Search

Women who contract a viral or bacterial infection during pregnancy have an increased risk of giving birth to a child with a neurodevelopmental or psychiatric disorder. The effects of maternal infection are likely mediated by the maternal immune response, as preclinical animal models have confirmed that maternal immune activation (MIA) leads to long lasting changes in offspring brain and behavior development. The present study sought to determine the impact of MIA-exposure during the first or second trimester on neuronal morphology in dorsolateral prefrontal cortex (DLPFC) and hippocampus from brain tissue obtained from MIA-exposed and control male rhesus monkey (Macaca mulatta) during late adolescence. MIA-exposed offspring display increased neuronal dendritic branching in pyramidal cells in DLPFC infra- and supragranular layers relative to controls, with no significant differences observed between offspring exposed to maternal infection in the first and second trimester. In addition, the diameter of apical dendrites in DLPFC infragranular layer is significantly decreased in MIA-exposed offspring relative to controls, irrespective of trimester exposure. In contrast, alterations in hippocampal neuronal morphology of MIA-exposed offspring were not evident. These findings demonstrate that a maternal immune challenge during pregnancy has long-term consequences for primate offspring dendritic structure, selectively in a brain region vital for socioemotional and cognitive development.

Chronic restraint stress is known to cause significant alterations of mitochondrial biology. However, its effects on effort-based behavior and the sensitivity of these effects to treatments that restore mitochondrial function have not been assessed. Based on the hypothesis that the behavioral consequences of this stressor should be more severe for an energy demanding activity than for an energy procuring activity, we compared the effects of chronic restraint stress on the performance of male mice trained to use a running wheel or to nose poke for a food reward in an operant conditioning cage. In accordance with our hypothesis, we observed that exposure of mice to 2-hour daily restraint sessions for 14 to 16 days during the light phase of the cycle reliably decreased voluntary wheel running but had no effect on working for food in a fixed ratio 10 schedule of food reinforcement or in a progressive ratio schedule of food reinforcement. This dissociation between the two types of behavioral activities could reflect an adaptive response to the constraint imposed by chronic restraint stress on mitochondria function and its negative consequences on energy metabolism. To determine whether it is the case, we administered mesenchymal stem cells intranasally to chronically restrained mice to repair the putative mitochondrial dysfunction induced by chronic restraint stress. This intervention had no effect on wheel running deficits. Assessment of mitochondrial gene expression in the brain of mice submitted to chronic restraint stress revealed an increase in the expression of genes involved in mitochondrial biology that showed habituation with repetition of daily sessions of restraint stress. These original findings can be interpreted to indicate that chronic restraint stress induces behavioral and mitochondrial adjustments that contribute to metabolic adaptation to this stressor and maintain metabolic flexibility.

Socioeconomic determinants are well-established modulators of inflammation and neuroendocrine activity. Less clear is whether neighbourhood-contextual or individual-compositional factors are more closely associated with gradients in these biomarkers. Here, we examine how immune and neuroendocrine activity are cross-sectionally and longitudinally nested in meso-level socioeconomic characteristics. Participants, male and female, aged ≥50, were recruited from the English Longitudinal Study of Ageing (ELSA). Neighbourhood (Index of Multiple Deprivation [IMD]) and individual (Wealth/Education/Occupational Social Class [Occupation]) factors were drawn from wave 4 (baseline; 2008). Immune and neuroendocrine biomarkers (indexed by C-reactive protein [CRP; n = 3,968]; fibrinogen [n = 3,932]; white blood cell counts [WBCC; n = 4,022]; insulin-like growth factor-1 [IGF-1; n = 4,056]) were measured at baseline and 4-years later (wave 6; 2012). Covariates at baseline included demographic, clinical, and lifestyle variables. Lower socioeconomic status was associated with heighted inflammation and lower neuroendocrine activity unadjusted both cross-sectionally and longitudinally. With few exceptions, cross-sectional associations remained significant after full adjustment. Prospectively, low IMD remained associated with higher CRP and WBCC; wealth with WBCC; and education and occupation with fibrinogen and WBCC. IMD-biomarker associations were reduced when wealth was simultaneously taken into account. Lifestyle accounted for the greatest variance in associations between socioeconomic indicators and inflammation (≤42.11%), but demographics were more salient to neuroendocrine activity (≤88.46%). Neighbourhood-contextual factors were stronger indicators of aberrant biomarker activity than individual-compositional factors in cross-sectional analyses but were largely explained by wealth differences prospectively. Therefore, immune and neuroendocrine changes depended on the composition of the population living in an area, rather than the area itself.

Repetitive bouts of binge drinking can lead to neuroplastic events that alter ethanol's pharmacologic effects and perpetuate excessive consumption. The corticotropin-releasing factor (CRF) system is an example of ethanol-induced neuroadaptations that drive excessive ethanol consumption. Our laboratory has previously shown that CRF antagonist, when infused into the central amygdala (CeA), reduces binge-like ethanol consumption. The present study extends this research by assessing the effects of silencing CRF-producing neurons in CeA on binge-like ethanol drinking stemming from "Drinking in the Dark" (DID) procedures. CRF-ires-Cre mice underwent surgery to infuse G

Exposure of Sardinian alcohol-preferring (sP) rats to an enriched environment (EE) reduced different aspects of operant alcohol self-administration. The present study was aimed at expanding investigation of the effect of EE exposure upon a model of binge drinking composed of daily 1-h drinking sessions with unpredictable access to multiple alcohol concentrations; binge-like alcohol intakes were observed when the drinking session occurred at the last hours of the dark phase of the light/dark cycle. Starting from postnatal day (PND) 21, male sP rats were kept under three different housing conditions: impoverished environment (IE; single housing with no environmental enrichment); standard environment (SE; 3 rats/cage and no environmental enrichment); EE (6 rats/cage and multiple elements of environmental enrichment). From PND 69, rats were exposed daily to a 1-hour drinking session under the 4-bottle "alcohol (10%, 20%, and 30%, v/v) vs. water" choice regimen, during the dark phase, and with timing of alcohol exposure changed each day. In all three rat groups (IE, SE, and EE), alcohol intake increased progressively as the drinking session moved from the first to last hours of the dark phase. The slope of the regression line was steeper in EE than IE and SE rats, suggestive of higher intakes of alcohol in EE than IE and SE rats when the drinking session occurred over the last hours of the dark phase. These results are discussed hypothesizing that the stressful attributes of alcohol expectation were potentiated by the increased "emotionality" that rats living in a comfortable environment (i.e., EE) may experience when facing new, challenging events or environments. Blood alcohol levels, assessed at the end of a final drinking session occurring at the 12th hour of the dark phase, did not differ among the three rat groups and averaged approximately 150 mg%, confirming that this experimental procedure may generate intoxicating levels of alcohol drinking in sP rats.

Examine the associations of sleep measures with kidney function changes over time among individuals from a community-based study.The sample includes 1657 participants (287 with chronic kidney disease [CKD]) in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (mean age: 57.7 years, male: 46.0%). We examined associations between a large set of sleep variables (polysomnography, actigraphy, and questionnaires) and cardiovascular disease risk factors and changes in estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio over approximately 5 years using high-dimensional regression. We investigated the modifying effect of sleep on the associations between cardiovascular disease risk factors and kidney function.Sleep metrics predicted kidney function decline only among individuals with baseline CKD. Among this group, eGFR decline was associated with decreased stage N3 sleep (0.32 mL/min/1.73 mReduced deep sleep, daytime napping, increased wake bouts, delayed sleep rhythms, and overnight hypoxemia are associated with longitudinal kidney function decline, with effects most apparent in individuals with CKD. Deep sleep, napping, and sleep timing modified the association between hemoglobin A1C and kidney function.

