Norepinephrine and serotonin imbalance in the locus coeruleus in bipolar disorder.
OBJECTIVE
Abnormalities in norepinephrine (NE) and serotonin (5-HT) are implicated in bipolar disorder (BD). We examined 5-HT input and NE neurons in the locus coeruleus (LC, the NE nucleus that innervates the forebrain) in BD by quantifying immunoreactivity (IR) for tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the biosynthetic enzymes for NE and 5-HT, respectively.


METHODS
Six suicides with BD were compared to matched normal controls and unipolar major depression suicides, using immunocytochemistry with computer-assisted quantification of immunoreactivity.


RESULTS
Depressed bipolar suicides had 26.7 +/- 1.3% of LC area occupied by the TH immunoreactive (TH-IR) process, while controls had 50.7 +/- 8% (p = 0.002) and unipolar depressed suicides had 50.3 +/- 2.5% (p = 0.003). In bipolars, these processes did not stain as darkly (1.9 +/- 0.5 x background) as controls (2.9 +/- 0.9 x background; p = 0.01) or unipolars (2.9 +/- 0.6 x background; p = 0.002). Bipolar suicides also had less TPH-IR processes in the LC (11.7 +/- 10%) compared with controls (32.8 +/- 8.8%; p = 0.01) or unipolar suicides (30.3 +/- 8%; p = 0.02). The TPH-IR intensity did not differ between groups.


CONCLUSIONS
We found less TH-IR and TPH-IR in the LC in depressed bipolar suicides, but not unipolar suicides, suggesting that both NE and 5-HT activity is lower in BD. Studies during manic or euthymic states will determine whether these changes are mood state dependent.
Wiste
Anna K
AK
Department of Psychiatry, Columbia College of Physicians and Surgeons, New York, NY, USA.
Arango
Victoria
V
Ellis
Steven P
SP
Mann
J John
JJ
Underwood
Mark D
MD
D000328:Adult; D000704:Analysis of Variance; D001344:Autopsy / Q000379:methods; D001714:Bipolar Disorder / Q000473:pathology*; D002452:Cell Count; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D009638:Norepinephrine