Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status.

Background: Major Depressive Disorder (MDD) is a heterogenous and etiologically complex disease often presenting with divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) which are closely related to comorbidities, including cardiometabolic disorders. Hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes. Yet, our understanding of associated biological correlates of Hyperphagic and Hypophagic MDD remain fragmented.

The Efficacy of GLP-1 Agonists in Treating Substance Use Disorder in Patients: A Scoping Review.

Substance use disorder (SUD) continues to be a leading cause of morbidity and mortality with limited treatments. There is interest in expanding the use of GLP-1 agonists in treating SUD. However, evidence for safety and efficacy in humans is limited.

Identification of State Markers in Anorexia Nervosa: Replication and Extension of Inflammation-Associated Biomarkers Using Multiplex Profiling.

Background: Proteomics offers potential for detecting and monitoring anorexia nervosa (AN) and its variant, atypical AN (atyp-AN). However, research has been limited by small protein panels, a focus on adult AN, and lack of replication.

Methods: In this study, we performed Olink multiplex profiling of 92 inflammation-related proteins in females with AN/atyp-AN ( = 64), all of whom were ≤90% of expected body weight, and age-matched healthy control individuals ( = 44).

Trajectory of ghrelin and PYY around a test meal in males and females with avoidant/restrictive food intake disorder versus healthy controls.

Disruptions in appetite-regulating hormones may contribute to the development and/or maintenance of avoidant/restrictive food intake disorder (ARFID). No study has previously assessed fasting levels of orexigenic ghrelin or anorexigenic peptide YY (PYY), nor their trajectory in response to food intake among youth with ARFID across the weight spectrum. We measured fasting and postprandial (30, 60, 120 minutes post-meal) levels of ghrelin and PYY among 127 males and females with full and subthreshold ARFID (n = 95) and healthy controls (HC; n = 32).

Intranasal Oxytocin for Obesity.

Background: Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity.

Methods: In this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks.

Association of Lower Rostral Anterior Cingulate GABA+ and Dysregulated Cortisol Stress Response With Altered Functional Connectivity in Young Adults With Lifetime Depression: A Multimodal Imaging Investigation of Trait and State Effects.

Objective: Preclinical work suggests that excess glucocorticoids and reduced cortical γ-aminobutyric acid (GABA) may affect sex-dependent differences in brain regions implicated in stress regulation and depressive phenotypes. The authors sought to address a critical gap in knowledge, namely, how stress circuitry is functionally affected by glucocorticoids and GABA in current or remitted major depressive disorder (MDD).

Methods: Multimodal imaging data were collected from 130 young adults (ages 18-25), of whom 44 had current MDD, 42 had remitted MDD, and 44 were healthy comparison subjects.

Effects of GABA, Sex, and Stress on Reward Learning in Current and Remitted Major Depression.

Background: Neurocognitive factors including aberrant reward learning, blunted GABA (gamma-aminobutyric acid), and potentiated stress sensitivity have been linked to anhedonia, a hallmark depressive symptom, possibly in a sex-dependent manner. However, previous research has not investigated the putative associations among these factors or the extent to which they represent trait- or state-based vulnerabilities for depression.

Methods: Young adults with current major depressive disorder (MDD) (n = 44), remitted MDD (n = 42), and healthy control participants (HCs) (n = 44), stratified by sex assigned at birth, underwent magnetic resonance spectroscopy to assess macromolecular contaminated GABA (GABA+) and then a reward learning task before and after acute stress.

Acute Stress Increases Striatal Connectivity With Cortical Regions Enriched for μ and κ Opioid Receptors.

Background: Understanding the neurobiological effects of stress is critical for addressing the etiology of major depressive disorder (MDD). Using a dimensional approach involving individuals with differing degree of MDD risk, we investigated 1) the effects of acute stress on cortico-cortical and subcortical-cortical functional connectivity (FC) and 2) how such effects are related to gene expression and receptor maps.

Methods: Across 115 participants (37 control, 39 remitted MDD, 39 current MDD), we evaluated the effects of stress on FC during the Montreal Imaging Stress Task.

Lower region-specific gray matter volume in females with atypical anorexia nervosa and anorexia nervosa.

Objective: Few studies have focused on brain structure in atypical anorexia nervosa (atypical AN). This study investigates differences in gray matter volume (GMV) between females with anorexia nervosa (AN) and atypical AN, and healthy controls (HC).

Method: Structural magnetic resonance imaging data were acquired for 37 AN, 23 atypical AN, and 41 HC female participants.

Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status.

Major Depressive Disorder (MDD) is a heterogenous and etiologically complex disease encompassing a broad spectrum of psychopathology, presumably arising from distinct pathophysiological mechanisms. Divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) are important clinical characteristics that are closely related to comorbidities, including cardiometabolic disorders. Prior evidence supports the notion that hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes.

Divergent transcriptomic profiles in depressed individuals with hyper- and hypophagia implicating inflammatory status.

Major Depressive Disorder (MDD) is a heterogenous and etiologically complex disease encompassing a broad spectrum of psychopathology, presumably arising from distinct pathophysiological mechanisms. Divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) are important clinical characteristics that are closely related to comorbidities, including cardiometabolic disorders. Prior evidence supports the notion that hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes.

Dynamic Amygdala Nuclei Alterations in Relation to Weight Status in Anorexia Nervosa Are Mediated by Leptin.

