Effects Of Social Stress Research Articles

Exploring the effects of adolescent social isolation stress on the serotonin system and ethanol-motivated behaviors.

Alcohol is one of the most frequently used drugs of abuse and has a major impact on human health worldwide. People assigned female at birth and those with adverse childhood experiences are stress-vulnerable and more likely to report drinking as a means of "self-medication." Prior studies in our laboratory showed that adolescent social isolation stress (SIS) increases vulnerability to ethanol (EtOH) intake and consumption despite negative consequences in female rats. Here, we explored modulation of the dorsal raphe nucleus (DRN)-serotonin (5-HT) system, a sexually dimorphic neurotransmitter system involved in stress-reward interactions, to determine its contribution to EtOH-motivated behaviors in rats that have undergone SIS. We employed electrophysiological and functional neuroanatomy strategies to show that both SIS and EtOH exposure induce persistent hypofunction of the DRN 5-HT system, particularly in females. Chemogenetic activation of DRN 5-HT neurons attenuated reward value for both EtOH and sucrose and elevated punished responding for EtOH in a stress-dependent manner. Our results highlight an inverse relationship between EtOH consumption and the 5-HT system, the sex- and stress-dependent nature of this relationship, and a connection between DRN 5-HT signaling and acute responding to rewards and punishment. These data support the DRN 5-HT system as a potential target to treat aberrant alcohol consumption and drinking despite negative consequences in stress-vulnerable populations.

Effect of antidepressants and social defeat stress on the activity of dorsal raphe serotonin neurons in free-moving animals.

Major depressive disorder (MDD) is among the most common mental disorders worldwide and is characterized by dysregulated reward processing associated with anhedonia. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for MDD; however, their onset of action is delayed. Recent reports have shown that serotonin neurons in the dorsal raphe nucleus (DRN) are activated by rewards and play a vital role in reward processing. However, whether antidepressant treatment affects the DRN serotonin neuronal response to rewards in awake animals remains unknown. In this study, we measured the activity of DRN serotonin neurons in awake mice and determined the effects of antidepressants and chronic stress on DRN serotonin neuronal activity. We found that acute treatment with citalopram, an SSRI, significantly decreased sucrose-induced activation of DRN serotonin neurons. The decrease in response to acute citalopram treatment was attenuated by chronic citalopram treatment. Acute treatment with (S)-WAY100135, a 5-HT1A receptor antagonist, dose-dependently inhibited the response to acute citalopram treatment. These results indicate that autoinhibition by activating 5-HT1A receptors via acute SSRI treatment may blunt the reward response, which can be recovered after chronic SSRI treatment.

Effect of Social Overcrowding and Isolation Stress on Alloxan-Induced Diabetic Male Albino Rats

Effect of Social Overcrowding and Isolation Stress on Alloxan-Induced Diabetic Male Albino Rats

Astrocyte-derived exosomes regulate sperm miR-34c levels to mediate the transgenerational effects of paternal chronic social instability stress

ABSTRACT The effects of chronically stressing male mice can be transmitted across generations by stress-specific changes in their sperm miRNA content, which induce stress-specific phenotypes in their offspring. However, how each stress paradigm alters the levels of distinct sets of sperm miRNAs is not known. We showed previously that exposure of male mice to chronic social instability (CSI) stress results in elevated anxiety and reduced sociability specifically in their female offspring across multiple generations because it reduces miR-34c levels in sperm of stressed males and their unstressed male offspring. Here, we describe evidence that astrocyte-derived exosomes (A-Exos) carrying miR-34c mediate how CSI stress has this transgenerational effect on sperm. We found that CSI stress decreases miR-34c carried by A-Exos in the prefrontal cortex and amygdala, as well as in the blood of males. Importantly, miR-34c A-Exos levels are also reduced in these tissues in their F1 male offspring, who despite not being exposed to stress, exhibit reduced sperm miR-34c levels and transmit the same stress-associated traits to their male and female offspring. Furthermore, restoring A-Exos miR-34c content in the blood of CSI-stressed males by intravenous injection of miR-34c-containing A-Exos restores miR-34c levels in their sperm. These findings reveal an unexpected role for A-Exos in maintaining sperm miR-34c levels by a process that when suppressed by CSI stress mediates this example of transgenerational epigenetic inheritance.

Repeated social stress increases posterior medial amygdala neuronal activity in stress-susceptible adult male rats.

