Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Studies investigating inflammatory markers in post-traumatic stress disorder (PTSD) have yielded mixed results. The aim of our study was to compare concentrations of inflammatory markers in patients with PTSD compared with healthy controls. METHODS: We did a meta-analysis and meta-regression of studies comparing inflammatory markers between patients with PTSD and healthy controls by searching PubMed, Embase, Scopus, Web of Science, and PsycINFO for articles published between Jan 1, 1960, and April 7, 2015. From eligible studies (ie, cross-sectional studies or baseline data from longitudinal studies of peripheral blood cytokine concentrations that compared adults with PTSD with healthy controls), we extracted outcomes of interest, such as mean and SD of peripheral blood cytokines, the time of day blood was collected, whether the study allowed patients with comorbid major depressive disorder in the PTSD group, whether patients were medication free, and severity of PTSD symptoms. We undertook meta-analyses whenever values of inflammatory markers were available in two or more studies. A random-effects model with restricted maximum-likelihood estimator was used to synthesise the effect size (assessed by standardised mean difference [SMD]) across studies. FINDINGS: 8057 abstracts were identified and 20 studies were included. Interleukin 6 (SMD 0.88; p=0.0003), interleukin 1ß (SMD 1.42; p=0.045), and interferon γ (SMD 0.49; p=0.002) levels were higher in the PTSD group than in healthy controls. Subgroup meta-analysis of patients who were not given medication showed higher tumour necrosis factor α (TNFα; SMD 0.69, 95% CI 0.35-1.02; p<0.0001) in the PTSD group than the control group in addition to the aforementioned cytokines. TNFα (SMD 1.32, 0.13-2.50; p=0.003), interleukin 1ß (SMD 2.35, 0.01-4.68; p=0.048), and interleukin 6 (SMD 1.75, 0.97-2.53; p<0.0001) levels remained increased in the PTSD group in a subgroup meta-analysis of studies that excluded comorbid major depressive disorder. Illness duration was positively associated with interleukin 1ß levels (b=0.33, p<0.0001) and severity with interleukin 6 (b=0.02, p=0.042). A model composed of several variables-presence of comorbid major depressive disorder, use of psychotropic medications, assay used, and time of day blood was collected-explained the large amount of heterogeneity between interleukin 1ß, interleukin 6, and C-reactive protein studies. Egger's linear regression test revealed a potential publication bias for interleukin 1ß. Additionally, for most inflammatory markers, study heterogeneity was reported to be high (I(2)>75%). INTERPRETATION: PTSD is associated with increased interleukin 6, interleukin 1ß, TNFα, and interferon γ levels. This information might be useful for consideration of chronic low-grade inflammation as a potential target or biomarker in PTSD treatment. Use of psychotropic medication and presence of comorbid major depressive disorder were important moderators that might explain the inconsistency between results of previous studies. Our search strategy used a range of databases and we made exhaustive effort to acquire data by contacting the authors. Notably, high levels of between-study heterogeneity were recorded for most cytokine variables measured in our analysis. However, meta-regression analysis could explain a large amount of this heterogeneity. FUNDING: None.

Functioning in early and late stages of schizophrenia / Funcionalidade nos estágios inicial e final da esquizofrenia

INTRODUCTION: Schizophrenia is frequently associated with a debilitating course and prominent impairment in social and occupational functioning. Although the criteria for classification into stages have not been defined in the literature, illness duration and functioning seem to be good candidates. OBJECTIVE: To compare functioning of patients with schizophrenia at different stages of the disease (early vs. late) and healthy sex- and age-matched controls. METHODS: This double-blinded, case-controlled study included 79 individuals: 23 patients with schizophrenia diagnosed up to 5 years earlier; 19 patients with schizophrenia diagnosed at least 20 years earlier; and healthy matched controls. Diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis I Disorder. Functioning was assessed using the Functioning Assessment Short Test (FAST). RESULTS: Patients in the early stage had significantly higher scores than healthy controls in total FAST and in autonomy, occupational functioning, cognitive functioning and interpersonal relationships. Individuals in the late stage had significantly poorer functioning than controls in all domains. The comparison of functioning between the two groups of patients revealed no significant differences, except in occupational functioning, in which late stage patients had a poorer performance. CONCLUSION: Functioning impairment in schizophrenia tends to remain stable despite illness duration. Therefore, functioning should be effectively assessed at an early stage, as illness duration alone may not be the most reliable criterion to stage patients with schizophrenia (AU)

