Persistent Exposure Research Articles

Trained innate immunity as a potential link between preeclampsia and future cardiovascular disease

Preeclampsia (PE) is a complex pregnancy syndrome characterized by hypertension with or without proteinuria, affecting 2–6% of pregnancies globally. PE is characterized by excessive release of damage-associated molecular patterns (DAMPs) into the maternal circulation. This DAMP-rich milieu acts on innate immune cells, inducing a proinflammatory state characterized by elevated cytokines such as IL-1β and IL-18. This proinflammatory state in the mother and placenta results in the endothelial dysfunction strongly associated with cardiovascular disorders. While the immediate maternal and fetal risks of PE are well-documented, accumulating evidence indicates that PE also confers long-term cardiovascular risks to the mother, including hypertension, coronary heart disease, stroke, and heart failure. The underlying mechanisms connecting PE to these chronic cardiovascular conditions remain unclear. This article explores the potential role of trained innate immunity (TRIM) as a mechanistic link between PE and increased long-term cardiovascular risk. We propose that the persistent exposure to DAMPs during PE may epigenetically reprogram maternal innate immune cells and their progenitors, leading to TRIM. This reprogramming enhances the inflammatory response to subsequent stimuli, potentially contributing to endothelial dysfunction and chronic inflammation that predispose women to cardiovascular diseases later in life. Understanding the role of TRIM in PE could provide novel insights into the pathophysiology of PE-related cardiovascular complications and identify potential targets for therapeutic intervention. Further research is warranted to investigate the epigenetic and metabolic alterations in innate immune cells induced by PE and to determine how these changes may influence long-term maternal cardiovascular health.

Exploring the Trajectories of Depressive Symptoms Associated With Bullying Victimization: The Intersection of Gender and Family Support.

Children from multicultural families in South Korea are at high risk of bullying victimization, highlighting the need for a deeper understanding of the challenges they face. This study explores the gendered dynamics of depressive symptoms associated with persistent exposure to bullying victimization among these youths, as well as the role of family support. This study utilizes data from nine waves of the Multicultural Adolescents Panel Study (MAPS), spanning from 2011 (Wave 1) to 2019 (Wave 9). MAPS is a nationally representative longitudinal survey of adolescents with multicultural backgrounds and their mothers. Participants include 1375 families (51.1% girls; grade 4-13). Fixed-effects models were estimated to address the possibility of bias due to unobserved time-invariant confounders. Gender-stratified analyses and interaction models were employed to examine the moderating role of gender and family support. Depressive symptoms among girls were higher with persistent bullying victimization; however, this association was observed up to two consecutive waves of exposure (an immediate and short-term pattern). In contrast, persistent bullying victimization was associated with a cumulative increase in depressive symptoms up to three or more consecutive waves of exposure in boys (an immediate and cumulative pattern). Moreover, while family support was associated with lower levels of depressive symptoms among bullied girls, bullied boys exhibited a similar pattern of a cumulative increase in depressive symptoms regardless of the level of family support. The study's findings suggest potential considerations for gendered interventions related to mental health outcomes of bullying victimization among multicultural family youth in Korea.

The effect of persistent exposure to thiocyanate and the impact on inhibition of ferrous iron oxidation in an industrial strain of Acidiplasma cupricumulans

The effect of persistent exposure to thiocyanate and the impact on inhibition of ferrous iron oxidation in an industrial strain of Acidiplasma cupricumulans

Pesticide exposure patterns in honey bees during migratory pollination

Monitoring pesticide exposures in honey bees provides fundamental risk information that informs efforts to improve regulatory policy, pesticide use, and beekeeping management so pollinators are protected in realistic field conditions. We investigated pesticide exposures to bee colonies while colonies moved along commercial migratory routes in 2022 and 2023 to pollinate multiple pollinator-dependent, high-value U.S. specialty crops (e.g., almonds in California and apples and cherries in Washington). We found evident pesticide exposure patterns, including increasing exposures (both levels and number of pesticides) to fungicides during almond pollination, higher exposures to insecticides and persistent exposures to fungicides during springtime fruit pollination, and declining exposures in summer. Exposure risk assessment by risk quotient (RQ) model based on residues in bee bread indicates no concern of acute toxicity to adult honey bees during pollination, however, during colony inspections we found severe brood mortality in fields associated with high exposure to buprofezin, an insect growth regulator (IGR) thought to be safe for adult bees, which is permitted for use any time across the season. Our results suggest a need to improve compliance with insecticide label requirements during tree fruit pollination and a need for further research into the negative impacts of IGR on colony health especially on immature bees to inform potential policy changes.