The medial amygdala (MeA) is activated by social stimuli and manipulations of the MeA disrupt a wide range of social behaviors. Social stress can shift social behaviors and may accomplish this partly via effects on the MeA. However, very little is known about the effects of social stress on the electrophysiological activity of MeA neurons. The posterior division of the MeA (MeAp) has been implicated in driving social engagement. We hypothesized that repeated social stress would cause parallel changes in in vivo activity of MeAp neurons and social behavior. The resident-intruder paradigm was used to produce a repeated social stress in adult male rats. After repeated social stress, MeAp neurons were recorded with in vivo single-unit electrophysiology in anesthetized rats. MeAp neurons, specifically those in the posterodorsal subnucleus (MeApd), fired faster in stressed rats than controls, and this effect was directly associated with stressor intensity. The MeAp sends dense projections to the posterior bed nucleus of stria terminalis (pBNST) and ventromedial hypothalamus (VMH), and both regions are essential for social engagement and are sensitive to social stressors. MeAp projections to pBNST had higher activity after stress, while projections to the VMH were not affected. These effects were significant only in rats that displayed susceptibility to this social stressor, as demonstrated by lower weight gain. Furthermore, the effect of stress on MeApd and MeAp-pBNST neuronal firing was correlated with lower social interaction. These results indicate that heightened MeApd and MeA-pBNST activity may contribute to alterations in social behaviors following social stress.

The relationship of neuroticism to individual differences in the dynamics of brain activity during social interactions

Social interactions in the context of cooperation and competition are the most important type of activity of people, determining their well-being and success in life. The neural bases of this activity, as well as the role of personality-related individual differences, are insufficiently studied. In particular, the literature lacks data on the relationship between neuroticism and individual differences in brain activity during cooperative and competitive interactions, and the aim of our work was to fill this gap. fMRI data were recorded during task performance in individual, cooperative, and competitive modes and analyzed using the inter-subject representative similarity analysis. The results indicate that in emotionally instable individuals, social interactions, in both cooperative and competitive contexts, are associated with greater strain, manifested in the activity of social brain, emotion regulation, and attentional centers. This can potentially lead to the accumulation of the effects of social stress and the emergence of symptoms of mental health problems.

Chronic social stress induces p16-mediated senescent cell accumulation in mice.

Life stress can shorten lifespan and increase risk for aging-related diseases, but the biology underlying this phenomenon remains unclear. Here we assessed the effect of chronic stress on cellular senescence-a hallmark of aging. Exposure to restraint stress, a psychological non-social stress model, increased p21Cip1 exclusively in the brains of male, but not female mice, and in a p16Ink4a-independent manner. Conversely, exposure to chronic subordination stress (only males were tested) increased key senescent cell markers in peripheral blood mononuclear cells, adipose tissue and brain, in a p16Ink4a-dependent manner. p16Ink4a-positive cells in the brain of chronic subordination stress-exposed mice were primarily hippocampal and cortical neurons with evidence of DNA damage that could be reduced by p16Ink4a cell clearance. Clearance of p16Ink4a-positive cells was not sufficient to ameliorate the adverse effects of social stress on measured metrics of healthspan. Overall, our findings indicate that social stress induces an organ-specific and p16Ink4a-dependent accumulation of senescent cells, illuminating a fundamental way by which the social environment can contribute to aging.

BLAKOR inputs to the BNST regulate social stress-escalated alcohol consumption.

Aversive social experiences can lead to escalated drug consumption and increase the risk of relapse to drug seeking. Individuals who consume alcohol to alleviate the effects of social stress are more likely to develop an alcohol use disorder (AUD). Repeated social defeat stress (SDS) enhances the rewarding and reinforcing effects of alcohol. However, the neural mechanisms that underlie social stress-escalated alcohol drinking are not well understood. Here we explored the role of the dynorphin/kappa opioid receptor (Dyn/KOR) system in regulating social stress-escalated alcohol consumption. Male and female mice were subjected to repeated SDS for 10 days following which they were left undisturbed in their home cages. They were then subject to intermittent access (IA) two-bottle choice alcohol consumption procedure. The effects of systemic and BNST-specific KOR antagonism using the selective KOR antagonist NorBNI on stress-escalated drinking were evaluated. Using chemogenetic approaches in Oprk1-Cre mice, we examined the role of KOR expressing cells in the basolateral amygdala (BLAKORs) and BLAKOR-BNST pathway in social stress-escalated alcohol consumption. Repeated SDS increased alcohol consumption and preference in both males and females. Systemic KOR antagonism attenuated SDS-escalated alcohol consumption in both males and females. BNST -specific KOR antagonism also attenuated stress-escalated drinking in males. Finally, selective chemogenetic activation of BLAKORs and BKAKOR-BNST pathway attenuated social stress-escalated alcohol consumption in both sexes. Our results suggest a significant role for BLAKOR projections to the BNST in regulating social stress-escalated alcohol consumption. Our results provide further evidence that the Dyn/KOR system maybe a viable target for medications development to tareat comorbid stress and AUD.

