Stress-related Disorders Research Articles

Aromatic Serenity: How Lavender Eases Stress and Anxiety - A Literature Review

In today's fast-paced society, rising stress levels necessitate effective management strategies. While pharmacological treatments are common, their side effects have spurred interest in alternative therapies, particularly those rooted in natural remedies. Lavender (Lavandula angustifolia), long esteemed for its calming properties, has emerged as a promising non-pharmacological option. Historical use in herbal medicine for anxiety and stress-related disorders has inspired modern scientific research to explore its potential. This review synthesizes recent studies on lavender essential oil, examining its mechanisms—such as neurotransmitter modulation—and its effectiveness in diverse settings, from reducing stress among healthcare professionals to improving sleep quality. Despite promising results, limitations like small sample sizes and variability in application methods highlight the need for more rigorous research to establish lavender's efficacy and optimize its therapeutic use in stress management and mental health care.

Sex-specific GABAergic microcircuits that switch vulnerability into resilience to stress and reverse the effects of chronic stress exposure.

Clinical and preclinical studies have identified somatostatin (SST)-positive interneurons as critical elements that regulate the vulnerability to stress-related psychiatric disorders. Conversely, disinhibition of SST neurons in mice results in resilience to the behavioral effects of chronic stress. Here, we established a low-dose chronic chemogenetic protocol to map these changes in positively and negatively motivated behaviors to specific brain regions. AAV-hM3Dq-mediated chronic activation of SST neurons in the prelimbic cortex (PLC) had antidepressant drug-like effects on anxiety- and anhedonia-like motivated behaviors in male but not female mice. Analogous manipulation of the ventral hippocampus (vHPC) had such effects in female but not male mice. Moreover, the activation of SST neurons in the PLC of male mice and the vHPC of female mice resulted in stress resilience. Activation of SST neurons in the PLC reversed prior chronic stress-induced defects in motivated behavior in males but was ineffective in females. Conversely, activation of SST neurons in the vHPC reversed chronic stress-induced behavioral alterations in females but not males. Quantitation of c-Fos+ and FosB+ neurons in chronic stress-exposed mice revealed that chronic activation of SST neurons leads to a paradoxical increase in pyramidal cell activity. Collectively, these data demonstrate that GABAergic microcircuits driven by dendrite targeting interneurons enable sex- and brain-region-specific neural plasticity that promotes stress resilience and reverses stress-induced anxiety- and anhedonia-like motivated behavior. The data provide a rationale for the lack of antidepressant efficacy of benzodiazepines and superior efficacy of dendrite-targeting, low-potency GABAA receptor agonists, independent of sex and despite striking sex differences in the relevant brain substrates.

Transcriptome signatures of the medial prefrontal cortex underlying GABAergic control of resilience to chronic stress exposure.

Analyses of postmortem human brains and preclinical studies of rodents have identified somatostatin (SST)-positive, dendrite-targeting GABAergic interneurons as key elements that regulate the vulnerability to stress-related psychiatric disorders. Conversely, genetically induced disinhibition of SST neurons (induced by Cre-mediated deletion of the γ2 GABAA receptor subunit gene selectively from SST neurons, SSTCre:γ2f/f mice) results in stress resilience. Similarly, chronic chemogenetic activation of SST neurons in the medial prefrontal cortex (mPFC) results in stress resilience but only in male and not in female mice. Here, we used RNA sequencing of the mPFC of SSTCre:γ2f/f mice to characterize the transcriptome changes underlying GABAergic control of stress resilience. We found that stress resilience of male but not female SSTCre:γ2f/f mice is characterized by resilience to chronic stress-induced transcriptome changes in the mPFC. Interestingly, the transcriptome of non-stressed SSTCre:γ2f/f (stress-resilient) male mice resembled that of chronic stress-exposed SSTCre (stress-vulnerable) mice. However, the behavior and the serum corticosterone levels of non-stressed SSTCre:γ2f/f mice showed no signs of physiological stress. Most strikingly, chronic stress exposure of SSTCre:γ2f/f mice was associated with an almost complete reversal of their chronic stress-like transcriptome signature, along with pathway changes suggesting stress-induced enhancement of mRNA translation. Behaviorally, the SSTCre:γ2f/f mice were not only resilient to chronic stress-induced anhedonia - they also showed an inversed, anxiolytic-like behavioral response to chronic stress exposure that mirrored the chronic stress-induced reversal of the chronic stress-like transcriptome signature. We conclude that GABAergic dendritic inhibition by SST neurons exerts bidirectional control over behavioral vulnerability and resilience to chronic stress exposure that is mirrored in bidirectional changes in the expression of putative stress resilience genes, through a sex-specific brain substrate.

