Effects of Transcranial Direct Current Stimulation Treatment for Anorexia Nervosa.

Background: Anorexia nervosa (AN) is a life-threatening illness with poor treatment outcomes. Although transcranial direct current stimulation (tDCS) is a promising non-invasive brain stimulation method, its effect in patients with AN remains unclear. Objective: This study investigated changes in maladaptive eating behavior, body mass index (BMI), and depression after 10 sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC). Methods: In this double-blind, randomized controlled trial, 43 inpatients with AN were divided to receive either active (n = 22) or sham (n = 21) tDCS over the left DLPFC (anode F3/cathode Fp2, 2 mA for 30 min). All patients filled the Eating Disorder Examination Questionnaire (EDE-Q) and Zung Self-Rating Depression Scale (ZUNG), and their BMI was measured. These values were obtained repeatedly in four stages: (1) before tDCS treatment, (2) after tDCS treatment, (3) in the follow-up after 2 weeks, and (4) in the follow-up after 4 weeks. Results: Primary outcomes (EDE-Q) based on the ANOVA results do not show any between-group differences either after the active part of the study or in the follow-up. Secondary analysis reveals a reduction in some items of EDE-Q. Compared with sham tDCS, active tDCS significantly improved self-evaluation based on body shape (p < 0.05) and significantly decreased the need of excessive control over calorie intake (p < 0.05) in the 4-week follow-up. However, the results do not survive multiple comparison correction. In both sham and active groups, the BMI values improved, albeit not significantly. Conclusion: We did not observe a significant effect of tDCS over the left DLPFC on complex psychopathology and weight recovery in patients with AN. tDCS reduced the need to follow specific dietary rules and improved body image evaluation in patients with AN. Tests with a larger sample and different positions of electrodes are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03273205.

The intestinal microbiota and metabolites in patients with anorexia nervosa.

Brain-gut microbiota interactions are intensively studied in connection with various neurological and psychiatric diseases. While anorexia nervosa (AN) pathophysiology is not entirely clear, it is presumably linked to microbiome dysbiosis. We aimed to elucidate the gut microbiota contribution in AN disease pathophysiology. We analyzed the composition and diversity of the gut microbiome of patients with AN (bacteriome and mycobiome) from stool samples before and after renourishment, and compared them to healthy controls. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFA) were analyzed in stool samples by MS and NMR, respectively. Biochemical, anthropometric, and psychometric profiles were assessed. The bacterial alpha-diversity parameter analyses revealed only increased Chao 1 index in patients with AN before the realimentation, reflecting their interindividual variation. Subsequently, core microbiota depletion signs were observed in patients with AN. Overrepresented OTUs (operation taxonomic units) in patients with AN taxonomically belonged to Alistipes, Clostridiales, Christensenellaceae, and Ruminococcaceae. Underrepresented OTUs in patients with AN were Faecalibacterium, Agathobacter, Bacteroides, Blautia, and Lachnospira. Patients exhibited greater interindividual variation in the gut bacteriome, as well as in metagenome content compared to controls, suggesting altered bacteriome functions. Patients had decreased levels of serotonin, GABA, dopamine, butyrate, and acetate in their stool samples compared to controls. Mycobiome analysis did not reveal significant differences in alpha diversity and fungal profile composition between patients with AN and healthy controls, nor any correlation of the fungal composition with the bacterial profile. Our results show the changed profile of the gut microbiome and its metabolites in patients with severe AN. Although therapeutic partial renourishment led to increased body mass index and improved psychometric parameters, SCFA, and neurotransmitter profiles, as well as microbial community compositions, did not change substantially during the hospitalization period, which can be potentially caused by only partial weight recovery.

Altered Serum Immunological and Biochemical Parameters and Microbiota Composition in Patients With AN During Realimentation.

Anorexia nervosa (AN) is a life-threatening psychiatric disorder with not well-described pathogenesis. Besides the genetic and sociological factors, autoimmunity is also considered to take part in AN pathogenesis. We evaluated general serological factors showing the physiological state of 59 patients with AN at hospital admission and their discharge. We detected the altered levels of some general biochemical and immunological parameters. We also detected decreased levels of appetite-regulating alpha-melanocyte stimulating hormone (α-MSH) in patients at hospital admission. Moreover, elevated anti-α-MSH IgM levels and decreased anti-α-MSH IgA levels were observed in patients with AN. Therefore, we analyzed the gut microbiota composition with special focus on α-MSH antigen-mimetic containing microbes from the Enterobacteriaceae family. We correlated gut bacterial composition with anti-α-MSH Ig levels and detected decreasing IgG levels with increasing alpha diversity. The upregulation of pro-inflammatory cytokines IL-6, IL-17, and TNF-α were detected in patients with AN both prior and after hospitalization. We also evaluated the treatment outcome and improvement was observed in the majority of patients with AN. We provide new data about various serum biochemical parameters and their changes during the patients' hospitalization, with emphasis on the immune system, and its possible participation in AN pathogenesis.