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Novel Dimensional Approach Uncovers Biomarker for Inattention

Summary: Greater variability in reaction time is associated with reduced gray matter volume in the ventromedial prefrontal cortex, a new study reports.

Source: Larner College of Medicine.

Despite diagnoses for attention-deficit/hyperactivity disorder (ADHD) occurring in a reported 11 percent of U.S. school-aged kids, clinicians still don’t fully understand the underlying causes of this common condition. Now a brain marker may be on the horizon, thanks to a new approach that provides evidence of a relationship between brain structure and dimensional measures of ADHD symptoms. The study’s results are reported in an Article in Press in Biological Psychiatry.

Using data from the IMAGEN study, researchers, including Matthew Albaugh, Ph.D., from the Larner College of Medicine at the University of Vermont (UVM), took a multi-informant approach to investigate whether or not dimensional measures of ADHD symptoms and brain imaging data could shed new light on the root source of ADHD’s symptoms, including inattention, hyperactivity and impulsivity. Their work represents the largest structural imaging study to date on ADHD symptoms in adolescents.

“Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples,” say Albaugh and the study’s authors, who rather than taking what is called a “categorical” approach – a comparison of ADHD patients and controls – took a quantitative, dimensional, multi-informant approach. This method dovetails with work done by UVM’s Thomas Achenbach, Ph.D., and colleagues, revealing aspects of dimensionality with regard to many psychiatric conditions, including ADHD.

“It’s not whether or not one has attention problems, it is the degree to which one is inattentive,” says Albaugh.

For the study, Albaugh and his colleagues examined psychopathology and imaging data from 1538 adolescents. The data included parent ratings of ADHD symptoms collected through the Strengths and Difficulties Questionnaire (SDQ), and self-reports from the adolescents in the study through the youth version of the SDQ. The team also derived ADHD symptom counts from parent interviews – and then related ADHD symptom counts to brain structure.

When they overlaid the imaging results from all of their analyses – using behavioral questionnaire data and symptom counts – they found an anatomical region of convergence; ADHD symptomatology reported by parents and adolescents was related to reduced gray matter volume in an area of the prefrontal cortex, the ventromedial prefrontal cortex (vmPFC). This relationship was particularly true for symptoms of inattention.

Image shows brain scans of people with ADHD.

The figure on the left illustrates the overlap between the ADHD symptom count from parent interview (red), Hyperactive/Inattentive score on parent questionnaire (green), and Hyperactive/Inattentive score on youth self-report (blue) in axial MRI image view. Age, gender, total gray matter volume, site, pubertal development, Performance IQ, Verbal IQ, and socio-economic status were controlled for in all analyses. The figure on the right depicts the region of convergence across all measures, including reaction time variability, in axial view. NeuroscienceNews.com image is credited to Matthew Albaugh, Ph.D.

The team also found that this area of anatomical convergence was related to an objective behavioral measure of attention that has been previously associated with ADHD, reaction time variability. Past research by others has shown that ADHD youths exhibit more variability in their response times, and this is believed to reflect inattention and distractibility. Albaugh and colleagues found that greater variability in reaction time was associated with reduced volume in the the vmPFC.

The connection of reduced vmPFC volume to inattention sets the stage for follow-up research, says Albaugh, who believes these findings could affect future ADHD interventions to strengthen this region of the brain. The work may also help to identify which youth go on to experience elevated symptom levels later in adulthood.

“We are finding that volume in this brain area predicts symptom change from adolescence to adulthood,” says Albaugh. “It’s exciting to think that, down the road, there might be real clinical utility to these results.”

About this neuroscience research article

Funding: This work was funded by European Union, Consortium on Vulnerability to Externalizing Disorders and Addictions, VR, FORTE, FORMAS, Medical Research Council, Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge.

Source: Jennifer Nachbur – Larner College of Medicine
Image Source: NeuroscienceNews.com image is credited to Matthew Albaugh, Ph.D.
Original Research: Abstract for “Inattention and Reaction Time Variability Are Linked to Ventromedial Prefrontal Volume in Adolescents” by Matthew D. Albaugh’Correspondence information about the author Matthew D. Albaugh, Catherine Orr, Bader Chaarani, Robert R. Althoff, Nicholas Allgaier, Nicholas D’Alberto, Kelsey Hudson, Scott Mackey, Philip A. Spechler, Tobias Banaschewski, Rüdiger Brühl, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Anna Cattrell, Patricia J. Conrod, Sylvane Desrivières, Herta Flor, Vincent Frouin, Jürgen Gallinat, Robert Goodman, Penny Gowland, Yvonne Grimmer, Andreas Heinz, Viola Kappel, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Jani Penttila¨, Luise Poustka, Tomáš Paus, Michael N. Smolka, Maren Struve, Henrik Walter, Robert Whelan, Gunter Schumann, Hugh Garavan, and Alexandra S. Potter in Biological Psychiatry. Published online January 14 2017 doi:10.1016/j.biopsych.2017.01.003

Cite This NeuroscienceNews.com Article
Larner College of Medicine “Novel Dimensional Aproach Uncovers Biomarker for Inattention.” NeuroscienceNews. NeuroscienceNews, 8 March 2017.
<http://neurosciencenews.com/inattention-biomarker-6216/>.
Larner College of Medicine (2017, March 8). Novel Dimensional Aproach Uncovers Biomarker for Inattention. NeuroscienceNew. Retrieved March 8, 2017 from http://neurosciencenews.com/inattention-biomarker-6216/
Larner College of Medicine “Novel Dimensional Aproach Uncovers Biomarker for Inattention.” http://neurosciencenews.com/inattention-biomarker-6216/ (accessed March 8, 2017).

Abstract

Inattention and Reaction Time Variability Are Linked to Ventromedial Prefrontal Volume in Adolescents

Background
Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have most commonly reported volumetric abnormalities in the basal ganglia, cerebellum, and prefrontal cortices. Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples. We investigated the relationship between dimensional measures of ADHD symptomatology, brain structure, and reaction time variability—an index of lapses in attention. We also tested for associations between brain structural correlates of ADHD symptomatology and maps of dopaminergic gene expression.

Methods
Psychopathology and imaging data were available for 1538 youths. Parent ratings of ADHD symptoms were obtained using the Development and Well-Being Assessment and the Strengths and Difficulties Questionnaire (SDQ). Self-reports of ADHD symptoms were assessed using the youth version of the SDQ. Reaction time variability was available in a subset of participants. For each measure, whole-brain voxelwise regressions with gray matter volume were calculated.

Results

Parent ratings of ADHD symptoms (Development and Well-Being Assessment and SDQ), adolescent self-reports of ADHD symptoms on the SDQ, and reaction time variability were each negatively associated with gray matter volume in an overlapping region of the ventromedial prefrontal cortex. Maps of DRD1 and DRD2 gene expression were associated with brain structural correlates of ADHD symptomatology.

Conclusions

This is the first study to reveal relationships between ventromedial prefrontal cortex structure and multi-informant measures of ADHD symptoms in a large population-based sample of adolescents. Our results indicate that ventromedial prefrontal cortex structure is a biomarker for ADHD symptomatology. These findings extend previous research implicating the default mode network and dopaminergic dysfunction in ADHD.

“Inattention and Reaction Time Variability Are Linked to Ventromedial Prefrontal Volume in Adolescents” by Matthew D. Albaugh’Correspondence information about the author Matthew D. Albaugh, Catherine Orr, Bader Chaarani, Robert R. Althoff, Nicholas Allgaier, Nicholas D’Alberto, Kelsey Hudson, Scott Mackey, Philip A. Spechler, Tobias Banaschewski, Rüdiger Brühl, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Anna Cattrell, Patricia J. Conrod, Sylvane Desrivières, Herta Flor, Vincent Frouin, Jürgen Gallinat, Robert Goodman, Penny Gowland, Yvonne Grimmer, Andreas Heinz, Viola Kappel, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Jani Penttila¨, Luise Poustka, Tomáš Paus, Michael N. Smolka, Maren Struve, Henrik Walter, Robert Whelan, Gunter Schumann, Hugh Garavan, and Alexandra S. Potter in Biological Psychiatry. Published online January 14 2017 doi:10.1016/j.biopsych.2017.01.003

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