There is a well-known association of traumatic experiences and posttraumatic stress disorder (PTSD) with body size and composition, including consistent differences between sexes. However, the biology underlying these associations is unclear. To understand the genetic underpinnings of this complex relationship, we investigated genome-wide datasets informative of African and European ancestries from

The hippocampus is a highly plastic brain region sensitive to environmental stress. It shows dynamic changes in epigenetic marks associated with stress related learning. Previous work has shown that acute stress induces substantial transient changes in histone H3 lysine 9 trimethylation (H3K9me3). Moreover, increased H3K9me3 is enriched in hippocampal gene deserts accumulating within endogenous retroviruses

Corticotropin-releasing factor (CRF) signaling in the mesocorticolimbic system is known to modulate anxiety-like behavior and alcohol consumption, behaviors that also have been associated with the hyper-glutamatergic state of the lateral habenula (LHb) neurons in rats. However, the role of CRF signaling in the LHb on the glutamate transmission, anxiety-like behaviors and alcohol consumption is unknown

Adenosine deaminase acting on RNA1 (ADAR1) is a newly discovered epigenetic molecule marker that is sensitive to environmental stressors. A recent study has demonstrated that ADAR1 affects BDNF expression via miR-432 and is involved in antidepressant action. However, the detailed molecular mechanism is still unclear. We have uncovered a new molecular mechanism showing the involvement of miR-432 and

The adverse effects of stress on brain and behavior have long been known and well-studied, with abundant evidence linking stress to, among other things, mood and anxiety disorders. Likewise, many have investigated potential treatments for stress-related mood and anxiety phenotypes and demonstrated good response to standard antidepressant medications like selective serotonin reuptake inhibitors (SSRIs)

Many individuals will be exposed to some form of traumatic stress in their lifetime which, in turn, increases the likelihood of developing stress-related disorders such as post-traumatic stress disorder (PTSD), major depressive disorder (MDD) and anxiety disorders (ANX). The development of these disorders is also influenced by genetics and have heritability estimates ranging between ∼30 and 70%. In

Background Studies reporting accelerated ageing in children with affective disorders or maltreatment exposure have relied on algorithms for estimating epigenetic age derived from adult samples. These algorithms have limited validity for epigenetic age estimation during early development. We here use a pediatric buccal epigenetic (PedBE) clock to predict DNA methylation-based ageing deviation in children

Post-traumatic stress disorder (PTSD) is a severe, long-term psychological disorder triggered by distressing events. The neural basis and underlying mechanisms of PTSD are not completely understood. Therefore, it is important to determine the pathology of PTSD using reliable animal models that mimic the symptoms of patients. However, the lack of evidence on the clinical relevance of PTSD animal models

Background Posttraumatic stress disorder (PTSD) is twice as prevalent among females as compared to males following potentially traumatic events. While there is evidence for aberrant functional connectivity between hubs of the central executive network (CEN), salience network (SN), and the default mode network (DMN) in PTSD, little is known regarding sex-specificity of this connectivity. The current

Emerging evidence has shown that stress responsivity and psychiatric diseases are associated with alterations in N6-methyladenosine (m6A) mRNA epigenetic modifications. Fat mass and obesity-associated protein (FTO) is an m6A demethylase that has been linked to increased body mass and obesity. Here, we show that tricyclic antidepressants (TCAs) with weight-gain side effects, such as imipramine and amitriptyline

Chronic stress exposure in adolescence can lead to a lasting change in stress responsiveness later in life and is associated with increased mental health issues in adulthood. Here we investigate whether the Chronic Social Instability (CSI) paradigm influences the behavioral and molecular responses to novel acute stressors in mice, and whether it alters physiological responses influenced by the noradrenergic

Understanding sex differences in behavioral and molecular effects of stress has important implications for understanding the vulnerability to chronic psychiatric disorders associated with stress response circuitry. The amygdala is critical for emotional learning and generating behavioral responses to stressful stimuli, and preclinical studies indicate that amygdalar endocannabinoid (eCB) signaling

Stressful events impact memory formation, in particular for emotionally arousing stimuli. Although these stress effects on emotional memory formation have potentially far-reaching implications, the underlying neural mechanisms are not fully understood. Specifically, the temporal processing dimension of the mechanisms involved in emotional memory formation under stress remains elusive. Here, we used