Abstract B035: Reciprocal macrophage - T cell interactions regulate anti-tumor immunity

Abstract Cancer immunotherapy (including immune checkpoint blockade (ICB)) has shown great promise in the treatment of some solid cancers, but responses in breast cancer patients are limited. While breast cancer is generally considered poorly immunogenic, the abundance of CD8+ T cells correlates with clinical response. CD8+ T cells are critical mediators of anti-tumor immunity and the main target for ICB. However, the onset of terminal functional T cell exhaustion poses a major challenge. Although T cell exhaustion has been linked to persistent antigen exposure, it remains unclear how the immune composition of the breast tumor microenvironment (TME) contributes to this dysfunctional T cell state. Breast cancers are heavily infiltrated with tumor-associated macrophages (TAMs) and their abundance correlates with T cell exhaustion and poor prognosis. Previously, we discovered a spatiotemporal co-dependency between exhausted T cells (TEX) and TAMs in mouse models of melanoma and breast cancer. We showed that TEX actively recruit monocytes to the TME and shape their differentiation trajectory into TAMs. Reciprocally, these TAMs ‘capture’ T cells in long-lived synaptic interactions that contribute to functional T cell exhaustion. Our current work is focused on studying the TEX-derived chemokines that regulate these TAM – T cell interactions in the breast TME with the ultimate goal to alleviate immune evasion and improve responsiveness of breast cancer to immunotherapy. Citation Format: Meenakshi Sudhakaran, Sofia Lombardi, Sophie Ayma, Matthew F. Krummel, Kelly Kersten. Reciprocal macrophage - T cell interactions regulate anti-tumor immunity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B035.

The dynamics and assembly patterns of airborne pathogen communities in the municipal food waste treatment system and its risk implications

While municipal solid waste (MSW) provides an ideal habitat for pathogen propagation, the dynamics and assembly of airborne pathogen communities in these environments remain largely unknown. Here, we combined amplicon and metagenomics with spatiotemporal sampling to study inhalable particulate matter-carried potential pathogenic bacteria at full-scale food waste treatment plants (FWTPs), alongside comparisons to urban air in the area. The results showed that pathogenic bacteria constituted a notable portion (64.5 % ± 20.6 %, n = 75) of the total bacterial communities in FWTPs-impacted air, with species and relative abundance 2–4 times higher than that of urban air, and contributed over 50 % of pathogens to the outdoor air. Airborne pathogen community structures were highly shaped by sampling sites (i.e. treatment units), but conserved across seasons (summer vs. winter) and particle sizes (PM2.5vs. PM10). Notably, Acinetobacter johnsonii-dominated pathogens (i.e. biofilm-related species) presented high levels of aerosolization and consistently occupied the upper-representative niches in all neutral models, highlighting their persistent exposure risk. Furthermore, pathogen community assembly was strongly driven by stochastic processes (58.8 %–96.8 %), while environmental variables explained only limited variations (3.4 %–28.7 %). In particular, the relative importance of stochastic processes clearly increased along an outdoor-to-indoor gradient (84.9 %–96.5 % vs. 71.3 %–76 %), which might be related to indoor anthropogenic activities that weaken microbial network stability and environmental filtering effects. This work enhances our knowledge of the dynamic behaviors and risk of airborne pathogen communities in MSW disposal and underscores the role of FWTPs in disseminating airborne pathogens.

Vulnerability of kelp, Ecklonia radiata, to persistent nitrogen pollution and coastal darkening

