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Alterations in B cell subsets correlate with body composition parameters in female adolescents with anorexia nervosa.

ABSTRACT: Anorexia nervosa (AN) is a severe eating disorder and often associated with altered humoral immune responses. However, distinct B cell maturation stages in peripheral blood in adolescents with AN have not been characterized. Treatment effects and the relationship between clinical and B cell parameters are also not fully understood. Here we investigated the phenotype of circulating B cell subsets and the relationship with body composition in adolescents with AN before (T0, n = 24) and after 6 weeks (T1, n = 20) of treatment. Using multi-parameter flow cytometry, we found increased percentages of antigen-experienced B cells and plasmablasts in patients with AN compared to healthy controls (n = 20). In contrast, percentages of CD1d⁺CD5⁺ B cells and transitional B cells with immunoregulatory roles were reduced at T0 and T1. These B cell frequencies correlated positively with fat mass, fat mass index (FMI), free fat mass index, and body mass index standard deviation score. In addition, scavenger-like receptor CD5 expression levels were downregulated on transitional B cells and correlated with fat mass and FMI in AN. Our findings that regulatory B cell subgroups were reduced in AN and their strong relationship with body composition parameters point toward an impact of immunoregulatory B cells in the pathogenesis of AN.

SUBMITTER: Freff J

PROVIDER: S-EPMC7806719 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Alterations in B cell subsets correlate with body composition parameters in female adolescents with anorexia nervosa.

Freff Jana J Schwarte Kathrin K Bröker Lisa L Bühlmeier Judith J Kraft Isabelle I Öztürk Dana D Hinney Anke A Arolt Volker V Dannlowski Udo U Romer Georg G Baune Bernhard T BT Hebebrand Johannes J Föcker Manuel M Alferink Judith J

Scientific reports 20210113 1

Anorexia nervosa (AN) is a severe eating disorder and often associated with altered humoral immune responses. However, distinct B cell maturation stages in peripheral blood in adolescents with AN have not been characterized. Treatment effects and the relationship between clinical and B cell parameters are also not fully understood. Here we investigated the phenotype of circulating B cell subsets and the relationship with body composition in adolescents with AN before (T0, n = 24) and after 6 wee ...[more]

PMID: 33441933

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Project description:ObjectiveWomen with anorexia nervosa (AN) have been shown to demonstrate differences in functional connectivity in brain regions associated with cognitive control, somatosensory processing, and emotion regulation. However, previous studies have been conducted on small samples and have inconsistent findings. Therefore, this study aimed to identify aberrant brain networks related to the core clinical symptoms of AN and to explore the longitudinal association with clinical outcome in a large population of adolescents experiencing their first episode of AN.MethodsFunctional MRI (fMRI) of brain resting-state functional connectivity (RS-FC) of female adolescents with first-onset AN (n = 56) were compared to age- and education-matched typically developing (TD) adolescents (n = 64). To account for the severity of underweight, separate analyses were performed to investigate differences in RS-FC between underweight AN participants and TD adolescents, as well as between underweight (n = 30) and weight-restored AN (n = 26) participants. Clinical outcomes, i.e. body mass index and eating disorder (ED) symptoms, were assessed at baseline and one-year follow-up. Independent component analyses (ICA) were used to extract the brain networks of interest: the default mode (DMN), left and right frontoparietal (FPN), and the insular (IN) networks. Linear regression analyses were conducted to assess differences in RS-FC between AN and TD participants, as well as to assess whether RS-FC was associated with clinical symptoms at baseline and at one-year of follow-up. Two statistical models were used: model 1 adjusted for age and socioeconomic status (SES), and model 2 additionally adjusted for baseline anxiety and depressive symptoms.ResultsUnderweight AN participants had lower RS-FC between the DMN-IN, as well as between the FPN-IN compared to the TD adolescents. After correction for multiple testing, no significant differences in RS-FC were found between underweight AN participants and weight-restored AN participants, as well as between the whole AN group and the TD group. RS-FC was not associated with the severity of clinical symptoms at baseline nor at one-year of follow-up.ConclusionAN is associated with changes in RS-FC between the FPN-IN and DMN-IN during the underweight state. These changes in RS-FC were no longer observed in weight-restored AN participants, emphasizing the impact of underweight on RS-FC in AN. Changes in these brain networks may partly explain the impaired cognitive control and difficulties with emotion and behavioral regulation in individuals with AN during the underweight state.

