White matter endophenotype candidates for ADHD: a diffusion imaging tractography study with sibling design

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Attention-deficit/hyperactivity disorder (ADHD) is linked to brain structural changes in affected individuals.
• Investigating unaffected siblings of ADHD probands can reveal familial risk factors and genetic predispositions.
• Understanding white matter tract integrity in siblings offers insights into ADHD's heritability.

Purpose of the Study:

• To examine the microstructural integrity of white matter tracts in unaffected siblings of ADHD probands.
• To assess the association between white matter alterations and clinical/neuropsychological manifestations in siblings.
• To evaluate the potential familial risk for ADHD.

Main Methods:

• Diffusion spectrum imaging (DSI) was used for whole-brain tractography in ADHD probands, unaffected siblings, and controls.
• Microstructural properties (GFA, FA, MD, RD, AD) of 76 white matter tracts were analyzed.
• Tract-based analysis compared white matter integrity across the three groups.

Main Results:

• ADHD probands exhibited higher axial diffusivity (AD) in several white matter tracts compared to controls.
• Unaffected siblings showed intermediate AD values between ADHD probands and controls.
• Sibling AD values correlated with ADHD symptoms, sustained attention, and working memory, except for the perpendicular fasciculus.

Conclusions:

• Abnormal white matter tract AD values in unaffected siblings indicate familial risk for ADHD.
• The right frontostriatal tract (FS-VLPFC) may play a role in mitigating ADHD-related behaviors.
• These findings highlight the neurobiological underpinnings of familial ADHD risk.