Genomic patterns linked to gray matter alterations underlying working memory deficits in adults and adolescents with attention-deficit/hyperactivity disorder

被引：3

作者：

Duan, Kuaikuai ^{[1
,2
]}

Chen, Jiayu ^{[2
,3
]}

Calhoun, Vince D. D. ^{[1
,2
,3
,4
]}

Jiang, Wenhao ^{[4
]}

Rootes-Murdy, Kelly ^{[4
]}

Schoenmacker, Gido ^{[5
]}

Silva, Rogers F. F. ^{[2
]}

Franke, Barbara ^{[5
,6
]}

Buitelaar, Jan K. K. ^{[7
]}

Hoogman, Martine ^{[5
,6
]}

Oosterlaan, Jaap ^{[8
]}

Hoekstra, Pieter J. J. ^{[9
]}

Heslenfeld, Dirk ^{[10
]}

Hartman, Catharina A. A. ^{[11
]}

Sprooten, Emma ^{[7
]}

Arias-Vasquez, Alejandro ^{[5
,6
]}

Turner, Jessica A. A. ^{[2
,4
]}

Liu, Jingyu ^{[2
,3
]}

机构：

[1] Georgia Inst Technol, Dept Elect & Comp Engn, Atlanta, GA USA

[2] Triinst Ctr Translat Res Neuroimaging & Data Sci T, Atlanta, GA 30303 USA

[3] Georgia State Univ, Dept Comp Sci, Atlanta, GA 30302 USA

[4] Georgia State Univ, Dept Psychol, Atlanta, GA USA

[5] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Human Genet, Med Ctr, Nijmegen, Netherlands

[6] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Psychiat, Med Ctr, Nijmegen, Netherlands

[7] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Med Ctr, Nijmegen, Netherlands

[8] Vrije Univ Amsterdam, Dept Clin Neuropsychol, Amsterdam, Netherlands

[9] Univ Groningen, Univ Med Ctr Groningen, Dept Child & Adolescent Psychiat, Groningen, Netherlands

[10] Vrije Univ Amsterdam, Fac Behav & Movement Sci, Amsterdam, Netherlands

[11] Univ Groningen, Dept Psychiat, Groningen, Netherlands

来源：

TRANSLATIONAL PSYCHIATRY | 2023年 / 13卷 / 01期

基金：

美国国家卫生研究院;

关键词：

AGE-OF-ONSET; FOLLOW-UP; HYPERACTIVITY DISORDER; TRANSCRIPTION FACTOR; EXECUTIVE FUNCTION; VOLUME REDUCTIONS; BRAIN-DEVELOPMENT; YOUNG-ADULTS; ADHD; METAANALYSIS;

D O I：

10.1038/s41398-023-02349-x

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder, with onset in childhood and a considerable likelihood to persist into adulthood. Our previous work has identified that across adults and adolescents with ADHD, gray matter volume (GMV) alteration in the frontal cortex was consistently associated with working memory underperformance, and GMV alteration in the cerebellum was associated with inattention. Recent knowledge regarding ADHD genetic risk loci makes it feasible to investigate genomic factors underlying these persistent GMV alterations, potentially illuminating the pathology of ADHD persistence. Based on this, we applied a sparsity-constrained multivariate data fusion approach, sparse parallel independent component analysis, to GMV variations in the frontal and cerebellum regions and candidate risk single nucleotide polymorphisms (SNPs) data from 341 unrelated adult participants, including 167 individuals with ADHD, 47 unaffected siblings, and 127 healthy controls. We identified one SNP component significantly associated with one GMV component in superior/middle frontal regions and replicated this association in 317 adolescents from ADHD families. The association was stronger in individuals with ADHD than in controls, and stronger in adults and older adolescents than in younger ones. The SNP component highlights 93 SNPs in long non-coding RNAs mainly in chromosome 5 and 21 protein-coding genes that are significantly enriched in human neuron cells. Eighteen identified SNPs have regulation effects on gene expression, transcript expression, isoform percentage, or methylation level in frontal regions. Identified genes highlight MEF2C, CADM2, and CADPS2, which are relevant for modulating neuronal substrates underlying high-level cognition in ADHD, and their causality effects on ADHD persistence await further investigations. Overall, through a multivariate analysis, we have revealed a genomic pattern underpinning the frontal gray matter variation related to working memory deficit in ADHD.

引用

页数：10

共 99 条

[1] Postnatal Loss of Mef2c Results in Dissociation of Effects on Synapse Number and Learning and Memory [J].

Adachi, Megumi ;

Lin, Pei-Yi ;

Pranav, Heena ;

Monteggia, Lisa M. .

BIOLOGICAL PSYCHIATRY, 2016, 80 (02) :140-148

[2] Evaluation of the Persistence, Remission, and Emergence of Attention-Deficit/Hyperactivity Disorder in Young Adulthood [J].

Agnew-Blais, Jessica C. ;

Polanczyk, Guilherme V. ;

Danese, Andrea ;

Wertz, Jasmin ;

Moffitt, Terrie E. ;

Arseneault, Louise .

JAMA PSYCHIATRY, 2016, 73 (07) :713-720

[3] Common obesity risk alleles in childhood attention-deficit/hyperactivity disorder [J].