The COVID-19 pandemic is an ongoing stressor that has resulted in the exacerbation of mental health problems worldwide. However, longitudinal studies that identify preexisting behavioral and neurobiological factors associated with mental health outcomes during the pandemic are lacking. Here, we examined associations between prepandemic coping strategy engagement and frontolimbic circuitry with internalizing symptoms during the pandemic. In 85 adults (71.8% female; age 18-30 years), we assessed prototypically adaptive coping strategies (Connor-Davidson Resilience Scale), resting-state functional magnetic resonance imaging functional connectivity (FC) of frontolimbic circuitry, and depression and anxiety symptoms (Beck Depression Inventory, Screen for Child Anxiety-Related Emotional Disorders-Adult, respectively). We conducted general linear models to test preregistered hypotheses that (1) lower coping engagement prepandemic and (2) weaker frontolimbic FC prepandemic would predict elevated symptoms during the pandemic; and (3) coping would interact with FC to predict symptoms during the pandemic. Depression and anxiety symptoms worsened during the pandemic (ps.001). Prepandemic adaptive coping engagement and frontolimbic FC were not associated with depression or anxiety symptoms during the pandemic (uncorrected ps.05). Coping interacted with insula-rostral anterior cingulate cortex (ACC) FC (p = .003, pFDR = .014) and with insula-ventral ACC FC (p.001, pFDR.001) to predict depression symptoms, but these findings did not survive FDR correction after removal of outliers. Findings from our preregistered study suggest that specific prepandemic factors, particularly adaptive coping and frontolimbic circuitry, are not robustly associated with emotional responses to the pandemic. Additional studies that identify preexisting neurobehavioral factors implicated in mental health outcomes during global health crises are needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Major depressive disorder (MDD) is a debilitating disease with a high worldwide prevalence. Despite its greater prevalence in women, male animals are used in most preclinical studies of depression even though there are many sex differences in key components of depression, such as stress responses and immune system functions. In the present study, we found that chronic restraint stress-induced depressive-like behaviors are quite similar in male and female mice, with both sexes displaying increased immobility time in the tail suspension test and reduced social interactions, and both sexes exhibited deficits in working and spatial memories. However, in contrast to the similar depressive-like behaviors developed by male and female mice in response to stress, they displayed different patterns of pro-inflammatory cytokine increases in the periphery and the brain, different changes in microglia, and different changes in the expression of Toll-like receptor 4 in response to stress. Treatment with (+)-naloxone, a Toll-like receptor 4 antagonist that previously demonstrated anti-depressant-like effects in male mice, was more efficacious in male than female mice in reducing the deleterious effects of stress, and its effects were not microbiome-mediated. Altogether, these results suggest differential mechanisms to consider in potential sex-specific treatments of depression.

Gut microbiota alterations might affect the development of Alzheimer's disease (AD) through microbiota-derived metabolites. For example, microbiota-derived Indoles via tryptophan metabolism prevented Aβ accumulation and Tau hyperphosphorylation, restored synaptic plasticity, and then promoted the cognitive and behavioral ability of APP/PS1 mice. The imbalanced compositions of Indoles-producing bacteria with tryptophan deficiency were found in male APP/PS1 mice, but the molecular mechanisms remained unclear. Our current study revealed that Indoles (including indole, indole-3-acetic acid and indole-3-propionic acid) upregulated the production of aryl hydrocarbon receptor (AhR), inhibited the activation of the NF-κB signal pathway as well as the formation of the NLRP3 inflammasome, reduced the release of inflammatory cytokines, including TNF-α, IL-6, IL-1β and IL-18, alleviating the inflammatory response of APP/PS1 mice. These findings demonstrated the roles of Indoles-producing bacteria in activating the AhR pathway to regulate neuroinflammation of AD through gut microbiota-derived Indoles, which implied a novel way for AD treatment.

There is a need for early therapeutic interventions after traumatic brain injury (TBI) to prevent neurodegeneration. Microglia/macrophage (M/M) depletion and repopulation after treatment with colony stimulating factor 1 receptor (CSF1R) inhibitors reduces neurodegeneration. The present study investigates short- and long-term consequences after CSF1R inhibition during the early phase after TBI.Sex-matched mice were subjected to TBI and CSF1R inhibition by PLX3397 for 5 days and sacrificed at 5 or 30 days post injury (dpi). Neurological deficits were monitored and brain tissues were examined for histo- and molecular pathological markers. RNAseq was performed with 30 dpi TBI samples.At 5 dpi, CSF1R inhibition attenuated the TBI-induced perilesional M/M increase and associated gene expressions by up to 50%. M/M attenuation did not affect structural brain damage at this time-point, impaired hematoma clearance, and had no effect on IL-1β expression. At 30 dpi, following drug discontinuation at 5 dpi and M/M repopulation, CSF1R inhibition attenuated brain tissue loss regardless of sex, as well as hippocampal atrophy and thalamic neuronal loss in male mice. Selected gene markers of brain inflammation and apoptosis were reduced in males but increased in females after early CSF1R inhibition as compared to corresponding TBI vehicle groups. Neurological outcome in behaving mice was almost not affected. RNAseq and gene set enrichment analysis (GSEA) of injured brains at 30 dpi revealed more genes associated with dendritic spines and synapse function after early CSF1R inhibition as compared to vehicle, suggesting improved neuronal maintenance and recovery. In TBI vehicle mice, GSEA showed high oxidative phosphorylation, oxidoreductase activity and ribosomal biogenesis suggesting oxidative stress and increased abundance of metabolically highly active cells. More genes associated with immune processes and phagocytosis in PLX3397 treated females vs males, suggesting sex-specific differences in response to early CSF1R inhibition after TBI.M/M attenuation after CSF1R inhibition via PLX3397 during the early phase of TBI reduces long-term brain tissue loss, improves neuronal maintenance and fosters synapse recovery. Overall effects were not sex-specific but there is evidence that male mice benefit more than female mice.

Initiating alcohol use in adolescence significantly increases the likelihood of developing adult alcohol use disorder (AUD). However, it has been difficult to replicate adolescent alcohol exposure leading to increased adult alcohol intake across differing preclinical models. In the present study, differentially housed male rats (group vs. single cages) were used to determine the effects of voluntary intermittent exposure of saccharin-sweetened ethanol during adolescence on adult intake of unsweetened 20% ethanol. Adolescent male rats were assigned to group- or isolated-housing conditions and underwent an intermittent 2-bottle choice in adolescence (water only or water vs. 0.2% saccharin/20% ethanol), and again in adulthood (water vs. 20% ethanol). Intermittent 2-bottle choice sessions lasted for 24 h, and occurred three days per week, for five weeks. Rats were moved from group or isolated housing to single-housing cages for 2-bottle choice tests and returned to their original housing condition on off days. During adolescence, rats raised in isolated-housing conditions consumed significantly more sweetened ethanol than rats raised in group-housing conditions, an effect that was enhanced across repeated exposures. In adulthood, rats raised in isolated-housing conditions and exposed to sweetened ethanol during adolescence also consumed significantly higher levels of unsweetened 20% ethanol compared to group-housed rats. The effect was most pronounced over the first five re-exposure sessions. Housing conditions alone had little effect on adult ethanol intake. These preclinical results suggest that social isolation stress, combined with adolescent ethanol exposure, may play a key role in adult AUD risk.

Alcoholism affects about 2 billion people worldwide. Withdrawal causes a neuroinflammatory response that increases anxiety. α-tocopherol is the most important antioxidant that has its in vivo action currently known. Therefore, this study aimed to evaluate the effect of α-tocopherol on the neuroinflammatory process in brain regions involved in anxiety and its anxiolytic potential during alcohol withdrawal. For this, male Wistar rats were divided into four groups and submitted to a procedure of forced and chronic self-administration of liquid diet containing 6% and 8% ethanol for 15 days, followed by abrupt interruption of treatment. Animals in the control group received the liquid diet without ethanol. Twenty-four or 48 h after ethanol discontinuation, and 30 min after the last administration of α-tocopherol or saline, animals were evaluated in the elevated plus maze, light/dark box, and open field tests. At the end of the tests, each experimental group underwent brain tissue collection for analysis of cytokine levels. The results showed that: alcohol induces the neuroinflammatory process and anxiety; the stress generated by withdrawal can induce oxidative stress, which alters the production of inflammatory cytokines in the amygdaloid nuclei (AN) and medial hypothalamic nucleus (mHN); α-tocopherol exhibited anxiolytic and anti-inflammatory activity, attenuating the anxious behavior of abstinent animals and reducing neuroinflammation in AN and mHN; and the intensity of the anxiolytic and anti-inflammatory effect of α-tocopherol is dose-dependent. These results identify α-tocopherol as a potential therapeutic target supporting the fight against relapse during alcohol withdrawal.

