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The link between the oral microbiome and neurodevelopmental disorders remains a compelling hypothesis, still requiring confirmation in large-scale datasets. Leveraging over 7000 whole-genome sequenced salivary samples from 2025 US families with children diagnosed with autism spectrum disorders (ASD), our cross-sectional study shows that the oral microbiome composition can discriminate ASD subjects from neurotypical siblings (NTs, AUC = 0.66), with 108 differentiating species ( q  < 0.005). The relative abundance of these species is highly correlated with cognitive impairment as measured by Full-Scale Intelligence Quotient (IQ). ASD children with IQ < 70 also exhibit lower microbiome strain sharing with parents ( p  < 10 −6 ) with respect to NTs. A two-pronged functional enrichment analysis suggests the contribution of enzymes from the serotonin, GABA, and dopamine degradation pathways to the distinct microbial community compositions observed between ASD and NT samples. Although measures of restrictive eating diet and proxies of oral hygiene show relatively minor effects on the microbiome composition, the observed associations with ASD and IQ may still represent unaccounted-for underlying differences in lifestyle among groups. While causal relationships could not be established, our study provides substantial support to the investigation of oral microbiome biomarkers in ASD. Here, Manghi et al. identify potential salivary microbial biomarkers for autism through a large-scale metagenomic analysis of 2,000 families, revealing shifts in neurotransmitter-related pathways

: Stressful events increase the risk for treatment-resistant depression (TRD), and trauma-focused psychotherapy can be useful for TRD patients exposed to early life stress (ELS). Epigenetic processes are known to be related to depression and ELS, but there is no evidence of the effects of trauma-focused psychotherapy on methylation alterations. : We performed the first epigenome-wide association study to investigate methylation changes related to trauma-focused psychotherapies effects in TRD patients. : Thirty TRD patients assessed for ELS underwent trauma-focused psychotherapy, of those, 12 received trauma-focused cognitive behavioural therapy, and 18 Eye Movement Desensitization and Reprocessing (EMDR). DNA methylation was profiled with Illumina Infinium EPIC array at T0 (baseline), after 8 weeks (T8, end of psychotherapy) and after 12 weeks (T12 - follow-up). We examined differentially methylated CpG sites and regions, as well as pathways analysis in association with the treatment. : Main results obtained have shown 110 differentially methylated regions (DMRs) with a significant adjusted -value area associated with the effects of trauma-focused psychotherapies in the entire cohort. Several annotated genes are related to inflammatory processes and psychiatric disorders, such as , , , and Gene enrichment analyses revealed statistically significant processes related to tumour necrosis factor (TNF) receptor and TNF signalling pathway. Stratified analyses by type of trauma-focused psychotherapy showed statistically significant adjusted -value area in 141 DMRs only for the group of patients receiving EMDR, with annotated genes related to inflammation and psychiatric disorders, including and . Gene set enrichment analyses in the EMDR group indicated biological processes related to inflammatory response, particularly the TNF signalling pathway. : We provide preliminary valuable insights into global DNA methylation changes associated with trauma-focused psychotherapies effects, in particular with EMDR treatment.

Background Electroconvulsive therapy (ECT) benefits patients with treatment-resistant depression (TRD), but the underlying biological processes are unclear. We conducted an epigenome-wide association study in 32 TRD patients undergoing ECT to depict ECT-associated methylation changes. Illness severity and ECT outcomes were assessed with the Montgomery–Åsberg Depression Rating Scale at baseline (T0) and 1 month after its end (T1). Methylation was profiled at T0 and T1 with the Illumina Infinium Methylation EPIC BeadChip array. Results Longitudinal T0–T1 analyses showed 3 differentially methylated probes (DMPs) with nominal p values ≤ 10 −5 , with 2 annotated in the genes CYB5B and PVRL4 . Including covariates, we found 4 DMPs for symptoms variation, annotated in FAM20C , EPB41 , OTUB1 and ADARB1 , and 3 DMPs for response status, with 2 annotated in IQCE and FAM20C . Regional analysis revealed 54 differentially methylated regions (DMRs) with nominal p value area ≤ 0.05, with 9 presenting adjusted p -value area ≤ 0.10, annotated in MCF2L , SLC25A24 , RUNX3 , MIR637 , FOXK2 , FAM180B , POU6F1 , ALS2CL and CCRL2 . Considering covariates, we found 21 DMRs for symptoms variation and 26 DMRs for response (nominal p value area ≤ 0.05), with 4 presenting adjusted p -value area ≤ 0.10 for response, annotated in SNORD34 , NLRP6 , GALNT2 and SFT2D3 . None remained significant after false discovery rate correction. Notably, ADARB1 variants are associated with suicide attempt in patients with psychiatric disorders, and SLC25A24 relates to conduct disorder. Several DMPs and DMRs are annotated in genes associated with inflammatory/immune processes. Longitudinal analyses on females (n = 22) revealed statistically significant DMRs (adjusted p value area ≤ 0.05) and trend-significant DMRs (adjusted p value area ≤ 0.07) for symptoms variation and response status, annotated in genes related to psychiatric disorders ( ZFP57 , POLD4, TRIM10, GAS7, ADORA2A, TOLLIP ), trauma exposure ( RIPOR2 ) and inflammatory/immune responses ( LAT , DLX4 , POLD4 , FAM30A, H19 ). Pathway analysis on females revealed enrichment for transcriptional activity, growth factors, DNA maintenance, and immune pathways including IRF7 and IRF2 . Conclusion Although no significant results were found for the whole cohort, the study provides insights into ECT-associated methylation changes, highlighting DMPs and DMRs related to ECT outcomes. Analyses on females revealed significant DMRs and pathways related to psychiatric disorders and inflammatory/immune processes.

Stress is a primary risk factor for psychiatric disorders such as Major Depressive Disorder (MDD) and Post Traumatic Stress Disorder (PTSD). The response to stress involves the regulation of transcriptional programs, which is supposed to play a role in coping with stress. To evaluate transcriptional processes implemented after exposure to unavoidable traumatic stress, we applied microarray expression analysis to the PFC of rats exposed to acute footshock (FS) stress that were sacrificed immediately after the 40 min session or 2 h or 24 h after. While no substantial changes were observed at the single gene level immediately after the stress session, gene set enrichment analysis showed alterations in neuronal pathways associated with glia development, glia–neuron networking, and synaptic function. Furthermore, we found alterations in the expression of gene sets regulated by specific transcription factors that could represent master regulators of the acute stress response. Of note, these pathways and transcriptional programs are activated during the early stress response (immediately after FS) and are already turned off after 2 h—while at 24 h, the transcriptional profile is largely unaffected. Overall, our analysis provided a transcriptional landscape of the early changes triggered by acute unavoidable FS stress in the PFC of rats, suggesting that the transcriptional wave is fast and mild, but probably enough to activate a cellular response to acute stress.