Search

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. [ABSTRACT FROM AUTHOR]

Background: Although several types of risk factors for anorexia nervosa (AN) have been identified, including birth-related factors, somatic, and psychosocial risk factors, their interplay with genetic susceptibility remains unclear. Genetic and epidemiological interplay in AN risk were examined using data from Danish nationwide registers. AN polygenic risk score (PRS) and risk factor associations, confounding from AN PRS and/or parental psychiatric history on the association between the risk factors and AN risk, and interactions between AN PRS and each level of target risk factor on AN risk were estimated. Methods: Participants were individuals born in Denmark between 1981 and 2008 including nationwide-representative data from the iPSYCH2015, and Danish AN cases from the Anorexia Nervosa Genetics Initiative and Eating Disorder Genetics Initiative cohorts. A total of 7003 individuals with AN and 45 229 individuals without a registered AN diagnosis were included. We included 22 AN risk factors from Danish registers. Results: Risk factors showing association with PRS for AN included urbanicity, parental ages, genitourinary tract infection, and parental socioeconomic factors. Risk factors showed the expected association to AN risk, and this association was only slightly attenuated when adjusted for parental history of psychiatric disorders or/and for the AN PRS. The interaction analyses revealed a differential effect of AN PRS according to the level of the following risk factors: sex, maternal age, genitourinary tract infection, C-section, parental socioeconomic factors and psychiatric history. Conclusions: Our findings provide evidence for interactions between AN PRS and certain risk-factors, illustrating potential diverse risk pathways to AN diagnosis. [ABSTRACT FROM AUTHOR]

Background: The age of onset (AOO), incidence and cumulative incidence of mental disorders are critical epidemiological measures, providing essential insights into the development and course of these disorders across the lifespan. This study aims to provide up‐to‐date estimates of the AOO, age‐specific incidence, and cumulative incidence for a comprehensive range of mental disorders using data from Danish registers. Methods: We conducted a follow‐up study encompassing all Danish residents from January 1, 2004, to December 31, 2021, totaling 91,613,465 person‐years. Data were sourced from the Danish Psychiatric Central Research Register, identifying individuals treated for various mental disorders in psychiatric hospitals, outpatient departments, and accident/emergency departments, that is, treated in secondary care settings. We investigated specific categories of mental disorders, including substance abuse disorders, schizophrenia, mood disorders, anxiety, eating disorders, borderline personality disorders, intellectual disabilities, pervasive developmental disorders, and behavioral and emotional disorders. Age‐sex‐specific incidence rates were estimated using Poisson generalized linear models, and cumulative incidence was calculated using Aalen–Johansen's competing risks model. The study provides estimates of AOO, incidence, and cumulative incidence for various mental disorders, including their age and sex distributions. Results: The cumulative incidence by age 80 years for any mental disorder was 30.72% (95% confidence interval: 30.62%–30.83%) for males and 34.46% (34.35%–34.57%) for females. The most common types of mental disorders were anxiety‐related disorders 16.27% (16.19%–16.36%) for males and 23.39% (23.29%–23.50%) for females, and followed by mood disorder 10.34% (10.27%–10.41%) for males and 16.67% (16.58%–16.77%) for females. For those who develop mental disorder, half will have developed their disorder by approximately age 22 years (median and interquartile range: males 21.37 (11.85–36.00); females 22.55 (16.31–36.08)). Conclusions: Approximately one in three individuals will seek treatment for at least one mental disorder in a secondary care setting by age 80. Given that half of these individuals develop mental disorders before age 22, it is crucial to tailor service planning to meet the specific needs of young individuals. Web‐based interactive data‐visualization tools are provided for clinical utility. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Comorbidity with general medical conditions is common in individuals with eating disorders. Many previous studies do not evaluate types of eating disorder. Aims: To provide relative and absolute risks of bidirectional associations between (a) anorexia nervosa, bulimia nervosa and eating disorders not otherwise specified and (b) 12 general medical conditions. Method: We included all people born in Denmark between 1977 and 2010. We collected information on eating disorders and considered the risk of subsequent medical conditions, using Cox proportional hazards regression. Absolute risks were calculated using competing risks survival analyses. We also considered risks for prior medical conditions and subsequent eating disorders. Results: An increased risk was seen for almost all disorder pairs (69 of 70). Hazard ratios for those with a prior eating disorder receiving a subsequent diagnosis of a medical condition ranged from 0.94 (95% CI 0.57−1.55) to 2.05 (95% CI 1.86−2.27). For those with a prior medical condition, hazard ratios for later eating disorders ranged from 1.35 (95% CI 1.26–1.45) to 1.98 (95% CI 1.71–2.28). Absolute risks for most later disorders were increased for persons with prior disorders, compared with reference groups. Conclusions: This is the largest and most detailed examination of eating disorder–medical condition comorbidity. The findings indicate that medical condition comorbidity is increased among those with eating disorders and vice versa. Although there was some variation in comorbidity observed across eating disorder types, magnitudes of relative risks did not differ greatly. [ABSTRACT FROM AUTHOR]

