| 1. |
- Andersson, Anneli, 1992-, et al.
(författare)
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Genetic overlap between ADHD and externalizing, internalizing and neurodevelopmental disorder symptoms : a systematic review and meta-analysis
- 2018
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Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 48:6, s. 455-456
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder (Wilens, Biederman & Spencer 2002) and affects approximately 5% of children (Polanczyk, de Lima, Horta, Biederman & Rohde 2007). About half of those diagnosed in childhood continue to have the diagnosis and symptoms in adulthood (Kessler et al. 2006). The co-occurrence of ADHD with other psychiatric disorder symptoms (Burt et al. 2001; Cole et al. 2009; Polderman et al. 2014) has been suggested to be partly explained by a shared genetic vulnerability (Polderman et al. 2014). However, the strength of the genetic overlap is currently unclear. Also, no study has examined whether the genetic correlations differs between age groups (childhood versus adulthood), by rater (self-report, other informant, combined (parent-teacher, parent-twin, teacher-twin)), or by type of psychiatric disorder symptoms (externalizing, internalizing, neu-rodevelopmental). To address this gap, we conducted a systematic literature search to identify relevant twin studies, in PubMed, PsycINFO, and EMBASE. A total of 31 articles were identified and included in the present study. The pooled estimates showed that the comorbidity between ADHD and diverse psychiatric disorder symptoms were explained by shared genetic effectsrg= 0.50 (0.43–0.56). A similar shared genetic overlap between ADHD and psychiatric disorder symptoms was observed in both childhood rg= 0.51(0.42–0.61) and adulthood rg= 0.47 (0.40–0.53). Similar results werealso found for self-reports rg= 0.49 (0.42–0.55), other informants rg= 0.50 (0.40–0.60), and combined raters rg= 0.51 (0.30–0.69). Further, the strength of the genetic correlations of ADHD with the externalizing rg= 0.49 (0.39–0.59), internalizing rg= 0.55 (0.40–0.68) and neurodevelopmental rg= 0.47 (0.40–0.53) spectrums were similar in magnitude. These findings emphasize the presence of a shared genetic liability between ADHD and externalizing, internalizing and neurodevelopmental disorder symptoms, independent of age and rater.ReferencesBurt, S. A., Krueger, R. F., McGue, M., Iacono, W. G. (2001).Sources of covariation among attention-deficit/hyperactivity disorder,oppositional defiant disorder, and conduct disorder: the importance ofshared environment.Journal of Abnormal Psychology, 4, 516–525.Cole, J., Ball, H. A., Martin, N. C., Scourfield, J., McGuffin, P.(2009). Genetic overlap between measures of hyperactivity/inatten-tion and mood in children and adolescents.J Am Acad Child AdolescPsychiatry48, 1094–1101.Kessler, R. C., Adler, L., Barkley, R., Biederman, J., Conners, C.K., Demler, O., Faraone, S. V., Greenhill, L. L., Howes, M. J., Secnik,K., Spencer, T., Ustun, T. B., Walters, E. E., Zaslavsky, A. M. (2006).The prevalence and correlates of adult ADHD in the United States:results from the National Comorbidity Survey Replication.Am JPsychiatry, 163, 716–723.Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., Rohde,L. A. (2007). The worldwide prevalence of ADHD: a systematicreview and metaregression analysis.Am J Psychiatry, 164, 942-8.Polderman, T. J., Hoekstra, R. A., Posthuma, D., Larsson, H.(2014). The co-occurrence of autistic and ADHD dimensions inadults: an etiological study in 17,770 twins.Transl Psychiatry2014;4: e435.Wilens, T. E., Biederman, J., Spencer, T. J. (2002). Attentiondeficit/hyperactivity disorder across the lifespan.Annual Review Med53:113–131.
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| 2. |
- Brander, Gustaf, et al.
(författare)
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Perinatal risk factors in Tourette's and chronic tic disorders : a total population sibling comparison study
- 2018
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 23:5, s. 1189-1197
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Tidskriftsartikel (refereegranskat)abstract
- Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.