Background Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design to examine sex differences in posttraumatic autonomic

Nearly 14 percent of Americans live in a socioeconomically disadvantaged neighborhood. Lower individual socioeconomic position (iSEP) has been linked to increased exposure to trauma and stress, as well as to alterations in brain structure and function; however, the neural effects of neighborhood SEP (nSEP) factors, such as neighborhood disadvantage, are unclear. Using a multi-modal approach with participants

Converging clinical and preclinical evidence demonstrates that depressive phenotypes are associated with synaptic dysfunction and dendritic simplification in cortico-limbic glutamatergic areas. On the other hand, the rapid antidepressant effect of acute ketamine is consistently reported to occur together with the rescue of dendritic atrophy and reduction of spine number induced by chronic stress in

Psychiatric stress has been associated with accelerated epigenetic aging (i.e., when estimates of cellular age based on DNA methylation exceed chronological age) in both blood and brain tissue. Little is known about the downstream biological effects of accelerated epigenetic age on gene expression. In this study we examined associations between DNA methylation-derived estimates of cellular age that

Early-life stress (ES) increases the risk for psychopathology and cognitive decline later in life. Because the neurobiological substrates affected by ES (i.e., cognition, neuroplasticity, and neuroinflammation) are also altered in aging, we set out to investigate if and how ES in the first week of life affects these domains at an advanced age, and how ES modulates the aging trajectory per se. We subjected

Accumulating evidence shows that Coronavirus Disease 19 (COVID-19) survivors may encounter prolonged mental issues, especially post-traumatic stress symptoms (PTSS). Despite manifesting a plethora of behavioral or mental issues in COVID-19 survivors, previous studies illustrated that static brain functional networks of these survivors remain intact. The insignificant results could be due to the conventional

The microbiome co-evolved with their mammalian host over thousands of years. This commensal relationship serves a pivotal role in various metabolic, physiological, and immunological processes. Recently we discovered impaired adrenal catecholamine stress responses in germ-free mice suggesting developmental modification of the reflex arc or absence of an ongoing microbiome signal. To determine whether

9-cis-13,14-dihydroretinoic acid (9CDHRA), acts as an endogenous ligand of the retinoid X receptors (RXRs), and is an active form of a suggested new vitamin, vitamin A5/X. Nutritional-relevance of this pathway as well as its detailed role in vertebrate physiology, remain largely unknown. Since recent GWAS data and experimental studies associated RXR-mediated signaling with depression, we explored here

Maternal depressive symptoms during pregnancy are a significant risk factor for adverse developmental and health outcomes of the offspring. The molecular mechanisms mediating the long-term effects of this exposure are not well understood. Previous studies have found association between prenatal exposure to maternal psychological distress and placental DNA methylation of candidate genes, which can influence

Depression is accompanied by neuronal atrophy and decreased neuroplasticity. Leucine-rich glioma-inactivated protein 1 (LGI1), a metastasis suppressor, plays an important role in the development of CNS synapses. We found that LGI1 expression was reduced in the hippocampi of mice that underwent chronic unpredictable stress (CUS), and could be rescued by the antidepressant, fluoxetine. Recombinant soluble

Both genetic predisposition and life events, particularly life stress, are thought to increase the risk for depression. Reward sensitivity appears to be attenuated in major depressive disorder (MDD), suggesting deficits in reward processing in these patients. We identified the VTA-BLA-NAc circuit as being activated by sex reward, and the VTA neurons that respond to sex reward are mostly dopaminergic

Chronic stress contributes to numerous human pathologies including cognition impairments and psychiatric disorders. Glucocorticoids are primary stress hormones that activate two closely related nuclear receptors, the glucocorticoid (GR) and mineralocorticoid receptor (MR), that are both highly expressed in the hippocampus. To investigate potential combinatorial actions of hippocampal GR and MR, we

Posttraumatic stress disorder (PTSD) is a debilitating condition that adversely affect mental and physical health. Recent studies have increasingly explored the role of the immune system in risk for PTSD and its related symptoms. Dysregulation of the immune system may lead to central nervous system tissue damage and impair learning and memory processes. Individuals with PTSD often have comorbid inflammatory

