| 1. |
- Latvala, Antti, et al.
(författare)
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A longitudinal study of resting heart rate and violent criminality in more than 700000 men
- 2015
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Ingår i: JAMA Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2168-6238 .- 2168-622X.
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Low resting heart rate is a well-replicated physiological correlate of aggressive and antisocial behavior in children and adolescents, but whether low resting heart rate increases the risk of violence and other antisocial and risk-taking behaviors in adulthood has not been studied in representative samples. OBJECTIVE: To study the predictive association of resting heart rate with violent and nonviolent criminality and with fatal and nonfatal injuries owing to assaults and unintentional injuries in the population. DESIGN, SETTING, AND PARTICIPANTS: We conducted a study of data from several Swedish national registers on 710 264 Swedish men in the general population born from 1958 to 1991, with a follow-up of up to 35.7 years. Outcome data were available and analyzed from January 1, 1973, through December 31, 2009. Resting heart rate was measured together with blood pressure at mandatory military conscription testing at a mean (SD) age of 18.2 (0.5) years. MAIN OUTCOMES AND MEASURES: Violent and nonviolent criminal convictions and medical treatments or deaths owing to assaults and unintentional injuries. RESULTS: In models adjusted for physical, cardiovascular, psychiatric, cognitive, and socioeconomic covariates, compared with 139 511 men in the highest quintile of the distribution of resting heart rate ( 83 beats/min), 132 595 men with the lowest quintile (heart rate, 60 beats/min) had a 39% (95%CI, 35%-44%) higher hazard of being convicted of violent crimes and a 25%(95%CI, 23%-28%) higher hazard of being convicted of nonviolent crimes. The corresponding hazard was 39% higher for assault injuries (95%CI, 33%-46%) and for unintentional injuries (95%CI, 38%-41%). Further adjustment for cardiorespiratory fitness in a subset of 572 610 men with data from an exercise test did not reduce the associations. Similar associations were found between low systolic blood pressure and violent and nonviolent criminality and for assault injuries when systolic blood pressure was studied instead of resting heart rate in more than 1 million men. CONCLUSIONS AND RELEVANCE Among men, low resting heart rate in late adolescence was associated with an increased risk for violent criminality, nonviolent criminality, exposure to assault, and unintentional injury in adulthood. Most of these results were replicated with low systolic blood pressure. Resting heart rate and other autonomic measures merit further study in the development and prevention of violence and antisocial behaviour.
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| 2. |
- Ljung, Therese, et al.
(författare)
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Common etiological factors of attention deficit hyperactivity disorder and suicidal behavior : a population-based study in Sweden
- 2014
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Ingår i: JAMA Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2168-622X .- 2168-6238.
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The prevention of suicidal behavior is one of the most important tasks for mental health clinicians. Although a few studies have indicated an increased risk of suicidal behavior among individuals with attention-deficit/hyperactivity disorder, the development of more effective ways of identifying and modifying the risk is hampered by our limited understanding of the underlying mechanisms for this association. OBJECTIVE: To explore whether attention-deficit/hyperactivity disorder and suicidal behavior share genetic and environmental risk factors. DESIGN, SETTING, AND PARTICIPANTS: Matched cohort design across different levels of family relatedness recorded from January 1, 1987, to December 31, 2009. We identified 51 707 patients with attention-deficit/hyperactivity disorder (through patient and prescribed drug registers) in Sweden and their relatives by linking longitudinal population-based registers. Control participants were matched 1:5 on sex and birth year. MAIN OUTCOMES AND MEASURES: Any record of suicide attempt or completed