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Norepinephrine and serotonin imbalance in the locus coeruleus in bipolar disorder

Authors

  • Anna K Wiste,

    1. Department of Psychiatry, Columbia College of Physicians and Surgeons
    2. Department of Neuroscience, New York State Psychiatric Institute, New York, NY, USA
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  • Victoria Arango,

    1. Department of Psychiatry, Columbia College of Physicians and Surgeons
    2. Department of Neuroscience, New York State Psychiatric Institute, New York, NY, USA
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  • Steven P Ellis,

    1. Department of Psychiatry, Columbia College of Physicians and Surgeons
    2. Department of Neuroscience, New York State Psychiatric Institute, New York, NY, USA
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  • J John Mann,

    1. Department of Psychiatry, Columbia College of Physicians and Surgeons
    2. Department of Neuroscience, New York State Psychiatric Institute, New York, NY, USA
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  • Mark D Underwood

    1. Department of Psychiatry, Columbia College of Physicians and Surgeons
    2. Department of Neuroscience, New York State Psychiatric Institute, New York, NY, USA
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  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

Corresponding author: Mark D Underwood, PhD, 1051 Riverside Drive, Unit 42, New York State Psychiatric Institute, New York, NY 10032, USA. Fax: +1 212 543 6017; e-mail: mu20@columbia.edu

Abstract

Objectives:  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 × background) as controls (2.9 ± 0.9 × background; p = 0.01) or unipolars (2.9 ± 0.6 × 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.

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