Functional dysconnection in the prefrontal-amygdala circuitry in unaffected siblings of patients with bipolar I disorder.
OBJECTIVE
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 (18) F-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.
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
Cheng-Ta
CT
Li
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
Pei-Chi
PC
Tu
Integrated Brain Research Unit, Division of Clinical Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Brain Science, Taipei, Taiwan.
Jen-Chuen
JC
Hsieh
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Hsin-Chen
HC
Lee
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
Ya-Mei
YM
Bai
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
Chia-Fen
CF
Tsai
Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Shyh-Jen
SJ
Wang
Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Ju-Wei
JW
Hsu
Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Kai-Lin
KL
Huang
Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Chen-Jee
CJ
Hong
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.|Institute of Brain Science, Taipei, Taiwan.
Tung-Ping
TP
Su
D000328:Adult; D000679:Amygdala / Q000473:pathology*; D001714:Bipolar Disorder / Q000473:pathology / Q000523:psychology; D016241:Child of Impaired Parents / Q000523:psychology*; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D017397:Prefrontal Cortex / Q000473:pathology*; D011599:Psychopathology; D035781:Siblings / Q000523:psychology
amygdala; bipolar disorder; fronto-limbic circuitry; functional connectivity; glucose utilization