Danish Psychiatric Central Research Register Research Articles

A comprehensive analysis of age of onset and cumulative incidence of mental disorders: A Danish register study.

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. 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. 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)). 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.

Patients with eosinophilic oesophagitis in Denmark have higher use of psychotropic drugs: A Danish nationwide study of psychotropic drug use in 3367 patients and 16,835 matched comparators.

Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated disease of the oesophagus. Eosinophilic oesophagitis is associated with a substantial disease burden affecting the quality of life and affecting mental health. There are limited data describing the incidence of psychiatric disorders and the use of psychotropic drugs (PDs) in EoE patients. The aim was to investigate whether EoE patients in Denmark have higher use of PDs, contacts with the department of psychiatry, and attempts of suicide or intentional self-harm compared with the general population after being diagnosed with EoE. This study was a nationwide, population-based register study including 3367 EoE patients and 16,835 age- and sex-matched comparators. A register-based EoE definition was used to identify cases. Incident PD use was extracted from the prescription register and information regarding psychiatric contacts was retrieved from the Danish Psychiatric Central Research Register. The 5-year incidence of PD use in EoE patients was 13.8% compared to 7.1% of the matched comparators (Hazard ratio 1.83; confidence interval 1.6-2.0; p≤0.001). Antidepressants were the most frequently prescribed PD, whereas antipsychotics were the least prescribed PD. Increasing age, lower educational level, and comorbidity (Charlson Comorbidity Index score ≥1) were associated with the prescription of PDs. The risk of PD use was lower in men than in women with EoE. Treatment with PDs were more common in EoE patients after they were diagnosed than in the general Danish population, indicating that EoE patients have an increased risk of psychiatric disorders.

Risk of homelessness after prison release and recidivism in Denmark: a nationwide, register-based cohort study

Transitional periods between and across services have been linked to homelessness. We aimed to investigate the association of previous history of homelessness and psychiatric disorders with risk of homelessness after release from prison. Additionally, we examined the association between homelessness after release and risk of recidivism. We did a nationwide, register-based cohort study of people aged 15 years or older who were released from prison for the first time in Denmark between Jan 1, 2001, and Dec 31, 2021. We obtained data using the Danish Civil Registration System with data linked across other registries (the Danish Central Criminal Register, the Danish Homeless Register, the Danish National Patient Register, and the Danish Psychiatric Central Research Register) on release date, homeless shelter contacts, psychiatric disorders, and new convictions. Outcomes were homelessness after release from prison, defined as first homeless shelter contact following release from first imprisonment, and recidivism within 2 years of release, defined as the first police-recorded criminal conviction after prison release. We calculated incidence rates per 1000 person-years, incidence rate ratios (IRRs) using Poisson regression analysis, and probability of homelessness and recidivism after release. Sex, age, calendar year, country of origin, highest educational level, relationship status, and length of index imprisonment were included as confounders. The study cohort included 37 382 individuals (34 792 males [93·1%] and 2590 females [6·9%]) aged 15-41 years, who were released from prison between Jan 1, 2001, and Dec 31, 2021, contributing 202 197 person-years at risk. Mean follow-up duration was 5·4 person-years (SD 5·6). Overall, 1843 (4·9%) of 37 382 individuals became homeless. 1 year after release from prison, 788 (2·1%) of 37 382 individuals had at least one homeless shelter contact, and among 1761 individuals with previous history of homelessness before index imprisonment, 357 (20·7%) became homeless. The incidence of homelessness after release was 102·5 cases per 1000 person-years for individuals with previous history of homelessness and 6·7 cases per 1000 person-years in individuals without (IRR 16·4, 95% CI 14·8-18·2; adjusted for sex, age, and calendar year). Individuals who additionally had a mental illness had a higher risk of homelessness (IRR 22·6, 19·7-25·9) compared with those without either previous homelessness or mental illness, and a substantially higher risk was observed for those with previous homelessness and drug use disorder (25·0, 21·6-28·9) compared with those without. Within 2 years of release from prison, the probability of recidivism was 73·2% (95% CI 72·8-73·7). The risk of recidivism was higher among people experiencing homelessness after release from prison than those who did not experience homelessness after release (IRR 1·5, 95% CI 1·3-1·7), adjusted for sex, age, and calendar year. Criminal justice services should review approaches to reduce risk of homelessness, and consider improving liaison with mental health and substance misuse services to prevent adverse outcomes on release from prison. Clinical guidelines applied to criminal justice settings should address the health of individuals who experience homelessness. Lundbeck Foundation.

