Associations of adverse childhood experiences with smoking initiation in adolescence and persistence in adulthood, and the role of the childhood environment: Findings from the 1958 British birth cohort.

Adverse childhood experiences (ACEs) have been identified as a strong determinant of smoking. We aimed to examine the association between ACEs and early smoking initiation and subsequent persistence and the contribution of five pathways including family factors, parental involvement, material living conditions, social activities and conscientiousness. Data are from 7414 individuals born in 1958 in Great Britain included in the National Child Development Study. ACEs were measured at ages 7, 11, and 16. Smoking initiation was derived from smoking variables from ages 16 to 42 and persistent smoking was derived from smoking variables from ages 23 to 42. We modelled the relationship between ACEs and smoking, and further assessed the contribution of each pathway using multinomial logistic regressions. During childhood, 20.9% of respondents experienced one ACE and 6.4% two or more. Those who experienced ACEs had a higher risk of initiating smoking by age 16 and of persistent smoking (RRR initiation by 16y = 1.89 [1.62; 2.20] for one ACE; RRR initiation by 16y = 2.36 [1.81; 3.08] for two or more ACEs, and RRR persistent smoking = 2.07 [1.73; 2.47] for one ACE, RRR persistent smoking = 2.59 [1.92; 3.49] for two or more ACEs). The factors that contributed most to explaining these associations were parental smoking, sibling order and conscientiousness. ACEs remained associated with persistent smoking after further adjusting for young adulthood variables. Smoking prevention measures may need to be tailored when considering adolescents from communities where ACEs are more prevalent to curtail initiation, intensity and persistence. FUNDING: This work was supported by the Institut National du Cancer & the Institut de recherche en santé publique (grant agreement: No. [2019-204]).

Cocaine and chronic stress exposure produce an additive increase in neuronal activity in the basolateral amygdala.

Cocaine addiction is a chronic, relapsing disorder. Stress and cues related to cocaine are two common relapse triggers. We have recently shown that exposure to repeated restraint stress during early withdrawal accelerates the time-dependent intensification or "incubation" of cue-induced cocaine craving that occurs during the first month of withdrawal, although craving ultimately plateaus at the same level observed in controls. These data indicate that chronic stress exposure during early withdrawal may result in increased vulnerability to cue-induced relapse during this period. Previous studies have shown that chronic stress exposure in drug-naïve rats increases neuronal activity in the basolateral amygdala (BLA), a region critical for behavioral responses to stress. Given that glutamatergic projections from the BLA to the nucleus accumbens are critical for the incubation of cue-induced cocaine craving, we hypothesized that cocaine withdrawal and chronic stress exposure produce separate increases that additively increase BLA neuronal activity. To assess this, we conducted in vivo extracellular single-unit recordings from the BLA of anesthetized adult male rats following cocaine or saline self-administration (6 h/day for 10 days) and repeated restraint stress or control conditions on withdrawal days (WD) 6-14. Recordings were conducted from WD15 to WD20. Interestingly, cocaine exposure alone increased the spontaneous firing rate in the BLA to levels observed following chronic stress exposure in drug-naïve rats. Chronic stress exposure during cocaine withdrawal further increased firing rate. These studies may identify a potential mechanism by which both cocaine and chronic stress exposure drive cue-induced relapse vulnerability during abstinence.

Preconception paternal mental disorders and child health: Mechanisms and interventions.

Mental illness is a significant global health issue with a steady prevalence. High heritability is suspected, but genome-wide association studies only identified a small number of risk genes associated with mental disorders. This 'missing inheritance' can be partially explained by epigenetic heredity. Evidence from numerous animal models and human studies supports the possibility that preconception paternal mental health influences their offspring's mental health via nongenetic means. Here, we review two potential pathways, including sperm epigenetics and seminal plasma components. The current review highlights the role of sperm epigenetics and explores epigenetic message origination and susceptibility to chronic stress. Meanwhile, possible spatiotemporal windows and events that induce sexually dimorphic modes and effects of paternal stress transmission are inferred in this review. Additionally, we discuss emerging interventions that could potentially block the intergenerational transmission of paternal psychiatric disorders and reduce the incidence of mental illness. Understanding the underlying mechanisms by which preconception paternal stress impacts offspring health is critical for identifying strategies supporting healthy development and successfully controlling the prevalence of mental illness.

Impact on pregnancy outcomes of exposure to military stress during the first or second trimester as compared with the third trimester.

