Avaliação de marcadores biológicos e sua associação com desfechos clínicos em pacientes com transtornos mentais submetidos a psicoterapias baseadas em evidências

Psicoterapias baseadas em evidências são tratamentos reconhecidos para diversos transtornos psiquiátricos, como depressão, transtorno afetivo bipolar e transtornos de ansiedade. A psicoterapia, associada ou não a psicofármacos, está relacionada a desfechos clínicos favoráveis, como a remissão de sintomas e estabilização clínica. Além dos desfechos citados, há evidências de que as psicoterapias possam levar a alterações em marcadores biológicos, tais como citocinas, neurotrofinas e metabolismo cerebral. Estudar esses marcadores é uma ferramenta para entender os mecanismos fisiológicos do tratamento psicoterápico e compreender a progressão da doença na vigência dessa terapia. O objetivo desta tese é analisar três marcadores biológicos: fator neurotrófico derivado do cérebro (BDNF), interleucina-6 (IL-6) e imagem por ressonância magnética funcional (fMRI) e suas associações com a resposta ao tratamento de psicoterapias baseadas em evidências. O primeiro artigo desta tese revisou sistematicamente os níveis de BDNF em pacientes com transtornos mentais submetidos a psicoterapias individuais, antes e após o tratamento (k=8). Apesar da heterogeneidade dos estudos, os resultados são promissores nos transtornos estudados, estando o aumento dos níveis da neurotrofina associados à melhora clínica, no entanto os resultados em pacientes com diagnóstico de depressão tenham sido inconclusivos. O segundo artigo investigou um biomarcador de atividade neurológica em pacientes com diagnóstico de depressão submetidos à psicoterapia: a ressonância magnética funcional, com paradigma e em repouso, através de uma revisão sistemática (k=19). Dentre múltiplas áreas, a revisão destacou o sistema límbico na resposta à psicoterapia, área associada ao comportamento e emoções. O terceiro artigo, um estudo naturalístico, analisou 52 pacientes submetidos a uma das três seguintes modalidades de psicoterapias baseadas em evidência: terapia interpessoal, terapia cognitivo comportamental e psicoterapia de orientação analítica em relação aos desfechos de internação psiquiátrica, tentativa de suicídio, qualidade de vida, sintomas depressivos e ansiosos associados aos níveis de IL-6. Os níveis de IL-6 nessa amostra não variaram significativamente e os sintomas de depressão, ansiedade e a qualidade de vida se mantiveram estáveis, mas houve redução de tentativa de suicídio (de 48.07% dos participantes para 3.84%; p=0.003) e internações psiquiátricas no período (de 40.38% para 3.84% p=0.003). Os resultados demonstram o perfil grave dos participantes e o papel da psicoterapia associada à medicação na estabilização desses pacientes. Por fim, o quarto artigo avaliou os níveis de BDNF de um estudo longitudinal naturalístico com amostra de 47 pacientes, considerando variáveis clínicas de histórico de hospitalização psiquiátrica e tentativa de suicídio associada a uso de psicofármacos na resposta ao tratamento e o impacto nos níveis de BDNF. Os resultados mostraram que o uso de lítio está associado ao aumento dos níveis do marcador e que psicoterapias baseadas em evidência reduzem internação (B 0.439; p=0.019) e tentativa de suicídio em pacientes com histórico prévio, porém os níveis de BFNF não se alteraram significativamente na amostra analisada (p=0.855). Os achados obtidos reforçam a hipótese de que as psicoterapias baseadas em evidência podem cursar com alterações fisiológicas na melhora clínica e sintomática de pacientes com transtornos mentais, porém, a interação com biomarcadores é complexa e a literatura ainda incipiente. A expansão do conhecimento destes mecanismos, a partir dos marcadores estudados, é imprescindível para o incentivo à pesquisa e o reforço no tratamento baseado em evidências com uso de biomarcadores.Evidence-based psychotherapies are recognized treatments for a variety of psychiatric disorders, such as depression, bipolar affective disorder, and anxiety. Psychotherapy, whether associated with psychotropic drugs, is associated to favorable clinical outcomes, such as symptom remission and clinical stabilization. In addition to the outcomes, there is evidence that psychotherapies can lead to changes in biological markers, such as cytokines, neurotrophins and brain activity. The evaluation of these markers is a tool to understand the physiological mechanisms of psychotherapeutic treatment and understand the progression of the disease during this therapy. Therefore, this thesis aimed to analyze 3 biological markers: brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6) and functional magnetic resonance imaging (fMRI) and their association with response to evidence-based psychotherapies. The first article systematically reviewed BDNF levels in patients undergoing individual psychotherapies, before and after treatment with individual psychotherapy (k=8). Despite the heterogeneity of the studies, the results were promising in the disorders studied, with the increase in BDNF levels being associated with clinical improvement, although the results in patients diagnosed with depression were inconclusive. The second article investigated a biomarker of neurological activity in patients diagnosed with depression undergoing psychotherapy: functional magnetic resonance imaging, with paradigm and at rest, through a systematic review (k=19). The studies highlighted the role of the limbic system in the response to psychotherapy, an area associated with behavior and emotions, which are altered in individuals with depression. The third article analyzed 52 patients undergoing one of the following three modalities of psychotherapies: interpersonal therapy, cognitive behavioral therapy and psychodynamic psychotherapy and the outcomes of reduced psychiatric hospitalization, suicide attempt, improvement in quality of life, associated depressive and anxiety symptoms. to interlekin-6 levels. Interleukin-6 levels in this sample did not vary significantly and symptoms of depression, anxiety and quality of life remained stable, but there was a reduction in suicide attempts (from 48.07% of participants to 3.84%; p=0.003) and psychiatric hospitalizations. in the period (from 40.38% to 3.84% p=0.003). The results demonstrated the severe profile of the participants and the role of psychotherapy associated with medication in patient stabilization Finally, the fourth article evaluated the BDNF levels through a naturalistic longitudinal study with a sample of 47 patients, considering clinical variables of psychiatric hospitalization history and suicide attempt associated with the use of psychotropic drugs in the response to treatment and the impact on BDNF levels. The results showed that lithium use is associated with increased marker levels and that the therapy reduces hospitalization (B 0.439; p=0.019) and suicide attempts, but that BFNF levels has not change significantly in the analyzed sample (p=0.855). The findings obtained reinforce the idea that evidence-based psychotherapies lead to physiological changes in the clinical and symptomatic improvement of patients with mental disorders. Knowledge of this mechanism is essential for encouraging research and strengthening evidence-based treatment using biomarkers

