White matter microstructure is associated with hyperactive/inattentive symptomatology and polygenic risk for attention-deficit/hyperactivity disorder in a population-based sample of adolescents

Albaugh, Matthew D.; Hudziak, James J.; Ing, Alex; Chaarani, Bader; Barker, Edward D.; Jia, Tianye; Lemaître, Hervé; Watts, Richard; Orr, Catherine; Spechler, Philip A.; Lepage, Claude; Fonov, Vladimir; Collins, D. Louis; Rioux, Pierre; Evans, Alan C.; Banaschewski, Tobias; Bokde, Arun L.W.; Bromberg, Uli; Büchel, Christian; Quinlan, Erin Burke; Desrivières, Sylvane; Flor, Herta; Frouin, Vincent; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Martinot, Jean Luc; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Paus, Tomáš; Poustka, Luise; Fröhner, Juliane H.; Smolka, Michael N.; Walter, Henrik; Whelan, Robert; Schumann, Günter; Garavan, Hugh; Potter, Alexandra

doi:10.1038/s41386-019-0383-y

Cited by 25 publications

(26 citation statements)

References 49 publications

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“…At baseline (age 13À14 years), assessment of psychopathology for the participants was conducted using the Development and Well-Being Assessment (DAWBA), 29 which is a computer-based composite of questionnaires, interviews, and rating scales designed to generate ICD and DSM psychiatric diagnoses on children and adolescents. As in prior investigations, 30,31 ADHD symptom severity scores were derived from the parent version of the DAWBA, which provides a total score and separate scores for both Hyperactivity/Impulsivity and Inattention. Additional assessments for possible mood, anxiety, and other symptomatology were also assessed using DAWBA, which is a reliable and valid measure of youth emotional and behavior symptoms.…”

Section: Sample Characteristics and Behavioral Measuresmentioning

confidence: 99%

Substance Use Initiation, Particularly Alcohol, in Drug-Naive Adolescents: Possible Predictors and Consequences From a Large Cohort Naturalistic Study

Ivanov¹,

Parvaz²,

Velthorst³

et al. 2021

Journal of the American Academy of Child & Adolescent Psych

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It is unclear whether deviations in brain and behavioral development, which may underpin elevated substance use during adolescence, are predispositions for or consequences of substance use initiation. Here, we examine behavioral and neuroimaging indices at early and mid-adolescence in drug-naive youths to identify possible predisposing factors for substance use initiation and its possible consequences. Method: Among 304 drug-naive adolescents at baseline (age 14 years) from the IMAGEN dataset, 83 stayed drug-naive, 133 used alcohol on 1 to 9 occasions, 42 on 10 to 19 occasions, 27 on 20 to 39 occasions, and 19 on >40 occasions at follow-up (age 16 years). Baseline measures included brain activation during the Monetary Incentive Delay task. Data at both baseline and follow-up included measures of trait impulsivity and delay discounting. Results: From baseline to follow-up, impulsivity decreased in the 0 and 1-to 9-occasions groups (p < .004), did not change in the 10-to 19-occasions and 20-to 29-occasions groups (p > .294), and uncharacteristically increased in the >40-occasions group (p ¼ .046). Furthermore, blunted medial orbitofrontal cortex activation during reward outcome at baseline significantly predicted higher alcohol use frequency at follow-up, above and beyond behavioral and clinical variables (p ¼ .008). Conclusion:These results suggest that the transition from no use to frequent drinking in early to mid-adolescence may disrupt normative developmental changes in behavioral control. In addition, blunted activity of the medial orbitofrontal cortex during reward outcome may underscore a predisposition toward the development of more severe alcohol use in adolescents. This distinction is clinically important, as it informs early intervention efforts in preventing the onset of substance use disorder in adolescents.

