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1.
  • Ahlberg, Rickard, 1970-, et al. (author)
  • Associations Between Attention-Deficit/Hyperactivity Disorder (ADHD), ADHD Medication and Shorter Height : A Quasi-Experimental and Family-based Study
  • 2023
  • In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier. - 0890-8567 .- 1527-5418. ; 62:12, s. 1316-1325
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: The association between attention-deficit/hyperactivity disorder (ADHD) and shorter height is unclear. This study examined the risk of shorter height in individuals with ADHD, and the influence of prenatal factors, ADHD medication, psychiatric comorbidity, socioeconomic factors and familial liability.METHOD: We draw on Swedish National Registers for two different study designs. First, height data for 14,268 individuals with ADHD and 71,339 controls were stratified into two groups: 1: Before and 2: After stimulant treatment were introduced in Sweden. Second, we used a family-based design including 833,172 relatives without ADHD with different levels of relatedness to the individuals with ADHD and matched controls.RESULTS: ADHD was associated with shorter height both before (below average height: OR=1.31, 95 % CI=1.22-1.41) and after (below average height: OR=1.21, 95 % CI=1.13-1.31) stimulants for ADHD were introduced in Sweden and was of similar magnitude in both cohorts. The association between ADHD and shorter height attenuated after adjustment for prenatal factors, psychiatric disorders and SES. Relatives of individuals with ADHD had an increased risk of shorter height (below average height in full siblings: OR=1.14, 95 % CI=1.09-1.19; maternal half siblings: OR=1.10, 95 % CI=1.01-1.20; paternal half siblings: OR=1.15, 95 % CI=1.07-1.24, first full cousins: OR=1.10, 95 % CI=1.08-1.12).CONCLUSION: Our findings suggest that ADHD is associated with shorter height. On a population level, this association was present both before and after ADHD-medications were available in Sweden. The association between ADHD and height was partly explained by prenatal factors, psychiatric comorbidity, low SES and a shared familial liability for ADHD.
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2.
  • Andersson, Anneli, 1992-, et al. (author)
  • Depression and anxiety disorders during the postpartum period in women diagnosed with attention deficit hyperactivity disorder
  • 2023
  • In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 325, s. 817-823
  • Journal article (peer-reviewed)abstract
    • Background: Attention deficit hyperactivity disorder (ADHD) is associated with an increased risk of poor mental health. However, the understanding of ADHD-related burden and impairments in women during the postpartum period is limited. The aim with the present study was to examine the risk of depression and anxiety disorders during the postpartum period among women with and without an ADHD diagnosis.Methods: We used register-based data to identify women who gave birth to their first and/or second child between 2005 and 2013 in Sweden (n = 773,047), of which 0.5 % (n = 3515) had a diagnosis of ADHD prior to pregnancy. Diagnoses of depression and anxiety disorders up to one year after delivery were collected from the national patient register.Results: A total of 16.76 % of the women with an ADHD diagnosis were also diagnosed with depression disorders in the postpartum period, prevalence ratio (PR) 5.09 (95 % confidence interval (CI), 4.68-5.54). A total of 24.92 % of the women with an ADHD diagnosis were also diagnosed with anxiety disorders in the postpartum period, PR 5.41 (5.06-5.78). Stratified results revealed that having a diagnosis of ADHD increased the risk for both depression and anxiety disorders postpartum, beyond other well-known risk factors.Limitations: There is a potential risk of surveillance bias as women diagnosed with ADHD are more likely to have repeated visits to psychiatric care and might have an enhanced likelihood of also being diagnosed with depression and anxiety disorders postpartum, compared to women without ADHD.Conclusions: ADHD is an important risk factor for both depression and anxiety disorders postpartum. Therefore, ADHD needs to be considered in the maternal care, regardless of sociodemographic factors and the presence of other psychiatric disorders.
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4.
  • Arnberg, Filip K, 1981-, et al. (author)
  • Psychiatric disorders and suicide attempts in Swedish survivors of the 2004 southeast Asia tsunami : a 5 year matched cohort study
  • 2015
  • In: The Lancet Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2215-0366 .- 2215-0374. ; 2:9, s. 817-824
  • Journal article (peer-reviewed)abstract
    • BackgroundSurvivors of natural disasters are thought to be at an increased risk of psychiatric disorders, however the extent of this risk, and whether it is linked to pre-existing psychopathology, is not known. We aimed to establish whether Swedish survivors of tsunamis from the 2004 Sumatra–Andaman earthquake had increased risks of psychiatric disorders and suicide attempts 5 years after repatriation.MethodsWe identified Swedish survivors repatriated from southeast Asia (8762 adults and 3742 children) and 864 088 unexposed adults and 320 828 unexposed children matched for sex, age, and socioeconomic status. We retrieved psychiatric diagnoses and suicide attempts from the Swedish patient register for the 5 years after the tsunami (from Dec 26, 2004, to Jan 31, 2010) and estimated hazard ratios (HRs), then adjusted for pre-tsunami psychiatric disorders, and, for children, for parental pre-tsunami disorders.Findings Exposed adults were more likely than unexposed adults to receive any psychiatric diagnosis (547 [6.2%] vs 47 734 [5.5%]; adjusted HR 1.21, 95% CI 1.11–1.32), particularly stress-related disorders (187 [2.1%] vs 8831 [1.0%]; 2.27, 1.96–2.62) and suicide attempts (38 [0.43%] vs 2752 [0.32%]; 1.54, 1.11–2.13), but not mood or anxiety disorders. Risk of psychiatric diagnoses did not differ between exposed and unexposed children and adolescents (248 [6.6] vs 22 081 [6.9%]; 0.98, 0.86–1.11), although exposed children and adolescents had a higher risk for suicide attempts with uncertain intent (1.43; 1.01–2.02) and stress-related disorders (1.79; 1.30–2.46), mainly during the first 3 months after the tsunami.InterpretationThe 2004 tsunami was, independently of previous psychiatric morbidity, associated with an increased risk of severe psychopathology, mainly stress-related disorders and suicide attempts, in children and adults. Survivors of natural disasters should be targeted with early interventions and active long-term follow-up to prevent, detect, and alleviate psychiatric disorders that might follow.
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5.
  • Butwicka, Agnieszka, et al. (author)
  • Association of Childhood-Onset Inflammatory Bowel Disease With Risk of Psychiatric Disorders and Suicide Attempt
  • 2019
  • In: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 173:10, s. 969-978
  • Journal article (peer-reviewed)abstract
    • Importance: Inflammatory bowel disease (IBD) has been associated with psychiatric morbidity in adults, although previous studies have not accounted for familial confounding. In children, IBD has an even more severe course, but the association between childhood-onset IBD and psychiatric morbidity remains unclear.Objective: To examine the risk of psychiatric morbidity in individuals with childhood-onset IBD, controlling for potential confounding shared between siblings.Design, Setting, and Participants: A population-based cohort study was conducted using data from the Swedish national health care and population registers of all children younger than 18 years born from 1973 to 2013. The study included 6464 individuals with a diagnosis of childhood-onset IBD (3228 with ulcerative colitis, 2536 with Crohn disease, and 700 with IBD unclassified) who were compared with 323 200 matched reference individuals from the general population and 6999 siblings of patients with IBD. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% CIs. Statistical analysis was performed from January 1, 1973, to December 1, 2013.Main Outcomes and Measures: The primary outcome was any psychiatric disorder and suicide attempt. Secondary outcomes were the following specific psychiatric disorders: psychotic, mood, anxiety, eating, personality, and behavioral disorders; substance misuse; attention-deficit/hyperactivity disorder; autism spectrum disorders; and intellectual disability.Results: The study included 6464 individuals with a diagnosis of childhood-onset IBD (2831 girls and 3633 boys; mean [SD] age at diagnosis of IBD, 13 [4] years). During a median follow-up time of 9 years, 1117 individuals with IBD (17.3%) received a diagnosis of any psychiatric disorder (incidence rate, 17.1 per 1000 person-years), compared with 38 044 of 323 200 individuals (11.8%) in the general population (incidence rate, 11.2 per 1000 person-years), corresponding to an HR of 1.6 (95% CI, 1.5-1.7), equaling 1 extra case of any psychiatric disorder per 170 person-years. Inflammatory bowel disease was significantly associated with suicide attempt (HR, 1.4; 95% CI, 1.2-1.7) as well as mood disorders (HR, 1.6; 95% CI, 1.4-1.7), anxiety disorders (HR, 1.9; 95% CI, 1.7-2.0) eating disorders (HR, 1.6; 95% CI, 1.3-2.0), personality disorders (HR, 1.4; 95% CI, 1.1-1.8), attention-deficit/hyperactivity disorder (HR, 1.2; 95% CI, 1.1-1.4), and autism spectrum disorders (HR, 1.4; 95% CI, 1.1-1.7) Results were similar for boys and girls. Hazard ratios for any psychiatric disorder were highest in the first year of follow-up but remained statistically significant after more than 5 years. Psychiatric disorders were particularly common for patients with very early-onset IBD (<6 years) and for patients with a parental psychiatric history. Results were largely confirmed by sibling comparison, with similar estimates noted for any psychiatric disorder (HR, 1.6; 95% CI, 1.5-1.8) and suicide attempt (HR, 1.7; 95% CI, 1.2-2.3).Conclusions and Relevance: Overall, childhood-onset IBD was associated with psychiatric morbidity, confirmed by between-sibling results. Particularly concerning is the increased risk of suicide attempt, suggesting that long-term psychological support be considered for patients with childhood-onset IBD.
