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Rosenqvist, M. A., Sjölander, A., Ystrom, E., Larsson, H. & Reichborn-Kjennerud, T. (2019). Adverse family life events during pregnancy and ADHD symptoms in five-year-old offspring. Journal of Child Psychology and Psychiatry and Allied Disciplines, 60(6), 665-675
Open this publication in new window or tab >>Adverse family life events during pregnancy and ADHD symptoms in five-year-old offspring
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2019 (English)In: Journal of Child Psychology and Psychiatry and Allied Disciplines, ISSN 0021-9630, E-ISSN 1469-7610, Vol. 60, no 6, p. 665-675Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Prenatal exposure to maternal adverse life events has been associated with offspring ADHD, but the role of familial confounding is unclear. We aimed to clarify if adverse life events during pregnancy are related to ADHD symptoms in offspring, taking shared familial factors into account.

METHOD: Data were collected on 34,751 children (including 6,427 siblings) participating in the population-based Norwegian Mother and Child Cohort Study. During pregnancy, mothers reported whether they had experienced specific life events. We assessed ADHD symptoms in five-year-old children with the Conners' Parent Rating Scale-Revised: short form. We modeled the associations between life events and mean ADHD scores with ordinary linear regression in the full cohort, and with fixed-effect linear regression in sibling comparisons to adjust for familial confounding.

RESULTS: Children exposed to adverse life events had higher ADHD scores at age 5, with the strongest effect observed for financial problems (mean differences 0.10 [95% CI: 0.09, 0.11] in adjusted model), and the weakest for having lost someone close (0.02 [95% CI 0.01, 0.04] in adjusted model). Comparing exposure-discordant siblings resulted in attenuated estimates that were no longer statistically significant (e.g. mean difference for financial problems -0.03 [95% CI -0.07, 0.02]). ADHD scores increased if the mother had experienced the event as painful or difficult, and with the number of events, whereas sibling-comparison analyses resulted in estimates attenuated toward the null.

CONCLUSIONS: These results suggest that the association between adverse life events during pregnancy and offspring ADHD symptoms is largely explained by familial factors.

Place, publisher, year, edition, pages
Blackwell Publishing, 2019
Keywords
ADHD, MoBa, adverse life events, antenatal stress, delayed effects, prenatal exposures, the Norwegian Mother and Child Cohort Study
National Category
Psychiatry Occupational Health and Environmental Health
Identifiers
urn:nbn:se:oru:diva-69888 (URN)10.1111/jcpp.12990 (DOI)000468398900008 ()30367686 (PubMedID)2-s2.0-85055549396 (Scopus ID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2015‐00075The Research Council of Norway, 231105
Note

Funding agencies:

National Institute of Neurological Disorders and Stroke (NIH/NINDS), UO1 NS 047537‐01, UO1 NS 047537‐06A1

Norwegian Ministry of Health and Care Services Services and the Ministry of Education and Research

National Institute of Environmental Health Sciences (NIH/NIEHS), N01‐ES‐75558

Available from: 2018-11-06 Created: 2018-11-06 Last updated: 2019-06-19Bibliographically approved
Sun, J., Zhan, Y., Mariosa, D., Larsson, H., Almqvist, C., Ingre, C., . . . Fang, F. (2019). Antibiotics Use and Risk of Amyotrophic Lateral Sclerosis in Sweden. European Journal of Neurology, 26(11), 1355-1361
Open this publication in new window or tab >>Antibiotics Use and Risk of Amyotrophic Lateral Sclerosis in Sweden
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2019 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 26, no 11, p. 1355-1361Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: Previous animal studies have suggested disrupted intestinal microbiome in amyotrophic lateral sclerosis (ALS). Due to the known effect of antibiotics on gut microflora, the potential role of antibiotics use on the risk of ALS deserves an investigation.