suicide defined by discharge diagnoses of the International Classification of Diseases. RESULTS: Individuals with attention-deficit/hyperactivity disorder (probands) had increased risks of attempted and completed suicide, even after adjusting for comorbid psychiatric disorders (odds ratio [OR] = 3.62 [95% CI, 3.29-3.98] and 5.91 [95% CI, 2.45-14.27], respectively). The highest familial risk was observed among first-degree relatives (attempted suicide: OR = 2.42 [95% CI, 2.36-2.49] among parents of probands with ADHD and OR = 2.28 [95% CI, 2.17-2.40] among full siblings of probands with ADHD; completed suicide: OR = 2.24 [95% CI, 2.06-2.43] and OR = 2.23 [1.83-2.73], respectively), whereas the risk was considerably lower among more genetically distant relatives (attempted suicide: OR = 1.59 [95% CI, 1.47-1.73] among maternal half siblings, OR = 1.57 [95% CI, 1.45-1.70] among paternal half siblings, and OR = 1.39 [95% CI, 1.35-1.43] among cousins; completed suicide: OR = 1.51 [95% CI, 1.08-2.10], OR = 2.02 [95% CI, 1.47-2.79], and OR = 1.51 [95% CI, 1.36-1.67], respectively). These familial aggregation patterns remained similar across sex, after excluding relatives with attention-deficit/hyperactivity disorder and probands with suicidalbehavior, and after excluding probands and relatives with severe comorbid disorders. CONCLUSIONS AND RELEVANCE: Attention-deficit/hyperactivity disorder is associated with an increased risk of both attempted and completed suicide. The pattern of familial risks across different levels of relatedness suggests that shared genetic factors are important for this association. This is an important first step toward identifying the underlying mechanisms for the risk of suicidal behavior in patients with attention-deficit/hyperactivity disorder and suggests that individuals with attention-deficit/hyperactivity disorder and their family members are important targets for suicide prevention and treatment.
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| 3. |
- Lu, Yi, et al.
(författare)
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Association between medication use and performance on higher education entrance tests in individuals with attention-deficit/hyperactivity disorder
- 2017
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Ingår i: JAMA Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2168-622X .- 2168-6238.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Individuals with attention-deficit/hyperactivity disorder (ADHD) are at greater risk for academic problems. Pharmacologic treatment is effective in reducing the core symptoms of ADHD, but it is unclear whether it helps to improve academic outcomes. Objective: To investigate the association between the use of ADHD medication and performance on higher education entrance tests in individuals with ADHD. Design, Setting, and Participants: This cohort study observed 61640 individuals with a diagnosis of ADHD from January 1, 2006, to December 31, 2013. Records of their pharmacologic treatment were extracted from Swedish national registers along with data from the Swedish Scholastic Aptitude Test. Using a within-patient design, test scores when patients were taking medication for ADHD were compared with scores when they were not taking such medication. Data analysis was performed from November 24, 2015, to November 4, 2016. Exposures: Periods with and without ADHD medication use. Main Outcomes and Measures: Scores from the higher education entrance examination (score range, 1-200 points). Results: Among 930 individuals (493 males and 437 females; mean [SD] age, 22.2 [3.2] years) who had taken multiple entrance tests (n = 2524) and used ADHD medications intermittently, the test scores were a mean of 4.80 points higher (95% CI, 2.26-7.34; P < .001) during periods they were taking medication vs nonmedicated periods, after adjusting for age and practice effects. Similar associations between ADHD medication use and test scores were detected in sensitivity analyses. Conclusions and Relevance: Individuals with ADHD had higher scores on the higher education entrance tests during periods they were taking ADHD medication vs nonmedicated periods. These findings suggest that ADHD medications may help ameliorate educationally relevant outcomes in individuals with ADHD.
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| 4. |
- Mataix-Cols, David, et al.