Objective: Previous literature has established an increased risk of eating disorders among individuals with other psychiatric disorders and vice versa. However, often studies have focused on eating disorders as a single diagnostic entity and/or investigated selected psychiatric comorbidities. We conducted a comprehensive study, exploring bidirectional associations between different types of eating disorders and broad groups of all other psychiatric disorders, to identify patterns of comorbidity. Method: We included all people born in Denmark 1963–2010. We collected information on eating disorders and considered the risk of subsequent psychiatric disorders using Cox‐proportional hazards regression. Absolute risks were calculated using competing risks survival analyses. We also considered prior psychiatric disorders and subsequent eating disorders. Results: An increased risk was seen for almost all disorder pairs of diagnoses evaluated. Following an anorexia nervosa (AN) diagnosis, the median hazard ratio for the different subsequent psychiatric disorders was 3.80 (range 2.48–6.15); following an other eating disorder (OED) diagnosis, it was 3.16 (range 2.05–5.14). After different psychiatric disorder diagnoses, the median hazard ratio was 2.66 for later AN (range 1.21–5.31), and 2.51 for later OED (range 1.25–4.10). Absolute risk of eating disorders was also higher among those with other psychiatric disorders than those without. Discussion: In this broad examination, we identified bidirectional increases in risk of comorbidity for those with both eating disorder diagnoses and psychiatric disorder diagnoses. Although our findings indicate different patterns of comorbidity between eating disorders, these variations were generally small. [ABSTRACT FROM AUTHOR]

• Cerebrospinal fluid (CSF) immune alterations are associated with mental disorders. • Routine CSF parameters are specific for diagnosing neurological disease. • Routine CSF parameters are highly specific for diagnosing CNS infections. • Relevant CSF biomarkers in psychiatry are yet to be discovered. Cerebrospinal fluid (CSF) immune alterations have been associated with mental disorders, neurological disease, and CNS infections; however, comprehensive large-scale longitudinal CSF studies are lacking. By using the Clinical Laboratory Information System (LABKA) Research Database in the Central Denmark Region (1994–2012), we included 15,030 individuals tested for CSF WBC, CSF/serum albumin ratio, IgG index, total protein, albumin, or IgG with follow-up for the risk of mental disorders, psychotropic prescriptions, neurological diseases, or CNS infections, estimated by Cox regression. Among individuals receiving a mental disorder diagnosis (N = 1,147) after a CSF test, 30 · 0% had an abnormal CSF test result, while for those with a neurological disease (N = 3,201), 39 · 9% had abnormal test results, and among individuals with CNS infections (N = 1,276), 73 · 0% had abnormal test results. Individuals with abnormal CSF test results had an increased risk of mental disorders (HR = 3 · 20; 95%CI = 2 · 86-3 · 59), neurological diseases (HR = 12 · 40; 95%CI = 11 · 65-13 · 20), and CNS infections (HR = 338 · 59; 95%CI = 299 · 06-383 · 35) compared to individuals not registered with a CSF test. However, the risk of mental disorders was higher (P < 0 · 001) after CSF test results within the normal range (HR = 4 · 45; 95%CI = 4 · 08-4 · 86), whereas for neurological diseases (HR = 9 · 72; 95%CI = 9 · 19-10 · 29) and CNS infections (HR = 55 · 17; 95%CI = 47 · 12-64 · 60), the risk was highest after abnormal CSF test results (all P < 0 · 001). The risk of organic mental disorders tended to be highest in individuals with abnormal CSF test results (HR = 19·30; 95%CI = 13·44-27·71) even though not significantly different from the risk in the group of individuals with CSF test results in the normal range (HR = 13·55; 95%CI = 9·36-19·60) (P ≥ 0 · 05). Abnormal CSF test results were associated with an elevated risk of psychotropic prescriptions (HR = 3 · 91; 95%CI = 3 · 66-4 · 18), as were CSF test results within the normal range (HR = 4 · 26; 95%CI = 4 · 03–4 · 51) (P < 0 · 05). Immunological CSF abnormalities are associated with an increased risk of mental disorders, neurological disease, and particularly CNS infections; however, the included CSF parameters were not specific for mental disorders and the relevant CSF biomarkers in psychiatry are yet to be discovered. [ABSTRACT FROM AUTHOR]