OBJECTIVES: To examine whether gender moderates the effects of childhood trauma on subjective and objective sleep measures. DESIGN: Secondary data analysis, exploratory SETTINGS: Sleep research lab PARTICIPANTS: A total of 213 men and 278 women aged 18–30 completed subjective measures. A subsample of 172 participants without any psychiatric, medical, or sleep disorders completed objective polysomnography for 1 night at baseline, before sleep manipulation. MEASUREMENTS: Subjective measures: Childhood Trauma Questionnaire (CTQ), Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Epworth Sleepiness Scale. Objective measures: Standard polysomnography measures. Multiple regressions determined whether gender moderated CTQ score on any objective or subjective sleep measures. If gender was not a moderator, we examined additive effects of gender and CTQ score. Models were adjusted for race and age. RESULTS: Gender and CTQ score interactions were non-significant for both subjective (p > .675) and objective (p > .110) sleep. Women demonstrated better subjective sleep quality (Pittsburgh Sleep Quality Index, B = −0.264, p = .041) and more delta sleep than men (B = 3.032, p =.005). Greater CTQ score was associated with increased sleepiness (Epworth Sleepiness Scale, B = 0.029, p = .042), increased insomnia severity (Insomnia Severity Index, B = 0.027, p = .005), and lower REM density (B = −0.132, p = .045). CONCLUSION: Our finding of greater delta sleep and better subjective overall sleep quality in women suggests that, among people without comorbidities, women may experience better sleep. Childhood trauma is associated with objective and subjective sleep measures, but this association is non-specific to gender. Clear links between childhood trauma and sleep are detectable in a sample of healthy sleepers with no comorbidities.

Although individual sleep characteristics are related to frailty, these characteristics do not occur separately. A multidimensional measure of sleep might provide a better estimation of frailty compared to isolated sleep characteristics. This study investigated the association of a multidimensional measure of sleep health with frailty both across and within sex groups.Data were from the Taiwan Longitudinal Study on Aging (2011), a survey with a nationally representative sample of Taiwanese older adults (N = 2,015). Frailty was defined using the Fried criteria. Self-reported sleep during the past month was used to conceptualize the five sleep health dimensions in the SATED model. Their relationship was estimated using logistic regression analysis adjusting for sociodemographic characteristics (age, sex, education), health status (comorbidity, cognitive function, pain, depressive symptoms [excluding items overlapping with frailty and sleep]), and health risk behaviors (drinking, smoking, lack of exercise).Having a better sleep health composite score was significantly related to lower odds of being frail in both sexes adjusting for sociodemographic characteristics. This association remained significant among women but not among men after adding health and risk behaviors to the models. Satisfaction and alertness in both sexes and duration among women were significantly associated with frailty adjusting for sociodemographic characteristics. Only alertness among men was significantly related to frailty in the model with all covariates.Our findings show that having better sleep health across multiple dimensions is related to a lower risk of being frail, with differential risks for women and men.

To examine the interactive association of neighborhood and family socio-economic characteristics (SEC) on children's sleep.Secondary data analyses were completed on the 2014 Ontario Child Health Study, a cross-sectional sample of 10,802 children aged 4-17.Children (aged 4-11, 50% male; N = 6264) with available sleep outcome data.Multilevel modeling was used to assess the interactive relationship between family- and neighborhood-level poverty in relation to child sleep outcomes (problems falling asleep, problems staying asleep, weekday and weekend time in bed), above the associations of variables known to be related to sleep at the child (ie, child age, sex, internalizing problems, externalizing problems, chronic illness), family (ie, negative parenting behaviors, family structure, parent mental health, years lived in neighborhood, parent education level), and neighborhood levels (ie, neighborhood size, antisocial behavior).Neighborhood poverty (plt; .01, ß = -0.001, 95% confidence interval [-0.007, -0.002]) was significantly related to shorter weekday time in bed and the interactive association of family and neighborhood poverty was significantly related to weekend time in bed (plt; .05, ß = 0.012, 95% confidence interval [0.004, 0.021]). Children living in low poverty neighborhoods with families of higher SEC backgrounds, and children living in high poverty neighborhoods with families of lower SEC backgrounds had the shortest weekend time in bed (9.7 hours).There is a compound relationship of family and neighborhood poverty on children's sleep above and beyond family- and child-level risk factors.

The ability to remember sequences of events is fundamental to episodic memory. While rodent studies have examined sex and estrous cycle in episodic-like spatial memory tasks, little is known about these biological variables in memory for sequences of events that depend on representations of temporal context. We investigated the role of sex and estrous cycle in rats during training and testing stages of a cross-species validated sequence memory task (Jayachandran et al., 2019). Rats were trained on a two four-odor sequence memory task delivered on opposite ends of a linear track. Training occurred in six successive stages starting with learning to poke in a nose-port for ≥ 1.2 s; eventually demonstrating sequence memory by holding their nose in the port ≥ 1 s for in-sequence odors and1 s for out-of-sequence odors. Performance was analyzed across sex and estrous cycle (proestrus, estrus, metestrus, and diestrus), the latter being determined by cellular composition of a daily vaginal lavage. We found no evidence of sex differences in asymptotic sequence memory performance, similar to humans performing an analogous task (Reeders et al., 2021). Likewise, no differences in sequence memory performance were found across the estrous cycle. Some caveats are that males acquired out-of-sequence trials faster during training with a 3-odor sequence, but this apparent advantage did not carry over to the 4-odor sequence. Additionally, males had shorter poke times overall which seem consistent with a decreased overall response inhibition because they occurred regardless of sequence demands. Together, these results suggest sex and estrous cycle are not major factors in sequence memory capacities. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

This study tested the preliminary effectiveness of an electronic health record (EHR)-automated population health management (PHM) intervention for smoking cessation among adult patients of a federally qualified health center in Chicago. Participants (N = 190; 64.7% women, 82.1% African American/Black, 8.4% Hispanic/Latino) were self-identified as smokers, as documented in the EHR, who completed the baseline survey of a longitudinal “needs assessment of health behaviors to strengthen health programs and services.” Four weeks later, participants were randomly assigned to the PHM intervention (N = 97) or enhanced usual care (EUC; N = 93). PHM participants were mailed a single-page self-determination theory (SDT)-informed letter that encouraged smoking cessation or reduction as an initial step. The letter also addressed low health literacy and low income. PHM participants also received automated text messages on days 1, 5, 8, 11, and 20 after the mailed letter. Two weeks after mailing, participants were called by the Illinois Tobacco Quitline. EUC participants were e-referred following a usual practice. Participants reached by the quitline were offered behavioral counseling and nicotine replacement therapy. Outcome assessments were conducted at weeks 6, 14, and 28 after the mailed letter. Primary outcomes were treatment engagement, utilization, and self-reported smoking cessation. In the PHM arm, 25.8% of participants engaged in treatment, 21.6% used treatment, and 16.3% were abstinent at 28 weeks. This contrasts with no quitline engagement among EUC participants, and a 6.4% abstinence rate. A PHM approach that can reach all patients who smoke and address unique barriers for low-income individuals may be a critical supplement to clinic-based care.

Recent work on bullying perpetration includes the hypothesis that bullying carries an evolutionary advantage for perpetrators in terms of health and reproductive success. We tested this hypothesis in the National Child Development Study (n = 4998 male, n = 4831 female), British Cohort Study 1970 (n = 4261 male, n = 4432 female), and TRacking Adolescents’ Individual Lives Survey (n = 486 male, n = 521 female), where bullying was assessed in adolescence (NCDS, BCS70: age 16, TRAILS: age 14) and outcomes in adulthood. Partial support for the evolutionary hypothesis was found as bullies had more children in NCDS and engaged in sexual intercourse earlier in TRAILS. In contrast, bullies reported worse health in NCDS and BCS70.

How disrupted sleep contributes to cognitive dysfunction over the dynamic course of Alcohol Use Disorder (AUD) is an emerging topic of investigation. Here, the Pittsburgh Sleep Quality Index (PSQI) was used to evaluate subjective sleep in 90 individuals with AUD sober for an average of 3 months and in 50 healthy controls. Relative to controls, AUD individuals had higher global PSQI scores (worse sleep), higher scores on the Beck Depression Inventory (BDI), worse Quality of Life (QoL) indicators, and poorer performance on cognitive composite tests (executive functioning, attention and working memory, visual and verbal learning or memory). Among AUD individuals, a higher PSQI score correlated with a higher BDI scores and worse QoL, but not with cognitive scales. Also noted in the AUD group were higher global PSQI scores in individuals also diagnosed with major depressive (MDD) or generalized anxiety (GAD) disorders. Together, the 4 variables explained 29.8% of the variance in AUD PSQI scores. In women with AUD, the 4 factors explained 39.3% of the variance in PSQI scores; in AUD men, the 4 measures explained 19.9% of the variance: MDD was salient in women, QoL in men with AUD suggesting differential factors associate with poor sleep in men and women with AUD even with sustained alcohol abstinence. Here, global PSQI scores were related to clinical diagnoses and life functioning but failed to predict cognitive performance in abstinent AUD individuals.

