Influence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia

Abstract Cytochrome P450 2D6 (CYP2D6) is expressed at high levels in the brain and plays a considerable role in the biotransformation and neurotransmission of dopamine. This raises the question of whether CYP2D6 variations and its impact on the brain can confer susceptibility to schizophrenia. We in...

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Autores principales:	Wonsuk Shin, Minji Bang, Anhye Kim, Doo-Yeoun Cho, Sang-Hyuk Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Psychiatry RC435-571
Acceso en línea:	https://doaj.org/article/a182e146ab9149d396ce0dc94cd46434
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spelling	oai:doaj.org-article:a182e146ab9149d396ce0dc94cd464342021-12-02T13:57:35ZInfluence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia10.1038/s41537-020-00134-z2334-265Xhttps://doaj.org/article/a182e146ab9149d396ce0dc94cd464342021-01-01T00:00:00Zhttps://doi.org/10.1038/s41537-020-00134-zhttps://doaj.org/toc/2334-265XAbstract Cytochrome P450 2D6 (CYP2D6) is expressed at high levels in the brain and plays a considerable role in the biotransformation and neurotransmission of dopamine. This raises the question of whether CYP2D6 variations and its impact on the brain can confer susceptibility to schizophrenia. We investigated the possible links among the CYP2D6 genotype, white matter (WM) integrity of the hippocampus, and the treatment response to antipsychotic drugs in Korean patients with schizophrenia (n = 106). Brain magnetic resonance imaging and genotyping for CYP2D6 were conducted at baseline. The severity of clinical symptoms and the treatment response were assessed using the Positive and Negative Syndrome Scale (PANSS). After genotyping, 43 participants were classified as intermediate metabolizers (IM), and the remainder (n = 63) were classified as extensive metabolizers (EM). IM participants showed significantly higher fractional anisotropy (FA) values in the right hippocampus compared to EM participants. Radial diffusivity (RD) values were significantly lower in the overlapping region of the right hippocampus in the IM group than in the EM group. After 4 weeks of antipsychotic treatment, the EM group showed more improvements in positive symptoms than the IM group. FAs and RDs in the CYP2D6-associated hippocampal WM region were significantly correlated with a reduction in the positive symptom subscale of the PANSS. Greater improvements in positive symptoms were negatively associated with FAs, and positively associated with RDs in the right hippocampal region. The findings suggest that CYP26D-associated hippocampal WM alterations could be a possible endophenotype for schizophrenia that accounts for individual differences in clinical features and treatment responses.Wonsuk ShinMinji BangAnhye KimDoo-Yeoun ChoSang-Hyuk LeeNature PortfolioarticlePsychiatryRC435-571ENnpj Schizophrenia, Vol 7, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Psychiatry RC435-571
spellingShingle	Psychiatry RC435-571 Wonsuk Shin Minji Bang Anhye Kim Doo-Yeoun Cho Sang-Hyuk Lee Influence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia
description	Abstract Cytochrome P450 2D6 (CYP2D6) is expressed at high levels in the brain and plays a considerable role in the biotransformation and neurotransmission of dopamine. This raises the question of whether CYP2D6 variations and its impact on the brain can confer susceptibility to schizophrenia. We investigated the possible links among the CYP2D6 genotype, white matter (WM) integrity of the hippocampus, and the treatment response to antipsychotic drugs in Korean patients with schizophrenia (n = 106). Brain magnetic resonance imaging and genotyping for CYP2D6 were conducted at baseline. The severity of clinical symptoms and the treatment response were assessed using the Positive and Negative Syndrome Scale (PANSS). After genotyping, 43 participants were classified as intermediate metabolizers (IM), and the remainder (n = 63) were classified as extensive metabolizers (EM). IM participants showed significantly higher fractional anisotropy (FA) values in the right hippocampus compared to EM participants. Radial diffusivity (RD) values were significantly lower in the overlapping region of the right hippocampus in the IM group than in the EM group. After 4 weeks of antipsychotic treatment, the EM group showed more improvements in positive symptoms than the IM group. FAs and RDs in the CYP2D6-associated hippocampal WM region were significantly correlated with a reduction in the positive symptom subscale of the PANSS. Greater improvements in positive symptoms were negatively associated with FAs, and positively associated with RDs in the right hippocampal region. The findings suggest that CYP26D-associated hippocampal WM alterations could be a possible endophenotype for schizophrenia that accounts for individual differences in clinical features and treatment responses.
format	article
author	Wonsuk Shin Minji Bang Anhye Kim Doo-Yeoun Cho Sang-Hyuk Lee
author_facet	Wonsuk Shin Minji Bang Anhye Kim Doo-Yeoun Cho Sang-Hyuk Lee
author_sort	Wonsuk Shin
title	Influence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia
title_short	Influence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia
title_full	Influence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia
title_fullStr	Influence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia
title_full_unstemmed	Influence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia
title_sort	influence of cytochrome p450 2d6 polymorphism on hippocampal white matter and treatment response in schizophrenia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a182e146ab9149d396ce0dc94cd46434
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Influence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia

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