Sex-dependent clinical presentation, body image, and endocrine status in long-term remitted anorexia nervosa.

OBJECTIVE: Although anorexia nervosa (AN) in males has recently gained attention, knowledge of its psychological and physiological outcomes is still scarce. We explore sex-specific characteristics of long-term remitted AN with respect to residual eating disorder (ED) psychopathology, body image, and endocrinology. METHOD: We recruited 33 patients with AN in remission for at least 18 months (24 women, 9 men) and 36 matched healthy controls (HCs). Eating disorder psychopathology and body image ideals were assessed via clinical interviews, questionnaires, and an interactive 3D body morphing tool. Plasma levels of leptin, free triiodothyronine, cortisol, and sex hormones were quantified. Univariate models controlled for age and weight were used to test for the effects of diagnosis and sex. RESULTS: Both patient groups showed residual ED psychopathology but normal weight and hormone levels relative to HCs. Male remitted patients demonstrated significantly stronger muscularity-focused body image ideals, evident in interviews, self-reports, and behavioural data, than both female patients and HCs. CONCLUSIONS: Sex-specific body image characteristics in patients with remitted AN point towards the need to adjust test instruments and diagnostic criteria to male-specific psychopathology. In the future, sufficiently powered studies should evaluate the risk of men with AN developing muscle dysmorphia in the long term.

Recovery-Associated Resting-State Activity and Connectivity Alterations in Anorexia Nervosa.

BACKGROUND: Previous studies provided controversial insight on the impact of starvation, disease status, and underlying gray matter volume (GMV) changes on resting-state functional magnetic resonance imaging alterations in anorexia nervosa (AN). Here, we adapt a combined longitudinal and cross-sectional approach to disentangle the effects of these factors on resting-state alterations in AN. METHODS: Overall, 87 female subjects were included in the study: adolescent patients with acute AN scanned at inpatient admission (n = 22, mean age 15.3 years) and at discharge (n = 21), patients who recovered from AN (n = 21, mean age 22.3 years), and two groups of healthy age-matched control subjects (both n = 22, mean age 16.0 and 22.5 years, respectively). Whole-brain measures of resting-state activity and functional connectivity were computed (network-based statistics, global correlation, integrated local correlation, and fractional amplitude of low-frequency fluctuations) to assess resting-state functional magnetic resonance imaging alterations over the course of AN treatment before and after controlling for underlying GMV. RESULTS: Patients with acute AN displayed strong and widespread prefrontal, sensorimotor, parietal, temporal, precuneal, and insular reductions of resting-state connectivity and activity. All alterations were independent of GMV and were largely normalized in short-term recovered AN and absent in long-term recovered patients. CONCLUSIONS: Resting-state functional magnetic resonance imaging alterations in AN constitute acute and GMV-independent, presumably starvation-related, phenomena. The majority of alterations found here normalized over the course of recovery without evidence for possible preexisting trait- or remaining "scar" effects.

Neuroendocrine stress responses predict catecholamine-dependent working memory-related dorsolateral prefrontal cortex activity.

It is generally thought that the effect of acute stress on higher-order functions such as working memory is, for an important part, mediated by central catecholamine activity. However, little is known about the association between neuroendocrine stress responses and catecholamine-dependent working memory-related brain function in the absence of stress. Here, we investigate for the first time in healthy humans (n = 18) how neuroendocrine responses to stress (cortisol and alpha-amylase) relate to fronto-parietal working memory activity changes in response to atomoxetine, a noradrenaline transporter inhibitor that selectively increases extracellular cortical dopamine and noradrenaline. We observed positive correlations between stress-induced cortisol (Pearson's r = 0.75, P < 0.001) and alpha amylase (r = 0.69, P = 0.02) increases and catecholamine-dependent working memory-related activity in dorsolateral prefrontal cortex. Stress-induced cortisol increases furthermore correlated with supramarginal gyrus working memory-related activity (r = 0.79, P < 0.001). Comparing high vs low stress responders revealed that these correlations were driven by decreased working memory activity on placebo and greater working memory activity increases following atomoxetine in high stress responders. These results further corroborate the notion that neuroendocrine responses to stress are an informative proxy of catecholamine function relevant to higher order functions and provide novel hints on the complex relationship between acute stress, catecholamine function and working memory.

Noradrenaline transporter blockade increases fronto-parietal functional connectivity relevant for working memory.

Experimental animal work has demonstrated that dopamine and noradrenaline play an essential role in modulating prefrontal cortex-mediated networks underlying working memory performance. Studies of functional connectivity have been instrumental in extending such notions to humans but, so far, have almost exclusively focussed on pharmacological agents with a predominant dopaminergic mechanism of action. Here, we investigate the effect of a single dose of atomoxetine 60mg, a noradrenaline transporter inhibitor, on working memory performance and associated functional connectivity during an n-back task in 19 healthy male volunteers. Atomoxetine increased functional connectivity between right anterior insula and dorsolateral prefrontal cortex, precentral gyrus, posterior parietal cortex and precuneus during the high-working memory load condition of the n-back task. Increased atomoxetine-induced insula-dorsolateral prefrontal cortex functional connectivity during this condition correlated with decreased reaction time variability and was furthermore predicted by working memory capacity. These results show for the first time that noradrenaline transporter blockade-induced increases in cortical catecholamines accentuate fronto-parietal working memory-related network integrity. The observation of significant inter-subject variability in response to atomoxetine has implications for inverted-U frameworks of dopamine and noradrenaline function, which could be useful to predict drug effects in clinical disorders with variable treatment response.