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6.
  • Butwicka, Agnieszka, et al. (author)
  • Celiac disease is associated with childhood psychiatric disorders : A Population-Based Study
  • 2017
  • In: Journal of Pediatrics. - : Elsevier. - 0022-3476 .- 1097-6833. ; 184, s. 87-93.e1
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To determine the risk of future childhood psychiatric disorders in celiac disease, assess the association between previous psychiatric disorders and celiac disease in children, and investigate the risk of childhood psychiatric disorders in siblings of celiac disease probands.STUDY DESIGN: This was a nationwide registry-based matched cohort study in Sweden with 10 903 children (aged <18 years) with celiac disease and 12 710 of their siblings. We assessed the risk of childhood psychiatric disorders (any psychiatric disorder, psychotic disorder, mood disorder, anxiety disorder, eating disorder, psychoactive substance misuse, behavioral disorder, attention-deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and intellectual disability). HRs of future psychiatric disorders in children with celiac disease and their siblings was estimated by Cox regression. The association between previous diagnosis of a psychiatric disorder and current celiac disease was assessed using logistic regression.RESULTS: Compared with the general population, children with celiac disease had a 1.4-fold greater risk of future psychiatric disorders. Childhood celiac disease was identified as a risk factor for mood disorders, anxiety disorders, eating disorders, behavioral disorders, ADHD, ASD, and intellectual disability. In addition, a previous diagnosis of a mood, eating, or behavioral disorder was more common before the diagnosis of celiac disease. In contrast, siblings of celiac disease probands were at no increased risk of any of the investigated psychiatric disorders.CONCLUSIONS: Children with celiac disease are at increased risk for most psychiatric disorders, apparently owing to the biological and/or psychological effects of celiac disease.
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7.
  • Butwicka, Agnieszka, et al. (author)
  • Hypospadias and increased risk for neurodevelopmental disorders
  • 2014
  • In: Journal of Child Psychology and Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0021-9630 .- 1469-7610.
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind a possible association, we also studied psychiatric outcomes among brothers of the hypospadias patients. METHODS: Registry study within a national cohort of all 9,262 males with hypospadias and their 4,936 healthy brothers born in Sweden between 1973 and 2009. Patients with hypospadias and their brothers were matched with controls by year of birth and county. The following outcomes were evaluated (1) any psychiatric (2) psychotic, (3) mood, (4) anxiety, (5) eating, and (6) personality disorders, (7) substance misuse, (8) attention-deficit hyperactivity disorder (ADHD), (9) autism spectrum disorders (ASD), (10) intellectual disability, and (11) other behavioral/emotional disorders with onset in childhood. RESULTS: Patients with hypospadias were more likely to be diagnosed with intellectual disability (OR 3.2; 95% CI 2.8-3.8), ASD (1.4; 1.2-1.7), ADHD (1.5; 1.3-1.9), and behavioral/emotional disorders (1.4; 1.2-1.6) compared with the controls. Brothers of patients with hypospadias had an increased risk of ASD (1.6; 1.3-2.1) and other behavioral/emotional disorders with onset in childhood (1.2; 0.9-1.5) in comparison to siblings of healthy individuals. A slightly higher, although not statistically significant, risk was found for intellectual disability (1.3; 1.0-1.9). No relation between other psychiatric diagnosis and hypospadias was found. CONCLUSIONS: This is the first study to identify an increased risk for neurodevelopmental disorders in patients with hypospadias, as well as an increased risk for ASD in their brothers, suggesting a common familial (genetic and/or environmental) liability.
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8.
  • Butwicka, Agnieszka, et al. (author)
  • Increased Risk for Substance Use-Related Problems in Autism Spectrum Disorders : A Population-Based Cohort Study
  • 2017
  • In: Journal of autism and developmental disorders. - New York, USA : Springer. - 0162-3257 .- 1573-3432. ; 47:1, s. 80-89
  • Journal article (peer-reviewed)abstract
    • Despite limited and ambiguous empirical data, substance use-related problems have been assumed to be rare among patients with autism spectrum disorders (ASD). Using Swedish population-based registers we identified 26,986 individuals diagnosed with ASD during 1973-2009, and their 96,557 non-ASD relatives. ASD, without diagnosed comorbidity of attention deficit hyperactivity disorder (ADHD) or intellectual disability, was related to a doubled risk of substance use-related problems. The risk of substance use-related problems was the highest among individuals with ASD and ADHD. Further, risks of substance use-related problems were increased among full siblings of ASD probands, half-siblings and parents. We conclude that ASD is a risk factor for substance use-related problems. The elevated risks among relatives of probands with ASD suggest shared familial (genetic and/or shared environmental) liability.
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10.
  • Butwicka, Agnieszka, et al. (author)
  • Risks of psychiatric disorders and suicide attempts in children and adolescents with type 1 diabetes : a population-based cohort study
  • 2015
  • In: Diabetes Care. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0149-5992 .- 1935-5548.
  • Journal article (peer-reviewed)abstract
    • Objective: To assess the risk of psychiatric disorders and suicide attempts in children with type 1 diabetes and their healthy siblings. Research Design and Methods: We performed a population-based case cohort study of individuals born in Sweden between 1973 and 2009. Children with type 1 diabetes (n=17,122) and their healthy siblings (n=18,847) were identified and followed until their 18th birthday. Their risk of psychiatric disorders was compared with matched controls. Results: The risk of psychiatric morbidity in children with type 1 diabetes compared to the general population was tripled within 6 months after the onset of diabetes (hazard ratio, HR 3.0, 95% confidence interval, CI 2.7-3.4) and doubled within the total observation period (HR 2.1, CI 2.0-2.2). An increased risk was noted in suicide attempts (HR 1.7, CI 1.4-2.0) and in most categories of psychiatric disorders. The risk of psychiatric disorders in probands declined from HR 2.7 (CI 2.2-3.3) for those in the cohort born 1973-1986 to 1.9 (CI 1.8-2.0) in those born 1997-2009. The risk for any psychiatric disorders among siblings of patients with type 1 diabetes was estimated to be HR 1.1 (CI 1.0-1.1) and there was no increased risk in any of the specific category of disorders. Conclusions: Children with type 1 diabetes are at high risk of psychiatric disorders, which seems to be a consequence of the disease rather than due to a common familial etiology. The results support recommendations on comprehensive mental health surveillance in children with type 1 diabetes, especially in recently diagnosed children.
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11.
  • Du Rietz, Ebba, et al. (author)
  • Associations between ADHD and medical disorders in adulthood : a large-scale genetically informed Swedish register study
  • 2020
  • In: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 50:6, s. 452-452
  • Journal article (other academic/artistic)abstract
    • Only a limited number of medical disorders have been thoroughly studied in relation to ADHD, and knowledge is especially lacking for disorders that develop in older ages. This study aimed to map out the phenotypic and aetiologic associations between ADHD and a wide range of medical disorders across adulthood.Full- and maternal half-siblings (N = 4,288,451 pairs), aged 18–81 years, were identified from Swedish Population Registers and linked to ICD-diagnoses from National Patient Registers. Logistic regression was used to estimate associations between ADHD and 35 medical disorders (8 disease groups) within-individuals, and across full- and half-siblings. Quantitative genetic modelling was performed to estimate genetic and environmental contributions to the associations with ADHD.Adults with ADHD had increased risk for most medical disorders (34/35), showing the strongest associations with nervous system (OR = 3.27) and respiratory (OR = 2.49) disease groups. Significantly (P < 0.001) stronger associations were found between full-siblings than half-siblings for nervous system, respiratory, musculoskeletal and metabolic disease groups. Subsequent quantitative genetic modelling showed that these associations with ADHD were largely explained by shared genetic factors, with the exception for nervous system disorders.Individuals with ADHD are at increased risk for a range of medical disorders, with long-term aspects into adult life. While numerous associations between ADHD and medical disorders were largely driven by genetic factors, others, such as nervous system and ageing disorders were mainly driven by individual-specific environmental factors. This mapping of aetiological sources of covariance can guide future research aiming to identify specific mechanisms that contribute to risk for medical disorders in ADHD
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12.