METHODS: A nested case-control study was conducted using several Swedish national registers. We included 2,484 ALS patients diagnosed between July 1, 2006 and December 31, 2013 as cases and randomly selected five controls per case who were individually matched to the case by sex, birth year, and area of residence from the general Swedish population. Information on antibiotics prescriptions before ALS diagnosis was extracted from the Prescribed Drug Register for both cases and controls. Conditional logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: After accounting for potential diagnostic delay in ALS by excluding all prescriptions within one year before diagnosis, any antibiotics use was associated with a higher risk of ALS. The ORs (95% CIs) were 1.06 (0.94-1.19), 1.13 (1.00-1.28), and 1.18 (1.03-1.35) when comparing one, 2-3, and ≥4 prescriptions to no prescription (P for trend = 0.0069). Similar results were noted for antibiotics used for respiratory infections and urinary tract as well as skin and soft tissue infections. Among different individual antibiotics, the risk of ALS was especially increased in relation to more than two prescriptions of beta-lactamase sensitive penicillin (OR=1.28; 95% CI 1.10-1.50).

CONCLUSIONS: Use of antibiotics, especially repeated, might be associated with a higher subsequent risk of ALS.

Place, publisher, year, edition, pages
Blackwell Publishing, 2019
Keywords
Amyotrophic lateral sclerosis, antibiotics, nested case-control study, register-based
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-74325 (URN)10.1111/ene.13986 (DOI)000488977000004 ()31087715 (PubMedID)
Available from: 2019-05-20 Created: 2019-05-20 Last updated: 2019-10-18Bibliographically approved
Chen, Q., Larsson, H., Almqvist, C., Chang, Z., Lichtenstein, P., D'Onofrio, B. M. & Ludvigsson, J. F. (2019). Association between pharmacotherapy for ADHD in offspring and depression-related specialty care visits by parents with a history of depression. BMC Psychiatry, 19, Article ID 224.
Open this publication in new window or tab >>Association between pharmacotherapy for ADHD in offspring and depression-related specialty care visits by parents with a history of depression
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2019 (English)In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 19, article id 224Article in journal (Refereed) Published
Abstract [en]

Background: Pharmacotherapy is effective in reducing the core symptoms of attention-deficit/hyperactivity disorder (ADHD). We aimed to investigate the concurrent association between pharmacotherapy for ADHD in offspring and depression-related specialty care visits by the parents with a history of depression.

Methods: Using data from a variety of Swedish national registers, we conducted a cohort study with 8-year follow-up of 5605 parents (3872 mothers and 1733 fathers) who had a history of depression and an offspring diagnosed with ADHD. The hazard rate for parental depression-related specialty care visits during exposed periods when the offspring was on medication for treatment of ADHD was compared with the hazard rate during unexposed periods when the offspring was off medication. Within-individual comparisons were employed to control for time-constant confounding factors.

Results: Among mothers, the crude rates of depression-related specialty care visits during exposed and unexposed periods were 61.33 and 63.95 per 100 person-years, respectively. The corresponding rates among fathers were 49.23 and 54.65 per 100 person-years. When the same parent was compared with him or herself, fathers showed a decreased hazard rate for depression-related visits during exposed periods when the offspring was on medication for treatment of ADHD as compared to unexposed periods (hazard ratio, 0.79 [95% confidence interval, 0.70 to 0.90]). No statistically significant associations were observed in mothers.

Conclusions: Among parents with a history of depression, pharmacotherapy for ADHD in offspring is concurrently associated with a decreased rate of depression-related specialty care visits in fathers but not in mothers. Future research with refined measures of parental depression and other time-varying familial factors is needed to better understand the mechanisms underlying the association.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
ADHD, Pharmacotherapy, Depression, Offspring, Parents
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-75725 (URN)10.1186/s12888-019-2211-7 (DOI)000475947500001 ()31315609 (PubMedID)2-s2.0-85069537504 (Scopus ID)
Funder
Swedish Research Council, 2013-2280
Note

Funding Agencies:

Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM)  340-2013-5867 

National Institute of Mental Health (NIMH)  1R01MH102221 

Available from: 2019-08-13 Created: 2019-08-13 Last updated: 2019-08-13Bibliographically approved
Butwicka, A., Olén, O., Larsson, H., Halfvarson, J., Almqvist, C., Lichtenstein, P., . . . Ludvigsson, J. F. (2019). Association of Childhood-Onset Inflammatory Bowel Disease With Risk of Psychiatric Disorders and Suicide Attempt. JAMA pediatrics
Open this publication in new window or tab >>Association of Childhood-Onset Inflammatory Bowel Disease With Risk of Psychiatric Disorders and Suicide Attempt
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2019 (English)In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211Article in journal (Refereed) Epub ahead of print
Abstract [en]

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.