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| 3. |
- Brikell, Isabell, et al.
(författare)
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Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder : A Nationwide Cohort Study
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 83:2, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated; however, the underlying factors contributing to their co-occurrence remain unclear. A shared genetic liability has been proposed as one possible mechanism. Therefore, our goal in this study was to investigate the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence.METHODS: We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers and linked each individual to his or her biological relatives. We used logistic regression to estimate the association between epilepsy and ADHD within individual and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder covariance into genetic and environmental factors.RESULTS: Individuals with epilepsy had a statistically significant increased risk of ADHD (odds ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33-3.62). This risk increase extended to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75-1.96), children whose fathers had epilepsy (OR = 1.64, 95% CI = 1.54-1.74), full siblings (OR = 1.56, 95% CI = 1.46-1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14-1.43), paternal half siblings (OR = 1.10, 95% CI = 0.96-1.25), and cousins (OR = 1.15, 95% CI = 1.10-1.20). The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors (49%, nonshared environmental correlation = 0.36, 95% CI = 0.23-0.49). The contribution of shared environmental factors to the cross-disorder overlap was not statistically significant (11%, shared environmental correlation = 0.32, 95% CI = 20.16-0.79).CONCLUSIONS: This study demonstrates a strong and etiologically complex association between epilepsy and ADHD, with shared familial factors and risk factors unique to the individual contributing to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may share less genetic risk as compared with other neurodevelopmental disorders.
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| 4. |
- Castellheim, Albert, et al.
(författare)
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The role of general anesthesia on traits of neurodevelopmental disorders in a Swedish cohort of twins.
- 2018
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Ingår i: Journal of child psychology and psychiatry, and allied disciplines. - : Wiley. - 1469-7610 .- 0021-9630. ; 59:9, s. 966-972
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Tidskriftsartikel (refereegranskat)abstract
- The role of general anesthetics as a risk factor for possible neurodevelopmental disorders (NDDs) in humans is unresolved. The investigation of the role of anesthetics in the development of postgeneral anesthesia (anesthesia onward) NDDs has proven to be complicated, partly because of the inherent confounding in clinical cohort studies, and partly by the fact that anesthetics are only one part in the complex process of anesthesia-surgery.Utilizing the Swedish databases Child and Adolescent Twins Study in Sweden (CATSS) and National Patient Register (NPR), we investigated twins discordant for anesthesia, born between 1997 and 2004 for traits of NDDs. We identified 68 twin pairs discordant for anesthesia and explored traits of Attention-Deficit/Hyperactivity Disorder (ADHD), Learning Disability (LD), and Autism Spectrum Disorder (ASD) in them while simultaneously taking congenital abnormalities and systemic disorders (CSDs) into account. We analyzed the possible effect of anesthesia on neurodevelopmental problems, and we analyzed the within-pair differences using conditional linear regression.Twins with a recorded episode of anesthesia had higher traits of NDDs than twins without; similarly twins with CSDs had higher mean scores on all traits than twins without CSDs. The within-pair analyses suggested that exposure to anesthesia was associated with higher scores of ADHD (regression coefficient 1.02 and 95% confidence intervals: 0.27-1.78) in monozygotic (MZ) twins discordant for anesthesia. This effect remained when adjusting for congenital abnormalities.Our finding that traits of ADHD were slightly associated with anesthesia in a genetically sensitive design is in need of replication and warrants further investigation. Future studies should aim to elucidate mechanisms behind this possible association (e.g. anesthetics doses, age at exposure, exposure duration).
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| 5. |
- Cortese, Samuele, et al.
