving cognitive domain, in patients with FEP. A confirmation of this finding in a larger sample and including other TCF4 polymorphisms will be needed to gain further validity of this result.
Authors: José R Teixeira; Ryan A Szeto; Vinicius M A Carvalho; Alysson R Muotri; Fabio Papes Journal: Transl Psychiatry Date: 2021-01-05 Impact factor: 6.222
Authors: D M Badowska; M M Brzózka; N Kannaiyan; C Thomas; P Dibaj; A Chowdhury; H Steffens; C W Turck; P Falkai; A Schmitt; S Papiol; V Scheuss; K I Willig; D Martins-de-Souza; J S Rhee; D Malzahn; M J Rossner Journal: Transl Psychiatry Date: 2020-10-09 Impact factor: 6.222