Alpha 2-adrenergic receptor function in depression. The cortisol response to yohimbine

Area of Science:

• Neuroscience
• Psychiatry
• Endocrinology

Background:

• Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is observed in depression.
• Central neurotransmitter receptor changes may underlie HPA axis abnormalities in depression.

Purpose of the Study:

• To investigate the role of alpha 2-adrenergic receptor function in HPA axis regulation in major depression.
• To assess noradrenergic and HPA axis responses to alpha 2-adrenergic receptor blockade.

Main Methods:

• Administered yohimbine hydrochloride (an alpha 2-adrenergic antagonist) to 40 patients with major depression and 16 healthy controls.
• Measured plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG) as an index of noradrenergic function.
• Measured plasma cortisol levels to assess HPA axis response.

Main Results:

• Melancholic depressed patients had elevated baseline cortisol levels compared to controls.
• Depressed patients exhibited a significantly greater cortisol response to yohimbine than controls.
• Noradrenergic function, assessed by MHPG levels, did not differ significantly between groups.

Conclusions:

• The heightened cortisol response to alpha 2-adrenergic blockade suggests a relative subsensitivity of postsynaptic alpha 2-adrenergic receptors in depression.
• This finding implicates altered alpha 2-adrenergic receptor function in the HPA axis dysregulation observed in major depression.