  • Du Rietz, Ebba, et al. (author)
  • Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden : a genetically informed register study
  • 2021
  • In: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 8:9, s. 774-783
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood.METHODS: We did a register study in Sweden and identified full-sibling and maternal half-sibling pairs born between Jan 1, 1932, and Dec 31, 1995, through the Population and Multi-Generation Registers. We excluded individuals who died or emigrated before Jan 1, 2005, and included full-siblings who were not twins and did not have half-siblings. ICD diagnoses were obtained from the National Patient Register. We extracted ICD diagnoses for physical conditions, when participants were aged 18 years or older, from inpatient (recorded 1973-2013) and outpatient (recorded 2001-13) services. Diagnoses were regarded as lifetime presence or absence. Logistic regression models were used to estimate the associations between ADHD (exposure) and 35 physical conditions (outcomes) in individuals and across sibling pairs. Quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD.FINDINGS: 4 789 799 individuals were identified (2 449 146 [51%] men and 2 340 653 [49%] women), who formed 4 288 451 unique sibling pairs (3 819 207 full-sibling pairs and 469 244 maternal half-sibling pairs) and 1 841 303 family clusters (siblings, parents, cousins, spouses). The mean age at end of follow-up was 47 years (range 18-81; mean birth year 1966); ethnicity data were not available. Adults with ADHD had increased risk for most physical conditions (34 [97%] of 35) compared with adults without ADHD; the strongest associations were with nervous system disorders (eg, sleep disorders, epilepsy, dementia; odds ratios [ORs] 1·50-4·62) and respiratory diseases (eg, asthma, chronic obstructive pulmonary disease; ORs 2·42-3·24). Sex-stratified analyses showed similar patterns of results in men and women. Stronger cross-disorder associations were found between full-siblings than between half-siblings for nervous system, respiratory, musculoskeletal, and metabolic diseases (p<0·007). Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60-69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors.INTERPRETATION: This mapping of aetiological sources of cross-disorder overlap can guide future research aiming to identify specific mechanisms contributing to risk of physical conditions in people with ADHD, which could ultimately inform preventive and lifestyle intervention efforts. Our findings highlight the importance of assessing the presence of physical conditions in patients with ADHD.FUNDING: Swedish Research Council; Swedish Brain Foundation; Swedish Research Council for Health, Working Life, and Welfare; Stockholm County Council; StratNeuro; EU Horizon 2020 research and innovation programme; National Institute of Mental Health.
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14.
  • Engberg, Hedvig, et al. (author)
  • Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: A total population study.
  • 2015
  • In: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 60, s. 195-205
  • Journal article (peer-reviewed)abstract
    • Congenital adrenal hyperplasia (CAH) is a chronic condition and individuals are exposed to elevated androgen levels in utero as a result of the endogenous cortisol deficiency. Prenatal androgen exposure has been suggested to influence mental health, but population based studies on psychiatric morbidity among girls and women with CAH are lacking. Therefore, we performed a cohort study based on Swedish nationwide registers linked with the national CAH register. Girls and women with CAH due to 21-hydroxylase deficiency (n=335) born between January 1915 and January 2010 were compared with aged-matched female (n=33500) and male controls (n=33500). Analyses were stratified by phenotype [salt wasting (SW), simple virilizing (SV), and non-classical type (NC)] and by CYP21A2 genotype subgroups (null, I2splice, I172N, and P30L). Results are presented as estimated risks (OR, 95%CI) of psychiatric disorders among girls and women with CAH compared with age-matched controls. Any psychiatric diagnoses were more common in CAH females compared with female and male population controls [1.9 (1.4-2.5), and 2.2 (1.7-2.9)]. In particular, the risk of alcohol misuse was increased compared with female and male population controls [2.8 (1.7-4.7) and 2.1 (1.2-3.5)], and appeared most common among the girls and women with the most severe null genotype [6.7 (2.6-17.8)]. The risk of stress and adjustment disorders was doubled compared with female population controls [2.1 (1.3-3.6)]. Girls and women with CAH have an increased risk of psychiatric disorders in general and substance use disorders in particular compared with unexposed females, with the highest risk among those with the most severe genotype. Prenatal androgen exposure and deficient endogenous cortisol and/or adrenaline production may provide explanations for these findings, but other factors related to CAH cannot be excluded.
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15.
  • Falhammar, Henrik, et al. (author)
  • Increased psychiatric morbidity in men with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
  • 2014
  • In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:3
  • Journal article (peer-reviewed)abstract
    • Context:Reports on psychiatric morbidity in males with congenital adrenal hyperplasia (CAH) are lacking.Objective:To study psychiatric disorders in CAH males.Design, Setting and Participants:We studied males with CAH (21-hydroxylase deficiency, n=253; CYP21A2 mutations known, n=185), and compared them with controls (n=25300). Data were derived through linkage of national population-based registers. We assessed the subgroups of CYP21A2 genotype separately (null, I2splice, I172N, P30L and NC), as well as outcomes before and after the introduction of national neonatal screening in 1986.Main Outcome Measures:Psychiatric disorders including attempted and completed suicide (suicidality).Results:Psychiatric disorders (suicidality not included), suicidality and alcohol misuse were increased in CAH males compared with controls (OR 1.5, 2.3, and 1.9; 95%CI 1.1-2.2, 1.1-5.0, and 1.0-3.5). In the null genotype group, no increased rates were seen; in the I2splice group, psychiatric disorders, personality disorders and alcohol misuse were increased; in the I172N group suicide attempt and drug misuse were increased; and in the P30L and NC group psychotic disorders were increased. In CAH males born before the neonatal screening, the rate of psychiatric disorders and suicidality were increased, but only psychotic disorders in those born after. There was no increased risk for any neurodevelopmental disorder.Conclusions:CAH males have an increased psychiatric morbidity. Psychiatric morbidity was not raised in the most severe genotype group. Late diagnosis of CAH may explain some of the findings. Those born before the introduction of neonatal screening were more affected, which may be explained by the higher age.
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16.
  • Ghirardi, Laura, et al. (author)
  • Familial and genetic associations between autism spectrum disorder and other neurodevelopmental and psychiatric disorders
  • 2021
  • In: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 62:11, s. 1274-1284
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Familial and genetic associations between autism spectrum disorder (ASD) and other neurodevelopmental and psychiatric disorders have been reported, sometimes with conflicting results. We estimated familial and genetic associations between ASD and nine disorder groups, and explored differences in these associations for ASD in the context of intellectual disability, epilepsy, chromosomal abnormalities, and congenital malformations.METHODS: Individuals born between 1985 and 2009 living in Sweden on their seventh birthday were linked to their biological parents in order to identify different types of relatives. We retrieved information on all the disorders considered from the National Patient Register. Logistic regression was used to estimate the familial association between ASD and other neurodevelopmental and psychiatric disorders in the different groups of relatives. Structural equation modeling was used to estimate phenotypic (rp ) and genetic associations (rg ), as well as the contribution of genetic influences to rp .RESULTS: The study included 2,398,608 individuals. Among relatives of individuals diagnosed with ASD, there was an increased risk of the disorders considered, compared to relatives of individuals who were not diagnosed with ASD. Stronger associations were detected for ASD without any additional diagnosis of intellectual disability, epilepsy, chromosomal abnormalities, and congenital malformations. The strongest genetic correlation was estimated between ASD and other neurodevelopmental disorders (rg  = 0.73; 95% CI = 0.66-0.79). Moderate genetic correlations were estimated for anxiety disorders (rg  = 0.47; 95% CI = 0.33-0.61), depression (rg  = 0.52; 95% CI = 0.37-0.66), and intentional self-harm (rg  = 0.54; 95% CI = 0.36-0.71).CONCLUSIONS: ASD shows familial and genetic association not only with other neurodevelopmental disorders, but also with other psychiatric disorders, such as anxiety, depression, and intentional self-harm. Family history of ASD comorbid with intellectual disability, epilepsy, congenital malformations, or chromosomal abnormalities is less related to other psychiatric disorders, potentially suggesting a different etiology for this subgroup of patients.
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17.
  • Hegvik, Tor-Arne, et al. (author)
  • Familial co-aggregation of attention-deficit/hyperactivity disorder and autoimmune diseases : a cohort study based on Swedish population-wide registers
  • 2022
  • In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 51:3, s. 898-909
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has been associated with several autoimmune diseases (AD), both within individuals and across relatives, implying common underlying genetic or environmental factors in line with studies indicating that immunological mechanisms are key to brain development. To further elucidate the relationship between ADHD and autoimmunity we performed a population-wide familial co-aggregation study.METHODS: We linked Swedish national registries, defined a birth cohort with their biological relatives and identified individuals diagnosed with ADHD and/or 13 ADs. The cohort included 5 178 225 individuals born between 1960 and 2010, of whom 118 927 (2.30%) had been diagnosed with ADHD. We then investigated the associations between ADHD and ADs within individuals and across relatives, with logistic regression and structural equation modelling.RESULTS: Within individuals, ADHD was associated with a diagnosis of any of the 13 investigated ADs (adjusted odds ratio (OR) =1.34, 95% confidence interval (CI) = 1.30-1.38) as well as several specific ADs. Familial co-aggregation was observed. For example, ADHD was associated with any of the 13 ADs in mothers (OR = 1.29, 95% CI = 1.26-1.32), fathers (OR = 1.14, 95% CI = 1.11-1.18), full siblings (OR = 1.19, 95% CI = 1.15-1.22), aunts (OR = 1.12, 95% CI = 1.10-1.15), uncles (OR = 1.07, 95% CI = 1.05-1.10) and cousins (OR = 1.04, 95% CI = 1.03-1.06). Still, the absolute risks of AD among those with ADHD were low. The genetic correlation between ADHD and a diagnosis of any of the investigated ADs was 0.13 (95% CI = 0.09-0.17) and the environmental correlation was 0.02 (95% CI = -0.03-0.06).CONCLUSIONS: We found that ADHD and ADs co-aggregate among biological relatives, indicating that the relationship between ADHD and autoimmune diseases may in part be explained by shared genetic risk factors. The patterns of familial co-aggregation of ADHD and ADs do not readily support a role of maternal immune activation in the aetiology of ADHD. The findings have implications for aetiological models of ADHD. However, screening for autoimmunity among individuals with ADHD is not warranted.