Crocin has a greater therapeutic role in the restoration of behavioral impairments caused by maternal social isolation in adolescent than in adult offspring probably through GSK-3beta downregulation

Parental stress drastically impairs cognitive and behavioral functions of the offspring. Social isolation, as one of the most stressful conditions for social animals including rats induces a wide range of destructive effects on behavioral functions. On the other hand, Crocin (active component of Crocus sativa) induces pro-cognitive and neuroprotective effects. In the present study, we aimed to investigate the effects of prolonged maternal social isolation (pre-gestational) and crocin treatment on cognitive and behavioral functions in both adolescent and adult offspring. Female adult rats (mothers) were socially isolated from PND 30 to PND 80 (50 days). The treatment was performed by intraperitoneal injections of crocin (10, 30, and 50 mg/kg) during PND 39–45 or PND 59–65 (7 consecutive days), in the rat offspring. Behavioral assessments were done when the offspring were on PND 45 (adolescent) or PND 65 (adult). The expression level of Glycogen synthase kinase-3 beta (GSK-3beta) in the hippocampus was measured using real-time PCR. The results showed maternal social isolation decreased locomotion and impaired memory in adolescents, and increased anxiety- and depressive-like behaviors and GSK-3beta level, and decreased pain threshold in both adolescents and adults. Crocin (30 and 50 mg/kg) restored or attenuated the effect of maternal social isolation on behavioral functions and GSK-3beta in adolescents and adults, with more effect in adolescents. In conclusion, we showed that crocin treatment can restore the destructive effects of maternal social isolation stress in the offspring, with stronger therapeutic effects in adolescents. Also, GSK-3beta downregulation may underlie the beneficial effects of crocin.

Lasting effects of adolescent social instability stress on dendritic morphology in the nucleus accumbens in female and male Long Evans rats

Social instability stress (SS) in adolescence in rats leads to long-lasting changes in social behaviour and reward-related behaviour relative to control rats. Given the role of the nucleus accumbens (NAc) in such behaviours, we investigated the morphology of medium spiny neurons (MSNs), which are most neurons in the NAc, in adult female and male rats exposed to SS in adolescence. Irrespective of sex, SS rats had increased number of dendritic spines in both the core and shell regions of the NAc (2.3 % and 18.1 % increase, respectively). In the core, SS rats had a 16 % reduction in the total dendritic lengths of MSNs, whereas in the shell, SS rats had a greater dendritic length closer to the soma, and particularly in SS female rats, whereas the opposite was found farther from the soma (SS 10.6 % > CTL overall). Although the extent to which such structural changes may underlie the enduring effects of SS in adolescence requires investigation, the results add to evidence that changes to the social environment in adolescence can determine adult neuronal structural.

Togetherness Reminded by the Earthquake: Relationship Between Stress and Peptic Ulcer Perforation

Background: Severe stress is one of the leading causes of peptic ulcer perforations. Peptic ulcer perfora-tion is a clinical condition that can be fatal if not treated urgently. This study aimed to investigate the effects of social stress caused by the earthquakes in Kahramanmaraş on peptic ulcer perforation. Materials and Methods: A retrospective evaluation was conducted on 66 peptic ulcer perforation cases operated on in three major centers in Şanlıurfa, considering two large earthquakes that occurred on February 6, 2023, and by comparing the 6-month periods before and after the earthquakes. Patients were assessed in terms of age, gender, diagnostic method, perforation site, surgical technique, operation time, length of hospital stay, and mortality. Our study also evaluated laboratory parameters such as white blood cell (WBC) count, hemoglobin, urea, creatinine, and albumin levels. Results: In the 6 months prior to the earthquakes, 21 patients underwent surgery for peptic ulcer perfo-ration, whereas 45 patients were operated on for the same reason in the 6 months following the earthquakes; there were two deaths in each group. The number of patients operated on after the earthquakes was significantly higher than the number of patients operated on before the earthquakes. Furthermore, the two groups were also compared in terms of demographic data and laboratory findings; no significant differences between the two groups were observed regarding these parameters. Conclusions: Stress plays a remarkable role in the development of peptic ulcer perforation. In stressful situations that affect the general population, such as earthquakes, it is essential to assess stress tenden-cies and dyspeptic complaints in patients presenting to the hospital. Patients with positive findings should undergo endoscopy if necessary, followed by appropriate gastric treatment.