BackgroundType 2 diabetes and obesity may be inversely associated with amyotrophic lateral sclerosis (ALS), but the evidence is controversial.MethodsUsing Danish, nationwide registries (1980-2016), we identified patients with a diagnosis of type 2 diabetes (N = 295,653) and patients with a diagnosis of obesity (N = 312,108). Patients were matched (1:3) to persons from the general population on birth year and sex. We computed incidence rates and Cox regression derived hazard ratios (HRs) of a diagnosis of ALS. In multivariable analyses, HRs were controlled for sex, birth year, calendar year, and comorbidities.ResultsWe observed 168 incident cases of ALS (0.7 [95% confidence interval (CI): 0.6–0.8] per 10,000 person-years) among patients with type 2 diabetes and 859 incident cases of ALS (0.9 [95% CI: 0.9–1.0] per 10,000 person-years) among matched comparators. The adjusted HR was 0.87 (95% CI: 0.72–1.04). The association was present among men (adjusted HR: 0.78 [95% CI: 0.62–0.99]) but not women (adjusted HR: 1.03 [95% CI: 0.78–1.37]), and among those aged ≥60 years (adjusted HR: 0.75 [95% CI: 0.59–0.96]) but not younger. We observed 111 ALS events (0.4 [95% CI: 0.4–0.5] per 10,000 person-years) among obesity patients and 431 ALS events (0.5 [95% CI: 0.5–0.6] per 10,000 person-years) among comparators. The adjusted HR was 0.88 (95% CI: 0.70–1.11).ConclusionsDiagnoses of type 2 diabetes and obesity were associated with a reduced rate of ALS compared with general population comparators, particularly among men and patients aged 60 years or above. However, absolute rate differences were small. Background: Type 2 diabetes and obesity may be inversely associated with amyotrophic lateral sclerosis (ALS), but the evidence is controversial. Methods: Using Danish, nationwide registries (1980-2016), we identified patients with a diagnosis of type 2 diabetes (N = 295,653) and patients with a diagnosis of obesity (N = 312,108). Patients were matched (1:3) to persons from the general population on birth year and sex. We computed incidence rates and Cox regression derived hazard ratios (HRs) of a diagnosis of ALS. In multivariable analyses, HRs were controlled for sex, birth year, calendar year, and comorbidities. Results: We observed 168 incident cases of ALS (0.7 [95% confidence interval (CI): 0.6–0.8] per 10,000 person-years) among patients with type 2 diabetes and 859 incident cases of ALS (0.9 [95% CI: 0.9–1.0] per 10,000 person-years) among matched comparators. The adjusted HR was 0.87 (95% CI: 0.72–1.04). The association was present among men (adjusted HR: 0.78 [95% CI: 0.62–0.99]) but not women (adjusted HR: 1.03 [95% CI: 0.78–1.37]), and among those aged ≥60 years (adjusted HR: 0.75 [95% CI: 0.59–0.96]) but not younger. We observed 111 ALS events (0.4 [95% CI: 0.4–0.5] per 10,000 person-years) among obesity patients and 431 ALS events (0.5 [95% CI: 0.5–0.6] per 10,000 person-years) among comparators. The adjusted HR was 0.88 (95% CI: 0.70–1.11). Conclusions: Diagnoses of type 2 diabetes and obesity were associated with a reduced rate of ALS compared with general population comparators, particularly among men and patients aged 60 years or above. However, absolute rate differences were small.

Assessing public support of health policies designed to reduce cancer risk is important for policy implementation. This study aimed to identify support for cancer prevention policies and factors associated with support. Data were obtained from the Health Information National Trends Survey. Support for three types of cancer prevention policies were evaluated: tobacco, alcohol, and junk food regulations. Linear and logistic regression analyses were employed to assess the relationship between support for the different types of policies and sociodemographic, lifestyle behaviors, and cancer beliefs. Certain policies, such as providing warning labels on cigarettes (69.9% support) and requiring specific health warnings on alcohol containers (65.1% support), were popular. Banning outdoor advertising of alcohol was not popular (34.4% support). There were individual differences associated with policy support. For example, respondents who were 75 years or older (B = 0.61, p.001) or female (B = 0.14, p.008) were more likely to support tobacco polices compared to their counterparts (i.e., younger or male). Respondents who identified as politically conservative (B = -0.20, p.004) or those who endorsed high cancer fatalistic beliefs (e.g., there's not much you can do to lower your chances of getting cancer, B = -0.07, p.012) were less likely to support alcohol policies compared to those who were liberal or had lower cancer fatalistic beliefs. Generally, support was high for most policy questions. However, support varied by different individual factors. The findings also highlight that there may be opportunities to increase understanding and awareness about cancer prevention policies, especially among some segments of the population.It is important to assess public support of cancer preventive health policies and to know which factors, such as individual characteristics (e.g., gender and political orientation) health behaviors, and cancer beliefs, are associated with support. In this study, we assessed support of cancer prevention policies and examined different factors possibly associated with support. We analyzed data from the Health Information National Trends Survey, a nationally representative dataset. Since there were multiple questions related to support of tobacco and alcohol policies, we combined each set of questions to create two combined scores, with higher scores indicating more support. We examined the policy related to junk food individually. We found certain policies, such as including warning labels on cigarettes, were popular, with over 60% support. However, there were group differences. For example, women and those aged 55 years or older were more supportive of policies, while politically conservative respondents were less supportive of policies. Beliefs about cancer were also associated with policy support. For example, those who believed “there’s not much you can do to lower your chances of getting cancer” were less supportive compared to those without that belief. These findings may help inform future policy research and public health campaigns.

To assess the association of insomnia phenotypes, being insomnia with short sleep duration (ISSD) and insomnia with normal sleep duration (INSD), with suicidality in a randomly selected population-based sample.Data were analyzed from the Penn State Adult Cohort. Participants (N = 1741, 52.5 years, 57.4% female) were randomly recruited from the general population between January 1990 through March 1999 and mortality data were available through December 2018. Insomnia symptoms were defined as self-reports of moderate-to-severe difficulties initiating or maintaining sleep, early morning awakening and non-restorative sleep, or having chronic insomnia (n = 719). Short sleep duration was defined as6 hours of in-lab polysomnography-measured sleep duration (n = 879). Suicidality (SAI; n = 102) was ascertained by a lifetime history of suicidal ideation (SI; n = 84), suicide attempts (SA; n = 48) or death by suicide (DBS; n = 10).Compared to normal sleepers who slept ≥6 hours, participants with ISSD and INSD were associated with 1.72-fold and 2.22-fold increased odds of SAI, respectively; these associations were significant for SI, with 2.09-fold and 2.24-fold increased odds, respectively, but not for SA, after adjusting for physical and mental health comorbidities. ISSD and INSD differed in SAI age of onset and hospitalizations after SA.The results of this cohort study suggest that both INSD and ISSD phenotypes are associated with increased suicidal ideation, while the INSD phenotype has an earlier age of onset and is more likely to experience hospitalizations after attempting suicide. These results highlight the importance of targeting insomnia symptoms to help prevent suicide.

Some individuals with alcohol use disorder (AUD) continue to drink because they have developed a habit where they do not consider the consequences of their actions. Genetically selected lines of alcohol-preferring and non-preferring rats allow for exploration of how specific endophenotypes, such as tendency to form habits, may be risk factors that interact with a genetic predisposition of AUD. While high alcohol drinking (HAD) and alcohol-preferring (P) rats were selectively bred to consume high amounts of freely available ethanol, they exhibit differences in alcohol-seeking behaviors as well as impulsive behaviors, and may represent different behavioral models of AUD. The goal of the current study was to compare the tendency to develop habitual behaviors across female and male HAD1, HAD2, and P rats and their respective alcohol non-preferring counterparts. Alcohol-naïve rats were trained on a variable interval schedule using a non-ethanol reinforcer and were then tested in two extinction sessions, one prior to a reinforcer devaluation (conditioned taste aversion) procedure and one after. There were no differences in total lever presses between P and alcohol non-preferring (NP) rats, but there were differences between HAD and low-alcohol drinking (LAD) rats. All six strains decreased lever pressing after reinforcer devaluation. However, P and NP females did not increase latency to first lever press after devaluation, suggesting some inclination toward habitual behavior that was not apparent in either the HAD or LAD lines. Selective breeding for alcohol preference does not seem to influence the tendency to form habits, whereas background strain and sex may have an influence on this behavior.