Cannabidiol inhibits transient receptor potential canonical 4 and modulates excitability of pyramidal neurons in mPFC

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been extensively studied for its potential therapeutic effects on various central nervous system (CNS) disorders, including epilepsy, chronic pain, Parkinson’s disease, and stress-related neuropsychiatric disorders. However, the pharmacological mechanisms of CBD have not been fully elucidated due to the complexity of their targets. In this study, we reported that the transient receptor potential canonical 4 (TRPC4) channel, a calcium-permeable, non-selective cation channel, could be inhibited by CBD. TRPC4 is highly abundant in the central nervous system and plays a critical role in regulating axonal regeneration, neurotransmitter release, and neuronal network activity. Here, we used whole-cell electrophysiology and intracellular calcium measurements to identify the inhibitory effects of CBD on TRPC4, in which CBD was found to inhibit TRPC4 channel with an IC50 value of 1.52 μM TRPC4 channels function as receptor-operated channels (ROC) and could be activated by epinephrine (EP) via G proteins. We show that CBD can inhibit EP-evoked TRPC4 current in vitro and EP-evoked neuronal excitability in the medial prefrontal cortex (mPFC). These results are consistent with the action of TRPC4-specific inhibitor Pico145, suggesting that TRPC4 works as a functional ionotropic receptor of CBD. This study identified TRPC4 as a novel target for CBD in the CNS and suggested that CBD could reduce the pyramidal neuron excitability by inhibiting TRPC4-containing channels in the mPFC.

Stress disrupts engram ensembles in lateral amygdala to generalize threat memory in mice.

Stress induces aversive memory overgeneralization, a hallmark of many psychiatric disorders. Memories are encoded by a sparse ensemble of neurons active during an event (an engram ensemble). We examined the molecular and circuit processes mediating stress-induced threat memory overgeneralization in mice. Stress, acting via corticosterone, increased the density of engram ensembles supporting a threat memory in lateral amygdala, and this engram ensemble was reactivated by both specific and non-specific retrieval cues (generalized threat memory). Furthermore, we identified a critical role for endocannabinoids, acting retrogradely on parvalbumin-positive (PV+) lateral amygdala interneurons in the formation of a less-sparse engram and memory generalization induced by stress. Glucocorticoid receptor antagonists, endocannabinoid synthesis inhibitors, increasing PV+ neuronal activity, and knocking down cannabinoid receptors in lateral amygdala PV+ neurons restored threat memory specificity and a sparse engram in stressed mice. These findings offer insights into stress-induced memory alterations, providing potential therapeutic avenues for stress-related disorders.

Sex Differences in the Neurobiology of Fear and Anxiety.

Although women are diagnosed with anxiety and stress-related disorders at twice the rate of men, there remains a lack of clarity around how to enhance treatment within each sex to reduce disparate rates of anxiety. However, in recent years, a growing literature has identified neural, cognitive, and physiological mechanisms that contribute to sex differences in fear and anxiety, with the promise of informing tailored treatment approaches. Here, we review recent findings, focusing on human studies among healthy populations as well as among patients with generalized anxiety, social anxiety disorder, post-traumatic stress disorder, and panic disorder. The literature reveals nuanced differences in the types of stimuli that preferentially evoke anxiety and stress responses in women and men, as well as sex differences in threat neurocircuitry that mediates the behavioral, physiological, and subjective components of fear and anxiety.

Mitophagy Unveiled: Exploring the Nexus of Mitochondrial Health and Neuroendocrinopathy.