Stress may have a negative effect on mental health and is the primary environmental risk factor in the aetiology of depression. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The hippocampus is a target structure of the adverse effects of stress, and hippocampal neurogenesis plays a crucial role. However, we do not know the mechanisms by which

The nucleus accumbens (NAc), consisting of core (NAcC) and shell (NAcS) sub-regions, has primarily been studied as a locus mediating the effects of drug reward and addiction. However, there is ample evidence that this region is also involved in regulating aversive responses, but the exact role of the NAc and its subregions in regulating associative fear processing remains unclear. Here, we investigated

Maternal psychosocial stress during pregnancy can impact the developing fetal brain and influence offspring mental health. In this context, animal studies have identified the hippocampus and amygdala as key brain regions of interest, however, evidence in humans is sparse. We, therefore, examined the associations between maternal prenatal psychosocial stress, newborn hippocampal and amygdala volumes

Stress is a frequent precipitant of relapse to drug use. Pharmacotherapies targeting a diverse array of neural systems have been assayed for efficacy in attenuating stress-induced drug-seeking in both rodents and in humans, but none have shown enough evidence of utility to warrant routine use in the clinic. We posit that a critical barrier in effective translation is inattention to sex as a biological

Rat and mouse strains differ in behavioral and physiological characteristics, and such differences can contribute to explain discrepant results between laboratories and better select the most appropriate strain for a particular purpose. Differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis are particularly important given the pivotal role of this system in determining consequences

The personality trait of neuroticism is considered a risk factor for stress vulnerability, putatively via its association with elevated limbic reactivity. Nevertheless, majority of evidence to date that relates neuroticism, neural reactivity and stress vulnerability stems from cross-sectional studies conducted in a “stress-free” environment. Here, using a unique prospective longitudinal design, we

We previously reported that GABAergic neurons within the ventral anterior lateral bed nucleus of the stria terminalis (alBST) express glucagon-like peptide 1 receptor (GLP1R) in rats, and that virally-mediated “knock-down” of GLP1R expression in the alBST prolongs the hypothalamic-pituitary-adrenal axis response to acute stress. Given other evidence that a GABAergic projection pathway from ventral

Exposure to early-life stress (ES) increases the risk to develop obesity later in life, and these effects may be sex-specific, but it is currently unknown what underlies the ES-induced metabolic vulnerability. We have previously shown that ES leads to a leaner phenotype under standard chow diet conditions, but to increased fat accumulation when exposed to an unhealthy obesogenic diet. However these

Trauma disorders are often associated with alterations in aversive anticipation and disruptions in emotion/fear circuits. Heightened or blunted anticipatory responding to negative cues in adulthood may be due to differential trauma exposure during development, and previous trauma exposure in childhood may also modify effects of subsequent trauma in adulthood. The aim of the current investigation was

Insulin resistance is a major contributor to the neuroplasticity deficits observed in patients with metabolic disorders. However, the relative contribution of peripheral versus central insulin resistance in the development of neuroplasticity deficits remains equivocal. To distinguish between peripheral and central insulin resistance, we developed a lentiviral vector containing an antisense sequence

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that afflicts many individuals. However, its molecular and cellular mechanisms remain largely unexplored. Here, we found PTSD susceptible mice exhibited significant up-regulation of alpha-Ca2+/calmodulin-dependent kinase II (αCaMKII) in the lateral amygdala (LA). Consistently, increasing αCaMKII in the LA not only caused PTSD-like behaviors

Adult-born dentate granule cells (aDGCs) at 4–6 weeks of age are particularly excitable but subsequently develop the quiet properties of mature cells. Most existing studies have focused on the hyperactivity of 4–6-week-old aDGCs or neurogenesis, which confers stress resilience or buffers stress responses. However, the function of the quiet property of new mature aDGCs remains unclear. Here we used

Stress is a fundamental biological response that can be associated with alterations in cognitive processes. Unhealthy dietary habits are proposed to modulate this effect, notably through their pro-inflammatory potential. This cross-sectional study aimed to evaluate the influence of an obesogenic dietary pattern with inflammatory potential on stress-induced cognitive alterations in healthy volunteers

