Co-existing mental and somatic conditions in Swedish children with the avoidant restrictive food intake disorder phenotype.

Background: Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder, characterized by limited variety and/or quantity of food intake impacting physical health and psychosocial functioning. Children with ARFID often present with a range of psychiatric and somatic symptoms, and therefore consult various pediatric subspecialties; large-scale studies mapping comorbidities are however lacking. To characterize health care needs of people with ARFID, we systematically investigated ARFID-related mental and somatic conditions in 616 children with ARFID and >30,000 children without ARFID. Methods: In a Swedish twin cohort, we identified the ARFID phenotype in 6-12-year-old children based on parent-reports and register data. From >1,000 diagnostic ICD-codes, we specified mental and somatic conditions within/across ICD-chapters, number of distinct per-person diagnoses, and inpatient treatment days between birth and 18th birthday (90 outcomes). Hazard ratios (HR) and incidence rate ratios (IRR) were calculated. Findings: Relative risks of neurodevelopmental, gastrointestinal, endocrine/metabolic, respiratory, neurological, and allergic disorders were substantially increased in ARFID (e.g., autism HR[CI95%]=9.7[7.5-12.5], intellectual disability 10.3[7.6-13.9], gastroesophageal reflux disease 6.7[4.6-9.9], pituitary conditions 5.6[2.7-11.3], chronic lower respiratory diseases 4.9[2.4-10.1], epilepsy 5.8[4.1-8.2]). ARFID was not associated with elevated risks of autoimmune illnesses and obsessive-compulsive disorder. Children with ARFID had a significantly higher number of distinct mental diagnoses (IRR[CI95%]=4.7[4.0-5.4]) and longer duration of hospitalizations (IRR[CI95%]=5.5[1.7-17.6]) compared with children without ARFID. Children with ARFID were diagnosed earlier with a mental condition than children without ARFID. No sex-specific differences emerged. Interpretation: This study yields the broadest and most detailed evidence of co-existing mental and somatic conditions in the largest sample of children with ARFID to date. Findings suggest a complex pattern of health needs in youth with ARFID, underscoring the critical importance of attention to the illness across all pediatric specialties. Funding: Fredrik and Ingrid Thurings Foundation, Mental Health Foundation.

Mental and physical health in children of women with a history of anorexia nervosa.

Few studies have investigated the offspring of women with anorexia nervosa (AN). The aim of this study was to examine perinatal status, mental and physical health in the offspring of mothers with a history of AN. Fifty-one individuals with adolescent-onset AN and 51 matched controls (COMP) have been followed prospectively. Presently, 30 years after AN onset, at a mean age of 44 years, female participants who had given birth (nAN = 40, nCOMP = 40) were interviewed regarding psychiatric health in their offspring using the Developmental and Well-Being Assessment and the MINI International Neuropsychiatric Interview. In addition, information on the offspring's perinatal status, psychiatric- and physical health was obtained from the Swedish Medical Birth Register and The Swedish National Patient Register. Data regarding mental and physical health were available for 83 and 86 offspring in the AN and COMP groups, respectively. At birth, all of weight, length, head circumference and ponderal index were significantly reduced in the offspring of mothers with a history of AN. In adolescence, parental interviews indicated an overrepresentation of current psychiatric diagnoses in the offspring of mothers with AN. Compared with the offspring in the COMP group, endocrinological, immune and metabolic disorders were much more common in the offspring of the AN group. In conclusion, a history of AN increases the risk of worse perinatal outcome of the offspring. Later on, in childhood and adolescence, psychiatric and physical morbidity may be overrepresented in the offspring of women with AN.

ARFID Genes and Environment (ARFID-GEN): study protocol.