INTRODUÇÃO: A esquizofrenia está frequentemente associada a um curso debilitante e a um importante comprometimento no funcionamento social e ocupacional. Embora os critérios para classificação em diferentes estágios ainda não tenham sido definidos, a duração da doença e a funcionalidade têm sido apontadas como bons candidatos. OBJETIVO: Comparar a funcionalidade de indivíduos com esquizofrenia no estágio inicial e final com controles saudáveis correspondentes em idade e sexo. MÉTODOS: Neste estudo caso-controle, duplo-cego, foram incluídos 79 pacientes: 23 com diagnóstico de esquizofrenia feito até 5 anos atrás (estágio inicial); 19 diagnosticados há pelo menos 20 anos (estágio final); e controles saudáveis pareados. O diagnóstico foi estabelecido pela Entrevista Clínica Estruturada para Transtornos do Eixo I do Manual Diagnóstico e Estatístico de Transtornos Mentais, 4ª edição (DSM-IV). A funcionalidade foi avaliada através da escala Teste Breve de Avaliação Funcional (FAST). RESULTADOS: Os pacientes em estágio inicial tiveram escores significativamente maiores do que controles saudáveis na escala FAST (escore total e domínios autonomia, funcionamento ocupacional, funcionamento cognitivo e relações interpessoais). Os indivíduos em estágio final apresentaram funcionalidade pior que os controles em todos os domínios. A comparação entre os dois grupos não mostrou diferenças, exceto no funcionamento ocupacional, em que os pacientes em estágio final apresentaram um desempenho pior. CONCLUSÃO: O prejuízo da funcionalidade na esquizofrenia tende a permanecer estável ao longo da doença. Portanto, a funcionalidade deve ser avaliada nos estágios iniciais da doença, já que a duração da doença por si só pode não ser o critério mais confiável para definir o estágio de pacientes com esquizofrenia (AU)

The theory of bipolar disorder as an illness of accelerated aging: implications for clinical care and research.

Bipolar Disorder (BD) has been conceptualized as both a cyclic and a progressive disorder. Mechanisms involved in neuroprogression in BD remain largely unknown although several non-mutually exclusive models have been proposed as explanatory frameworks. In the present paper, we propose that the pathophysiological changes observed in BD (e.g. brain structural alterations, cognitive deficits, oxidative stress imbalance, amyloid metabolism, immunological deregulation, immunosenescence, neurotrophic deficiencies and telomere shortening) converge on a model of accelerated aging (AA). Aging can be understood as a multidimensional process involving physical, neuropsychological, and social changes, which can be highly variable between individuals. Determinants of successful aging (e.g environmental and genetic factors), may also confer differential vulnerability to components of BD pathophysiology and contribute to the clinical presentation of BD. Herein we discuss how the understanding of aging and senescence can contribute to the search for new and promising molecular targets to explain and ameliorate neuroprogression in BD. We also present the strengths and limitations of this concept.

Functioning in early and late stages of schizophrenia.

INTRODUCTION: Schizophrenia is frequently associated with a debilitating course and prominent impairment in social and occupational functioning. Although the criteria for classification into stages have not been defined in the literature, illness duration and functioning seem to be good candidates. OBJECTIVE: To compare functioning of patients with schizophrenia at different stages of the disease (early vs. late) and healthy sex- and age-matched controls. METHODS: This double-blinded, case-controlled study included 79 individuals: 23 patients with schizophrenia diagnosed up to 5 years earlier; 19 patients with schizophrenia diagnosed at least 20 years earlier; and healthy matched controls. Diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis I Disorder. Functioning was assessed using the Functioning Assessment Short Test (FAST). RESULTS: Patients in the early stage had significantly higher scores than healthy controls in total FAST and in autonomy, occupational functioning, cognitive functioning and interpersonal relationships. Individuals in the late stage had significantly poorer functioning than controls in all domains. The comparison of functioning between the two groups of patients revealed no significant differences, except in occupational functioning, in which late stage patients had a poorer performance. CONCLUSION: Functioning impairment in schizophrenia tends to remain stable despite illness duration. Therefore, functioning should be effectively assessed at an early stage, as illness duration alone may not be the most reliable criterion to stage patients with schizophrenia.