• Infectious mononucleosis is often associated with prolonged fatigue. • The association with depression was unclear since large-scale studies were lacking. • This prospective cohort study included 12,510 individuals with the infection. • Infectious mononucleosis was associated with a 40% increased risk for depression. • The increased risk was significant to the period one year or later after the infection. Infectious mononucleosis is a clinical diagnosis characterized by fever, sore throat, lymph node enlargement and often prolonged fatigue, most commonly caused by Epstein-Barr virus infection. Previous studies have indicated that infectious mononucleosis can be followed by depression; however, large-scale studies are lacking. We used nationwide registry data to investigate the association between infectious mononucleosis and subsequent depression in this first large-scale study. Prospective cohort study using nationwide Danish registers covering all 1,440,590 singletons born (1977–2005) in Denmark by Danish born parents (21,830,542 person-years' follow-up until 2016); where 12,510 individuals had a hospital contact with infectious mononucleosis. The main outcome measures were a diagnosis of major depressive disorder (ICD-8: 296.09, 298.09, 300.4; ICD-10: F32) requiring hospital contact. Infectious mononucleosis was associated with a 40% increased hazard ratio (HR) for a subsequent depression diagnosis in the fully adjusted model (HR: 1.40, 95% CI: 1.26–1.56;n = 358), when compared to unexposed individuals. The increased risk of being diagnosed with depression was significant to the periods one to four years after the infectious mononucleosis diagnosis (HR: 1.40, 95% CI: 1.17–1.67;n = 121) and ≥ five years (HR: 1.40, 95% CI: 1.22–1.61;n = 207). We did not find any differences according to age (p = 0.61) nor sex (p = 0.30). In this largest study to date, infectious mononucleosis in childhood or adolescence was associated with an increased risk of a subsequent depression. Our findings have important clinical implications and identifies youth with infectious mononucleosis as a group at high risk of later depression in young adulthood. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Somatic diseases have been associated with an increased risk for subsequent schizophrenia; however, it is unknown whether prior somatic diseases negatively affect early treatment outcomes after a first-time schizophrenia diagnosis. We included all individuals born in Denmark after January 1st, 1977 and first-time diagnosed with schizophrenia between January 1st, 1996 and December 31st, 2015. We identified all life-time somatic hospital contacts and all prescriptions within the year before the first-time schizophrenia diagnosis and followed patients for up to five years regarding risk for schizophrenia (re)-hospitalization (relapse). We performed Cox regression analyses calculating hazard rate ratios (HRR) including 95%-confidence intervals (CI) and adjusted for relevant confounders. We followed a total of 11,856 patients with a first-time schizophrenia diagnosis (58.7% male, mean age 23.1 (SD = 4.7) years) for 39,033 person-years, whereof 5506 (46.4%) had relapse with schizophrenia re-hospitalization during 5-year of follow-up. Somatic hospital contacts ever before (95.4%; HRR = 1.30; 95%-CI = 1.07–1.59), and specifically during the year before schizophrenia diagnosis (42.5%; HRR = 1.36; 95%-CI = 1.11–1.66) were associated with an increased risk of schizophrenia relapse as were a greater number of prior somatic hospital contacts (p < 0.001). Individuals with up to four different prescriptions for somatic medications showed a trend towards a slightly lower risk of relapse. Somatic diseases and health seeking patterns might have an impact on the course of schizophrenia, where severe somatic comorbidity, specifically during the year before first-time schizophrenia diagnosis, seem to negatively affect early treatment course, whereas previous somatic medication use may indicate a better compliance and help-seeking behavior. [ABSTRACT FROM AUTHOR]