This study examines the reciprocal relationship between critical action and ethnic-racial identity (ERI) exploration in Black college students using a longitudinal cross-lagged model. Participants were Black students (N = 237; M

Sleep patterns change during college, and students may nap to compensate for lost sleep. Despite the increased prevalence of napping among students, few studies have investigated daily relations between napping and nocturnal sleep, as well as how timing of naps and nocturnal sleep might influence one another. The present study used daily diaries to capture the occurrence, timing, and duration of napping and relation to nocturnal sleep.Daily diary data, collected for 4-7 days, from 654 college students from a mid-sized midwestern university (81.5% female).Participants reported nightly sleep durations, bedtimes, and wake times as well as nap durations and nap start times.Multilevel modeling (MLM) and multi-level logistic regressions revealed bidirectional relations between nocturnal sleep and napping. Regarding nocturnal sleep and its relation to next day napping, nocturnal sleep (including shorter duration and later bedtime) was associated with increased odds of napping and longer napping the following day. Shorter sleep duration was also associated with taking an earlier nap, while later bedtime was associated with a later nap the following day. Regarding napping and its association with same-night nocturnal sleep, taking a nap was associated with longer sleep duration that night, however, later nap start times and longer nap durations were associated with later bedtimes that night.Findings provide evidence for bidirectional associations between napping and nocturnal sleep. Future studies are needed to explore how naps could be optimized to promote nocturnal sleep among college students, as well as for whom naps might be most beneficial.

The Spontaneously Hypertensive Rats (SHR) strain was developed through selective breeding for high systolic blood pressure. In our laboratory, we established a congenic rat strain named SHR.Lewis-Anxrr16 (SLA16). The SLA16 rat strain is genetically identical to the SHR except for the inserted Anxrr16 region in chromosome 4. Our objective was to evaluate the influence of this genomic region on ethanol consumption and blood pressure. First, we exposed SHR and SLA16 male and female rats to ethanol consumption. Results showed that, regardless of strain, females consumed more ethanol than males during forced (10% v/v) and spontaneous ethanol consumption (SEC; 2.5-20% v/v). Then, females from both strains were used to evaluate sensitivity to ethanol. No strain differences in the loss of righting reflex were observed after ethanol treatment (3 g/kg, 20% w/v, intraperitoneal [i.p.]). But, in the triple test, female SHR rats presented lower sensitivity to the ethanol (1.2 g/kg, 14% w/v, i.p.). Surprisingly, female SHR rats also presented higher blood pressure after SEC (10% v/v). Finally, losartan treatment was effective in decreasing the blood pressure of female rats of both strains, but had specific effects on SHR ethanol consumption. Our data suggest that SLA16 female rats consume less ethanol (10%), are more sensitive to its effects, and present lower blood pressure than SHR female rats. We demonstrated that the Anxrr16 locus in chromosome 4 is a genetic candidate to explain high ethanol consumption and blood pressure, at least in females.

The 2021 meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) was titled "Role of Parental Experiences in Offspring Outcomes". The theme was reflected in the presentations of two keynote speakers: Edward Levin, Ph.D., who spoke about the role of paternal exposures in offspring development, and Catherine Monk, Ph.D., who spoke about the effects of maternal exposures and maternal mental health on offspring development. The conference included updates from three government agencies, short presentations by junior and senior investigators showcasing late-breaking FASD research, a report on international efforts to streamline FASD classifications for research, a presentation of observations from adults with FASD, a short film of people with FASDs describing their experiences, and a poster session. The conference was capped by awarding the 2021 Henry Rosett award for career-long contributions to the field to Cynthia J.M. Kane, Ph.D.

Objectives: Poor sleep is common in the general population, with hyperarousal and stress often suggested as causal factors. Conversely, sleep might also affect the stress response, in which the hypothalamic-pituitary-adrenal (HPA) axis plays a key role. We assessed the longitudinal association of sleep and 24-hour activity rhythms with functioning of the negative feedback loop of the HPA axis, as indicated by the cortisol response to a very low dose of dexamethasone. Design: Longitudinal cohort. Setting: Population-based. Participants: This study included 410 participants (mean age: 56.1 ± 5.5 years, 59% women) from the Rotterdam Study. For 217 participants, the cortisol response to dexamethasone was assessed again after a median follow-up of 5.7 years (IQR = 5.5-5.8). Measurements: Between 2004 and 2007, sleep and 24-hour activity rhythms were estimated with actigraphy (mean duration: 146 ± 19.6 hours) and sleep quality with the Pittsburgh Sleep Quality Index. To assess the negative feedback loop of the HPA axis we measured cortisol before and after the intake of a very low-dose of dexamethasone (0.25 mg). Results: Unstable (B = 1.64, 95% CI = 0.78; 2.50) and fragmented (B = -1.31, 95% CI = -2.17; -0.45) 24-hour activity rhythms, and a poor self-rated sleep quality (B = -0.02, 95% CI = -0.04; 0.00) were associated with an enhanced cortisol response to dexamethasone over time, also in those without clinically relevant depressive symptoms and those not using psychoactive medication. Conclusions: This study demonstrates a longitudinal association of disturbed 24-hour activity rhythms and poor self-rated sleep quality with an enhanced cortisol response to dexamethasone, in other words stronger suppression of cortisol. Statement of significance: This study shows that disturbed 24-hour activity rhythms and a poor self-rated sleep quality are associated with functioning of the negative feedback loop over a period of years.

As the smallest mammal with a gyrencephalic cerebral cortex, ferrets are becoming increasingly important animal models to study neurological disorders. In order for them to be optimally used, typical behavioral measurements are highly desirable. To ascertain a baseline level of behavior, we conducted a battery of tests assessing motor, social, memory, headache, and aspects of depressive-like behavior. Adult male ferrets participated in open field, beam walk, sucrose preference, eye contact, light/dark box, socialization, and novel object recognition tests. The animals were assessed in three cohorts, which differed in age, with the youngest group being approximately 1 year younger than the oldest. Small, but significant, differences occurred between the youngest cohort and the older groups in several areas, suggesting that age may be an important factor when evaluating ferret behavior. Ferrets showed a high level of sociability in the eye contact tests and with novel animal preference. These experiments represent an important baseline of expected normative results that can provide a reference for normal ferret behavior and expected variability. The data reported here may serve as a reference for future intervention studies using the ferret. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Both men and women scoring high on psychopathy exhibit similar structural and functional neural abnormalities, including reduced volume of the orbitofrontal cortex (OFC) and reduced hemodynamic activity in the amygdala during affective processing experimental paradigms. The uncinate fasciculus (UF) is a white matter (WM) tract that connects the amygdala to the OFC. Reduced structural integrity of the UF, measured via fractional anisotropy (FA), is commonly associated with men scoring high on psychopathy. However, only one study to date has investigated the relationship between psychopathic traits and UF structural integrity in women, recruiting participants from a community sample. Here, we investigated whether Hare Psychopathy Checklist-Revised (PCL-R) facet scores (measuring interpersonal, affective, lifestyle/behavioral, and antisocial psychopathic traits, respectively) were associated with reduced FA in the left and right UF in a sample of 254 incarcerated women characterized by a wide range of psychopathy scores. We observed that PCL-R Facet 3 scores, assessing lifestyle/behavioral psychopathic traits, were associated with reduced FA in the left and right UF, even when controlling for participant's age and history of previous substance use. The results obtained in the current study help improve our understanding of structural abnormalities associated with women scoring high on psychopathy. Specifically, reduced UF structural integrity may contribute to some of the deficits commonly associated with women scoring high on psychopathy, including emotion dysregulation.

