Elisa Rodríguez-Toscano , Kenia Martínez , David Fraguas , Joost Janssen , Laura Pina-Camacho , Bárbara Arias , Eduard Vieta , Gisela Mezquida , Silvia Amoretti , Miguel Bernardo , Josefina Castro-Fornieles , Manuel Jesús Cuesta-Zorita , Antonio Lobo , Ana González-Pinto , Iluminada Corripio Collado , Anna Mané , Celso Arango , Mara Parellada , PEPs Group
{"title":"首发精神病患者的前额叶异常、执行功能障碍和症状严重程度受COMT Val158Met多态性的调节","authors":"Elisa Rodríguez-Toscano , Kenia Martínez , David Fraguas , Joost Janssen , Laura Pina-Camacho , Bárbara Arias , Eduard Vieta , Gisela Mezquida , Silvia Amoretti , Miguel Bernardo , Josefina Castro-Fornieles , Manuel Jesús Cuesta-Zorita , Antonio Lobo , Ana González-Pinto , Iluminada Corripio Collado , Anna Mané , Celso Arango , Mara Parellada , PEPs Group","doi":"10.1016/j.rpsm.2021.11.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Core dysfunctions proposed for psychotic disorders include prefrontal cortex (PFC) dopaminergic hypoactivity, executive function (EF) deficits and reduced gray matter in the PFC. The Val variant of <em>COMT</em> Val<sub>158</sub>Met polymorphism is associated with reduced dopaminergic signaling in the PFC. However, it is unclear how COMT Val<sub>158</sub>Met modulates PFC gray matter reduction, EF deficits and symptom severity at the time of the first psychotic episode.</p></div><div><h3>Methods</h3><p>The effect of COMT on both EF performance and prefrontal volume (PFC-VOL) was tested in 158 first episode psychosis (FEP) patients and 141 healthy controls (HC) matched for age (range 9–35 years), sex, ethnicity, handedness and COMT Val<sub>158</sub>Met distribution. EF and PFC-VOL were compared between FEP and HC groups within each polymorphism status (Met/Met versus Val carriers) to assess whether COMT influenced diagnostic differences. Next, correlations between PFC-VOL and EF performance were computed, as well as between both variables and other clinical characteristics of interest (PANSS scores, PAS infancy and premorbid IQ) in the FEP sample.</p></div><div><h3>Results</h3><p>COMT influenced the diagnostic differences mainly in PFC-VOL, but also in EF performance. FEP-Val carriers showed lower EF scores and reduced PFC-VOL compared to the HC group but also poorer EF performance than FEP Met/Met. Poorer EF performance was associated with smaller PFC-VOL, and both were related to increased severity of negative symptoms, poorer premorbid adjustment, and lower estimated premorbid IQ in FEP patients.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that COMT Val<sub>158</sub>Met polymorphism might contribute to PFC-VOL reductions, executive dysfunctions and symptom severity in FEP patients.</p></div>","PeriodicalId":21391,"journal":{"name":"Revista de psiquiatria y salud mental","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Prefrontal abnormalities, executive dysfunction and symptoms severity are modulated by COMT Val158Met polymorphism in first episode psychosis\",\"authors\":\"Elisa Rodríguez-Toscano , Kenia Martínez , David Fraguas , Joost Janssen , Laura Pina-Camacho , Bárbara Arias , Eduard Vieta , Gisela Mezquida , Silvia Amoretti , Miguel Bernardo , Josefina Castro-Fornieles , Manuel Jesús Cuesta-Zorita , Antonio Lobo , Ana González-Pinto , Iluminada Corripio Collado , Anna Mané , Celso Arango , Mara Parellada , PEPs Group\",\"doi\":\"10.1016/j.rpsm.2021.11.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Core dysfunctions proposed for psychotic disorders include prefrontal cortex (PFC) dopaminergic hypoactivity, executive function (EF) deficits and reduced gray matter in the PFC. The Val variant of <em>COMT</em> Val<sub>158</sub>Met polymorphism is associated with reduced dopaminergic signaling in the PFC. However, it is unclear how COMT Val<sub>158</sub>Met modulates PFC gray matter reduction, EF deficits and symptom severity at the time of the first psychotic episode.</p></div><div><h3>Methods</h3><p>The effect of COMT on both EF performance and prefrontal volume (PFC-VOL) was tested in 158 first episode psychosis (FEP) patients and 141 healthy controls (HC) matched for age (range 9–35 years), sex, ethnicity, handedness and COMT Val<sub>158</sub>Met distribution. EF and PFC-VOL were compared between FEP and HC groups within each polymorphism status (Met/Met versus Val carriers) to assess whether COMT influenced diagnostic differences. Next, correlations between PFC-VOL and EF performance were computed, as well as between both variables and other clinical characteristics of interest (PANSS scores, PAS infancy and premorbid IQ) in the FEP sample.