Exploring Bias:Comparing Approaches for Collecting Twitter Data

Molecular Epidemiolog

Eating Disorders: From Twin Studies to Candidate Genes and Beyond

Abstract Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way

The problem of overcontrol:Perfectionism, emotional inhibition, and personality disorders

Background and AimsSome individuals with Personality Disorders (PD), particularly of a non-Borderline type, present with difficulties relating to over-control of cognitions, emotion and behavior, perfectionistic traits, and impaired social interactions. The current study sought to evaluate the strength of association, and interactions of both emotional inhibition and perfectionism in PD's, after controlling for symptoms and interpersonal problems.MethodWe recruited a sample of 578 treatment seeking outpatients. Diagnosis of PD was made with the SCID-II. Individual's completed measures of perfectionism (Frost-MPS), Emotional Inhibition (EIS), Depression (BDI-II), Anxiety (STAI-Y), Global symptoms (SCL-90-R), and interpersonal problems (IIP-32).ResultsPerfectionism was related to interpersonal problems, to the majority of PD symptomatology and to PD severity via number of SCID-II criteria met. Emotional inhibition was linked to symptoms and interpersonal problems as well as with avoidant, dependent, depressive and paranoid PDs; and with overall PD Severity. Inhibition and perfectionism were correlated with each other. Both variables predicted PD above and beyond other variables assessed. Mediation modelling demonstrated that the effect of emotional inhibition on PD severity was fully mediated by perfectionism and interpersonal problems.ConclusionsPsychological mechanisms of overcontrol are a maintaining factor in many PDs. Both perfectionism and emotional inhibition impact on a broad range of PDs and there is an urgent need for research into these processes, and to adapt psychological interventions to consider these factors

Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Associations between attention-deficit/hyperactivity disorder and various eating disorders: a Swedish nationwide population study using multiple genetically informative approaches

BACKGROUND: Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently cooccur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa.METHODS: We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472).RESULTS: Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes.CONCLUSIONS: We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.Stress-related psychiatric disorders across the life spa

Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.AMSUNY DownstatePsychiatry and Behavioral SciencesInstitute for Genomics in HealthN/

Self-assessment of eating disorder recovery: Absence of eating disorder psychopathology is not essential

Objective The definition of recovery in eating disorders (EDs) according to researchers is not necessarily similar to the patient definition. This study aimed to explore the concept of recovery as assessed by those affected by an ED themselves. Method Participants from the Netherlands Eating disorder Registry (NER) who reported an (former) ED diagnosis (n = 814) assessed their own recovery level: current ED, partial or full recovery. Furthermore, research-based criteria (Bardone-Cone et al., Behaviour Research and Therapy, 2010, 48, 194-202) were applied to define recovery. Within the self-assessed full recovery group (n = 179), participants who also fulfilled the research-based criteria were compared to those who were only recovered based on self-assessment in the following domains: ED psychopathology, psychiatric comorbidity, quality of life, and social and societal participation. Results Ninety-six of the participants (54%) who considered themselves recovered did not fulfill the research-based definition. The two recovery groups did not significantly differ in psychiatric comorbidity, quality of life, and social and societal participation. Discussion Absence of ED characteristics was not essential for individuals to consider themselves recovered. Although the self-assessed recovery status may be subjective, it does advocate the use of additional health indicators besides ED psychopathology when defining recovery

Classifying eating disorders based on "healthy" and "unhealthy" perfectionism and impulsivity

Stress-related psychiatric disorders across the life spa