(författare)
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Familial risks of Tourette syndrome and chronic tic disorders : a population-based cohort study
- 2015
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Ingår i: JAMA Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2168-622X .- 2168-6238.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Chronic Tic Disorders (CTD), including Tourette Syndrome (TS), are assumed to be strongly familial and heritable. While gene-searching efforts are well underway, precise estimates of familial risk and heritability are lacking. Previous controlled family studies were small and typically conducted within specialist clinics, resulting in potential ascertainment biases. They were also underpowered to disentangle genetic from environmental factors contributing to the observed familiality. Twin studies have been either very small or based on parent-reported tics in population-based (non-clinical) twin samples. Objective: To provide unbiased estimates of familial risk and heritability of TS/CTD at the population level. Design and Setting: Population cohort, multigenerational, family study. Participants: Using a validated algorithm, we identified 4,826 individuals diagnosed with TS/CTD (76% male) in the Swedish National Patient Register between 1969-2009. Main outcome measure: Risks (Odds Ratios; OR) for TS/CTD in all biological relatives of probands, compared to relatives of unaffected individuals (matched on a 1:10 ratio) from the general population. Structural equation modeling was used to estimate the heritability of TS/CTD. Results: The risk for TS/CTD amongst relatives of TS/CTD probands increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives (OR= 18.69, 95% CI 14.53-24.05) were significantly higher than for second-degree relatives (OR= 4.58, 95% CI 3.22-6.52) and third-degree relatives (OR= 3.07, 95% CI 2.08-4.51). First-degree relatives at similar genetic distances (e.g. parents, siblings, offspring) had similar risks for TS/CTD, despite different degrees of shared environment. The risks for full siblings (50% genetic similarity; OR=17.68, 95% CI 12.90-24.23) were significantly higher than that for maternal-half siblings (25% genetic similarity; OR= 4.41, 95% CI 2.24-8.67), despite similar environmental exposures. The heritability of TS/CTD was estimated to be 0.77 (95% CI 0.70-0.85). There were no differences in familial risk or heritability between male and female patients. Conclusions and relevance: TS/CTD clusters in families primarily due to genetic factors and appears to be amongst the most heritable neuropsychiatric conditions.
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| 5. |
- Yao, Shuyang, et al.
(författare)
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Familial liability for eating disorders and suicide attempts : evidence from a population registry in Sweden
- 2017
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Ingår i: JAMA Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2168-622X .- 2168-6238.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Suicide attempts are common in individuals with eating disorders. More precise understanding of the mechanisms underlying their co-occurrence is needed. Objective: To examine the association between eating disorders and suicide attempts and whether familial risk factors contribute to the association. Design: A cohort design following a Swedish birth cohort 1979-2001 from age 6 until 31/12/2009. Setting: Information was acquired from Swedish national registers. Participants: Individuals born 1979-2001 and living in Sweden before age 6 (N= 2,268,786) were eligible for the study. Each individual was linked to his/her biological full-siblings, maternal half-siblings, paternal half-siblings, full-cousins, and half-cousins. Eating disorders were captured by three variables: any eating disorder, anorexia nervosa (AN), and bulimia nervosa (BN), identified by any lifetime diagnoses recorded in the registers. Suicide attempts were defined as any suicide attempts, including death by suicide, recorded in the registers. We examined the association between eating disorders and death by suicide separately, but were underpowered to explore familial liability for this association. Results: Individuals with any eating disorder had increased risk of suicide attempts (OR=5.28, 95%CI [5.04, 5.54]) and death by suicide (OR=5.39, 95%CI [4.00, 7.25]). The risks attenuated but remained significant after adjusting for comorbid major depressive disorder, anxiety disorders, and substance use disorder. Similar results were found for AN and BN, except that adjusted OR of death by suicide in BN became insignificant, possibly due to insufficient power. Individuals (index) who had a full-sibling with any eating disorder had increased risk of suicide attempts (OR=1.41, 95%CI [1.29, 1.53]). The risk attenuated for any eating disorder in more distant relatives (maternal half-siblings, OR=1.10, 95%CI [0.90, 1.34]; paternal half-siblings, OR=1.21, 95%CI [0.98, 1.49]; full-cousins, OR=1.11, 95%CI [1.06, 1.18]; half-cousins, OR=0.90, 95%CI [0.78, 1.03]). This familial pattern remained stable after adjusting for the index individuals’ eating disorders. Similar patterns were found for AN and BN. Conclusions and Relevance: Our results suggest increased risk of suicide attempts in individuals with lifetime eating disorders and their relatives. The pattern of familial co-aggregation suggests familial liability for the association between eating disorders and suicide. Psychiatric comorbidities partially explain this association, suggesting particularly high-risk presentations.
