Identification of women at high risk of postpartum psychiatric episodes: A population-based study quantifying relative and absolute risks following exposure to selected risk factors and genetic liability.

BACKGROUND: We quantified relative and absolute risks of postpartum psychiatric episodes (PPE) following risk factors: Young age, past personal or family history of psychiatric disorders, and genetic liability. METHODS: We conducted a register-based study using the iPSYCH2012 case-cohort sample. Exposures were personal history of psychiatric episodes prior to childbirth, being a young mother (giving birth before the age of 21.5 years), having a family history of psychiatric disorders, and a high (highest quartile) polygenic score (PGS) for major depression. PPE was defined within 12 months postpartum by prescription of psychotropic medication or in- and outpatient contact to a psychiatric facility. We included primiparous women born 1981-1999, giving birth before January 1st, 2016. We conducted Cox regression to calculate hazard ratios (HRs) of PPE, absolute risks were calculated using cumulative incidence functions. RESULTS: We included 8174 primiparous women, and the estimated baseline PPE risk was 6.9% (95% CI 6.0%-7.8%, number of PPE cases: 2169). For young mothers with a personal and family history of psychiatric disorders, the absolute risk of PPE was 21.6% (95% CI 15.9%-27.8%). Adding information on high genetic liability to depression, the risk increased to 29.2% (95% CI 21.3%-38.4%) for PPE. CONCLUSIONS: Information on prior personal and family psychiatric episodes as well as age may assist in estimating a personalized risk of PPE. Furthermore, additional information on genetic liability could add even further to this risk assessment.

Risk factors for anorexia nervosa: A population-based investigation of sex differences in polygenic risk and early life exposures.

OBJECTIVE: To examine sex differences in risk factors for anorexia nervosa (AN). METHOD: This population-based study involved 44,743 individuals (6,239 AN cases including 5,818 females and 421 males, and 38,504 controls including 18,818 females and 19,686 males) born in Denmark between May 1981 and December 2009. Follow-up began on the individual's sixth birthday and ended at AN diagnosis, emigration, death, or December 31, 2016, whichever occurred first. Exposures included socioeconomic status (SES), pregnancy, birth, and early childhood factors based on data from Danish registers, and psychiatric and metabolic polygenic risk scores (PRS) based on genetic data. Hazard ratios were estimated using weighted Cox proportional hazards models stratified by sex (assigned at birth), with AN diagnosis as the outcome. RESULTS: The effects of early life exposures and PRS on AN risk were comparable between females and males. Although we observed some differences in the magnitude and direction of effects, there were no significant interactions between sex and SES, pregnancy, birth, or early childhood exposures. The effects of most PRS on AN risk were highly similar between the sexes. We observed significant sex-specific effects of parental psychiatric history and body mass index PRS, though these effects did not survive corrections for multiple comparisons. CONCLUSIONS: Risk factors for AN are comparable between females and males. Collaboration across countries with large registers is needed to further investigate sex-specific effects of genetic, biological, and environmental exposures on AN risk, including exposures in later childhood and adolescence as well as the additive effects of exposures. PUBLIC SIGNIFICANCE: Sex differences in the prevalence and clinical presentation of AN warrant examination of sex-specific risk factors. This population-based study indicates that the effects of polygenic risk and early life exposures on AN risk are comparable between females and males. Collaboration between countries with large registers is needed to further investigate sex-specific AN risk factors and improve early identification of AN.

Familial co-aggregation of schizophrenia and eating disorders in Sweden and Denmark.

Eating disorders and schizophrenia are both moderately to highly heritable and share significant genetic risk despite distinct diagnostic criteria. Large-scale family studies on the co-aggregation of these disorders are lacking. Thus, we aimed to estimate the co-occurrence and familial co-aggregation of these disorders within the entire Swedish and Danish population. The proband cohort consisted of individuals born in Sweden (1977-2003) and Denmark (1984-2006) and still residing in their respective country at age six (NSweden = 2,535,191, NDenmark = 1,382,367). Probands were linked to their biological parents, siblings, grandparents, uncles/aunts, and cousins. Diagnoses for anorexia nervosa (AN) and other eating disorders (OED: bulimia nervosa, binge-eating disorder, and eating disorder not otherwise specified) for probands and schizophrenia diagnoses for both probands and relatives were obtained. The likelihood of having schizophrenia in those with AN or OED and their relatives was compared with individuals without eating disorder diagnoses and their relatives. Probands with AN or OED were more likely to have schizophrenia than probands without these disorders. All relatives of probands with AN or OED (except parents and uncles/aunts of probands with AN) were at increased risk of schizophrenia. In general, the magnitude of odds ratios attenuated with decreasing genetic relatedness. These results suggest familial liability contributes to the association between eating disorders and schizophrenia. Clinicians should be mindful of this comorbid and co-aggregation pattern as it may influence case conceptualization and treatment decisions.