Place, publisher, year, edition, pages
American Medical Association, 2019
National Category
Psychiatry Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-75913 (URN)10.1001/jamapediatrics.2019.2662 (DOI)31424531 (PubMedID)
Available from: 2019-08-26 Created: 2019-08-26 Last updated: 2019-08-26Bibliographically approved
Isung, J., Isomura, K., Almqvist, C., Lichtenstein, P., Larsson, H., Wester, T., . . . Mataix-Cols, D. (2019). Association of chronic and acute inflammation of the mucosa-associated lymphoid tissue with psychiatric disorders and suicidal behavior. Translational Psychiatry, 9(1), Article ID 227.
Open this publication in new window or tab >>Association of chronic and acute inflammation of the mucosa-associated lymphoid tissue with psychiatric disorders and suicidal behavior
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2019 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 9, no 1, article id 227Article in journal (Refereed) Published
Abstract [en]

Immune dysregulation due to chronic inflammation is a hypothesized risk factor underlying psychiatric disorders and suicidal behavior. Whether tonsillectomy and acute appendicitis used, respectively, as proxies for chronic and acute inflammation within the mucosa-associated lymphoid tissue (MALT) are associated with psychiatric disorders and suicidal behavior is currently unknown. A birth cohort study was conducted including 3,052,875 individuals born in Sweden between 1973 and 2003. We identified 210,686 individuals ever exposed to tonsillectomy and 86,928 individuals ever exposed to acute appendicitis, as well as 317,214 clusters of siblings discordant for tonsillectomy, and 160,079 sibling clusters discordant for acute appendicitis. Outcomes were an aggregate risk of 'any psychiatric disorder', 'any suicidal behavior', 12 individual psychiatric disorders, suicide attempts and deaths by suicide. Tonsillectomy was associated with increased odds of 'any psychiatric disorder' (adjusted odds ratio [aOR] = 1.39; 95% confidence interval (CI) = 1.38-1.41) and 'any suicidal behavior' (aOR = 1.41; 95% CI = 1.37-1.44), and most individual disorders. Acute appendicitis also increased the odds of 'any psychiatric disorder' and 'any suicidal behavior' (aOR = 1.23; 95% CI = 1.20-1.25, and aOR = 1.32; 95% CI = 1.28-1.37, respectively). Exposure to both tonsillectomy and appendicitis was associated with the highest odds of 'any psychiatric disorder' (aOR = 1.70; 95% CI = 1.59-1.82) and 'any suicidal behavior' (aOR = 1.90; 95% CI = 1.70-2.12). In sibling comparisons, the associations were attenuated but remained significant. We conclude that inflammation within the MALT, particularly when chronic, is robustly associated with a broad range of psychiatric disorders and suicidal behavior.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-76423 (URN)10.1038/s41398-019-0568-5 (DOI)000486267400003 ()31515504 (PubMedID)2-s2.0-85072141659 (Scopus ID)
Note

Funding Agencies:

Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet  

Stockholm Care Services, Stockholm County Council  

Fredrik & Ingrid Thuring's foundation  2017-00285

Available from: 2019-09-16 Created: 2019-09-16 Last updated: 2019-10-02Bibliographically approved
Pettersson, E., Larsson, H., D'Onofrio, B., Almqvist, C. & Lichtenstein, P. (2019). Association of Fetal Growth With General and Specific Mental Health Conditions. JAMA psychiatry, 76(5), 536-543
Open this publication in new window or tab >>Association of Fetal Growth With General and Specific Mental Health Conditions
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2019 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 76, no 5, p. 536-543Article in journal (Refereed) Published
Abstract [en]

Importance: It is unclear if the associations between fetal growth and later mental health conditions remain after controlling for familial factors and psychiatric comorbidity.

Objective: To examine the associations between fetal growth and general and specific mental health conditions, controlling for familial factors.

