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Environmental and Genetic Influences in Attention Deficit Hyperactivity Disorder (ADHD) and its Comorbidities
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Research in past decades has demonstrated the persistence of attention deficit hyperactivity disorder (ADHD) into adulthood, but many questions regarding prevalence, causes, and comorbidities of ADHD in adults remain to be investigated. Previous research focusing on childhood ADHD identified high heritability. Genetic and environmental influences on ADHD symptoms in adults and their association with comorbid conditions are not fully understood.

The overall aim of this thesis was to study adult ADHD symptoms in the population and investigate associations with substance use disorders (SUD) and binge eating. In all four papers, we used population-based self-report data from twins aged 20–46 years from the Swedish Twin Registry. We used twin methods to explore the role of genetic and environmental factors underlying ADHD symptoms and their comorbidities.

Study I examined the phenotypic association between ADHD and various forms of SUD. ADHD in adults was strongly associated with alcohol abuse and alcohol dependence, illicit drug use and regular nicotine use, with no differences between ADHD subtypes and no apparent substance preference. In Studies II and IV, we used bivariate twin models to examine the role of genetic and environmental factors in the association of adult ADHD symptoms with alcohol dependence (II) and with binge eating (IV). For ADHD symptoms and alcohol dependence, 64% of the overlap was explained by common genetic factors. The remaining variance was accounted for by environmental factors specific for each twin, with no sex differences for the overlap. Similarly, 91% of the association between ADHD symptoms and binge-eating behaviour was explained by common genetic factors. In Study III, using a within-twin pair analysis, we demonstrated that although most of the association between adult ADHD symptoms and self-reported childhood maltreatment (an environmental risk factor for ADHD) was explained by familial (genetic and environmental) confounding, our results were also consistent with a causal interpretation.

In conclusion, adult ADHD symptoms are associated with SUD and binge-eating behaviour. We replicated findings from adolescent studies regarding shared genetic risk factors for alcohol dependence and ADHD symptoms in adults. For binge eating, we showed for the first time that shared genetic factors mainly explained the association with ADHD symptoms. Alterations in mesolimbic reward processing as well as the frontal, executive and inhibitory systems have been described for ADHD, alcohol dependence and binge-eating behaviour, possibly suggesting common genetic and neurobiological factors for all three conditions. Results that support a causal hypothesis regarding the association between childhood maltreatment and ADHD symptoms in adults need follow-up in longitudinal clinical samples that can examine neurobiological underpinnings of environmental effects. Clinically, the results of this thesis support that ADHD in adults be considered and addressed in adults with SUD or binge-eating behaviour. Given the common genetic risk factors and the role of the early childhood environment, family interventions should be considered for these populations.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. , 92 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1522
National Category
Psychiatry Public Health, Global Health, Social Medicine and Epidemiology Clinical Medicine Social Sciences Interdisciplinary
Identifiers
URN: urn:nbn:se:liu:diva-130718DOI: 10.3384/diss.diva-130718ISBN: 9789176857588 (Print)OAI: oai:DiVA.org:liu-130718DiVA: diva2:954288
Public defence
2016-09-02, Belladonnasalen, Hus 511-001 plan 9 ingång 76, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2016-08-22 Created: 2016-08-22 Last updated: 2016-09-07Bibliographically approved
List of papers
1. Comorbidity of Adult ADHD and Its Subtypes With Substance Use Disorder in a Large Population-Based Epidemiological Study.
Open this publication in new window or tab >>Comorbidity of Adult ADHD and Its Subtypes With Substance Use Disorder in a Large Population-Based Epidemiological Study.
2016 (English)In: Journal of Attention Disorders, ISSN 1087-0547, E-ISSN 1557-1246Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: The objective of the study is to explore the role and possible substance preference in ADHD and subtypes in substance use disorder (SUD).

METHOD: Using self-report data on ADHD Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) symptoms and SUD (alcohol, illicit drugs, and nicotine) in 18,167 Swedish twins, aged 20 to 45 years, we obtained odds ratios (OR) from mixed effect logistic regression, controlling for age, sex, education, and nonindependence of twin data.

RESULTS: Increased ADHD symptoms were significantly associated with increased odds for all SUD. ORs ranged between 1.33 for regular nicotine (95% confidence interval [CI] = [1.12, 1.59]); 2.54 for multiple drug use (95% CI = [2.00, 3.23]), and 3.58 for alcohol dependence (95% CI = [2.86, 4.49]).

CONCLUSION: ADHD symptoms and subtypes in the population are associated with increased risks for all SUD outcomes, with no difference between ADHD subtypes, no substance preference, and no sex differences for the comorbidity. Clinicians need to consider ADHD evaluation and treatment as part of management of SUD in adults.