6579 Neuroendocrine Signatures of Social-Defeated Stress Expressed by Adrenal Hormones in Mice

Abstract Disclosure: J. Noh: None. J. Choi: None. S. Myung: None. M. Kim: None. M. Choi: None. While psychological stress is one of the prevalent contributors to depression, the precise role of metabolic phenotypes in the development of depression remains elusive. Abnormality in hypothalamus-pituitary-adrenal (HPA) axis is a classical feature of depression. Here, an animal model of social defeat stress (SDS) was established with five-week-old C57BL/6J mice to repeated episodes of social defeat for a period of 10 days, facilitated by an aggressive CD-1 mouse. Liquid chromatography-mass spectrometry-based profiling of 29 adrenocortical steroids and 6 medullary amines was employed for serum samples collected at 3, 5, 7, and 10 days during the modeling from both control (n = 28) and SDS (n = 32) group. In response to initial stress, corticosterone (B) and its two precursors were significantly increased (p < 0.03 for all) during 3 days, while 18-hydroxyB was remarkably elevated (p < 0.003 for 3 days and p < 0.005) in SDS mice. In contrast, dopamine (p < 0.03) and metanephrine (p < 0.008) were significantly increased during 5 days in SDS mice, while remarkably higher levels of norepinephrine were also observed during 7 days (p < 0.01). The SDS mice showed the increased levels of normetanephrine for all days of repeated stress exposure (p < 0.002 for all, except 10 days of p < 0.02). In this study, the HPA regulated negative feedback in short period, whereas sympathetic nervous system was continuously stimulated during repeated stress exposure. The present study may provide insight into the neuroendocrine effects of social stress on allostatic overload. Presentation: 6/2/2024

Nighttime-specific differential gene expression in suprachiasmatic nucleus and habenula is associated with resilience to chronic social stress

The molecular mechanisms that link stress and biological rhythms still remain unclear. The habenula (Hb) is a key brain region involved in regulating diverse types of emotion-related behaviours while the suprachiasmatic nucleus (SCN) is the body’s central clock. To investigate the effects of chronic social stress on transcription patterns, we performed gene expression analysis in the Hb and SCN of stress-naïve and stress-exposed mice. Our analysis revealed a large number of differentially expressed genes and enrichment of synaptic and cell signalling pathways between resilient and stress-naïve mice at zeitgeber 16 (ZT16) in both the Hb and SCN. This transcriptomic signature was nighttime-specific and observed only in stress-resilient mice. In contrast, there were relatively few differences between the stress-susceptible and stress-naïve groups across time points. Our results reinforce the functional link between circadian gene expression patterns and differential responses to stress, thereby highlighting the importance of temporal expression patterns in homoeostatic stress responses.

Effects of chronic social defeat stress on social behavior and cognitive flexibility for early and late adolescent

This study investigated the risk to social behavior and cognitive flexibility induced by chronic social defeat stress (CSDS) during early and late adolescence (EA and LA). Utilizing the “resident-intruder” stress paradigm, adolescent male Sprague-Dawley rats were exposed to CSDS during either EA (postnatal days 29–38) or LA (postnatal days 39–48) to explore how social defeat at different stages of adolescence affects behavioral and cognitive symptoms commonly associated with psychiatric disorders. After stress exposure, the rats were assessed for anxiety-like behavior in the elevated plus maze, social interaction, and cognitive flexibility through set-shifting and reversal-learning tasks under immediate and delayed reward conditions. The results showed that CSDS during EA, but not LA, led to impaired cognitive flexibility in adulthood, as evidenced by increased perseverative and regressive errors in the set-shifting and reversal-learning tasks, particularly under the delayed reward condition. This suggests that the timing of stress exposure during development has a significant impact on the long-term consequences for behavioral and cognitive function. The findings highlight the vulnerability of the prefrontal cortex, which undergoes critical maturation during early adolescence, to the effects of social stress. Overall, this study demonstrates that the timing of social stressors during adolescence can differentially shape the developmental trajectory of cognitive flexibility, with important implications for understanding the link between childhood/adolescent adversity and the emergence of psychiatric disorders.