Association of Early-, Middle-, and Late-Life Depression With Incident Dementia in a Danish Cohort

Late-life depressive symptoms are associated with subsequent dementia diagnosis and may be an early symptom or response to preclinical disease. Evaluating associations with early- and middle-life depression will help clarify whether depression influences dementia risk. To examine associations of early-, middle-, and late-life depression with incident dementia. This was a nationwide, population-based, cohort study conducted from April 2020 to March 2023. Participants included Danish citizens from the general population with depression diagnoses who were matched by sex and birth year to individuals with no depression diagnosis. Participants were followed up from 1977 to 2018. Excluded from analyses were individuals followed for less than 1 year, those younger than 18 years, or those with baseline dementia. Depression was defined using diagnostic codes from the International Classification of Diseases (ICD) within the Danish National Patient Registry (DNPR) and Danish Psychiatric Central Research Register (DPCRR). Incident dementia was defined using ICD diagnostic codes within the DPCRR and DNPR. Cox proportional hazards regression was used to examine associations between depression and dementia adjusting for education, income, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, anxiety disorders, stress disorders, substance use disorders, and bipolar disorder. Analyses were stratified by age at depression diagnosis, years since index date, and sex. There were 246 499 individuals (median [IQR] age, 50.8 [34.7-70.7] years; 159 421 women [64.7%]) with diagnosed depression and 1 190 302 individuals (median [IQR] age, 50.4 [34.6-70.0] years; 768 876 women [64.6%]) without depression. Approximately two-thirds of those diagnosed with depression were diagnosed before the age of 60 years (684 974 [67.7%]). The hazard of dementia among those diagnosed with depression was 2.41 times that of the comparison cohort (95% CI, 2.35-2.47). This association persisted when the time elapsed from the index date was longer than 20 to 39 years (hazard ratio [HR], 1.79; 95% CI, 1.58-2.04) and among those diagnosed with depression in early, middle, or late life (18-44 years: HR, 3.08; 95% CI, 2.64-3.58; 45-59 years: HR, 2.95; 95% CI, 2.75-3.17; ≥60 years: HR, 2.31; 95% CI, 2.25-2.38). The overall HR was greater for men (HR, 2.98; 95% CI, 2.84-3.12) than for women (HR, 2.21; 95% CI, 2.15-2.27). Results suggest that the risk of dementia was more than doubled for both men and women with diagnosed depression. The persistent association between dementia and depression diagnosed in early and middle life suggests that depression may increase dementia risk.

Associations of psychiatric disorders with sex chromosome aneuploidies in the Danish iPSYCH2015 dataset: a case-cohort study

Increased prevalence of mental illness has been reported in clinical studies of sex chromosome aneuploidies, but accurate population-based estimates of the prevalence and clinical detection rate of sex chromosome aneuploidies and the associated risks of psychiatric disorders are needed. In this study, we provide such estimates, valid for children and young adults of the contemporary Danish population. We used the iPSYCH2015 case-cohort dataset, which is based on a source population of single-born individuals born in Denmark between May 1, 1981, and Dec 31, 2008. The case sample comprises all individuals from the source population with a diagnosis of any index psychiatric disorder (schizophrenia spectrum disorder, bipolar disorder, major depressive disorder, autism spectrum disorder, or ADHD) by the end of follow-up (Dec 31, 2015), registered in the hospital-based Danish Psychiatric Central Research Register. The cohort consists of individuals randomly selected from the source population, and overlaps with the case sample. Biobanked blood samples for individuals in the case and cohort samples underwent genotyping and quality-control filtering, after which we analysed microarray data to detect sex chromosome aneuploidy karyotypes (45,X, 47,XXX, 47,XXY, and 47,XYY). We estimated the population-valid prevalence of these karyotypes from the cohort sample. Weighted Cox proportional hazards models were used to estimate the risks of each index psychiatric disorder associated with each sex chromosome aneuploidy karyotype, by use of date of first hospitalisation with the index disorder in the respective case group and the cohort as outcome. The clinical detection rate was determined by comparing records of clinical diagnoses of genetic conditions from the Danish National Patient Register with sex chromosome aneuploidy karyotype determined by our study. The assessed sample comprised 119 481 individuals (78 726 in the case sample and 43 326 in the cohort) who had genotyped and quality-control-filtered blood samples, including 64 533 (54%) people of gonadal male sex and 54 948 (46%) of gonadal female sex. Age during follow-up ranged from 0 to 34·7 years (mean 10·9 years [SD 3·5 years]). Information on ethnicity was not available. We identified 387 (0·3%) individuals as carriers of sex chromosome aneuploidies. The overall prevalence of sex chromosome aneuploidies was 1·5 per 1000 individuals. Each sex chromosome aneuploidy karyotype was associated with an increased risk of at least one index psychiatric disorder, with hazard ratios (HRs) of 2·20 (95% CI 1·42-3·39) for 47,XXY; 2·73 (1·25-6·00) for 47,XXX; 3·56 (1·01-12·53) for 45,X; and 4·30 (2·48-7·55) for 47,XYY. All karyotypes were associated with an increased risk of ADHD (HRs ranging from 1·99 [1·24-3·19] to 6·15 [1·63-23·19]), autism spectrum disorder (2·72 [1·72-4·32] to 8·45 [2·49-28·61]), and schizophrenia spectrum disorder (1·80 [1·15-2·80] to 4·60 [1·57-13·51]). Increased risk of major depressive disorder was found for individuals with 47,XXY (1·88 [1·07-3·33]) and 47,XYY (2·65 [1·12-5·90]), and of bipolar disorder for those with 47,XXX (4·32 [1·12-16·62]). The proportion of sex chromosome aneuploidy carriers who had been clinically diagnosed was 93% for 45,X, but lower for 47,XXY (22%), 47,XXX (15%), and 47,XYY (15%). Among carriers, the risk of diagnosis of at least one index psychiatric disorder did not significantly differ between those who had and had not been clinically diagnosed with sex chromosome aneuploidies (p=0·65). Increased risks of psychiatric disorders associated with sex chromosome aneuploidies, combined with low rates of clinical diagnosis of sex chromosome aneuploidies, compromise the adequate provision of necessary health care and counselling to affected individuals and their families, which might be helped by increased application of genetic testing in clinical settings. Lundbeck Foundation and National Institutes of Health.

