Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Heritability and polygenic predictionIn the EUR sample, the SNP-based heritability (h 2 SNP ) (that is, the proportion of variance in liability attributable to all measured SNPs)

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Extracellular vesicles (EVs) are present in numerous peripheral bodily fluids and function in critical biological processes, including cell-to-cell communication. Most relevant to the present study, EVs contain microRNAs (miRNAs), and initial evidence from the field indicates that miRNAs detected in circulating EVs have been previously associated with mental health disorders. Here, we conducted an exploratory longitudinal and cross-sectional analysis of miRNA expression in serum EVs from adolescent participants. We analyzed data from a larger ongoing cohort study, evaluating 116 adolescent participants at two time points (wave 1 and wave 2) separated by three years. Two separate data analyses were employed: A cross-sectional analysis compared individuals diagnosed with Major Depressive Disorder (MDD), Anxiety disorders (ANX) and Attention deficit/Hyperactivity disorder (ADHD) with individuals without psychiatric diagnosis at each time point. A longitudinal analysis assessed changes in miRNA expression over time between four groups showing different diagnostic trajectories (persistent diagnosis, first incidence, remitted and typically developing/control). Total EVs were isolated, characterized by size distribution and membrane proteins, and miRNAs were isolated and sequenced. We then selected differentially expressed miRNAs for target prediction and pathway enrichment analysis. In the longitudinal analysis, we did not observe any statistically significant results. In the cross-sectional analysis: in the ADHD group, we observed an upregulation of miR-328-3p at wave 1 only; in the MDD group, we observed a downregulation of miR-4433b-5p, miR-584-5p, miR-625-3p, miR-432-5p and miR-409-3p at wave 2 only; and in the ANX group, we observed a downregulation of miR-432-5p, miR-151a-5p and miR-584-5p in ANX cases at wave 2 only. Our results identified previously observed and novel differentially expressed miRNAs and their relationship with three mental health disorders. These data are consistent with the notion that these miRNAs might regulate the expression of genes associated with these traits in genome-wide association studies. The findings support the promise of continued identification of miRNAs contained within peripheral EVs as biomarkers for mental health disorders.

BackgroundLonger duration of untreated psychosis (DUP) predicts poor functional outcomes in patients with schizophrenia. The results are not so clear when addressing effects on specific dimensions of symptoms, which may be due to confounding effects of previous antipsychotic treatment. We investigated the association between DUP, specific dimensions and response to treatment in a 10-week follow up study of patients at First-Episode of Psychosis (FEP) with no previous antipsychotic use.MethodsWe assessed 158 antipsychotic naïve individuals with first-episode psychosis, admitted to a psychiatric emergency service. Diagnosis was established according to the Structured Clinical Interview for DSM-IV (SCID). Symptom severity was measured with the Positive And Negative Symptoms Scale (PANSS) and the Clinical Global Impressions Scale (CGI). Functionality was assessed with the Global Assessment of Functioning Scale (GAF). All patients were treated with risperidone and reassessed after 10 weeks of treatment. For analyses, we performed non-parametric correlation tests (Spearman’s correlation).ResultsAt baseline, we did not find a correlation between DUP and symptom severity and functionality. After the follow-up, DUP became significantly correlated to both symptomatic and functional outcomes. DUP showed significant association with PANSS positive score (r=0.282; p=0.008), PANSS negative score (r=0.295; p=0.005), PANSS total score (r=0.258; p=0.017), CGI total (r=0.305; p=0.003) and GAF (r=-0.294; p=0.004). We also found a negative correlation between DUP and response to treatment considering 30% of reduction of PANSS’ scores (r=-0.288; p=0.027).DiscussionOur findings support that DUP does not affect the severity of illness at baseline, but modifies the response to treatment and clinical severity after 10 weeks. This finding suggests that longer exposition to psychosis might be involved in biological abnormalities that modulate the response to antipsychotics, which could mediate poor response to treatment.

Telomeres are short tandem repeats of “TTAGGG” that protect the chromosome ends from deterioration or fusion of chromosomes. Their repeat length shortens with cell division acting as a biomarker of cellular aging. Traumatic stress events during adulthood or childhood have been associated with posttraumatic stress disorder (PTSD) and short leukocyte telomere length (LTL). This study investigated whether LTL was associated with PTSD in a Brazilian sample of sexually assaulted civilian women at two time points: baseline and 1-year follow-up. At baseline, we assessed 64 women with PTSD following sexual assault (cases) and 60 women with no previous history of sexual trauma or mental disorders (healthy controls – HC). At follow-up visit, 13 persistent PTSD cases, 11 HCs, and 11 PTSD remitters patients were evaluated. PTSD diagnosis and severity were assessed using Mini International Neuropsychiatric Interview (Diagnostic and Statistical Manual of Mental Disorders III/IV criteria) and Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), respectively. LTL was measured using multiplex real-time polymerase chain reaction (PCR). In the baseline analysis, we observed that LTL was associated with re-experiencing symptoms (B = −0.16; confidence interval (CI) 95% = −0.027—−0.005; Bonferroni-adjusted p-value = 0.02), but no association was observed between other PTSD symptoms and LTL. In the longitudinal analysis, telomere shortening was no longer observed in patients with PTSD and PTSD remitters. In conclusion, our findings indicate that shorter baseline LTL is associated with early stage of PTSD re-experiencing symptoms in recently sexually assaulted women.

Introduction. Sexual assault and a history of childhood sexual abuse (CSA) are related to posttraumatic stress disorder (PTSD) development. Long Interspersed Nuclear Elements (LINE-1) are transposable elements, and their methylation is used to infer DNA global methylation. DNA methylation can be affected by trauma exposition which in turn would be associated with PTSD. Thus, we investigated if the LINE-1 methylation pattern is related to PTSD symptoms in females with a history of CSA. Methods. This is a case-control study that examined, at baseline (W1), 64 women victims of sexual assault diagnosed with PTSD and 31 patients with PTSD who completed the 1-year follow-up (W2). Participants were categorized into two groups according to the presence of CSA (PTSDCSA+: NW1=19, NW2=10; PTSDCSA-: NW1=45, NW2=21). PTSD symptoms (re-experiencing, avoidance, hyperarousal, alterations in cognition/mood) were assessed using the Clinician-Administered PTSD Scale, and the history of CSA was assessed by the Childhood Trauma Questionnaire. LINE-1 methylation was measured in three sites (CpG1, CpG2, CpG3) located in the 5’UTR region using bisulfite conversion followed by pyrosequencing. Linear regression models were performed to test the relation between LINE-1 CpGs sites methylation and PTSD symptoms. Results. We found a negative association between CpG2 methylation and hyperarousal symptoms among PTSDCSA+ in W1 (adjusted p=0.003) compared to PTSDCSA- group (p>0.05). Still, no association was observed between other PTSD symptoms and other CpG sites. Further, in the longitudinal study, LINE-1 hypomethylation was no longer observed in PTSD participants exposed to CSA. Discussion/Conclusion. Our findings suggest that LINE-1 methylation may help understand the relationship between trauma and PTSD. However, more studies are needed to investigate LINE-1 as an epigenetic marker of psychiatric disorders.

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