Mitochondria play a pivotal role in cellular metabolism, energy production, and apoptotic signaling, making mitophagy, the selective degradation of damaged mitochondria, crucial for mitochondrial health. Dysregulation of mitophagy has been implicated in various neuroendocrinopathies, yet the mechanisms linking these processes remain poorly understood. This review aims to explore the intersection between mitophagy and neuroendocrinopathy, addressing the critical gaps in knowledge regarding how mitochondrial dysfunction may contribute to the pathophysiology of neuroendocrine disorders. We conducted a comprehensive literature review of studies published on mitophagy and neuroendocrinopathies, focusing on data that elucidate the pathways involved and the clinical implications of mitochondrial health in neuroendocrine contexts. Our findings indicate that altered mitophagy may lead to the accumulation of dysfunctional mitochondria, contributing to neuroendocrine dysregulation. We present evidence linking impaired mitochondrial clearance to disease models of conditions such as metabolic syndrome, depression, and stress-related disorders, highlighting the potential for therapeutic interventions targeting mitophagy. While significant advances have been made in understanding mitochondrial biology, the direct interplay between mitophagy and neuroendocrinopathies remains underexplored. This review underscores the necessity for further research to elucidate these connections, which may offer novel insights into disease mechanisms and therapeutic strategies for treating maladaptive neuroendocrine responses.

Distinct septo-hippocampal cholinergic projections separately mediate stress-induced emotional and cognitive deficits.

Patients suffering from chronic stress develop numerous symptoms, including emotional and cognitive deficits. The precise circuit mechanisms underlying different symptoms remain poorly understood. We identified two distinct basal forebrain cholinergic subpopulations in mice projecting to the dorsal hippocampus (dHPC) or ventral hippocampus (vHPC), which exhibited distinct input organizations, electrophysiological characteristics, transcriptomics, and responses to positive and negative valences of stimuli and were critical for cognitive and emotional modulation, respectively. Moreover, chronic stress induced elevated anxiety levels and cognitive deficits in mice, accompanied by enhanced vHPC but suppressed dHPC cholinergic projections. Chemogenetic activation of dHPC or inhibition of vHPC cholinergic projections alleviated stress-induced aberrant behaviors. Furthermore, we identified that the acetylcholinesterase inhibitor donepezil combined with blockade of muscarinic receptor 1-type muscarinic acetylcholine receptors in the vHPC rescued both stress-induced phenotypes. These data illuminated distinct septo-hippocampal cholinergic circuits mediated specific symptoms independently under stress, which may provide promising strategies for circuit-based treating of stress-related psychiatric disorders.

Photo-supported conversations about well-being (BeWellTM) for patients with exhaustion disorders – a controlled clinical intervention study

Introduction Health-promotion approaches to address stress-related exhaustion disorders, reduce personal suffering, improve coping and participation in everyday life are needed in primary care. The aim of this study was to investigate self-reported health and well-being before and after an intervention focusing on well-being with photo-supported conversations (BeWellTM). Material and methods Eighty-one patients (69 women), 20–67 years old, with exhaustion disorders were recruited at Swedish primary health care centres (PHCC) to a controlled clinical study. The intervention group (n = 40) were offered BeWell™ by therapists in addition to care as usual. Controls (n = 41) received only care as usual. The primary outcome, self-rated symptoms of exhaustion (Karolinska exhaustion disorder scale, KEDS), and secondary outcomes, anxiety and depression, sense of coherence, quality of life, occupational balance, and work ability, were assessed by validated questionnaires. Non-parametric statistical analyses were used to compare data collected directly after the treatment period with baseline measures. Results Demographics and self-rated baseline measures of health and well-being were comparable between the groups, apart from sick leave being more common in the intervention group. Participants in the intervention group reduced their level of exhaustion more than the control group (median difference on KEDS −9.0 vs −4.0, p = .035). However, the size of the KEDS reduction was related to baseline KEDS and, not independently associated with group assignment. Both groups improved regarding secondary outcome measures. Conclusion Stress-related symptoms decreased considerably over the treatment period for both groups. The potential benefit of the BeWell™, which was intended to facilitate recovery, needs to be further evaluated.

Neuroprotective Roles of Daidzein Through Extracellular Signal-Regulated Kinases Dependent Pathway In Chronic Unpredictable Mild Stress Mouse Model.

