Obesity is associated with an increased risk of depression and anxiety disorders, but the nature of the relationship(s) between obesity and mental illness remain highly controversial. Some argue that depression and/or anxiety lead to increased consumption of 'comfort foods,' the intake of which reduces negative affect and promotes obesity. In contrast, others have theorized that negative affect results from chronic excessive consumption of highly palatable foods. The brain serotonin (5-HT) system has long been implicated in both the development and treatment of mental illness. Preclinical studies have shown that low brain 5-HT exacerbates depression- and anxiety-like behavior induced by stress and blocks reductions in depression-like behavior induced by antidepressants, but the effects of brain 5-HT deficiency on responses to high fat diet (HFD) have not been explored. The current work used genetically modified mice to evaluate the effects of low 5-HT on behavioral and molecular alterations induced by chronic exposure to HFD. Our results reveal that HFD decreases depression-like behavior and increases some anxiety-like behaviors in wild-type (WT) mice. However, genetic brain 5-HT deficiency blocks HFD-induced reductions in forced swim immobility and prevents HFD-induced increases in hippocampal GSK3β phosphorylation despite having no significant effects on HFD-induced changes in body weight or anxiety-like behavior. Together, our results suggest that brain 5-HT deficiency significantly impacts a subset of behavioral and molecular responses to HFD, a finding that could help explain the complex relationships between obesity and mental illness.
Women exhibit higher rates of post‐traumatic stress disorder, major depression, and anxiety disorders than men, but the biological basis for this sex difference remains largely unknown. Stress has been implicated in anxiety, depression, and other mental disorders, and it has been hypothesized that sex differences in stress susceptibility could underlie the clinically observed gender differences in the incidence of mental illness. Preclinical studies examining sex differences in vulnerability to stress have reported mixed findings, but several recent studies have found that females, but not males, exhibit depression‐ and anxiety‐like behavior following sub‐chronic variable stress (SCVS). These prior studies further suggested that the differential responses of males and females to SCVS result at least in part from sex differences in the expression of DNA methyltransferase 3a (Dnmt3a) and nuclear factor kappa B (NFKB) in the striatum. To evaluate the generalizability of these published findings, the current study examined sex differences in response to a modified version of the SCVS model. Our results reveal that SCVS significantly increases the expression of Dnmt3a and the p105 subunit of NFKB in the striatum of females but not males. However, in contrast to prior research, both sexes displayed increased depression‐ and anxiety‐like behavior following SCVS, suggesting that males are not entirely resilient to SCVS. The identification of SCVS‐induced behavioral disturbances in males in the absence of SVCS‐induced alterations in Dnmt3a or NFKB suggests that the molecular mechanisms leading to depression‐ and anxiety‐like behavior may differ in males and females. Future research elucidating the sex differences in stress‐induced molecular pathology could prove critical for improving our ability to design rational therapeutic interventions that counteract the effects of stress in males and females.
Abstract There is a wealth of research linking adverse childhood experiences (ACEs) with negative outcomes later in life, but less research has focused on the effects of protective childhood experiences (PCEs). PCEs have been shown broadly to promote resilience, but the precise nature of this association is not clear, particularly in studies of at‐risk adults. The current investigation explored the association between recollection of early life experiences and in vivo emotional responses in at‐risk adults. In 2018, 56 active‐duty firefighters reported childhood experiences via a questionnaire. Using a semistructured interview, firefighters then responded to questions about recent emotionally evocative experiences (positive and negative) as a firefighter. Emotion was measured in vivo via sympathetic arousal and recorded facial expressions of emotion. Individuals who reported more PCEs expressed significantly more facial expressions of positive emotion across contexts, sr 2 = .11–.14. Early childhood experiences were not significantly associated with negative facial expressions or changes in sympathetic reactivity, but ACEs were associated with tonic levels of arousal in a negative context, r = ‐.36. Given the adaptive role of positive emotions in adjustment to adverse events, the current investigation suggests a potential protective association between PCEs and the expression of emotion even within a high‐risk context, which could help explain the resilience promoting role of PCEs.
Early life stress is known to increase the risk of depression and anxiety disorders, which are highly prevalent conditions that disproportionately affect women. However, the results of preclinical studies have been mixed, with some work suggesting that early life stress promotes anxiety-like behavior and/or increases susceptibility to subsequent stressors, and other research suggesting that early life stress reduces anxiety-like behavior and/or confers resilience to subsequent stress exposure. It is likely that factors such as sex and the timing and severity of early life and adult stress exposure dictate whether a particular early life experience promotes adaptive vs. maladaptive behavior later in life. Most work in this area has focused exclusively on males, but several sex differences in the effects of early life stress on subsequent stress susceptibility have been reported. The current study examined the impact of early life maternal separation on susceptibility to behavioral alterations induced by 3 days of variable stress in adulthood in male and female c57BL6 mice. Our results indicate that 3 days of adult stress is sufficient to increase anxiety-like behavior in several paradigms and to increase immobility in the forced swim test. In contrast, a history of maternal separation reduces anxiety-like behavior in several tests, particularly in males. These findings could contribute to our understanding of sex differences in mental illness by demonstrating that males are more likely than females to display adaptive responses to mild early life stressors.