Objective: Prior studies have indicated that both high and low school grades are associated with development of bipolar disorder (BD), but these studies have not adjusted for parental history of mental disorder, which is a likely confounder. Furthermore, the association between school grades and bipolar I disorder (BD-I) has not been studied. Therefore, we aimed to study the association between school exam grades and subsequent development of BD and BD-I while adjusting for parental history of mental disorder. Methods: We conducted a register-based nationwide cohort study following 505 688 individuals born in Denmark between 1987 and 1995. We investigated the association between school exam grades and development of BD or BD-I with a Cox model adjusting for family history of mental disorder and other potential confounders. Results: During follow-up, 900 individuals were diagnosed with BD and 277 of these with BD-I. The risk for BD and BD-I was significantly increased for individuals not having completed the exams at term [adjusted hazard ratio (aHR) for BD (aHR=1.71, 95% CI: 1.43–2.04) and for BD-I (aHR=1.57, 95% CI: 1.13–2.19)]. Also, having low exam grades in mathematics was associated with increased risk of both BD (aHR=2.41, 95% CI: 1.27–4.59) and BD-I (aHR=2.71, 95% CI: 1.41–5.21). Females with very high exam grades in Danish (percentile group>97.7) had a significantly increased risk of BD-I (aHR=2.49, 95% CI: 1.19–5.23). Conclusions: The potential to develop BD seems to affect the school results of individuals negatively even before BD is diagnosed – with females having the potential to develop BD-I as a possible exception. [ABSTRACT FROM AUTHOR]

Summary: Objective: This study aims to examine the association between maternal age, paternal age, and parental age difference at the time of birth and the risk of epilepsy in the offspring. Methods: We carried out a prospective population‐based register study of all singletons born in Denmark between 1981 and 2012. Cox regression was used to estimate hazard ratios (HRs) of epilepsy and their corresponding 95% confidence intervals (CIs), adjusted for relevant confounders. Results: We followed 1 587 897 individuals for a total of ~25 million person‐years and identified 21 797 persons with epilepsy during the study period. An excess risk of epilepsy was found in individuals born to mothers younger than 20 years (HR = 1.17, 95% CI = 1.07‐1.29) and born to parental couples where paternal age exceeded maternal age by at least 5 years. The risk of epilepsy increased with increasing parental age gap and was highest when the father was ≥15 years older than the mother (adjusted HR = 1.28, 95% CI = 1.16‐1.41). In contrast to maternal age, we found that paternal age did not independently contribute to offspring epilepsy risk, once we accounted for the parental age difference (P = .1418). The observed associations with maternal age and parental age gap were invariant to epilepsy subtypes, but were modified by age of epilepsy onset, with the effect being most pronounced in the first 10 years of the child's life. Significance: Maternal age and parental age gap, but not paternal age, were associated with the offspring's risk of epilepsy. Our results do not support the hypothesis that de novo mutations associated with advanced paternal age increase the risk of epilepsy in the offspring. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Anxiety disorders and anorexia nervosa are frequently acknowledged to be highly comorbid conditions, but still, little is known about the clinical and aetiological cohesion of specific anxiety diagnoses and anorexia nervosa. Using the comprehensive Danish population registers, we aimed to determine the risk of anorexia nervosa in patients with register-detected severe anxiety disorders. We also explored whether parental psychopathology was associated with offspring's anorexia nervosa. Anxiety disorders increased the risk of subsequent anorexia nervosa, with the highest risk observed in obsessive-compulsive disorder. Especially, male anxiety patients were at an increased risk for anorexia nervosa. Furthermore, an increased risk was observed in offspring of fathers with panic disorder. A diagnosis of an anxiety disorder, specifically obsessive-compulsive disorder, constitutes a risk factor for subsequent diagnosis of anorexia nervosa. These observations support the notion that anxiety disorders and anorexia nervosa share etiological mechanisms and/or that anxiety represents one developmental pathway to anorexia nervosa. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association. [ABSTRACT FROM AUTHOR]

