Observational studies suggested an association between childhood maltreatment and neuropsychiatric disorders; however, mediators remain disputed.

We aimed to confirm the relationship between childhood maltreatmen and neuropsychiatric disorders, and to identify addiction-related, biological, behavioural, cognitive, socioeconomic and epigenetic mediators.

We used two-sample Mendelian randomisation and publicly available genome-wide association data to evaluate the effect of genetically predicted childhood maltreatment (N = 143 473) on the risk of six neuropsychiatric disorders (up to N = 500 199). We used two-step Mendelian randomisation to determine the proportion of the effect of childhood maltreatment on disorders that was mediated by mediators. We used multivariable Mendelian randomisation to determine the direct effect of childhood maltreatment on disorders accounting for mediators. We used epigenetic Mendelian randomisation to determine the effect of DNA methylation at childhood maltreatment-associated CpG sites on disorders.

Childhood maltreatment was significantly associated with higher risk of attention-deficit/hyperactivity disorder (ADHD) (odds ratio 10.09, 95% CI: 4.76–21.40), major depressive disorder (MDD) (odds ratio 1.89, 95% CI: 1.32–2.70) and schizophrenia (odds ratio: 5.89, 95% CI: 1.46–23.78). We determined that 4.14–22.17% of the effect of childhood maltreatment was mediated by addiction-related behaviours (smoking initiation, leisure screen time and substance abuse), cognitive traits (executive functioning, intelligence and risk tolerance) and educational attainment. We found that the direct effects of childhood maltreatment on ADHD (odds ratio 2.57) and schizophrenia (odds ratio 5.10) were less than the total effects, while the direct effect on MDD (odds ratio 1.95) remained relatively unchanged. We found altered DNA methylation levels at 3, 4 and 19 CpG sites to be significantly associated with ADHD, MDD and schizophrenia, respectively.

These results emphasise the need for preventative strategies to reduce childhood maltreatment prevalence, including strengthening support for high-risk families and responsive strategies to mitigate consequences for victims, with clinical screening for childhood maltreatment history and holistic approaches addressing addiction-related, cognitive and socioeconomic mediators.

Opioid use disorder (OUD) is a major global-scale social issue affecting public health. The high potential for addiction and dependence makes opioid use a significant concern, contributing to substance-related disorders. Both genetic and environmental factors contribute to the predisposition to OUD, with the opioidergic, dopaminergic, and GABAergic systems playing primary roles in itsonset.

This narrative review documents the association between genes and their variants related to these three systems, along with current evidence on epigenetic interventions in OUD. Relevant studies investigating candidate-gene associations and molecular mechanisms were synthesized to highlight genetic variants and epigenetic processes linked to OUD.

Genetic associations play a prominent role in OUD, with several single-nucleotide variants identified in affected populations. Key genes implicated include OPRM1, OPRD1, OPRK1, PDYN, OPRL1, and POMC from the opioidergic system; DRD1, DRD2, DRD3, DRD4, ANKK1, and COMT from the dopaminergic system; and GABRA2, GABRB3, GABRG2, GAD1, and GAD2 from the GABAergic system. Evidence also indicates that chronic opioid use is associated with epigenetic changes through posttranslational histone modifications and DNA methylation. However, limitations in existing studies include small sample sizes, limited replication, and potential stratification biases.

Although many candidate-gene associations have been proposed for OUD, robust evidence remains limited. Large, ancestrally diverse genome-wide association studies (GWAS) and systematic replication studies are urgently needed. A deeper understanding of the genetic, epigenetic, and neurobiological bases of addiction will be essential for the development of precisely targeted medications to improve prevention and treatment outcomes for OUD.

During the perinatal period, women may be more susceptible to depressive symptoms because of fluctuating oestrogen levels. Genetic variations, epigenetic modifications and varying gene expression levels of oestrogen receptor genes may contribute to inter-individual differences in the encoded receptors’ sensitivity to oestrogen, ultimately modulating the susceptibility to depressive symptoms.

The aim of this systematic review was to provide an overview of the literature on the association between oestrogen receptor genes and perinatal depression symptoms by including genetic, epigenetic and gene expression studies.

A systematic search of three public databases, PubMed, PsycINFO and Web of Science, was conducted in accordance with the PRISMA guidelines (PROSPERO registration number: CRD42023447446). Two independent reviewers extracted data and assessed study quality.

A total of 29 studies were finally included, of which 16 investigated genetic variants, five investigated epigenetic modifications and eight investigated gene expression levels of oestrogen receptor genes. A limited number of genetic variations were found to be associated with perinatal depression symptoms, most of them in ESR1. Moreover, DNA methylation marks involved in oestrogen signalling, and gene expression levels of ESR1 and ESR2, were found to be associated with perinatal depression symptoms.

Genetic variations, epigenetic modifications and gene expression levels of oestrogen receptor genes are associated with susceptibility to perinatal depression symptoms. The underlying mechanism might be the inter-individual modulation of the encoded receptors’ sensitivity to oestrogen. Future research employing more comprehensive and integrative approaches is needed to better understand the aetiology of perinatal depression symptoms.

Primary neoplasm of the external auditory canal has historically been documented to have a low incidence rate of between one and six per million internationally, with UK incidence yet to be officially cited.

Here, we report a rise in incidence at a single UK trust with seven carcinomas (six T4 external auditory canal squamous cell and one T4 basal cell) reported within an 18-month period. All tumours underwent next generation sequencing.

The cases recorded represented a twofold rise in incidence in reference to international literature from a population-adjusted estimate of 0.5–3 cases for the catchment area to seven cases. All cases were treated with temporal bone resections (n = 7) and with post-operative radiotherapy in six cases. Tumour analysis showed all were TP53 mutant and human papilloma virus (HPV)/P16 negative.

We suggest chronic inflammation and genetic alterations as putative contributory factors in our case series and outline clinical strategies for timely detection of external auditory canal neoplasms.

Up to 30% of people infected with SARS-CoV-2 report disabling symptoms 2 years after the infection. Over 100 persistent symptoms have been associated with Post-Acute COVID-19 Symptoms (PACS) and/or long-COVID, showing a significant clinical heterogeneity. To develop effective, patient-targeted treatment, a better understanding of underlying mechanisms is needed. Epigenetics has helped elucidating the pathophysiology of several health conditions and it might help unravelling inter-individual differences in patients with PACS and long-COVID. As accumulating research is exploring epigenetic mechanisms in PACS and long-COVID, we systematically summarized the available literature on the topic.

We interrogated five databases (Medline, Embase, Web of Science, Scopus and medXriv/bioXriv) and followed PRISMA and SWiM guidelines to report our results.

Eight studies were included in our review. Six studies explored DNA methylation in PACS and/or long-COVID, while two studies explored miRNA expression in long-COVID associated with lung complications. Sample sizes were mostly small and study quality was low or fair. The main limitation of the included studies was a poor characterization of the patient population that made a homogeneous synthesis of the literature challenging. However, studies on DNA methylation showed that mechanisms related to the immune and the autonomic nervous system, and cell metabolism might be implicated in the pathophysiology of PACS and long-COVID.

Epigenetic changes might help elucidating PACS and long-COVID underlying mechanisms, aid subgrouping, and point towards tailored treatments. Preliminary evidence is promising but scarce. Biological and epigenetic research on long-COVID will benefit millions of people suffering from long-COVID and has the potential to be transferable and benefit other conditions as well, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We urge future research to employ longitudinal designs and provide a better characterization of included patients.