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18.
  • Hirvikoski, Tatja, et al. (author)
  • Association of Intellectual Disability with All-Cause and Cause-Specific Mortality in Sweden
  • 2021
  • In: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 4:6
  • Journal article (peer-reviewed)abstract
    • © 2021 American Medical Association. All rights reserved.Importance: Knowledge of the health challenges and mortality in people with intellectual disability (ID) should guide health policies and practices in contemporary society. Objective: To examine premature mortality in individuals with ID. Design, Setting, and Participants: This population-based longitudinal cohort study obtained data from several national health care, education, and population registers in Sweden. Two registers were used to identify individuals with ID: the National Patient Register and the Halmstad University Register on Pupils With Intellectual Disability. Two cohorts were created: cohort 1 comprised young adults (born between 1980 and 1991) with mild ID, and cohort 2 comprised individuals (born between 1932 and 2013) with mild ID or moderate to profound ID; each cohort had matched reference cohorts. Data analyses were conducted between June 1, 2020, and March 31, 2021. Exposures: Mild or moderate to profound ID. Main Outcomes and Measures: The primary outcome was overall (all-cause) mortality, and the secondary outcomes were cause-specific mortality and potentially avoidable mortality. Results: Cohort 1 included 13 541 young adults with mild ID (mean [SD] age at death, 24.53 [3.66] years; 7826 men [57.8%]), and its matched reference cohort consisted of 135410 individuals. Cohort 2 included 24059 individuals with mild ID (mean [SD] age at death, 52.01 [16.88] years; 13649 male individuals [56.7%]) and 26602 individuals with moderate to profound ID (mean [SD] age at death, 42.16 [21.68] years; 15338 male individuals [57.7%]); its matched reference cohorts consisted of 240590 individuals with mild ID and 266020 with moderate to profound ID. Young adults with mild ID had increased overall mortality risk compared with the matched reference cohort (odds ratio [OR], 2.86; 95% CI, 2.33-3.50), specifically excess mortality in neoplasms (OR, 3.58; 95% CI, 2.02-6.35), diseases of the nervous system (OR, 40.00; 95% CI, 18.43-86.80) and circulatory system (OR, 9.24; 95% CI, 4.76-17.95). Among deaths that were amenable to health care (OR, 7.75; 95% CI, 4.85-12.39), 55% were attributed to epilepsy. In cohort 2, increased risk of overall mortality was observed among both individuals with mild ID (OR, 6.21; 95% CI, 5.79-6.66) and moderate to profound ID (OR, 13.15; 95% CI, 12.52-13.81) compared with the matched reference cohorts. Those with moderate to profound ID had a higher risk in several cause-of-death categories compared with those with mild ID or the matched reference cohort. Adjustment for epilepsy and congenital malformations attenuated the associations. The relative risk of premature death was higher in women (OR, 6.23; 95% CI, 4.42-8.79) than in men (OR, 1.99; 95% CI, 1.53-2.60), but the absolute risk of mortality was similar (0.9% for women vs 0.9% for men). Conclusions and Relevance: This study found excess premature mortality and high risk of deaths with causes that were potentially amenable to health care intervention among people with ID. This finding suggests that this patient population faces persistent health challenges and inequality in health care encounters..
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19.
  • Kanina, Aleksandra, et al. (author)
  • Association between cumulative psychosocial adversity in the family and ADHD and autism : a family-based cohort study
  • 2023
  • In: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Cumulative exposure to psychosocial adversity at an early age has been shown to be a risk factor for attention-deficit hyperactivity disorder (ADHD) and autism that often co-occur. However, it is not clear if this association reflects a causal effect or familial confounding. We aimed to assess whether cumulative psychosocial adversity in the family increases the risk for ADHD and autism in offspring while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born in Sweden between 1990 and 2009. Participants were followed from the age of 3 until 2013, with a median follow up time of 13.8 years. We created a cumulative index based on 7 psychosocial adversity factors. We used Cox regression to estimate the hazard ratios (HRs) relating neurodevelopmental conditions to cumulative psychosocial adversity. To address familial confounding, the analyses were repeated in groups of relatives of different kinship: siblings and half-siblings and cousins. A dose-response relationship was observed between cumulative exposure to psychosocial adversity and ADHD at a general population level (covariate adjusted HRs (aHRs) with 95% confidence intervals ranged from 1.55 [one adversity; 1.53-1.58] to 2.65 [ ≥ 4 adversities; 1.98-3.54]). No clear dose-response relation was seen for autism (aHRs ranged from 1.04 [.59-1.84] to 1.37 [1.30-1.45]). HRs of ADHD and autism decreased with increasing level of kinship in the analysis of relatives. Cumulative exposure to psychosocial adversity was associated with both ADHD and autism in the general population, these associations were partly explained by unmeasured familial confounding between relatives. This highlights the need for using family-based designs in studies of psychosocial adversity and ADHD and autism.
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20.
  • Kanina, Aleksandra, et al. (author)
  • Association Between Cumulative Psychosocial Adversity in the Family and Neurodevelopmental Disorders; a Family-Based Cohort Study
  • 2022
  • In: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 52:6, s. 368-369
  • Journal article (other academic/artistic)abstract
    • Cumulative exposure to psychosocial adversity (PSA) at an early age is a risk factor for developing neuro developmental disorders(NDDs) such as attention-deficit hyperactivity disorder (ADHD) and autism. However, it is not clear if this statistical association reflects a true causal effect. We aimed to assess the degree to which cumulative PSA increases the risk for ADHD and autism while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born from 1990 to 2009 in Sweden who were followed from the age of 3. We created a cumulative index based on 7 PSA factors: large family size, parental bereavement, divorce, low income and education, crime conviction, psychiatric history. We used Cox regression to estimate hazard ratios (HRs) for cumulative PSA and ADHD/autism with 95% confidence intervals (CI) in the general population and among groups of relatives (siblings, half-siblings, and cousins) to address familial confounding. We observed a dose–response relationship between cumulative PSA and ADHD in the general population (adjusted HRs with 95% CI ranged from 1.55 [one adversity: 1.52–1.58] to 2.61 [C 4 adversities: 1.95–3.49]). No clear dose–response relation was seen for autism (adjusted HRs ranged from 1.06 [0.60–1.87] to 1.34 [1.30–1.38]). HRs of ADHD and autism decreased with increasing levels of kinship in the analyses of groups of relatives. These results suggest that familial confounding is an important factor to consider for the associations between cumulative PSA and ADHD/autism which hasn't been done in previous studies.
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21.
  • Khemiri, Lotfi, et al. (author)
  • Parental substance use disorder and risk of intellectual disability in offspring in Sweden : a national register study
  • 2023
  • In: eClinicalMedicine. - London : Elsevier. - 2589-5370. ; 63
  • Journal article (peer-reviewed)abstract
    • Background: Intellectual disability (ID) is a disorder with unknown aetiology in many cases. Maternal alcohol use is a known risk factor for ID, but less is known about the importance of maternal and paternal substance use disorder (SUD) and risk of ID in offspring.Methods: Data from multiple nationwide registers were used to create a cohort of children born from January 01, 1978 to December 31, 2002. All participants were born in Sweden, had available parental identification information and did not emigrate or die before age 12 (n = 1,940,820). Logistic regression modelling was performed with exposure defined as having a parent who received any SUD diagnosis, including alcohol use disorder (AUD) and drug use disorder (DUD). The outcome was registration of diagnosis of any form of ID. First, we analysed the risk of ID if parental SUD was registered prior to childbirth with stepwise adjustment of multiple covariates. Second, the effect of timing of SUD diagnosis in relation to childbirth was analysed.Findings: Of 37,410 offspring with parental SUD registered prior to birth, 3.0% (n = 1110) had any form of ID compared to 1.2% (n = 23,168) of those 1,903,410 individuals without parental SUD prior birth. Parental SUD prior birth was associated with an increased risk of any form of ID (Odds Ratio [OR]: 2.3 [2.2-2.5]), with ORs similar for maternal (OR: 2.3 [2.1-2.5]) and paternal SUD (OR: 2.3 [2.1-2.5]). These ORs were reduced but remained statistically significant after adjusting for parental education, migration, psychiatric comorbidity, and co-parent SUD (OR parental SUD: 1.6 [1.5-1.8]; OR maternal SUD: 1.4 [1.2-1.5]; OR paternal SUD: 1.6 [1.5-1.7]). Parental SUD was associated with increased risk of ID in offspring irrespective of timing of diagnosis, but if mothers or fathers were diagnosed with AUD during pregnancy (OR maternal AUD: 5.0 [3.1-8.2]; OR paternal AUD: 2.8 [2.2-3.6]), the risk was significantly greater than if the AUD diagnosis was first registered after childbirth (OR maternal AUD: 1.9 [1.8-2.0]; OR paternal AUD: 1.6 [1.6-1.7]).Interpretation: Both paternal and maternal SUD were associated with an increased risk of ID in offspring, with greatest risk observed when AUD was diagnosed during pregnancy. Possible mechanisms may involve shared genetic and environmental factors, including toxic effects from alcohol intake. These findings have clinical implications in suggesting that parental SUD in either parent represents a possibly modifiable risk factor to consider when developing prevention, diagnostics and treatment programs for children with ID.