Depression is a stress-related neuropsychiatric disorder causing behavioural, biochemical, molecular dysfunctions and cognitive impairments. Previous studies suggested connection between neuropsychiatric diseases like depression with estrogen and estrogen receptors (ER). Daidzein is a phytoestrogen that functions as mammalian estrogen and regulates gene expressions through extracellular signal-regulated kinases (ERKs) dependent pathway by activating ERβ. ERβ modulates stress responses, physiological processes by activating protein kinases and plays a significant role in various neurological diseases like depression. However, significant roles of daidzein in depression involving ERK1/2, pERK1/2, and mTOR still unknown. Herein, we examined neuroprotective role of daidzein in chronic unpredictable mild stress (CUMS) mouse model. CUMS model was prepared, and placed in six groups namely, control, CUMS, CUMS vehicle, CUMS DZ (Daidzein 1mg/kgbw, orally), CUMS PHTPP (ERβ blocker, 0.3mg/kgbw, i..p.) and CUMS Untreated. Supplementation of daidzein to CUMS mice exhibits decrease depressive and anxiety-like behaviour, improved motor coordination and memory. Further, immunofluorescence results showed daidzein improved ERK1/2, pERK1/2 and mTOR expressions in the cortex, hippocampus and medulla of stressed mice. SOD, catalase and acetylcholinesterase levels were also improved. Blocking of ERβ with PHTPP stressed mice showed deficits in behaviour, low expression of ERK1/2, pERK1/2 and mTOR, and no significant changes in SOD, catalase and acetylcholinesterase level. Collectively, this study suggests that daidzein may ameliorate depressive and anxiety-like behaviour through ERK downregulating pathway by activating ERβ through ERK1/2, pERK1/2 and mTOR. Such study may be useful to understand daidzein dependent neuroprotection through ERβ in depression.

Common and divergent neuroimaging features in major depression, posttraumatic stress disorder and their comorbidity

Abstract Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are common stress-related psychiatric disorders. Genetic and neurobiology research has supported the viewpoint that PTSD and MDD may possess common and disorder-specific underlying mechanisms. In this systematic review, we summarized evidence for the similarities and differences in brain functional and structural features of MDD, PTSD and their comorbidity, as well as the effects of extensively used therapies in patients with comorbid PTSD and MDD (PTSD + MDD). These functional magnetic resonance imaging (MRI) studies highlight the 1) shared hypoactivation in the prefrontal cortex during cognitive and emotional processing in MDD and PTSD, 2) higher activation in fear processing regions including amygdala, hippocampus and insula in PTSD compared to MDD, and 3) distinct functional deficits in brain regions involved in fear and reward processing in patients with PTSD + MDD relative to those with PTSD-alone. These structural MRI studies suggested that PTSD and MDD share features of reduced volume in focal frontal areas. The treatment effects in patients with PTSD + MDD may correlate with the normalization trend of structural alterations. Neuroimaging predictors of repetitive transcranial magnetic stimulation response in patients with PTSD + MDD may differ from the mono-diagnostic groups. In summary, neuroimaging studies to date have provided limited information about the shared and disorder-specific features in MDD and PTSD. Further research is essential to pave the way for developing improved diagnostic markers and eventually targeted treatment approaches for the shared and distinct brain alterations presented in patients with MDD and PTSD.

Association of self-harm and suicidality with psychiatric co-occurring conditions in autistic individuals: a systematic review and pooled analysis