Keyword
ADHD subtypes; adult ADHD; alcohol; comorbidity; substance-related disorders
National Category
Psychiatry
Identifiers
urn:nbn:se:liu:diva-126285 (URN)10.1177/1087054715626511 (DOI)26838558 (PubMedID)
Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2016-08-22
2. Genetic and environmental contributions to the association between attention deficit hyperactivity disorder and alcohol dependence in adulthood: A large population-based twin study.
Open this publication in new window or tab >>Genetic and environmental contributions to the association between attention deficit hyperactivity disorder and alcohol dependence in adulthood: A large population-based twin study.
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2015 (English)In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 168, no 6, 414-422 p.Article in journal (Refereed) Published
Abstract [en]

Previous research indicates that attention deficit hyperactivity disorder (ADHD) frequently co-occurs with alcohol dependence; however, the extent to which shared genetic risk factors underpin this association remains unclear. The aim of this study is to investigate the relative importance of genetic, shared, and nonshared environmental factors for the overlap between ADHD and alcohol dependence in adults. Almost 18,000 adult twins aged 20-45 years, from more than 12,000 twin pairs (5,420 complete pairs), from the population-representative Swedish Twin Registry, were included. Self-ratings were used to assess symptoms of ADHD and alcohol dependence. Twin analysis was used to determine the role of additive genetic (A), shared (C), and nonshared environmental (E) factors. As a result, we found a significant association between ADHD and alcohol dependence (odds ratio 3.58; 95% confidence interval, 2.85-4.49). Twin analysis suggested that shared genetic risk factors explained 64% of the overlap between ADHD and alcohol dependence. Nonshared environmental factors accounted for the remaining 36%, whereas the contribution of shared environmental factors was minimal. We found no support for statistically significant sex differences in the overlap between ADHD and alcohol dependence. In conclusion the overlap between ADHD and alcohol dependence in adulthood was largely explained by shared genetic risk factors. This is an important step toward understanding the underlying nature of the risk of alcohol dependence in patients with ADHD and suggests that individuals with ADHD and their family members are important targets for alcohol prevention and treatment.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2015
National Category
Substance Abuse
Identifiers
urn:nbn:se:liu:diva-116624 (URN)10.1002/ajmg.b.32300 (DOI)000360052200003 ()25711682 (PubMedID)
Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2016-08-22
3. Childhood maltreatment and attention deficit hyperactivity disorder symptoms in adults: a large twin study
Open this publication in new window or tab >>Childhood maltreatment and attention deficit hyperactivity disorder symptoms in adults: a large twin study
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2016 (English)In: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, Vol. 46, no 12, 2637-2646 p.Article in journal (Refereed) Published
Abstract [en]

Background

Childhood maltreatment (CM) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) in children and adults. It is, however, unclear whether this association is causal or due to familial confounding.

Method

Data from 18 168 adult twins, aged 20–46 years, were drawn from the population-based Swedish twin registry. Retrospective self-ratings of CM (emotional and physical neglect, physical and sexual abuse and witnessing family violence), and self-ratings for DSM-IV ADHD symptoms in adulthood were analysed. Possible familial confounding was investigated using a within twin-pair design based on monozygotic (MZ) and dizygotic (DZ) twins.

esults

CM was significantly associated with increased levels of ADHD symptom scores in adults [regression coefficient: 0.40 standard deviations, 95% confidence interval (CI) 0.37–0.43]. Within twin-pair analyses showed attenuated but significant estimates within DZ (0.29, 95% CI 0.21–0.36) and MZ (0.18, 95% CI 0.10–0.25) twin pairs. Similar results emerged for hyperactive/impulsive and inattentive ADHD symptom scores separately in association with CM. We conducted sensitivity analyses for early maltreatment, before age 7, and for abuse and neglect separately, and found similarly reduced estimates in DZ and MZ pairs. Re-traumatization after age 7 did not significantly influence results.

Conclusions

CM was significantly associated with increased ADHD symptoms in adults. Associations were partly due to familial confounding, but also consistent with a causal interpretation. Our findings support cognitive neuroscience studies investigating neural pathways through which exposure to CM may influence ADHD. Clinicians treating adults with ADHD should be aware of the association with maltreatment.

Place, publisher, year, edition, pages
Cambridge: Cambridge University Press, 2016
Keyword
Adult ADHD; childhood maltreatment; environmental risk; familial confounding; twins
National Category
Public Health, Global Health, Social Medicine and Epidemiology Psychiatry Environmental Health and Occupational Health Other Medical Sciences not elsewhere specified
Identifiers
urn:nbn:se:liu:diva-130714 (URN)10.1017/S0033291716001021 (DOI)27376862 (PubMedID)
Available from: 2016-08-22 Created: 2016-08-22 Last updated: 2016-08-29Bibliographically approved

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