Marcadores inflamatórios em mulheres vítimas de abuso sexual com transtorno de estresse pós-traumático
Data
2022-05-27
Autores
D'Elia, Ana Teresa de Campos Delfino 
Orientadores
Mello, Andrea de Abreu Feijó de
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A violência sexual é um dos eventos traumáticos com maior risco para o desenvolvimento de transtorno de estresse pós-traumático (TEPT), que é caracterizado por uma resposta biológica disfuncional ao estresse marcada pelo desequilíbrio do eixo Hipotálamo-Hipófise-Adrenal (HPA), atividade imune alterada e mudanças na estrutura e no funcionamento cerebral. O TEPT está altamente relacionado a níveis aumentados de marcadores inflamatórios, maior comorbidade com doenças clínicas e prejuízo funcional importante.
Objetivo: A presente tese objetiva investigar anormalidades em níveis de marcadores inflamatórios e hormônios do eixo HPA em mulheres que sofreram violência sexual e desenvolveram TEPT em dois momentos, no início do quadro e um ano depois. Além de comparar se há diferença em relação aos níveis hormonais e marcadores inflamatórios entre dois grupos de pacientes com TEPT que receberam tratamento com sertralina ou psicoterapia.
Método: 58 mulheres com TEPT em decorrência de violência sexual com intervalo máximo para inclusão de seis meses após o trauma, foram comparadas a 44 controles saudáveis. No momento de triagem para entrada das pacientes no estudo (momento 1), foi aplicado um questionário sociodemográfico e foram aplicados os seguintes instrumentos: Entrevista Neuropsiquiátrica internacional (MINI), Questionário sobre Traumas na Infância (QUESI), Inventário de Depressão de Beck (BDI), Inventário de Ansiedade de Beck (BAI) e Escala de TEPT Administrada pelo Clínico (Clinician Administered PTSD Scale-CAPS-5), além da dosagem sérica de ACTH, IL-1β, IL-6, TNF-α, MCP-1, PCR e cortisol salivar. As pacientes foram randomizadas para receber tratamento com sertralina ou psicoterapia interpessoal (IPT) por 14 semanas, quando foram reaplicados o BDI, BAI e CAPS-5 (momento 2). O seguimento se deu por um ano, com o tratamento usual, conforme a necessidade. Os instrumentos BDI, BAI e CAPS-5 foram reaplicados e os mesmos exames foram coletados ao final de um ano (momento 3). Este estudo visou avaliar os momentos 1 e 3.
Resultados: Cinquenta e seis pacientes apresentaram TEPT e episódio depressivo, segundo a MINI. No momento 1, os níveis de ACTH no grupo com TEPT foram maiores quando comparados ao grupo controle. Essa diferença foi proporcional à
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gravidade do TEPT, avaliada pela CAPS-5 (p=0,026) e também pela subescala D, que avalia sintomas negativos do humor (p=0,045), e proporcional à gravidade dos sintomas depressivos avaliados pela BDI (p<0,0001). Os níveis de cortisol medidos às 22 horas foram maiores para o grupo TEPT comparado ao grupo controle (p=0,037). Na avaliação inicial, não houve diferença significativa entre os marcadores inflamatórios das pacientes comparadas às do grupo controle. Ao final de um ano, houve aumento significativo dos níveis dos marcadores inflamatórios no grupo de pacientes comparadas ao grupo controle, IL-1β (p<0,0001), MCP-1 (p<0,0001), TNF-α (p<0,0001) e PCR (p<0,0001) e níveis de cortisol (p=0,046). Houve melhora significativa dos sintomas depressivos (p<0,001) e de TEPT (p<0,001), independentemente do grupo de tratamento após um ano.