Autistic individuals frequently experience psychiatric co-occurring conditions, but the association with self-harm/suicidality according to these conditions was not yet elucidated. We aimed to summarize the association between self-harm/suicidality and psychiatric co-occurring conditions in autistic people. We systematically searched PubMed, Scopus, Embase, Web of Science, and Cochrane Database of Systematic Reviews until June 4, 2024 (PROSPERO registration number: CRD42023412860). Observational studies were included that provided information to calculate the odds ratio (OR) regarding the association between self-harm/suicidality and psychiatric co-occurring conditions in autistic individuals. We summarized the identified associations by presenting OR range or meta-analyzing when 7 or more estimates are available. The systematic search found 20 eligible studies with 301,841 participants. Our findings suggested that autistic individuals with any psychiatric disorder (k=1; OR 3.55; 95% CI 1.27-9.98), ADHD (k=3; OR range: 1.07-1.65), or mood disorder (k=1; OR 1.26; 95% CI 1.05-1.51) may be associated with higher odds of self-harm than those without these conditions. We identified potential positive associations between suicidality and the following co-occurring conditions: any psychiatric disorder (k=1; OR 11.65; 95% CI 10.68-12.71), psychotic disorder (k=4; OR range: 1.95-10.97), mood disorder (k=3; OR range: 1.75-9.82), bipolar disorder (k=2; ORrange: 2.55-4.95), depressive disorder (k=10; pooled OR 2.29; 95% CI 1.39-3.77), trauma- and stress-related disorder (k=2; OR range: 1.28-10.47), and adjustment disorder (k=1; OR 3.52; 95% CI 2.89-4.28). We found psychiatric co-occurring conditions that may be associated with higher odds of self-harm/suicidality in autistic individuals. However, our findings should be interpreted with caution considering the limited number of included studies. We suggested that clinicians should remain vigilant for autistic individuals with psychiatric co-occurring conditions for their potentially higher likelihood of self-harm and suicidality. This research was supported by a grant of the R&D project, funded by the National Center for Mental Health (grant number: MHER22A01).

Plasma proteomic signature of chronic psychosocial stress in mice

Chronic stress significantly impacts both physical and mental wellbeing, increasing risk of cardiovascular disease, immune dysregulation, and psychiatric conditions such as depression and anxiety disorders. The plasma proteome is a valuable source of biomarkers of health and disease, but the limited number of studies exploring the potential of the plasma proteome as a biomarker for stress-related disorders underscores the importance of further investigation of the effects of chronic stress on the plasma proteome. The aim of this study was to examine the effect of a 5-week chronic psychosocial stress paradigm on the plasma proteome in mice and to determine if any affected proteins correlated with stress-induced changes in behaviour and physiology, and thus might represent biomarkers of negative impacts of chronic stress. Using LC-MS/MS proteomic analysis, 38 proteins in the mouse plasma proteome were identified to be affected by chronic psychosocial stress. Functional analysis revealed that these proteins clustered into biological functions including inflammatory response, regulation of the immune response, complement and coagulation cascades, lipid metabolic process, and high-density lipoprotein particles Correlation analyses of the identified proteins with stress-induced behavioural or physiological changes stress revealed significant correlations between stress-induced anxiety-like behaviour and Phosphatidylinositol-glycan-specific phospholipase D, Complement C2, Epidermal growth factor receptor, Prosaposin, Actin-related protein 2/3 complex subunit 1B, Maltase-glucoamylase, Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA and Fibrinogen-like protein 1. Chronic psychosocial stress blunted acute stress-induced corticosterone release, and this correlated with abundance of Pyrethroid hydrolase Ces2a; N-fatty-acyl-amino acid synthase/hydrolase Pm20d1, Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA, Alpha-2-macroglobulin-P and L-selectin. Finally, stress-induced reductions in both brown and epididymal fat correlated with Phosphatidylinositol-glycan-specific phospholipase D, Complement C2, Epidermal growth factor receptor, Kininogen-1, Apolipoprotein M, Angiopoietin-related protein 3, Proprotein convertase subtilisin/kexin type 9, and Lipopolysaccharide-binding protein. These findings demonstrate that chronic psychosocial stress induces alterations in plasma proteins implicated in key biological processes and pathways related to stress response, immune function, and lipid metabolic regulation. Further investigation into these proteins may provide new avenues for identification of biomarkers or mediators of stress-induced pathology.

Inflammation as a shared mechanism of chronic stressrelated disorders with potential novel therapeutic targets.

Stress is a subjective experience that varies across individuals depending on their sensitivity, resilience, and length of exposure to stressors. Stress may be categorised as acute (positive stress) or chronic (negative stress). Acute stress is advantageous for the human body, but chronic stress results in changes in cardiovascular, neuroendocrine, autonomic, and immunological functions, eventually causing different illnesses. The specific process relating stress to chronic stress associated diseases is still a topic of continuing debate. Inflammation has been recognised as a new and fascinating physiological mechanism that connects chronic stress and its associated illnesses. This article explored the relationships between chronic stress, inflammation, and chronic illnesses, including depression, cancer, and cardiovascular disease. This article also emphasises on various possible therapeutic targets for the management of chronic stressrelated illnesses by targeting inflammation, namely lipoxins and alpha7 nicotinic receptors. These therapeutic targets may be useful in developing new and safe therapies for the management of chronic stressrelated dysfunctions.