BACKGROUND: The Avoidant Restrictive Food Intake Disorder - Genes and Environment (ARFID-GEN) study is a study of genetic and environmental factors that contribute to risk for developing ARFID in children and adults. METHODS: A total of 3,000 children and adults with ARFID from the United States will be included. Parents/guardians and their children with ARFID (ages 7 to 17) and adults with ARFID (ages 18 +) will complete comprehensive online consent, parent verification of child assent (when applicable), and phenotyping. Enrolled participants with ARFID will submit a saliva sample for genotyping. A genome-wide association study of ARFID will be conducted. DISCUSSION: ARFID-GEN, a large-scale genetic study of ARFID, is designed to rapidly advance the study of the genetics of eating disorders. We will explicate the genetic architecture of ARFID relative to other eating disorders and to other psychiatric, neurodevelopmental, and metabolic disorders and traits. Our goal is for ARFID to deliver "actionable" findings that can be transformed into clinically meaningful insights. TRIAL REGISTRATION: ARFID-GEN is a registered clinical trial: clinicaltrials.gov NCT05605067.

Arfid Genes and Environment (ARFID-GEN): Study Protocol.

Background: The Avoidant Restrictive Food Intake Disorder Genes and Environment (ARFID-GEN) study is a study of genetic and environmental factors that contribute to risk for developing ARFID in children and adults. Methods: A total of 3,000 children and adults with ARFID from the United States will be included. Parents/guardians and their children with ARFID (ages 7 to 17) and adults with ARFID (ages 18+) will complete comprehensive online consent, parent verification of child assent (when applicable), and phenotyping. Enrolled participants with ARFID will submit a saliva sample for genotyping. A genome-wide association study of ARFID will be conducted. Discussion: ARFID-GEN, a large-scale genetic study of ARFID, is designed to rapidly advance the study of the genetics of eating disorders. We will explicate the genetic architecture of ARFID relative to other eating disorders and to other psychiatric, neurodevelopmental, and metabolic disorders and traits. Our goal is for ARFID to deliver "actionable" findings that can be transformed into clinically meaningful insights. Trial registration: ARFID-GEN is a registered clinical trial: clinicaltrials.gov NCT05605067.

Self-reported expertise and confidence in diagnosing and treating avoidant restrictive food intake disorder among Swedish clinicians.

OBJECTIVE: To assess self-reported knowledge and confidence regarding avoidant restrictive food intake disorder (ARFID) diagnosis and treatment in Swedish clinicians from various disciplines. METHOD: The study included 489 clinicians who attended educational lectures about ARFID. Participants responded to 20 ARFID-related questions and statements using the online audience engagement platform Mentimeter. Items assessed ARFID-related knowledge, education, and experience, as well as treatment methods offered to ARFID patients at clinicians' healthcare units. RESULTS: We found predominantly correct responses to three basic knowledge-based items about ARFID. However, most participants (64.0%) reported never having received education about ARFID, and few participants reported feeling confident in their ability to diagnose (13.4%) and treat (10.7%) ARFID. Nearly half the sample reported either not knowing which ARFID treatments their unit offered (22.3%) or that no treatment was offered (21.3%). CONCLUSION: Experience and confidence in diagnosing and treating ARFID are generally low in Swedish clinicians, and many individuals with ARFID do not receive treatment. We identify a pressing need for resources, clearer organisation, and structure, and for additional education and training opportunities for clinicians meeting individuals with ARFID.

Etiology of the Broad Avoidant Restrictive Food Intake Disorder Phenotype in Swedish Twins Aged 6 to 12 Years.

