scholarly journals Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures

2019 ◽  
Author(s):  
Nina Roth Mota ◽  
Geert Poelmans ◽  
Marieke Klein ◽  
Bàrbara Torrico ◽  
Noèlia Fernàndez-Castillo ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Circadian Rhythm ◽  
Attention Deficit ◽  
Gwas Data ◽  
Overlapping Genes ◽  
Biological Mechanisms ◽  
Brain Volumes ◽  
Dopaminergic Neurotransmission ◽  
Hyperactivity Disorder ◽  
Genome Wide

ABSTRACTAttention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N=53,293, N=681,275, and N=98,697, respectively). We then conducted genome-wide ADHD-BMI and ADHD-obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD-BMI overlapping genes with brain volumes (primary GWAS data N=10,720–10,928; replication data N=9,428). The dopaminergic gene set was associated with both ADHD (P=5.81×10−3) and BMI (P=1.63×10−5), the circadian rhythm was associated with BMI (P=1.28×10−3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD-BMI and ADHD-obesity results. The ADHD-BMI overlapping genes were associated with putamen volume (P=7.7×10−3; replication data P=3.9×10−2) – a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD-obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.

scholarly journals Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures

2020 ◽  
Vol 45 (7) ◽  
pp. 1188-1195 ◽  
Author(s):  
Nina Roth Mota ◽  
Geert Poelmans ◽  
Marieke Klein ◽  
Bàrbara Torrico ◽  
Noèlia Fernàndez-Castillo ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Circadian Rhythm ◽  
Attention Deficit ◽  
Gwas Data ◽  
Overlapping Genes ◽  
Biological Mechanisms ◽  
Brain Volumes ◽  
Dopaminergic Neurotransmission ◽  
Hyperactivity Disorder ◽  
Genome Wide

AbstractAttention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N = 53,293, N = 681,275, and N = 98,697, respectively). We then conducted genome-wide ADHD–BMI and ADHD–obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD–BMI overlapping genes with brain volumes (primary GWAS data N = 10,720–10,928; replication data N = 9428). The dopaminergic gene set was associated with both ADHD (P = 5.81 × 10−3) and BMI (P = 1.63 × 10−5); the circadian rhythm was associated with BMI (P = 1.28 × 10−3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD–BMI and ADHD–obesity results. The ADHD–BMI overlapping genes were associated with putamen volume (P = 7.7 × 10−3; replication data P = 3.9 × 10−2)—a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD–obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.

Schizophrenia, Parkinson’s disease, and attention deficit hyperactivity disorder

2018 ◽  
Author(s):  
Richard J. Beninger
Keyword(s):  
Parkinson’S Disease ◽  
Attention Deficit Hyperactivity Disorder ◽  
Parkinson's Disease ◽  
Attention Deficit ◽  
Antipsychotic Treatment ◽  
Incentive Learning ◽  
Dopaminergic Drugs ◽  
Dopaminergic Neurotransmission ◽  
Hyperactivity Disorder ◽  
Incentive Value

Schizophrenia, Parkinson’s disease, and attention deficit hyperactivity disorder (ADHD) discusses how hyperactive dopaminergic neurotransmission appears to underlie schizophrenia’s positive symptoms, loss of dopaminergic neurons in adulthood leads to Parkinson’s disease, and dopamine neuron hypofunction in childhood and adolescence may underlie ADHD. Positive schizophrenia symptoms may arise from excessive incentive learning that is gradually lost with antipsychotic treatment. Declarative learning and memory may contribute to delusions based on excessive incentive learning. Loss of responsiveness to environmental stimuli in Parkinson’s may result from a decrease of their conditioned incentive value and inverse incentive learning. Conditioned incentive stimuli not encountered while in a state of decreased dopaminergic neurotransmission may retain their incentive value, producing apparent kinesia paradoxa. Dopamine hypofunction in juveniles does not lead to hypokinesia but may result in loss of incentive learning that focuses attention. Pro-dopaminergic drugs have a calming effect in ADHD, presumably because they reinstate normal incentive learning.