The microglial innate immune receptor TREM2 participates in fear memory formation through excessive prelimbic cortical synaptic pruning.

Fear memory formation has been implicated in fear- and stress-related psychiatric disorders, including post-traumatic stress disorder (PTSD) and phobias. Synapse deficiency and microglial activation are common among patients with PTSD, and induced in animal models of fear conditioning. Increasing studies now focus on explaining the specific mechanisms between microglia and synapse deficiency. Though newly-identified microglia regulator triggering receptor expressed on myeloid cells 2 (TREM2) plays a role in microglial phagocytic activity, its role in fear-formation remains unknown. We successfully constructed a fear- formation model by foot-shock. Four days after foot-shock, microglial capacity of synaptic pruning was investigated via western blotting, immunofluorescence and Golgi-Cox staining. Prelimbic chemical deletion or microglia inhibition was performed to detect the role of microglia in synaptic loss and neuron activity. Finally, Trem2 knockout mice or wild-type mice with Trem2 siRNA injection were exposed to foot-shock to identify the involvement of TREM2 in fear memory formation. The results herein indicate that the foot-shock protocol in male mice resulted in a fear formation model. Mechanistically, fear conditioning enhanced the microglial capacity for engulfing synapse materials, and led to glutamatergic neuron activation in the prelimbic cortex. Prelimbic chemical deletion or microglia inhibition improved fear memory formation. Further investigation demonstrated that TREM2 regulates microglial phagocytosis, enhancing synaptic pruning. Trem2 knockout mice showed remarkable reductions in prelimbic synaptic pruning and reduced neuron activation, with decreased fear memory formation. Our cumulative results suggest that prelimbic TREM2-mediated excessive microglial synaptic pruning is involved in the fear memory formation process, leading to development of abnormal stress-related behavior.

BDNF methylation associated with stress in women: Novel insights in epigenetics and inflammation

The brain-derived neurotrophic factor (BDNF) gene plays an important role in modulating the stress-response axis and inflammation, which can be regulated by epigenetic mechanisms. BNDF methylation has been associated with stress-related psychiatric disorders such as depression, anxiety and post-traumatic stress. Previous studies have reported that stressful events are involved with long-lasting alterations in DNA methylation (DNAm) of the BNDF exon IV promoter, suggesting that glucocorticoids and inflammatory cytokines can regulate this process. We previously found that perceived psychological stress is modulated by inflammatory cytokines, such as interleukin (IL)-6, IL-8 and IL-10, and IL-12p70, suggesting their role in mediating the stress response. However, the epigenetic mechanism mediating this response has yet to be fully understood. In this study, we propose that high perceived stress and high serum levels of inflammatory cytokines may correlate with specific methylation sites within the BNDF exon IV promoter. To address these questions, we conducted a cross-sectional study of 82 adult women teachers working in basic education in Brazil. The perceived stress scale was used to assess stress and blood samples were collected for the measurement of inflammatory markers and BNDF methylation through flow cytometry assay and DNA pyrosequencing, respectively. We detected differentially methylated CpG sites in the BNDF gene, where 5 CpG sites were directly correlated with high stress levels. However, 4 CpG sites showed inverse effects, indicating that changes in methylation levels in those sites could lead to a protective effect on perceived stress. About inflammatory markers, IL-6 and IL-8 were associated with high perceived stress. However, only IL-8 and IL-10 showed simultaneous modulation of perceived stress, while IL-10 and IL12p70 correlated with DNAm. We found that higher levels in IL-10 and IL-12p70 serum decrease methylation in CpG11. A direct relationship was also found to IL-12p70, where higher levels in serum increase methylation in CpG5 and 13, respectively. Taken as a whole, our findings reinforce the hypothesis regarding stress-sensitive regions within the BDNF gene, mainly for CpG5, 11, and 13. In addition to these results, CpG7 and 9 may be regarded as stress-protective regions. Our data suggest that BDNF DNAm in the blood may represent a novel biomarker for early detection of adverse effects of chronic exposure to stress in healthy individuals.