Coastal darkening is expected to have pervasive impacts on benthic primary producers. However, the effects of nitrogen enrichment, an often-co-occurring stressor, on benthic primary producers and their functions is less clear. This study investigates the interactive effects of coastal darkening and nitrogenous eutrophication, including nitrogen source (NH4+ vs. NO3−), on the function of the kelp Ecklonia radiata. First, an in-situ experiment was used to assess the differential impacts of NH4+ and NO3− pulse enrichment on the photosynthetic performance and pH modulation capacity of E. radiata. Second, a laboratory experiment was used to assess the longer-term impacts of nitrogen enrichment under low-light conditions mimicking coastal darkening on service provisioning, including photosynthetic performance, pH modulation, nutrient uptake and growth. While pulse nitrogen enrichment had no impacts on the photosynthetic performance of E. radiata in-situ, persistent exposure to either NH4+ or NO3− acted as a stressor to sporophytes as indicated by elevated rates of dark respiration and lamina erosion and reduced photosynthetic efficiency and growth rates. Furthermore, low-light conditions elicited reduced photosynthetic capacity at saturating irradiance, which extended to a reduction in the extent of pH modulation, and significantly increased lamina erosion. While the two stressors appeared to act on distinct parameters, ultimately, both darkening and eutrophication directly reduced net primary production, especially when in combination. These results demonstrate the negative interactive effects of coastal darkening and eutrophication on E. radiata function, while suggesting a vulnerability of E. radiata to even moderate levels of persistent nitrogen enrichment. This vulnerability highlights the need to consider environmental conditions during kelp conservation and restoration, and when attempting to valorise kelp ecophysiology for nature-based solutions.

Impact of residential solid fuel usage and fuel conversion on children's lung function.

Solid fuel combustion exposure is a leading global health risk factor, yet evidence on its effects, especially on vulnerable children, is sparse. This large-scale, multi-center prospective study aimed to address this gap by involving 9997 schoolchildren across China between 2013 and 2015. Here we show that lung function levels exhibited a marginally significant decline among children exposed to solid fuel usage. Specifically, FVC and FEV1 decreased by 21.2 mL (95% CI: -15.7, 58.1) and 24.1 mL (-8.4, 56.6), respectively. Additionally, PEF, FEF25 and FEF75 decreased by 25.7 mL/s (-46.5, 98.0), 32.7 mL/s (-42.7, 108.2), and 35.4 mL/s (-5.9, 76.7), respectively. Persistent exposure to solid fuel usage in children led to greater lung damage. Children with allergy history were more susceptible to solid fuel exposure. Our study highlights the adverse impact of solid fuel usage on children and the need to promote clean fuel usage for this vulnerable population.

Neurobehavioral and bioaccumulative toxicity in adult in-vivo zebrafish model due to prolonged cadmium exposure in the presence of ketoprofen.

Increasing industrial activity causes the release of chemical compounds into aquatic habitats, including toxic heavy metals like cadmium and medications like ketoprofen, posing considerable ecological concerns. Although previous studies have shown that cadmium and ketoprofen individually cause cognitive impairment, there is a lack of information on the combined neurological effects of the two substances. We investigated the neurological consequences of persistent cadmium exposure in the presence of ketoprofen on adult zebrafish, providing an essential model for understanding cumulative impacts on vertebrate organisms. Behavioral assessments, bioaccumulation rates, biochemical studies, and histopathological exams were conducted over 42 days in authentic environmental settings. The results of our study show that cadmium (10 µg/L) and ketoprofen (10 and 100 µg/L) at environmentally relevant concentrations had a significant impact on locomotor activity, social interactions, and cognitive responses, indicating cumulative neurotoxicity in co-exposure groups compared to single pollutant groups. Biochemical tests show disturbances in antioxidant defense systems, while histological examinations reveal structural changes in zebrafish brain regions. Ketoprofen influences cadmium accumulation in the brain, underscoring the importance of conducting complete evaluations to understand the intricate interactions between environmental pollutants. This study improves our understanding of the complex interactions between heavy metals and medications, stressing the need to consider combined exposure when assessing the neurological effects on vertebrate models.

Exploring the Role of Deutetrabenazine in the Treatment of Chorea Linked with Huntington's Disease.

This review investigates the efficacy of deutetrabenazine in the management of chorea related to HD. Motor, psychological, and cognitive symptoms characterize HD, a neurodegenerative disease. One prominent movement disorder associated with HD is chorea, which results in uncontrollably jerky movements of the muscles. HD has no known cure; instead, symptom management with a variety of medication options is the main goal. Effective management is essential because chorea has a significant impact on patients' quality of life. Dutetrabenazine is the first deuterated medication to receive approval from the US Food and Drug Administration (FDA) for the therapeutic treatment of chorea in Huntington's disease (HD). Treating chorea associated with HD may benefit from the use of deutetrabenazine. The novel compound deutetrabenazine contains deuterium. It inhibits CYP2D6 metabolism, prolongs the half-lives of active metabolites, and may cause persistent systemic exposure while maintaining significant pharmacological action. Deutetrabenazine decreases the release of monoamines, including dopamine, in the synaptic cleft by inhibiting the VMAT2 vesicular monoamine transporter. For chorea, this mechanism has a therapeutic effect. For the treatment of choreiform movement and tardive dyskinesia in HD, the FDA approved deutetrabenazine in 2017. Here we highlight, Deutetrabenazine as a promising new treatment for Huntington's disease chorea, for patients with chorea, deutetrabenazine offers hope for an enhanced quality of life. To completely understand its effectiveness and potential advantages, additional research is necessary, including direct comparison studies, as a result of the mixed study results.

