| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Zayats, T, et al.
(författare)
-
Exome chip analyses in adult attention deficit hyperactivity disorder
- 2016
-
Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 6:10
-
Tidskriftsartikel (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E-06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E-08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E-07); the PSD locus (P=7.58E-08) and ZCCHC4 locus (P=1.79E-06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E-05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.
|
|
| 5. |
- Ribasés, M., et al.
(författare)
-
Genetic Architecture of ADHD and Overlap With Other Psychiatric Disorders And Cognition-Related Phenotypes
- 2023
-
Ingår i: Neuroscience and Biobehavioral Reviews. - : Pergamon Press. - 0149-7634 .- 1873-7528. ; 153
-
Forskningsöversikt (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) co-occurs with many other psychiatric disorders and traits. In this review, we summarize and interpret the existing literature on the genetic architecture of these comorbidities based on hypothesis-generating approaches. Quantitative genetic studies indicate that genetic factors play a substantial role in the observed co-occurrence of ADHD with many different disorders and traits. Molecular genetic correlations derived from genome-wide association studies and results of studies based on polygenic risk scores confirm the general pattern but provide effect estimates that are smaller than those from twin studies. The identification of the specific genetic variants and biological pathways underlying co-occurrence using genome-wide approaches is still in its infancy. The first analyses of causal inference using genetic data support causal relationships between ADHD and comorbid disorders, although bidirectional effects identified in some instances point to complex relationships. While several issues in the methodology and inferences from the results are still to be overcome, this review shows that the co-occurrence of ADHD with many psychiatric disorders and traits is genetically interpretable.
|
|
| 6. |
- Rovira, P, et al.
(författare)
-
Shared genetic background between children and adults with attention deficit/hyperactivity disorder
- 2020
-
Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 1740-634X .- 0893-133X. ; 45:10, s. 1617-1626
-
Tidskriftsartikel (refereegranskat)abstract
- Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.
|
|
| 7. |
- Kobayashi, N.F., et al.
(författare)
-
Initiation of the European multicentre study “bipcom” to unravel medical comorbidities in bipolar disorder
- 2023
-
Ingår i: Neuroscience Applied. - : Elsevier. - 2772-4085. ; 2:Sup. 2
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Bipolar Disorder (BD) is a severe and heritable psychiatric disorder. It represents a substantial public health problem, due to its prevalence, its high degree of disability and psychiatric and somatic comorbidities, especially cardiometabolic disturbances. Such comorbidities pose a significant additive burden for patients with BD. Considering the clinical heterogeneity of these patients, a better characterization of this population is required to develop personalised treatment approaches.Objective: BIPCOM is a multicentre study funded by the EU within the ERAperMed Call, involving six centres from different countries (Italy, France, Germany, Norway, Spain, Sweden). The purpose of BIPCOM is to identify somatic comorbidities in BD patients to develop precision medicine approaches.Aims: BIPCOM aims to define the prevalence rates, risk and protective factors and the natural course of somatic comorbidities of BD patients. Those data will be integrated to develop a tool to support individualized clinical decision-making in BD.Method: BIPCOM comprises three separate clinical studies to define patient characteristics and a subsequent exploitation element. In the first study, data will be obtained from the Nordic biobanks and medical registries. In the second study, the study centres together will contribute standardized data of at least 1500 patients comprising 24 pre-specified variables (among others past and current comorbidities and treatment). Emphasis will be given to chronic somatic disorders (diabetes mellitus, metabolic syndrome, dyslipidaemia, obesity or endocrine disorders). The third study has a prospective element with in depth characterization of 400 patients including a one-year follow up with a focus on metabolic syndrome. Patients aged from 18 – 65 with a primary diagnosis of BD, who had at least one contact with mental health services in the last year will be included. A “patient schedule” will include each participant’s socio-demographic, clinical and treatment-related data at baseline (T0) and at 1-year follow-up (T1). Five aspects of metabolic syndrome (MetS, waist circumference, triglyceride level, HDL level, blood pressure and fasting glucose) will be determined and subjected to clustering analysis to identify common presentation dynamics. The primary objective of this part is to identify the strongest criteria for the MetS diagnosis at T0 and/orT1 in patients with BD. Moreover, at least 20 patients per site stratified in MetS+ and MetS-, will receive in depth physical activity determinations. For this, patients will be asked to wear accelerometers for one week 3 times a year, to determine physical activity, sedentary time and circadian rhythms. With this data the association between activity and selected clinical markers will be determined. Ultimately, the data of the three studies will be integrated to aid patient care in BD by means of a clinical support tool.Conclusions: The results of BIPCOM will provide a better understanding of the somatic comorbidities in patients with BD. Focussing especially on MetS the data will help to predict the occurrence of comorbidities to assist physicians in the management of these patients. Ultimately, BIPCOM aims to improve comorbidity management, prevention, early detection and effective treatment of somatic disorders in patients with BD.
