Abstract Background Emotional neglect is associated with multiple negative outcomes, particularly increased risk for depression. Motivated by increasing evidence of reward-related ventral striatum ...(VS) dysfunction in depression, we investigated the role of developmental changes in VS activity on the emergence of depressive symptomatology as a function of emotional neglect. Methods We examined relationships between longitudinal neuroimaging of reward-related VS activity, assessments of mood, and measures of emotional neglect in 106 participants first scanned between ages 11 to 15 and then 2 years later. Results We found that greater levels of emotional neglect were associated with blunted development of reward-related VS activity between the first and second assessments (as indexed by lower residualized change scores). Additionally, we found that decreases in this reward-related VS activity were related to greater depressive symptomatology and partially mediated the association between emotional neglect and subsequent depressive symptomatology. Conclusions Our results provide an important demonstration that blunted development of reward-related VS activity as a function of emotional neglect predicts the emergence of depressive symptoms in adolescents. Further, our results are consistent with emerging evidence for the importance of reward-related VS dysfunction in the etiology and pathophysiology of depression. These results are a first step toward developing the ability to predict, prevent, and treat stress-related psychopathology through the targeting of specific neural phenotypes.
Despite extensive study of the neurobiological correlates of post-traumatic stress disorder (PTSD), little is known about its molecular determinants. Here, differential gene expression and network ...analyses of four prefrontal cortex subregions from postmortem tissue of people with PTSD demonstrate extensive remodeling of the transcriptomic landscape. A highly connected downregulated set of interneuron transcripts is present in the most significant gene network associated with PTSD. Integration of this dataset with genotype data from the largest PTSD genome-wide association study identified the interneuron synaptic gene ELFN1 as conferring significant genetic liability for PTSD. We also identified marked transcriptomic sexual dimorphism that could contribute to higher rates of PTSD in women. Comparison with a matched major depressive disorder cohort revealed significant divergence between the molecular profiles of individuals with PTSD and major depressive disorder despite their high comorbidity. Our analysis provides convergent systems-level evidence of genomic networks within the prefrontal cortex that contribute to the pathophysiology of PTSD in humans.
Objective:Although heightened amygdala reactivity is observed in patients with major depression, two critical gaps in our knowledge remain. First, it is unclear whether heightened amygdala reactivity ...is a premorbid vulnerability or a consequence of the disorder. Second, it is unknown how and when this neural phenotype develops. The authors sought to address these gaps by evaluating developmental change in threat-related amygdala reactivity in adolescents at high or low risk for depression based on family history, before onset of disorder.Method:At baseline and again 2 years later, adolescents (initially 11–15 years of age) participated in a functional MRI paradigm that elicited threat-related amygdala reactivity. After quality control, data were available for 232 adolescents at wave 1 and 197 adolescents at wave 2; longitudinal data meeting quality control at both waves were available for 157 of these participants. Change in amygdala reactivity was assessed as a function of family history of depression and severity of stressful life events.Results:Threat-related amygdala reactivity increased with age in participants with a positive family history regardless of the severity of life stress reported, and it increased in adolescents with a negative family history who reported relatively severe life stress. These changes in amygdala reactivity with age occurred in the absence of clinical disorder or increases in depressive symptoms.Conclusions:These results suggest that heightened amygdala reactivity emerges during adolescence, prior to the development of depression, as a function of familial risk or, in the absence of familial risk, stressful life events.
Objective:The amygdala is especially reactive to threatening stimuli, and the degree of reactivity predicts individual differences in the expression of depression and anxiety. Emerging research ...suggests that emotional neglect during childhood as well as hypercortisolemia may lead to heightened threat-related amygdala reactivity. This raises the possibility that genetic variation affecting hypothalamic-pituitary-adrenal (HPA) axis function contributes to individual differences in amygdala reactivity, both independently and as a function of childhood emotional neglect.
Method:This study assessed whether the mineralocorticoid receptor iso/val polymorphism (rs5522), a functional genetic variant affecting HPA axis function, influenced threat-related amygdala reactivity in 279 individuals in late childhood and early adolescence. The study also explored the extent to which any effects of the genotype on amygdala reactivity were contingent upon previous childhood emotional neglect.
Results:Prior childhood emotional neglect and the val allele were associated with greater amygdala reactivity. Moreover, a significant genotype-by-emotional neglect interaction was observed whereby greater amygdala reactivity in val allele carriers was independent of previous childhood emotional neglect, while greater reactivity in iso homozygotes was revealed only in the context of a history of elevated emotional neglect. At relatively low levels of previous emotional neglect, val carriers had heightened amygdala reactivity relative to iso homozygotes.
Conclusions:These results suggest that relatively greater amygdala reactivity may represent a biological mechanism through which childhood adversity and functional genetic variation in HPA axis responsiveness to stress may mediate risk for psychopathology.
