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  • 1. Chang, Zheng
    et al.
    Lichtenstein, Paul
    Halldner, Linda
    D'Onofrio, Brian
    Serlachius, Eva
    Fazel, Seena
    Långström, Niklas
    Larsson, Henrik
    Stimulant ADHD medication and risk for substance abuse.2014In: Journal of Child Psychology and Psychiatry and Allied Disciplines, ISSN 0021-9630, E-ISSN 1469-7610, Vol. 55, no 8, p. 878-85Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are persistent concerns of long-term effects of stimulant ADHD medication on the development of substance abuse.

    METHODS: Using Swedish national registers, we studied all individuals born between 1960 and 1998 and diagnosed with ADHD (26,249 men and 12,504 women). We investigated the association between stimulant ADHD medication in 2006 and substance abuse during 2009. Substance abuse was indexed by substance-related death, crime, or hospital visits.

    RESULTS: ADHD medication was not associated with increased rate of substance abuse. Actually, the rate during 2009 was 31% lower among those prescribed ADHD medication in 2006, even after controlling for medication in 2009 and other covariates (hazard ratio: 0.69; 95% confidence interval: 0.57-0.84). Also, the longer the duration of medication, the lower the rate of substance abuse. Similar risk reductions were suggested among children and when investigating the association between stimulant ADHD medication and concomitant short-term abuse.

    CONCLUSIONS: We found no indication of increased risks of substance abuse among individuals prescribed stimulant ADHD medication; if anything, the data suggested a long-term protective effect on substance abuse. Although stimulant ADHD medication does not seem to increase the risk for substance abuse, clinicians should remain alert to the potential problem of stimulant misuse and diversion in ADHD patients.

  • 2. Halldner, Linda
    et al.
    Tillander, Annika
    Lundholm, Cecilia
    Boman, Marcus
    Långström, Niklas
    Larsson, Henrik
    Lichtenstein, Paul
    Relative immaturity and ADHD: findings from nationwide registers, parent- and self-reports.2014In: Journal of Child Psychology and Psychiatry and Allied Disciplines, ISSN 0021-9630, E-ISSN 1469-7610, Vol. 55, no 8, p. 897-904Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We addressed if immaturity relative to peers reflected in birth month increases the likelihood of ADHD diagnosis and treatment.

    METHODS: We linked nationwide Patient and Prescribed Drug Registers and used prospective cohort and nested case-control designs to study 6-69 year-old individuals in Sweden from July 2005 to December 2009 (Cohort 1). Cohort 1 included 56,263 individuals diagnosed with ADHD or ever used prescribed ADHD-specific medication. Complementary population-representative cohorts provided DSM-IV ADHD symptom ratings; parent-reported for 10,760 9-year-old twins born 1995-2000 from the CATSS study (Cohort 2) and self-reported for 6,970 adult twins age 20-47 years born 1959-1970 from the STAGE study (Cohort 3). We calculated odds ratios (OR:s) for ADHD across age for individuals born in November/December compared to January/February (Cohort 1). ADHD symptoms in Cohorts 2 and 3 were studied as a function of calendar birth month.

    RESULTS: ADHD diagnoses and medication treatment were both significantly more common in individuals born in November/December versus January/February; peaking at ages 6 (OR: 1.8; 95% CI: 1.5-2.2) and 7 years (OR: 1.6; 95% CI: 1.3-1.8) in the Patient and Prescribed Drug Registers, respectively. We found no corresponding differences in parent- or self-reported ADHD symptoms by calendar birth month.

    CONCLUSION: Relative immaturity compared to class mates might contribute to ADHD diagnosis and pharmacotherapy despite absence of parallel findings in reported ADHD symptom loads by relative immaturity. Increased clinical awareness of this phenomenon may be warranted to decrease risk for imprecise diagnostics and treatment. We speculate that flexibility regarding age at school start according to individual maturity could reduce developmentally inappropriate demands on children and improve the precision of ADHD diagnostic practice and pharmacological treatment.

  • 3. Hirvikoski, T
    et al.
    Jonsson, U
    Halldner, L
    Lundequist, A
    de Schipper, E
    Nordin, V
    Bölte, S
    A Systematic Review of Social Communication and Interaction Interventions for Patients with Autism Spectrum Disorder2015In: Scandinavian Journal of Child and Adolescent Psychiatry and Psychology, E-ISSN 2245-8875, Vol. 3, no 3, p. 147-168Article in journal (Refereed)
  • 4. Lichtenstein, Paul
    et al.
    Halldner, Linda
    Zetterqvist, Johan
    Sjölander, Arvid
    Serlachius, Eva
    Fazel, Seena
    Långström, Niklas
    Larsson, Henrik
    Medication for attention deficit-hyperactivity disorder and criminality.2012In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 367, no 21, p. 2006-14Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is a common disorder that has been associated with criminal behavior in some studies. Pharmacologic treatment is available for ADHD and may reduce the risk of criminality.

    METHODS: Using Swedish national registers, we gathered information on 25,656 patients with a diagnosis of ADHD, their pharmacologic treatment, and subsequent criminal convictions in Sweden from 2006 through 2009. We used stratified Cox regression analyses to compare the rate of criminality while the patients were receiving ADHD medication, as compared with the rate for the same patients while not receiving medication.

    RESULTS: As compared with nonmedication periods, among patients receiving ADHD medication, there was a significant reduction of 32% in the criminality rate for men (adjusted hazard ratio, 0.68; 95% confidence interval [CI], 0.63 to 0.73) and 41% for women (hazard ratio, 0.59; 95% CI, 0.50 to 0.70). The rate reduction remained between 17% and 46% in sensitivity analyses among men, with factors that included different types of drugs (e.g., stimulant vs. nonstimulant) and outcomes (e.g., type of crime).

