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Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review.

ABSTRACT: Schizophrenia is a psychiatric disorder which has a lifetime prevalence of ~1%. Multiple candidate mechanisms have been proposed in the pathogenesis of schizophrenia. One such mechanism is the involvement of neuroinflammation. Clinical studies, including neuroimaging, peripheral biomarkers and randomized control trials, have suggested the presence of neuroinflammation in schizophrenia. Many studies have also measured markers of neuroinflammation in postmortem brain samples from schizophrenia patients. The objective of this study was to conduct a systematic search of the literature on neuroinflammation in postmortem brains of schizophrenia patients indexed in MEDLINE, Embase and PsycINFO. Databases were searched up until 20th March 2016 for articles published on postmortem brains in schizophrenia evaluating microglia, astrocytes, glia, cytokines, the arachidonic cascade, substance P and other markers of neuroinflammation. Two independent reviewers extracted the data. Out of 5385 articles yielded by the search, 119 articles were identified that measured neuroinflammatory markers in schizophrenic postmortem brains. Glial fibrillary acidic protein expression was elevated, lower or unchanged in 6, 6 and 21 studies, respectively, and similar results were obtained for glial cell densities. On the other hand, microglial markers were increased, lower or unchanged in schizophrenia in 11, 3 and 8 studies, respectively. Results were variable across all other markers, but SERPINA3 and IFITM were consistently increased in 4 and 5 studies, respectively. Despite the variability, some studies evaluating neuroinflammation in postmortem brains in schizophrenia suggest an increase in microglial activity and other markers such as SERPINA3 and IFITM. Variability across studies is partially explained by multiple factors including brain region evaluated, source of the brain, diagnosis, age at time of death, age of onset and the presence of suicide victims in the cohort.

SUBMITTER: Trepanier MO

PROVIDER: S-EPMC4960446 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review.

Trépanier M O MO Hopperton K E KE Mizrahi R R Mechawar N N Bazinet R P RP

Molecular psychiatry 20160607 8

Schizophrenia is a psychiatric disorder which has a lifetime prevalence of ~1%. Multiple candidate mechanisms have been proposed in the pathogenesis of schizophrenia. One such mechanism is the involvement of neuroinflammation. Clinical studies, including neuroimaging, peripheral biomarkers and randomized control trials, have suggested the presence of neuroinflammation in schizophrenia. Many studies have also measured markers of neuroinflammation in postmortem brain samples from schizophrenia pat ...[more]

PMID: 27271499

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Project description:Recommendations for managing patients with cerebral cryptococcomas are scarce across multiple clinical guidelines. Due to the deficiency of high-quality data coupled with an increasing number of at-risk patients, the purpose of this review is to describe the demographic characteristics, causative pathogen, intracranial imaging, surgical and/or pharmacological interventions, as well as outcomes of patients with cerebral cryptococcomas to improve recognition and management. We conducted a scoping review in accordance with the PRISMA guidelines using PubMed and Web of Science. Reports were included if the following details were presented: (1) site of infection; (2) treatment details which at least include the specific antifungal therapy administered, if applicable; and (3) patient outcome. A total of 40 records representing 47 individual patients were included, of which the median age was 48.5 years, 75% were male, and 60% reported a significant past medical, surgical, or social history. C. neoformans was isolated more often than C. gattii (74% vs. 26%, respectively). Patients most often presented with headache, altered mental status and/or confusion, and vomiting occurring over a median of 30 days; though few were noted to have significant findings on physical examination. More than 50% of patients had a single cerebral cryptococcoma lesion, whereas perilesional edema was present in 73% of cases. Surgical intervention occurred in 49% of patients. An amphotericin B-based formulation was administered as "induction" therapy to 91% of patients, but combined with flucytosine or fluconazole in only 58%, for an overall median of 42 days. Fifty two percent of patients received "maintenance" therapy for a median of 126 days, in which fluconazole was most often used. Corticosteroids were administered to approximately 30% of patients for a median of 31.5 days. Overall, mortality was 34%. Based on our findings, management should include antifungal therapy for a minimum of 6 months with considerations for concomitant corticosteroids in the setting of perilesional edema, as well as surgical intervention. Emphasis should be placed on providing well-documented treatment details in future case reports and series to allow for the development of more concise evidence-based recommendations.

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Project description:BackgroundSchizophrenia (SZ) is a disorder diagnosed by specific symptoms and duration and is highly heterogeneous, clinically and pathologically. Although there are an increasing number of studies on the association between genetic and environmental factors in the development of SZ, the actual distribution of the population with different levels of influence of these factors has not yet been fully elucidated. In this study, we focused on stress as an environmental factor and stratified SZ based on the expression levels of stress-responsive molecules in the postmortem prefrontal cortex.MethodsWe selected the following stress-responsive molecules: interleukin (IL) -1β, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, glucocorticoid receptor, brain-derived neurotrophic factor, synaptophysin, S100 calcium-binding protein B, superoxide dismutase, postsynaptic density protein 95, synuclein, apolipoprotein A1 (ApoA1), ApoA2, and solute carrier family 6 member 4. We performed RNA sequencing in the prefrontal gray matter of 25 SZ cases and 21 healthy controls and conducted a hierarchical cluster analysis of SZ based on the gene expression levels of stress-responsive molecules, which yielded two clusters. After assessing the validity of the clusters, they were designated as the high stress-response SZ group and the low stress-response SZ group, respectively. Ingenuity Pathway Analysis of differentially expressed genes (DEGs) between clusters was performed, and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was conducted on four cases each in the high and low stress-response SZ groups to validate DNA damage.ResultsWe found higher prevalence of family history of SZ in the low stress-response SZ group (0/3 vs. 5/4, p = 0.04). Pathway analysis of DEGs between clusters showed the highest enrichment for DNA double-strand break repair. TUNEL staining showed a trend toward a lower percentage of TUNEL-positive cells in the high stress-response SZ group.ConclusionOur results suggest that there are subgroups of SZ with different degrees of stress impact. Furthermore, the pathophysiology of these subgroups may be associated with DNA damage repair. These results provide new insights into the interactions and heterogeneity between genetic and environmental factors.

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Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review.

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Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review.

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