Common Genetic Variation And Age at Onset Of Anorexia Nervosa

Background Genetics and biology may influence the age at onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to AN age at onset and to investigate the genetic associations between age at onset of AN and age at menarche. Methods A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed which included 9,335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age at onset, early-onset AN (< 13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (SNP-h2) were 0.01-0.04 for age at onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age at onset and early-onset AN estimated from independent GWASs significantly predicted age at onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions Our results provide evidence consistent with a common variant genetic basis for age at onset and implicate biological pathways regulating menarche and reproduction.Peer reviewe

Eating disorders in adolescents and young adults : diagnosis, occurrence, treatment, and outcome

Background and aims: Eating disorders are severe mental health issues that undermine psychological and physical health and quality of life. This thesis aimed to investigate the occurrence of eating disorders in a community sample of adolescents and young adults. Eating disorders were defined using the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). A second major aim was to describe how often individuals with eating disorders were detected and received treatment and what kind of treatment was offered. Finally, the natural course and outcome of different subcategories of eating disorders were also examined. Methods: The study used two population-based Finnish twin datasets and one clinical dataset. FinnTwin12 followed all twins born in Finland between 1983 and 1987, whereas FinnTwin16 followed all twins born between 1975 and 1979, from adolescence to adulthood. From the FinnTwin12 data, we studied the occurrence, detection and treatment of eating disorders in health care and the natural course of these diseases. From the FinnTwin16 data, we examined the effects of diagnostic changes on the occurrence and prognosis of anorexia nervosa. From the clinical data of the Helsinki and Uusimaa Hospital District (HUS) Adolescent Psychiatry Eating Disorders Unit, we examined the treatment and prognosis of adolescents with typical and atypical anorexia nervosa. In all studies, we analysed the outcome of eating disorders using survival analysis. Results: Eating disorders were common. Up to one in 6 females and 1 in 40 males had suffered from an eating disorder during their development towards adulthood. Changes in diagnostic criteria increased the lifetime prevalence of anorexia nervosa by more than half and increased diagnostic heterogeneity. Overall, anorexia nervosa and related subthreshold symptoms were prevalent among females: One in 10 young women had suffered from a restrictive eating disorder by early adulthood. We also found that eating disorder symptoms in a community setting were diverse, and many reported eating disorder symptoms that could not be clearly labelled. This was particularly true among boys and men. Many individuals with eating disorders also described an unmet need for care; healthcare professionals diagnosed only one-third and even fewer received treatment. In addition, eating disorder symptoms were highly persistent: Five years after disease onset, less than two-fifths of the females and two-thirds of the males had recovered. The likelihood of recovery was similar between those who had and who had not received treatment, but more severe cases were more likely to receive treatment. Conclusions: Overall, this thesis showed that eating disorders are common, and their symptoms are highly diverse among Finnish adolescents and young adults. Considering the magnitude of the problem, detection and treatment approaches for eating disorders are still inadequate and mainly focused on typical presentations of eating disorders. In addition, eating disorder symptoms often persisted for years. Future research should determine how the prevention and detection of eating disorders could be improved in Finland. The threshold for access to treatment should also be lowered, and additional interventions should be developed. Future studies should investigate whether these actions could eventually lead to better outcomes.Tausta ja tavoitteet: Syömishäiriöt ovat vakavia psyykkistä ja fyysistä terveyttä sekä elämänlaatua uhkaavia mielenterveyden häiriöitä. Tämän väitöstutkimuksen tavoitteena oli selvittää Amerikan psykiatriyhdistyksen uusimpien kriteereiden mukaisten syömishäiriöiden yleisyyttä suomalaisilla nuorilla ja nuorilla aikuisilla. Lisäksi tutkimuksessa kartoitettiin syömishäiriöiden tunnistamista terveydenhuollossa ja saatua hoitoa, sekä tutkittiin syömishäiriöiden luonnollista kulkua ja diagnooseihin liittyvää ennustetta. Menetelmät: Tutkimuksessa hyödynnettiin kahta väestöpohjaista kaksosaineistoa ja yhtä kliinistä potilasaineistoa. Kaksosten kehitys ja terveys- tutkimuksessa (FinnTwin12) pyrittiin seuraamaan kaikkia Suomessa vuosina 1983–1987 ja Nuorten kaksosten terveystutkimuksessa (FinnTwin 16) kaikkia vuosina 1975 – 1979 syntyneitä kaksosia nuoruudesta aikuisuuteen saakka. FinnTwin12 aineistosta kartoitettiin syömishäiriöiden yleisyyttä, tunnistamista ja hoitoa terveydenhuollossa sekä sairauden kestoa ja toipumista. FinnTwin16 aineistosta tarkasteltiin diagnoosimuutosten vaikutusta laihuushäiriön yleisyyteen ja ennusteeseen. Helsingin ja Uudenmaan sairaanhoitopiirin (HUS) nuorisopsykiatrian syömishäiriöyksikön aineistosta selvitettiin laihuushäiriötä ja epätyypillistä laihuushäiriötä sairastavien nuorten hoitoa ja diagnoosin merkitystä ennusteeseen. Tulokset: Tämän väitöstutkimuksen tulokset osoittivat, että syömishäiriöt ovat Suomessa yleisiä. Varhaisaikuisuuteen mennessä jopa joka kuudes nainen ja joka neljäskymmenes mies oli sairastanut syömishäiriön. Kokonaisuudessaan tytöillä ja nuorilla naisilla laihuushäiriö ja sen taudinkuvaa muistuttavat syömishäiriöt olivat yleisiä, sillä joka kymmenes nuori nainen oli kärsinyt restriktiivisestä syömishäiriöstä varhaisaikuisuuteen mennessä. Lisäksi väestössä esiintyvien syömishäiriöiden havaittiin olevan oirekuvaltaan monimuotoisia. Diagnoosimuutoksista huolimatta määrittämättömät syömishäiriöt olivat yhä yleisiä ja muodostivat pojilla ja miehillä yleisimmän syömishäiriöluokan. Lisäksi monen syömishäiriöön sairastuneen todettiin jäävän ilman apua, sillä vain kolmasosa tunnistettiin terveydenhuollossa, ja vielä harvempi sai hoitoa. Erityisen huonosti hoidon piiriin pääsivät epätyypillisistä syömishäiriöistä kärsivät. Syömishäiriöoireiden havaittiin myös olevan pitkäaikaisia, sillä viisi vuotta taudin puhkeamisen jälkeen alle kaksi viidesosaa naisista ja kaksi kolmasosaa miehistä oli toipunut. Hoitoa saaneiden toipumisen todennäköisyys ei eronnut hoitoa vaille jääneiden toipumisen todennäköisyydestä, mutta hoitoa saaviin valikoitui mahdollisesti vaikeammin oireilevia. Johtopäätökset: Kokonaisuudessaan tämä väitöstutkimus osoittaa, että suomalaisilla nuorilla ja nuorilla aikuisilla syömishäiriöt ovat yleisiä ja oirekuviltaan monimuotoisia. Syömishäiriöiden tunnistaminen ja hoito ovat vielä puutteellisia ongelman suuruusluokka huomioiden ja keskittyneet lähinnä tyypillisiin oirekuviin. Lisäksi syömishäiriöoireista kärsitään usein vuosia. Tulevissa tutkimuksissa tulisikin selvittää, miten syömishäiriöiden ehkäisyä ja tunnistamista voitaisiin parantaa Suomessa. Hoitoon pääsemisen kynnystä tulisi myös madaltaa sekä kehittää hoitoja, ja tutkia näiden toimien vaikutusta syömishäiriöiden ennusteeseen