Autoimmune CD4+ T cells fine-tune TCF1 expression to maintain function and survive persistent antigen exposure during diabetes

Self-reactive Tcells experience chronic antigen exposure but do not exhibit signs of exhaustion. Here, we investigated the mechanisms for sustained, functioning autoimmune CD4+ Tcells despite chronic stimulation. Examination of Tcell priming showed that CD4+ Tcells activated in the absence of infectious signals retained TCF1 expression. At later time points and during blockade of new Tcell recruitment, most islet-infiltrating autoimmune CD4+ Tcells were TCF1+, although expression was reduced on a per Tcell basis. The Tcf7 locus was epigenetically modified in circulating autoimmune CD4+ Tcells, suggesting a pre-programmed de novo methylation of the locus in early stages of autoimmune CD4+ Tcell differentiation. This mirrored the epigenetic profile of recently recruited CD4+CD62L+ Tcells in the pancreas. Collectively, these data reveal a unique environment during autoimmune CD4+ Tcell priming that allows Tcells to fine-tune TCF1 expression and maintain long-term survival and function.

Metabolic Shifts Induced by Helminth Infections and Their Contribution to Stunting in Vulnerable Populations

Aims: to revisit the condition of chronic metabolic shifting caused by immunomodulatory sequence facilitated by helminth infection together with other deteriorating condition such as persistent exposure to infection which contributes to stunting formation. Discussion: During dynamic interaction between active helminth infection and the host, the helminth and its excretory/secretory products induce and arouse the type 2 immune response which drives host tolerance and plays an important role in promoting tissue repair. Helminths also activates M2 Macrophages and induce a metabolic shift, even metabolic reprogramming towards reliance on oxidative phosphorylation, lipid oxidation and amino acid metabolism. Helminth-induced activation and metabolic reprogramming of macrophages precede the improvement in overall whole-body metabolism, denoted by improved insulin sensitivity, body mass in response to high-fat diet and atherogenic index in mammals. Contributions of altered nutrient uptake, adipose tissue function and/or the intestinal microbiota with the ability of helminths to alter metabolic status play a pivotal role in increased metabolism rate and may lead to wasting and even stunting formation. Conclusion: Helminth drives the type 2 immunity and activates its cell line which is responsible for metabolic shifting and reprogramming.

Intersecting impacts: urban noise pollution on sleep quality and mental health outcomes

This study probes the intricate dynamics between urban noise pollution, sleep quality, and mental health, centering on Generation Z-those in their formative years and early adulthood. It aims to illuminate the particular impacts of environmental noise on the well-being of these younger urban dwellers. Through a multidisciplinary lens, the research assesses how persistent urban noise exposure perturbs sleep-a critical factor in psychological health-and fosters stress, anxiety, and depression in this demographic. By integrating objective acoustical measurements with Gen Z's subjective health reports, the methodology quantifies urban noise's influence on sleep and its ripple effects on mental health. Additionally, it evaluates noise mitigation strategies like soundproofing and urban greenery, for their potential to mitigate these adverse outcomes. Mapping the nexus between environmental noise, sleep disturbance, and mental health concerns among Generation Z, the study seeks to enrich understanding and guide interventions for improved urban habitats, better sleep, and enhanced mental well-being, addressing a significant public health issue.

Symbiont community assembly shaped by insecticide exposure and feedback on insecticide resistance of Spodoptera frugiperda

Exploring the mechanism of microbiota assembly and its ecological consequences is crucial for connecting microbiome variation to ecosystem function. However, the influencing factors underlying microbiota assembly in the host-microbe system and their impact on the host phenotype remain unclear. Through investigating the prevalent and worsening ecological phenomenon of insecticide resistance in global agriculture, we found that insecticide exposure significantly changed the gut microbiota assembly patterns of a major agricultural invasive insect pest, Spodoptera frugiperda. The relative importance of various microbiota assembly processes significantly varied with habitat heterogeneity and heterogeneous selection serving as a potential predictor of the host’s insecticide resistance in field populations. Moreover, disturbance of the gut microbiota assembly through antibiotics was revealed to significantly affect the rate and heritability of insecticide resistance evolution, leading to a delay in insecticide resistance evolution in this insect pest. These findings indicate that the gut microbiota assembly process of the insect host is influenced by persistent exposure to habitat conditions, particularly insecticides. This variation in insecticide exposure-related community assembly process subsequently influences the insect host’s insecticide resistance phenotype. This study provides insights into gut microbiota assembly processes from a symbiotic perspective and underscores the significant impact of symbiotic community changes on host phenotypic variation.

