Neurofunctional Differences Among Youth With and at Varying Risk for Developing Mania

Area of Science:

• Neuroscience
• Psychiatry
• Developmental Psychology

Background:

• Identifying early biomarkers for bipolar disorder (BP-I) in youth is crucial for timely intervention.
• Emotional processing deficits are implicated in BP-I, but neural correlates in at-risk youth require further investigation.

Purpose of the Study:

• To investigate prefrontal and amygdala activation during emotional processing in adolescents with first-episode BP-I and varying levels of familial risk.
• To identify potential central prodromal risk biomarkers for mania.

Main Methods:

• Functional magnetic resonance imaging (fMRI) was used in four groups of adolescents (10-20 years): BP-I, at-risk depressed (ARD), at-risk healthy (ARH), and healthy controls (HC).
• Participants completed a continuous performance task with emotional and neutral distracters.
• Region-of-interest analyses focused on the amygdala, ventrolateral prefrontal cortex (vlPFC), and anterior cingulate cortex (ACC).

Main Results:

• No significant group differences in amygdala or vlPFC (Brodmann area [BA] 45/47) activation were found during emotional or neutral stimuli.
• Adolescents with first-episode BP-I showed reduced right pregenual ACC activation compared to HC.
• Increased left BA 44 activation was observed in ARH and ARD groups versus HC, while BP-I and ARD groups exhibited blunted right BA 10 activation compared to ARH.

Conclusions:

• Amygdala and vlPFC (BA 45/47) activation during emotional processing is comparable across youth with or at risk for BP-I.
• Blunted pregenual ACC activation in first-episode BP-I may serve as an illness biomarker.
• Elevated prefrontal BA 10 and BA 44 activation in at-risk youth could represent biomarkers of risk or resilience, meriting longitudinal study.