(författare)
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Association between attention deficit hyperactivity disorder and asthma : a systematic review and meta-analysis and a Swedish population-based study
- 2018
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Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 5:9, s. 717-726
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Forskningsöversikt (refereegranskat)abstract
- Background: Several studies have assessed the possible association between attention deficit hyperactivity disorder (ADHD) and asthma. However, existing evidence is inconclusive as to whether this association remains after controlling for possible important confounders. To fill this knowledge gap, we did a systematic review and meta-analysis, followed by a population-based study.Methods: For the systematic review and meta-analysis, we searched PubMed, PsycINFO, Embase, Embase Classic, Ovid MEDLINE, and Web of Knowledge databases up to Oct 31, 2017, for observational studies allowing estimation of the association between asthma and ADHD. No restrictions to date, language, or article type were applied. Unpublished data were collected from authors of the identified studies. We extracted unadjusted and adjusted odds ratios (ORs) from the identified studies and calculated ORs when they were not reported. We assessed study quality using the Newcastle-Ottawa Scale and study heterogeneity using I (2) statistics. A random-effects model was used to calculate pooled ORs. The systematic review is registered with PROSPERO (CRD42017073368). To address the fact that the ORs obtained in the meta-analysis were adjusted for confounders that inevitably varied across studies, we did a population-based study of individuals in multiple national registers in Sweden. We calculated an unadjusted OR and an OR that was simultaneously adjusted for all confounders identified in a directed acyclic graph based on the studies of asthma and ADHD identified in our systematic review.Findings: We identified 2649 potentially eligible citations, from which we obtained 49 datasets including a total of 210 363 participants with ADHD and 3 115 168 without. The pooled unadjusted OR was 1.66 (95% CI 1.22-2.26; I-2 = 99.47) and the pooled adjusted OR was 1.53 (1.41-1.65; I-2 = 50.76), indicating a significant association between asthma and ADHD. Possible lack of representativeness of the study population was detected with the Newcastle-Ottawa Scale in 42 of 49 datasets. In the population-based study, we included 1 575 377 individuals born between Jan 1, 1992, and Dec 31, 2006, of whom 259 253 (16.5%) had asthma and 57 957 (3.7%) had ADHD. Asthma was significantly associated with ADHD (OR 1.60, 95% CI 1.57-1.63) in the crude model adjusting for sex and year of birth, and this association remained significant after simultaneous adjustment for all covariates (1.45, 1.41-10.48).Interpretation: The combined results of the meta-analysis and the population-based study support a significant association between asthma and ADHD, which remained even after simultaneously controlling for several possible confounders in the population-based study. Awareness of this association might help to reduce delay in the diagnosis of both ADHD and asthma.
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| 6. |
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| 7. |
- Isomura, Kayoko, et al.
(författare)
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Metabolic and Cardiovascular Complications in Obsessive-Compulsive Disorder : A Total Population, Sibling Comparison Study With Long-Term Follow-up
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 84:5, s. 324-331
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with increased mortality, but the causes of this increase are poorly understood. This study examined whether OCD is associated with an increased risk of metabolic and cardiovascular complications.METHODS: Individuals diagnosed with OCD (n = 25,415) were identified from a cohort of 12,497,002 individuals living in Sweden between 1973 and 2013. Cox proportional hazard regression analyses were used to investigate the risk of metabolic and cardiovascular complications in OCD patients compared with the general population and unaffected full siblings of OCD individuals. Exploratory analyses were used to examine the effect of treatment with serotonin reuptake inhibitors, with or without antipsychotics, on the outcomes of interest.RESULTS: Individuals with OCD had a higher risk of any metabolic or cardiovascular complications compared with the general population (adjusted hazard ratio = 1.45; 95% confidence interval = 1.42-1.49) and their unaffected full siblings (adjusted hazard ratio = 1.47; 95% confidence interval = 1.40-1.54). In the fully adjusted sibling comparison models, patients had higher risks of obesity, type 2 diabetes mellitus, and circulatory system diseases. The risks were already evident from the beginning of the follow-up period and remained largely unchanged when excluding different groups of psychiatric comorbidities. Compared with patients who were not taking serotonin reuptake inhibitors, patients taking higher doses of serotonin reuptake inhibitors and who had a longer duration of treatment had significantly lower risks of metabolic and cardiovascular complications, regardless of whether they were also taking antipsychotics.CONCLUSIONS: OCD is associated with an increased risk of metabolic and cardiovascular complications. Our results underscore the importance of carefully monitoring metabolic and cardiovascular health in patients with OCD early in the course of the disorder.