Health risk assessment of heavy metals in groundwater sources: carcinogenic and non-carcinogenic evaluation

ABSTRACT Persistent exposure to arsenic, chromium, cadmium, lead, and selenium in drinking water above permissible levels poses significant health risks, including increased incidences of skin, lung, bladder, and kidney cancers. This study evaluated 34 water samples from Rupnagar district, Punjab, for heavy metal content. Health risks were assessed using hazard quotient (HQ) and chronic daily intake metrics. Aluminium concentrations were highest in Block Nurpur Bedi (36.43 mg/L). Arsenic levels in Ropar and Anandpur Sahib were 0.09 and 0.068 mg/L, respectively. Cadmium was highest in Nurpur Bedi (0.041 mg/L). Morinda had the highest selenium concentration (0.0038 mg/L). Lead was detected across all blocks, peaking in Chamkaur Sahib (2.176 mg/L). The HQ exceeded unity in nearly all areas, indicating significant health risks from aluminium, arsenic, and lead. The hazard index was highest in Nurpur Bedi (2.66) for adults. Incremental Life Cancer Risk (ILCR) values indicated a high cancer risk from arsenic, chromium, and lead across all blocks. One-way analysis of variance revealed significant differences among Fe, As, and Al concentrations (p < 0.05). The findings underscore the need for targeted treatment technologies and policies to mitigate heavy metal contamination and its health impacts in Punjab.

PM2.5 exposure disparities persist despite strict vehicle emissions controls in California.

As policymakers increasingly focus on environmental justice, a key question is whether emissions reductions aimed at addressing air quality or climate change can also ameliorate persistent air pollution exposure disparities. We examine evidence from California's aggressive vehicle emissions control policy from 2000 to 2019. We find a 65% reduction in modeled statewide average exposure to PM2.5 from on-road vehicles, yet for people of color and overburdened community residents, relative exposure disparities increased. Light-duty vehicle emissions are the main driver of the exposure and exposure disparity, although smaller contributions from heavy-duty vehicles especially affect some overburdened groups. Our findings suggest that a continued trend of emissions reductions will likely reduce concentrations and absolute disparity but may not reduce relative disparities without greater attention to the systemic factors leading to this disparity.

Applications of mixture methods in epidemiological studies investigating the health impact of persistent organic pollutants exposures: a scoping review.

Persistent organic pollutants (POPs) are environmental chemicals characterized by long half-lives in nature and human bodies, posing significant health risks. The concept of the exposome, encompassing all lifetime environmental exposures, underscores the importance of studying POP as mixtures rather than in isolation. The increasing body of evidence on the health impacts of POP mixtures necessitates the proper application of statisticalmethods. We aimed to summarize studies on the overall effects of POP mixtures, identify patterns in applications of mixture methods-statistical methods for investigating the association of mixtures-and highlight current challenges in synthesizing epidemiologic evidence of POP mixtures on health effects as illustrated through a case study. We conducted a systematic literature search on PubMed and Embase for epidemiological studies published between January 2011 and April 2023. We included 240 studies that met our eligibility criteria. 126 studies focused on per- and polyfluoroalkyl substances (PFAS) mixtures only, while 40 analyzed three or more classes of POPs in mixture analyses. We identified 23 unique mixture methods used to estimate the overall effects of POP mixtures, with Bayesian Kernel Machine Regression (BKMR), a type of response-surface modeling, being the most common. Additionally, 22.9% of studies used a combination of methods, including response-surface modeling, index modeling, dimension reduction, and latent variable models. The most extensively explored health outcome category was body weight and birth sizes (n = 43), and neurological outcomes (n = 41). In the case study of PFAS mixtures and birth weight, 12 studies showed negative associations, while 4 showed null results, and 2 showed positive associations. This scoping review consolidates the existing literature on the overall effects of POP mixtures using statistical methods. By providing a comprehensive overview, our study illuminates the present landscape of knowledge in this field and underscores the methodological hurdles prevalent in epidemiological studies focused on POP mixtures. Through this analysis, we aim to steer future research directions, fostering a more nuanced comprehension of the intricate dynamics involved in assessing the health effects of POP mixtures. Our work stands as a significant contribution to the ongoing exploration of the chemicalexposome.