Associations between parental socioeconomic-, family-, and sibling status and risk of eating disorders in offspring in a Danish national female cohort.

OBJECTIVE: Studies on parental socioeconomic status (SES) and family risk factors for eating disorders (EDs) have yielded inconsistent results; however, several studies have identified high parental educational attainment as a risk factor. The aim was to evaluate associations of parental SES and family composition with anorexia nervosa (AN), bulimia nervosa (BN), and eating disorders not otherwise specified (EDNOS) in the offspring, adjusting for parental age and parental mental health. METHODS: The cohort included women born in Denmark between January 1, 1989 and December 31, 2010, derived from Danish national registers. Each person was followed from their sixth birthday until onset of the disorder of interest or to December 31, 2016. Exposure variables were: childhood SES, defined as individually evaluated parental level of income, occupation, and education; sibling status; and family composition. Outcomes were: AN, BN, EDNOS, and major depressive disorder (MDD), included as a psychiatric comparison disorder. Risks were estimated using Cox proportional hazards. RESULTS: High parental SES was associated with increased risk of especially AN, and less so BN and EDNOS, in offspring. In comparison, low SES was associated with a higher risk of MDD. No differences between maternal or paternal socioeconomic risk factors were found. Family composition and sibling status showed limited influence on ED risk. DISCUSSION: SES shows opposite associations with AN than MDD, whereas associations with BN and EDNOS are intermediate. The socioeconomic backdrop of AN differs markedly from that reported in other psychiatric disorders. Whether that is due to genetic and/or environmental factors remains unknown. PUBLIC SIGNIFICANCE STATEMENT: Parental socioeconomic background (SES) may influence eating disorders risk in offspring somewhat differently than other psychiatric disorders. In Denmark, higher parental SES was associated with increased risk of, particularly, anorexia nervosa (AN). Importantly AN does strike across the SES spectrum. We must ensure that individuals of all backgrounds have equal access to care and are equally likely to be detected and treated appropriately for eating disorders.

Prenatal and perinatal factors and risk of eating disorders.

BACKGROUND: Among the most disabling and fatal psychiatric illnesses, eating disorders (EDs) often manifest early in life, which encourages investigations into in utero and perinatal environmental risk factors. The objective of this study was to determine whether complications during pregnancy and birth and perinatal conditions are associated with later eating disorder risk in offspring and whether these associations are unique to EDs. METHODS: All individuals born in Denmark to Danish-born parents 1989-2010 were included in the study and followed from their 6th birthday until the end of 2016. Exposure to factors related to pregnancy, birth, and perinatal conditions was determined using national registers, as were hospital-based diagnoses of anorexia nervosa (AN), bulimia nervosa, and eating disorder not otherwise specified during follow-up. For comparison, diagnoses of depressive, anxiety, and obsessive-compulsive disorders were also included. Cox regression was used to compare hazards of psychiatric disorders in exposed and unexposed individuals. RESULTS: 1 167 043 individuals were included in the analysis. We found that similar to the comparison disorders, prematurity was associated with increased eating disorder risk. Conversely, patterns of increasing risks of EDs, especially in AN, with increasing parental ages differed from the more U-shaped patterns observed for depressive and anxiety disorders. CONCLUSIONS: Our results suggest that pregnancy and early life are vulnerable developmental periods when exposures may influence offspring mental health, including eating disorder risk, later in life. The results suggest that some events pose more global transdiagnostic risk whereas other patterns, such as increasing parental ages, appear more specific to EDs.

Self-harm in women with postpartum mental disorders.