Importance: Avoidant restrictive food intake disorder (ARFID) is characterized by an extremely limited range and/or amount of food eaten, resulting in the persistent failure to meet nutritional and/or energy needs. Its etiology is poorly understood, and knowledge of genetic and environmental contributions to ARFID is needed to guide future research. Objective: To estimate the extent to which genetic and environmental factors contribute to the liability to the broad ARFID phenotype. Design, Setting, and Participants: This nationwide Swedish twin study includes 16 951 twin pairs born between 1992 and 2010 whose parents participated in the Child and Adolescent Twin Study in Sweden (CATSS) at twin age 9 or 12 years. CATSS was linked to the National Patient Register (NPR) and the Prescribed Drug Register (PDR). Data were collected from July 2004 to April 2020, and data were analyzed from October 2021 to October 2022. Main Outcomes and Measures: From CATSS, NPR, and PDR, all parent reports, diagnoses, procedures, and prescribed drugs that were relevant to the DSM-5 ARFID criteria were extracted when twin pairs were aged 6 to 12 years and integrated into a composite measure for the ARFID phenotype (ie, avoidant/restrictive eating with clinically significant impact, such as low weight or nutritional deficiency, and with fear of weight gain as an exclusion). In sensitivity analyses, autism and medical conditions that could account for the eating disturbance were controlled for. Univariate liability threshold models were fitted to estimate the relative contribution of genetic and environmental variation to the liability to the ARFID phenotype. Results: Of 33 902 included children, 17 151 (50.6%) were male. A total of 682 children (2.0%) with the ARFID phenotype were identified. The heritability of ARFID was 0.79 (95% CI, 0.70-0.85), with significant contributions from nonshared environmental factors (0.21; 95% CI, 0.15-0.30). Heritability was very similar when excluding children with autism (0.77; 95% CI, 0.67-0.84) or medical illnesses that could account for the eating disturbance (0.79; 95% CI, 0.70-0.86). Conclusions and Relevance: Prevalence and sex distribution of the broad ARFID phenotype were similar to previous studies, supporting the use of existing epidemiological data to identify children with ARFID. This study of the estimated genetic and environmental etiology of ARFID suggests that ARFID is highly heritable, encouraging future twin and molecular genetic studies.

Association of autism diagnosis and polygenic scores with eating disorder severity.

Among individuals with eating disorders (ED), those with co-occurring autism are often considered to have more severe presentations and poorer prognosis. However, previous findings have been contradictory and limited by small sample size and/or cross-sectional assessment of autistic traits. We examine the hypothesis that autism diagnosis and autism polygenic score (PGS) are associated with increased ED severity in a large ED cohort using a broad range of ED severity indicators. Our cohort included 3189 individuals (64 males) born 1977-2000 with current or previous anorexia nervosa who participated in the Anorexia Nervosa Genetics Initiative-Sweden (ANGI-SE) and for whom genotypes and linkage to national registers were available. We identified 134 (4.2%) individuals with registered autism diagnoses. Individuals with confirmed autism diagnosis had significantly more severe ED across three sets of severity indicators. Some of the largest effects were found for the proportion of individuals who attempted suicide and who received tube feeding (higher in autism), and for the time spent in inpatient care (longer in autism). Results for autism PGS were not statistically significant. Adapting ED treatment to the needs of individuals with co-occurring autism is an important research direction to improve treatment outcome in this group.

How genetic analysis may contribute to the understanding of avoidant/restrictive food intake disorder (ARFID).

Avoidant/restrictive food intake disorder (ARFID) was introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Unlike anorexia nervosa, ARFID is characterised by avoidant or restricted food intake that is not driven by weight or body shape-related concerns. As with other eating disorders, it is expected that ARFID will have a significant genetic risk component; however, sufficiently large-scale genetic investigations are yet to be performed in this group of patients. This narrative review considers the current literature on the diagnosis, presentation, and course of ARFID, including evidence for different presentations, and identifies fundamental questions about how ARFID might fit into the fluid landscape of other eating and mental disorders. In the absence of large ARFID GWAS, we consider genetic research on related conditions to point to possible features or mechanisms relevant to future ARFID investigations, and discuss the theoretical and clinical implications an ARFID GWAS. An argument for a collaborative approach to recruit ARFID participants for genome-wide association study is presented, as understanding the underlying genomic architecture of ARFID will be a key step in clarifying the biological mechanisms involved, and the development of interventions and treatments for this serious, and often debilitating disorder.