Conclusão: A maioria da amostra com TEPT apresentou sintomas depressivos concomitantes aos sintomas de TEPT, o que pode ser considerado parte de uma psicopatologia relacionada a trauma, especificamente ao trauma de violência sexual, sugerindo uma variabilidade fenotípica inter-indivíduo. A essa especificidade psicopatológica pode-se implicar um funcionamento peculiar do eixo HPA, que se apresenta hiperestimulado e com funcionamento mais semelhante ao modelo de transtorno depressivo maior, com maiores níveis de cortisol, observado principalmente após um ano. O aumento dos marcadores inflamatórios após um ano, mesmo com a melhora dos sintomas, pode indicar que o TEPT em decorrência de violência sexual em mulheres evolui com alterações inflamatórias persistentes, que expõem essas mulheres a um maior risco de doenças crônicas e inflamatórias, muitas vezes relacionadas a um pior prognóstico clínico e mortalidade precoce. Este estudo traz novas perspectivas para o conhecimento atual da neurobiologia do TEPT e contribui para o estímulo de desenvolvimento de novas abordagens que possam atuar nesse desfecho.
Introduction: Sexual violence is one of the traumatic events with greater risk of developing post-traumatic stress disorder (PTSD). PTSD is characterized by a biological response marked by the hypothalamic-pituitary-adrenal (HPA) axis, altered immune activity and changes on the cerebral structure and functioning. Besides that, PTSD is also highly related to increased levels of inflammatory markers, greater comorbidity with clinical diseases and relevant functional loss. Objective: This thesis aims at evaluating abnormalities in the inflammatory markers levels and HPA axis hormones in women who suffered sexual violence and developed PTSD in two moments, at the baseline, and one year later. To compare whether there is a difference in hormone and inflammatory markers levels between the two groups of PTSD patients who received treatment with sertraline or psychotherapy. Methods: Fifty-eight women with PTSD due to sexual violence with a maximum inclusion interval of six months were compared to forty-four healthy controls. At the time of screening for patients to enter the study (time 1) a socio-demographic questionnaire as well as the following instruments were applied: InternationalNeuropsychiatric Interview (MINI), Childhood Trauma Questionnaire (CTQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Clinician Administered PTSD Scale-CAPS-5 in addition to serum ACTH, IL-1β, IL-6, TNF-α, MCP-1, PCR and salivary cortisol. The patients were randomized to receive either sertraline treatment or interpersonal psychotherapy (IPT) for 14 weeks (time 2) when the BDI, BAI and CAPS-5 instruments were reapplied and the same exams were collected at the end of one year (time 3). This study aimed to evaluate moments 1 and 3. Results: Fifty-six patients presented PTSD and depressive episode, according to the MINI. At time 1, ACTH levels on the PTSD group were higher when compared to the control group. This difference was proportional to PTSD severity, assessed by CAPS- 5 (p=0.026) and also by the CAPS-5 subscale D, which assesses negative mood symptoms (p=0.045) and proportional to the severity of depressive symptoms assessed by BDI (p<0.0001). The cortisol levels measured at 10 pm were higher for the PTSD group compared to the control group (p=0.037). On the initial evaluation, x there was not any significant difference among the patients’ inflammatory markers compared to the controls. By the end of one year there was a significant increase on the level of inflammatory markers on the patient group compared to the controls IL-1β (p = <0,0001), MCP-1 (p <0,0001), TNF-α (p<0,0001) and PCR (p<0,0001) and cortisol levels (p=0.046). There was significant improvement on the depressive symptoms (p<0.0001) and PTSD (p<0,001), regardless the group after one year. Discussion: Most of the PTSD sample presented depressive symptoms concomitant with the PTSD, which can be considered part of a trauma-related psychopathology, specifically the trauma of sexual violence, suggesting an inter-individual phenotypic variability. This psychopathological specificity may imply a peculiar functioning of the HPA axis, which is hyperstimulated and functioning more similarly to the model of major depressive disorder, with higher levels of cortisol, observed mainly after one year. The increase in inflammatory markers after one year, even with the improvement of symptoms, may indicate that PTSD in women due to sexual violence evolves with persistent inflammatory changes, which expose these women to a greater risk of chronic and inflammatory diseases, often related to a worse clinical prognosis and early mortality. This study brings new perspectives to the current knowledge of the neurobiology of PTSD and contributes to stimulating the development of new approaches that can act on this outcome.