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22.
  • Latvala, Antti, et al. (author)
  • Association of intellectual disability with violent and sexual crime and victimization : a population-based cohort study
  • 2023
  • In: Psychological Medicine. - Cambridge : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 35:9, s. 1-9
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Intellectual disability (ID) is associated with violent and sexual offending and victimization, but the importance of neuropsychiatric comorbidity and severity of disability remains unclear.METHODS: In a register-based cohort study of people born in Sweden 1980-1991 (n = 1 232 564), we investigated associations of mild and moderate/severe ID with any, violent and sexual crimes, and with assault victimization, stratified by comorbid autism and attention deficit hyperactivity disorder (ADHD). We defined ID by attendance at a special school or registered diagnosis and obtained data on criminal convictions and injuries or deaths due to assaults from nationwide registers until end of 2013.RESULTS: Compared to people without ID, autism or ADHD, men and women with mild or moderate/severe ID and comorbid ADHD had elevated risks of violent crimes [range of hazard ratios (HRs) 4.4-10.4] and assault victimization (HRs 2.0-7.7). Women with mild ID without comorbidities or with comorbid autism also had elevated risks of violent crimes and victimization (HRs 1.8-4.6) compared to women without ID, autism or ADHD. The relative risks of sexual offending and victimization were elevated in men and women with ID without comorbidities (HRs 2.6-12.7). The highest risks for sexual offending in men (HRs 9.4-11.0) and for sexual assault victimization in women (HRs 11.0-17.1) related to ID and comorbid ADHD.CONCLUSIONS: The elevated risk of violent offending and assault victimization in people with ID is largely explained by comorbid ADHD, whereas ID is independently associated with sexual crimes and victimization, even though absolute risks are low.
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23.
  • Lebwohl, Benjamin, et al. (author)
  • Psychiatric disorders in patients with a diagnosis of celiac disease during childhood from 1973 to 2016
  • 2021
  • In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 19:10, s. 2093-2101.e13
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: Few studies have explored the link between childhood celiac disease and long-term psychiatric comorbidities. We performed a population-based cohort study of associations between childhood celiac disease and psychiatric disorders and investigated whether risk persists into adulthood.METHODS: We performed a nationwide study in Sweden using data from the ESPRESSO cohort. In this cohort, 19,186 children with a diagnosis of biopsy-verified celiac disease from 1973 through 2016 were identified from Sweden's 28 pathology departments. Each patient was matched with as many as 5 reference children (controls, n=94,249). Data on psychiatric disorders were obtained from the patient register. We used Cox proportional modeling to estimate hazard ratios (HRs).RESULTS: During a median follow-up time of 12.3 years, 3174 children (16.5%) with celiac disease received a new diagnosis of a psychiatric disorder, compared with 13,286 controls (14.1%). Corresponding incidence rates were 12.2 per 1000 person-years (95% Cl, 11.8-12.7) vs 10.3 per 1000 person-years (95% Cl, 10.2-10.5). Childhood celiac disease was associated with a 19% increase in risk of any psychiatric disorder (95% Cl, 1.14-1.23); the increase in risk was observed in all childhood age groups. The highest HRs were seen in the first year after celiac diagnosis (HR, 1.70; 95% Cl, 1.41-2.05). The risk increase persisted into adulthood (older than 18 years: HR, 1.11; 95% Cl, 1.04-1.17). We found increased risks of mood disorders (HR, 1.20; 95% CI, 1.12-1.28), anxiety disorders (HR, 1.12; 95% CI, 1.06-1.19), eating disorders (HR, 1.34; 95% CI, 1.18-1.51), attention deficit hyperactivity disorder (HR, 1.29; 95% CI, 1.20-1.39), and autism spectrum disorder (HR, 1.47; 95% CI, 1.32-1.64). We found no statistically significant risk increase for psychotic disorders, psychoactive substance misuse, behavioral disorders, personality disorders, suicide attempt, or suicide. Celiac disease was also linked to an increased use of psychiatric drugs (HR, 1.34; 95% CI, 1.24-1.43). A conditional logistic regression found that psychiatric disorders were also more common prior to diagnosis of celiac disease (odds ratio, 1.56; 95% Cl, 1.39-1.76).CONCLUSIONS: Childhood celiac disease is associated with increased risk of subsequent psychiatric disorders, which persists into adulthood. Mental health surveillance should be integral in the care of celiac disease.
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24.
  • Leone, Marica, et al. (author)
  • FAMILIAL LIABILITY FOR ENDOCRINE-METABOLIC DISORDERS AND DEPRESSION
  • 2021
  • In: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 51, s. e112-e112
  • Journal article (other academic/artistic)abstract
    • Background: Endocrine-metabolic disorders are common in individuals with depression. Better understanding of the underlying factors contributing to their concomitant occurrence is needed. This study investigates the familial co-aggregation of depression and endocrine-metabolic disorders and estimates the contribution of genetic and environmental risk factors to their co-occurrence.Methods: We conducted a population-based cohort study using Swedish national data. A total of 2,263,311 individuals born between 1973 and 1996 were included and followed up until death, emigration, or December 31, 2013, whichever occurred first. Each participant was linked to their biological parents, allowing identification of full-, maternal half-, and paternal half-siblings. We investigated clinical diagnoses of depression and endocrine-metabolic disorders diagnosed at any point during the follow-up period, grouping the latter into autoimmune disorders (i.e., hypothyroidism, Graves’ disease, and type 1 diabetes) and non-autoimmune disorders (i.e., type 2 diabetes, obesity, and polycystic ovarian syndrome). Logistic regression and Cox proportional hazards regression were used to estimate the association between endocrine-metabolic disorders and depression within the same individual and across siblings. Quantitative genetic modeling was performed to investigate the relative contribution of genetic and environmental influences.Results: Individuals diagnosed with endocrine-metabolic disorders had significantly higher risk of depression, with odds ratios ranging from 1.43 [95% CI, 1.30-1.57] for Graves’ disease to 2.44 [2.37-2.50] for obesity. Overall, increased risks extended to full- and half-siblings. Quantitative genetic modeling showed that shared genetic factors explained the phenotypic correlations between endocrine-metabolic disorders and depression to different extents (ranging from 36% for autoimmune hypothyroidism, to 74% for obesity), except for type 1 diabetes, for which the association was mainly explained by non-shared environmental factors (84%).Discussion: Endocrine-metabolic disorders and depression co-occur in individuals and display familial co-aggregation. Shared genetic risk factors explained much of this relationship, but unique environmental influences also contributed significantly. These findings expand the current knowledge of the etiological sources of comorbidity between somatic and psychiatric disorders, which could guide future research aiming at identifying the pathophysiological mechanisms and potentially intervention targets.
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25.
  • Leone, Marica, et al. (author)
  • Genetic and Environmental Contribution to the Co-Occurrence of Endocrine-Metabolic Disorders and Depression : A Nationwide Swedish Study of Siblings
  • 2022
  • In: American Journal of Psychiatry. - : HighWire Press. - 0002-953X .- 1535-7228. ; 179:11, s. 824-832
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Depression is common in individuals with endocrine-metabolic disorders and vice versa, and a better understanding of the underlying factors contributing to the comorbidity of these disorders is needed. This study investigated the familial coaggregation of depression and endocrine-metabolic disorders and estimated the contribution of genetic and environmental factors to their co-occurrence.METHODS: This population-based cohort study included 2.2 million individuals born in Sweden between 1973 and 1996, with follow-up through 2013. Participants were linked to their biological parents, allowing identification of full siblings, maternal half siblings, and paternal half siblings. Diagnoses of depression and endocrine-metabolic conditions were investigated, with the latter grouped into autoimmune disorders (autoimmune hypothyroidism, Graves' disease, and type 1 diabetes) and non-autoimmune disorders (type 2 diabetes, obesity, and polycystic ovary syndrome). Logistic regression and Cox regression were used to estimate the associations between endocrine-metabolic disorders and depression within the same individual and across siblings. Quantitative genetic modeling was performed to investigate the relative contribution of genetic and environmental influences.RESULTS: Individuals with endocrine-metabolic disorders had a significantly higher risk of depression, with odds ratios ranging from 1.43 (95% CI=1.30, 1.57) for Graves' disease to 3.48 (95% CI=3.25, 3.72) for type 2 diabetes. Increased risks extended to full and half siblings. These correlations were mainly explained by shared genetic influences for non-autoimmune conditions, and by nonshared environmental factors for autoimmune disorders, especially for type 1 diabetes.CONCLUSIONS: These findings provide phenotypic and etiological insights into the co-occurrence of depression and various endocrine-metabolic conditions, which could guide future research aiming at identifying pathophysiological mechanisms and intervention targets.
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26.