Aggression occurs frequently and severely between rival groups. Although there has been much study into the psychological and socio-ecological determinants of intergroup aggression, the neuroscience of this phenomenon remains incomplete. To examine the neural correlates of aggression directed at outgroup (versus ingroup) targets, we recruited 35 healthy young male participants who were current or former students of the same university. While undergoing functional MRI, participants completed an aggression task against both an ingroup and an outgroup opponent in which their opponents repeatedly provoked them at varying levels and then participants could retaliate. Participants were then socially included and then excluded by two outgroup members and then completed the same aggression task against the same two opponents. Both before and after outgroup exclusion, aggression toward outgroup members was positively associated with activity in the ventral striatum during decisions about how aggressive to be toward their outgroup opponent. Aggression toward outgroup members was also linked to greater post-exclusion activity in the rostral and dorsal medial prefrontal cortex during provocation from their outgroup opponent. These altered patterns of brain activity suggest that frontostriatal mechanisms may play a significant role in motivating aggression toward outgroup members.

Central place foraging field crickets are an ideal system for studying the adaptive value of learning and memory, but more research is needed on ecologically relevant cognition in these invertebrates. Here, we test the visuospatial place learning of Texas field crickets (Gryllus texensis) in a radial arm maze. Our study expands previous work on G. texensis cognition for accuracy measures and extends our previous findings on females to both sexes. Additionally, our study examines whether crickets use intra- or extra-maze cues to locate a food reward using a maze rotation that puts the cues in conflict. We found that male and female crickets improved performance over trials when measured by accuracy variables but not latency variables. Thigmotaxis negatively impacted performance in both sexes. In a reward-absent trial, both male and female crickets demonstrated place memory. When intra- and extra-maze cues conflicted during a rotation trial, crickets' performance was not better than chance. Our rotation results suggest that crickets may experience reciprocal overshadowing of conflicting cues - a result most often seen in other taxa with conflicting multi-modal cues. We conclude that crickets do not rely solely on: (1) a single-cue association, (2) route-following, or (3) their own scent cues to navigate the maze. Instead, male and female Texas field crickets seem to learn the location of the reward using a combination of proximal and distal cues. The possibility to test large numbers of wild-caught or laboratory-reared individuals opens the door to future investigations on the evolutionary ecology of visuospatial learning in these invertebrates.

Sectarian tensions underlie conflicts across the Middle East, but little is known about their roots and associated beliefs. We conducted a large-scale empirical analysis, drawing on an original, geographically representative survey of over 4,000 devout Shiites across Iran and Iraq. We find that sectarian animosity is linked to economic deprivation, political disillusionment, lack of out-group contact and a sect-based view of domestic politics-paralleling patterns seen in ethno-nationalism elsewhere. In contrast, two alternative accounts are largely unsupported: sectarian animosity is not consistently associated with solidarity with a transnational sect-based community, nor does it seem to stem from disputes over religious doctrine. Nonetheless, this identity's religious roots manifest in differences from typical ethno-nationalism; practising men are less sectarian, consistent with official doctrine encouraging unity, whereas practising women are more sectarian. These gendered patterns suggest an understudied mechanism: religiously mediated socialization, or the transmission of non-religious norms through religious practice.

Individuals who use cocaine exhibit maladaptive decision-making, overweighting rewards, and underweighting potential risks. We previously showed that chronic cocaine self-administration in young adult male rats causes long-lasting increases in risk taking. The present study expanded upon these findings to determine whether effects of cocaine on risk taking depend on the route of cocaine administration and extend to females. To address the former question, rats in Experiment 1 were trained on the Risky Decision-making Task (RDT), received passively administered cocaine, and were retested in the RDT. Surprisingly, passive cocaine had no effect on risk taking. Experiment 2 determined whether cocaine self-administration increases risk taking in females in a manner comparable to males. Males and females were trained in the RDT, underwent cocaine self-administration, and were retested in the RDT. Unexpectedly, cocaine self-administration had no effect on risk taking in either sex. Because Experiments 1 and 2 involved cocaine exposure at a considerably older age than in previous work, Experiments 3 and 4 determined if cocaine effects on risk taking depend on the age of exposure. Rats began cocaine self-administration at postnatal (PN) day 77 (Experiment 3) or passive cocaine injections starting on PN day 63 (Experiment 4) and were tested in the RDT 3 weeks after cocaine cessation. In these experiments, cocaine increased risk taking in both sexes. These results reveal a limited time window during young adulthood of vulnerability to the effects of chronic cocaine on risk taking. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

To determine associations between serum long-chain (LC) omega-3 fatty acid levels and sleep parameters among adults (N = 1314) in NHANES 2011-2012.Regression analyses accounting for the complex-survey design were used to assess associations between serum LC omega-3 fatty acid levels, sleep duration, difficulty falling sleeping and sleep disorder.Overall, 48.6% were male, the mean age was 47.2 years, 5% reported very short sleep, 29% short sleep, 63% normal sleep and 3% long sleep. The sum of LC omega-3 fatty acid levels was lower among adults with short versus normal sleep, although differences were attenuated with adjustment for sociodemographic factors. Relative to normal sleep, adults with very short sleep had lower levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and sum of LC omega-3 fatty acids. Differences remained significant (p.05 for all) with adjustment for sociodemographic factors. No associations were observed with difficulty falling sleeping or sleep disorder.Our results suggest that omega-3 fatty acid levels are associated with healthy sleep duration, although, interventions are needed to clarify causality.

Administration of cholecystokinin (CCK) or the glucagon-like peptide 1 (GLP-1) receptor agonist Exendin-4 (Ex-4) reduces food intake. Findings in the literature suggest CCK reduces intake primarily as a satiety signal whereas GLP-1 may play a role in both satiety and reward-related feeding signals. Compounds that humans describe as “sweet” and “fatty” are palatable yet are signaled via separate transduction pathways. Here, unconditioned lick responses to sucrose and intralipid were measured in a brief-access lick procedure in food-restricted male rats in response to i.p. administration of Ex-4 (3 h before test), CCK (30 min before test), or a combination of both. The current experimental design measures lick responses to water and varying concentrations of both sucrose (0.03, 0.1, and 0.5 M) and intralipid (0.2%, 2%, and 20%) during 10-s trials across a 30-min single test session. This design minimized postingestive influences. Compared with saline-injected controls, CCK (1.0, 3.0, or 6.0 µg/kg) did not change lick responses to sucrose or intralipid. Number of trials initiated and lick responses to both sucrose and intralipid were reduced in rats injected with 3.0 µg/kg, but not 1.0 µg/kg Ex-4. The supplement of CCK did not alter lick responses or trials initiated compared with Ex-4 administration alone. These findings support a role for GLP-1 but not CCK in the oral responsiveness to palatable stimuli. Furthermore, Ex-4-induced reductions were observed for both sucrose and intralipid, compounds representing “sweet” and “fat,” respectively.

The racial socialization (RS) strategies used by White parents have received limited empirical attention. Thus, the current study examined the frequency and content of White parents' RS messages to their White children during an observed parent-child discussion task on discrimination when youth were 14 years old. Participants were 243 White caregivers and their adolescent children (47.7% female). Overall, parents provided few RS messages, but when they did, they often relayed egalitarian messages or messages minimizing racism. Other types of RS strategies that emerged included acknowledging racism targeting people of color, discriminatory attitudes, and false beliefs in reverse racism.

Experiences during immature phases of development, especially social experiences with individuals of the opposite sex, have implications for adult sexual behavior. Nevertheless, whether and how early experience can affect sexual learning in adulthood is still unclear. We present two experiments exploring how early experience impacts adult sexual Pavlovian conditioning in male Japanese quail. In Experiment 1, 25 male Japanese quail divided into three groups received different stimuli presentations at an early age, namely paired presentations of a conditioned stimulus (CS; a terry cloth model) and an unconditioned stimulus (US; an adult female quail), unpaired presentations of CS and US, and no exposure to stimuli. When they reached sexual maturity, we performed a sexual Pavlovian conditioning procedure with all groups using the same stimuli and tested their conditional response. In Experiment 2, we replicated the first experiment but with younger subjects and additional control variables. In the first experiment, we observed shorter approaching latencies to the CS and longer times near the CS in subjects with paired CS-US presentations compared to unpaired stimuli presentations. This was not replicated in Experiment 2. In both experiments, we found shorter approaching latencies and longer times near the CS in the groups with early exposure to the stimuli (paired or unpaired) compared to the group without this experience. Our findings indicate that the early presentations of stimuli at early stages of life can influence males' (speed of) sexual Pavlovian conditioning during adulthood. © 2022. The Psychonomic Society, Inc.

