[Genetics and epigenetics of attention deficit hyperactivity disorder]

Area of Science:

• Neurogenetics
• Psychiatric Genetics
• Molecular Psychiatry

Background:

• Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a significant genetic component.
• Heritability estimates for ADHD range from 70-80%, indicating a strong genetic influence.
• Previous research identified associations between ADHD and genes involved in neurotransmitter systems, metabolic pathways, and cell membrane functions.

Purpose of the Study:

• To explore the genetic underpinnings of ADHD, focusing on unifying mechanisms.
• To investigate the role of copy number variations (CNVs) and retroelements in ADHD pathogenesis.
• To identify potential targets for diagnostic algorithms and personalized medicine in ADHD.

Main Methods:

• Review of molecular genetic studies, including association studies and copy number variation (CNV) analyses.
• Examination of the role of specific gene families (dopaminergic, serotoninergic, glutamatergic) and other genetic factors.
• Exploration of the potential involvement of retroelements and transposons in ADHD etiology.

Main Results:

• Multiple genes across various functional categories are implicated in ADHD etiology.
• Copy number variations (CNVs), potentially driven by retroelements/transposons, show promise as unifying factors.
• Dysregulation of transposons may impact gene regulation and epigenetic mechanisms in ADHD.
• Comorbidity with other psychiatric disorders suggests shared genetic risk factors.

Conclusions:

• A polygenic model is supported, with emerging evidence for retroelements and transposons as key players in ADHD pathogenesis.
• Transposon dysregulation could explain the heterogeneous nature of ADHD through altered gene regulation and epigenetics.
• Further research into noncoding RNAs and transposons is crucial for developing diagnostic tools and personalized psychiatric treatments for ADHD.