The association between mental disorders and subsequent years of working life: a Danish population-based cohort study

Mental disorders can affect workforce participation via a range of mechanisms. In this study, we aimed to estimate the association between different types of mental disorders and working years lost, defined as the number of years not actively working or enrolled in an educational programme. In this population-based cohort study, we included all people aged 18-65 years (mean 38·0 [SD 13·9]) in the Danish Civil Registration System from Jan 1, 1995 to Dec 31, 2016. Information on mental disorders was obtained from the Danish Psychiatric Central Research Register and information on labour market characteristics was obtained from administrative registers. Follow-up started at age 18 years, immigration to Denmark, or on Jan 1, 1995, whichever came later; and it ended at age 65 years, death, emigration from Denmark, disability pension, voluntary early retirement, or Dec 31, 2016 (whichever came earlier). As the main outcome, we estimated working years lost for those diagnosed with any mental disorder and 24 types of mental disorders, as well as for the general population of same age and sex. We decomposed total working years lost into periods of unemployment or sick leave, disability pension, voluntary early retirement, or death. Data on ethnicity were not available through administrative registers. A total of 5 163 321 individuals, 2 642 383 men and 2 520 938 women, were followed up for 65·4 million person-years. Overall, 488 775 (9·47%) individuals were diagnosed with a mental disorder. On average, individuals with mental disorders lost an additional 10·52 (95% CI 10·48-10·57) years of working life compared with the general Danish population. Receiving a disability pension (7·54 [7·49-7·59] years) and longer periods of unemployment (2·24 [2·21-2·27] years) accounted for most of this difference. Our findings foreground the substantial impact of mental disorders on workforce participation. There is a need to invest in programmes that reduce the burden of working years lost and assist people with mental disorders in returning to the workforce. Lundbeck Foundation and Danish National Research Foundation.

Adverse childhood experiences among children of parents who are refugees affected by trauma in Denmark: a register-based cohort study

Children in families who are refugees might experience more adversities than their peers. Adverse childhood experiences (ACEs) are well known risk factors for poorer adulthood health and adjustment. The risk of ACEs for children with a parent who is a refugee affected by trauma is unknown. We aimed to estimate the hazard of individual and cumulative ACEs using a unique sample of children with parents who are refugees affected by and seeking treatment for trauma and population level data. This was a register-based cohort study carried out in Denmark. All children aged 0-15 years, residing in Denmark between Jan 1, 1990, and Dec 31, 2016, were followed up from birth or migration into the country to their 15th birthday. We linked data from the Danish Civil Registration System, the Danish National Patient Register, the Danish Psychiatric Central Research Register, the Employment Classification Module, the Register of Causes of Death, and the Income Statistics Register to investigate ten ACE categories (parental: natural and unnatural death, serious mental illness, substance use disorder, somatic illness, and disability; child: residential instability, family disruption, poverty, and stressors) and the cumulative number of ACE categories for children with a parent from a refugee-sending country and children with a parent who is a refugee in treatment for trauma. The main outcome was the hazard ratio (HR) of the individual and cumulative ACEs among children with a parent from a refugee-sending country and children with a parent who is a refugee affected by trauma, compared with the general population of children in Denmark, both adjusted and unadjusted for parental country of origin. 2 688 794 children were included in the study, 252 310 of whom had parents from refugee-sending countries. 11 603 children had parents affected by trauma and seeking treatment, of whom 1163 (10%) migrated to Denmark before their second birthday and 10 440 (90%) were born in Denmark. Compared with the general population of children in Denmark, the hazard for most ACEs was significantly higher for both children with parents from a refugee-sending country and children with parents who are refugees affected by trauma. For children with a parent from a refugee-sending country, the highest HR was related to the child living in relative poverty for 3 years (3·62 [95% CI 3·52-3·73]). After adjusting for parental country of origin, the hazards for five ACEs were significantly greater for children of parents who are refugees affected by trauma compared with the remaining children of parents from the same countries. The highest HR for this child group was for parental serious mental illness (1·98 [1·85-2·12]). The hazard for experiencing multiple ACEs was significantly higher for both child groups compared with the general population. Our findings suggest that children with parents from refugee-sending countries have a higher rate of several ACEs compared with the general population. Furthermore, having a parent who is a refugee affected by trauma and seeking treatment seems to be an independent risk factor for poorer health and adjustment in adulthood. This study informs decision makers and caregivers that there might be much added value in addressing needs within the whole family, as opposed to only attending to the parent who is seeking treatment. The Lundbeck Foundation.

Serious Mental Illness Exacerbation Post-Bereavement: A Population-Based Study of Partners and Adult Children.