The effects of individual psychotherapy in BDNF levels of patients with mental disorders : a systematic review

Background: Brain-derived Neurotrophic Factor (BDNF) is considered the main cerebral neurotrophin and is produced in the central neural system and peripherals. Its levels are reduced in patients with several psychiatric disorders, but it is unclear if the response to psychotherapy can alter its concentration. Objective: To carry out a systematic review evaluating the effects of individual psychotherapy in BDNF levels in patients with mental disorders. Methods: The databases PubMed, EMBASE, PsycArticles, SciELO, Web of Science, and CENTRAL; the last search was performed on October 2019 for trials evaluating the effects of individual psychotherapy in BDNF levels in adults with mental disorders. PROSPERO registration: CRD42018108144. Results: Eight of 293 studies were included. A rise in BDNF levels was observed in depressive patients when psychotherapy was combined with medication. Patients with post-traumatic stress disorder (PTSD) who responded to therapy presented a raise in BDNF levels mostly when combined with physical activity. There was a rise in BDNF levels in those who responded to psychotherapy in patients with bulimia, in borderline patients, and in insomniacs. Conclusions: The BDNF seems to present variations after psychotherapy especially in patients with bulimia, PTSD, insomnia, and borderline. These subjects also have symptom reduction. Thereby, BDNF could be a supplemental tool to analyze the success to psychotherapy. BDNF levels in patients with major depression after therapy are still controversial and the short follow-up of most studies is a limiting factor