    CONCLUSIONS: Among patients with ADHD, rates of criminality were lower during periods when they were receiving ADHD medication. These findings raise the possibility that the use of medication reduces the risk of criminality among patients with ADHD. (Funded by the Swedish Research Council and others.).

  • 5. Molero, Y
    et al.
    Gumpert, C
    Serlachius, E
    Lichtenstein, P
    Walum, H
    Johansson, D
    Anckarsäter, H
    Westberg, L
    Eriksson, E
    Halldner, L
    A study of the possible association between adenosine A2A receptor gene polymorphisms and attention-deficit hyperactivity disorder traits.2013In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 12, no 3, p. 305-10Article in journal (Refereed)
    Abstract [en]

    The adenosine A2A receptor (ADORA2A) is linked to the dopamine neurotransmitter system and is also implicated in the regulation of alertness, suggesting a potential association with attention-deficit hyperactivity disorder (ADHD) traits. Furthermore, animal studies suggest that the ADORA2A may influence ADHD-like behavior. For that reason, the ADORA2A gene emerges as a promising candidate for studying the etiology of ADHD traits. The aim of this study was to examine the relationship between ADORA2A gene polymorphisms and ADHD traits in a large population-based sample. This study was based on the Child and Adolescent Twin Study in Sweden (CATSS), and included 1747 twins. Attention-deficit hyperactivity disorder traits were assessed through parental reports, and samples of DNA were collected. Associations between six single nucleotide polymorphisms (SNPs) and ADHD traits were examined, and results suggested a nominal association between ADHD traits and three of these SNPs: rs3761422, rs5751876 and rs35320474. For one of the SNPs, rs35320474, results remained significant after correction for multiple comparisons. These results indicate the possibility that the ADORA2A gene may be involved in ADHD traits. However, more studies replicating the present results are warranted before this association can be confirmed.

  • 6. Törn, Peggy
    et al.
    Pettersson, Erik
    Lichtenstein, Paul
    Anckarsäter, Henrik
    Lundström, Sebastian
    Hellner Gumpert, Clara
    Larsson, Henrik
    Kollberg, Linnea
    Långström, Niklas
    Halldner, Linda
    Childhood neurodevelopmental problems and adolescent bully victimization: population-based, prospective twin study in Sweden.2015In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 24, no 9, p. 1049-59Article in journal (Refereed)
    Abstract [en]

    Bully victimization is a common problem among children with neurodevelopmental disorders, including attention deficit/hyperactivity disorder and autism spectrum disorder. Previous research was mostly cross-sectional and seldom accounted for co-morbid psychopathology, which makes it difficult to draw conclusions about causality and specificity of any association. Using a genetically informative prospective design, we investigated the association between various neurodevelopmental problems (NDPs) in childhood and bully victimization in adolescence, and the relative contributions of genetic and environmental factors to this association. We obtained parent-reports of NDPs at age 9/12 years and self-reported bully victimization at age 15 for 3,921 children participating in the The Child and Adolescent Twin Study in Sweden (CATSS). Structural equation modelling was used to control for NDP co-morbidity and bully victimization at baseline. Cholesky decomposition was used to analyse genetic and environmental contributions to observed associations. Because most of the NDPs were associated to later bully victimization, a common effect of all NDPs was summarized into a general NDP factor. Controlling for this general factor, only problems with social interaction and motor control uniquely predicted subsequent bully victimization in girls. General and unique associations were influenced by both genetic and unique environmental factors. NDPs in general and social interaction and motor problems in particular predicted later bully victimization. The longitudinal design and twin analyses indicated that these associations might be causal. Knowledge of these vulnerabilities may be important when designing risk assessment and prevention strategies.

  • 7. Zetterqvist, J
    et al.
    Asherson, P
    Halldner, L
    Långström, N
    Larsson, H
    Stimulant and non-stimulant attention deficit/hyperactivity disorder drug use: total population study of trends and discontinuation patterns 2006-2009.2013In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 128, no 1, p. 70-7Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To explore the prevalence and discontinuation of dispensed medications for attention deficit/hyperactivity disorder (ADHD) drugs from 2006 to 2009.

    METHOD: A total population cohort of all individuals aged 6-45 years, alive and registered as residents in Sweden during any calendar year from 2006 to 2009 (N = 5 149 791) included 41 700 patients dispensed with an ADHD drug (methylphenidate, atomoxetine, amphetamine, or dexamphetamine). The dispensing prevalence was calculated for each year, stratified on sex and age. A longitudinal analysis was also performed to compare the rates of treatment discontinuation across the strata.

    RESULTS: The dispensing prevalence increased from 2.93 per 1000 in 2006 to 6.98 in 2009 (PR = 2.38, 95% CI = 2.34-2.43). The prevalence ratio (PR) was 3.40 for adults, 22-45 years old; 2.41 for adolescents, 15-21 years old; and 1.90 for children aged 6-14. The increase was also greater in women than in men (PR = 2.92 vs. 2.19). Patients aged 15-21 were the most likely to discontinue treatment; after 3 years and 11 months, 27% of those patients were still under treatment.

    CONCLUSION: From 2006 to 2009, the number of prescriptions dispensed for ADHD drugs increased substantially. The rate of treatment discontinuation in the age interval 15-21 is higher than expected considering the persistence rates of the disorder.

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