Astrocyte-Derived Exosomes Regulate Sperm miR-34c Levels to Mediate the Transgenerational Effects of Paternal Chronic Social Instability Stress.

The effects of chronically stressing male mice can be transmitted across generations by stress-specific changes in their sperm miRNA content that induce stress-specific phenotypes in their offspring. But how each stress paradigm alters the levels of distinct sets of sperm miRNAs is not known. We showed previously that exposure of male mice to chronic social instability (CSI) stress results in elevated anxiety and reduced sociability specifically in their female offspring across multiple generations because it reduces miR-34c levels in sperm of stressed males and their unstressed male offspring. Here we describe evidence that a strocyte-derived exos omes ( A-Exos ) carrying miR-34c mediate how CSI stress has this transgenerational effect on sperm. We found that CSI stress decreases miR-34c carried by A-Exos in the prefrontal cortex and amygdala, as well as in the blood of males. Importantly, miR-34c A-Exos levels are also reduced in these tissues in their F1 male offspring, who despite not being exposed to stress exhibit reduced sperm miR-34c levels and transmit the same stress-associated traits to their male and female offspring. Furthermore, restoring A-Exos miR-34c content in the blood of CSI-stressed males by intravenous injection of miR-34c-containing A-Exos restores miR-34c levels in their sperm. These findings reveal an unexpected role for A-Exos in maintaining sperm miR-34c levels by a process that when suppressed by CSI stress mediates this example of transgenerational epigenetic inheritance.

Social interactions of dairy cows and their association with milk yield and somatic cell count

The social environment experienced by livestock can have implications for their health, welfare, and subsequently, their productivity. Changes in the dairy industry have led to larger herd sizes and altered management of cows, which has impacted their social environment. Studies have shown that mixing of animals can lead to social instability of groups and expansion of herds can lead to high stocking densities resulting in social stress and negative effects on production. Yet few studies have assessed the putative impact of positive cow-cow interactions, such as proximity to preferred herd mates and engaging in grooming, on milk production and udder health. To address this, we used cattle proximity as a proxy for affiliative interactions between cows in three dairy herds in south-west England over one week study periods. We created proximity networks of dairy cows and measured cow-cow associations according to milk yield, somatic cell count (SCC; an indicator of mastitis), parity (number of lactations in the cow’s lifetime), and lactation stage (grouped by days in milk for current lactation). We then assessed associations between social factors and production and health measures (milk yield and SCC). In all three herds, cows interacted more with cows in the same parity, suggesting early social bonding may be evident later in life and that grouping animals in terms of parity might encourage affiliative interactions. Cows did not associate according to milk yield, SCC, or lactation stage. There was no significant association between milk production or SCC and the total time spent in social contact with other cows, the mean time spent with the four closest herd mates, or the number of closest herd mates of the same parity. We suggest that further research on positive social environments for dairy cattle is warranted in the interests of improving welfare and enabling a more robust assessment of the putative effects on production and health parameters

Effects of social dominance and acute social stress on morphology of microglia and structural integrity of the medial prefrontal cortex

Chronic stress increases activity of the brain’s innate immune system and impairs function of the medial prefrontal cortex (mPFC). However, whether acute stress triggers similar neuroimmune mechanisms is poorly understood. Across four studies, we used a Syrian hamster model to investigate whether acute stress drives changes in mPFC microglia in a time-, subregion-, and social status-dependent manner. We found that acute social defeat increased expression of ionized calcium binding adapter molecule 1 (Iba1) in the infralimbic (IL) and prelimbic (PL) and altered the morphology Iba1+ cells 1, 2, and 7 days after social defeat. We also investigated whether acute defeat induced tissue degeneration and reductions of synaptic plasticity 2 days post-defeat. We found that while social defeat increased deposition of cellular debris and reduced synaptophysin immunoreactivity in the PL and IL, treatment with minocycline protected against these cellular changes. Finally, we tested whether a reduced conditioned defeat response in dominant compared to subordinate hamsters was associated with changes in microglia reactivity in the IL and PL. We found that while subordinate hamsters and those without an established dominance relationships showed defeat-induced changes in morphology of Iba1+ cells and cellular degeneration, dominant hamsters showed resistance to these effects of social defeat. Taken together, these findings indicate that acute social defeat alters microglial morphology, increases markers of tissue degradation, and impairs structural integrity in the IL and PL, and that experience winning competitive interactions can specifically protect the IL and reduce stress vulnerability.

