| 1. |
- Borg, J., et al.
(författare)
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Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain
- 2016
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Ingår i: Molecular Psychiatry. - London, United Kingdom : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 51, s. 879-879
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about the regulation of receptor and transporter density levels. This lack of knowledge obscures interpretation of differences in protein availability reported in psychiatric patients. In this study, we used positron emission tomography (PET) in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [(11)C]raclopride binding to the D2- and D3-dopamine receptor and [(11)C]WAY100635 binding to the serotonin 5-HT1A receptor. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for regional D2/3 and 5-HT1A receptor availability in projection areas. We found a major contribution of genetic factors (0.67) on individual variability in striatal D2/3 receptor binding and a major contribution of environmental factors (pairwise shared and unique individual; 0.70-0.75) on neocortical 5-HT1A receptor binding. Our findings indicate that individual variation in neuroreceptor availability in the adult brain is the end point of a nature-nurture interplay, and call for increased efforts to identify not only the genetic but also the environmental factors that influence neurotransmission in health and disease.
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| 2. |
- Brikell, I., et al.
(författare)
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ADHD medications and the risk of epileptic seizures : a pharmacoepidemiological study using nationwide register data
- 2017
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 27:Suppl. 4, s. S1113-S1114
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Attention-deficit/hyperactivity disorder (ADHD) affects 10–30% of children with epilepsy, making it one of the most common comorbidities in epilepsy. Stimulant medications are first line pharmacological treatment of ADHD, yet there areconcerns regarding the safety of stimulant treatment in patients with comorbid ADHD and epilepsy. This is due to the long held view that stimulants may lower the seizure threshold and increase seizure frequency [1]. Evidence for such an effect are however inconsistent and largely based on studies with small sample sizes, highly selected patient populations and observational studies that have not sufficiently addressed issues of confounding [2]. The aim of this pharmacoepidemiological register based study wastherefore to estimate the risk of seizures in relation to ADHD medication use in a population based cohort of individuals with a history of seizures.Methods: Using Swedish national registers, we identified a cohort of 62,361 individuals (48% female) born in Sweden between 1960 and 2004, with at least one seizure episode according to ICD codes. Each individual was followed from January 1st 2006, their first seizure or age five, up until December 31st 2013 or death, whichever came first. We identified periods of ADHD medication use (methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine, and atomoxetine) from the Swedish National Prescribed Drug Register. A period was defined as on-medication when two consecutive prescriptions where no more than 183 days apart, and off-medication if more than 183 daysapart. We obtained information on medical visit for unplanned seizures events from the Swedish National Patient register using ICD codes. We estimated the population level association between ADHD medications and the rate of seizures during medicated and non-medication periods using a cox proportional hazards regression model. To adjust for individual-specific confounding that may influence both seizure risk and the likelihood of receiving ADHD medication, we used a stratified Cox regression model to estimate the rate of seizures during medicated and non-medicated periods, within the same individual.Preliminary Result: A total of 59,749 seizure events occurred during 361,501 person years of follow-up. ADHD medications were not associated with the rate of seizures at the population level (HR = 1.06, 95%CI 0.91–1.23). In the within-individual analysis, ADHD medication periods were associated with a reduced rate of seizures (HR = 0.70, 95%CI 0.62–0.79), compared to non-medicated periods. Estimates did not differ across sex, nor in age restricted analyses including only ages 5 and 20 years. All analyses were adjusted for age as a time-varying covariate. Population level analyses were additionally adjusted for sex.Conclusions: Our findings suggest that ADHD medications are not associated with an increased risk of seizures. Rather, results from the within-individual analysis, which adjusts for factors that are constant within the individual, such as genetic factors and underlying disorder severity, suggest a protective effect of ADHD medication treatment on seizure rates. Next, we will study the effect of concurrent antiepileptic medication use and whether the observed effect differs by stimulant and non-stimulant ADHD medications. We will also further investigate possible mechanisms contributing to the observed protective effect of ADHD medications on seizure rates.References[1] Williams, A.E., Giust, J.M., Kronenberger, W.G., Dunn, D.W., 2016. Epilepsy and attention-deficit hyperactivity disorder: links, risks, and challenges. Neuropsychiatr Dis Treat 12, 287–296.[2] Ravi, M., Ickowicz, A., 2016. Epilepsy, Attention-Deficit/Hyperactivity Disorder and Methylphenidate: Critical Examination of Guiding Evidence. Journal of the Canadian Academy of Child and Adolescent Psychiatry 25 (1), 50.
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| 3. |
- Chen, C., et al.
(författare)
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Associations between general and specific mental health conditions in young adulthood and cardiometabolic complications in middle adulthood : A 40-year longitudinal familial coaggregation study of 672 823 Swedish individuals
- 2023
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Ingår i: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 66:Suppl. 1, s. S67-S68
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Most mental disorders, when examined individually, are associated with an increased risk of cardiometabolic complications. However, these associations might be attributed to a general liability toward psychopathology or confounded by unmeasured familial factors.Objectives: To examine whether the associations between psychiatric diagnoses and increased risk of cardiometabolic complications are attributable to a general liability toward psychopathology, or confounded by unmeasured familial factors.Methods: We conducted a cohort study in Sweden and identified all individuals and their siblings born in Sweden 1955-1962 with follow-up through 2013. After excluding individuals who died or emigrated before 1987, the final sample consisted 672 823 individuals. We extracted ICD-coded diagnoses (recorded 1973-1987) for ten psychiatric conditions and criminal convictions when participants were aged 18-25 years, and ICD-coded diagnoses (recorded 1987-2013) for five cardiometabolic complications (obesity, hypertensive diseases, hyperlipidemia, type 2 diabetes mellitus, and cardiovascular diseases) when the participants were 51-58 years old. Logistic regression models were used to estimate the bivariate associations between psychiatric conditions or criminal convictions and cardiometabolic complications in individuals. A general factor model was used to identify general, internalizing, externalizing, and psychotic factors based on the psychiatric conditions and criminal convictions. We then regressed the cardiometabolic complications on the latent general factor and three uncorrelated specific factors within a structural equation modeling framework in individuals and across sibling pairs.Results: Each psychiatric conditions significantly increased the risk of cardiometabolic complications; however, most of these associations were attributable to the general factor of psychopathology, rather than to specific psychiatric conditions. There were no or only small associations between individuals’ general psychopathology and their siblings’ cardiometabolic complications, suggesting that the associations were not attributable to genetic or environmental confounding factors shared within families. The same pattern was evident for the specific internalizing and psychotic factors.Conclusions: Individuals with mental disorders in early life had an increased long term risk of cardiometabolic complications, which appeared attributable to a general liability toward psychopathology. Sibling analyses suggested that the elevated risk could not beattributed to confounds shared within families. This highlights the importance of transdiagnostic and lifestyle based interventions to reduce the risk of cardiometabolic complications, particularly in patients with several mental disorders.
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| 4. |
- Ghirardi, L., et al.
(författare)
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The familial co-aggregation of ASD and ADHD : a register-based cohort study
- 2018
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Ingår i: Molecular Psychiatry. - London, United Kingdom : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 23:2, s. 257-262
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. The presence of a genetic link between ASD and ADHD symptoms is supported by twin studies, but the genetic overlap between clinically ascertained ASD and ADHD remains largely unclear. We therefore investigated how ASD and ADHD co-aggregate in individuals and in families to test for the presence of a shared genetic liability and examined potential differences between low- and high-functioning ASD in the link with ADHD. We studied 1 899 654 individuals born in Sweden between 1987 and 2006. Logistic regression was used to estimate the association between clinically ascertained ASD and ADHD in individuals and in families. Stratified estimates were obtained for ASD with (low-functioning) and without (high-functioning) intellectual disability. Individuals with ASD were at higher risk of having ADHD compared with individuals who did not have ASD (odds ratio (OR)=22.33, 95% confidence interval (CI): 21.77-22.92). The association was stronger for high-functioning than for low-functioning ASD. Relatives of individuals with ASD were at higher risk of ADHD compared with relatives of individuals without ASD. The association was stronger in monozygotic twins (OR=17.77, 95% CI: 9.80-32.22) than in dizygotic twins (OR=4.33, 95% CI: 3.21-5.85) and full siblings (OR=4.59, 95% CI: 4.39-4.80). Individuals with ASD and their relatives are at increased risk of ADHD. The pattern of association across different types of relatives supports the existence of genetic overlap between clinically ascertained ASD and ADHD, suggesting that genomic studies might have underestimated this overlap.
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| 5. |
- Johansson Capusan, Andrea, et al.
(författare)
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Childhood maltreatment and attention deficit hyperactivity disorder symptoms in adults : a large twin study
- 2016
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Ingår i: Psychological Medicine. - New York, USA : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 46:12, s. 2637-2646
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Tidskriftsartikel (refereegranskat)abstract
- 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.Results: 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.
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| 6. |
- Johansson Capusan, Andrea, et al.
(författare)
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Genetic and environmental aspects in the association between attention-deficit hyperactivity disorder symptoms and binge-eating behavior in adults : a twin study
- 2017
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 47:16, s. 2866-2878
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prior research demonstrated that attention-deficit hyperactivity disorder (ADHD) is associated with binge-eating behavior, binge-eating disorder (BED), and bulimia nervosa (BN). The aim of this study was to investigate these associations in an adult twin population, and to determine the extent to which ADHD symptoms and binge-eating behavior share genetic and environmental factors.Methods: We used self-reports of current ADHD symptoms and lifetime binge-eating behavior and associated characteristics from a sample of over 18 000 adult twins aged 20-46 years, from the population-based Swedish Twin Registry. Mixed-effects logistic regression was used to examine the association between ADHD and lifetime binge-eating behavior, BED, and BN. Structural equation modeling was used in 13 773 female twins to determine the relative contribution of genetic and environmental factors to the association between ADHD symptoms and binge-eating behavior in female adult twins.Results: ADHD symptoms were significantly associated with lifetime binge-eating behavior, BED, and BN. The heritability estimate for current ADHD symptoms was 0.42 [95% confidence interval (CI) 0.41-0.44], and for lifetime binge-eating behavior 0.65 (95% CI 0.54-0.74). The genetic correlation was estimated as 0.35 (95% CI 0.25-0.46) and the covariance between ADHD and binge-eating behavior was primarily explained by genetic factors (91%). Non-shared environmental factors explained the remaining part of the covariance.Conclusions: The association between adult ADHD symptoms and binge-eating behavior in females is largely explained by shared genetic risk factors.
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| 7. |
- Kastrati, Gránit, et al.
(författare)
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Genetic influences on central and peripheral nervous system activity during fear conditioning.
- 2022
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Fear conditioning is an evolutionarily conserved type of learning serving as a model for the acquisition of situationally induced anxiety. Brain function supporting fear conditioning may be genetically influenced, which in part could explain genetic susceptibility for anxiety following stress exposure. Using a classical twin design and functional magnetic resonance imaging, we evaluated genetic influences (h2) on brain activity and standard autonomic measures during fear conditioning. We found an additive genetic influence on mean brain activation (h2 = 0.34) and autonomic responses (h2 = 0.24) during fear learning. The experiment also allowed estimation of the genetic influence on brain activation during safety learning (h2 = 0.55). The mean safety, but not fear, related brain activation was genetically correlated with autonomic responses. We conclude that fear and safety learning processes, both involved in anxiety development, are moderately genetically influenced as expressed both in the brain and the body.
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| 8. |
- Khemiri, L, et al.
(författare)
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Genetic overlap between impulsivity and alcohol dependence : a large-scale national twin study
- 2016
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 46:5, s. 1091-1102
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alcohol dependence is associated with increased levels of impulsivity, but the genetic and environmental underpinnings of this overlap remain unclear. The purpose of the current study was to investigate the degree to which genetic and environmental factors contribute to the overlap between alcohol dependence and impulsivity.METHOD: Univariate and bivariate twin model fitting was conducted for alcohol dependence and impulsivity in a national sample of 16 819 twins born in Sweden from 1959 to 1985.RESULTS: The heritability estimate for alcohol dependence was 44% [95% confidence interval (CI) 31-57%] for males and 62% (95% CI 52-72%) for females. For impulsivity, the heritability was 33% (95% CI 30-36%) in males and females. The bivariate twin analysis indicated a statistically significant genetic correlation between alcohol dependence and impulsivity of 0.40 (95% CI 0.23-0.58) in males and 0.20 (95% CI 0.07-0.33) in females. The phenotypic correlation between alcohol dependence and impulsivity was 0.20 and 0.17 for males and females, respectively, and the bivariate heritability was 80% (95% CI 47-117%) for males and 53% (95% CI 19-86%) for females. The remaining variance in all models was accounted for by non-shared environmental factors.CONCLUSIONS: The association between alcohol dependence and impulsivity can be partially accounted for by shared genetic factors. The genetic correlation was greater in men compared with women, which may indicate different pathways to the development of alcohol dependence between sexes. The observed genetic overlap has clinical implications regarding treatment and prevention, and partially explains the substantial co-morbidity between alcohol dependence and psychiatric disorders characterized by impulsive behaviour.
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| 9. |
- Liu, S., et al.
(författare)
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Association and familial co-aggregation of type 1 diabetes with depression, anxiety and stress-related disorders : a population-based cohort study
- 2021
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 64:Suppl. 1, s. 18-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: People with type 1 diabetes are known to be at heightened risk of common mental health problems. However, it remains unknown whether genetic liability contributes to the elevated risk. This study aimed to investigate the association and familial co-aggregation of type 1 diabetes with depression, anxiety and stress-related disorders.Materials and methods: Using multiple Swedish nationwide registers, we obtained a population sample of individuals born 1973-2007 and still residing in Sweden at age 5. Individuals were linked to their biological parents, full-siblings, half-siblings, full-cousins and half-cousins. We obtained information from the National Patient Register (since 1973) on the diagnoses of type 1 diabetes, depression, anxiety and stress-related disorders using ICD codes and from the Prescribed Drug Register (since 2005) on the prescribed antidepressants and anxiolytics using ATC codes. Primary outcomes were any or specific diagnosis of 1) depression, 2) anxiety and 3) stress-related disorders. We examined a secondary outcome of using antidepressants or anxiolytics in those who resided in Sweden after 2005.Results: In this cohort study of about 3.5 million individuals, 20005 (53.9% male) were diagnosed with childhood-onset type 1 diabetes (< 18 years of age, the median age at onset: 9.7). We used Cox models to estimate the association between type 1 diabetes and each outcome. Individuals were regarded as unexposed before diagnosis and exposed after. During a median follow-up of 22.2 years, individuals with type 1 diabetes were at a higher risk of all outcomes after adjusting for sex and birth year: any diagnosis (HR [95%CI]: 1.73 [1.67-1.80]), depression (1.93 [1.84-2.02]), anxiety (1.41[1.33-1.50]), stress-related disorders (1.75 [1.62-1.89]) and using antidepressants or anxiolytics (1.30 [1.26-1.34]). Familial co-aggregation was evaluated using Cox models, where an individual’s relative was regarded unexposed before the individual’s diabetes diagnosis and exposed after. Overall, higher risks of all outcomes were observed in relatives of individuals with diabetes and declined proportionally with decreasing genetic relatedness. Highest HRs were found in parents: any diagnosis (1.21 [1.16, 1.26]), depression (1.20 [1.13-1.26]), anxiety (1.22 [1.15, 1.30]), stress-related disorders (1.25 [1.17-1.34]) and using antidepressants or anxiolytics (1.18 [1.16, 1.21]). HRs decreased but remained significant in full-siblings after adjusting for sex and birth year of the sibling: any diagnosis (1.11 [1.05, 1.17]), depression (1.11 [1.03-1.19]), anxiety (1.10 [1.02, 1.1]), stress-related disorders (1.20 [1.08-1.32]) and using antidepressants or anxiolytics (1.05 [1.01, 1.09]). HRs decreased and were not significant in maternal and paternal half-siblings (HRs 0.90-1.10; 1.00-1.11), full-cousins (HRs 0.98-1.05) and half-cousins (HRs 0.80-1.02).Conclusion: Our findings support existing evidence that individuals with childhood-onset type 1 diabetes were at higher risks of depression, anxiety, stress-related disorders and using antidepressants and anxiolytics and suggest that familial liability may contribute to these associations. The results highlight the importance of family support integrated with pediatric diabetes care.
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| 10. |
- Liu, S. X., et al.
(författare)
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Association and Familial Coaggregation of Childhood-Onset Type 1 Diabetes With Depression, Anxiety, and Stress-Related Disorders: A Population-Based Cohort Study
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:9, s. 1987-1993
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To estimate the association and familial coaggregation of childhood-onset type 1 diabetes with depression, anxiety, and stress-related disorders. RESEARCH DESIGN AND METHODS This was a population-based cohort study with use of data from Swedish nationwide registers. A total of similar to 3.5 million individuals born in Sweden 1973-2007 were linked to their biological parents, full siblings and half-siblings, and cousins. Cox models were used to estimate the association and familial coaggregation of type 1 diabetes with depression, anxiety, and stress-related disorders. RESULTS Individuals diagnosed with childhood-onset type 1 diabetes (n = 20,005) were found to be at greater risks of all outcomes: any psychiatric diagnosis (adjusted hazard ratio [aHR] 1.66 [95% CI 1.59-1.72]) or specific diagnoses of depression (1.85 [1.76-1.94]), anxiety (1.41[1.33-1.50]), and stress-related disorders (1.75 [1.62-1.89]), as well as use of antidepressants or anxiolytics (1.30 [1.26-1.34]), compared with individuals without type 1 diabetes. Overall, relatives of individuals with type 1 diabetes were at elevated risks of developing these outcomes, with the highest risks seen in parents (aHRs 1.18-1.25), followed by full siblings (aHRs 1.05-1.20), and the magnitudes of risk estimates appear proportional to familial relatedness. CONCLUSIONS These results support existing evidence that children and adolescents with type 1 diabetes are at greater risks of developing depression, anxiety, and stress-related disorders and indicate that shared familial factors might contribute to these elevated risks. Our findings highlight the need for psychological consulting for children and their families in diabetes care. Quantitative and molecular genetic studies are warranted to further understand the etiology of these psychiatric disorders in type 1 diabetes.
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