DSM-5 eating disorders among adolescents and young adults in Finland: A public health concern

OBJECTIVE: We aimed to assess the lifetime prevalence, 10-year incidence, and peak periods of onset for eating disorders as defined by the Fifth Diagnostic and Statistical Manual of Mental Disorders (DSM-5) among adolescents and young adults born in the 1980s in Finland. METHOD: Virtually all Finnish twins born in 1983-1987 (n = 5,600) were followed prospectively from the age of 12 years. A subsample of participants (n = 1,347) was interviewed using a semi-structured diagnostic interview in their early twenties. RESULTS: The prevalence of lifetime DSM-5 eating disorders was 17.9% for females and 2.4% for males (pooled across genders, 10.5%). The estimated lifetime prevalences for females and males, respectively, were 6.2 and 0.3% for anorexia nervosa (AN), 2.4 and 0.16% for bulimia nervosa (BN), 0.6 and 0.3% for binge-eating disorder (BED), 4.5 and 0.16% for other specified feeding or eating disorder (OSFED), and 4.5 and 1.6% for unspecified feeding or eating disorder (UFED). Among females, the prevalence of OSFED subcategories was as follows: atypical AN 2.1%, purging disorder 1.3%, BED of low frequency/limited duration 0.7%, and BN of low frequency/limited duration 0.4%. The 10-year incidence rate of eating disorders was 1,700 per 100,000 person-years among females (peak age of onset 16-19 years) and 220 per 100,000 person-years among males. DISCUSSION: Eating disorders are a common public health concern among youth and young adults, affecting one in six females and one in 40 males. Adequate screening efforts, prevention, and interventions are urgently needed.Peer reviewe

Common Genetic Variation and Age of Onset of Anorexia Nervosa

Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche. Methods: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (<13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism–h2) were 0.01–0.04 for age of onset, 0.16–0.25 for early-onset AN, and 0.17–0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction