Inter-hemispherical asymmetry in default-mode functional connectivity and BAIAP2 gene are associated with anger expression in ADHD adults

R Hasler; M G Preti; D E Meskaldji; J Prados; W Adouan; C Rodriguez; S Toma; N Hiller; T Ismaili; J Hofmeister; I Sinanaj; P Baud; S Haller; P Giannakopoulos; S Schwartz; N Perroud; D Van De Ville

doi:10.1016/j.pscychresns.2017.09.004

Inter-hemispherical asymmetry in default-mode functional connectivity and BAIAP2 gene are associated with anger expression in ADHD adults

Psychiatry Res Neuroimaging. 2017 Nov 30:269:54-61. doi: 10.1016/j.pscychresns.2017.09.004. Epub 2017 Sep 12.

Authors

R Hasler¹, M G Preti², D E Meskaldji³, J Prados⁴, W Adouan⁵, C Rodriguez⁶, S Toma⁶, N Hiller⁶, T Ismaili⁶, J Hofmeister⁷, I Sinanaj⁸, P Baud⁶, S Haller⁹, P Giannakopoulos¹⁰, S Schwartz¹¹, N Perroud¹⁰, D Van De Ville¹²

Affiliations

¹ Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland; Department of Psychiatry, University of Geneva, Switzerland; Department of Neuroscience, Faculty of Medicine of the University of Geneva, Switzerland.
² Department of Radiology and Medical Informatics, University of Geneva, Switzerland; Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Switzerland. Electronic address: maria.preti@epfl.ch.
³ Department of Radiology and Medical Informatics, University of Geneva, Switzerland; Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Switzerland; Institute of Mathematics, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
⁴ Department of Psychiatry, University of Geneva, Switzerland; Department of Neuroscience, Faculty of Medicine of the University of Geneva, Switzerland.
⁵ Department of Neuroscience, Faculty of Medicine of the University of Geneva, Switzerland.
⁶ Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland.
⁷ Department of Radiology and Medical Informatics, University of Geneva, Switzerland; Department of Neuroscience, Faculty of Medicine of the University of Geneva, Switzerland.
⁸ Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland; Department of Neuroscience, Faculty of Medicine of the University of Geneva, Switzerland; Swiss Center for Affective Studies, University of Geneva, Switzerland.
⁹ Department of Radiology and Medical Informatics, University of Geneva, Switzerland.
¹⁰ Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland; Department of Psychiatry, University of Geneva, Switzerland.
¹¹ Department of Psychiatry, University of Geneva, Switzerland.
¹² Department of Radiology and Medical Informatics, University of Geneva, Switzerland; Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Switzerland.

PMID: 28938222
DOI: 10.1016/j.pscychresns.2017.09.004

Abstract

Attention deficit hyperactivity disorder (ADHD) is accompanied by resting-state alterations, including abnormal activity, connectivity and asymmetry of the default-mode network (DMN). Concurrently, recent studies suggested a link between ADHD and the presence of polymorphisms within the gene BAIAP2 (i.e., brain-specific angiogenesis inhibitor 1-associated protein 2), known to be differentially expressed in brain hemispheres. The clinical and neuroimaging correlates of this polymorphism are still unknown. We investigated the association between BAIAP2 polymorphisms and DMN functional connectivity (FC) asymmetry as well as behavioral measures in ADHD adults. Resting-state fMRI was acquired from 30 ADHD and 15 healthy adults. For each subject, rs7210438 and rs8079626 within the gene BAIAP2 were genotyped. ADHD severity, impulsiveness and anger were assessed for the ADHD group. Using multivariate analysis of variance, we found that genetic features do have an impact on DMN FC asymmetry. In particular, polymorphism rs8079626 affects medial frontal gyrus and inferior parietal lobule connectivity asymmetry, lower for AA than AG/GG carriers. Further, when combining FC asymmetry and the presence of the rs8079626 variant, we successfully predicted increased externalization of anger in ADHD. In conclusion, a complex interplay between genetic vulnerability and inter-hemispherical DMN FC asymmetry plays a role in emotion regulation in adult ADHD.

Keywords: Attention deficit hyperactivity disorder; Behavioral measures; Default Mode Network; Gene polymorphism; Magnetic Resonance Imaging; Resting-state; fMRI.

MeSH terms

Adult
Anger / physiology*
Attention Deficit Disorder with Hyperactivity / diagnostic imaging*
Attention Deficit Disorder with Hyperactivity / genetics*
Brain Mapping / methods
Cerebrum / diagnostic imaging*
Cerebrum / physiology*
Female
Humans
Magnetic Resonance Imaging / methods
Male
Middle Aged
Nerve Net / diagnostic imaging
Nerve Tissue Proteins / genetics*
Neural Pathways / diagnostic imaging
Neural Pathways / physiology
Prefrontal Cortex / diagnostic imaging

Substances

BAIAP2 protein, human
Nerve Tissue Proteins