Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on aging at the cellular level. A newly derived tool provides an additional means to investigate cellular aging by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular aging will show increased aging. We expect that particularly in individuals that developed symptoms of post--traumatic stress disorder (PTSD) increases in these aging parameters would stand out.From an existing longitudinal cohort study, ninety--six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self--Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19--item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic aging was estimated using the DNAm age estimator procedure.The association of trauma with telomere length was in the expected direction but not significant (B=--10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p= 0.018). In concordance, trauma significantly accelerated epigenetic aging (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic aging (B=--0.10, p= 0.044). Blood cell count, medication and premorbid early life trauma exposure did not confound the results.Overall, in this longitudinal study of military personnel deployed to Afghanistan we show an acceleration of ageing by trauma. However, development of PTSD symptoms was associated with telomere lengthening and reversed epigenetic aging. These findings warrant further study of a perhaps dysfunctional compensatory cellular aging reversal in PTSD.3

Findings from epidemiological studies, biomarker measurements and animal experiments suggest a role for aberrant immune processes in the pathogenesis of major depressive disorder (MDD). Microglia, the resident immune cells of the brain, are likely to play a key role in these processes. Previous post-mortem studies reported conflicting findings regarding microglial activation and an in-depth profiling of those cells in MDD is lacking. The aim of this study was therefore to characterize the phenotype and function of microglia in MDD. We isolated microglia from post-mortem brain tissue of patients with MDD (n = 13-19) and control donors (n = 12-25). Using flow cytometry and quantitative Polymerase Chain Reaction (qPCR), we measured protein and mRNA levels of a panel of microglial markers across four different brain regions (medial frontal gyrus, superior temporal gyrus, thalamus, and subventricular zone). In MDD cases, we found a significant upregulation of CX3CR1 and TMEM119 mRNA expression and a downregulation of CD163 mRNA expression and CD14 protein expression across the four brain regions. Expression levels of microglial activation markers, such as HLA-DRA, IL6, and IL1β, as well as the inflammatory responses to lipopolysaccharide and dexamethasone were unchanged. Our findings suggest that microglia enhance homeostatic functions in MDD but are not immune activated.

Patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis usually develop characteristic neurologic and psychiatric symptoms. Some patients have isolated psychiatric symptoms, mimicking a schizophrenia-like psychotic episode. 1,2 Therefore, it has been hypothesized that a subgroup of patients diagnosed as having schizophrenia actually has anti-NMDAR encephalitis, 2 which would have important clinical implications. Anti-NMDAR encephalitis is caused by IgG-type autoantibodies to the GluN1 subunit of the NMDAR. Conflicting reports have been published regarding the seroprevalence of anti-NMDAR autoantibodies in schizophrenia, ranging from 0% to 8%. 2,3 Some studies that reported high seroprevalences included patients with schizophrenia with atypical features, such as seizures and movement disorders. We hypothesized that the use of a single antibody detection assay, without any further validation of the findings, may have contributed to the inconsistent findings. 3 Here, we investigated the presence of anti-GluN1 IgG autoantibodies in 475 patients with a schizophrenia spectrum disorder and included the cross-validation of positive samples. Methods | The current study included 3 cohorts. Cohort 1 involved 415 patients with schizophrenia who were screened over 2 years with a full laboratory screening for studying meta

Genetic, epidemiological, and biomarker studies suggest that the immune system is involved in the pathogenesis of bipolar disorder (BD). It has therefore been hypothesized that immune activation of microglia, the resident immune cells of the brain, is associated with the disease. Only a few studies have addressed the involvement of microglia in BD so far and a more detailed immune profiling of microglial activation is lacking. Here, we applied a multi-level approach to determine the activation state of microglia in BD post-mortem brain tissue. We did not find differences in microglial density, and mRNA expression of microglial markers in the medial frontal gyrus (MFG) of patients with BD. Furthermore, we performed in-depth characterization of human primary microglia isolated from fresh brain tissue of the MFG, superior temporal gyrus (STG), and thalamus (THA). Similarly, these ex vivo isolated microglia did not show elevated expression of inflammatory markers. Finally, challenging the isolated microglia with LPS did not result in an increased immune response in patients with BD compared to controls. In conclusion, our study shows that microglia in post-mortem brain tissue of patients with BD are not immune activated.