Plasma Brain-Derived Neurotrophic Factor (BDNF) Levels and BDNF Promoters’ DNA Methylation in Workers Exposed to Occupational Stress and Suffering from Psychiatric Disorders

Introduction: Decreased plasma BDNF (pBDNF) levels have been proposed as a biomarker in the illness phases of mood disorders. This cross-sectional study aimed to evaluate the pBDNF and BDNF promoters’ DNA methylation levels in workers exposed to occupational stress and suffering from work-related stress disorders. Methods: the pBDNF and BDNF exon I and IV promoters’ methylation levels were measured by specific immunoassays and methylation-sensitive high-resolution melting (MS-HRM) in 62 patients with adjustment disorders (AD), 79 patients with major depressive disorder (MDD) and 44 healthy controls. Occupational stress was evaluated in the patients and controls using the Job Content Questionnaire (JCQ). Results: the pBDNF levels were significantly higher in the MDD (p < 0.001) and AD (p < 0.0001) patients than in the controls. The MDD patients showed significantly lower pBDNF levels than the AD ones (p = 0.01). The BDNF exon I and IV promoters’ methylation levels were significantly higher in the MDD patients than in the AD ones (exon I promoter: p = 0.0001, exon IV promoter: p < 0.0001) and controls (exon I promoter: p = 0.0001, exon IV promoter: p < 0.0001). In the patients, but not in the controls, the BDNF promoters’ methylation levels showed significant negative correlations with occupational stress. Conclusions: BDNF could play a key role in the pathophysiology of stress-related disorders and the peripheral elevation of it observed in patients exposed to occupational stress could suggest a protective mechanism for neurons from stress-mediated damage. The elevation of the pBDNF levels, even in MDD, may characterize a “reactive” subtype of depressive episode, while the significant elevation of the BDNF promoters’ methylation levels in depressed patients could indicate a predisposition to more severe illness under stress. Further research is needed, focusing on biomarkers for stress-related disorders as a potential tool for the diagnosis and prevention of occupational diseases.

Prevalence and severity of insomnia in adult outpatients attending Kasralainy Psychiatry and Addiction Treatment Hospital

BackgroundInsomnia is common among patients with psychiatric disorders and affects the clinical presentation and outcomes of the psychiatric disorder. The presentation of insomnia varies according to the type and severity of the psychiatric disorder.ObjectivesThis cross-sectional study aimed to assess the prevalence and severity of insomnia in adult psychiatric outpatients attending Psychiatry and Addiction Medicine Hospital, Faculty of Medicine, Cairo University. The study included 390 patients diagnosed with the following disorders: depressive disorders (n = 126 (32.2%)), anxiety disorders (n = 69 (17.6%)), psychotic spectrum disorders (n = 67 (17.1%)), bipolar and related disorders (n = 50 (12.8%)), trauma and stress-related disorders (n = 46 (11.8%)), obsessive–compulsive disorder (n = 30 (7.7%)), and somatic symptoms disorders (n = 2 (0.5%)). Patients were assessed using the Sleep Disorder Interview, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Global Assessment of Functioning Scale (GAF).ResultsAmong the assessed patients, 314 (80.5%) had insomnia, with a higher prevalence in females (91.5%) compared to males (67.2%). The prevalence of insomnia was 96% in depressive disorders, 97.1% in anxiety disorders, 49.3% in psychotic disorders, and 32% in bipolar and related disorders; while all patients with trauma and stress-related disorders, obsessive–compulsive disorders, and somatic symptoms disorders had insomnia.The severity of insomnia as measured by ISI was positively correlated with the global functioning score (r = 0.341, p = < 0.001) and negatively correlated with the duration of the psychiatric illness (r = − 0.285, p = < 0.001).ConclusionsInsomnia is highly prevalent in outpatients with psychiatric disorders.

