Mapping the cortico-striatal transcriptome in attention deficit hyperactivity disorder

• Published in: Molecular psychiatry Vol. 28; no. 2; pp. 792 - 800
• Main Authors: Sudre, Gustavo, Gildea, Derek E., Shastri, Gauri G., Sharp, Wendy, Jung, Benjamin, Xu, Qing, Auluck, Pavan K., Elnitski, Laura, Baxevanis, Andreas D., Marenco, Stefano, Shaw, Philip
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2023; Nature Publishing Group
• Subjects: 38/91; 631/208; 631/378; 692/699/476/1311; Attention Deficit Disorder with Hyperactivity - metabolism; Attention deficit hyperactivity disorder; Behavioral Sciences; Biological Psychology; Brain - metabolism; Brain Mapping; Brain research; Caudate nucleus; Corpus Striatum - metabolism; Cortex (cingulate); Dissection; Gene expression; Gene mapping; Genetic diversity; Genomes; Genomics; Glutamatergic transmission; Humans; Hyperactivity; Magnetic Resonance Imaging; Medicine; Medicine & Public Health; Mental disorders; Mental health; Neostriatum; Neurodevelopmental disorders; Neurosciences; Neurotransmitters; Pharmacotherapy; Psychiatry; Quality control; Research centers; Software packages; Transcriptome - genetics; Transcriptomes; Transcriptomics
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/s41380-022-01844-9

Despite advances in identifying rare and common genetic variants conferring risk for ADHD, the lack of a transcriptomic understanding of cortico-striatal brain circuitry has stymied a molecular mechanistic understanding of this disorder. To address this gap, we mapped the transcriptome of the caudate nucleus and anterior cingulate cortex in post-mortem tissue from 60 individuals with and without ADHD. Significant differential expression of genes was found in the anterior cingulate cortex and, to a lesser extent, the caudate. Significant downregulation emerged of neurotransmitter gene pathways, particularly glutamatergic, in keeping with models that implicate these neurotransmitters in ADHD. Consistent with the genetic overlap between mental disorders, correlations were found between the cortico-striatal transcriptomic changes seen in ADHD and those seen in other neurodevelopmental and mood disorders. This transcriptomic evidence points to cortico-striatal neurotransmitter anomalies in the pathogenesis of ADHD, consistent with current models of the disorder.