Summary Background To examine the risk of schizophrenia in a Danish population after exposure to early life stress, and whether this risk is modified by DNA sequence variation, specifically two single nucleotide polymorphisms (SNPs) (rs5479 and rs56303414) from the gene HSD11B2 . This gene encodes the enzyme 11-β hydroxysteroid dehydrogenase type 2 which converts active cortisol into inactive cortisone. Methods A two-stage analysis involving (1) a population-based cohort study, and (2) a nested case-control study using genotype information. Stage 1 included 1,141,447 people; here, we calculated incidence rate ratios (IRR) for the risk of schizophrenia among children of mothers who experienced loss or serious illness of close relatives before, during, and after pregnancy. In stage 2, we genotyped rs5479 and rs56303414 among 1275 schizophrenia cases and 1367 controls, and investigated interactions between genotypes and early life stress on the risk of schizophrenia. Results In stage 1, no increased risk of schizophrenia was found in offspring after exposure during pregnancy, but offspring exposed to early life stress at age 0–2 years had a significantly increased risk of schizophrenia (adjusted IRR 1.18, 95% confidence interval 1.07–1.31). For rs5479, the minor allele was nucleotide A, and the major allele was nucleotide C. No interaction was found between rs5479 and exposure during pregnancy. Individuals with the minor A allele of rs5479, however, had a significantly increased risk of schizophrenia after exposure to early life stress at age 3–9 years (adjusted IRR 2.06, 1.04–4.06). No interaction was found between rs56303414 and exposure in any of the time periods. Conclusion No association was found between exposure to early life stress during pregnancy and schizophrenia in the offspring investigated, whereas individuals exposed to early life stress within the first two years of life had an increased risk. No interaction was found between HSD11B2 and exposure during pregnancy, but individuals with the A allele of rs5479 had an increased risk of schizophrenia after exposure at age 3–9 years. [ABSTRACT FROM AUTHOR]

Psychotic experiences (PE) in individuals of the general population are hypothesized to mark the early expression of the pathology underlying psychosis. This notion of PE as an intermediate phenotype is based on the premise that PE share genetic liability with psychosis. We examined whether PE in childhood was predicted by a family history of mental disorder with psychosis rather than a family history of nonpsychotic mental disorder and whether this association differed by severity of PE. The study examined data on 1632 children from a general population birth cohort assessed at age 11-12 years by use of a semistructured interview covering 22 psychotic symptoms. The Danish national registers were linked to describe the complete family history of hospital-based psychiatric diagnoses. Uni- and multivariable logistic regressions were used to test whether a family history of any mental disorder with psychosis, or of nonpsychotic mental disorder, vs no diagnoses was associated with increased risk of PE in offspring (hierarchical exposure variable). The occurrence of PE in offspring was significantly associated with a history of psychosis among the first-degree relatives (adjusted relative risk [RR] = 3.29, 95% CI: 1.82-5.93). The risk increased for combined hallucinations and delusions (adjusted RR = 5.90, 95% CI: 2.64-13.16). A history of nonpsychotic mental disorders in first-degree relatives did not contribute to the risk of PE in offspring nor did any mental disorder among second-degree relatives. Our findings support the notion of PE as a vulnerability marker of transdiagnostic psychosis. The effect of psychosis in first-degree relatives may operate through shared genetic and environmental factors. [ABSTRACT FROM AUTHOR]