PurposeThe death of a close family member is commonly accompanied by intense grief, stress, and loss of social support. We hypothesized that recent bereavement would be associated with an increase in symptom exacerbations among adults with serious mental illness (SMI) whose partners or parents had died.Patients and MethodsAdults whose partners and parents had died in Denmark between January 1, 2010, and June 30, 2016, were identified using linked population-based registries. History of SMI was defined as having a diagnosis of schizophrenia and schizoaffective disorders, major depression, and bipolar disorder in the five years preceding their family member’s death in the Danish Psychiatric Central Research Register using International Classification of Diseases-10 codes. The odds of SMI exacerbation (ie, attempt or completion of suicide or psychiatric hospitalization) among partners and children in the first two years after death in 3-month intervals were estimated with generalized estimating equations.Results12.8% of partners and 15.0% of adult children with a history of SMI experienced any SMI exacerbation two years after bereavement. Among bereaved partners, older age (80+ years) was associated with a lower risk of experiencing an SMI exacerbation compared with partners aged 18–49 years (ORadj=0.29, [0.18–0.45]). Partners with a history of SMI had significantly increased odds of SMI exacerbations three months after their partners’ death compared to prior to their partners’ death (ORadj = 1.43, [1.13–1.81]). There was no evidence that adult children with SMI experience increased SMI exacerbations after the death of their parents compared to prior to death.ConclusionAdults with a history of SMI whose partners had died are at increased risk for an SMI exacerbation post bereavement. Additional bereavement resources and support should be provided to those with a history of SMI, especially in the period immediately after death.

Association of Lithium Treatment With the Risk of Osteoporosis in Patients With Bipolar Disorder

Osteoporosis, a systemic skeletal disorder associated with substantial morbidity and mortality, may be particularly common among individuals with bipolar disorder. Lithium, a first-line mood-stabilizing treatment for bipolar disorder, may have bone-protecting properties. To evaluate if treatment with lithium is associated with a decrease in risk of osteoporosis among patients with bipolar disorder. This retrospective cohort study included 22 912 adults from the Danish Psychiatric Central Research Register who received an initial diagnosis of bipolar disorder in the period from January 1, 1996, to January 1, 2019. For each patient with bipolar disorder, 5 age- and sex-matched individuals were randomly selected from the general population as reference individuals. Individuals with bipolar disorder prior to January 1, 1996, those with a diagnosis of schizophrenia or schizoaffective disorder prior to being diagnosed with bipolar disorder, and those with osteoporosis prior to the index date were excluded. Of the 114 560 reference individuals included, 300 were diagnosed with bipolar disorder during follow-up and were censored from the reference group from the date of diagnosis forward. For patients with bipolar disorder, treatment periods with lithium, antipsychotics, valproate, and lamotrigine were identified. Analyses were performed between January 2021 and January 2022. Bipolar disorder and treatment with lithium, antipsychotics, valproate, and lamotrigine. The primary outcome was osteoporosis, identified via hospital diagnoses and prescribed medications. First, incidence of osteoporosis was compared between patients with bipolar disorder and reference individuals (earliest start of follow-up at age 40 years) using Cox regression. Subsequently, incidence of osteoporosis for patients receiving treatment with lithium, antipsychotics, valproate, and lamotrigine, respectively, was compared with that of patients who were not treated with these medications. A total of 22 912 patients with bipolar disorder (median [IQR] age, 50.4 [41.2-61.0] years; 12 967 [56.6%] women) and 114 560 reference individuals (median [IQR] age, 50.4 [41.2-61.0] years; 64 835 [56.6%] women) were followed up for 1 213 695 person-years (median [IQR], 7.68 [3.72-13.24] years). The incidence of osteoporosis per 1000 person-years was 8.70 (95% CI, 8.28-9.14) among patients and 7.90 (95% CI, 7.73-8.07) among reference individuals, resulting in a hazard rate ratio (HRR) of 1.14 (95% CI, 1.08-1.20). Among patients with bipolar disorder, 8750 (38.2%) received lithium, 16 864 (73.6%) received an antipsychotic, 3853 (16.8%) received valproate, and 7588 (33.1%) received lamotrigine (not mutually exclusive). Patients with bipolar disorder treated with lithium had a decrease in risk of osteoporosis (HRR, 0.62; 95% CI, 0.53-0.72) compared with patients not receiving lithium. Treatment with antipsychotics, valproate, and lamotrigine was not associated with reduced risk of osteoporosis. In this study, bipolar disorder was associated with an increase in risk of osteoporosis, and lithium treatment was associated with a decrease in risk of osteoporosis. These findings suggest that bone health should be a priority in the clinical management of bipolar disorder and that the potential bone-protective properties of lithium should be subjected to further study, both in the context of bipolar disorder and in osteoporosis.

Temporal changes in sex- and age-specific incidence profiles of mental disorders-A nationwide study from 1970 to 2016.

ObjectiveInformation on mental disorders over time is critical for documenting changes in population burden, and aiding understanding of potential causal and non‐causal factors. The aim of this study was to provide temporal changes in the sex‐ and age‐specific incidence rates (IR) of mental disorders diagnosed in Danish hospitals during five decades and investigate whether such changes may be attributable to changes in administrative reporting practice.MethodsThis population‐based cohort study included all people living in Denmark between 1970 and 2016. Mental disorders diagnoses were obtained from the Danish Psychiatric Central Research Register. We estimated the IR of each mental disorder (all persons, and sex‐ and age‐specific IRs) and examined the impact of two administrative changes.ResultsOur study included 9 107 157 people, followed for 233.0 million person‐years. During follow‐up, 9.5% were diagnosed with at least one mental disorder. The IR for any mental disorder was 39.0 per 10,000 person‐years. Despite fluctuations, this increased between 1970–84 and 2005–2016, from 28.9 to 63.0 per 10,000 person‐years. Increases were most pronounced for younger age groups. Administrative changes did appear to influence incidence rates.ConclusionMental disorder IRs have increased in Denmark since 1970, with age of diagnosis shifting downwards. Both trends were likely impacted by administrative changes, while the latter is likely to be (partly) attributable to earlier detection and increased reporting of child‐onset conditions. Our findings may provide valuable context of the epidemiology of mental disorders across age groups for comparison with other studies and populations.

