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Shared alterations in resting-state brain connectivity in adults with attention-deficit/hyperactivity disorder and their unaffected first-degree relatives.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Pironti, Valentino Antonio 
Sahakian, Barbara Jacquelyn 

Abstract

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a developmental condition that often persists into adulthood with extensive negative consequences on quality of life. Despite emerging evidence indicating the genetic basis of ADHD, investigations into the familial expression of latent neurocognitive traits remain limited. METHODS: In a group of adult ADHD probands (n = 20), their unaffected first-degree relatives (n = 20) and typically developing control participants (n = 20), we assessed endophenotypic alterations in the default mode network (DMN) connectivity during resting-state functional magnetic resonance imaging in relation to cognitive performance and clinical symptoms. In an external validation step, we also examined the dimensional nature of this neurocognitive trait in a sample of unrelated healthy young adults (n = 100) from the Human Connectome Project (HCP). RESULTS: The results illustrated reduced anti-correlations between the posterior cingulate cortex/precuneus and right middle frontal gyrus that was shared between adult ADHD probands and their first-degree relatives, but not with healthy controls. The observed connectivity alterations were linked to higher ADHD symptoms that was mediated by performance in a sustained attention task. Moreover, this brain-based neurocognitive trait dimensionally explained ADHD symptom variability in the HCP sample. CONCLUSIONS: Alterations in the default mode connectivity may represent a dimensional endophenotype of ADHD, hence a significant aspect of the neuropathophysiology of this disorder. As such, brain network organisation can potentially be employed as an important neurocognitive trait to enhance statistical power of genetic studies in ADHD and as a surrogate efficacy endpoint in the development of novel pharmaceuticals.

Description

Keywords

Attention-deficit/hyperactivity disorder, default mode network, dimensional, endophenotype, functional connectivity, resting state, sustained attention, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Brain, Case-Control Studies, Connectome, Endophenotypes, Family, Female, Frontal Lobe, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Neural Pathways, Parietal Lobe, Quality of Life, Young Adult

Journal Title

Psychol Med

Conference Name

Journal ISSN

0033-2917
1469-8978

Volume Title

51

Publisher

Cambridge University Press (CUP)
Sponsorship
Medical Research Council (G1000183)
Wellcome Trust (093875/Z/10/Z)