Project description:BackgroundAdolescence is a critical developmental period for the study of anorexia nervosa (AN), an illness characterized by extreme restriction of food intake. The maturation of the reward system during adolescence combined with recent neurobiological models of AN led to the hypothesis that early on in illness, restrictive food choices would be associated with activity in nucleus accumbens reward regions, rather than caudate regions identified among adults with AN.MethodsHealthy adolescents (HC, n = 41) and adolescents with AN or atypical AN (atypAN, n = 76) completed a Food Choice Task during fMRI scanning. Selection of high-fat foods and choice-related activation in nucleus accumbens and anterior caudate regions-of-interest (ROIs) were compared between individuals with AN/atypAN and HC. Associations were examined between choice-related activation and choice preferences among the AN group. Exploratory analyses examined associations between choice-related activation and psychological assessments among the patient group.ResultsAdolescents with AN or atypAN selected fewer high-fat foods than HC (t = -5.92, p < .001). Counter to predictions, there were no significant group differences in choice-related activation in the ROIs. Among individuals with AN or atypAN, choice-related neural activity in the anterior caudate was significantly negatively associated with high-fat food selections in the task (r = -.32, p = .024). In exploratory analyses, choice-related anterior caudate activation was positively associated with psychological measures of illness severity among patients (p's < .05, uncorrected).ConclusionsIn this large cohort of adolescents with AN/atypAN, there was no evidence of altered reward system engagement during food choice. While there was no group difference in choice-related caudate activation, the associations with choices and psychological measures continue to suggest that this neural region is implicated in illness. Longitudinal analyses will clarify whether neural variability relates to longer-term course.

Project description:ObjectiveBody dissatisfaction (BD) is a risk factor for the development of an eating disorder (ED) and a negative predictor for treatment outcome in adolescents with anorexia nervosa (AN). As a clinical core symptom and a relevant maintaining factor of AN, body image disturbance and BD are highly relevant target variables for therapeutic interventions. Body exposure (BE) was found as being effective for reducing BD in adolescents with EDs and high BD. However, the underlying mechanisms of BE are still not clear, with habituation processes being discussed as one possible mechanism.MethodsAffective and neurobiological processes during a four-session computer-based BE intervention were investigated. Within a controlled design comparing adolescents with AN (n = 34) vs. adolescent patients with high BD (n = 17) but without a diagnosed ED, subjective (stress ratings; 11-point Likert scale) and objective (salivary cortisol and alpha-amylase [sAA]) stress measures were assessed at four time points at each exposure session (start, +10 min, +30 min/end, +60 min/recovery). ED and depressive psychopathology were assessed via self-rating questionnaires.ResultsA between-session habituation effect was found for subjective stress ratings and sAA levels with decreasing scores throughout the four sessions. A within-session habituation was found for cortisol levels. Higher psychopathology was associated with subjective stress ratings. There were no group differences between AN and BD regarding ED psychopathology or subjective or objective stress measures. Subjective and objective stress measures were mainly not associated with each other.ConclusionsHabituation processes were found for subjective and objective stress, which might enhance motivation to continue BE interventions and thus increase their impact. BD seems to be a transdiagnostic phenomenon with BE as a successful intervention independent of psychiatric diagnosis. Current findings should be validated in larger samples, and the hypothesis of a transdiagnostic BD should be investigated in future research.

Project description:Individuals with anorexia nervosa (AN) typically display anxious traits prior to the onset of food avoidance and weight loss that characterize the disorder. Meal associated anxiety is an especially common clinical feature in these patients, and heightened sensitivity to sympathetically mediated interoceptive sensations has also been observed. However, it remains unclear how heightened interoceptive sensitivity relates to experiences of anxiety before and after meals. To investigate this relationship, we experimentally induced anxiety and panic symptoms with isoproterenol, a peripheral sympathetic agonist similar to adrenaline, across several different conditions: during panic provocation, during anticipation of a 1,000 Calorie meal, and after meal consumption. Fifteen AN and 15 age- and sex-matched healthy comparisons received bolus infusions of isoproterenol and saline in a double-blinded, randomized design. Participants rated anxiety symptoms after each infusion, completed panic rating scales, and traced the location of perceived palpitations on a manikin to index interoceptive "body map" representation. The AN group reported significantly elevated anxiety relative to healthy comparisons during infusions before and after the meal, but surprisingly, not during panic provocation. These symptoms were accompanied by geographical differences in patterns of perceived heartbeat sensations across each condition. In particular, the AN group localized heartbeat sensations disproportionately to the chest during meal related saline infusions, when no cardiorespiratory modulation actually occurred. The AN group also showed a trend toward higher panic attack rates during the meal anticipation period. Correcting for anxiety levels reported during saline infusions abolished group differences in anxiety change across all conditions, suggesting a significant contribution of anxious traits in AN. The observation of meal related "visceral illusions" provides further evidence that AN is associated with abnormal interoceptive representation of the heartbeat and suggests that meal consumption, particularly when anticipated, preferentially alters the processing of interoception related signals in AN.

Dataset Information

Alterations in B cell subsets correlate with body composition parameters in female adolescents with anorexia nervosa.

Publications

Alterations in B cell subsets correlate with body composition parameters in female adolescents with anorexia nervosa.

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