Differential changes in frontolimbic functional connectivity following 12-week psychostimulant monotherapy in ADHD youth with and without familial risk for bipolar I disorder.
Qian Li, Fei Li, Kun Qin et al.
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In 30 seconds
This randomized controlled trial examined whether 12 weeks of psychostimulant monotherapy was associated with different changes in amygdala–ventrolateral prefrontal cortex functional connectivity in youth with ADHD, with or without a first-degree relative with bipolar I disorder. The study included 116 youth; high-risk participants were randomized to mixed amphetamine salts extended release or placebo, while low-risk participants received the medication. Connectivity did not change during emotional processing. During task-related attention, the high-risk medication group had a greater increase in right-sided negative connectivity than both comparison groups (P = 0.034 vs low-risk medication; P = 0.007 vs high-risk placebo).
Key findings
- Neither low-risk nor high-risk youth receiving medication showed changes in bilateral amygdala–VLPFC connectivity during emotional processing.
- During attentional processing, high-risk youth receiving medication had a greater increase in right amygdala–VLPFC negative connectivity than low-risk medicated youth (P = 0.034) and high-risk youth receiving placebo (P = 0.007).
- Low-risk medicated youth showed greater reductions in ADHD total and inattention symptoms than high-risk medicated youth.
Why it matters
The findings indicate that familial bipolar I disorder risk may be associated with a different neurofunctional response to psychostimulant treatment during attention-related processing, even when emotional-processing connectivity does not change. This distinction may help frame research into how familial risk relates to treatment response and brain function in youth with ADHD, while the connectivity findings do not establish clinical benefit or harm.
What to keep in mind
The low-risk group did not have a placebo comparator, and the abstract reports brain-connectivity outcomes over 12 weeks rather than longer-term clinical outcomes.