BACKGROUND: Women suffering from first onset postpartum mental disorders (PPMD) have a highly elevated risk of suicide. The current study aimed to: (1) describe the risk of self-harm among women with PPMD and (2) investigate the extent to which self-harm is associated with later suicide. METHODS: We conducted a register-based cohort study linking national Danish registers. This identified women with any recorded first inpatient or outpatient contact to a psychiatric facility within 90 days after giving birth to their first child. The main outcome of interest was defined as the first hospital-registered episode of self-harm. Our cohort consisted of 1 202 292 women representing 24 053 543 person-years at risk. RESULTS: Among 1554 women with severe first onset PPMD, 64 had a first-ever hospital record of self-harm. Women with PPMD had a hazard ratio (HR) for self-harm of 6.2 (95% CI 4.9-8.0), compared to mothers without mental disorders; but self-harm risk was lower in PPMD women compared to mothers with non-PPMD [HR: 10.1, (95% CI 9.6-10.5)] and childless women with mental disorders [HR: 9.3 (95% CI 8.9-9.7)]. Women with PPMD and records of self-harm had a significantly greater risk for later suicide compared with all other groups of women in the cohort. CONCLUSIONS: Women with PPMD had a high risk of self-harm, although lower than risks observed in other psychiatric patients. However, PPMD women who had self-harmed constituted a vulnerable group at significantly increased risk of later suicide.

Psychotic experiences from preadolescence to adolescence: when should we be worried about adolescent risk behaviors?

Psychotic experiences (PE), below the threshold of psychotic disorder, are common in the general population. PE are associated with risk behaviors such as suicidality, non-suicidal self-injury (NSSI) and substance use. However, PE as specific or causal phenomena of these risk behaviors are still debated. We aimed to examine the longitudinal trajectories of PE from preadolescence to adolescence and their associated risk behaviors in adolescence. A total of 1138 adolescents from the Copenhagen Child Cohort 2000 were assessed for PE and risk behaviors (NSSI, suicide ideation and -attempts and substance use) at age 11 and 16 years, along with measures of general psychopathology and depressive symptoms specifically. Self-reported impact of general psychopathology tended to be associated with more PE persistence. PE were associated with all risk behaviors in cross section at both follow-ups. Persistent PE from ages 11 to 16 and incident PE at age 16 were associated with risk behaviors at age 16, whereas remitting PE from age 11 to 16 were not. After adjustment for co-occurring depressive symptoms and general psychopathology, all associations were markedly reduced. After exclusion of preadolescents who already had expressed risk behavior at age 11, PE in preadolescence did not stand out as an independent predictor of incident adolescent risk behaviors. The current study suggests that PE in preadolescence and adolescence may not play a direct causal role regarding NSSI, suicidality, and substance use. However, PE are still useful clinical markers of severity of psychopathology and associated risk behaviors.

Psychosocial Adversity in Infancy and Mortality Rates in Childhood and Adolescence: A Birth Cohort Study of 1.5 Million Individuals.

BACKGROUND: Childhood and adolescent mortality accounts for a substantial proportion of years lost prematurely. Reducing childhood and adolescent mortality relies on knowing characteristics of those at elevated risk of dying young. We therefore aimed to identify such characteristics; our main hypothesis is that psychosocial adversity in infancy is linked to increased mortality rates in childhood and adolescence. METHODS: We conducted a register-based cohort study involving all 1,549,581 children born to Danish-born parents in Denmark between 1 January 1981 and 31 December 2010. For each infant, we extracted data relevant to Rutter's indicators of adversity (low social class, parents not cohabiting, large family size, paternal criminality, maternal mental disorder, and placement in out-of-home care). Follow-up began on the cohort member's first birthday. We estimated the association between adversity score (the number of Rutter's indicators of adversity present in infancy) and death via. Cox regression. RESULTS: During follow-up (18,874,589 person-years), 2,081 boys and 1,420 girls died before or on their 18th birthday. The hazard ratios for death were 2.3 (95% CI = 1.9, 2.9) and 2.1 (95% CI = 1.6, 2.7) for boys and girls with adversity scores of 3-6 compared with those with a score of 0. These associations were driven by causes of death with known links to psychosocial adversity. CONCLUSION: While absolute mortality rates were low, infants with adversity scores of 3-6 were approximately twice as likely to die prematurely compared with infants with adversity scores of 0. Whether these associations generalize to other countries should be subjected to further study.