|
|
| 8. |
|
|
| 9. |
- Hartman, Catharina A, et al.
(författare)
-
Anxiety, mood, and substance use disorders in adult men and women with and without Attention-Deficit/Hyperactivity Disorder : a substantive and methodological overview
- 2023
-
Ingår i: Neuroscience and Biobehavioral Reviews. - : Pergamon Press. - 0149-7634 .- 1873-7528. ; 151
-
Forskningsöversikt (refereegranskat)abstract
- Knowledge on psychiatric comorbidity in adult ADHD is essential for prevention, detection, and treatment of these conditions. This review (1) focuses on large studies (n> 10,000; surveys, claims data, population registries) to identify (a) overall, (b) sex- and (c) age-specific patterns of comorbidity of anxiety disorders (ADs), major depressive disorder (MDD), bipolar disorder (BD) and substance use disorders (SUDs) in adults with ADHD relative to adults without ADHD; and (2) describes methodological challenges relating to establishing comorbidity in ADHD in adults as well as priorities for future research. Meta-analyses (ADHD: n=550,748; no ADHD n=14,546,814) yielded pooled odds ratios of 5.0(CI:3.29-7.46) for AD, 4.5(CI:2.44-8.34) for MDD, 8.7(CI:5.47-13.89) for BD and 4.6(CI:2.72-7.80) for SUDs, indicating strong differences in adults with compared to adults without ADHD. Moderation by sex was not found: high comorbidity held for both men and women with sex-specific patterns as in the general population: higher prevalences of ADs, MDD and BD in women and a higher prevalence of SUDs in men. Insufficient data on different phases of the adult lifespan prevented conclusions on developmental changes in comorbidity. We discuss methodological challenges, knowledge gaps, and future research priorities.
|
|
| 10. |
- Kittel-Schneider, Sarah, et al.
(författare)
-
Non-mental diseases associated with ADHD across the lifespan : Fidgety Philipp and Pippi Longstocking at risk of multimorbidity?
- 2022
-
Ingår i: Neuroscience and Biobehavioral Reviews. - : Pergamon Press. - 0149-7634 .- 1873-7528. ; 132, s. 1157-1180
-
Forskningsöversikt (refereegranskat)abstract
- Several non-mental diseases seem to be associated with an increased risk of ADHD and ADHD seems to be associated with increased risk for non-mental diseases. The underlying trajectories leading to such brain-body co-occurrences are often unclear - are there direct causal relationships from one disorder to the other, or does the sharing of genetic and/or environmental risk factors lead to their occurring together more frequently or both? Our goal with this narrative review was to provide a conceptual synthesis of the associations between ADHD and non-mental disease across the lifespan. We discuss potential shared pathologic mechanisms and genetic background and treatments in co-occurring diseases. For those co-occurrences for which published studies with sufficient sample sizes exist, meta-analyses have been published by others and we discuss those in detail. We conclude that non-mental diseases are common in ADHD and vice versa and add to the disease burden of the patient across the lifespan. Insufficient attention to such co-occurring conditions may result in missed diagnoses and suboptimal treatment in the affected individuals.
|
|