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| 9. |
- Akingbuwa, W. A., et al.
(författare)
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Genetic Associations between Childhood Psychopathology and Adult Depression and Associated Traits in 42998 Individuals: A Meta-Analysis
- 2020
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Ingår i: JAMA Psychiatry. - : American Medical Association (AMA). - 2168-622X .- 2168-6238. ; 77:7, s. 715-728
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits. Objective: To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders. Design, Setting, and Participants: This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019. Exposures: Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI). Main Outcomes and Measures: Regression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater. Results: The sample included 42998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023-0.042 [95% CI, 0.017-0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, -0.026 to -0.046 [95% CI, -0.020 to -0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (Δβ, 0.0561 [Δ95% CI, 0.0318-0.0804]; ΔSE, 0.0124) and social problems (Δβ, 0.0528 [Δ95% CI, 0.0282-0.0775]; ΔSE, 0.0126), and between BMI PGS and ADHD and social problems (Δβ, -0.0001 [Δ95% CI, -0.0102 to 0.0100]; ΔSE, 0.0052), compared with internalizing problems (Δβ, -0.0310 [Δ95% CI, -0.0456 to -0.0164]; ΔSE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (Δβ, -0.0032 [Δ 95% CI, -0.0048 to -0.0017]; ΔSE, 0.0008). Conclusions and Relevance: Results from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.. © 2020 Lippincott Williams and Wilkins. All rights reserved.
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| 10. |
- Al-Haddad, Benjamin J S, et al.
(författare)
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Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero.
- 2019
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 76:6, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- The developmental origins of mental illness are incompletely understood. Although the development of autism and schizophrenia are linked to infections during fetal life, it is unknown whether more common psychiatric conditions such as depression might begin in utero.To estimate the risk of psychopathologic conditions imparted from fetal exposure to any maternal infection while hospitalized during pregnancy.A total of 1 791 520 Swedish children born between January 1, 1973, and December 31, 2014, were observed for up to 41 years using linked population-based registries. Children were excluded if they were born too late to contribute person-time, died before being at risk for the outcome, or were missing particular model data. Infection and psychiatric diagnoses were derived using codes from hospitalizations. Directed acyclic graphs were developed from a systematic literature review to determine Cox proportional hazards regression models for risk of psychopathologic conditions in the children. Results were evaluated using probabilistic and simple bias analyses. Statistical analysis was conducted from February 10 to October 17, 2018.Hospitalization during pregnancy with any maternal infection, severe maternal infection, and urinary tract infection.Inpatient diagnosis of autism, depression, bipolar disorder, or psychosis among offspring.A total of 1 791 520 Swedish-born children (48.6% females and 51.4% males) were observed from birth up to age 41 years, with a total of 32 125 813 person-years. Within the directed acyclic graph framework of assumptions, fetal exposure to any maternal infection increased the risk of an inpatient diagnosis in the child of autism (hazard ratio [HR], 1.79; 95% CI, 1.34-2.40) or depression (HR, 1.24; 95% CI, 1.08-1.42). Effect estimates for autism and depression were similar following a severe maternal infection (autism: HR, 1.81; 95% CI, 1.18-2.78; depression: HR, 1.24; 95% CI, 0.88-1.73) or urinary tract infection (autism: HR, 1.89; 95% CI, 1.23-2.90; depression: HR, 1.30; 95% CI, 1.04-1.61) and were robust to moderate unknown confounding. Within the directed acyclic graph framework of assumptions, the relationship between infection and depression was vulnerable to bias from loss to follow-up, but separate data from the Swedish Death Registry demonstrated increased risk of suicide among individuals exposed to pregnancy infection. No evidence was found for increased risk of bipolar disorder or psychosis among children exposed to infection in utero.These findings suggest that fetal exposure to a maternal infection while hospitalized increased the risk for autism and depression, but not bipolar or psychosis, during the child's life. These results emphasize the importance of avoiding infections during pregnancy, which may impart subtle fetal brain injuries contributing to development of autism and depression.
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