Dimethyl Fumarate Prevents the Development of Chronic Social Stress-Induced Hypertension in Borderline Hypertensive Rats.

This study investigated the effects of chronic crowding-induced social stress and dimethyl fumarate (DMF) on borderline hypertensive rats, focusing on the transcription nuclear factor (erythroid-derived 2)-like 2 (NRF2) gene Nfe2l2, on the expression of selected NFR2-mediated gene expressions in the heart, and on vascular function. Rats were exposed to chronic crowding, DMF treatment (30 mg/kg/day, p.o.), or a combination of both for six weeks. Blood pressure (BP) was measured non-invasively, gene expressions were analysed using RT-qPCR, and vascular function was assessed by measuring noradrenaline (NA)-induced vasoconstriction and endothelium-dependent and -independent relaxations in the femoral arteries using a wire myograph. Chronic stress increased BP, Nfe2l2 expression, and NA-induced vasoconstriction, though it did not affect relaxation responses nor the left heart ventricle-to-body weight (LHV/BW) ratio. DMF elevated Nfe2l2 expression (as the main effect) in the heart but did not alter BP and vascular functions vs. control when administered alone. Interestingly, DMF increased the LHV/BW ratio, supposedly due to reductive stress induced by continuous NRF2 activation. When combined with stress, DMF treatment prevented stress-induced hypertension and mitigated NA-induced vasoconstriction without altering relaxation functions. In addition, the combination of stress and DMF increased Tnf and Nos2 expression and the expressions of several genes involved in iron metabolism. In conclusion, these findings suggest that DMF can prevent chronic stress-induced hypertension by reducing vascular contractility. Moreover, DMF itself may produce reductive stress in the heart and induce inflammation when combined with stress. This indicates a need for the careful consideration of long-term DMF treatment considering its impact on the heart.

Keep me posted, but don’t stress me out: how the positive effect of social networking services on civil servants’ information use and political capacities can be attenuated by social media stress

Public policy and administration debates typically assume that ICT tools, including social networking services (SNS), increase the amount of information that is communicated and thus harnessed for policymaking processes. At the same time, behavioral approaches point to the potentially detrimental effects of social media stress resulting from an overexposure to SNS. Because systematic research on the individual-level effects of SNS in policy formulation is rare, this paper explores the effect of SNS on the use of policy-relevant information and, thus, on individual political capacities. A moderated mediation analysis was performed based on survey data from central ministerial bureaucracies in Germany, Italy, and Norway, considering not only the amount of information utilized in legislative drafting but also the variability and concentration of the information sources. The results indicate that SNS positively relate to policy officials’ information use, which, in turn, increases their self-reported political capacities. However, the positive relationship between SNS and both the amount and the variability of information use was found to be diminished when levels of social media stress are high rather than low. The conclusions discuss the implications for civil servants and policymaking.

Social and environmental stressors of cardiometabolic health

Exposures to social and environmental stressors arise individual behavioural response and thus indirectly affect cardiometabolic health. The aim of this study was to investigate several social and environmental stressors and the paths of their influence on cardiometabolic health. The data of 2154 participants (aged 25–64 years) from the cross-sectional population-based study were analysed. The composite score of metabolic disorders (MS score) was calculated based on 5 biomarkers: waist circumference, blood pressure, fasting blood glucose, HDL-cholesterol, triglycerides. The effects of social stressors (education level, income), environmental stressors (NO2, noise) and behavioural factors (unhealthy diet, smoking, alcohol consumption, sedentary behaviours) on MS score were assessed using a structural model. We observed a direct effect of education on MS score, as well as an indirect effect mediated via an unhealthy diet, smoking, and sedentary behaviours. We also observed a significant indirect effect of income via sedentary behaviours. The only environmental stressor predicting MS was noise, which also mediated the effect of education. In summary, the effect of social stressors on the development of cardiometabolic risk had a higher magnitude than the effect of the assessed environmental factors. Social stressors lead to an individual’s unhealthy behaviour and might predispose individuals to higher levels of environmental stressors exposures.