Albayrak, Oezguer ;

Puetter, Carolin ;

Volckmar, Anna-Lena ;

Cichon, Sven ;

Hoffmann, Per ;

Noethen, Markus M. ;

Joeckel, Karl-Heinz ;

Schreiber, Stefan ;

Wichmann, H-Erich ;

Faraone, Stephen V. ;

Neale, Benjamin M. ;

Herpertz-Dahlmann, Beate ;

Lehmkuhl, Gerd ;

Sinzig, Judith ;

Renner, Tobias J. ;

Romanos, Marcel ;

Warnke, Andreas ;

Lesch, Klaus-Peter ;

Reif, Andreas ;

Schimmelmann, Benno G. ;

Scherag, Andre ;

Hebebrand, Johannes ;

Hinney, Anke .

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2013, 162B (04) :295-305

[4] Attention-Deficit/Hyperactivity Disorder (ADHD) and Working Memory in Adults: A Meta-Analytic Review [J].

Alderson, R. Matt ;

Kasper, Lisa J. ;

Hudec, Kristen L. ;

Patros, Connor H. G. .

NEUROPSYCHOLOGY, 2013, 27 (03) :287-302

[5]

American Psychiatric Association, 2013, Diagnostic and Statistical Manual of Mental Disorders DSM-5, V5th ed., DOI [10.1176/appi.books.9780890425596, DOI 10.1176/APPI.BOOKS.9780890425596]

[6] Anterior cingulate cortex gray matter abnormalities in adults with attention deficit hyperactivity disorder: A voxel-based morphometry study [J].

Amico, Francesco ;

Stauber, Jonathan ;

Koutsouleris, Nikolaos ;

Frodl, Thomas .

PSYCHIATRY RESEARCH-NEUROIMAGING, 2011, 191 (01) :31-35

[7] The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans [J].

Ardlie, Kristin G. ;

DeLuca, David S. ;

Segre, Ayellet V. ;

Sullivan, Timothy J. ;

Young, Taylor R. ;

Gelfand, Ellen T. ;

Trowbridge, Casandra A. ;

Maller, Julian B. ;

Tukiainen, Taru ;

Lek, Monkol ;

Ward, Lucas D. ;

Kheradpour, Pouya ;

Iriarte, Benjamin ;

Meng, Yan ;

Palmer, Cameron D. ;

Esko, Tonu ;

Winckler, Wendy ;

Hirschhorn, Joel N. ;

Kellis, Manolis ;

MacArthur, Daniel G. ;

Getz, Gad ;

Shabalin, Andrey A. ;

Li, Gen ;

Zhou, Yi-Hui ;

Nobel, Andrew B. ;

Rusyn, Ivan ;

Wright, Fred A. ;

Lappalainen, Tuuli ;

Ferreira, Pedro G. ;

Ongen, Halit ;

Rivas, Manuel A. ;

Battle, Alexis ;

Mostafavi, Sara ;

Monlong, Jean ;

Sammeth, Michael ;

Mele, Marta ;

Reverter, Ferran ;

Goldmann, Jakob M. ;

Koller, Daphne ;

Guigo, Roderic ;

McCarthy, Mark I. ;

Dermitzakis, Emmanouil T. ;

Gamazon, Eric R. ;

Im, Hae Kyung ;

Konkashbaev, Anuar ;

Nicolae, Dan L. ;

Cox, Nancy J. ;

Flutre, Timothee ;

Wen, Xiaoquan ;

Stephens, Matthew .

SCIENCE, 2015, 348 (6235) :648-660

[8] A Potential Role for the STXBP5-AS1 Gene in Adult ADHD Symptoms [J].

Arias-Vasquez, A. ;

Groffen, A. J. ;

Spijker, S. ;

Ouwens, K. G. ;

Klein, M. ;

Vojinovic, D. ;

Galesloot, T. E. ;

Bralten, J. ;

Hottenga, J. J. ;

van der Most, P. J. ;

Kattenberg, V. M. ;

Pool, R. ;

Nolte, I. M. ;

Penninx, B. W. J. H. ;

Fedko, I. O. ;

Dolan, C., V ;

Nivard, M. G. ;

den Braber, A. ;

van Duijn, C. M. ;

Hoekstra, P. J. ;

Buitelaar, J. K. ;

Kiemeney, L. A. ;

Hoogman, M. ;

Middeldorp, C. M. ;

Draisma, H. H. M. ;

Vermeulen, S. H. ;

Sanchez-Mora, C. ;

Ramos-Quiroga, J. A. ;

Ribases, M. ;

Hartman, C. A. ;

Kooij, J. J. S. ;

Amin, N. ;

Smit, A. B. ;

Franke, B. ;

Boomsma, D., I .

BEHAVIOR GENETICS, 2019, 49 (03) :270-285

[9] Cortical Gray Matter in Attention-Deficit/Hyperactivity Disorder: A Structural Magnetic Resonance Imaging Study [J].

Batty, Martin J. ;

Liddle, Elizabeth B. ;

Pitiot, Alain ;

Toro, Roberto ;

Groom, Madeleine J. ;

Scerif, Gaia ;

Liotti, Mario ;

Liddle, Peter F. ;

Paus, Tomas ;

Hollis, Chris .

JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, 2010, 49 (03) :229-238

[10] Predictors of persistence in girls with attention deficit hyperactivity disorder: results from an 11-year controlled follow-up study [J].

Biederman, J. ;

Petty, C. R. ;

O'Connor, K. B. ;

Hyder, L. L. ;

Faraone, S. V. .

ACTA PSYCHIATRICA SCANDINAVICA, 2012, 125 (02) :147-156

← 1 2 3 4 5 6 7 8 9 10 →