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. IBD are associated with a high prevalence of cognitive, behavioural and emotional comorbidities, including anxiety and depression. The link between IBD and the development of behavioural comorbidities is poorly understood. As the intestinal microbiota profoundly influences host behaviour, we sought to determine whether the altered gut microbiota associated with intestinal inflammation contributes to the development of behavioural abnormalities. Using the dextran sulphate sodium (DSS) model of colitis, we characterized intestinal inflammation, behaviour (elevated plus maze and tail suspension test) and the composition of the microbiota in male mice. Cecal contents from colitic mice were transferred into germ-free (GF) or antibiotic (Abx)-treated mice, and behaviour was characterized in recipient mice. Gene expression was measured using qPCR. DSS colitis was characterized by a significant reduction in body weight and an increase in colonic inflammatory markers. These changes were accompanied by increased anxiety-like behaviour, an altered gut microbiota composition, and increased central Tnf expression. Transfer of the cecal matter from colitic mice induced similar behavioural changes in both GF and Abx-treated recipient mice, with no signs of colonic or neuroinflammation. Upon characterization of the microbiota in donor and recipient mice, specific taxa were found to be associated with behavioural changes, notably members of the Lachnospiraceae family. Behavioural abnormalities associated with intestinal inflammation are transmissible via transfer of cecal matter, suggesting that alterations in the composition of the gut microbiota play a key role in driving behavioural changes in colitis.

Associations between depression and non-communicable disease have been well-described. However, the evidence for its role in the development of infectious disease is less understood. We aimed to examine prospective associations between depression and risk of hospitalisation for infection in middle-aged adults from the UK Biobank (linked with Hospital Episode Statistics) and assessed the role of several depression-related factors.We assessed prospective associations between depression status at the baseline assessment (2006-2010) and hospitalisations for infection up to the end of March 2016 in 460,418 middle-aged adults enrolled in the UK Biobank (mean age = 56.23 ± 8.11 years, 53.5% female). Cox regression was used to assess associations between depression and subsequent hospitalisations for any infections, as well as infection subtypes, viral infections, and bacterial infections. Amongst those with depression, we also examined the role of depression duration, the age of onset, and the use of antidepressants in hospitalisation risk.Depression at baseline was prospectively associated with an increased risk of hospitalisation for infection (adjusted hazard ration (aHR) = 1.20, 95% confidence interval (CI) = 1.16 to 1.25). This association was found for all infection subtypes apart from infections of the central nervous system (p = 0.911) and the skin (p = 0.313). Receipt of a depression diagnosis in late adulthood and use of antidepressants (but only in those with none/mild depressive symptoms at baseline) increased the risk of hospitalisation for infection amongst those with depression.These findings suggest that depression might be a risk factor which could be used to identify those at risk of hospitalisation for infection. Future research is required to understand the underlying factors that might result in this increased risk, so that targeted interventions can be developed.AD and AR are funded by Guy's Charity grant number EIC180702 (MLTC Challenge Fund); AD and JAT are co-funded by MRC and NIHR through grant number MR/S028188/1. IB is supported by the NIHR Maudsley BRC and by the NIHR Collaboration for Leadership in Applied Health Research and Care South Londnoo at King's College Hospital NHS Foundation Trust, King's College London. The views expressed are those of the author[s] and not necessarily those of the ESRC, NIHR, the Department of Health and Social Care or King's College London.

Obesity in adulthood is associated with reduced physical functioning (PF) at older ages. However, mechanisms underpinning this association are not well understood. We investigated whether and the extent to which C-reactive protein (CRP) mediates the association between early-adult obesity and mid-life PF.We used data from 8495 participants in the 1958 British birth cohort study. Body mass index (BMI), CRP and PF were measured at 33, 45 and 50y, respectively. Poor PF was defined as the lowest (sex-specific) 10% on the Short-form 36 Physical Functioning subscale. We accounted for prospectively measured confounders in early-life (e.g., social class at birth) and in mid-adulthood (e.g., 42y comorbidities). We decomposed the total effect of early-adult obesity on mid-life PF into direct and indirect (via CRP) effects, by employing a mediation analysis based on parametric g-computation.The estimated total effect of obesity at 33y on poor PF at 50y, expressed as an odds ratio (OR), was 2.41 (95% CI: 1.89, 3.08). The direct effect of obesity on poor PF (i.e., not operating via CRP), was 1.97 (95% CI: 1.51, 2.56), with an indirect effect of 1.23 (95% CI: 1.10, 1.37). As such, the proportion of the total effect which was mediated by the effect of obesity on CRP at 45y, was 23.27% (95% CI: 8.64%, 37.90%).Obesity in early-adulthood was associated with over twice the odds of poor PF in mid-life, with approximately 23% of the obesity effect operating via a downstream effect on CRP. As current younger generations are likely to spend greater proportions of their life course in older age and with obesity, both of which are associated with poor PF, there is an urgent need to identify mechanisms, and thus potential modifiable intermediaries, linking obesity to poor PF.

INTRODUCTION The process of neuroinflammation occurring after traumatic brain injury (TBI) has received significant attention as a potential prognostic indicator and interventional target to improve patients' outcomes. Indeed, many of the secondary consequences of TBI have been attributed to neuroinflammation and peripheral inflammatory changes. However, inflammatory biomarkers in blood have not yet emerged as a clinical tool for diagnosis of TBI and predicting outcome. The controlled cortical impact model of TBI in the rodent gives reliable readouts of the dynamics of post-TBI neuroinflammation. We now extend this model to include a panel of plasma cytokine biomarkers measured at different time points post-injury, to test the hypothesis that these markers can predict brain microstructural outcome as quantified by advanced diffusion-weighted magnetic resonance imaging (MRI). METHODS Fourteen 8-10-week-old male rats were randomly assigned to sham surgery (n���=���6) and TBI (n���=���8) treatment with a single moderate-severe controlled cortical impact. We collected blood samples for cytokine analysis at days 1, 3, 7, and 60 post-surgery, and carried out standard structural and advanced diffusion-weighted MRI at day 60. We then utilized principal component regression to build an equation predicting different aspects of microstructural changes from the plasma inflammatory marker concentrations measured at different time points. RESULTS The TBI group had elevated plasma levels of IL-1 �� and several neuroprotective cytokines and chemokines (IL-7, CCL3, and GM-CSF) compared to the sham group from days 3 to 60 post-injury. The plasma marker panels obtained at day 7 were significantly associated with the outcome at day 60 of the trans-hemispheric cortical map transfer process that is a frequent finding in unilateral TBI models. DISCUSSION These results confirm and extend prior studies showing that day 7 post-injury is a critical temporal window for the reorganisation process following TBI. High plasma level of IL-1 �� and low plasma levels of the neuroprotective IL-7, CCL3, and GM-CSF of TBI animals at day 60 were associated with greater TBI pathology.

Adolescent alcohol abuse is a significant public health concern, with approximately 4.3 million U.S. adolescents reporting monthly binge drinking. Excessive ethanol consumption during adolescence has been linked to dysregulation of the neuroimmune system, particularly in the hippocampus. Because there are sex differences in both neuroimmune responses and ethanol's pharmacologic actions, this study tested whether there were disparate effects based on sex in glial cells and neurodegeneration in adulthood after the adolescent intermittent ethanol (AIE) model. Male and female adolescent Sprague-Dawley rats underwent AIE. In adulthood, immunohistochemical techniques were utilized to determine the effects of AIE on astrocytes and microglia, and Fluoro-Jade C (FJC) was used to assess neurodegeneration in the hippocampus. AIE exposure significantly increased astrocyte activation in the cornu ammonis 1 (CA1), CA2/3, and dentate gyrus (DG) in both male and female rats with no discernible sex differences in immunoreactivity. Likewise, the number of GFAP + cells was significantly increased by AIE across the hippocampus. In our microglial assessment, AIE only led to increased Iba1 immunoreactivity in the CA1 but not CA2/3 or DG regions. However, the number of Iba1+ cells was increased by AIE in both the CA1 and DG subregions. In the DG, the ethanol effect was observed in both sexes, but in the CA1, AIE-induced increased Iba1 cells were only observed in females. In regard to neurodegeneration, there were no persisting AIE effects on FJC + cells. These findings indicate that AIE alters hippocampal glial cells in adulthood, in the absence of active neurodegeneration. However, while AIE induced long-term elevation of astroglial measures in both males and females, persisting AIE-induced microglial activation was more sparse and sex-dependent. While the majority of these findings suggest that AIE has similar effects on glial morphology and number between males and females, additional work should determine whether there are molecular differences as well as innate sex differences in glial interaction with AIE's influence on glial functions in behavior.