Childhood infections and schizophrenia: The impact of parental SES and mental illness, and childhood adversities.

Childhood infection has been proposed as an important etiologic factor for schizophrenia. However, it is unclear to what extent the association between childhood infection and schizophrenia is confounded by parental socioeconomic status and mental illness, and childhood adversity, and whether the association is explained by familial liability for infections. We used a historical, population-based cohort design, selecting all singletons born in Denmark between 1981 and 1998 (n = 882,813). We identified exposure to infection as having been hospitalized with an infection in the Danish national registers. Data from a range of population-based registers were used to construct a childhood adversity index. The index included the following adversities: family disruption, parental incarceration, parental chronic somatic disease, death of a parent, parent permanently outside of workforce, childhood abuse and placement in out-of-home care. We also assessed parental socioeconomic status and mental illness. Multiple admissions with infections during childhood increased the risk of schizophrenia with an Incidence Rate Ratio (IRR) of 1.28 (95% CI: 1.19-1.38) for 1 infection to an IRR of 1.43 (95% CI: 1.30-1.58) for 2-3 infections and an IRR of 1.95 (95% CI: 1.66-2.29) for ≥4 infections. Parental socioeconomic status and mental illness, and childhood adversities increased the odds of acquiring childhood infections and was associated with schizophrenia, but did not explain the results. Similarly did familial liability for infection increase the risk of schizophrenia, but did not explain the association between infection and schizophrenia. Parental mental health modified the association between childhood infection and schizophrenia (p-value 0.02), and we found no significant effect of childhood infection in those with propensity for psychotic disorders.

Early childhood adversities and risk of eating disorders in women: A Danish register-based cohort study.

OBJECTIVE: Previous studies evaluating the association between early childhood adversities and eating disorders have yielded conflicting results. The aim of this study is to examine the association between a range of adversities and risk of anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS) in 495,244 women. METHOD: In this nationwide, register-based cohort study, nine types of early childhood adversity (family disruption, residential instability, placement in out-of-home care, familial death, parental somatic illness, parental psychiatric illness, parental disability, severe parental criminality, and parental substance use disorder) were defined and exposure during the first 6 years of life was determined. Hazard ratios for eating disorders were calculated using Cox regression. RESULTS: Few adversities were significantly associated with AN, and for each, the presence of the adversity was associated with lower risk for AN. BN, and EDNOS were positively associated with several types of adversities. AN rates were unchanged or reduced by up to 54% by adversities, whereas rates of BN and EDNOS were unchanged or increased by adversities by up to 49 and 89%, respectively. DISCUSSION: Our findings indicate that childhood adversities appear to be associated with an increased risk of BN and in particular EDNOS, whereas they seem to be either unassociated or associated with a decreased risk of AN.

Incidence of eating disorders in Danish psychiatric secondary healthcare 1970-2008.

OBJECTIVE: Is an increased focus on eating disorders during the past few decades reflected by increasing occurrence in the psychiatric health service system. METHOD: All first-time diagnoses of eating disorders identified in the Danish Central Psychiatric Research Register 1970-2008 constitute the present research database. Age-standardized rates per 100,000 inhabitants were calculated and autoregressive models were fitted for males and females separately as well as for in- and outpatients. RESULTS: The incidence of eating disorders diagnosed in Danish psychiatric secondary healthcare has increased considerably during a nearly 40-year period of observation both within the general category of eating disorders and also specifically for anorexia nervosa. The steepest increase is seen within females aged 15-19 years, where the highest incidences are also found. Anorexia nervosa constitutes the vast majority of all eating disorders. Throughout the time interval investigated, the number of males, however, is negligible compared to females. Most patients are seen in outpatient services, increasing towards recent years. However, the number of patients being treated as inpatients has increased linearly through the entire four decenniums investigated. CONCLUSIONS: Changes in registration principles, public awareness and higher acceptance of mental disorders in the public is the most obvious explanation for the incidence increase of anorexia nervosa and other eating disorders. This study does not answer whether there has been an increase in true incidence in the population.

A nationwide study on delirium in psychiatric patients from 1995 to 2011.