Design, Setting, and Participants: This register-based study conducted in Sweden analyzed 546 894 pairs of full siblings born between January 1, 1973, and December 31, 1998. Sibling pairs were followed up through December 31, 2013. First, population-based and within-sibling pair associations (which controlled for time-invariant familial confounders) between fetal growth and the outcomes were estimated. Second, exploratory factor analysis was applied to the outcomes to derive 1 general factor and 4 specific and independent factors. Third, the general and specific factors were regressed on fetal growth. Statistical analysis was performed from March 27, 2017, to October 27, 2018.

Main Outcome and Measures: The outcomes were 11 psychiatric diagnoses (depression, anxiety, obsessive-compulsive disorder, posttraumatic stress disorder, bipolar disorder, alcohol abuse, drug use, attention-deficit/hyperactivity disorder, autism, schizophrenia, and schizoaffective disorder) and court convictions of violent crimes. Birth weight (in kilograms) statistically adjusted for gestational age was the exposure.

Results: The mean (SD) age of the 1 093 788 participants was 27.2 (6.8) years (range, 15.1-40.9 years) and 51.5% were male. Nine outcomes were significantly associated with birth weight in the population at large: depression (odds ratio [OR], 0.96; 95% CI, 0.95-0.98), anxiety (OR, 0.94; 95% CI, 0.92-0.95), posttraumatic stress disorder (OR, 0.91; 95% CI, 0.89-0.93), bipolar disorder (OR, 0.94; 95% CI, 0.89-1.00), alcohol abuse (OR, 0.89; 95% CI, 0.87-0.91), drug use (OR, 0.83; 95% CI, 0.80-0.85), violent crimes (OR, 0.85; 95% CI, 0.83-0.86), attention-deficit/hyperactivity disorder (OR, 0.88; 95% CI, 0.86-0.90), and autism (OR, 0.95; 95% CI, 0.92-0.97). Only depression (OR, 0.95; 95% CI 0.92-0.98), obsessive-compulsive disorder (OR, 0.93; 95% CI, 0.87-0.99), attention-deficit/hyperactivity disorder (OR, 0.86; 95% CI, 0.82-0.89), and autism (OR, 0.72; 95% CI, 0.69-0.76) remained significantly associated within sibling pairs. An exploratory factor analysis indicated that 1 general and 4 specific factors (capturing anxiety, externalizing, neurodevelopmental, and psychotic conditions) fit the outcomes well. Across almost all sensitivity analyses, an increase in birth weight by 1 kg significantly reduced the general (β, -0.047; 95% CI, -0.071 to -0.023) and the specific neurodevelopmental factors (β, -0.159; 95% CI, -0.190 to -0.128) within sibling pairs.

Conclusions and Relevance: Controlling for familial confounders, reduced fetal growth was associated with a small but significant increase in the general factor of psychopathology and a moderate increase in a specific neurodevelopmental factor.

Place, publisher, year, edition, pages
American Medical Association, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-72370 (URN)10.1001/jamapsychiatry.2018.4342 (DOI)000467491200015 ()30725083 (PubMedID)2-s2.0-85061261014 (Scopus ID)
Note

Funding Agency:

Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM)  340-2013-5867

Available from: 2019-02-12 Created: 2019-02-12 Last updated: 2019-06-18Bibliographically approved
Taylor, M. J., Martin, J., Lu, Y., Brikell, I., Lundström, S., Larsson, H. & Lichtenstein, P. (2019). Association of Genetic Risk Factors for Psychiatric Disorders and Traits of These Disorders in a Swedish Population Twin Sample. JAMA psychiatry, 76(3), 280-289
Open this publication in new window or tab >>Association of Genetic Risk Factors for Psychiatric Disorders and Traits of These Disorders in a Swedish Population Twin Sample
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2019 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 76, no 3, p. 280-289Article in journal (Refereed) Published
Abstract [en]

Importance: Psychiatric traits associated with categorically defined psychiatric disorders are heritable and present to varying degrees in the general population. It is commonly assumed that diagnoses represent the extreme end of continuously distributed traits in the population, but this assumption has yet to be robustly tested for many psychiatric phenotypes.

Objective: To assess whether genetic risk factors associated with psychiatric disorders are also associated with continuous variation in milder population traits.

Design, Setting, and Participants: This study combined a novel twin analytic approach with polygenic risk score (PRS) analyses in a large population-based twin sample. Phenotypic and genetic data were available from the Child and Adolescent Twin Study in Sweden. Inpatient data were available for January 1, 1987, to December 31, 2014, and outpatient data for January 1, 2001, to December 31, 2013. The last day of follow-up was December 31, 2014. Data analysis was performed from January 1, 2017, to September 30, 2017.

