Psychiatric comorbidity in individuals with bullous pemphigoid and all bullous disorders in the Danish national registers

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering skin disease that takes a profound physical and mental toll on those affected. The aim of the study was to investigate the bidirectional association between BP and all bullous disorders (ABD) with a broad array of psychiatric disorders, exploring the influence of prescribed medications. METHODS: This nationwide, register-based cohort study encompassed 6,470,450 individuals born in Denmark and alive from 1994 to 2016. The hazard ratios (HRs) of a subsequent psychiatric disorder in patients with BP/ABD and the reverse exposure and outcome were evaluated. RESULTS: Several psychiatric disorders were associated with increased risk of subsequent BP (4.18-fold for intellectual disorders, 2.32-fold for substance use disorders, 2.01-fold for schizophrenia and personality disorders, 1.92-1.85-1.49-fold increased risk for organic disorders, neurotic and mood disorders), independent of psychiatric medications. The association between BP and subsequent psychiatric disorders was not significant after adjusting for BP medications, except for organic disorders (HR 1.27, CI 1.04-1.54). Similar results emerged with ABD. CONCLUSION: Psychiatric disorders increase the risk of a subsequent diagnosis of BP/ABD independent of medications, whereas medications used for the treatment of BP/ABD appear to account for the subsequent onset of psychiatric disorders. Clinically, an integrated approach attending to both dermatological and psychiatric symptoms is recommended, and dermatologists should remain vigilant for early symptoms of psychiatric disorders to decrease mental health comorbidity

Association of Exposure to Infections in Childhood with Risk of Eating Disorders in Adolescent Girls

Importance: Infections are recognized as playing a critical role in the risk of psychiatric disorders and suicidal behavior; however, few studies have evaluated the risk of eating disorders. Objective: To evaluate the association of hospitalization for infections and treatment with anti-infective agents with the risk of an eating disorder diagnosis. Design, Setting, and Participants: A nationwide, population-based, prospective cohort study of 525643 girls born from January 1, 1989, to December 31, 2006, and followed up until December 31, 2012, was conducted using individual-level data drawn from Danish longitudinal registers. Data were analyzed from January 15 to June 15, 2018, using survival analysis models and adjusted for age, calendar period, parental educational level, and parental history of psychiatric illness. Exposures: Hospital admission for infections and prescribed anti-infective agents for infections. Main Outcomes and Measures: The main outcome of interest was diagnosis of an eating disorder (anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified) in a hospital, outpatient clinic, or emergency department setting. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and accompanying 95% CIs. Results: The study population consisted of 525643 adolescent girls: 2131 received a diagnosis of anorexia nervosa (median [range] age, 15.2 [8.6-21.3] years), 711 received a diagnosis of bulimia nervosa (median [range] age, 17.9 [13.4-22.7] years), and 1398 received a diagnosis of an eating disorder not otherwise specified (median [range] age, 15.6 [8.6-21.6] years). A total of 525643 adolescent girls were followed up for 4601720.4 person-years until a mean age of 16.2 years (range, 10.5-22.7 years). Severe infections that required hospitalization were associated with an increased risk of a subsequent diagnosis of anorexia nervosa by 22% (HR, 1.22; 95% CI, 1.10-1.35), bulimia nervosa by 35% (HR, 1.35; 95% CI, 1.13-1.60), and eating disorder not otherwise specified by 39% (HR, 1.39; 95% CI, 1.23-1.57) compared with adolescent girls without hospitalizations for infections. Infections treated with anti-infective agents were associated with an increased risk of a subsequent diagnosis of anorexia nervosa by 23% (HR, 1.23; 95% CI, 1.10-1.37), bulimia nervosa by 63% (HR, 1.63; 95% CI, 1.32-2.02), and eating disorder not otherwise specified by 45% (HR, 1.45; 95% CI, 1.25-1.67) compared with adolescent girls without infections treated with anti-infective agents. Conclusions and Relevance: The findings suggest that hospital-treated infections and less severe infections treated with anti-infective agents are associated with increased risk of subsequent anorexia nervosa, bulimia nervosa, and eating disorders not otherwise specified and that future studies should investigate whether these associations are causal and identify the exact mechanisms between infections and subsequent inflammatory processes with eating disorders

Autoimmune psychosis: an international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin

There is increasing recognition in the neurological and psychiatric literature of patients with so-called isolated psychotic presentations (ie, with no, or minimal, neurological features) who have tested positive for neuronal autoantibodies (principally N-methyl-D-aspartate receptor antibodies) and who have responded to immunotherapies. Although these individuals are sometimes described as having atypical, mild, or attenuated forms of autoimmune encephalitis, some authors feel that that these cases are sufficiently different from typical autoimmune encephalitis to establish a new category of so-called autoimmune psychosis. We briefly review the background, discuss the existing evidence for a form of autoimmune psychosis, and propose a novel, conservative approach to the recognition of possible, probable, and definite autoimmune psychoses for use in psychiatric practice. We also outline the investigations required and the appropriate therapeutic approaches, both psychiatric and immunological, for probable and definite cases of autoimmune psychoses, and discuss the ethical issues posed by this challenging diagnostic category.Thomas A Pollak, Belinda R Lennox, Sabine Müller, Michael E Benros, Harald Prüss, Ludger Tebartz van Elst, Hans Klein, Johann Steiner, Thomas Frodl, Bernhard Bogerts, Li Tian, Laurent Groc, Alkomiet Hasan, Bernhard T Baune, Dominique Endres, Ebrahim Haroon, Robert Yolken, Francesco Benedetti, Angelos Halaris, Jeffrey H Meyer, Hans Stassen, Marion Leboyer, Dietmar Fuchs, Markus Otto, David A Brown, Angela Vincent, Souhel Najjar, Karl Bechte

Alteration of gut microbiome in patients with schizophrenia indicates links between bacterial tyrosine biosynthesis and cognitive dysfunction

BACKGROUND: Schizophrenia (SCZ) is a heterogeneous neuropsychiatric disorder, for which current treatment has insufficient efficacy and severe adverse effects. The modifiable gut microbiome might be a potential target for intervention to improve neurobiological functions through the gut-microbiome-brain axis. METHODS: In this case-control study, gut microbiota of 132 patients with SCZ and increased waist circumference was compared to gut microbiota of two age- and sex-matched control groups, comprising 132 healthy individuals (HC) and 132 individuals with metabolic syndrome (MS). Shotgun sequencing was used to characterize fecal samples at taxonomic and functional level. Cognition of the SCZ patients was evaluated using the Brief Assessment of Cognition instrument. RESULTS: SCZ gut microbiota differed significantly from those of HC and MS in terms of richness and global composition. SCZ gut microbiota was notably enriched in Flavonifractor plautii, Collinsella aerofaciens, Bilophila wadsworthia and Sellimonas intestinalis, while depleted in Faecalibacterium prausnitzii, Ruminococcus lactaris, Ruminococcus bicirculans and Veillonella rogosae. Functional potential of the gut microbiota accounted for 11% of the cognition variability. In particular, the bacterial functional module for synthesizing tyrosine, a precursor for dopamine, was in SCZ cases positively associated to cognitive score (rho = 0.34, q = 0.1). CONCLUSIONS: Overall, this study shows that the gut microbiome of SCZ patients differs greatly from that of healthy or MS controls. Cognitive function of SCZ patients is associated with the potential for gut bacterial biosynthesis of tyrosine, a precursor for dopamine, suggesting gut microbiota might be an intervention target for alleviation of cognitive dysfunction in SCZ

Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.Therapeutic cell differentiatio