Objective: The amygdaloid complex is a subcortical limbic group of distinct nuclei. In a previous patient-control study, differential amygdala nuclei alterations were found in acute anorexia nervosa (AN); rostral-medial nuclei involved in fear and reward processing were substantially reduced in volume and associated with hypoleptinemia, a key neuroendocrine characteristic of AN. Here, longitudinal amygdala nuclei alterations in AN were investigated in relation to weight status and their associations with leptin levels.

Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa.

Objective: The amygdaloid complex plays a pivotal role in emotion processing and has been associated with rumination transdiagnostically. In anorexia nervosa (AN), we previously observed differential reductions of amygdala nuclei volumes (rostral-medial cluster substantially affected) and, in another study, elevated food-/weight-related rumination. Both amygdala volumes and rumination frequency correlated with characteristically suppressed leptin levels in AN.

Identification of State Markers in Anorexia Nervosa: Replication and Extension of Inflammation Associated Biomarkers Using Multiplex Profiling in Anorexia Nervosa and Atypical Anorexia Nervosa.

Proteomics provides an opportunity for detection and monitoring of anorexia nervosa (AN) and its related variant, atypical-AN (atyp-AN). However, research to date has been limited by the small number of proteins explored, exclusive focus on adults with AN, and lack of replication across studies. This study performed Olink Proseek Multiplex profiling of 92 proteins involved in inflammation among females with AN and atyp-AN (N = 64), all < 90% of expected body weight, and age-matched healthy controls (HC; N=44).

Neural activation of regions involved in food reward and cognitive control in young females with anorexia nervosa and atypical anorexia nervosa versus healthy controls.

Anorexia nervosa (AN) and atypical AN (AtypAN) are complex neurobiological illnesses that typically onset in adolescence with an often treatment-refractory and chronic illness trajectory. Aberrant eating behaviors in this population have been linked to abnormalities in food reward and cognitive control, but prior studies have not examined respective contributions of clinical characteristics and metabolic state. Research is needed to identify specific disruptions and inform novel intervention targets to improve outcomes.

The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets: A Report from the 23rd Annual Harvard Nutrition Obesity Symposium.

Obesity is increasing at an alarming rate. The effectiveness of currently available strategies for the treatment of obesity (including pharmacologic, surgical, and behavioral interventions) is limited. Understanding the neurobiology of appetite and the important drivers of energy intake (EI) can lead to the development of more effective strategies for the prevention and treatment of obesity.

Neural response to stress differs by sex in young adulthood.

Increase in stress-related disorders in women begins post-puberty and persists throughout the lifespan. To characterize sex differences in stress response in early adulthood, we used functional magnetic resonance imaging while participants underwent a stress task in conjunction with serum cortisol levels and questionnaires assessing anxiety and mood. Forty-two healthy subjects aged 18-25 years participated (21M, 21F).

Lower Ghrelin Levels Are Associated With Higher Anxiety Symptoms in Adolescents and Young Adults With Avoidant/Restrictive Food Intake Disorder.

Avoidant/restrictive food intake disorder (ARFID) is associated with increased risk for anxiety, which may adversely affect prognosis. The appetite-stimulating hormone, ghrelin, increases in response to stress, and exogenous ghrelin decreases anxiety-like behaviors in animal models. The aim of this study was to evaluate the relationship between ghrelin levels and measures of anxiety in youth with ARFID.

Association Between Ghrelin and Body Weight Trajectory in Individuals With Anorexia Nervosa.

Importance: Individuals with anorexia nervosa maintain extremely low body weights despite elevations in the circulating orexigenic hormone ghrelin. Whether circulating levels of endogenous ghrelin are associated with weight gain in anorexia nervosa is unknown.

Objective: To examine the association between baseline ghrelin and future weight change in individuals with anorexia nervosa.

A randomized, double-blind, placebo-controlled clinical trial of 8-week intranasal oxytocin administration in adults with obesity: Rationale, study design, and methods.

Background: Obesity affects more than one-third of adults in the U.S., and effective treatment options are urgently needed.

Alterations in resting-state functional activity and connectivity for major depressive disorder appetite and weight disturbance phenotypes.

Background: Major depressive disorder (MDD) is often accompanied by changes in appetite and weight. Prior task-based functional magnetic resonance imaging (fMRI) findings suggest these MDD phenotypes are associated with altered reward and interoceptive processing.

Methods: Using resting-state fMRI data, we compared the fractional amplitude of low-frequency fluctuations (fALFF) and seed-based connectivity (SBC) among hyperphagic ( = 77), hypophagic ( = 66), and euphagic ( = 42) MDD groups and a healthy comparison group ( = 38).

Eighteen-month Course and Outcome of Adolescent Restrictive Eating Disorders: Persistence, Crossover, and Recovery.

Objective: In adults, low-weight restrictive eating disorders, including anorexia nervosa (AN), are marked by chronicity and diagnostic crossover from restricting to binge-eating/purging. Less is known about the naturalistic course of these eating disorders in adolescents, particularly atypical AN (atyp-AN) and avoidant/restrictive food intake disorder (ARFID). To inform nosology of low-weight restrictive eating disorders in adolescents, we examined outcomes including persistence, crossover, and recovery in an 18-month observational study.

Perceived Stress, Cortical GABA, and Functional Connectivity Correlates: A Hypothesis-Generating Preliminary Study.

Stress exposures and dysregulated responses to stress are implicated in psychiatric disorders of mood, anxiety, and cognition. Perceived stress, an individual's appraisal of experienced stress and ability for coping, relates to dysregulated functioning in resting state brain networks. Alterations in GABAergic function may underlie perceived stress-related functional dysregulation in resting state networks but this has not yet been explored.

Reverse-translational identification of a cerebellar satiation network.

The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control. Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation.