Pseudogenes are thought to be inactive gene sequences, but recent evidence of extensive pseudogene transcription raised the question of potential function. Here we discover and characterize the sets of mouse lncRNAs induced by inflammatory signaling via TNFα. TNFα regulates hundreds of lncRNAs, including 54 pseudogene lncRNAs, several of which show exquisitely selective expression in response to specific cytokines and microbial components in a NF-κB-dependent manner. Lethe, a pseudogene lncRNA, is selectively induced by proinflammatory cytokines via NF-κB or glucocorticoid receptor agonist, and functions in negative feedback signaling to NF-κB. Lethe interacts with NF-κB subunit RelA to inhibit RelA DNA binding and target gene activation. Lethe level decreases with organismal age, a physiological state associated with increased NF-κB activity. These findings suggest that expression of pseudogenes lncRNAs are actively regulated and constitute functional regulators of inflammatory signaling.DOI: http://dx.doi.org/10.7554/eLife.00762.001

Background: Individuals with eating disorders (EDs) have increased rates of major depressive disorder (MDD) and anxiety disorders. Yet, few studies have investigated rates of EDs and their symptoms in individuals presenting with MDD/anxiety disorders. Identifying potential disordered eating in people with MDD/anxiety disorders is important because even subclinical disordered eating is associated with reduced quality of life, and undiagnosed eating pathology may hinder treatment progress for both MDD/anxiety disorders and comorbid EDs. Method: We compared rates of EDs (anorexia nervosa, bulimia nervosa, binge-eating disorder, and other specified feeding and eating disorders) and their symptoms in 130 women with, and 405 women without, lifetime MDD or an anxiety disorder (generalized anxiety disorder, obsessive-compulsive disorder, social phobia, specific phobia, panic disorder, agoraphobia, or post-traumatic stress disorder) recruited from the population-based Michigan State University Twin Registry. Lifetime ED and MDD/anxiety diagnoses, and lifetime clinically significant disordered eating behaviors (e.g., binge eating, excessive exercise) were assessed using the Structured Clinical Interview for DSM-IV (SCID). Results: Among participants with lifetime MDD or any anxiety disorder, 13% met criteria for a lifetime ED and 39% reported engaging in at least one lifetime clinically significant disordered eating behavior (e.g., binge eating) on the SCID. In contrast, only 3% of participants without a history of MDD/an anxiety disorder met criteria for a lifetime ED, and only 11% reported lifetime clinically significant disordered eating behavior. Discussion: Our findings suggest that women with MDD and anxiety disorders have elevated rates of EDs, and it is therefore imperative to screen for disordered eating in these populations.

No abstract

Emerging evidence suggests socioeconomic disadvantage may increase risk for eating disorders (EDs). However, there are very few studies on the association between disadvantage and EDs, and all have focused on individual-level risk factors (e.g., family income). Neighborhood disadvantage (i.e., elevated poverty and reduced resources in one's neighborhood) is associated with increased risk for anxiety/depression and poor physical health. To date, no studies have examined phenotypic associations between neighborhood disadvantage and disordered eating, or how any form of disadvantage may interact with genetic individual differences in risk for EDs. We examined phenotypic and etiologic associations between neighborhood disadvantage and disordered eating in 2,922 girls ages 8-17 from same-sex twin pairs recruited through the Michigan State University Twin Registry. Parents rated the twins on nine items assessing core disordered eating symptoms (e.g., weight preoccupation, binge eating), and neighborhood disadvantage was calculated from 17 indicators of contextual disadvantage (e.g., median home value, neighborhood unemployment). Puberty was measured using the Pubertal Development Scale to examine whether associations were consistent across development. At a phenotypic level, greater neighborhood disadvantage was associated with significantly greater disordered eating symptoms in girls at all stages of puberty (b = .07). Moreover, Genotype 3 Environment models showed that girls living in more disadvantaged neighborhoods exhibited stronger and earlier (i.e., during pre/ early puberty) activation of genetic influences on disordered eating. Results highlight the critical importance of considering contextual disadvantage in research on etiology and risk for disordered eating, and the need for increased screening and treatment for EDs in disadvantaged youth. General Scientific SummaryThis was the first study to examine the association between neighborhood disadvantage and disordered eating in girls. We found that neighborhood disadvantage was associated with significantly greater disordered eating symptoms across all stages of puberty in girls, and that girls living in disadvantaged neighborhoods exhibited stronger and earlier (i.e., during pre/early puberty) activation of genetic influences on disordered eating. Results indicate that neighborhood disadvantage is a critical contextual factor with implications for etiology and risk for disordered eating in girls.