Effect of antipsychotics on mortality risk in patients with dementia with and without comorbidities.

We investigated the mortality risk associated with the initiation of antipsychotic treatment among patients with dementia and whether comorbidities related to the cardiovascular system and diabetes interact with antipsychotic treatment to increase the mortality risk beyond the risk of death independently associated with antipsychotics and comorbidity alone. We designed a matched cohort study using nationwide registry data. All Danish residents aged 65-95 years diagnosed with dementia between 2009 and 2014 were included. Dementia was assessed as a first-time registered dementia diagnosis in the Danish National Patient Register or the Danish Psychiatric Central Research Register and/or a first-time prescription for antidementia medication. Patients exposed to antipsychotics were matched with up to three unexposed patients. Cox proportional hazards models were used to compare rates of death within 180 days after the initiation of antipsychotic treatment. The models were adjusted for potential confounders. Analyses were stratified for diabetes, heart disease, and cerebrovascular disease, and we calculated the relative excess risk due to interaction (RERI). The study cohort included 8244 exposed patients and 24,730 unexposed patients. A total of 5938 patients died during the first 180 days of follow-up. Patients exposed to antipsychotics had a significantly higher adjusted risk of death (hazard ratio: 1.35, 95% confidence interval: 1.27-1.43) than unexposed patients. Crude mortality rates were higher among patients with heart disease and diabetes when antipsychotic treatment was initiated compared with patients without comorbidities. Relative risk estimates did not differ between patients with and without heart disease, cerebrovascular disease, and diabetes, and RERI suggested no positive additive interaction. Risk analysis suggested higher mortality in patients without cerebrovascular disease who initiated antipsychotics. This nationwide study adds to the evidence that antipsychotic treatment is associated with increased mortality and suggests that attention should be paid to all initiators of antipsychotics irrespective of cardiovascular disease and diabetes.

Study Calculates Disability Caused by Schizophrenia

Back to table of contents Previous article Next article Clinical & ResearchFull AccessStudy Calculates Disability Caused by SchizophreniaNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:23 Aug 2021https://doi.org/10.1176/appi.pn.2021.9.31AbstractAn analysis using Danish registry data finds that though major depression was the most prevalent mental disorder in Denmark, schizophrenia was the leading cause of disability due to mental illness for both men and women, accounting for 273 years living with disability per 100,000 person-years.Making use of the abundant medical data available in Danish national health registries, researchers have developed new estimates on the amount of disability associated with different mental health and substance use disorders.When factoring in both the duration of illness and severity of disability, John McGrath, M.D., Ph.D., the Niels Bohr Professor at the National Centre for Register-based Research at Aarhus University in Denmark, and colleagues found schizophrenia to be the most burdensome mental illness at both an individual and population level. Personality disorders were second most disabling in both sexes, followed by anxiety disorder in women and alcohol use disorder in men. These findings were published in The Lancet Psychiatry.While previous studies have examined how mental and substance use disorders contribute to years lived with disability (YLD), these studies have largely relied on average incidence, remission, and prevalence rates in the population. McGrath’s team, together with researchers from Queensland Centre for Mental Health Research in Brisbane, Australia, instead relied on individual data from medical registries to calculate YLD. Such data included when people were diagnosed, how severe their symptoms were, and if/when they achieved remission.Using data from the Danish Psychiatric Central Research Register, McGrath and colleagues calculated the YLD for 18 mental health and substance use disorders. The YLD is calculated by multiplying the duration of an illness with a predefined disability index ranging from 0 to 1. (For example, the disability index of major depression is 0.15 for mild symptoms, 0.40 for moderate symptoms, and 0.66 for severe symptoms.)Though major depression was the most prevalent disorder in Denmark, schizophrenia was the leading cause of disability due to mental illness for both men and women, accounting for 273 YLDs per 100,000 person-years. Personality disorders were the secondmost disabling, followed by anxiety disorders.In contrast, most substance use disorders (with the exception of alcohol) contributed relatively little YLDs in the population. McGrath said these data should not imply that substance use is a minor societal concern in Denmark. “Our study focused on disability; if we had also looked at mortality, then substance use disorders would be near the top,” McGrath said. “Whether it’s overdoses, traffic accidents, or liver disease, alcohol and drugs are huge when it comes to years of life lost.”To gain more insight into disability at an individual level, McGrath and colleagues devised a metric called the Health Loss Proportion (HeLP) to quantify the disability associated with all mental comorbidities experienced by a person. On the individual level, schizophrenia was still the most disabling, as the researchers calculated the average person with schizophrenia loses 73% of his or her healthy life per year. Opioid use disorder (OUD) was second, resulting in a 67% loss of healthy life each year. (OUD is rare in Denmark, which is why it was not one of the top disorders for YLD at the population level.)For patients with schizophrenia and a comorbid disorder, the schizophrenia itself was the primary contributor of the disability, as was the case for patients with comorbid conduct disorder and autism spectrum disorder. But among other disorders, notably various substance use disorders, disability was heavily influenced by comorbid conditions the patients had.“These HeLP data reveal the subtle nuances in how different mental health disorders affect a person’s quality of life,” McGrath told Psychiatric News. “These HeLP metrics provide compelling evidence that we need mental health services that are better equipped as one-stop shots for a range of problems.”This study was supported by the Danish National Research Foundation. ■“Register-based Metrics of Years Lived With Disability Associated With Mental and Substance Use Disorders: A Register-Based Cohort Study in Denmark” is posted here. ISSUES NewArchived