OBJECTIVES: Delirium shares symptoms with some mental illnesses. This may lead to misdiagnosis of delirium in psychiatric patients and a risk of inadequate management. Moreover, literature on delirium in psychiatric patients is sparse. The aim was to analyse possible changes in the diagnostic incidence of delirium in psychiatric patients from 1995 to 2011, and to investigate the patients with regard to sex, age, and type of patient. METHODS: All first time ever diagnoses of delirium among psychiatric patients were identified in the nationwide Danish Psychiatric Central Research Register (DPCRR) from 1995 to 2011. The delirium diagnoses include (1) delirium unspecified, (2) delirium with dementia, and (3) drug-related delirium, all in accordance with International Classification of Diseases-10. The incidence rates were age standardised. RESULTS: A total of 15 680 persons diagnosed with delirium for the first time were identified in the DPCRR between 1995 and 2011. The total incidence rate of delirium has decreased, reaching 8.4/1000 person-years in 2011. In 2011, 2.6% of the demented patients were diagnosed with delirium with dementia. Diagnosis of delirium is significantly more common in men, and the three groups of delirium showed a characteristic age distribution. CONCLUSION: Our incidences were markedly lower when compared with previous studies. This suggests a possible underdiagnosis of delirium in psychiatric hospitals and should be investigated further, as delirium is a serious state and identifying the syndrome is important for sufficient treatment.

Diagnosed eating disorders in Danish registers - incidence, prevalence, mortality, and polygenic risk.

Eating disorders are a group of severe and potentially enduring psychiatric disorders associated with increased mortality. Compared to other severe mental illnesses, they have received relatively limited research attention. Epidemiological studies often only report relative measures despite these being difficult to interpret having limited practical use. The aims of this study were to evaluate the incidence and prevalence of diagnosed anorexia nervosa (AN), bulimia nervosa, and eating disorder not otherwise specified recorded in Danish hospital registers and estimate both relative and absolute measures of subsequent mortality - both all-cause and cause-specific in a general nationwide population of 1,667,374 individuals. In a smaller, genetically informed case-cohort sample, the prediction of polygenic scores for AN, body fat percentage, and body mass index on AN prevalence and severity was estimated. Despite males being less likely to be diagnosed with an eating disorder, those that do have significantly increased rates of mortality. AN prevalence was highest for individuals with high AN and low body fat percentage/body mass index polygenic scores.

Are migrants diagnosed with a trauma-related disorder at risk of premature mortality? A register-based cohort study in Denmark.

Background: Mental illness is common among refugees displaced by conflict and war. While evidence points to the relatively good health in terms of longevity of migrants resettled in the destination country, less is known about the mortality of the most vulnerable migrants with a trauma-related diagnosis alone and those with an additional comorbid psychotic disorder. This study aimed to provide an overview of the number and mortality of foreign-born individuals diagnosed with Post-Traumatic Stress Disorder or Enduring Personality Change after a Catastrophic Event (PTSD/EPCACE), a psychotic disorder or both. Methods: A nationwide register-based cohort study, including residents in Denmark, followed from 1 January 1995 to 31 December 2016. The exposure was PTSD/EPCACE and psychotic disorders as well as region of origin. Relative all-cause mortality was estimated using Cox proportional hazards regression models and calculated for migrants with one or both groups of disorders compared to those from the same region without the disorder. Results: During the study period, 6,580,000 individuals (50.4% women) were included in the cohort. Of these 1,249,654 (50.5% women) died during follow-up. For men and women from the former Yugoslavia, the Middle East and Northern Africa, a PTSD/EPCACE diagnosis alone or with comorbid psychotic disorder was not associated with increased mortality after adjusting for region of origin. A psychotic disorder alone, however, was associated with an increased mortality rate. Conclusion: Despite the severity of many refugees' traumatic experiences, a diagnosis of a trauma-related psychiatric disorder did not appear to increase the mortality rates.

The role of early-life family composition and parental socio-economic status as risk factors for obsessive-compulsive disorder in a Danish national cohort.