Avoidant/restrictive food intake disorder (ARFID) can be a severe and debilitating eating disorder, where individuals limit food intake for reasons unrelated to the weight and body image concerns observed in anorexia nervosa. Although genetics is known to play a significant role in other eating disorders such as anorexia nervosa and bulimia nervosa, only one study has investigated the genetic background of ARFID, and this was limited to those with ARFID within an autism cohort. This narrative review describes current knowledge about the clinical characteristics of ARFID and highlights current knowledge gaps, setting the scene for a discussion of how existing research findings about the genetics of related conditions might help guide genetic research about ARFID. A large genome-wide association study (GWAS) is recommended as the first step to addressing some of the fundamental biological questions around ARFID and will lay the framework for development of interventions and treatments that target ARFID at a biological level.

Validity of eating disorder diagnoses in the Swedish national patient register.

The Swedish National Patient Register (NPR) includes population-level longitudinal data, and determining the validity of NPR diagnoses is critical to undergirding the research and policy recommendations they inform. Sweden also has the integrated "Riksät" and "Stepwise" National Quality Registers (QR), with data from specialized eating disorder (ED) treatment based on structured, valid assessment methods. To validate NPR ED diagnoses, we compared ICD-10-based anorexia nervosa (AN), bulimia nervosa (BN), and unspecified ED in NPR to DSM-IV-based AN, BN, and ED not otherwise specified category (EDNOS) in QR. Patients' first diagnoses registered in QR between February 2008 and August 2013 were compared with NPR diagnoses entered within ±1 month (N = 2074). QR registration includes the semi-structured DSM-IV-based Structured ED Interview. Each ED diagnosis was analyzed separately for degree of match using several indices: overall agreement, sensitivity, positive predictive value, specificity, negative predictive value, area under the curve, and Cohen's kappa. Results showed moderate to excellent agreement depending on estimate (e.g. positive predictive values AN: 0.747; BN:.836; EDNOS: 0.761), except for a somewhat low sensitivity for BN, and EDNOS agreement was overall the lowest. Case prevalence in the NPR and QR was highly similar for AN, and within five percentage points for BN and EDNOS. Generalizability is hampered by limited age range and diagnostic resolution as well as few males. Available data precluded study of presence/absence of ED, and complementary approaches are considered for future research. We conclude that NPR ED diagnoses have acceptable validity and are appropriate for use in research.

Effects of autism on 30-year outcome of anorexia nervosa.

BACKGROUND: Long-term consequences of comorbid autism spectrum disorder (ASD) in individuals with anorexia nervosa (AN) are inadequately investigated. METHODS: In the 1980s, 51 adolescent-onset AN cases (AN group) and 51 matched controls (COMP group) were recruited from the community. They have been examined on five occasions. The four last assessments included the Morgan-Russell Outcome Assessment Schedule (MROAS) to assess eating disorder outcomes (weight, dieting, menstruation), and related problems including psychiatric, psychosexual and socioeconomic state. In the present study, at age 44, when 30 years had elapsed, MROAS data were compared with previous results. At age 16, 21, 24 and 32 years, all individuals had been assessed regarding ASD. At the 30-year follow-up, the impact of the ASD on the MROAS data was analysed. RESULTS: In the AN group, all core anorectic symptoms (weight, dieting, menstruation) were on a par with the COMP group at the 30-year follow-up, but the positive outcomes were limited to those who had never had an ASD diagnosis. Psychiatric state was significantly worse in the AN group, particularly in the subgroup who had an ASD diagnosis assigned. The AN group-again particularly those with ASD-had a more negative attitude to sexual matters than the COMP group. The AN group had worse outcomes than the COMP group for 'personal contacts', 'social contacts,' and 'employment record' at the 30-year follow-up and the outcomes were worse the more often an ASD diagnosis had been assigned. LIMITATIONS: Rare data collection points throughout 30 years (only 5 assessments). ASD was assessed in the first four studies but was not assessed again at the 30-year follow-up. CONCLUSIONS: Mental health, psychosexual, and socioeconomic status were compromised up to 30 years after AN onset. Coexisting ASD contributed to the poor outcome. Core anorectic symptoms had "normalised" three decades after AN onset. Some individuals with anorexia nervosa (AN) also suffer from autism. In this study we have investigated outcome of AN 30 years after the onset of AN and whether the presence of autism affects the outcome. Since the 1980s we have followed 51 individuals with teenage-onset AN and 51 healthy controls. They have been examined on five occasions, and an instrument that measures symptoms of AN (weight, dieting, body image), psychiatric symptoms, ability to work, and relationships with partner, family, and friends has been used to assess outcome. Autism was assessed in the first four studies. Symptoms of AN had normalised at 30-year follow-up, but only among those without autism. Psychiatric symptoms, ability to work, and relationships were issues that persisted after 30 years in the AN group, and those who had both autism and a history of AN had even more pronounced problems in these areas. The AN group had a more negative attitude to sexual matters than the control group, the outcome was worse the more often an autism diagnosis had been assigned. CONCLUSIONS: Mental health, psychosexual, and socioeconomic status are affected up to 30 years after AN onset, particularly among those with autism.

