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

SuPAR in major depression: Association with 26 weeks antidepressant response and 10-year depression outcomes

Introduction: Inflammation has been associated with depression and differential antidepressant (AD) treatment response. Soluble urokinase plasminogen activator receptor (suPAR) is a novel measure of chronic inflammation. We investigated whether suPAR is associated with depression severity and AD response. Methods: We included 90 patients with major depressive disorder (MDD) who participated in a part-randomized clinical trial of 26 weeks of treatment with escitalopram or nortriptyline. suPAR levels were measured in serum samples collected at baseline and after 8, 12 and 26 weeks. Mixed effects models for the association between suPAR levels and AD response were performed. By merging with Danish nationwide registers, we included information on psychiatric hospital contacts during ten years after the GENDEP trial. Cox regression analyses calculated the hazard rate ratios between suPAR levels and subsequent hospitalizations. Results: At baseline, higher suPAR levels were not associated with overall depression severity but with greater severity of neurovegetative depressive symptoms, specifically appetite and weight changes. 57 (63.3%) patients responded positively to treatment. Among 57 (63.3%) patients who achieved response, those who responded had significantly higher baseline suPAR levels levels, and response was associated with a significant decrease in suPAR during AD treatment. Remitters decreased from 3.1 ng/ml at baseline to 2.8 ng/ml after 26 weeks (p = 0.003) and responders from 3.0 to 2.8 ng/ml (p = 0.02), whereas non-remitters and non-responders showed unchanged suPAR levels. We found no correlation between a change in suPAR and a change in MADRS, but a lowering of suPAR correlated with a decrease in neurovegetative symptoms. We found no association between suPAR levels and 10-year risk for hospitalizations. Discussion: The present study suggests that an elevated level of chronic inflammation, measured as the suPAR level, is associated with better response to AD treatment

Metabolic profile at first-time schizophrenia diagnosis: a population-based cross-sectional study

Henriette Thisted Horsdal,1,2 Michael Eriksen Benros,2,3 Ole Köhler-Forsberg,2–4 Jesper Krogh,3 Christiane Gasse1,2,5 1National Centre for Register-based Research, Department of Economics and Business Economics, Aarhus BSS, Aarhus University, Aarhus, 2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, 3Faculty of Health Sciences, Mental Health Centre Copenhagen, University of Copenhagen, Copenhagen, 4Psychosis Research Unit, Aarhus University Hospital, Risskov, 5Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark Objective: Schizophrenia and/or antipsychotic drug use are associated with metabolic abnormalities; however, knowledge regarding metabolic status and physician’s monitoring of metabolic status at first schizophrenia diagnosis is sparse. We assessed the prevalence of monitoring for metabolic blood abnormalities and characterized the metabolic profiles in people with a first-time schizophrenia diagnosis. Methods: This is a population-based cross-sectional study including all adults born in Denmark after January 1, 1955, with their first schizophrenia diagnosis between 2000 and 2012 in the Central Denmark Region. Information on metabolic parameters was obtained from a clinical laboratory information system. Associations were calculated using Wilcoxon rank-sum tests, chi-square tests, logistic regression, and Spearman’s correlation coefficients. Results: A total of 2,452 people with a first-time schizophrenia diagnosis were identified, of whom 1,040 (42.4%) were monitored for metabolic abnormalities. Among those monitored, 58.4% had an abnormal lipid profile and 13.8% had an abnormal glucose profile. People who had previously filled prescription(s) for antipsychotic drugs were more likely to present an abnormal lipid measure (65.7% vs 46.8%, P<0.001) and abnormal glucose profile (16.4% vs 10.1%, P=0.01). Conclusion: Metabolic abnormalities are common at first schizophrenia diagnosis, particularly among those with previous antipsychotic prescription(s). Increased metabolic abnormalities already present in the early phase of schizophrenia emphasize the need for increased monitoring and management. Keywords: schizophrenia, metabolism, epidemiology, lipids, glucos

Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: a systematic review

Neurodevelopmental disorders – including attention‐deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders – manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome‐wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence – from two or more studies from independent research groups, with results going into the same direction – of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi‐level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost‐effectiveness, before they can be implemented in daily clinical practice