  • Leone, Marica, et al. (author)
  • MELATONIN USE AND THE RISK OF SELF-HARM AND UNINTENTIONAL INJURIES IN YOUTHS
  • 2022
  • In: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 63, s. E113-E113
  • Journal article (other academic/artistic)abstract
    • Background: Sleep disorders in youth have been associated with increased risks of injury, including suicidal behavior. This study investigated whether melatonin, which is themost common medication for sleep disturbances in youth in Sweden, is associated with a decreased risk of injury.Methods: This population-based cohort study included 25,575 youths who initiated melatonin treatment between ages 6 and 18. Poisson regression was used to estimate rate of injuries in the year prior to and following melatonin-treatment initiation. A within-individual design was used to estimate relative risks by comparing injury risk in the last unmedicated month with injury risks in the 12 months after medication initiation. Analyses were stratified by sex, in-jury type, psychiatric comorbidities, and age at melatonin-treatment initiation.Results: While body injuries, falls, and transport accident rates were comparable in the year before and after melatonin-treatment initiation, the risk of self-injurious behavior was highest in the months immediately prior medication and decreased thereafter. This was particularly prominent among adolescents with depression and/or anxiety, with females displaying greater absolute risks than males. Compared to the last unmedicated month, the 12 months post medication initiation had decreased relative risks for self-harm, with an IRR [95% CI] in the month following melatonin-treatment initiation of 0.46 [0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.Discussion: Decreased risk of intentional injury was observed following melatonin-treatment initiation among females with depression and anxiety, suggesting that sleep interventions could be considered in an effort to reduce risk of self-injurious behavior in this population.
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27.
  • Leone, Marica, et al. (author)
  • Melatonin use and the risk of self-harm and unintentional injuries in youths with and without psychiatric disorders
  • 2023
  • In: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 64:7, s. 1027-1036
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Sleep disorders in youth have been associated with increased risks of injury, including suicidal behavior. This study investigated whether melatonin, which is the most common medication for sleep disturbances in youth in Sweden, is associated with a decreased risk of injury.METHODS: This population-based cohort study included 25,575 youths who initiated melatonin treatment between ages 6 and 18. Poisson regression was used to estimate rate of injuries in the year prior to and following melatonin treatment initiation. A within-individual design was used to estimate relative risks by comparing injury risk in the last unmedicated month with injury risks in the 12 months after medication initiation. Analyses were stratified by sex, injury type, psychiatric comorbidities and age at melatonin-treatment initiation.RESULTS: While body injuries, falls and transport accident rates were comparable in the year before and after melatonin-treatment initiation, the risk of self-harm was highest in the months immediately prior to medication, and decreased thereafter. This was particularly prominent among adolescents with depression and/or anxiety, with females displaying greater absolute risks than males. Compared to the last unmedicated month, the 12 months post medication initiation had decreased relative risks for self-harm, with an IRR [95% CI] in the month following melatonin-treatment initiation of 0.46 [0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.CONCLUSIONS: Decreased risk of intentional self-harm was observed following melatonin-treatment initiation among females with depression and anxiety, suggesting that sleep interventions could be considered in an effort to reduce risk of self-harm in this population.
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28.
  • Li, Lin, 1989-, et al. (author)
  • Associations of Prescribed ADHD Medication in Pregnancy with Pregnancy-Related and Offspring Outcomes : A Systematic Review
  • 2020
  • In: CNS Drugs. - : Adis International. - 1172-7047 .- 1179-1934. ; 34:7, s. 731-747
  • Research review (peer-reviewed)abstract
    • BACKGROUND: Increasing numbers of reproductive-aged women are using attention-deficit/hyperactivity disorder (ADHD) medications. Findings from studies exploring the safety of these medications during pregnancy are mixed, and it is unclear whether associations reflect causal effects or could be partially or fully explained by other factors that differ between exposed and unexposed offspring.OBJECTIVES: The aim of this systematic review was to evaluate the adverse pregnancy-related and offspring outcomes associated with exposure to prescribed ADHD medication during pregnancy with a focus on how studies to date have handled the influence of confounding.METHODS: We searched PubMed, Embase, PsycINFO, and Web of Science up to 1 July 2019 without any restrictions on language or date of publication. We included all observational studies (e.g., cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) with pregnant women of any age or from any setting who were prescribed ADHD medications and evaluated any outcome, including both short- and long-term maternal and offspring outcomes. Two independent authors then used the Newcastle-Ottawa Scale to rate the quality of the included studies.RESULTS: Eight cohort studies that estimated adverse pregnancy-related and offspring outcomes associated with exposure to ADHD medication during pregnancy were included in the qualitative review. The included studies had substantial methodological differences in data sources, type of medications examined, definitions of studied pregnancy-related and offspring outcomes, types of control groups, and confounding adjustment. There was no convincing evidence for teratogenic effects according to the relative risk of pregnancy-related and offspring outcomes, and the observed differences in absolute risks were overall small in magnitude. Adjustment for confounding was inadequate in most studies, and none of the included studies adjusted for ADHD severity in the mothers.CONCLUSION: The current evidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman's specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate specific confounding factors, the potential impact of timing of exposure, and potential long-term outcomes in the offspring.
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29.
  • Lichtenstein, Paul, et al. (author)
  • Familial risk and heritability of intellectual disability : a population-based cohort study in Sweden
  • 2022
  • In: Journal of Child Psychology and Psychiatry. - Hoboken, New Jersey : Wiley-Blackwell Publishing Inc.. - 0021-9630 .- 1469-7610. ; 63:9, s. 1092-1102
  • Journal article (peer-reviewed)abstract
    • Background: Intellectual disability (ID) aggregates in families, but factors affecting individual risk and heritability estimates remain unknown. Methods: A population-based family cohort study of 4,165,785 individuals born 1973–2013 in Sweden, including 37,787 ID individuals and their relatives. The relative risks (RR) of ID with 95% confidence intervals (95% CI) were obtained from stratified Cox proportional-hazards models. Relatives of ID individuals were compared to relatives of unaffected individuals. Structural equation modeling was used to estimate heritability. Results: Relatives of ID individuals were at increased risk of ID compared to individuals with unaffected relatives. The RR of ID among relatives increased proportionally to the degree of genetic relatedness with ID probands; 256.70(95% CI 161.30–408.53) for monozygotic twins, 16.47(13.32–20.38) for parents, 14.88(12.19–18.16) for children, 7.04(4.67–10.61) for dizygotic twins, 8.38(7.97–8.83) for full siblings, 4.56(4.02–5.16) for maternal, 2.90(2.49–3.37) for paternal half-siblings, 3.03(2.61–3.50) for nephews/nieces, 2.84(2.45–3.29) for uncles/aunts, and 2.04(1.91–2.20) for cousins. Lower RRs were observed for siblings of probands with chromosomal abnormalities (RR 5.53, 4.74–6.46) and more severe ID (mild RR 9.15, 8.55–9.78, moderate RR 8.13, 7.28–9.08, severe RR 6.80, 5.74–8.07, and profound RR 5.88, 4.52–7.65). Male sex of relative and maternal line of relationship with proband was related to higher risk (RR 1.33, 1.25–1.41 for brothers vs. sisters and RR 1.49, 1.34–1.68 for maternal vs. paternal half-siblings). ID was substantially heritable with 0.95(95% CI 0.93–0.98) of the variance in liability attributed to genetic influences. Conclusions: The risk estimates will benefit researchers, clinicians, families in understanding the risk of ID in the family and the whole population. The higher risk of ID related to male sex and maternal linage will be of value for planning and interpreting etiological studies in ID. © 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health
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30.
  • Liu, Shengxin, et al. (author)
  • Age-related physical health of older autistic adults in Sweden : a longitudinal, retrospective, population-based cohort study
  • 2023
  • In: The lancet. Healthy longevity. - : Elsevier. - 2666-7568. ; 4:7, s. e307-e315
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Research of health outcomes in older autistic adults (≥45 years) is concerningly scarce, and little is known about whether intellectual disability and sex affect the health outcomes of this population. The aim of this study was to investigate the association between autism and physical health conditions in older adults and to examine these associations by intellectual disability and sex.METHODS: We conducted a longitudinal, retrospective, population-based cohort study of the Swedish population born between Jan 1, 1932, and Dec 31, 1967, using linked data from the nationwide Total Population Register and the National Patient Register. We excluded individuals who died or emigrated before the age of 45 years, or with any chromosomal abnormalities. Follow-up started at age 45 years for all individuals, and ended at emigration, death, or Dec 31, 2013 (the latest date of available follow-up), whichever was soonest. Diagnoses of autism, intellectual disability, 39 age-related physical conditions, and five types of injury (outcomes) were obtained from the National Patient Register. For each outcome, we calculated 25-year cumulative incidence and used Cox models to estimate hazard ratios (HRs). All analyses were repeated separately by intellectual disability and sex.FINDINGS: Of 4 200 887 older adults (2 063 718 women [49·1%] and 2 137 169 men [50·9%]) in the study cohort, 5291 (0·1%) had a diagnosis of autism recorded in the National Patient Register. Older autistic adults (median follow-up 8·4 years [IQR 4·2-14·6]) had higher cumulative incidence and HRs of various physical conditions and injuries than their non-autistic counterparts (median follow-up 16·4 years [8·2-24·4]). In autistic individuals, the highest cumulative incidence was observed for bodily injuries (50·0% [95% CI 47·6-52·4]). Conditions that autistic adults were at higher risk of than were non-autistic adults included heart failure (HR 1·89 [95% CI 1·61-2·22]), cystitis (2·03 [1·66-2·49]), glucose dysregulation (2·96 [2·04-4·29]), iron deficiency anaemia (3·12 [2·65-3·68]), poisoning (4·63 [4·13-5·18]), and self-harm (7·08 [6·24-8·03]). These increased risks mainly persisted regardless of intellectual disability or sex.INTERPRETATION: Our data indicate that older autistic adults are at substantially increased risk of age-related physical conditions and injuries compared with non-autistic adults. These findings highlight the need for collaborative efforts from researchers, health services, and policy makers to provide older autistic individuals with the necessary support to attain healthy longevity and a high quality of life.