625 The association between circadian rhythms and psychosocial functioning in children with attention deficit hyperactivity disorder

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A245-A245
Author(s):  
Xiao Li ◽  
Ka Sin Caroline Shea ◽  
Lok Fan Lau ◽  
Ching Kwong Dino Wong ◽  
Waiyan Vivian Chiu ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Circadian Rhythm ◽  
Attention Deficit ◽  
Psychosocial Functioning ◽  
Emotional Problems ◽  
Activity Level ◽  
Adhd Symptoms ◽  
Children With Adhd ◽  
Hyperactivity Disorder ◽  
Rest Activity

Abstract Introduction Circadian rhythm disturbances, including delayed circadian rhythm and increased motor activity, are commonly seen in attention-deficit hyperactivity disorder (ADHD). Previous research suggested a link between circadian rhythm disturbances and poor psychosocial functioning in children, but such a relationship has not been examined in children with ADHD. This study aimed at examining the association between circadian-related parameters and psychosocial functioning in children with ADHD. Methods Seventy-nine children with ADHD were recruited into this study (age range: 6–12 years, 75.9% male). They were assessed by parent-report questionnaires on sleep problems (Children’s Sleep Habits Questionnaire, CSHQ), ADHD symptoms (Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour Scale, SWAN), and psychosocial functioning (Strengths and Difficulties Questionnaire, SDQ). Actigraphic data collected for seven consecutive days were analyzed using parametric and nonparametric methods. The relationship between circadian parameters and psychosocial functioning was analyzed using multiple regression while controlling for age, sex, ADHD medication, total sleep time, and CSHQ total score. Results Later acrophase was significantly associated with higher scores on SDQ emotional problems (St. β = 0.30, p = 0.03) and SWAN inattention subscale (St. β = 0.27, p = 0.043). Lower relative amplitude was associated with higher scores on SDQ hyperactivity symptoms (St. β = -0.29, p = 0.045) and SDQ total difficulties (St. β = -0.31, p = 0.036). Higher levels of mean activity level during the least active 5-h period (L5) were related to higher scores on SDQ peer problems (St. β = 0.38, p = 0.021), SDQ internalizing problems (St. β = 0.38, p = 0.020) and SDQ total difficulties (St. β = 0.33, p = 0.036). Later onset of L5 was associated with increased SDQ emotional problems (St. β = 0.26, p = 0.046). Conclusion Circadian rest-activity rhythm disturbances (delayed phase, blunted rest-activity rhythms, higher level of nocturnal activity, and later onset of nocturnal rest) were associated with poor psychosocial functioning in children with ADHD. Further longitudinal studies are needed to examine the effects of circadian disruption on psychosocial functioning in children with ADHD. Support (if any) This work was supported by the Health and Medical Research Fund (Project No.: 30160604).

scholarly journals A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts

2016 ◽  
Vol 55 (10) ◽  
pp. 896-905.e6 ◽  
Author(s):  
Christel M. Middeldorp ◽  
Anke R. Hammerschlag ◽  
Klaasjan G. Ouwens ◽  
Maria M. Groen-Blokhuis ◽  
Beate St. Pourcain ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Meta Analysis ◽  
Population Based ◽  
Genome Wide Association ◽  
Hyperactivity Disorder ◽  
Genome Wide ◽  
A Genome

scholarly journals Meta-analysis of genome-wide linkage scans of attention deficit hyperactivity disorder

2008 ◽  
Vol 147B (8) ◽  
pp. 1392-1398 ◽  
Author(s):  
Kaixin Zhou ◽  
Astrid Dempfle ◽  
Mauricio Arcos-Burgos ◽  
Steven C. Bakker ◽  
Tobias Banaschewski ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Meta Analysis ◽  
Hyperactivity Disorder ◽  
Genome Wide

Implications of ADHD for Learning

1996 ◽  
Vol 13 (1) ◽  
pp. 24-28 ◽  
Author(s):  
Margot Prior
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Early Intervention ◽  
Attention Deficit ◽  
Learning Difficulties ◽  
Behaviour Problems ◽  
Reading Problems ◽  
Biological Mechanisms ◽  
Hyperactivity Disorder ◽  
Current Emphasis

AbstractMany different reasons may account for the well documented relationship between attention deficit hyperactivity disorder and learning difficulties. Longitudinal Australian data support the earlier occurrence of behaviour problems than reading problems, especially for boys. Language, motivation, and biological mechanisms, and combinations of these factors, may contribute to this association. Current emphasis must be placed on early intervention for behaviour problems, assessment of LDs which are suspected by the Grade 2 or 7-year-old level, and a long-term perspective on the management of both conditions.

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