War Exposure and DNA Methylation in Syrian Refugee Children and Adolescents.

Importance: Exposure to war is associated with poor mental health outcomes. Adverse and traumatic experiences can lead to long-lasting DNA methylation changes, potentially mediating the link between adversity and mental health. To date, limited studies have investigated the impact of war on DNA methylation in children or adolescents, hampering our understanding of the biological impact of war exposure.

The role of environmental sensitivity in the mental health of Syrian refugee children: a multi-level analysis.

Individuals with high environmental sensitivity have nervous systems that are disproportionately receptive to both the protective and imperilling aspects of the environment, suggesting their mental health is strongly context-dependent. However, there have been few consolidated attempts to examine putative markers of sensitivity, across different levels of analysis, within a single cohort of individuals with high-priority mental health needs. Here, we examine psychological (self-report), physiological (hair hormones) and genetic (polygenic scores) markers of sensitivity in a large cohort of 1591 Syrian refugee children across two waves of data.

Hair hormone data from Syrian refugee children: Perspectives from a two-year longitudinal study.

For numerous issues of convenience and acceptability, hair hormone data have been increasingly incorporated in the field of war trauma and forced displacement, allowing retrospective examination of several biological metrics thought to covary with refugees' mental health. As a relatively new research method, however, there remain several complexities and uncertainties surrounding the use of hair hormones, from initial hair sampling to final statistical analysis, many of which are underappreciated in the extant literature, and restrict the potential utility of hair hormones. To promote awareness, we provide a narrative overview of our experiences collecting and analyzing hair hormone data in a large cohort of Syrian refugee children ( = 1594), across two sampling waves spaced 12 months apart.

PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons.

Dipeptide repeat proteins are a major pathogenic feature of C9orf72 amyotrophic lateral sclerosis (C9ALS)/frontotemporal dementia (FTD) pathology, but their physiological impact has yet to be fully determined. Here we generated C9orf72 dipeptide repeat knock-in mouse models characterized by expression of 400 codon-optimized polyGR or polyPR repeats, and heterozygous C9orf72 reduction. (GR)400 and (PR)400 knock-in mice recapitulate key features of C9ALS/FTD, including cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction.

Risk and resilience in Syrian refugee children: A multisystem analysis.

Refugee children are often exposed to substantial trauma, placing them at increased risk for mental illness. However, this risk can be mitigated by a capacity for resilience, conferred from multiple ecological systems (e.g.

Effects of war exposure on pubertal development in refugee children.

Increasing research shows pubertal development accelerates following threats while it decelerates following deprivation. Yet, these environmental stressors are unlikely to occur in isolation. We investigated how war exposure and energetic stress impact pubertal development using data from the longitudinal Biological Pathways of Risk and Resilience in Syrian Refugee Children study.

War exposure, post-traumatic stress symptoms and hair cortisol concentrations in Syrian refugee children.

Altered secretion of cortisol, the primary effector of the hypothalamus-pituitary-adrenal axis, has been proposed as a means by which traumatic experiences compromise later mental health. However, despite the popularity of cortisol as a potential biomarker for stress and adversity, findings are inconsistent, and little is known about the impact of war-related trauma on stress physiology of children and adolescents. Here we aimed to evaluate the relationships between war exposure, current living conditions, hair cortisol concentrations (HCC) and post-traumatic stress disorder (PTSD) symptoms in a large cohort of Syrian refugee children and adolescents (6-18 years) and their caregiver.

Cohort profile: biological pathways of risk and resilience in Syrian refugee children (BIOPATH).

The BIOPATH cohort was established to explore the interplay of psychosocial and biological factors in the development of resilience and mental health problems in Syrian refugee children. Based in Lebanon, a middle-income country significantly impacted by the refugee crisis, it is the first such cohort of refugees in the Middle East. Families were recruited from informal tented settlements in the Beqaa region using purposive cluster sampling.

Lithium treatment and human hippocampal neurogenesis.

Lithium is a first-line treatment for bipolar disorder, where it acts as a mood-stabilizing agent. Although its precise mechanism remains unclear, neuroimaging studies have shown that lithium accumulates in the hippocampus and that chronic use amongst bipolar disorder patients is associated with larger hippocampal volumes. Here, we tested the chronic effects of low (0.

The role of epigenetics in psychological resilience.

There is substantial variation in people's responses to adversity, with a considerable proportion of individuals displaying psychological resilience. Epigenetic mechanisms are hypothesised to be one molecular pathway of how adverse and traumatic events can become biologically embedded and contribute to individual differences in resilience. However, not much is known regarding the role of epigenetics in the development of psychological resilience.

Telomere length and human hippocampal neurogenesis.

Short telomere length is a risk factor for age-related disease, but it is also associated with reduced hippocampal volumes, age-related cognitive decline and psychiatric disorder risk. The current study explored whether telomere shortening might have an influence on cognitive function and psychiatric disorder pathophysiology, via its hypothesised effects on adult hippocampal neurogenesis. We modelled telomere shortening in human hippocampal progenitor cells in vitro using a serial passaging protocol that mimics the end-replication problem.

Prolactin, Estradiol and Testosterone Differentially Impact Human Hippocampal Neurogenesis in an In Vitro Model.

Previous studies have indicated that sex hormones such as prolactin, estradiol and testosterone may play a role in the modulation of adult hippocampal neurogenesis (AHN) in rodents and non-human primates, but so far there has been no investigation of their impact on human hippocampal neurogenesis. Here, we quantify the expression levels of the relevant receptors in human post-mortem hippocampal tissue and a human hippocampal progenitor cell (HPC) line. Secondly, we investigate how these hormones modulate hippocampal neurogenesis using a human in vitro cellular model.

Polygenic risk for circulating reproductive hormone levels and their influence on hippocampal volume and depression susceptibility.

Altered reproductive hormone levels have been associated with the pathophysiology of depressive disorders and this risk may be imparted by their modulatory effect upon hippocampal structure and function. Currently it is unclear whether altered levels of reproductive hormones are causally associated with hippocampal volume reductions and the risk of depressive disorders. Here, we utilize genome-wide association study (GWAS) summary statistics from a GWAS focusing on reproductive hormones, consisting of 2913 individuals.

Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood.

Hippocampal volumes are smaller in psychiatric disorder patients and lower levels of hippocampal neurogenesis are the hypothesized cause. Understanding which molecular processes regulate hippocampal progenitor differentiation might aid in the identification of novel drug targets that can promote larger hippocampal volumes. Here we use a unique human cell line to assay genome-wide expression changes when hippocampal progenitor cells differentiate.

The Role of Lipid Biomarkers in Major Depression.

In the UK, the lifetime-documented prevalence of major depressive disorder (MDD) is currently 10%. Despite its increasing prevalence and devastating impact on quality of life, the pathophysiological mechanisms underpinning MDD remain to be fully elucidated. Current theories of neurobiological components remain incomplete and protein-centric, rendering pharmacological treatment options suboptimal.