An overview on neurobiology and therapeutics of attention-deficit/hyperactivity disorder
Bruna Santos da Silva, Eugenio Horácio Grevet, Luíza Carolina Fagundes Silva, João Kleber Neves Ramos, Diego Luiz Rovaris, Claiton H.D. Bau · 2023 · 117 citationsRead the paper
Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition characterized by developmentally inappropriate symptoms of inattention and/or hyperactivity/impulsivity, which leads to impairments in the social, academic, and professional contexts. ADHD diagnosis relies solely on clinical assessment based on symptom evaluation and is sometimes challenging due to the substantial heterogeneity of the disorder in terms of clinical and pathophysiological aspects. Despite the difficulties imposed by the high complexity of ADHD etiology, the growing body of research and technological advances provide good perspectives for understanding the neurobiology of the disorder. Such knowledge is essential to refining diagnosis and identifying new therapeutic options to optimize treatment outcomes and associated impairments, leading to improvements in all domains of patient care. This review is intended to be an updated outline that addresses the etiological and neurobiological aspects of ADHD and its treatment, considering the impact of the "omics" era on disentangling the multifactorial architecture of ADHD.
What the full text shows
Shown in the lab- Total heritability of ADHD is estimated to be high and stable across childhood and adolescence. — 70–80% (Twin studies)
- Common genetic variants (SNP) explain a smaller portion of phenotypic variation than total heritability. — 14% to 22% h2 SNP (GWAS meta-analyses)
- Hazard ratio for ADHD in relatives compared to unaffected people varies by kinship. — 70 for monozygotic twins, 8 for dizygotic twins/full siblings, 1.5 for half cousins (Large population sample)
- Children with ADHD exhibit reduced volumes in specific subcortical brain regions and total intracranial volume. — '' (ENIGMA consortium meta-analysis)
- Lower fractional anisotropy (FA) in specific white matter fasciculi is associated with ADHD diagnosis and symptoms. — '' (Inferior longitudinal (ILF) and left uncinate (UNC) fasciculi)
- Increased abundance of specific gut microbiota genera is associated with ADHD. — Increased Enterococcus, Bifidobacterium, and Odoribacter; decreased Faecalibacterium (Gut-brain axis studies)
- Setup
- Multiple cohorts including iPSYCH, deCODE, PGC, and ENIGMA; sample sizes ranging from 20k to 225k individuals.
- How
- Literature review and synthesis of GWAS, EWAS, neuroimaging (fMRI, DTI), and Mendelian Randomization studies.
- Limitations
- Lack of unique biomarkers to guide diagnosis or treatment. · Over-representation of European ancestry in genomic studies. · Causality inferences for environmental factors remain elusive due to confounding. · Inconsistent DTI findings due to methodological differences (e.g., head motion).
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