Impaired implicit learning in adults with anorexia nervosa.

OBJECTIVE: Cognitive alterations play an important role in the pathophysiology and treatment of anorexia nervosa (AN). Previous studies suggest that some implicit learning processes may be inhibited in AN. However, this has not yet been fully explored. The purpose of this study is to analyze implicit learning in patients with AN in comparison to healthy controls. METHODS: In this pilot-study, a total of 21 patients diagnosed with AN and 21 matched controls were administered the weather prediction task (WPT), a probabilistic implicit category learning task that consists of two sub-variants. During the feedback (FB) version of the task, participants learn associations between tarot cards and weather outcomes via an operant learning model through which they receive immediate FB on their answers, whereas during the paired associate (PA) variant, participants are directly asked to memorize given associations. RESULTS: AN patients showed selective impairment on the FB task where they scored significantly lower both in comparison to controls (p = .001) who completed the same task and when compared to their own performance on the PA variant (p = .006). Clinical measures showed no significant correlations with test scores. DISCUSSION: Our results demonstrate implicit FB learning deficiencies in adult patients with AN. These impairments may have an impact on the effect of psychotherapeutic interventions and could partially explain the lack of treatment response in AN. Further studies are necessary to derive when and through which mechanisms these alterations originate, and to what extent they should be considered during treatment of the disorder. PUBLIC SIGNIFICANCE: Cognitive impairments pose a challenge in the management of anorexia nervosa. Improved comprehension of cognitive alterations could lead to a greater understanding of the disease and adaptation of psychotherapeutic treatments. In this study, we found that implicit feedback learning in anorexia nervosa is impaired compared to healthy controls. This could indicate the necessity of treatment adaptations in the form of therapy tools without feedback and a larger focus on psychoeducation.

Gut Microbiome Composition and Its Association with Sleep in Major Psychiatric Disorders.

INTRODUCTION: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality. METHODS: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera. RESULTS: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI ≤8). CONCLUSION: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.

Association of fibroblast growth factor 21 with alcohol consumption and alcohol liver cirrhosis.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is produced in the liver and binds to different complex receptor/coreceptor systems. Besides many other processes, FGF21 regulates the intake of simple sugars and alcohol. Increased levels of FGF21 decrease harmful alcohol intake in mice. To increase our understanding on the relationship between FGF21 and alcohol intake in humans, we aimed to measure FGF21 levels in patients with alcoholic liver cirrhosis (ALC) in comparison to patients with nonalcoholic liver cirrhosis (NALC) and healthy persons based on their present alcohol consumption. METHODS: Alcohol intake was verified by urinary ethyl glucuronide (uETG) levels, eating and drinking behaviour by a Food Frequency Questionnaire and FGF 21 plasma levels were determined by ELISA in 96 persons (ALC n = 41; NALC n = 34; healthy n = 21). RESULTS: Both ALC and NALC patients with elevated ETG levels (≥0.5 µg/ml; indicating alcohol consumption in the last 12-72 h) showed significantly higher FGF21 plasma levels in comparison to patients with negative ETG levels. Eating behaviour did not have an impact on FGF21 plasma levels. CONCLUSIONS: Increased FGF21 levels in patients with recent alcohol consumption (verified by ETG) confirmed the first part of the liver-brain endocrine axis: alcohol consumption was associated with increased FGF21 levels. We could not confirm that elevated FGF21 levels were associated with reduced alcohol intake as a result. That points towards a pathology in this pathway, which might be caused by a malfunction of ß­Klotho or FGF receptors according to other studies and chronic alcohol dependency. Further research is required to clarify these pathologies, which may open new pharmacological treatment for patients with alcohol use disorder and alcohol dependence.

Exome sequencing of a Pakistani family with spastic paraplegia identified an 18 bp deletion in the cytochrome B5 domain of FA2H.