Alterations in white matter integrity of several cortical and subcortical circuits have been reported in relation to unipolar major depressive disorder. It is not clear whether these white matter ...changes precede the onset of illness. In all, 13 adolescent volunteers with no personal or family history of a psychiatric disorder (controls) and 18 adolescent volunteers with no personal history of a psychiatric illness including depression, but who were at high risk for developing unipolar depression by virtue of parental depression (high-risk youth), underwent diffusion tensor imaging studies. An automated tract-based spatial statistics method, a whole-brain voxel-by-voxel analysis, was used to analyze the scans. Population average diffusion parameter values were also calculated for each tract. Adolescents at high risk for unipolar depression had lower fractional anisotropy (FA) values in the left cingulum, splenium of the corpus callosum, superior longitudinal fasciculi, uncinate, and inferior fronto-occipital fasciculi than did controls. Altered white matter integrity in healthy adolescents at familial risk for unipolar depression suggests that it might serve as a vulnerability marker for the illness.
As discussion of stress and stress-related disorders rapidly extends beyond the brain, gut microbiota have emerged as a promising contributor to individual differences in the risk of illness, disease ...course, and treatment response. Here, we employed chronic mild social defeat stress and 16S rRNA gene metagenomic sequencing to investigate the role of microbial composition in mediating anxiety- and depressive-like behavior. In socially defeated animals, we found significant reductions in the overall diversity and relative abundances of numerous bacterial genera, including Akkermansia spp., that positively correlated with behavioral metrics of both anxiety and depression. Functional analyses predicted a reduced frequency of signaling molecule pathways, including G-protein-coupled receptors, in defeated animals. Collectively, our data suggest that shifts in microbial composition may play a role in the pathogenesis of anxiety and depression.
Identifying biological mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step toward developing strategies for personalized treatment ...and, ultimately, prevention. Preclinical studies have identified epigenetic modification of gene expression as one such mechanism. Recent clinical studies have suggested that epigenetic modification, particularly methylation of gene regulatory regions, also acts to shape human brain function associated with risk for mental illness. However, it is not yet clear whether differential gene methylation as a function of adversity contributes to the emergence of individual risk for mental illness. Using prospective longitudinal epigenetic, neuroimaging and behavioral data from 132 adolescents, we demonstrate that changes in gene methylation associated with lower socioeconomic status (SES) predict changes in risk-related brain function. Specifically, we find that lower SES during adolescence is associated with an increase in methylation of the proximal promoter of the serotonin transporter gene, which predicts greater increases in threat-related amygdala reactivity. We subsequently demonstrate that greater increases in amygdala reactivity moderate the association between a positive family history for depression and the later manifestation of depressive symptoms. These initial results suggest a specific biological mechanism through which adversity contributes to altered brain function, which in turn moderates the emergence of general liability as individual risk for mental illness. If replicated, this prospective pathway may represent a novel target biomarker for intervention and prevention among high-risk individuals.
Abstract
Study Objectives:
To determine the prevalence, correlates, and predictors of insomnia in US Army personnel prior to deployment.
Methods:
Cross-sectional cohort design assessing insomnia and ...other psychosocial variables in active duty service members (n = 4,101), at Fort Hood, Texas, prior to military deployment. Insomnia was defined as an Insomnia Severity Index ≥ 15.
Results:
The prevalence of insomnia was 19.9%. Enlisted personnel were five times more likely to report insomnia than officers (odds ratio OR = 5.17). Insomnia was higher among American Indian/Alaskan Natives than other groups (ORs = 1.86–2.85). Those in the Insomnia Group were older, had longer military careers, and reported more marriages, children, and military deployments (ds = 0.13–0.34) than the No Insomnia group. The Insomnia Group reported more severe mental health symptoms, more recent stressful life events, greater childhood abuse, and lower levels of trait resilience, social support, and unit cohesion (Cohen ds = 0.27–1.29). After controlling for covariates, the Insomnia Group was more likely to have a history of head injuries and clinically significant posttraumatic stress disorder (PTSD), anxiety, depression, alcohol use problems, back pain, extremity pain, headaches, and fatigue (ORs = 1.40–3.30). A simultaneous logistic regression found that greater PTSD, depression, fatigue, stressful life events, headaches, anxiety, alcohol use problems, extremity pain, history of head injury, childhood physical neglect, back pain, number of times married, and lower leader support/unit cohesion and tangible social support were statistically significant predictors of insomnia status.
Conclusions:
Insomnia occurs in about one of five service members prior to a military deployment and is associated with a wide array of psychosocial stressors and mental and physical health problems.
Surgical Ethics Training Paneitz, Dane C.; Jefferson, Hallie L.; Hanto, Douglas W. ...
Annals of surgery,
12/2023, Letnik:
278, Številka:
6
Journal Article
PDF
