Functional dysconnection in the prefrontal-amygdala circuitry in unaffected siblings of patients with bipolar I disorder

Cheng Ta Li, Pei Chi Tu, Jen Chuen Hsieh, Hsin Chen Lee, Ya Mei Bai, Chia Fen Tsai, Shyh Jen Wang, Ju Wei Hsu, Kai Lin Huang, Chen Jee Hong, Tung Ping Su*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Objectives: Bipolar I disorder (BD) is a highly heritable disorder characterized by mood swings between high-energy and low-energy states. Amygdala hyperactivity and cortical inhibitory hypoactivity [e.g., of the dorsolateral prefrontal cortex (dlPFC)] have been found in patients with BD, as evidenced by their abnormal resting-state functional connectivity (FC) and glucose utilization (GU). However, it has not been determined whether functional abnormalities of the dlPFC-amygdala circuit exist in unaffected, healthy siblings of the patients with BD (BDsib). Methods: Twenty euthymic patients with BD, 20 unaffected matching BDsib of the patient group, and 20 well-matched healthy control subjects were recruited. We investigated seed-based FC (seeds: dlPFC) with resting-state functional magnetic resonance imaging and GU in the regions of interest (e.g., dlPFC and amygdala) using 18F-fluorodeoxyglucose positron emission tomography. Results: The FC in the dlPFC (right)-amygdala circuit was statistically abnormal in patients with BD and BDsib, but only the patients with BD demonstrated hypoactive GU bilaterally in the dlPFC and hyperactive GU bilaterally in the amygdala. Facilitating differentiation between the BD groups, the altered FC between dlPFC (right) and amygdala (left) was even more prominent in the patients with BD (p < 0.05). Conclusions: There was a dysfunctional connection with intact GU in the dlPFC-amygdala circuit of the BDsib, which highlights the vulnerability in families with BD. Diminished top-down control from the bilateral dlPFC, which prevents adequate inhibition of limbic hyperactivity, might mediate the development of BD.

Original languageEnglish
Pages (from-to)626-635
Number of pages10
JournalBipolar Disorders
Issue number6
StatePublished - 1 Sep 2015


  • Amygdala
  • Bipolar disorder
  • Fronto-limbic circuitry
  • Functional connectivity
  • Glucose utilization


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