DNA damage in bipolar disorder

Andreazza, Ana Cristina; Frey, Benício N.; Erdtmann, Bernardo; Salvador, Mirian; Rombaldi, Fernanda; Santin, Ana Paula; Gonçalves, Carlos Alberto; Kapczinski, Flávio

doi:10.1016/j.psychres.2006.03.025

Cited by 146 publications

(81 citation statements)

References 34 publications

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“…15 In contrast, Mansour et al 16 reported no difference in telomere length between BD patients and a healthy control group. Multiple mechanisms might be implicated in telomere shortening in BD, including oxidative stress 28 leading to secondary DNA damage, 29 inflammation, 30 and glucocorticoid load. 7 Mechanistically, oxidative stress can lead to the formation of 8-oxo-7,8-dihydro-2 0 -deoxyguanosine (8-oxodG) at the GGG triplet in telomere sequences, 31 which is noted to be increased in patients with BD.…”

Section: Discussionmentioning

confidence: 99%

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Barbé-Tuana

Parisi

Panizzutti

et al. 2016

Rev. Bras. Psiquiatr.

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Objective: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age-and gender-matched healthy controls. Methods: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of medication, smoking status, and lifestyle. Conclusion: This study is concordant with previous evidence of telomere shortening in BD, in both early and late stages of the disorder, and supports the notion of accelerated aging in BD.

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Section: Discussionmentioning

confidence: 99%

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Barbé-Tuana

Parisi

Panizzutti

et al. 2016

Rev. Bras. Psiquiatr.

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“…This modification has been shown to be both cytotoxic and mutagenic (Wood et al, 1990 ;Chen et al, 1995 ;Choi et al, 1999 ;Klungland et al, 1999) and is followed by induction of the stress response as well as antioxidant and DNA repair enzymes (Lenaz, 2001 ;. Recent studies have shown evidence of DNA damage in BD, findings corroborated by our results (Andreazza et al, 2007 ;Buttner et al, 2007 ;Mustak et al, 2010). Buttner et al (2007) reported higher DNA fragmentation in post-mortem anterior cingulate cortex of BD patients (Buttner et al, 2007).…”

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confidence: 89%

Estudo de associação entre disfunção neurocognitiva, estresse oxidativa e polimorfismos em pacientes jovens com Transtornos Bipolar tipo I

Soeiro-de-Souza¹

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O Transtorno Bipolar (TB) tipo I é uma doença caracterizada por episódios de mania e depressão recorrentes com importante prejuízo do funcionamento global e comprometimento das funções cognitivas. Além disso, sabe-se que o número de episódios de humor patológico ao longo da vida pode também influenciar o funcionamento cognitivo destes sujeitos. Neste cenário, ocorreu a necessidade de se investigar marcadores genéticos para disfunção cognitiva no TB com o objetivo de estudar este fenômeno. Dentre os potenciais genes responsáveis por influenciar a cognição destacam-se os polimorfismos funcionais do fator neurotrófico derivado do cérebro (BDNF), da catecol-O-metiltransferase (COMT), da apolipoproteína-E (APOE) e do canal de cálcio de baixa voltagem subunidade α1-C (CACNA1C). Sabe-se, também, que no TB os marcadores de estresse oxidativo estão aumentados durante todas as fases da doença, entretanto, não é claro qual impacto destes na disfunção cognitiva de indivíduos com TB. O objetivo dessa tese foi avaliar o desempenho cognitivo de pacientes jovens com bipolaridade tipo I e sua associação com o genótipo de BDNF, COMT, APOE e CACNA1C e também com os níveis plasmáticos de oxidação da guanosina (8-OHdG) e citosina (5-Mec) durante os episódios de humor, eutimia e em controles. Para investigar essa associação foram incluídos 116 pacientes (79 em episódio de humor patológico e 37 eutímicos) com diagnóstico de TB tipo I (DSMIV-TR); 97 controles saudáveis foram submetidos à avaliação neuropsicológica e coleta de sangue para extração de DNA visando genotipagem para BDNF (rs6265), COMT (rs4680; rs165599), APOE (rs429358 e rs7412), CACNA1C (rs1006737), 8-OhdG e 5-Mec. A análise dos dados obtidos revelou que pacientes portadores do genótipo Met/Met rs4680/rs165599 do COMT apresentam comprometimento cognitivo mais grave (função executiva, fluência verbal, memória e inteligência) comparado ao genótipo Val/Met ou Val/Val durante episódios maníacos ou mistos. Na mesma direção destes resultados, verificou-se que pacientes portadores do alelo Met rs4680 do COMT apresentam comprometimento do reconhecimento de emoções faciais em episódios de mania e depressão. Nenhum efeito do COMT foi observado em controles. O alelo de risco Met do CACNA1C se associou a um pior comprometimento executivo independente dos sintomas maníacos ou depressivos no TB, porém nenhum efeito se observou nos controles. O alelo Met do BDNF rs6265 ou a presença do alelo ε4 da APOE não representa um fator que identifique um grupo com desempenho cognitivo diferenciado durante as fases do TB ou em controles. Sujeitos com TB apresentaram níveis mais elevados de 8-OHdG e tais níveis eram diretamente proporcionais ao número de episódios maníacos ao longo da vida, sugerindo um papel dos episódios hiperdopaminérgicos na oxidação das bases de DNA. Concluiu-se que a genotipagem para COMT e CACNA1C em pacientes com TB pode identificar um grupo de pacientes associados a pior disfunção cognitiva durante as fases maníacas e mistas do TB. Tal dado pode ser um indicador do envolvi...