Early neurodevelopmental problems and risk for avoidant/restrictive food intake disorder (ARFID) in 4-7-year-old children: A Japanese birth cohort study.

Background: An overrepresentation of neurodevelopmental problems (NDPs) has been observed in individuals with avoidant/restrictive food intake disorder (ARFID). Previous studies on the association between ARFID and NDPs have been limited by cross-sectional data from clinical samples of small size. This study aimed to extend previous research by using prospectively collected data in a non-clinical child cohort. We examined the occurrence of early NDPs in 4-7-year-old children with suspected ARFID and how predictive early NDPs are of ARFID. Methods: Data were collected via parent-report a sub-sample of the Japan Environment and Children's Study (JECS) including 3728 children born 2011-2014 in Kochi prefecture. NDPs were assessed biannually between 0.5 and 3 years of age with the Ages and Stages Questionnaire-3, at age 2.5 years with the ESSENCE-Q, and at age 1 and 3 years via parent-reported clinical diagnoses. ARFID was identified cross-sectionally (at age 4-7 years) using a newly developed screening tool. Logistic regressions were used to test association of (1) a composite early NDP risk score, (2) specific early NDPs, and (3) neurodevelopmental trajectories over time with ARFID. Results: Children in the highest risk percentiles of the NDP risk score had roughly three times higher odds of having suspected ARFID; the absolute risk of later ARFID for children above the 90th percentile was 3.1%. Early NDPs (excluding early feeding problems) were more predictive of later ARFID than were early feeding problems. Specific NDPs predictive of ARFID were problems with general development, communication/language, attention/concentration, social interaction, and sleep. Neurodevelopmental trajectories of children with and without suspected ARFID started to divert after age 1 year. Conclusions: The results mirror the previously observed overrepresentation of NDPs in ARFID populations. In this non-clinical child cohort, early feeding problems were common and rarely developed into ARFID; however, our findings imply that they should be monitored closely in children with high NDP risk to prevent ARFID.

Development of a parent-reported screening tool for avoidant/restrictive food intake disorder (ARFID): Initial validation and prevalence in 4-7-year-old Japanese children.

The prevalence of avoidant/restrictive food intake disorder (ARFID) in the general child population is still largely unknown and validated screening instruments are lacking. The aims of this study were (1) to investigate the prevalence of children screening positive for ARFID in a Japanese birth cohort using a newly developed parent-reported screening tool, (2) to estimate the prevalence of children with ARFID experiencing physical versus psychosocial consequences of their eating pattern, and (3) to provide preliminary evidence for the validity of the new screening tool. Data were collected from 3728 4-7-year-old children born between 2011 and 2014 in Kochi prefecture, Japan (response rate was 56.5%); a sub-sample of the Japan Environment and Children's Study (JECS). Parents completed a questionnaire including the ARFID screener and several other measures to assess convergent validity. The point prevalence of children screening positive for ARFID was 1.3%; half of them met criteria for ARFID based on psychosocial impairment alone, while the other half met diagnostic criteria relating to physical impairment (and additional psychosocial impairment in many cases). Sensory sensitivity to food characteristics (63%) and/or lack of interest in eating (51%) were the most prevalent drivers of food avoidance. Children screening positive for ARFID were lighter in weight and shorter in height, they showed more problem behaviors related to mealtimes and nutritional intake, and they were more often selective eaters and more responsive to satiety, which together provides preliminary support for the validity of the new screening tool. This is the largest screening study to date of ARFID in children up to 7 years. Future studies should examine the diagnostic validity of the new ARFID screener using clinically ascertained cases. Further research on ARFID prevalence in the general population is needed.

Paediatric Acute onset Neuropsychiatric Syndrome: Exploratory study finds no evidence of HLA class II association but high rate of autoimmunity in first-degree relatives.

AIM: Paediatric acute-onset neuropsychiatric syndrome (PANS) is defined by an acute onset of obsessive-compulsive disorder and/or eating restrictions and at least two other severe neuropsychiatric symptoms. The condition is suspected to have an immune-mediated pathophysiology, but reliable biomarkers have not been identified. METHODS: We hypothesised that PANS, like narcolepsy, might have a human leucocyte antigen (HLA) association, as found in 95% of children developing narcolepsy after H1N1 immunisation. Low resolution genotyping of the MHC class II antigens HLA-DRB1 and HLA-DQB1 was performed using two different PCR-based methods. In addition, parents were interviewed regarding a detailed family history of autoimmune diseases in first-degree relatives. A total of 18 children, aged 5-14 (mean 8.2) years at onset of PANS met symptom criteria. RESULTS: No evident association between PANS and the specific HLA alleles examined was observed. In first-degree relatives of 10 of the 18 children, an autoimmune disease had been diagnosed, and three of the 18 children themselves had an autoimmune disease. CONCLUSION: No HLA allele association such as seen in children with narcolepsy after H1N1 immunisation could be confirmed in this group of children with PANS. However, more than half the group had a first-degree relative with a diagnosed autoimmune disease.

Feeding Problems Including Avoidant Restrictive Food Intake Disorder in Young Children With Autism Spectrum Disorder in a Multiethnic Population.

We examined feeding problems, including Avoidant Restrictive Food Intake Disorder (ARFID), in preschool children with Autism Spectrum Disorder (ASD). Data were collected from a prospective longitudinal study of 46 children with ASD in a multiethnic, low resource area in Gothenburg, Sweden. Feeding problems were found in 76% of the children with ASD, and in 28%, the criteria for ARFID were met. The study highlights early onset age, the heterogeneity of feeding problems, and the need for multidisciplinary assessments in ASD as well as in feeding problems, and also the need for further elaboration of feeding disorder classifications in children.

Assessment of avoidant restrictive food intake disorder, pica and rumination disorder: interview and questionnaire measures.

PURPOSE OF REVIEW: This article reviews available assessment instruments for three of the feeding and eating disorder diagnostic categories: avoidant restrictive food intake disorder (ARFID), pica, and rumination disorder (RD). It includes an overview of the current status of screening tools, questionnaire measures, and diagnostic instruments. RECENT FINDINGS: Screening instruments are available for all three disorders; however, for pica and RD, these typically include single screening items only and do not cover any specific features of these presentations. Only one questionnaire suitable for clinical populations is included, covering ARFID only. Standardized diagnostic interviews are limited to two covering both pica and RD, only one of which provides further clinical information. Of the five diagnostic instruments for ARFID described here, two include diagnostic items as well as allowing more detailed assessment of clinical features. SUMMARY: There are a limited number of assessment measures available for all three disorders, with instruments for ARFID being the greatest in number and widest in terms of scope. A commonly encountered difficulty is that many assessment instruments do not adequately cover diagnostic exclusion criteria, which raises the likelihood of false positive findings. All currently available measures require further study to determine their reliability and validity.

No neurochemical evidence of neuronal injury or glial activation in children with Paediatric Acute-onset Neuropsychiatric Syndrome. An explorative pilot study.

Objective: Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterised by an acute onset of obsessive compulsive disorder, combined with at least two other neuropsychiatric symptoms with acute onset. Diagnostic criteria also require that no specific medical aetiology is identified. Although there are no verified aetiological biomarkers, PANS is assumed to be a neuroinflammatory disorder with a possible autoimmune aetiology. Neurochemical markers such as neurofilament light (NfL, a neuronal injury marker) and glial fibrillary acidic protein (GFAP, an astrocytic activation marker) have not been published for this patient group.Method: Blood samples from 17 children meeting diagnostic criteria for PANS, after assessment at a child neuropsychiatry clinic were analysed for serum concentrations of NfL and GFAP. Ten age-matched children without any neurological or psychiatric disorder served as a comparison group.Results: No difference was found in mean NfL and mean GFAP serum concentrations between children with PANS and controls.Conclusion: Neuronal injury and astrocyte activation do not seem to be a major event in PANS. The study group was small, and even if findings may be reassuring for parents and patients, they should be interpreted with caution and verified in larger cohorts and possibly with other markers in both serum and CSF.

The co-occurrence of neurodevelopmental problems in dyslexia.

The primary aim of this study was to explore the overlaps between dyslexia and a range of neurodevelopmental disorders and problems (NDPs), specifically symptoms of attention-deficit/hyperactivity disorder, autism spectrum disorder, atypical sensory perception and developmental coordination disorder. Capitalizing on a population-based sample of twins, secondary aims included estimating the heritability of dyslexia and reporting on the measurement characteristics of the scale used to assess dyslexia. A telephone interview regarding symptoms of dyslexia and other NDPs was conducted with parents of 1,688 nine-year-old twins. The prevalence and the heritability of dyslexia were estimated at 8 and 52%, respectively. The boy: girl ratio was 1.5:1. Results revealed that there was more than an eight-fold increase in (diagnostic proxy) NDPs prevalence in the dyslexia group as compared to typical readers. Quantitatively measured symptoms of inattention, oral language problems and atypical sensory perception significantly predicted dyslexia status in a multivariate analysis. By contrast, ASD-related inflexibility was inversely associated with dyslexia in the multivariate model. In sum, dyslexia often overlaps with other NDPs. The current study provides new knowledge supporting the position to move beyond isolated diagnostic categories into behavioural profiles of co-occurring problems when trying to understand the pattern of strengths and needs in individuals with dyslexia.

Association of etiological factors across the extreme end and continuous variation in disordered eating in female Swedish twins.

BACKGROUND: Accumulating evidence suggests that many psychiatric disorders etiologically represent the extreme end of dimensionally distributed features rather than distinct entities. The extent to which this applies to eating disorders (EDs) is unknown. METHODS: We investigated if there is similar etiology in (a) the continuous distribution of the Eating Disorder Inventory-2 (EDI-2), (b) the extremes of EDI-2 score, and (c) registered ED diagnoses, in 1481 female twin pairs at age 18 years (born 1992-1999). EDI-2 scores were self-reported at age 18. ED diagnoses were identified through the Swedish National Patient Register, parent-reported treatment and/or self-reported purging behavior of a frequency and duration consistent with DSM-IV criteria. We differentiated between anorexia nervosa (AN) and other EDs. RESULTS: The heritability of the EDI-2 score was 0.65 (95% CI 0.61-0.68). The group heritabilities in DeFries-Fulker extremes analyses were consistent over different percentile-based extreme groups [0.59 (95% CI 0.37-0.81) to 0.65 (95% CI 0.55-0.75)]. Similarly, the heritabilities in liability threshold models were consistent over different levels of severity. In joint categorical-continuous models, the twin-based genetic correlation was 0.52 (95% CI 0.39-0.65) between EDI-2 score and diagnoses of other EDs, and 0.26 (95% CI 0.08-0.42) between EDI-2 score and diagnoses of AN. The non-shared environmental correlations were 0.52 (95% CI 0.32-0.70) and 0.60 (95% CI 0.38-0.79), respectively. CONCLUSIONS: Our findings suggest that some EDs can partly be conceptualized as the extreme manifestation of continuously distributed ED features. AN, however, might be more distinctly genetically demarcated from ED features in the general population than other EDs.