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Section: Sample Characteristics and Behavioral Measuresmentioning

confidence: 99%

Substance Use Initiation, Particularly Alcohol, in Drug-Naive Adolescents: Possible Predictors and Consequences From a Large Cohort Naturalistic Study

Ivanov¹,

Parvaz²,

Velthorst³

et al. 2021

Journal of the American Academy of Child & Adolescent Psych

Self Cite

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“…The Strengths and Difficulties Questionnaire (SDQ), assessed at both baseline and follow-up in IMAGEN, is a validated assessment tool for mental health problems in youth (30), and has been demonstrated to be a promising assessment for ADHD symptoms in IMAGEN (31)(32)(33)(34). The hyperactivity-inattention subscale is composed of 5 items covering 3 key symptom domains for ADHD with the internal consistency (Cronbach's α=0.…”

Section: Adhdmentioning

confidence: 99%

Neural Correlates of the Dual-Pathway Model for ADHD in Adolescents

Shen

Luo

Jia

et al. 2020

AJP

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The dual pathway model has been proposed to explain the heterogeneity in symptoms of attention-deficit/hyperactivity disorder (ADHD) by two independent psychological pathways based on distinct brain circuits. The authors aimed to test whether the hypothesized cognitive and motivational pathways had separable neural correlates.Method: Using a longitudinally community-based cohort of 1,963 adolescents, the neuroanatomical correlates of ADHD were identified by a voxel-wise association analysis, and then validated using an independent clinical sample (99 never-medicated patients with ADHD, 56 medicated patients with ADHD and 267 heathy controls). The cognitive and motivational pathways were assessed by neuropsychological tests of working memory (WM), intra-subject variability (ISV), stop signal reaction time and delay discounting (DD). The associations were tested between the identified neuroanatomical correlates and both the ADHD symptoms 2 years later and the polygenic risk score for ADHD.Results: Gray matter volumes (GMV) of both a prefrontal cluster and a posterior-occipital cluster were negatively associated with inattention. Compared with healthy controls, never-medicated, but not medicated patients had significantly lower GMVs in these two clusters. WM and ISV were associated with the posterior-occipital cluster while DD was independently associated with both clusters. The baseline GMV of the posterior-occipital cluster predicted the inattention symptoms in a 2-year followup and was associated with the genetic risk for ADHD. Conclusions:The dual pathway model has both shared and separable neuroanatomical correlates, and the shared correlate in the occipital cortex has a potential to serve as an imaging trait marker of ADHD, especially the inattention symptom domain.

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“…Indeed, the polygenic risk score (PRS) analysis summarizing statistically all the SNP results from a large genome-wide association study (GWAS) has shown some promising results 50 . For example, ADHD-PRS was found to associate with symptoms of hyperactivity-impulsivity and to be mediated by white matter microstructure in brain regions that have been suggested to have a role in ADHD pathology 51 , 52 . In addition, ADHD-PRS was found to predict educational achievement 53 , to be linked with the severity of the clinical profile in those with high PRS 54 , and even to predict MPH response 55 .…”

Section: Introductionmentioning

confidence: 99%

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

et al. 2020

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Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric neurodevelopmental disorders in children and adolescents. Although ADHD has been studied for nearly a century, the cause and pathophysiology of ADHD is yet largely unknown. However, findings from previous studies have resulted in the formation of a new hypothesis: Apart from the well-known multifactorial etiology of ADHD, recent evidence suggests that the interaction between genetic and environmental factors and especially Wnt- and mTOR-signaling pathways might have an important role in the pathophysiology of ADHD. The Wnt-signaling pathway is known to orchestrate cellular proliferation, polarity, and differentiation, and the mTOR pathway is involved in several significant processes of neurodevelopment and synaptic plasticity. As a result, dysregulations of these pathways in a time-dependent manner could lead to neurodevelopmental delays, resulting in ADHD phenotype. This review presents further evidence supporting our hypothesis by combining results from studies on ADHD and Wnt- or mTOR-signaling and the influence of genetics, methylphenidate treatment, Omega-3 supplementation, and stress.

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White matter microstructure is associated with hyperactive/inattentive symptomatology and polygenic risk for attention-deficit/hyperactivity disorder in a population-based sample of adolescents

Cited by 25 publications

References 49 publications

Substance Use Initiation, Particularly Alcohol, in Drug-Naive Adolescents: Possible Predictors and Consequences From a Large Cohort Naturalistic Study

Substance Use Initiation, Particularly Alcohol, in Drug-Naive Adolescents: Possible Predictors and Consequences From a Large Cohort Naturalistic Study

Neural Correlates of the Dual-Pathway Model for ADHD in Adolescents

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

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