Psychiatric disorders in individuals with neurofibromatosis 1 in Denmark: A nationwide register-based cohort study.

The aim of this study was to assess the risks of psychiatric disorders in a large cohort of 905 individuals with NF1 and 7614 population comparisons matched on sex and year of birth. The cohort was linked to the Danish Psychiatric Central Research Register to ascertain information on hospital contacts for psychiatric disorders based on the International Classification of Diseases version 8 and 10. The hazard ratio (HR) for a first psychiatric hospital contact was higher in girls (4.19, 95% confidence interval [CI] 1.81-9.69) and boys with NF1 (5.02, 95% CI 3.27-7.69) <7 years of age than in the population comparisons. Both sexes had increased HRs for developmental disorders, including attention deficit/hyperactivity disorders, autism spectrum disorders, and intellectual disabilities in childhood. Females with NF1 had also increased HRs for unipolar depression, other emotional and behavioral disorders, and severe stress reaction and adjustment disorders in early adulthood. The HRs for psychoses, schizophrenia, bipolar disorders, and substance abuse were similar in individuals with NF1 and the population comparisons. Finally, the cumulative incidence of a first hospital contact due to any psychiatric disorder by age 30 years was 35% (95% CI 29-41) in females and 28% (95% CI 19-37) in males with NF1. Thus, screening for psychiatric disorders may be important for early diagnosis and facilitation of appropriate and effective treatment in individuals with NF1.

What can we learn about eating disorder mortality from eating disorder diagnoses at initial assessment? A Danish nationwide register follow-up study using record linkage, encompassing 45 years (1970–2014)

Increased risk for premature mortality is well established for women and girls diagnosed with anorexia nervosa (AN), but less is known for other types of eating disorder (ED), and especially the mortality outcome for boys and men is under-studied. In this registry-based observational epidemiological study, we included all people appearing in the Danish Psychiatric Central Research Register with an eating disorder (ED) diagnosis in the time period from Jan 1,1970 to Dec 31, 2014 (N: 22,633). For each patient four controls without ED were selected, matched for age, sex and place of residence (N: 90486). In all 802 people with ED died over 255762.6 person-years of observation. Standardized mortality ratio (SMR) for all-cause mortality and suicide mortality was significantly increased for all ED-diagnoses in women. The SMRs for men were similar, but only reached significance for the diagnoses AN and unspecified ED. Mortality by natural causes and accidents was significantly increased in most ED-diagnoses in women. The unequal female-to-male ratio in this, and most other studies of ED-patients, suggests that boys and men with ED have unmet needs.

Food addiction comorbid to mental disorders in adolescents: a nationwide survey and register-based study.

Adolescence is a high-risk period for development of addictive behavior. This may also apply to addiction-like eating of highly processed foods-commonly referred to as "food addiction". Adolescents with mental disorder may be at particularly elevated risk of developing food addiction as addiction often accompanies mental disorder. However, there are only few studies in adolescents investigating this potential comorbidity. Therefore, the primary aim of this study was to examine the food addiction symptom load, as measured by the dimensional Yale Food Addiction Scale for Children-version 2.0 (dYFAS-C 2.0), among adolescents with a clinically verified mental disorder. A total of 3529 adolescents aged 13-17 were drawn from the Danish Psychiatric Central Research Register, stratified on six major diagnostic categories of mental disorders; psychotic disorders, affective disorders, anxiety disorders, eating disorders, autism spectrum disorders, and attention deficit disorders. Via their parents, these adolescents were invited to participate in a web-based survey. Data on health and socioeconomic factors from the Danish registers were linked to both respondents and non-respondents, allowing for thorough attrition analysis and estimation of weighted dYFAS-C 2.0 scores. A total of 423 adolescents participated in the survey (response rate 12.0%). The mean weighted dYFAS-C 2.0 total score was 13.9 (95% CI 12.6; 14.9) for the entire sample and varied substantially across the diagnostic categories being highest for those with psychotic disorder, mean 18.4 (95% CI 14.6; 14.9), and affective disorders, mean 19.4. (95% CI 16.3; 22.5). Furthermore, the dYFAS-C 2.0 total score was positively correlated with body mass index (BMI) (r = 0.33, p < 0.05). Food addiction symptomatology seems to be prevalent among adolescents with mental disorder, particularly affective and psychotic disorders. As obesity is a tremendous problem in individuals with mental disorder further investigation of food addiction in young people with mental disorder is called for. This could potentially aid in the identification of potential transdiagnostic targets for prevention and treatment of obesity in this group. Level IV, Observational cross-sectional descriptive study combined with retrospective register data.