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| 8. |
- Pérez-Vigil, Ana, et al.
(författare)
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Association of Obsessive-Compulsive Disorder With Objective Indicators of Educational Attainment : A Nationwide Register-Based Sibling Control Study
- 2018
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Ingår i: JAMA psychiatry. - Chicago, USA : American Medical Association. - 2168-6238 .- 2168-622X. ; 75:1, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- Importance: To our knowledge, the association of obsessive-compulsive disorder (OCD) and academic performance has not been objectively quantified.Objective: To investigate the association of OCD with objectively measured educational outcomes in a nationwide cohort, adjusting for covariates and unmeasured factors shared between siblings.Design, Setting, And Participants: This population-based birth cohort study included 2 115 554 individuals who were born in Sweden between January 1, 1976, and December 31, 1998, and followed up through December 31, 2013. Using the Swedish National Patient Register and previously validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, we identified persons with OCD; within the cohort, we identified 726 198 families with 2 or more full siblings, and identified 11 482 families with full siblings discordant for OCD. Data analyses were conducted from October 1, 2016, to September 25, 2017.Main Outcomes and Measures: The study evaluates the following educational milestones: eligibility to access upper secondary school after compulsory education, finishing upper secondary school, starting a university degree, finishing a university degree, and finishing postgraduate education.Results: Of the 2 115 554 individuals in the cohort, 15 120 were diagnosed with OCD (59% females). Compared with unexposed individuals, those with OCD were significantly less likely to pass all core and additional courses at the end of compulsory school (adjusted odds ratio [aOR] range, 0.35-0.60) and to access a vocational or academic program in upper secondary education (aOR, 0.47; 95% CI, 0.45-0.50 and aOR, 0.61; 95% CI, 0.58-0.63, for vocational and academic programs, respectively). People with OCD were also less likely to finish upper secondary education (aOR, 0.43; 95% CI, 0.41-0.44), start a university degree (aOR, 0.72; 95% CI, 0.69-0.75), finish a university degree (aOR, 0.59; 95% CI, 0.56-0.62), and finish postgraduate education (aOR, 0.52; 95% CI, 0.36-0.77). The results were similar in the sibling comparison models. Individuals diagnosed with OCD before age 18 years showed worse educational attainment across all educational levels compared with those diagnosed at or after age 18 years. Exclusion of patients with comorbid neuropsychiatric disorders, psychotic, anxiety, mood, substance use, and other psychiatric disorders resulted in attenuated estimates, but patients with OCD were still impaired across all educational outcomes.Conclusions and Relevance: Obsessive-compulsive disorder, particularly when it has an early onset, is associated with a pervasive and profound decrease in educational attainment, spanning from compulsory school to postgraduate education.
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| 9. |
- Pérez-Vigil, Ana, et al.