Research on early-life family environment on obsessive-compulsive disorder (OCD) risk is limited, and sex differences have not been sufficiently studied. We investigated early-life family composition and parental socio-economic status (SES) as OCD risk factors while stratifying for sex in a sample of 1,154,067 individuals from the Danish population (7550 of whom had OCD). Data on early-life family composition (birth order, number of siblings, number of parents in household at proband age 6), parental SES at age 6 (parental income, occupation, and education level), history of parental psychiatric illness, and parental age at birth on OCD risk (i.e., an ICD-10 diagnosis of F42.x) were obtained from Danish population registers. Survival analyses using Cox regression were performed with age as the underlying time variable. Analyses were adjusted for calendar time, and differential effect by sex was tested for exposures. We found that birth order and advanced maternal age were risk factors for OCD in males, and being an only child was associated with increased OCD risk in both sexes. Early childhood SES variables including parental education, occupation, and income were associated with OCD risk, and these effects were more pronounced in females. Significant interaction effects for parental education/occupation and the presence of non-OCD psychiatric diagnoses in the proband also emerged. Our results suggest that early-life SES and family composition may be important risk factors for OCD, and heterogeneity in OCD cases in terms of psychiatric comorbidities, as well as sex differences should be carefully examined in relation to risk factors.

Anorexia nervosa and inflammatory bowel diseases-Diagnostic and genetic associations.

Background: Anorexia nervosa (AN), a serious eating disorder, and inflammatory bowel diseases (IBD) share a number of key symptoms, for example, discomfort during eating and early satiety. Despite the symptom overlap, studies on comorbidity are limited and mostly conducted in relatively small samples. This study investigates the comorbidity of diagnosed AN with IBD, and the subtypes Crohn's disease and ulcerative colitis, in a population-based sample and explores whether genetic factors could play a role in the overlap. Methods: The study included 1,238,813 individuals born in Denmark 1981-2005 selected from the population register (5067 diagnosed with AN and 6947 diagnosed with any IBD), including a subsample of 23,236 individuals with genetic information (4271 with AN and 176 with any IBD). By combining hospital-based diagnoses recorded in health registers until 2013 with polygenic scores (PGS) of AN and IBD, we investigated possible associations between diagnoses of each disorder, both within individuals and families, and between PGS of one disorder and diagnosis of the other disorder. Analyses were conducted using Cox regression and logistic regression. Results: We found that a prior diagnosis of AN was associated with hazard ratios of 1.44 (1.05, 1.97) for any IBD, 1.60 (1.04, 2.46) for Crohn's disease, and 1.66 (1.15, 2.39) for ulcerative colitis, whereas IBD diagnoses were not significantly associated with later AN diagnosis. No significant within-families associations were observed. We found no associations between AN and IBD using PGS. Conclusions: AN was associated with later risk of IBD, Crohn's disease, and ulcerative colitis; however, the reverse was not observed. It is important for clinicians to be aware of this association to evaluate IBD as a differential diagnosis or an emergent condition in patients with AN.

Risk of diabetic complications and subsequent mortality among individuals with schizophrenia and diabetes - a population-based register study.

BACKGROUND: Individuals with schizophrenia often develop diabetes, but little is known about their risk of diabetic complications. We aimed to study incidence of registered diabetic complications and subsequent mortality in individuals with schizophrenia and diabetes compared to individuals with diabetes only. METHODS: We conducted a cohort study using nationwide registers and followed all individuals in the entire Danish population diagnosed with diabetes from 1997 to 2017. Incidence rate ratios (IRR) of diabetic complications, all-cause and cause-specific mortality rate ratios (MRR) were estimated by Cox regression comparing individuals diagnosed with schizophrenia and diabetes to individuals diagnosed only with diabetes. RESULTS: In a cohort of 239,118 individuals with diagnosed diabetes, the incidence of any diabetic complication was similar in females with schizophrenia and diabetes compared to females with diabetes only; IRR = 0.93 (95%CI: 0.84-1.02), and significantly lower in males; IRR = 0.85 (95%CI: 0.78-0.92). The all-cause mortality for individuals with a diagnosis of a diabetic complication was higher in individuals with schizophrenia and diabetes than in those with diabetes only; MRR = 1.92 (95%CI: 1.65-2.23) for females and MRR = 1.69 (95%CI: 1.49-1.92) for males. Among those without diabetic complications, schizophrenia was also associated with a higher mortality. CONCLUSIONS: Individuals with schizophrenia and diabetes had similar or lower rates of diabetic complications, compared to those with diabetes only. Among those with diabetic complications, schizophrenia was associated with higher mortality. Similar, among those without diabetic complications, schizophrenia was also associated with higher mortality. Hence, diabetic complications do not seem to explain the excess mortality seen in individuals with schizophrenia.