Long-term persistent exposure to cigarette smoke induces AhR driven corneal endothelial dysfunction in mice

Epidemiological studies show cigarette smoking enhances corneal endothelial dysfunction, but mechanisms remain unclear. Our study reveals that prolonged smoke exposure activates the aryl hydrocarbon receptor (AhR), increasing CYP1B1 expression and accelerating senescence and fibrosis in corneal endothelium, potentially reflecting adaptive responses to maintain corneal resilience. Although these molecular modifications indicate early endothelial dysfunction, no pathological changes were observed. The findings indicate that while chronic cigarette smoke exposure triggers initial molecular alterations and endothelial dysfunction, the progression to Fuchs endothelial corneal dystrophy likely requires additional environmental or genetic factors beyond smoke exposure alone.

The Prevalence of Self-Reported Systemic Allergic Reaction to Hymenoptera Venom in Beekeepers Worldwide: A Systematic Literature Review and Meta-Analysis.

Beekeepers represent a high-allergic risk population group due to their unavoidable seasonal or persistent exposure to the elicitors of Hymenoptera venom allergy, bees in particular. A systematic literature review and meta-analysis aimed to estimate the prevalence of self-reported systemic allergic reaction to Hymenoptera venom among beekeepers worldwide. We rigorously reviewed and conducted meta-analysis on observational studies retrieved from seven electronic databases (MEDLINE via PubMed, Web of Science Core Collection, Scopus, Academic Search Complete, ScienceDirect, Cumulative Index to Nursing and Allied Health Literature, Zoological Record), spanning data from inception to August 1, 2023. The Joanna Briggs Institute Prevalence Critical Appraisal Tool was employed to assess the risk of bias. A meta-analysis was conducted to synthesize evidence. Out of 468 studies, eight original articles met the inclusion criteria. The estimated overall lifetime and one-year prevalence of self-reported systemic allergic reaction to bee venom were 23.7% (95% CI: 7.7-53.4) and 7.3% (95% CI: 5.8-9.2), respectively. The estimated lifetime prevalence of self-reported systemic allergic reaction to bee venom for grades III-IV (severe systemic allergic reaction) was 6.0% (95% CI: 3.0-11.7). In general, substantial heterogeneity and a high risk of bias were observed across the majority of studies. The impact of geographical location and climate differences on the estimated lifetime prevalence is suggestive for severe systemic allergic reaction. Future observational cross-sectional studies should employ rigorous study designs, using validated questionnaires, and thoroughly report the observed health outcomes, verified by physicians.

Navigating Mental Health Challenges in Conflict Zones: A Mixed Method Literature Review

According to the World Mental Health Report (2022), 22% of the population living in conflict-afflicted areas have mental health disorders, including anxiety, depression, and Post-Traumatic Stress Disorder (PTSD). Mental health disorders are one of the most serious and underrepresented effects of surviving in conflict-afflicted areas. To investigate the prevalence of mental health disorders and potential risk factors that impact individuals residing in conflict regions and explore their lived experiences. A mixed-method literature review of the studies was conducted between January 2015 to August 2024. It combined substantial evidence from 15 quantitative (n=8) and qualitative (n=6) studies that were exposed to large-scale conflicts in the past ten years. The data was gathered through a range of databases (Google Scholar, Scopus, PubMed, PsycINFO. Initially, 187 studies were identified, and 51 remained after screening. In total, 15 studies met the inclusion and exclusion criteria. The results suggested that individuals in conflicted areas have a high prevalence of severe mental health disorders like PTSD, anxiety, and depression. Moreover, some risk factors that contributed were persistent exposure to violence, loss of livelihood, and displacement. Consequently, religious and psychosocial coping mechanisms did provide some relief. However, these mechanisms dominated the treatment-seeking decisions and prevented individuals from opting for biomedical healthcare practices. Conclusion: This review highlighted the need for a multidisciplinary approach to curb these areas' growing mental health imbalance. In addition to being a humanitarian right and necessity, providing adequate mental health facilities is a vital component of rebuilding and recovering the affected communities.