Objective
To determine the mortality for persons with epilepsy and schizophrenia by absolute and relative measures.
Methods
This is a population‐based nationwide cohort study of persons born in ...Denmark from 1960 to 1987 who were alive and residing in Denmark on their 25th birthday. We identified persons diagnosed with epilepsy and schizophrenia prior to their 25th birthday and followed them to death, emigration, or December 31, 2012, whichever came first. The primary outcome was overall mortality. Data were analyzed using Cox regressions.
Results
Persons were followed for 24 167 573 person years; the median was 15 years. The mortality rate ratio was 4.4 (95% confidence interval CI = 4.1‐4.7) for persons with epilepsy, 6.6 (95% CI = 6.1‐7.1) for persons with schizophrenia, and 12.8 (95% CI = 9.1‐18.1) for persons with both disorders, compared with persons without these disorders. The estimated cumulative mortality at the age of 50 years was 3.1% (95% CI = 3.0‐3.1) for persons without epilepsy and schizophrenia, 10.7% (95% CI = 9.7‐11.8) for persons with epilepsy, 17.4% (95% CI = 16.0‐18.8) for persons with schizophrenia, and 27.2% (95% CI = 15.7‐40.1) for persons with both disorders.
Significance
Persons with epilepsy and schizophrenia have very high mortality; more than one in four persons with both disorders died between the age of 25 and 50 years, indicating that these patients need special clinical attention.
Depression and anxiety disorders are highly comorbid conditions and a worldwide disease burden; however, large-scale studies delineating their association are scarce. In this retrospective study, we ...aimed to assess the effect of severe anxiety disorders on the risk and course of depression.
We did a population-based cohort study with prospectively gathered data in Denmark using data from three Danish population registers: The Danish Civil Registration System, the Danish Psychiatric Central Register, and the Danish National Hospital Registry. We selected the cohort from people born in Denmark between Jan 1, 1955, and Dec 31, 2002, who we followed up from Jan 1, 1994, to Dec 31, 2012. The cohort was restricted to individuals with known parents. First, we investigated the effect of specific anxiety diagnoses on risk of single depressive episodes and recurrent depressive disorder. Second, we investigated the effect of comorbid anxiety on risk of readmission for depression, adjusting for sex, age, calendar year, parental age, place at residence at time of birth, and the interaction of age with sex.
We included 3,380,059 individuals in our study cohort. The adjusted incidence rate ratio (IRR) for single depressive episodes was 3·0 (95% CI 2·8-3·1, p<0·0001) and for recurrent depressive disorder was 5·0 (4·8-5·2) in patients with severe anxiety disorders compared with the general population. Compared with control individuals, the offspring of parents with anxiety disorders were more likely to be diagnosed with single depressive episodes (1·9, 1·8-2·0) or recurrent depressive disorder (2·1, 1·9-2·2). Comorbid anxiety increased the readmission rates in both patients with single depressive episodes and patients with recurrent depressive disorder.
Severe anxiety constitutes a significant risk factor for depression. Focusing on specific anxiety disorders might help to identify individuals at risk of depression, thereby providing new insights for prevention and treatment.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH).
Many patients with schizophrenia experience psychiatric symptoms long before being diagnosed. We investigated patterns of pre-diagnostic psychopharmacological treatment in individuals diagnosed with ...first-episode schizophrenia during the last two decades.
Using Danish nationwide healthcare registers, we identified all individuals aged ≥10 years registered with their first ICD-10 schizophrenia diagnosis between January 1999 and March 2019. For each calendar year from 1999 to 2019, we calculated the proportion of patients – among those having received their first schizophrenia diagnosis in the respective calendar year – who redeemed prescriptions for various psychotropics in the two years preceding the schizophrenia diagnosis. We calculated proportions of all pre-diagnostic prescriptions since 1995 for a sub-population diagnosed 2011–2019 and for an age- and sex-matched reference group without schizophrenia.
Among 33,361 individuals with schizophrenia (58 % males), the schizophrenia incidence rate was stable during the study period but the mean age at diagnosis decreased by >10 years. In the two pre-diagnostic years, 69 % received psychopharmacological treatment (52 % antipsychotics, 40 % antidepressants). This was stable between 1999 and 2019. Among 14,425 individuals diagnosed 2011–2019, psychotropic drug use was observed among 14–20 % between 24 and 10 years before the diagnosis, being four times higher than the reference group. Particularly antipsychotic and antidepressant drug use increased steadily during the ten pre-diagnostic years.