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31.
  • Liu, Shengxin, et al. (author)
  • Early-Onset Type 2 Diabetes and Mood, Anxiety, and Stress-Related Disorders: A Genetically Informative Register-Based Cohort Study.
  • 2022
  • In: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 45:12, s. 2950-2956
  • Journal article (peer-reviewed)abstract
    • To assess the association and familial coaggregation between early-onset type 2 diabetes (diagnosed before age 45 years) and mood, anxiety, and stress-related disorders and estimate the contribution of genetic and environmental factors to their co-occurrence.This population-based cohort study included individuals born in Sweden during 1968-1998, from whom pairs of full siblings, half-siblings, and cousins were identified. Information on diagnoses of early-onset type 2 diabetes and mood (including unipolar depression and bipolar disorder), anxiety, and stress-related disorders was obtained from the National Patient Register. Logistic and Cox regression models were used to assess the phenotypic association and familial coaggregation between type 2 diabetes and psychiatric disorders. Quantitative genetic modeling was conducted in full and maternal half-sibling pairs to estimate the relative contributions of genetic and environmental factors to the association.Among a total of 3,061,192 individuals, 7,896 (0.3%) were diagnosed with early-onset type 2 diabetes. These individuals had higher risks of any diagnosis (odds ratio [OR] 3.62 [95% CI 3.44, 3.80]) and specific diagnosis of unipolar depression (3.97 [3.75, 4.22]), bipolar disorder (4.17 [3.68, 4.73]), anxiety (3.76 [3.54, 3.99]), and stress-related disorders (3.35 [3.11, 3.61]). Relatives of individuals with early-onset type 2 diabetes also had higher overall risks of the examined psychiatric disorders (ORs 1.03-1.57). These associations are largely explained by genetic factors (51-78%), with the rest explained by nonshared environmental factors.Our findings highlight the burden of mood, anxiety, and stress-related disorders in early-onset type 2 diabetes and demonstrate that shared familial liability may contribute to their co-occurrence, suggesting that in the future research investigators should aim to identify shared risk factors and ultimately refine preventive and intervention strategies.
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32.
  • Liu, Shengxin, et al. (author)
  • Psychotropic Medication Use in Children and Adolescents With Type 1 Diabetes
  • 2023
  • In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:10
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE: Children and adolescents with type 1 diabetes (T1D) face elevated risks of psychiatric disorders. Despite their nonnegligible adverse effects, psychotropic medications are a common cost-effective approach to alleviating psychiatric symptoms, but evidence regarding their dispensation to children and adolescents with T1D remains lacking. OBJECTIVE: To examine the trends and patterns of psychotropic medication dispensation among children and adolescents with T1D in Sweden between 2006 and 2019.DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from multiple Swedish registers. The main study cohort included children and adolescents residing in Sweden from 2006 to 2019 and was followed up until the earliest of December 31, 2019, 18th birthday, emigration, or death. Data analyses were conducted from November 1, 2022, to April 30, 2023.EXPOSURES: Type 1 diabetes.MAIN OUTCOMES AND MEASURES: The primary outcomes were trends and patterns of psychotropic medication dispensation (including antipsychotics, antidepressants, anxiolytics, hypnotics, mood stabilizers, and medications for attention-deficit/hyperactivity disorder [ADHD]), psychotropic medication initiation, and history of neurodevelopmental and psychiatric diagnosis. Cumulative incidence curves and Cox proportional hazard models were used to estimate the aggregated incidence and hazard ratios of medication initiation after diabetes onset. RESULTS: Of 3 723 745 children and adolescents (1 896 199 boys [50.9%]), 13 200 (0.4%; 7242 boys [54.9%]) had T1D (median [IQR] age at diagnosis, 11.1 [7.6-14.7] years). Between 2006 and 2019, psychotropic medication dispensation increased from 0.85% (95% CI, 0.65%-1.10%) to 3.84% (3.11%-4.69%) among children and from 2.72% (95% CI, 2.15%-3.39%) to 13.54% (95% CI, 12.88%-14.23%) among adolescents with T1D, consistently higher than their peers without T1D. The most commonly dispensed medications included hypnotics, ADHD medications, anxiolytics, and selective serotonin reuptake inhibitors, and all exhibited increasing trends. For those with T1D, psychiatric care was the primary prescription source, and up to 50.1% of treatments lasted more than 12 months. In addition, children and adolescents with T1D showed higher cumulative incidence and hazard ratios of medication initiation after diabetes onset than their same-age and same-sex counterparts.CONCLUSIONS AND RELEVANCE: This cohort study found an increasing trend in psychotropic medication dispensation among children and adolescents with T1D from 2006 to 2019, persistently higher than those without T1D. These findings call for further in-depth investigations into the benefits and risks of psychotropic medications within this population and highlight the importance of integrating pediatric diabetes care and mental health care for early detection of psychological needs and careful monitoring of medication use.
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33.
  • Ludvigsson, Jonas F., 1969-, et al. (author)
  • Association between inflammatory bowel disease and psychiatric morbidity and suicide : A Swedish nationwide population-based cohort study with sibling comparisons
  • 2021
  • In: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 15:11, s. 1824-1836
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is linked to psychiatric morbidity, but few studies have assessed general population comparators. We aimed to investigate the risk of psychiatric morbidity and suicide in adult-onset IBD patients.METHODS: Nationwide population-based cohort study in Sweden (1973-2013). We studied the risk of psychiatric disorders and suicide in 69,865 adult-onset IBD patients (ulcerative colitis, UC: n=43,557; Crohn's disease, CD: n=21,245; and IBD-unclassified: n=5063) compared to 3,472,913 general population references and 66,292 siblings.RESULTS: During a median follow-up of 11 years, we found 7,465 (10.7%) first psychiatric disorders in IBD (incidence rate, IR/1000 person-years 8.4) and 306,911 (9.9%) in the general population (IR 6.6), resulting in 1.8 extra psychiatric morbidity per 100 patients followed-up for 10 years and a hazard ratio (HR) of 1.3 (95% confidence interval, 95%CI=1.2-1.3). The highest risk of overall psychiatric morbidity was seen in the first year after IBD diagnosis (HR=1.4, 95%CI=1.2-1.6) and in patients with extraintestinal manifestations (HR=1.6, 95%CI=1.5-1.7). Psychiatric morbidity was more common in all IBD subtypes (HRs 1.3 to 1.5). An increased risk of suicide attempts was observed among all IBD types (HRs=1.2 to 1.4), whereas completed suicide was explicitly associated with CD (HR=1.5) and elderly-onset (diagnosed at the age of >60 years) IBD (HR=1.7).CONCLUSION: Adult-onset IBD was associated with an increased risk of psychiatric disorders and suicide attempts. Psychological follow-up should be provided to patients with IBD, especially those with extraintestinal manifestations and elderly-onset IBD. This follow-up should transpire within the first year after IBD diagnosis.
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34.
  • Martini, Miriam, et al. (author)
  • Heritability of Clinical Diagnosis in Autistic Adults and Etiological Stability of Autistic Traits from Childhood to Adulthood
  • 2022
  • In: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 52:6, s. 377-377
  • Journal article (other academic/artistic)abstract
    • Increasing evidence indicates a persistence of autism and autistic traits into adulthood, necessitating a lifespan approach to autism. Little is known about why autism persists into adulthood, and how genetic and environmental factors contribute over time. Genetically informative research has mostly focused on childhood and longitudinal designs following autistic individuals into adulthood are scarce. We aimed to determine the heritability of clinically diagnosed autism in adulthood and the etiological stability of autistic traits from childhood to adulthood. From 23,849 twin pairs in the Swedish Twin Register born between 1959 and 2010, we identified 485 individuals (1.01%, 31.5% female) diagnosed with autism. Using a liability threshold model, we estimated the relative contribution of genetic, shared environmental and non-shared environmental influences to autism liability in childhood (birth years 1996–2010) and adulthood (birth years 1959–1995). The heritability of autism was 96% (95% confidence interval, CI, 80–98%) in childhood and 89% (95% CI,67–94%) in adulthood. Non-shared environmental factors explained 4% (95% CI, 2–9%) of the variance in childhood and 11% (95% CI, 6–19%) in adulthood while shared environmental factors did not contribute. These results suggest that genetic factors play an important role for autism across the lifespan and that the shared environment is of minor importance. Additional analyses using data of 2925 twins from the longitudinal Twin Study of Child and Adolescent Development using Cholesky decomposition found stable as well as newly emerging genetic influences on autistic traits from age 8/9 to 19/20, as well as unique non-shared environmental influences at each age.
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35.
  • Martini, Miriam I., et al. (author)
  • Age effects on autism heritability and etiological stability of autistic traits
  • 2024
  • In: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610.