Allergic inflammation during pregnancy increases risk for a diagnosis of neurodevelopmental disorders such as Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) in the offspring. Previously, we found a model of such inflammation, allergy-induced maternal immune activation (MIA), produced symptoms analogous to those associated with neurodevelopmental disorders in rats, including reduced juvenile play behavior, hyperactivity, and cognitive inflexibility. These behaviors were preceded by perinatal changes in microglia colonization and phenotype in multiple relevant brain regions. Given the role that microglia play in synaptic patterning as well as evidence for altered synaptic architecture in neurodevelopmental disorders, we investigated whether allergic MIA altered the dynamics of dendritic spine patterning throughout key regions of the rat forebrain across neurodevelopment. Adult virgin female rats were sensitized to the allergen, ovalbumin, with alum adjuvant, bred, and allergically challenged on gestational day 15. Brain tissue was collected from male and female offspring on postnatal days (P) 5, 15, 30, and 100-120 and processed for Golgi-Cox staining. Mean dendritic spine density was calculated for neurons in brain regions associated with cognition and social behavior, including the medial prefrontal cortex (mPFC), basal ganglia, septum, nucleus accumbens (NAc), and amygdala. Allergic MIA reduced dendritic spine density in the neonatal (P5) and juvenile (P15) mPFC, but these mPFC spine deficits were normalized by P30. Allergic inflammation reduced spine density in the septum of juvenile (P30) rats, with an interaction suggesting increased density in males and reduced density in females. MIA-induced reductions in spine density were also found in the female basal ganglia at P15, as well as in the NAc at P30. Conversely, MIA-induced increases were found in the NAc in adulthood. While amygdala dendritic spine density was generally unaffected throughout development, MIA reduced density in both medial and basolateral subregions in adult offspring. Correlational analyses revealed disruption to amygdala-related networks in the neonatal animals and cortico-striatal related networks in juvenile and adult animals in a sex-specific manner. Collectively, these data suggest that communication within and between these cognitive and social brain regions may be altered dynamically throughout development after prenatal exposure to allergic inflammation. They also provide a basis for future intervention studies targeted at rescuing spine and behavior changes via immunomodulatory treatments.

Using the frameworks of Latino Critical Race Theory (LatCrit) and an integrative model of developmental competencies, this study examined the roles of cultural mistrust toward education and natural mentoring relationship quality in the academic outcomes of Latinx adolescents. Participants were 294 Latinx students (52.9% female; mean age 15 years in 9th grade; 21% first-generation, 63% second-generation, and 6% third-generation immigrants) who completed surveys in 9th and 10th grades. The negative effect of cultural mistrust on educational aspirations was greater for students who had poorer quality mentoring relationships. This study addresses gaps in the literature related to cultural mistrust as a coping strategy and discusses the ways in which mentors can serve a protective role.

Previous neuroimaging studies have demonstrated that sleep is associated with brain functional changes in some specific brain regions. However, few studies have examined the relationship between all possible functional connectivities (FCs) within the sensory/somatomotor network (SSN) and the sleep quality of young male samples. The SSN consists of two motor cortices and is known to play a critical role in sleep. Poor sleep quality may be associated with increased sensory/somatomotor functional connectivity during rest. Hence, 202 young male participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and completed the Pittsburgh Sleep Quality Index (PSQI). Results indicated that increased functional connectivity within the SSN was associated with poor sleep quality. Specifically, the total PSQI score was positively correlated with the increased functional connectivity of the left paracentral lobule (PCL), bilateral precentral gyrus (PreCG), supplementary motor area (SMA) and bilateral postcentral gyrus (PoCG). Additionally, our findings also exhibited that (a) the subjective sleep quality factor of PSQI was positively correlated with FC between the bilateral PoCG and the bilateral PCL as well as between the left PreCG and the right SMA; (b) the sleep latency factor of PSQI was positively correlated with FC between the left PoCG and the right precuneus (PCUN); (c) the sleep disturbances factor of PSQI was positively correlated with FC between the left PCL and the right PoCG, and (d) the daytime dysfunction factor of PSQI was positively correlated with FC between the bilateral PoCG and the left PCL as well as between the bilateral PreCG and the SMA. In short, our findings can be comprehensively understood as neural mechanisms of intrinsic SSN connectivity are associated with sleep quality of man. Meanwhile, it may expand our knowledge and provide new insight into a deeper understanding of the neurobiological mechanisms of sleep or sleep problems.

The contribution of brain regions to visuospatial abilities according to sex differences and gender identity is inconsistently described. One potential explaining factor may be the different tasks employed requiring a variable load of working memory and other cognitive resources. Here we asked to 20 cis and 20 transgender participants to undergo functional Magnetic Resonance Imaging during performance of a judgement line of orientation test that was adapted to explore the basic visuospatial processing while minimizing the working memory load. We show that V1 activation may be viewed as a brain area with enhanced activation in males, regardless of participants’ gender identity. On its turn, gender identity exclusively influences the visuospatial processing of extrastriate visual areas (V5) in women with gender dysphoria. They showed enhanced V5 activation and an increased functional connectivity between V5 and V1. Overall our neuroimaging results suggest that the basic visuospatial abilities are associated with different activations pattern of cortical visual areas depending on the sex assigned at birth and gender identity.

Attention Deficit Hyperactivity Disorder (ADHD) is a highly prevalent and disabling disorder that frequently persists into adulthood. Many patients are considered nonresponders to typical pharmacological treatments due to insufficient symptoms' reduction or the inability to tolerate the side effects of these medications. Agmatine is an endogenous neuromodulator with emotional- and cognitive-enhancing properties that arises as a promising agent to manage several Central Nervous System disorders. Here, we investigated the effects of chronic treatment with agmatine on behavioral impairments exhibited by adult Spontaneously Hypertensive Rats (SHR), an animal model for the study of ADHD. Adult male Wistar and SHR (3-4 months old) received intraperitoneal (i.p.) treatment with saline (NaCl 0.9%) or agmatine (30 mg/kg/day) during 20 consecutive days and were evaluated in a battery of behavioral tasks. Agmatine treatment improved olfactory and recognition memory impairments of SHR evaluated in the olfactory discrimination, object recognition, and social recognition memory tasks. In addition, agmatine administration improved the cognitive flexibility in the water maze test. Agmatine did not alter SHR's locomotor activity and hedonic-like behaviors observed in the open-field and splash tests, respectively. No changes were observed in SHR's systolic blood pressure following agmatine treatment. This study provides the first evidence that agmatine improves olfactory and cognitive impairments observed in an animal model of ADHD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

STUDY OBJECTIVES: Trauma exposure likely contributes to poor sleep, but relatively few studies have empirically tested this, instead focusing on posttraumatic stress disorder. Moreover, little is known about sex differences in sleep after trauma. The current study used a cross-sectional and retrospective design to test hypotheses that trauma exposure would be associated with subsequent insomnia symptoms, particularly among women, even after accounting for important covariates. METHOD: Data from Wave 3 (1993–1996) of the Baltimore Epidemiologic Catchment Area Study (N=1920) were used to examine associations between remote (prior to past year) and recent (past year) trauma and current sleep disturbance (insomnia, hypersomnia symptoms) in the total sample (M(age)= 55, 63.2% women, 57.7% white), and separately in men and women. Sensitivity analyses were conducted among individuals with no pre-trauma sleep disturbance to examine incident sleep disturbance. RESULTS: Among all participants, both remote (OR=1.95, 95% CI [1.34, 2.85]) and recent (OR=1.94, 95% CI [1.31, 2.87) trauma exposure were associated with increased odds of insomnia (OR=2.41, 95% CI [1.54, 3.76]) but not hypersomnia. Associations between trauma and insomnia were particularly strong among women, but null among men. The relationship between trauma exposure and insomnia symptoms persisted among individuals with no pre-trauma history of insomnia. CONCLUSION: Results suggest women may be vulnerable to insomnia symptoms as sequelae of trauma. Future research should examine prospective associations between trauma and sleep in larger samples and how assessment and treatment of insomnia among women trauma survivors reduces the public health impact of trauma and poor sleep.