Mental Health Service Use and Psychopharmacological Treatment Following Psychotic Experiences in Preadolescence.

OBJECTIVE: Psychotic experiences affect more than 10% of children and often co-occur with nonpsychotic mental disorders. However, longitudinal studies of the outcome of psychotic experiences based on unbiased information on mental health service use and psychotropic medications are scarce. The authors investigated whether psychotic experiences at ages 11-12 predicted a psychiatric diagnosis or treatment with psychotropic medications by ages 16-17. METHODS: In a longitudinal register-based follow-up study of the Copenhagen Child Cohort 2000, a total of 1,632 children ages 11-12 were assessed for psychotic experiences in face-to-face interviews. The children were also assessed for mental disorders and IQ. National registries provided information on perinatal and sociodemographic characteristics, on psychiatric disorders diagnosed at child and adolescent mental health services, and on prescribed psychotropic medications through ages 16-17. RESULTS: Among children who had not been previously diagnosed, and after adjustment for sociodemographic and perinatal adversities and IQ, psychotic experiences at ages 11-12 predicted receiving a psychiatric diagnosis in child and adolescent mental health services before ages 16-17 (adjusted hazard ratio=3.13, 95% CI=1.93, 5.07). The risk was increased if the child met criteria for a co-occurring mental disorder (not diagnosed in mental health settings) at baseline compared with no psychotic experiences or diagnosis at baseline (adjusted hazard ratio=7.85, 95% CI=3.94, 15.63), but having psychotic experiences alone still marked a significantly increased risk of later psychiatric diagnoses (adjusted hazard ratio=2.76, 95% CI=1.48, 5.13). Similar patterns were found for treatment with psychotropic medications. CONCLUSIONS: Psychotic experiences in childhood predict mental health service use and use of psychotropic medications during adolescence. The study findings provide strong evidence that psychotic experiences in preadolescence index a transdiagnostic vulnerability for diagnosed psychopathology in adolescence.

Sex Differences in Comorbidity Patterns of Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To investigate sex differences in associations between attention-deficit/hyperactivity disorder (ADHD) and a spectrum of comorbid disorders. METHOD: The study population included all children born in Denmark from 1981 through 2013 (N = 1,665,729). Data were merged from Danish registers and information was obtained on birth characteristics, socioeconomic status, familial psychiatric history, and diagnoses of ADHD (n = 32,308) and comorbid disorders. To estimate absolute and relative risks of comorbid disorders, incidence rates and adjusted hazard ratios (HRs) with 95% CIs were calculated for female and male individuals. In addition, interactions between ADHD and sex in association with comorbid disorders were estimated as HR ratios (HRRs) in female and male individuals (95% CIs). RESULTS: Individuals diagnosed with ADHD had significantly increased absolute and relative risks of all 12 comorbid psychiatric disorders investigated. ADHD-sex interactions were found for some comorbid disorders. Compared with male individuals, ADHD in female individuals showed a stronger association with autism spectrum disorder (HRR 1.86, 95% CI 1.62-2.14), oppositional defiant/conduct disorder (HRR 1.97, 95% CI 1.68-2.30), intellectual disability (HRR 1.79, 95% CI 1.54-2.09), personality disorders (HRR 1.23, 95% CI 1.06-1.43), schizophrenia (HRR 1.21, 95% CI 1.02-1.43), substance use disorders (HRR 1.21, 95% CI 1.07-1.38), and suicidal behavior (1.28, 95% CI 1.12-1.47). The remaining disorders showed no significant sex differences in association with ADHD. CONCLUSION: This study indicates that the association between ADHD and several comorbid disorders is stronger in female than in male individuals. These important findings add to the literature on sex differences in ADHD and suggest that female individuals diagnosed with ADHD are a more vulnerable group of patients.

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 525 643 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 525 643 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 525 643 adolescent girls were followed up for 4 601 720.4 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.