Pre-diagnostic psychotropic drug use in schizophrenia was frequent but stable between 1999 and 2019 despite an earlier identification of schizophrenia patients. Our findings emphasize the continued importance of thorough diagnostic interviews, particularly among patients in need of antipsychotic treatment.
Infections and activated immune responses can affect the brain through several pathways that might also affect cognition. However, no large-scale study has previously investigated the effect of ...infections on the general cognitive ability in the general population.
Danish nationwide registers were linked to establish a cohort of all 161,696 male conscripts during the years 2006-2012 who were tested for cognitive ability, which was based on logical, verbal, numerical and spatial reasoning at a mean age of 19.4 years. Test scores were converted to a mean of 100.00 and with a standard deviation (SD) of 15. Data were analyzed as a cohort study with severe infections requiring hospitalization as exposure using linear regression.
Adjusted effect sizes were calculated with non-exposure to severe infections as reference, ranging from 0.12 SD to 0.63 SD on general cognitive ability. A prior infection was associated with significantly lower cognitive ability by a mean of 1.76 (95%CI: -1.92 to -1.61; corresponding to 0.12 SD). The cognitive ability was affected the most by the temporal proximity of the last infection (P<0.001) and by the severity of infection measured by days of admission (P<0.001). The number of infections were associated with decreased cognitive ability in a dose-response relationship, and highest mean differences were found for ≥10 hospital contacts for infections (Mean: -5.54; 95%CI: -7.20 to -3.89; corresponding to 0.37 SD), and for ≥5 different types of infections (Mean: -9.44; 95%CI: -13.2 to -5.69; corresponding to 0.63 SD). Hospital contacts with infections had occurred in 35% of the individuals prior to conscription.
Independent of a wide range of possible confounders, significant associations between infections and cognitive ability were observed. Infections or related immune responses might directly affect the cognitive ability; however, associated heritable and environmental factors might also account for the lowered cognitive ability.
•There was no significant association between the polygenic risk score (PRS) for bipolar disorder and not completing 9th grade at term.•Among randomly selected population controls, who completed the ...9th grade at term, there was a statistically significant positive linear relationship between the PRS for bipolar disorder and exam grades in Danish (i.e., native language).•Among randomly selected population controls, who completed the 9th grade at term, having very low PRS for bipolar disorder was associated with obtaining exam grades below the average.
Bidirectional Associations Between Asthma and Types of Mental Disorders Liu, Xiaoqin; Plana-Ripoll, Oleguer; McGrath, John J ...
Journal of allergy and clinical immunology. In practice/The Journal of allergy and clinical immunology. In practice,
03/2023, Volume:
11, Issue:
3
Journal Article
Peer reviewed
Open access
Asthma and mental disorders frequently co-occur. Studies of their comorbidity have generally focused on associations related to a subset of mental disorders.
To estimate bidirectional associations ...between asthma and 10 broad types of mental disorders.
In a population-based cohort study, including all individuals born in Denmark between 1955 and 2011 (N = 5,053,471), we considered diagnoses of comorbid mental disorders among those with asthma, and vice versa, between 2000 and 2016. We used Cox regression models to calculate overall and time-dependent hazard ratios for mental disorder-asthma pairs and competing-risks survival analyses to estimate absolute risks.
Altogether, 376,756 individuals were identified as having an incident mental disorder and 364,063 incident asthma during follow-up. An increased risk was seen for all bidirectional mental disorder-asthma pairs. Following an asthma diagnosis, adjusted hazard ratios for different subsequent mental disorders ranged from 1.75 (95% CI, 1.64-1.87) for organic disorders to 2.75 (95% CI, 2.69-2.81) for personality disorders. Following a prior mental disorder diagnosis, hazard ratios for asthma ranged from 1.06 (95% CI, 1.00-1.12) for developmental disorders to 2.33 (95% CI, 2.28-2.39) for substance use disorders. Risks varied with time since prior disorder diagnosis but remained elevated. Cumulative incidence of (1) asthma after a mental disorder and (2) a mental disorder after asthma was higher in those with prior disorders than in matched reference groups.