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Autism and autistic traits onset in childhood but persist into adulthood. Little is known about how genetic and environmental factors influence autism and autistic traits into adulthood. We aimed to determine age effects on the heritability of clinically diagnosed autism and the etiological stability of autistic traits from childhood to adulthood using twin methods.METHODS: From 23,849 twin pairs in the Swedish Twin Register born between 1959 and 2010, we identified 485 individuals (1.01%, 31.5% female) with a clinical autism diagnosis. We estimated and compared the relative contribution of genetic, shared, and nonshared environmental influences to autism in childhood and adulthood. We further used multivariate twin analysis with four measurement points among 1,348 twin pairs in the longitudinal Twin Study of Child and Adolescent Development to assess the phenotypic and etiological stability of autistic traits - measured with three scales from the Child Behavior Checklist - from childhood to adulthood.RESULTS: Autism heritability was comparable from childhood, (96% [95% CI, 76-99%]) to adulthood (87% [67-96%]). Autistic traits were moderately stable (phenotypic correlation = 0.35-0.61) from childhood to adulthood, and their heritability varied between 52 and 71%. We observed stable as well as newly emerging genetic influences on autistic traits from ages 8-9 to 19-20, and unique nonshared environmental influences at each age.CONCLUSIONS: Genetic factors are important for autism and autistic traits in adulthood and separate genetic studies in adults are warranted.
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36.
  • Nordenström, Anna, et al. (author)
  • Are carriers of CYP21A2 mutations less vulnerable to psychological stress? A population-based national cohort study
  • 2016
  • In: Clinical Endocrinology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0300-0664 .- 1365-2265.
  • Journal article (peer-reviewed)abstract
    • Background: Congenital adrenal hyperplasia (CAH) is one of the most common monogenic autosomal recessive disorders with an incidence of one in 15 000. About one in 70 individuals in the general population are carriers of a severe CYP21A2 mutation. It has been suggested that this confers a survival advantage, perhaps as a result of increased activity in the hypothalamic–pituitary–adrenal axis. We investigated vulnerability to psychological stress in obligate carriers. Method: The Swedish CAH Registry encompasses more than 600 patients. Parents, that is obligate carriers of the CYP21A2 mutation, were identified through the Multigeneration Register. The diagnosis of the child was used as the psychological stressor. Psychiatric diagnoses before and after the birth of a child with CAH were compared to those of controls derived from (i) the general population, (ii) parents of children with hypospadias and (iii) parents of children with diabetes mellitus type 1 (T1DM). Results: Parents of children with CAH had less risk of being diagnosed with any psychiatric disorder (OR, 0 6), an affective disorder (OR, 0 5) or substance misuse (OR, 0 5) after the diagnosis of the child, compared to the general population. Their risk was also decreased compared to parents of a child with hypospadias (OR, 0 6, 0 4 and 0 2, respectively) and parents of a child with T1DM (OR 0 7, 0 6 and 0 2, respectively). The CYP21A2 carriers had a lower risk of developing mood and stress-related disorders after the diagnosis of the child. Conclusion: Obligate CYP21A2 carriers had a reduced risk of a psychiatric diagnosis and were less vulnerable to a psychologically stressful situation, at least with respect to receiving a psychiatric diagnosis. This indicates a better ability to cope with psychological stress among heterozygous carriers of severe CYP21A2 mutations, which may contribute to the apparent survival advantage
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37.
  • Påhlsson-Notini, Andreas, et al. (author)
  • Substance use-related problems in mild intellectual disability : A Swedish nationwide population-based cohort study with sibling comparison
  • 2024
  • In: JCPP Advances. - Chichester : John Wiley & Sons. - 2692-9384. ; 4:2
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Evidence for substance use-related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use-related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding.METHODS: We conducted a population-based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use-related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use-related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol-related somatic disease, conviction for a substance-related crime, and substance-related death.RESULTS: Individuals with mild intellectual disability had a higher risk of any substance use-related problem compared to the general population (HR, 1.81; 95% CI, 1.72-1.91), both in males (HR, 1.76; 95% CI, 1.65-1.89) and females (HR, 1.89; 95% CI, 1.74-2.05). The risks of substance use-related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21-8.24). The associations were attenuated in the sibling comparison models.CONCLUSIONS: Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use-related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use-related problems.
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38.
  • Röjler, Lovisa, 1983-, et al. (author)
  • Individuals With Eosinophilic Esophagitis Are at Greater Risk of Later Psychiatric Disorder
  • 2022
  • In: American Journal of Gastroenterology. - : Lippincott Williams & Wilkins. - 0002-9270 .- 1572-0241. ; 117:7, s. 1046-1055
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Several gastrointestinal and allergic diseases have been linked to psychiatric disease, but there are limited data on psychiatric disease in eosinophilic esophagitis (EoE). Our aim was to study the association between EoE and later psychiatric disorders.METHODS: This was a population-based nationwide cohort study. Individuals with EoE diagnosed during 1989-2017 in Sweden (n = 1,458) were identified through the ESPRESSO histopathology cohort that represents all gastrointestinal biopsy reports in Sweden's 28 pathology departments. Individuals with EoE were matched with up to 5 reference individuals on sex, age, county, and calendar year (n = 6,436). Cox proportional hazard modeling estimated adjusted hazard ratios (HRs). In a secondary analysis, we compared individuals with EoE with their siblings to adjust for intrafamilial confounding. RESULTS: The median age at EoE diagnosis was 39 years, and 76% of the enrolled individuals with EoE were male. During a median follow-up of 4 years, 106 individuals with EoE (15.96/1,000 person-years) developed a psychiatric disorder compared with 331 reference individuals (10.93/1,000 person-years), corresponding to an HR of 1.50 (95% confidence interval = 1.20-1.87). The increased risk was seen in the first 5 years of follow-up, but not thereafter. The highest relative risks were seen in individuals diagnosed with EoE in childhood. Compared with siblings, individuals with EoE were at an increased risk of psychiatric disease (HR = 1.62; 95% confidence interval = 1.14-2.31). EoE was linked to mood disorders, anxiety disorder, and attention-deficit hyperactivity disorder.DISCUSSION: Individuals with EoE may be at greater risk of psychiatric disease than their siblings and the general population. This risk needs to be considered in clinical care to detect, prevent, and treat comorbidity.
  •  
39.
  • Taylor, Mark J., et al. (author)
  • A twin study of genetic and environmental contributions to attention-deficit/hyperactivity disorder over time
  • 2023
  • In: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 64:11, s. 1608-1616
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is an increasingly commonly diagnosed neurodevelopmental condition. One possibility is that this reflects a genuine increase in the prevalence of ADHD due to secular environmental changes, yet this hypothesis remains untested. We therefore investigated whether the genetic and environmental variance underlying ADHD, and traits of ADHD, has changed over time.METHODS: We identified twins born from 1982 to 2008 from the Swedish Twin Registry (STR). We linked the STR with the Swedish National Patient Register and Prescribed Drug Register to identify diagnoses of ADHD and prescriptions of ADHD medication for these twins. We also utilized data collected from participants in the Child and Adolescent Twin Study in Sweden (CATSS), born from 1992 to 2008. Their parents completed a structured ADHD screening tool, which was used to measure traits of ADHD and assign broad screening diagnoses of ADHD. We used the classical twin design to test whether the degree to which variation in these measures was influenced by genetic and environmental variation changed over time.RESULTS: We included 22,678 twin pairs from the STR and 15,036 pairs from CATSS. The heritability of ADHD in the STR ranged from 66% to 86% over time, although these fluctuations were not statistically significant. We observed a modest increase in variance in ADHD traits, from 0.98 to 1.09. This was driven by small increases in the underlying genetic and environmental variance, with heritability estimated as 64%-65%. No statistically significant changes in variance in screening diagnoses were observed.CONCLUSIONS: The relative contribution of genetic and environmental factors to ADHD has remained stable over time, despite its increasing prevalence. Thus, changes in the underlying etiology of ADHD over time are unlikely to explain the increase in ADHD diagnoses.
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40.
  •  
41.
  • Zhang, Le, et al. (author)
  • Comedication and Polypharmacy With ADHD Medications in Adults : A Swedish Nationwide Study
  • 2021
  • In: Journal of Attention Disorders. - : Sage Publications. - 1087-0547 .- 1557-1246. ; 25:11, s. 1519-1528
  • Journal article (peer-reviewed)abstract
    • Objective: Evidence regarding comedication among individuals with ADHD is lacking, especially in adults. This study investigated comedication and polypharmacy with ADHD medications in adults.Method: We identified adults dispensed with ADHD medications during 2013 in Sweden and matched them to controls. Logistic regression was used to calculate odds ratios (ORs) of receiving other medications.Results: Individuals receiving ADHD medications had higher risk of receiving any major classes of somatic medications (ORs ranged from 4.1, 95% confidence interval [CI] = [4.0, 4.3], to 7.4, 95% CI = [6.5, 8.5] across age groups). They were more likely to receive respiratory system, alimentary tract and metabolic system, and cardiovascular system medications. In addition, they had higher risk of receiving any other psychotropic medications. The proportion of polypharmacy with five or more medication classes increased from 10.1% to 60.4% from 18 to 64 years. Conclusion: Comedication was more common in adults receiving ADHD medications. Potential benefits and harms of comedication and polypharmacy require further research. 
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