SARS-CoV-2 Infection And COVID-19 Outcomes Among Mental Disorders: A Register-based Study in Catalonia

Abstract This study aimed to study the risk of SARS-CoV-2 infection and severe COVID-19 outcomes across different mental diagnoses and to assess the role of sex in these associations. We used electronic health records from Catalonia to identify adults receiving inpatient/outpatient mental health care between 2017-2019 with diagnosis of non-affective psychosis (NAP), bipolar disorder (BD), depressive disorder (DEP), stress-related disorders, neurotic/somatoform disorders (NSD), and substance misuse (SUB) (exposed). Outcomes included SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19-related death. Adjusted logistic regression analyses were conducted. 785,378 adults were included (70.3% &amp;lt; 65 years old; 57.1% women). Compared to unexposed, those with NAP [OR (95%CI): 0.84 (0.80-0.88)], BD [0.80 (0.75-0.86)], DEP [0.97 (0.94-1.00)] and SUB [0.81 (0.78-0.84)] had a lower risk of SARS-CoV-2 infection, while people with NSD presented an increased risk [1.03 (1.01-1.06)]. Among those infected, people with DEP, NSD, and SUB had a lower risk of COVID-19 hospitalization, but higher risk of COVID-19-related death [1.23 (1.07-1.41); 1.26 (1.07-1.48); 1.48 (1.24-1.71), respectively]. A higher COVID-19-related death was also found in people with NAP and BD [1.68 (1.34-2.12); 2.02 (1.50-2.73)]. Sex-stratified analysis showed that women with NSD were especially vulnerable to infection [1.07 (1.03-1.11)], and women with DEP and NSD to COVID-19-related death [1.24 (1.05-1.47); 1.26 (1.02-1.54)]. These results suggest different vulnerabilities to infection and COVID-19 hospitalization and death across mental disorders. These findings have implications for pandemic preparedness, highlighting the need for specific public health strategies to mitigate the excess of mortality of people with certain mental disorders.

Age-dependent associations with the risk of mental disorders in patients with myocardial infarction: a UK Biobank cohort study

Abstract Background Despite an overall decrease in cardiovascular mortality in recent decades due to effective preventive strategies, a concerning trend is emerging among young adults, with a rising incidence of myocardial infarction (MI) and its poor prognosis. Previous studies report that a significant association between mental disorders and the incidence and prognosis of MI. However, a detailed age-specific information is still lacking. Purpose We aimed to determine whether the risk of developing mental disorders after MI differs based on age and to stratify individuals at a higher risk. Methods From the UK Biobank prospective database (n=502,386), we collected data on patients with a prior MI (n=10,840) and compared them to age- and sex-matched controls (n=54,197) in a 1:5 ratio. Diagnoses of mental disorders were ascertained through linked hospital admission and mortality data, using the appropriate ICD-10-CM codes. Mental disorders were defined by at least two inpatient or outpatient claims within 1 year. The primary outcome was a composite of incident mental disorders, including depression, anxiety, stress-related, and somatoform disorders. Follow-up was done until the first diagnosis of mental disorders or the end of 2022. Results During a median follow-up of 13.7 years (interquartile range 12.8-14.5 years), the incidence rate of the primary outcome was 9.28 vs. 5.37/1,000 person-years among patients with MI and controls, respectively (p&amp;lt;0.001). A prior MI history demonstrated an independent association with the risk of incident mental disorders, yielding an adjusted hazard ratio (aHR) of 1.41 (95% confidence interval [CI], 1.29–1.54; p&amp;lt;0.001) after adjusting for confounders. This was comparable to heavy drinking and family history of depression. Notably, the risk of mental disorders attributed to previous MI was more prominent in younger individuals aged &amp;lt;55 years than their older counterpart (aHR 1.61 vs. 1.33) (p-for-interaction 0.020). Similar results were observed in the analysis of two important components: depression and anxiety disorder. Furthermore, in younger patients with MI (&amp;lt;55 years), mental disorders significantly increased the risk of mortality, while not in older patients. Conclusion MI was associated with a higher risk of incident mental disorders, resulting in poor prognosis, particularly in young individuals. Active surveillance and prevention for incident mental disorders after young MI may be beneficial.Cumulative Incidence of Mental Disorders