Main Outcomes and Measures: Questionnaires that assessed traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, tic disorders (TDs), obsessive-compulsive disorder (OCD), anxiety, major depressive disorder (MDD), mania, and psychotic experiences were administered to a large Swedish twin sample. Individuals with clinical psychiatric diagnoses were identified using the Swedish National Patient Register. Joint categorical/continuous twin modeling was used to estimate genetic correlations between psychiatric diagnoses and continuous traits. The PRSs for psychiatric disorders were calculated based on independent discovery genetic data. The association between PRSs for each disorder and associated continuous traits was tested.

Results: Phenotype data were available for 13 923 twin pairs (35.1% opposite sex and 31.7% same-sex females) at 9 years of age, 5165 pairs (36.9% opposite sex and 34.0% same-sex females) at 15 years of age, and 4273 pairs (36.5% opposite sex and 34.4% same-sex females) at 18 years of age. Genetic data were available for 13 412 individuals (50.2% females). Twin genetic correlations between numerous psychiatric diagnoses and corresponding traits ranged from 0.31 to 0.69. Disorder PRSs were associated with related population traits for ASD (β [SE] = 0.04 [0.01] at 9 years of age), ADHD (β [SE] = 0.27 [0.03] at 9 years of age), TDs (β [SE] = 0.02 [0.004] at 9 years of age), OCD (β [SE] = 0.13 [0.05] at 18 years of age), anxiety (β [SE] = 0.18 [0.08] at 9 years of age; β [SE] = 0.07 [0.02] at 15 years of age; and β [SE] = 0.40 [0.17] at 18 years of age), MDD (β [SE] = 0.10 [0.03] at 9 years of age; β [SE] = 0.11 [0.02] at 15 years of age; and β [SE] = 0.41 [0.10] at 18 years of age), and schizophrenia (β [SE] = 0.02 [0.01] at 18 years of age). Polygenic risk scores for depressive symptoms were associated with MDD diagnoses (odds ratio, 1.16; 95% CI, 1.02-1.32).

Conclusions and Relevance: These results suggest that genetic factors associated with psychiatric disorders are also associated with milder variation in characteristic traits throughout the general population for many psychiatric phenotypes. This study suggests that many psychiatric disorders are likely to be continuous phenotypes rather than the categorical entities currently defined in diagnostic manuals, which has strong implications for genetic research in particular.

Place, publisher, year, edition, pages
American Medical Association, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-71751 (URN)10.1001/jamapsychiatry.2018.3652 (DOI)000460506700011 ()30566181 (PubMedID)2-s2.0-85059175163 (Scopus ID)
Funder
Wellcome trust, 106047Forte, Swedish Research Council for Health, Working Life and Welfare, 2012-1678 2014-0834 2014-0322Swedish Research Council, 340-2013-5867 2014-3831
Note

Funding Agencies:

Judah Foundation  

Tourette Association of America  

National Institutes of Health  NS40024  NS016648  MH079489  MH073250 

American Recovery and Re-investment Act  MH079489  NS040024-0751  NSw040024-09S1  MH092289  MH092290  MH092291  MH092292  RO1MH092293  MH092513  MH092516  MH092520  NS40024-07S1  NS16648-29S1  MH071507  MH079487  MH079488  MH079494 

New Jersey Center for Tourette Syndrome and Associated Disorders 

Available from: 2019-01-23 Created: 2019-01-23 Last updated: 2019-06-18Bibliographically approved
Sun, S., Kuja-Halkola, R., Faraone, S. V., D'Onofrio, B. M., Dalsgaard, S., Chang, Z. & Larsson, H. (2019). Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder. JAMA psychiatry
Open this publication in new window or tab >>Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder
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2019 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622XArticle in journal (Refereed) Epub ahead of print
Abstract [en]

Importance: A previous register-based study reported elevated all-cause mortality in attention-deficit/hyperactivity disorder (ADHD), but cause-specific risks and the potential associations of psychiatric comorbidities remain unknown.