Clozapine use decreases the number of hospitalizations per year in patients with treatment-resistant schizophrenia

For years, the management of schizophrenia has represented a challenge for clinicians, with antipsychotic treatments usually resulting in relapses and new hospitalizations. Clozapine has been shown to be an effective medication for treatment-resistant schizophrenia (TRS), but is currently underused due to its potential side effects. Nevertheless, research has suggested that clozapine reduces future hospitalizations in patients with TRS. This study aims to verify the rates of hospitalizations in patients with TRS under long-term use of clozapine. We retrospectively analyzed clinical data from 52 individuals with TRS before and after the use of clozapine. The mean duration of treatment with and without clozapine was 6.6 (± 3.9) and 8.5 years (± 6.6), respectively. Patients had a median of 0.5 (0.74) hospitalizations per year before the use of clozapine and 0 (0.74) hospitalizations after it (p = 0.001). Therefore, the use of clozapine resulted in an expected reduction in the number of hospitalizations per year in individuals with TRS

Protective factors against depressive symptoms among Brazilian healthcare workers during the initial stages of the COVID-19 pandemic : a cross-sectional study

Objectives This study aims to assess the prevalence of depressive symptoms among healthcare workers and possible factors associated with this outcome (resilience, spirituality, social support, quality of life, among other individual variables). Our hypothesis is that some of these factors can have a protective effect on depressive symptoms. Design Web-based cross-sectional survey. Setting Participants were recruited online from 16 April to 23 April 2020. Participants 1043 healthcare workers, predominantly Brazilians, aged 18 years or older. Primary and secondary outcome measures Depression was the primary outcome, measured using the Patient Health Questionnaire-9 (PHQ-9). Possible protective factors were measured in the following ways: social support was assessed by the modified Medical Outcomes Study Social Support Survey (mMOS-SS); spirituality, religiousness and personal beliefs (SRPB) were evaluated using the 9-item SRPB module of the brief WHO Quality of Life instrument (WHOQoL-SRPB-bref); quality of life was assessed using the brief EUROHIS instrument for Quality of Life (EUROHISQoL 8-item); resilience was assessed using the 10-item Connor-Davidson Resilience Scale (CD-RISC 10). Results 23% met the criteria for depression according to the PHQ-9 scale. Quality of life (B=−3.87 (−4.30 to −3.43), β=−0.37, p<0.001), social support (B=−0.32 (−0.59 to −0.05), β=−0.04, p=0.022), resilience (B=−0.19 (−0.23 to −0.15), β=−0.20, p<0.001), SRPB (B=−0.03 (−0.05 to −0.02), β=−0.01, p<0.001) and physical exercise (B=−0.95 (−1.40 to −0.51), β=−0.08, p<0.001) demonstrated protective effects against depression. Conclusion Healthcare workers have a high risk of developing depressive symptoms during the COVID-19 pandemic, especially those working in the front line. However, there are factors that seem to work as protective mechanisms against depression, notably perceived quality of life

Long-term treatment with clozapine and verbal memory performance in schizophrenia

Clozapine is more efficacious than first-generation antipsychotics for positive and negative symptoms, although it is related with serious adverse effects. Because of this profile, it could also have an impact on cognition. Therefore, we evaluated learning ability of 31 treatment-resistant individuals with SZ using clozapine uninterruptedly for 18.23 ± 4.71 years and 26 non-treatment-resistant using other antipsychotics that never used clozapine. Long-term treatment with clozapine did not improve verbal learning ability better than other antipsychotics. Although clozapine has a unique profile for reducing clinical symptoms, it may not have an additional benefit for cognition when started later on the course of schizophrenia