The hypothalamo-pituitary-adrenal (HPA) axis is one of the major output systems of the vertebrate stress response. It controls the release of cortisol or corticosterone from the adrenal gland. These hormones regulate a range of processes throughout the brain and body, with the main function of mobilizing energy reserves to improve coping with a stressful situation. This axis is regulated in response

Over the past decade, critical, non-redundant roles of the ten-eleven translocation (TET) family of dioxygenase enzymes have been identified in the brain during developmental and postnatal stages. Specifically, TET-mediated active demethylation, involving the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine and subsequent oxidative derivatives, is dynamically regulated in response

Actin dynamics in dendritic spines can be associated with the neurobiological mechanisms supporting the comorbidity between stress exposure and cocaine increase rewards. The actin cytoskeleton remodeling in the nucleus accumbens (NA) has been implicated in the expression of stress-induced cross-sensitization with cocaine. The present study evaluates the involvement of cofilin, a direct regulator of

A high degree of regional, temporal and molecular specificity is evident in the regulation of GABAergic signaling in stress-responsive circuitry, hampering the use of systemic GABAergic modulators for the treatment of stress-related psychopathology. Here we investigated the effectiveness of local intervention with the GABA synthetic enzymes GAD65 and GAD67 in the dorsal dentate gyrus (dDG) vs ventral

Childhood abuse (CA) is a prevalent global health concern, increasing the risk of negative mental health outcomes later in life. In the literature, CA is commonly defined as physical, sexual, and emotional abuse, as well as neglect. Several mental disorders have been associated with CA, including depression, bipolar disorder, schizophrenia, and post-traumatic stress disorder, along with an increased

The mammalian dorsomedial prefrontal cortex (dmPFC) receives diverse inputs and plays important roles in adaptive behavior and cognitive flexibility. Stress, a major risk factor for many psychiatric disorders, compromises the structure and function of multiple brain regions and circuits. Here we show that 7-day restraint stress impairs reversal learning in the 4-choice odor discrimination test, a decision-making

Models of posttraumatic stress disorder (PTSD) suggest that the hippocampus is key to the persistence of traumatic memory. Yet very little is known about the precise changes that take place in this structure, nor their relation with PTSD symptoms. Previous studies have mostly used magnetic resonance imaging (MRI) at low resolutions, making it impossible to identify sensitive anatomical landmarks, or

Despite studies providing insight into the neurobiology of chronic stress, depression and anxiety, long noncoding RNA (lncRNA)-mediated mechanisms underlying the common and distinct pathophysiology of these stress-induced disorders remain nonconclusive. In a previous study, we used the chronic mild stress paradigm to separate depression-susceptible, anxiety-susceptible and insusceptible rat subpopulations

Prenatal stress (PS) can impact fetal brain structure and function and contribute to higher vulnerability to neurodevelopmental and neuropsychiatric disorders. To understand how PS alters evoked and spontaneous neocortical activity and intrinsic brain functional connectivity, mesoscale voltage imaging was performed in adult C57BL/6NJ mice that had been exposed to auditory stress on gestational days

Recent research has emphasized rumination as an important maintaining factor in various mental disorders. However, operationalization and therefore induction of rumination in experimental settings poses a major challenge in terms of ecological validity. As stress seems to play a key role in everyday situations eliciting rumination, we conducted two stress paradigms while assessing behavioral and neurophysiological

Alterations in the brain-gut system have been implicated in various disease states, but little is known about how early-life adversity (ELA) impacts development and adult health as mediated by brain-gut interactions. We hypothesize that ELA disrupts components of the brain-gut system, thereby increasing susceptibility to disordered mood. In a sample of 128 healthy adult participants, a history of ELA

Childhood maltreatment (CM) is an established major risk factor for a number of negative health outcomes later in life. While epigenetic mechanisms, such as DNA methylation (DNAm), have been proposed as a means of embedding this environmental risk factor, little is known about its timing and trajectory, especially in very young children. It is also not clear whether additional environmental adversities

The precise mechanisms underlying the detrimental effects of early life adversity (ELA) on adult mental health remain still elusive. To date, most studies have exclusively targeted neuronal populations and not considered neuron-glia crosstalk as a crucially important element for the integrity of stress-related brain function. Here, we have investigated the impact of ELA, in the form of a limited bedding