Hereditary spastic paraplegias (HSPs) are a diverse class of neurodegenerative disorders that mainly affect the corticospinal tract of the body and result in various clinical conditions such as lower limb spasticity and muscle weakness in the lower extremities. Worldwide, more than 70 chromosomal loci/genes have been reported to be associated with HSPs, out of which, six genes viz., ATL1, FA2H, GJC2, AP4E1, ALDH18A1 and ATP13A2 have been mapped in Pakistani families. In the present genetic study, we report on a large consanguineous Pakistani family with a complex form of HSP segregating with a 18 bp deletion in the first exon of the Fatty Acid 2-Hydroxylase (FA2H) gene (NM_024306.5:c.159_176del). The identified in-frame deletion results in loss of six amino acids (p.Arg53_Ile58del) within the cytochrome B5 domain of the protein. FA2H is required for alpha-hydroxylation of free fatty acids to form alpha-hydroxylated sphingolipids. Its cytochrome b5-like heme-binding domain, which spans from residues 15 to 85, imparts the redox activity to FA2H. This mutation has previously been reported in a Pakistani family presenting with a similar form of complex HSP. Together with our findings the pathogenic role of the observed variant is further supported. Mutation studies on additional Pakistani families for FA2H will further elucidate its mutational spectrum, which may help in developing a prenatal diagnostic test for Khyber Pakhtunkhwa resident Pakistani families.

Interleukin-6 is associated with tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption.

The aim of the present study was to investigate possible associations between interleukin-6 (IL-6), interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), lactoferrin and lipopolysaccharide binding protein (LBP) with TRP metabolism and signs of depression in a large cohort of outpatients referred for carbohydrate malabsorption testing. Serum concentrations of IL-6, INF-γ, TNF-α, lactoferrin, LBP, tryptophan (TRP), kynurenine (KYN) and kynuric acid were determined in 250 adults referred for lactose and fructose malabsorption testing. All participants filled out the Beck Depression Inventory (BDI). Serum IL-6 levels were positively correlated with the BDI score (p = 0.001, ρ = 0.205) and indicators of TRP metabolism (KYN/TRP ratio, KYN) (P-values < 0.05, ρ = 0.176 and 0.136). Ninety-five individuals with a BDI score > 13 showed significantly higher IL-6 serum levels (1.7 [1.0 - 2.8] vs. 1.1 [0.8 - 1.7] pg/mL, p < 0.001) compared to 115 individuals with a BDI score ≤ 13. LBP showed a positive correlation with the KYN/TRP ratio (p = 0.005, ρ = 0.177). IL-6 and LBP were associated with indicators of TRP metabolism. IL-6 was found to be linked to signs of depression. Individuals with the presence of depressive symptoms showed higher serum IL-6 levels compared to individuals without depressive symptoms.

Associations between tryptophan and iron metabolism observed in individuals with and without iron deficiency.

Current literature proposes associations between tryptophan metabolism and anaemia. However, study cohorts are rather small and final conclusions are still lacking. Here, we evaluated potential associations of tryptophan, kynurenine, and kynurenic acid with indicators of iron metabolism (i.e., mean corpuscular volume, mean corpuscular haemoglobin, ferritin, transferrin saturation, serum iron, transferrin, soluble transferrin receptor, reticulocyte haemoglobin) and haemoglobin in 430 individuals grouped by the presence or absence of iron deficiency or anaemia. Indicators of tryptophan metabolism were positively correlated with haemoglobin and markers of iron metabolism (p-values: <0.001-0.038; r-values: 0.100-0.305). The strongest correlation was observed between tryptophan and haemoglobin (p < 0.001, r = 0.305). The cubic regression model yielded the highest R-square values between haemoglobin and tryptophan markers. Overall, 115 patients with iron deficiency showed lower tryptophan and kynurenic acid concentrations compared to 315 individuals without iron deficiency. Six patients with anaemia of chronic disease were observed with the lowest serum tryptophan levels and the highest kynurenine/tryptophan ratio compared to 11 individuals with iron deficiency anaemia and 413 non-anaemic patients. This study showed little/moderate associations between haemoglobin, biomarkers of iron metabolism and tryptophan markers. Further studies are needed to get better insight in the causality of these findings.