Register-based metrics of years lived with disability associated with mental and substance use disorders: a register-based cohort study in Denmark

Mental disorders account for a substantial proportion of the years lived with disability (YLDs) globally. These estimates have generally been calculated top down based on summary statistics. The aim for this study was to calculate YLDs and a novel related measure, Health Loss Proportion (HeLP), for 18 mental and substance use disorders, based on person-level register data (bottom up). A cohort of 6 989 627 Danish residents (5·9% had a diagnosis of a mental or substance use disorder registered in the Danish Psychiatric Central Research Register) was investigated. YLDs (the duration of disease multiplied by a disability weight) were calculated for the disorder of interest and for comorbid mental and substance use disorders. HeLPs were estimated as YLDs associated with an index disorder and comorbid mental and substance use disorders divided by person-years at risk in persons with the index disorder. All analyses were adjusted for mental and substance use comorbidity using a multiplicative model of disability weights. Major depressive disorder was the most prevalent disorder, although schizophrenia was the leading cause of YLDs in both sexes combined (YLDs 273·3 [95 % CI 232·3-313·6] per 100 000 person-years). People diagnosed with schizophrenia lost the equivalent of 73% (63-83%) of healthy life per year due to mental and substance use disorders, the largest HeLP of all mental and substance use disorders. Comorbidity of mental and substance use disorders accounted for 69-83% of HeLPs in people with either cannabis use disorders, other drug use disorder and ADHD. By contrast, comorbidity explained 11-23% of the HeLPs in people with autism spectrum disorders, conduct disorder, and schizophrenia. Substantial variation in disability was observed across age, sex, and disorders. The new HeLP metric provides novel details of the contribution of comorbidity to the disability associated with mental and substance use disorders. The Danish National Research Foundation, Queensland Government Department of Health, European Union's Horizon 2020, Lundbeck Foundation, Stanley Medical Research Institute. For the Danish translation of the abstract see Supplementary Materials section.

Food addiction comorbid to mental disorders: A nationwide survey and register-based study.

Substance use disorder is highly prevalent among individuals with mental disorders. However, it remains largely unknown whether this is also the case for "food addiction"-a phenotype characterized by an addiction-like attraction to predominantly highly processed foods with a high content of refined carbohydrates and fat. Therefore, the primary aim of this study was to estimate the weighted prevalence of food addiction among individuals with mental disorders. A total of 5,000 individuals aged 18-62 were randomly drawn from eight categories of major mental disorders from the Danish Psychiatric Central Research Register and invited to participate in an online questionnaire-based survey, which included the Yale Food Addiction Scale 2.0. Data on health care and sociodemographics from the Danish registers were linked to all invitees-enabling comprehensive attrition analysis and calculation of the weighted prevalence of food addiction. A total of 1,394 (27.9%) invitees participated in the survey. Across all diagnostic categories, 23.7% met the criteria for food addiction. The weighted prevalence of food addiction was highest among individuals with eating disorders (47.7%, 95%CI: 41.2-54.2), followed by affective disorders (29.4%, 95%CI: 22.9-36.0) and personality disorders (29.0%, 95%CI: 22.2-35.9). When stratifying on sex, the prevalence of food addiction was higher among women in most diagnostic categories. Food addiction is highly prevalent among individuals with mental disorders, especially in those with eating disorders, affective disorders and personality disorders. Food addiction may be an important target for efforts aimed at reducing obesity among individuals with mental disorders.

The validity of child and adolescent depression diagnoses in the Danish psychiatric central research register.

This study examined the validity of childhood depression diagnoses in the Danish Psychiatric Central Research Register (DPCRR) and identified predictors of validity. A nationwide random sample of 500 children (6-17years) diagnosed with depression between 1996 and 2016 was identified in the DPCRR. Psychiatric hospital records were reviewed and rated using an online checklist. The primary outcome was whether depressive symptoms and functional impairment documented in hospital records justified a depressive disorder diagnosis based on ICD-10 or DSM-5 diagnostic criteria. Diagnostic validity was calculated as the positive predictive value. Binary logistic regression analysis was used to identify potential predictors of diagnostic validity, and these were included in a multiple logistic regression. Psychiatric hospital records were available for 393 patients (78.6%). The documentation in the records justified an ICD-10 depressive episode diagnosis in 72.8%, and DSM-5 major depressive disorder in 73.3% of the patients registered with a depression diagnosis. We identified three predictors of diagnostic validity: (i) The validity increased almost linearly from 2000 to 2016 (OR 1.14, 95% CI 1.07-1.20, p<0.001), (ii) antidepressant use was associated with increased diagnostic validity (OR 2.27, 95% CI 1.35-3.82, p=0.002) and (iii) emergency department admission predicted low diagnostic validity (OR 0.33, 95% CI 0.12-0.93, p=0.036). Childhood depression diagnoses registered in the DPCRR show a satisfactory validity according to both ICD-10 and DSM-5 diagnostic criteria. Diagnostic validity increased steadily from 2000 to 2016 and was positively correlated with antidepressant use. Depression diagnoses assigned in emergency departments had low diagnostic validity.