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“…[11][12][13][14][15][16][17] There is an emerging body of data suggesting that BD is associated with decreased neurotrophins (BDNF, NGF and NT-3), 18,19 an increased oxidative 20,21 and DNA damage. 22 The group that is leading the INCT-TM has proposed a new animal model of mania, focusing on both acute and prophylactic treatments. The reversal model is designed to reproduce the management of an acute manic episode.…”

Section: Methodsmentioning

confidence: 99%

Instituto Nacional de Ciência e Tecnologia em Medicina Translacional (INCT-TM): abordagens metodológicas

Hallak

Crippa

Quevedo

et al. 2010

Rev. Bras. Psiquiatr.

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Objective: Translational medicine has been described as the integrated application of innovative pharmacology tools, biomarkers, clinical methods, clinical technologies and study designs to improve the understanding of medical disorders. In medicine, translational research offers an opportunity for applying the findings obtained from basic research to every-day clinical applications. The National Science and Technology Institute for Translational Medicine is comprised of six member institutions (Universidade Federal do Rio Grande do Sul, Universidade de São Paulo-Ribeirão Preto, Universidade Federal do Rio de Janeiro, Pontifícia Universidade Católica do Rio Grande do Sul, Universidade Estadual de Santa Catarina and a core facility that serves all centers). The objectives of the project are divided into four areas: Institutional, Research, Human Resources and Technology for the Community and Productive Sector. Method: In this manuscript, we describe some of the approaches used to attain the main objectives of the National Science and Technology Institute for Translational Medicine, which include the development of 1) animal models for bipolar disorder; 2) strategies to investigate neurobehavioral function and cognitive dysfunction associated with brain disorders; 3) experimental models of brain function and behavior, neuropsychiatric disorders, cell proliferation, and cancer; 4) Simulated Public Speaking and 5) Virtual reality simulation for inducing panic disorder and agoraphobia. Conclusion: The main focus of the National Science and Technology Institute for Translational Medicine is the development of more useful methods that allow for a better application of basic research-based knowledge to the medical field. Descriptors

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DNA damage in bipolar disorder

Cited by 146 publications

References 34 publications

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Estudo de associação entre disfunção neurocognitiva, estresse oxidativa e polimorfismos em pacientes jovens com Transtornos Bipolar tipo I

Instituto Nacional de Ciência e Tecnologia em Medicina Translacional (INCT-TM): abordagens metodológicas

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