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Neurocognição, ansiedade e depressão na Hepatite C : contributo para uma caracterização psicobiológica
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O vírus da Hepatite C (VHC) representa uma das infecções mais importantes a nível global, com 71 milhões de pessoas infectadas. Para além do carácter crónico desta doença e do peso económico que acarreta, estes indivíduos demonstram frequentemente sintomas neuropsiquiátricos como fadiga, ansiedade, depressão ou disfunção cognitiva. Os modelos da depressão associada à terapêutica com interferão-α, têm sido alvo de interesse, tendo sido muito estudados no tratamento de doentes infectados pelo vírus da hepatite C. Com a recente mudança no paradigma da abordagem terapêutica da hepatite C (com a introdução dos novos fármacos, antivirais de acção directa), importa caracterizar o perfil psicológico e neurocognitivo associado às novas terapêuticas, antes e depois do tratamento, comparando estas dimensões entre tratamentos e a existência de um possível efeito de género. Interessa ainda estudar a relação da possível neurotoxicidade do vírus da hepatite C e as perturbações neuropsiquiátrica e neurocognitivas. Assim, constituiu-se como objectivo central deste trabalho fazer uma caracterização psicobiológica dos aspectos associados ao VHC, designadamente da ansiedade, da depressão e das dimensões de funcionamento neurocognitivo. O desenho do estudo agora apresentado é de tipo longitudinal com dois momentos de avaliação. A população inclui 86 doentes com hepatite C avaliados antes de iniciar tratamento com interferão-α ou Ledipasvir/Sofosbuvir e a mesma avaliação foi repetida no final dos respectivos tratamentos em 45 doentes. Os doentes foram submetidos a uma avaliação psicológica (depressão e ansiedade), neuropsicológica (atenção, memória, velocidade de processamento e funções executivas), bioquímica (PCR, Haptoglobina e Interleucina 6) e a um estudo dos polimorfismos genéticos (IDO1, IL β, IL 6, TNF-α, haptoglobina e transportador da serotonina).
Os resultados obtidos apontam para a existência de diferenças estatisticamente significativas na interacção entre o tempo e os grupos de tratamento para a ansiedade e para a depressão com prejuízo para o grupo tratado com IFN-α. Não se encontraram resultados com significado estatístico nesta mesma interacção em relação à neurocognição. Foram ainda encontradas associações significativas entre as variáveis bioquímicas em estudo e os sintomas depressivos, ansiosos e neurocognitivos como a memória e funções executivas, quer antes quer depois do tratamento. Os resultados obtidos apontam ainda para um efeito de género, com as mulheres a apresentarem valores mais elevados de ansiedade e depressão e um pior desempenho nas funções executivas e na memória de trabalho, em comparação com os homens.
No que diz respeito ao estudo genético, verificámos que as frequências de genótipos dos vários polimorfismos estudados na população com infecção pelo vírus da hepatite C, face aos controlos saudáveis, apresentam diferenças estatisticamente significativas em genótipos associados ao TNF-α (genótipo AA) e à IDO1 (genótipo CC). Analisando a relação entre as variáveis psicológicas, neuropsicológicas, bioquímicas e os diferentes polimorfismos, estas apontam no sentido da importância das diferenças entre genótipos da IL 1b e score do Hamilton depressão, bem como, entre genótipos do TNF-a e valores da PCR. Na nossa amostra surge um predomínio do genótipo CC no polimorfismo da IDO e diferenças significativas entre genótipos para o score do Hamilton depressão.
Em síntese, os resultados da investigação permitem clarificar as relações entre as variáveis estudadas e sugerem a necessidade de aprofundar alguns aspectos numa perspectiva biológica e psicossocial nos doentes infectados com o vírus da hepatite C.