Objectives: To investigate the all-cause and cause-specific mortality risks in ADHD and to explore the potential role of psychiatric comorbidities.

Design, Setting, and Participants: This prospective cohort study used Swedish national registers to identify 2 675 615 individuals born in Sweden from January 1, 1983, through December 31, 2009, as the study population, among whom 86 670 individuals (3.2%) received a diagnosis of ADHD during follow-up. Follow-up was completed December 31, 2013, and data were analyzed from October 2018 through March 2019.

Exposures: Attention-deficit/hyperactivity disorder identified by first clinical diagnosis or first prescription of ADHD medications as recorded in Swedish registers. Clinical diagnosis of psychiatric comorbidity was available in the National Patient Register.

Main Outcomes and Measures: All-cause and cause-specific mortalities and hazard ratios (HRs) using Cox proportional hazards regression models.

Results: In the overall cohort of 2 675 615 individuals, 1 374 790 (51.4%) were male (57 919 with an ADHD diagnosis) and 1 300 825 (48.6%) were female (28 751 with an ADHD diagnosis). Mean (SD) age at study entry was 6.4 (5.6) years. During follow-up, 424 individuals with ADHD and 6231 without ADHD died, resulting in mortality rates of 11.57 and 2.16 per 10 000 person-years, respectively. The association was stronger in adulthood (HR, 4.64; 95% CI, 4.11-5.25) compared with childhood (HR, 1.41; 95% CI, 0.97-2.04) and increased substantially with the number of psychiatric comorbidities with ADHD (HR for individuals with only ADHD, 1.41 [95% CI, 1.01-1.97]; HR for those with ≥4 comorbidities, 25.22 [95% CI, 19.60-32.46]). In adulthood, when adjusting for early-onset psychiatric comorbidity, the association between ADHD and risk of death due to natural causes was attenuated substantially and was no longer statistically significant (HR, 1.32; 95% CI, 0.94-1.85). When adjusting for later-onset psychiatric disorders, the association was attenuated to statistical nonsignificance for death due to suicide (HR, 1.13; 95% CI, 0.88-1.45) but remained statistically significant for death caused by unintentional injury (HR, 2.14; 95% CI, 1.71-2.68) or other external causes (HR, 1.75; 95% CI, 1.23-2.48).

Conclusions and Relevance: Psychiatric comorbidity appears to play an important role in all-cause and cause-specific mortality risks in ADHD. In adulthood, early-onset psychiatric comorbidity contributed primarily to the association with death due to natural causes, whereas later-onset psychiatric comorbidity mainly influenced death due to unnatural causes, including suicide and unintentional injury. These findings suggest that health care professionals should closely monitor specific psychiatric comorbidities in individuals with ADHD to identify high-risk groups for prevention efforts.

Place, publisher, year, edition, pages
American Medical Association, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-75815 (URN)10.1001/jamapsychiatry.2019.1944 (DOI)31389973 (PubMedID)
Available from: 2019-08-23 Created: 2019-08-23 Last updated: 2019-08-23Bibliographically approved
Brander, G., Isomura, K., Chang, Z., Kuja-Halkola, R., Almqvist, C., Larsson, H., . . . Fernández de la Cruz, L. (2019). Association of Tourette Syndrome and Chronic Tic Disorder With Metabolic and Cardiovascular Disorders. JAMA Neurology, 76(4), 454-461
Open this publication in new window or tab >>Association of Tourette Syndrome and Chronic Tic Disorder With Metabolic and Cardiovascular Disorders
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2019 (English)In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 76, no 4, p. 454-461Article in journal (Refereed) Published
Abstract [en]

Importance: There are limited data concerning the risk of metabolic and cardiovascular disorders among individuals with Tourette syndrome (TS) or chronic tic disorder (CTD).

Objective: To investigate the risk of metabolic and cardiovascular disorders among individuals with TS or CTD over a period of 40 years.

Design, Settings, and Participants: This longitudinal population-based cohort study included all individuals living in Sweden between January 1, 1973, and December 31, 2013. Families with clusters of full siblings discordant for TS or CTD were further identified. Data analyses were conducted from August 1, 2017, to October 11, 2018.

Exposures: Previously validated International Classification of Diseases diagnoses of TS or CTD in the Swedish National Patient Register.