Association of Prenatal Exposure to Valproate and Other Antiepileptic Drugs With Intellectual Disability and Delayed Childhood Milestones

There is concern about neurodevelopmental outcomes associated with prenatal exposure to valproate and other antiepileptic drugs (AEDs) among children of mothers with or without epilepsy. To study the risk of intellectual disability and delayed development in childhood milestones among children of women who used valproate or other AEDs during pregnancy. This population-based cohort study analyzed information on use of AEDs from the Danish National Prescription Registry and register diagnoses from the Danish Psychiatric Central Research Register and Danish National Patient Registry. The study included all live-born singletons in Denmark from January 1, 1997, to December 31, 2011. Data were analyzed in April 2020. Prenatal exposure to maternal valproate and other AEDs. The main measures were adjusted Cox regression estimates of hazard ratios (aHRs) for intellectual disability and a combined outcome of intellectual disability with delayed childhood milestones. A total of 913 302 children (468 708 [51.3%] boys; mean [SD] age, 10.3 [4.4] years and median [interquartile range] age, 10.1 [6.5-14.0] years at final follow-up) were identified and contributed more than 10.2 million person-years of observation, including 580 children exposed to valproate (302 [51.3%] boys). At end of follow-up, 6958 children (0.8%) were identified as having intellectual disability and 14 967 children (1.6%) were identified as having intellectual disability with delayed childhood milestones. Compared with offspring not exposed to valproate prenatally, offspring of women who used valproate during pregnancy had increased risk of intellectual disability (aHR, 4.48; 95% CI, 2.97-6.76) and intellectual disability with delayed childhood milestones (aHR, 6.07; 95% CI, 4.67-7.89). Among mothers with epilepsy, offspring exposed prenatally to valproate had increased risk of intellectual disability (aHR, 1.95; 95% CI, 1.21-3.14) and intellectual disability with delayed childhood milestones (aHR, 3.07; 95% CI, 2.24-4.20) compared with offspring without prenatal exposure. Compared with offspring without prenatal exposure to AEDs, increased risk of intellectual disability was identified in children with prenatal exposure to maternal monotherapy use of carbamazepine (aHR, 3.84; 95% CI, 2.32-6.38), clonazepam (aHR, 2.41; 95% CI, 1.09-5.35), and oxcarbazepine (aHR, 3.70; 95% CI, 2.11-6.51) but not lamotrigine (aHR, 1.33; 95% CI, 0.71-2.48). These findings suggest that prenatal exposure to valproate was associated with increased risk of intellectual disability and delayed childhood milestones. Statistically significant associations were also found for prenatal exposure to other AEDs. These findings suggest that women of childbearing potential may need to be counseled on use of AEDs.

Homelessness and police-recorded crime victimisation: a nationwide, register-based cohort study

Homelessness is associated with crime victimisation, which is a leading cause of death, exacerbates health problems, and increases the risk of violence. We aimed to study the risk of police-recorded crime victimisation in individuals with experiences of homelessness compared with the general population. We did a nationwide, register-based cohort study of people aged 15 years or older, who were alive in 2001 and born in Denmark between 1980 and 2001. The cohort was constructed using the Danish Civil Registration System, with data linked across other registries (including the Danish Homeless Register, Danish Psychiatric Central Research Register, and the Danish Central Crime Register) by use of personal identification numbers. The exposure, experience of homelessness, was defined as at least one contact with a homeless shelter. The outcome was the date of first police-recorded crime victimisation. We calculated incidence rates per 1000 person-years, incidence rate ratios (IRRs), and cumulative probability of any crime victimisation and of violent crime victimisation. Psychiatric disorders, socioeconomic markers, and history of criminal offences were included as confounders. Within the study period (Jan 1, 2001, to Dec 31, 2015), 1 182 749 individuals (9 831 776 person-years) aged 15-35 years were included, of which 184 813 (15·6%) had at least one crime victimisation incident (73 999 [40%] of which were violent victimisations). 4286 individuals (22 240 person-years) had at least one homeless shelter contact. Relative to the general population, and adjusting for age and calendar year, individuals with experience of homelessness had an increased risk of any crime victimisation (IRR 2·7 [95% CI 2·4-3·0]) in females and 2·3 [2·1-2·5] in males), and especially of violent crime victimisation (7·2 [6·3-8·2] in females and 3·6 [3·2-4·0] in males). This increased risk remained significant after further adjustments for potential confounders. People with both a psychiatric diagnosis and experience of homelessness had the highest risk of violent victimisation (IRR 10·1 [95% CI 8·6-11·9] in females and 4·3 [3·8-4·9] in males), while people with no psychiatric diagnosis or experience of homelessness (the reference group) had the lowest risk. In the 5 years after an individual's first homeless shelter contact, the cumulative probabilities of any crime victimisation were 23% (95% CI 21-26) in females and 16% (15-18) in males, which were substantially higher than those of the general population. Homeless populations are at substantially increased risk of crime victimisation, highlighting the need for strategic and targeted approaches to prevent homelessness and to help people out of homelessness. Improvements in multiagency working (such as between homeless shelters, health-care services, substance misuse services, and police forces) might be important to reduce the risk of victimisation in marginalised populations, such as those with complex psychiatric or social problems, with experience of homelessness. Lundbeck Foundation.