Hepatitis C virus (HCV) is one of the most important infections worldwide, with 71 million people infected. In addition to the chronic nature of this disease and its economic burden, these individuals often demonstrate neuropsychiatric symptoms such as fatigue, anxiety, depression or cognitive dysfunction. The models of depression associated with interferon-α therapy, have been of interest and have been extensively studied in the treatment of patients infected with hepatitis C. With the recent change in the paradigm of the therapeutic approach to hepatitis C (with the introduction of new drugs, direct action antivirals), it is important to characterize the psychological and neurocognitive profile associated with the new therapies, before and after the treatment, comparing these dimensions between treatments and also the existence of a gender effect. It is also interesting to study the relation of the possible neurotoxicity of the hepatitis C virus and the neuropsychiatric and neurocognitive disorders. Thus, it was the central objective of this work to make a psychobiological characterization of aspects associated with hepatitis C virus, namely anxiety, depression and neurocognitive functioning. The study design presented here is a longitudinal type with two evaluation moments. The population includes 86 hepatitis C patients evaluated before starting treatment with interferon-α or Ledipasvir/Sofosbuvir and the same evaluation was repeated at the end of the treatments (n=45). Patients underwent a psychological evaluation (depression and anxiety), neuropsychological (attention, memory, processing speed and executive functions), biochemistry (PCR, Haptoglobin and Interleukin 6) and a study of genetic polymorphisms (IDO1, IL β, IL 6, TNF-α, haptoglobin and the serotonin transporter). The obtained results point to the existence of statistically significant differences in the interaction between time and treatment groups for anxiety and depression with impairment for the group treated with IFN-α. No statistically significant results were found in this same interaction in relation to neurocognition. Significant associations were also found between the biochemical variables under study and the depressive symptoms, anxious symptoms and some symptoms, and memory and executive functions, both before and after treatment. The results also point to a gender effect, with women having higher values of anxiety and depression, and worse performance in executive functions and working memory compared to men. Regarding the genetic study, we observe that the genotype frequencies of the various polymorphisms studied in the population with hepatitis C virus infection, when compared to healthy controls, showed statistically significant differences in genotypes associated with TNF-α (genotype AA) and IDO1 (CC genotype). Analyzing the relationship between the psychological, neuropsychological, biochemical variables and the different polymorphisms, we observe that these point towards the importance of differences between genotypes of IL 1b and Hamilton depression score, as well as between genotypes of TNF-α and CRP values. In our sample, a predominance of the CC genotype appears in the IDO polymorphism as well as significant differences between genotypes for the Hamilton depression score. In summary, the results of this research allow us to clarify the relations between the studied variables and suggest the need to deepen some aspects from a biological and psychosocial perspective in patients infected with the hepatitis C virus.
Hepatitis C virus (HCV) is one of the most important infections worldwide, with 71 million people infected. In addition to the chronic nature of this disease and its economic burden, these individuals often demonstrate neuropsychiatric symptoms such as fatigue, anxiety, depression or cognitive dysfunction. The models of depression associated with interferon-α therapy, have been of interest and have been extensively studied in the treatment of patients infected with hepatitis C. With the recent change in the paradigm of the therapeutic approach to hepatitis C (with the introduction of new drugs, direct action antivirals), it is important to characterize the psychological and neurocognitive profile associated with the new therapies, before and after the treatment, comparing these dimensions between treatments and also the existence of a gender effect. It is also interesting to study the relation of the possible neurotoxicity of the hepatitis C virus and the neuropsychiatric and neurocognitive disorders. Thus, it was the central objective of this work to make a psychobiological characterization of aspects associated with hepatitis C virus, namely anxiety, depression and neurocognitive functioning. The study design presented here is a longitudinal type with two evaluation moments. The population includes 86 hepatitis C patients evaluated before starting treatment with interferon-α or Ledipasvir/Sofosbuvir and the same evaluation was repeated at the end of the treatments (n=45). Patients underwent a psychological evaluation (depression and anxiety), neuropsychological (attention, memory, processing speed and executive functions), biochemistry (PCR, Haptoglobin and Interleukin 6) and a study of genetic polymorphisms (IDO1, IL β, IL 6, TNF-α, haptoglobin and the serotonin transporter). The obtained results point to the existence of statistically significant differences in the interaction between time and treatment groups for anxiety and depression with impairment for the group treated with IFN-α. No statistically significant results were found in this same interaction in relation to neurocognition. Significant associations were also found between the biochemical variables under study and the depressive symptoms, anxious symptoms and some symptoms, and memory and executive functions, both before and after treatment. The results also point to a gender effect, with women having higher values of anxiety and depression, and worse performance in executive functions and working memory compared to men. Regarding the genetic study, we observe that the genotype frequencies of the various polymorphisms studied in the population with hepatitis C virus infection, when compared to healthy controls, showed statistically significant differences in genotypes associated with TNF-α (genotype AA) and IDO1 (CC genotype). Analyzing the relationship between the psychological, neuropsychological, biochemical variables and the different polymorphisms, we observe that these point towards the importance of differences between genotypes of IL 1b and Hamilton depression score, as well as between genotypes of TNF-α and CRP values. In our sample, a predominance of the CC genotype appears in the IDO polymorphism as well as significant differences between genotypes for the Hamilton depression score. In summary, the results of this research allow us to clarify the relations between the studied variables and suggest the need to deepen some aspects from a biological and psychosocial perspective in patients infected with the hepatitis C virus.
Descrição
Palavras-chave
Hepatite C Ansiedade Depressão Neurocognição Inflamação Polimorfismos genéticos