Main Outcomes and Measures: Registered diagnoses of obesity, dyslipidemia, hypertension, type 2 diabetes, and cardiovascular diseases (including ischemic heart diseases, arrhythmia, cerebrovascular diseases and transient ischemic attack, and arteriosclerosis).

Results: Of the 14 045 026 individuals in the cohort, 7804 individuals (5964 males [76.4%]; median age at first diagnosis, 13.3 years [interquartile range, 9.9-21.3 years]) had a registered diagnosis of TS or CTD in specialist care. Of 2 675 482 families with at least 2 singleton full siblings, 5141 families included siblings who were discordant for these disorders. Individuals with TS or CTD had a higher risk of any metabolic or cardiovascular disorders compared with the general population (hazard ratio adjusted by sex and birth year [aHR], 1.99; 95% CI, 1.90-2.09) and sibling controls (aHR for any disorder, 1.37; 95% CI, 1.24-1.51). Specifically, individuals with TS or CTD had higher risks for obesity (aHR, 2.76; 95% CI, 2.47-3.09), type 2 diabetes (aHR, 1.67; 95% CI, 1.42-1.96), and circulatory system diseases (aHR, 1.76; 95% CI, 1.67-1.86). The risk of any cardiometabolic disorder was significantly greater in males than in females (aHR, 2.13; 95% CI, 2.01-2.26 vs aHR, 1.79; 95% CI, 1.64-1.96), as was the risk of obesity (aHR, 3.24; 95% CI, 2.83-3.70 vs aHR, 1.97; 95% CI, 1.59-2.44). The risks were already evident from childhood (the groups were significantly different by age 8 years) and were significantly reduced with the exclusion of individuals with comorbid attention-deficit/hyperactivity disorder (aHR, 1.52; 95% CI, 1.42-1.62), while excluding other comorbidities did not significantly affect the results. Compared with patients with TS or CTD who were not taking antipsychotics, patients with a longer duration of antipsychotic treatment (>1 year) had significantly lower risks of metabolic and cardiovascular disorders.

Conclusions and Relevance: The findings of this study suggest that TS and CTD are associated with a substantial risk of metabolic and cardiovascular disorders. The results highlight the importance of carefully monitoring cardiometabolic health in patients with TS or CTD across the lifespan, particularly in those with comorbid attention-deficit/hyperactivity disorder.

Place, publisher, year, edition, pages
American Medical Association, 2019
National Category
Psychiatry Neurology
Identifiers
urn:nbn:se:oru:diva-71659 (URN)10.1001/jamaneurol.2018.4279 (DOI)000463873600014 ()30640363 (PubMedID)2-s2.0-85059958711 (Scopus ID)
Funder
The Karolinska Institutet's Research FoundationForte, Swedish Research Council for Health, Working Life and Welfare, 2014-2780 2015-00569
Note

Funding Agencies:

Tourettes Action  TALFC17

Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences  340-2013-5867

Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-06-18Bibliographically approved
Yao, S., Larsson, H., Bergen, A., Berrettini, W., Boni, C., Perica, V. B., . . . Bulik, C. (2019). Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches. Biological Psychiatry, 86(8), 577-586
Open this publication in new window or tab >>Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches
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2019 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 86, no 8, p. 577-586Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently cooccur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa.

METHODS: We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472).

RESULTS: Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes.

CONCLUSIONS: We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
ADHD, Anorexia nervosa, Bulimia nervosa, Eating disorders, Genetic epidemiology, Polygenic risk score
National Category
Neurology Psychiatry
Identifiers
urn:nbn:se:oru:diva-77215 (URN)10.1016/j.biopsych.2019.04.036 (DOI)000487249300005 ()31301758 (PubMedID)2-s2.0-85068526535 (Scopus ID)
Funder
Wellcome trust, 106047Swedish Research Council, 2017-00641 2014-3831 538-2013-8864Forte, Swedish Research Council for Health, Working Life and Welfare
Note

Funding Agencies:

China Scholarship Council

United States Department of Health & Human Services National Institutes of Health (NIH) - USA K01MH109782

Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework  340-2013-5867

Shire

Available from: 2019-10-14 Created: 2019-10-14 Last updated: 2019-10-14Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6851-3297

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