(författare)
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Association of Tourette Syndrome and Chronic Tic Disorders With Objective Indicators of Educational Attainment : A Population-Based Sibling Comparison Study
- 2018
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 75:9, s. 1098-1105
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The influence of Tourette syndrome and chronic tic disorders on academic performance has not been objectively quantified.Objective: To investigate the association of Tourette syndrome and chronic tic disorders with objectively measured educational outcomes, adjusting for measured covariates and unmeasured factors shared between siblings and taking common psychiatric comorbidities into account.Design, Setting, and Participants: A population-based birth cohort consisting of all individuals born in Sweden from 1976 to 1998 was followed up until December 2013. Individuals with organic brain disorders, mental retardation, and 2 foreign-born parents were excluded. We further identified families with at least 2 singleton full siblings and families with siblings discordant for Tourette syndrome or chronic tic disorders.Exposures: Previously validated International Classification of Diseases diagnoses of Tourette syndrome or chronic tic disorders in the Swedish National Patient Register.Main Outcomes and Measures: Eligibility to access upper secondary school after compulsory education, finishing upper secondary school, starting a university degree, and finishing a university degree.Results: Of the 2 115 554 individuals in the cohort, 3590 had registered a diagnosis of Tourette syndrome or a chronic tic disorder in specialist care (of whom 2822 [78.6%] were male; median [interquartile] age at first diagnosis, 14.0 [11-18] years). Of 726 198 families with at least 2 singleton full siblings, 2697 included siblings discordant for these disorders. Compared with unexposed individuals, people with Tourette syndrome or chronic tic disorders were significantly less likely to pass all core and additional courses at the end of compulsory school (odds ratios ranging from 0.23 [95% CI, 0.20-0.26] for the handcraft textile/wood course to 0.36 [95% CI, 0.31-0.41] for the English language course) and to access a vocational program (adjusted OR [aOR], 0.31; 95% CI, 0.28-0.34) or academic program (aOR, 0.43; 95% CI, 0.39-0.47) in upper secondary education. Individuals with the disorders were also less likely to finish upper secondary education (aOR, 0.35; 95% CI, 0.32-0.37), start a university degree (aOR, 0.41; 95% CI, 0.37-0.46), and finish a university degree (aOR, 0.39; 95% CI, 0.32-0.48). The results were only marginally attenuated in the fully adjusted sibling comparison models. Exclusion of patients with neuropsychiatric comorbidities, particularly attention-deficit/hyperactivity disorder and pervasive developmental disorders, resulted in attenuated estimates, but patients with Tourette syndrome or chronic tic disorders were still significantly impaired across all outcomes.Conclusions and Relevance: Help-seeking individuals with Tourette syndrome or chronic tic disorders seen in specialist settings experience substantial academic underachievement across all educational levels, spanning from compulsory school to university, even after accounting for multiple confounding factors and psychiatric comorbidities.
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| 10. |
- Song, Jie, et al.
(författare)
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Specificity in Etiology of Subtypes of Bipolar Disorder : Evidence From a Swedish Population-Based Family Study
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 84:11, s. 810-816
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Tidskriftsartikel (refereegranskat)abstract
- Background: Uncertainty remains whether bipolar I disorder (BDI) and bipolar II disorder (BDII) differ etiologically. We used a population-based family sample to examine the etiological boundaries between BDI and BDII by assessing their familial aggregation/coaggregation and by assessing the coaggregation between them and schizophrenia, depression, attention-deficit/hyperactivity disorder, eating disorders, autism spectrum disorder, substance use disorders, anxiety disorders, and personality disorders.Methods: By linking Swedish national registers, we established a population-based cohort (N = 15,685,511) and identified relatives with different biological relationships. Odds ratios (ORs) were used to measure the relative risk of BDI and BDII in relatives of individuals diagnosed with BDI (n = 4309) and BDII (n = 4178). The heritability for BDI and BDII and the genetic correlation across psychiatric disorders were estimated by variance decomposition analysis.Results: Compared with the general population, the OR of BDI was 17.0 (95% confidence interval [CI] 13.1-22.0) in first-degree relatives of BDI patients, higher than that of BDII patients (OR 9.8, 95% CI 7.7-12.5). The ORs of BDII were 13.6 (95% CI 10.2-18.2) in first-degree relatives of BDII patients and 9.8 (95% CI 7.7-12.4) in relatives of BDI patients. The heritabilities for BDI and BDII were estimated at 57% (95% CI 32%-79%) and 46% (95% CI 21%-67%), respectively, with a genetic correlation estimated as 0.78 (95% CI 0.36-1.00). The familial coaggregation of other psychiatric disorders, in particular schizophrenia, showed different patterns for BDI and BDII.Conclusions: Our results suggest a distinction between BDI and BDII in etiology, partly due to genetic differences.
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