Background Nonsteroidal anti-inflammatory drugs ( NSAIDs) and paracetamol have been shown to yield the potential of adjunctive antidepressant treatment effects to selective serotonin reuptake inhibitors ( SSRIs); however, when investigating treatment effects of concomitant use, simultaneous evaluation of potential adverse events is important. The objective was thus to investigate treatment effectiveness and safety aspects of concomitant SSRI use with NSAIDs or paracetamol. Methods Within a 25% random sample of the Danish population, we identified all incident SSRI users between 1997 and 2006 ( N = 123,351). Effectiveness and safety measures were compared between periods of SSRI use only and periods of combined SSRI and NSAID or paracetamol use by applying Cox regression. Results Among 123,351 SSRI users (follow-up: 53,697.8 person-years), 21,666 (17.5%) used NSAIDs and 10,232 (8.3%) paracetamol concomitantly. Concomitant NSAID use increased the risk of any psychiatric contact [Hazard rate ratio (95%-confidence interval): 1.22 (1.07; 1.38)] and with depression [1.31 (1.11; 1.55)]. Low-dose acetylsalicylic acid reduced the risk of psychiatric contact in general [0.74 (0.56; 0.98)] and with depression [0.71 (0.50; 1.01)]. Ibuprofen reduced the risk of psychiatric contacts [0.76 (0.60; 0.98)]. Concerning safety, paracetamol was associated with increased mortality [3.18 (2.83; 3.58)], especially cardiovascular [2.51 (1.93; 3.28)]. Diclofenac [1.77 (1.22; 2.55)] and the selective COX-2 inhibitors [1.75 (1.21; 2.53)] increased mortality risks. Conclusions Concomitant use of SSRIs and NSAIDs occurred frequently, and effectiveness and safety outcomes varied across individual NSAIDs. Especially low-dose acetylsalicylic acid may represent an adjunctive antidepressant treatment option. The increased mortality risk of concomitant use of paracetamol needs further investigation. [ABSTRACT FROM AUTHOR]

Background: Pre- and perinatal factors and preschool body size may help identify children developing overweight, but these factors might have changed during the development of the obesity epidemic. Objective: We aimed to assess the associations between early life risk indicators and overweight at the age of 9 and 15 years at different stages of the obesity epidemic. Methods: We used two population-based Northern Finland Birth Cohorts including 4111 children born in 1966 (NFBC1966) and 5414 children born in 1985–1986 (NFBC1986). In both cohorts, we used the same a priori defined prenatal factors, maternal body mass index (BMI), birth weight, infant weight (age 5 months and 1 year), and preschool BMI (age 2–5 years). We used internal references in early childhood to define percentiles of body size (<50, 50–75, 75–90 and >90) and generalized linear models to study the association with overweight, according to the International Obesity Taskforce (IOTF) definitions, at the ages of 9 and 15 years. Results: The prevalence of overweight at the age of 15 was 9% for children born in 1966 and 16% for children born in 1986. However, medians of infant weight and preschool BMI changed little between the cohorts, and we found similar associations between maternal BMI, infant weight, preschool BMI, and later overweight in the two cohorts. At 5 years, children above the 90th percentile had approximately a 12 times higher risk of being overweight at the age of 15 years compared to children below the 50th percentile in both cohorts. Conclusions: The associations between early body size and adolescent overweight showed remarkable stability, despite the increase in prevalence of overweight over the 20 years between the cohorts. Using consequently defined internal percentiles may be a valuable tool in clinical practice. [ABSTRACT FROM AUTHOR]

Background: If preschool measures of body size routinely collected at preventive health examinations are associated with adult central obesity and metabolic syndrome, a focused use of these data for the identification of high risk children is possible. The aim of this study was to test the associations between preschool weight and body mass index (BMI) and adult BMI, central obesity and metabolic alterations. Methods: The Northern Finland Birth Cohort 1966 (NFBC1966) (N = 4111) is a population-based cohort. Preschool weight (age 5 months and 1 year) and BMI (age 2–5 years) were studied in relation to metabolic syndrome as well as BMI, waist circumference, lipoproteins, blood pressure, and fasting glucose at the age of 31 years. Linear regression models and generalized linear regression models with log link were used. Results: Throughout preschool ages, weight and BMI were significantly linearly associated with adult BMI and waist circumference. Preschool BMI was inversely associated with high-density lipoprotein levels from the age of 3 years. Compared with children in the lower half of the BMI range, the group of children with the 5% highest BMI at the age of 5 years had a relative risk of adult obesity of 6.2(95% CI:4.2–9.3), of adult central obesity of 2.4(95% CI:2.0–2.9), and of early onset adult metabolic syndrome of 2.5(95% CI:1.7–3.8). Conclusions: High preschool BMI is consistently associated with adult obesity, central obesity and early onset metabolic syndrome. Routinely collected measures of body size in preschool ages can help to identify children in need of focused prevention due to their increased risk of adverse metabolic alterations in adulthood. [ABSTRACT FROM AUTHOR]