Obesity is associated with an increased risk of depression and anxiety disorders, but the nature of the relationship(s) between obesity and mental illness remain highly controversial. Some argue that depression and/or anxiety lead to increased consumption of ‘comfort foods’ to reduce negative affect and that chronic consumption of these foods promotes obesity. Alternatively, it has been suggested that chronic excessive consumption of highly palatable foods, such as those high in fats, could induce negative affective states in susceptible individuals. However, the genetic factors that influence food consumption and behavioral responses to high fat diets (HFDs) remain largely unknown. The brain serotonin (5‐HT) system has long been implicated in both the development and treatment of mental illness. Preclinical studies have shown that low brain 5‐HT exacerbates depression‐ and anxiety‐like behavior induced by stress and blocks reductions in depression‐like behavior induced by antidepressants, but the effects of brain 5‐HT deficiency on responses to HFD have not been explored. The current work used genetically modified mice to evaluate the effects of low brain 5‐HT on behavioral and molecular alterations induced by chronic exposure to HFD. Real‐time PCR was used to measure mRNA expression, and Western blotting was used to study protein phosphorylation. Our results reveal that HFD decreases depression‐like behavior and increases some anxiety‐like behaviors in wild‐type mice. However, genetic brain 5‐HT deficiency blocks HFD‐induced reductions in forced swim immobility and prevents HFD‐induced increases in hippocampal GSK3β phosphorylation. These effects occur despite the fact that low 5‐HT does not influence HFD‐induced changes in body weight or anxiety‐like behavior in the novel open field test or the elevated plus maze. Together, our results suggest that although brain 5‐HT deficiency does not alter HFD intake, low brain 5‐HT prevents therapeutic‐like responses to HFD and blocks the inhibition of GSK3 by HFD. Although GSK3 inhibition has been shown to lead to antidepressant‐like effects, whether GSK3 inhibition is required for the antidepressant‐like effects of HFD has not been established. Nonetheless, our results indicate that brain 5‐HT plays a major role in mediating some of the effects of HFD, which could help explain the complex relationships between obesity and mental illness.
Abstract Background Dominant psychotherapies target how individuals experience and understand their daily emotion. Therefore, research examining how daily emotions influence long-term mental health outcomes may help inform treatment development. Methods This investigation applied a multi-cohort ( n = 378; n = 460), longitudinal design to test how reports of daily emotion predict psychological symptoms, loneliness, and wellbeing one-year later. Dynamic indices (polarity, inertia) reflecting “how” emotional experiences are conceptualized moment-to-moment and static indices (person-mean, standard deviation) of emotion were extracted from 10 daily reports. Each index was modelled individually, in concert with others, and in relation to a key dispositional factor in symptom development: trait anxiety. Results Dynamic indices predicted outcomes one-year later, but only the effect of positive emotional inertia remained significant after accounting for mean intensity of affect. Daily reports of emotion also predicted small but significant variance in outcomes beyond trait anxiety. Conclusions Results highlight the role of daily subjective experiences of emotion in long-term mental health outcomes and reinforce their importance as targets for treatment.
Social support is a key protective factor in the psychological adjustment of individuals to traumatic events. However, since March 2020, extant research has revealed evidence of increased loneliness, social isolation, and disconnection, likely due to COVID-19 pandemic-related recommendations that restricted day-to-day contact with others.In this investigation, we applied a case-control design to test the direct impacts of the pandemic on social support in United States adults recovering from a significant injury caused by PTSD-qualifying, traumatic events (e.g., motor vehicle crashes, violence, etc.). We compared individuals who experienced trauma during the pandemic, the "cases" recruited and evaluated between December 2020 to April 2022, to trauma-exposed "controls," recruited and evaluated pre-pandemic, from August 2018 through March 9, 2020 (prior to changes in public health recommendations in the region). Cohorts were matched on key demographics (age, sex, education, race/ethnicity, income) and injury severity variables. We tested to see if there were differences in reported social support over the first 5 months of adjustment, considering variable operationalizations of social support from social network size to social constraints in disclosure. Next, we tested to see if the protective role of social support in psychological adjustment to trauma was moderated by cohort status to determine if the impacts of the pandemic extended to changes in the process of adjustment.The results of our analyses suggested that there were no significant cohort differences, meaning that whether prior to or during the pandemic, individuals reported similar levels of social support that were generally protective, and similar levels of psychological symptoms. However, there was some evidence of moderation by cohort status when examining the process of adjustment. Specifically, when examining symptoms of post-traumatic stress over time, individuals adjusting to traumatic events during COVID-19 received less benefit from social support.Although negative mental health implications of the pandemic are increasingly evident, it has not been clear how the pandemic impacted normative psychological adjustment processes. These results are one of the first direct tests of the impact of COVID-19 on longitudinal adjustment to trauma and suggest some minimal impacts.
Binge eating disorder (BED), the most common eating disorder in the USA, negatively impacts psychological and physical health. Although the neurobiological basis of BED remains unknown, serotonergic dysfunction has been hypothesized to contribute to this condition. This study tested the hypothesis that brain serotonin deficiency will increase binge eating and block reductions in binge eating induced by fluoxetine. Binge eating was measured in wild-type and serotonin-deficient mice after acute and chronic fluoxetine administration. RNA was isolated from the raphe, and real-time PCR was performed to evaluate gene expression. Males with low serotonin binge ate more than wild-type mice at baseline, and fluoxetine reduced binge eating in both genotypes. Gene expression analyses revealed no significant genotype or drug effects on p11 expression in males, but fluoxetine significantly reduced the expression of 5HT1A receptor but not 5HT2A. In females, fluoxetine reduced binge eating in wild-type but not serotonin-deficient mice, and no baseline difference in binge eating was observed. Real-time PCR revealed no significant main effects of genotype or drug on p11, 5HT1A, or 5HT2A expression. However, a significant genotype by drug interaction was observed for p11 expression in which fluoxetine reduced p11 expression in wild-type mice and increased it in serotonin-deficient animals. These results highlight the importance of sex as a modifying factor in the relationship between binge eating and serotonin levels and suggest that serotonin deficiency can modify sensitivity to fluoxetine-induced reductions in binge eating, perhaps by impacting transcriptional responses to fluoxetine.