Anorexia nervosa and autism: a prospective twin cohort study.

BACKGROUND: Anorexia nervosa (AN) and autism spectrum disorder (ASD) may be phenotypically and etiologically linked. However, due to the absence of prospective studies, it remains unclear whether the elevation of autistic traits in AN is evident in early childhood. Here, we prospectively investigated autistic traits before and after the first diagnosis of AN. METHODS: In a population-based sample of 5,987 individuals (52.4% female) from the Child and Adolescent Twin Study in Sweden, parents reported autistic traits at ages 9 and 18. AN and ASD diagnoses were retrieved from the Swedish National Patient Register. In addition, AN diagnoses were ascertained by parent-reported treatment for AN. We compared whether individuals with and without AN differed in autistic traits before the first diagnosis of AN (age 9) and after the first diagnosis of AN (age 18). RESULTS: We did not find evidence for elevated autistic traits in 9-year-old children later diagnosed with AN. At age 18, however, there was a marked elevation in restricted/repetitive behavior and interests, but only in the subgroup of individuals with acute AN. A less pronounced elevation was observed for social communication problems. CONCLUSIONS: Coping strategies in individuals with ASD and the somewhat different female ASD phenotype may explain why we did not find elevated autistic traits in children who later developed AN. Alternatively, it is possible that elevated autistic traits were not present prior to the onset of AN, thus questioning the previously reported elevated prevalence of ASD in AN. Future studies should use tailored measurements in order to investigate whether autistic traits in individuals with AN are best conceptualized as an epiphenomenon of the acute AN phase or whether these symptoms indeed represent ASD as a clinically verifiable neurodevelopmental disorder.

Thirty years after anorexia nervosa onset, serum neurofilament light chain protein concentration indicates neuronal injury.

Little is known about the long-term consequences of anorexia nervosa (AN) in terms of possible brain neuronal injury. We aimed at investigating whether women with adolescent-onset AN exhibit increased serum levels of neurofilament light chain protein (NfL), a biomarker for neuronal injury, compared with matched controls at 30-year follow-up. Blood samples were collected from 34 women with adolescent-onset AN and 38 matched healthy comparison women (COMP), at a mean age of 44 years (range 38-48 years). NfL was measured in serum using the in-house single molecule array (Simoa) method. The individuals were asked whether they or their parents had been diagnosed with dementia. The Swedish National Patient Register was searched for diagnoses related to dementia. Serum NfL concentrations were significantly higher in the AN group (AN 27.7 pg/ml; COMP 19.0 pg/ml; p = 0.041). When individuals with medical/neurological disorders in the AN and COMP groups were excluded, there was a statistically non-significant trend towards higher concentrations in the AN group (AN 27.4 pg/ml; COMP 18.8 pg/ml; p = 0.060). None of the participants had been diagnosed with dementia. There was no significant correlation between serum NfL and AN duration (r = 0.15). There was a moderate negative correlation between the serum NfL concentration and the current BMI in the AN group (r = 0.44). This is the first time that serum NfL has been assessed in middle-aged women with a history of adolescent-onset AN. The results suggest that there might be increased axonal degeneration as a sequel of AN. Individuals remaining underweight had higher serum NfL concentrations than those with a normal/high BMI. Additional studies are needed to confirm increased serum NfL concentrations in individuals recovered from AN. There is a need for further study of axonal degeneration as a consequence of AN.