• 92 % of those with recorded eating disorder diagnoses in Denmark are female. • However, diagnosed males have especially high rates of subsequent mortality. • Increased mortality following eating disorder is mainly due to suicide or accidents. • Higher risk of anorexia nervosa for genetic variants associated with lower body fat. 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. [ABSTRACT FROM AUTHOR]

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. • Birth order and advanced maternal age risk factors for OCD, especially in males. • Being an only child associated with OCD risk. • Early life parental SES variables increased OCD risk, especially in females. • Interaction between parental education and proband psychiatric comorbidities observed for OCD risk. • Sex differences should be carefully examined in relation to risk factors. [ABSTRACT FROM AUTHOR]

• Childhood infections increase the risk of schizophrenia in a dose-dependent manner. • Adversities in childhood increase the risk of acquiring infections. • Adversities do not confound the association between infection and schizophrenia. • Familial liability for infection increases schizophrenia risk. • Parental mental health modifies association between infection and schizophrenia. 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. [ABSTRACT FROM AUTHOR]

Abstract Background Studies have suggested that poor school achievement is associated with increased risk of schizophrenia; however, the possible genetic contribution to this association is unknown. We investigated the possible effect of the polygenic risk score (PRS) for schizophrenia (PRS SCZ) and for educational attainment (PRS EDU) on the association between school performance and later schizophrenia. Methods We conducted a case-cohort study on a Danish population-based sample born from 1987 to 1995 comprising 1470 individuals with schizophrenia and 7318 subcohort noncases. Genome-wide data, school performance, and family psychiatric and socioeconomic background information were obtained from national registers and neonatal biobanks. PRS SCZ and PRS EDU were calculated using discovery effect size estimates from a meta-analysis of 34,600 cases and 45,968 controls and 293,723 individuals. Results Higher PRS SCZ increased the risk (incidence rate ratio [IRR]: 1.28; 95% confidence interval [CI], 1.19–1.36), whereas higher PRS EDU decreased the risk of schizophrenia (IRR, 0.87; 95% CI, 0.82–0.92) per standard deviation. Not completing primary school and receiving low school marks were associated with increased risk of schizophrenia (IRR, 2.92; 95% CI, 2.37–3.60; and IRR, 1.58; 95% CI, 1.27–1.97, respectively), which was not confounded by PRS SCZ or PRS EDU. Adjusting for social factors and parental psychiatric history, effects of not completing primary school and receiving low school marks were attenuated by up to 25% (IRR, 2.19; 95% CI, 1.75–2.73; and IRR, 1.39; 95% CI, 1.11–1.75, respectively). Increasing PRS EDU correlated with better school performance (p <.01; R 2 = 7.6%). PRS SCZ and PRS EDU was significantly negatively correlated (r = −.31, p <.01). Conclusions The current PRS did not account for the observed association between primary school performance and risk of schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: No medications have been indicated for the treatment of anorexia nervosa (AN). Nonetheless, individuals with AN are frequently treated pharmacologically. The present study maps nationwide pharmacotherapy two years before to five years after first AN diagnosis.Methods: We identified all medication prescriptions in a national register-based study of patients with a first diagnosis of AN between 1998 and 2011, and age and gender matched controls (1:10). Medication classes were compared using odds ratios (OR) between patients and controls; between patients below and above 15 years; between patients with and without comorbidity; and between those diagnosed before or after 2005.Results: The odds of pharmacotherapy were increased in patients for all classes of medication except a small residual class. Highest odds were found for alimentary (OR 2.8, p < 0.001) and psychopharmacological (OR 5.5, p < 0.001) medication. The former peaked one year prior to first diagnosis and the latter one year after. Older patients had increased risk of almost all medication classes with cardiovascular medication showing a fivefold OR (p < 0.001). Patients with psychiatric comorbidity had a threefold OR for psychopharmacological medication (p < 0.001) compared to patients without psychiatric comorbidity. Calendar year showed few and small differences.Conclusion: The extended use of all medication classes both prior to and after first diagnosis of AN highlights the severe cause and complexity of AN. The results encourage clinical caution of pharmacotherapy, highlight the need for pharmacotherapy guidelines for AN, and emphasize the urgency of research in pharmacotherapy in AN. [ABSTRACT FROM AUTHOR]