OBJECTIVE: To compare pregnancy outcomes after exposure to military stress in different trimesters of pregnancy. METHODS: A retrospective study of medical records of deliveries in the Wolfson (WMC) and Barzilai (BMC) medical centers in Israel between July 2014 and April 2015. All parturients were exposed to military stress for 51 days during pregnancy. Pregnancy outcomes were compared between those exposed to military stress in the first or second trimester, and those exposed in the third trimester. Outcomes were also compared between WMC (a new-onset military stress exposure area) and BMC (a chronic military stress exposure area). RESULTS: At WMC, women exposed in the first or second trimester (n=2657) had a higher rate of preterm delivery (<37 weeks) as compared with those exposed in the third trimester (n=2037; 214 [8.1%] vs 121 [5.9%]; P=0.005). At BMC, women exposed in the first or second trimester (n=2208) had a tendency toward lower rates of diabetes mellitus (P=0.055) and macrosomia [103 (4.7%) vs 84 (6.3%); P=0.037], as compared with those exposed in the third trimester (n=1337). CONCLUSION: Exposure to military stress during pregnancy had different impacts on pregnancy outcomes, depending on the time of exposure and whether continuous exposure to stress occurred.

The mediating role of hippocampal networks on stress regulation in amnestic mild cognitive impairment.

OBJECTIVES: To examine the role of the hippocampus in stress regulation in older adults with amnestic mild cognitive impairment (aMCI). METHODS: This study combined resting-state functional MRI, structural MRI, self-reported chronic stress exposure, and an electrocardiography-based acute stress protocol to compare aMCI group (n = 17) to their cognitively healthy counterparts (HC, n = 22). RESULTS: For the entire sample, there was a positive correlation between chronic stress exposure and acute stress regulation. The aMCI group showed significantly smaller volumes in the right hippocampus than HC. The two groups did not differ in chronic stress exposure or acute stress regulation. In the HC group, the left hippocampal connectivity with inferior parietal lobe was significantly correlated with both the chronic stress and acute stress. In the aMCI group, the left hippocampal connectivity with both the right insula and the left precentral gyrus was significantly correlated to chronic stress exposure and acute stress regulation. Additionally, the left hippocampal connectivity with right insula significantly mediated the relationship between chronic stress exposure and acute stress regulation in aMCI group. CONCLUSIONS: Extra hippocampal networks may be recruited as compensation to attend the maintenance of relatively normal stress regulation in aMCI by alleviating the detrimental effects of chronic stress exposure on acute stress regulation.

Comparison of miRNA expression profiles in pituitary-adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure.

MicoRNAs (miRNAs), usually as gene regulators, participate in various biological processes, including stress responses. The hypothalamus-pituitary-adrenal axis (HPA axis) is an important pathway in regulating stress response. Although the mechanism that HPA axis regulates stress response has been basically revealed, the knowledge that miRNAs regulate stress response within HPA axis, still remains poor. The object of this study was to investigate the miRNAs in the pituitary and adrenal cortex that regulate chronic stress response with high-throughput sequencing. The pituitary and adrenal cortex of beagles and Chinese Field dogs (CFD) from a stress exposure group (including beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)) and a control group (including beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)), were selected for miRNA-seq comparisons. Comparisons, that were made in pituitary (including BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1 and BP2 vs. CFDP2) and adrenal cortex (including BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2), showed that a total of 39 and 18 common differentially expressed miRNAs (DE-miRNAs) (Total read counts > 1,000, Fold change > 2 & p-value < 0.001), that shared in at least two pituitary comparisons and at least two adrenal cortex comparisons, were detected separately. These identified DE-miRNAs were predicted for target genes, thus resulting in 3,959 and 4,010 target genes in pituitary and adrenal cortex, respectively. Further, 105 and 10 differentially expressed genes (DEGs) (Fold change > 2 & p-value < 0.05) from those target genes in pituitary and adrenal cortex were obtained separately, in combination with our previous corresponding transcriptome study. Meanwhile, in line with that miRNAs usually negatively regulated their target genes and the dual luciferase reporter assay, we finally identified cfa-miR-205 might play an important role by upregulating MMD in pituitary and hippocampus, thus enhancing the immune response, under chronic stress exposure. Our results shed light on the miRNA expression profiles in the pituitary and adrenal cortex with and without chronic stress exposure, and provide a new insight into miR-205 with its feasible role in regulating chronic stress in the pituitary and hippocampus through targeting MMD.