Our findings provide evidence of bidirectional associations between asthma and each of the mental disorder types, suggesting possible shared etiological factors or pathophysiologic processes.
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with early onset. ADHD is associated with significant morbidity and mortality, partly due to delayed ...diagnosis. Identification of children at high risk for developing ADHD could lead to earlier diagnosis and potentially change the negative trajectory of the illness for the better. Since early psychosocial adversity is considered to be a likely etiological risk factor for ADHD, markers of this construct may be useful for early identification of children at high risk. Therefore, we sought to investigate whether Rutter's indicators of adversity (low social class, severe marital discord, large family size, paternal criminality, maternal mental disorder, and placement in out-of-home care) assessed in infancy could serve as early predictors for the development of ADHD.
Using data from the Danish nationwide population-based registers, we established a cohort consisting of all 994,407 children born in Denmark between January 1st 1993 and December 31st 2011 and extracted dichotomous values for the six Rutter's indicators of adversity at age 0-12 months (infancy) for each cohort member. The cohort members were followed from their second birthday and the association between the sum of Rutter's indicators of adversity (RIA-score) in infancy and subsequent development of ADHD was estimated by means of Cox regression. Also, the number needed to screen (NNS) to detect one case of ADHD based on the RIA-scores in infancy was calculated. During follow-up (9.6 million person-years), 15,857 males and 5,663 females from the cohort developed ADHD. For both males and females, there was a marked dose-response relationship between RIA-scores assessed in infancy and the risk for developing ADHD. The hazard ratios for ADHD were 11.0 (95%CI: 8.2-14.7) and 11.4 (95%CI: 7.1-18.3) respectively, for males and females with RIA-scores of 5-6, compared to males and females with RIA-scores of 0. Among males with RIA-scores of 5-6, 37.6% (95%CI: 27.0-50.7) had been diagnosed with ADHD prior to the age of 20, corresponding to a NNS of 3.0 (95%CI: 2.2-4.0).
Rutter's indicators of adversity assessed in infancy strongly predicted ADHD. This knowledge may be important for early identification of ADHD.
Weight trajectories might reflect individual health status. In this study, we aimed to examine the clinical and genetic associations of adult weight trajectories using electronic health records ...(EHRs) in the BioMe Biobank.
We constructed four weight trajectories based on a-priori definitions of weight changes (5% or 10%) using annual weight in EHRs (stable weight, weight gain, weight loss, and weight cycle); the final weight dataset included 21 487 participants with 162 783 annual weight measures. To confirm accurate assignment of weight trajectories, we manually reviewed weight trajectory plots for 100 random individuals. We then did a hypothesis-free phenome-wide association study (PheWAS) to identify diseases associated with each weight trajectory. Next, we estimated the single-nucleotide polymorphism-based heritability (h
) of weight trajectories using GCTA-GREML, and we did a hypothesis-driven analysis of anorexia nervosa and depression polygenic risk scores (PRS) on these weight trajectories, given both diseases are associated with weight changes. We extended our analyses to the UK Biobank to replicate findings from a patient population to a generally healthy population.
We found high concordance between manually assigned weight trajectories and those assigned by the algorithm (accuracy ≥98%). Stable weight was consistently associated with lower disease risks among those passing Bonferroni-corrected p value in our PheWAS (p≤4·4 × 10
). Additionally, we identified an association between depression and weight cycle (odds ratio OR 1·42, 95% CI 1·31-1·55, p≤7·7 × 10
). The adult weight trajectories were heritable (using 5% weight change as the cutoff: h
of 2·1%, 95% CI 0·9-3·3, for stable weight; 4·1%, 1·4-6·8, for weight gain; 5·5%, 2·8-8·2, for weight loss; and 4·7%, 2·3-7·1%, for weight cycle). Anorexia nervosa PRS was positively associated with weight loss trajectory among individuals without eating disorder diagnoses (OR
1·16, 95% CI 1·07-1·26, per 1 SD higher PRS, p=0·011), and the association was not attenuated by obesity PRS. No association was found between depression PRS and weight trajectories after permutation tests. All main findings were replicated in the UK Biobank (p<0·05).
Our findings suggest the importance of considering weight from a longitudinal aspect for its association with health and highlight a crucial role of weight management during disease development and progression.
Klarman Family Foundation, US National Institute of Mental Health (NIMH).
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