Introduction: Sexual violence is one of the traumatic events with greater risk of developing post-traumatic stress disorder (PTSD). PTSD is characterized by a biological response marked by the hypothalamic-pituitary-adrenal (HPA) axis, altered immune activity and changes on the cerebral structure and functioning. Besides that, PTSD is also highly related to increased levels of inflammatory markers, greater comorbidity with clinical diseases and relevant functional loss. Objective: This thesis aims at evaluating abnormalities in the inflammatory markers levels and HPA axis hormones in women who suffered sexual violence and developed PTSD in two moments, at the baseline, and one year later. To compare whether there is a difference in hormone and inflammatory markers levels between the two groups of PTSD patients who received treatment with sertraline or psychotherapy. Methods: Fifty-eight women with PTSD due to sexual violence with a maximum inclusion interval of six months were compared to forty-four healthy controls. At the time of screening for patients to enter the study (time 1) a socio-demographic questionnaire as well as the following instruments were applied: InternationalNeuropsychiatric Interview (MINI), Childhood Trauma Questionnaire (CTQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Clinician Administered PTSD Scale-CAPS-5 in addition to serum ACTH, IL-1β, IL-6, TNF-α, MCP-1, PCR and salivary cortisol. The patients were randomized to receive either sertraline treatment or interpersonal psychotherapy (IPT) for 14 weeks (time 2) when the BDI, BAI and CAPS-5 instruments were reapplied and the same exams were collected at the end of one year (time 3). This study aimed to evaluate moments 1 and 3. Results: Fifty-six patients presented PTSD and depressive episode, according to the MINI. At time 1, ACTH levels on the PTSD group were higher when compared to the control group. This difference was proportional to PTSD severity, assessed by CAPS- 5 (p=0.026) and also by the CAPS-5 subscale D, which assesses negative mood symptoms (p=0.045) and proportional to the severity of depressive symptoms assessed by BDI (p<0.0001). The cortisol levels measured at 10 pm were higher for the PTSD group compared to the control group (p=0.037). On the initial evaluation, x there was not any significant difference among the patients’ inflammatory markers compared to the controls. By the end of one year there was a significant increase on the level of inflammatory markers on the patient group compared to the controls IL-1β (p = <0,0001), MCP-1 (p <0,0001), TNF-α (p<0,0001) and PCR (p<0,0001) and cortisol levels (p=0.046). There was significant improvement on the depressive symptoms (p<0.0001) and PTSD (p<0,001), regardless the group after one year. Discussion: Most of the PTSD sample presented depressive symptoms concomitant with the PTSD, which can be considered part of a trauma-related psychopathology, specifically the trauma of sexual violence, suggesting an inter-individual phenotypic variability. This psychopathological specificity may imply a peculiar functioning of the HPA axis, which is hyperstimulated and functioning more similarly to the model of major depressive disorder, with higher levels of cortisol, observed mainly after one year. The increase in inflammatory markers after one year, even with the improvement of symptoms, may indicate that PTSD in women due to sexual violence evolves with persistent inflammatory changes, which expose these women to a greater risk of chronic and inflammatory diseases, often related to a worse clinical prognosis and early mortality. This study brings new perspectives to the current knowledge of the neurobiology of PTSD and contributes to stimulating the development of new approaches that can act on this outcome.
Descrição
Citação
D'ELIA, A.T.C.D. Marcadores inflamatórios em mulheres vítimas de abuso sexual com transtorno de estresse pós-traumático. São Paulo, 2022. 126 f. Tese (Doutorado em Psiquiatria e Psicologia Médica) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo, São Paulo, 2022.