</p></div><div><h3>Results</h3><p>COMT influenced the diagnostic differences mainly in PFC-VOL, but also in EF performance. FEP-Val carriers showed lower EF scores and reduced PFC-VOL compared to the HC group but also poorer EF performance than FEP Met/Met. Poorer EF performance was associated with smaller PFC-VOL, and both were related to increased severity of negative symptoms, poorer premorbid adjustment, and lower estimated premorbid IQ in FEP patients.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that COMT Val<sub>158</sub>Met polymorphism might contribute to PFC-VOL reductions, executive dysfunctions and symptom severity in FEP patients.</p></div>\",\"PeriodicalId\":21391,\"journal\":{\"name\":\"Revista de psiquiatria y salud mental\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2022-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Revista de psiquiatria y salud mental\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1888989121001245\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Revista de psiquiatria y salud mental","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1888989121001245","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Prefrontal abnormalities, executive dysfunction and symptoms severity are modulated by COMT Val158Met polymorphism in first episode psychosis
Introduction
Core dysfunctions proposed for psychotic disorders include prefrontal cortex (PFC) dopaminergic hypoactivity, executive function (EF) deficits and reduced gray matter in the PFC. The Val variant of COMT Val158Met polymorphism is associated with reduced dopaminergic signaling in the PFC. However, it is unclear how COMT Val158Met modulates PFC gray matter reduction, EF deficits and symptom severity at the time of the first psychotic episode.
Methods
The effect of COMT on both EF performance and prefrontal volume (PFC-VOL) was tested in 158 first episode psychosis (FEP) patients and 141 healthy controls (HC) matched for age (range 9–35 years), sex, ethnicity, handedness and COMT Val158Met distribution. EF and PFC-VOL were compared between FEP and HC groups within each polymorphism status (Met/Met versus Val carriers) to assess whether COMT influenced diagnostic differences. Next, correlations between PFC-VOL and EF performance were computed, as well as between both variables and other clinical characteristics of interest (PANSS scores, PAS infancy and premorbid IQ) in the FEP sample.
Results
COMT influenced the diagnostic differences mainly in PFC-VOL, but also in EF performance. FEP-Val carriers showed lower EF scores and reduced PFC-VOL compared to the HC group but also poorer EF performance than FEP Met/Met. Poorer EF performance was associated with smaller PFC-VOL, and both were related to increased severity of negative symptoms, poorer premorbid adjustment, and lower estimated premorbid IQ in FEP patients.
Conclusions
Our findings suggest that COMT Val158Met polymorphism might contribute to PFC-VOL reductions, executive dysfunctions and symptom severity in FEP patients.
期刊介绍:
The Spanish Journal of Psychiatry and Mental Health (SJPMH), incorporated into ISSN 1888-9891, is the official scientific publication of the Spanish Society of Psychiatry and Mental Health. The journal focuses on studying mental illnesses, their pathological processes, and their psychosocial consequences, and aims to disseminate scientific advances in all areas related to mental health and illness. SJPMH accepts unpublished works on psychiatry and mental health, including their medical and social implications. The journal provides space for research in the biological, clinical, and psychosocial fields. Manuscripts undergo peer-review by external reviewers before being accepted for publication. SJPMH is indexed in Index Medicus/Medline, IBECS, Social Sciences Citation Index Journal Citation Reports/Social Sciences Edition, and Current Contents/Social and Behavioral Sciences.