Elevated levels of tyrosine hydroxylase in the locus coeruleus in major depression

Background: Levels of tyrosine hydroxylase (TH) are regulated in the noradr energic locus coeruleus (LC) in response to changes in the activity of LC n eurons and in response to changes in brain levels of norepinephrine. To stu dy the potential role of central noradrenergic neurons in the pathobiology of major depression, TH protein was measured in the LC from postmortem brai ns of 13 subjects with a diagnosis of major depression and 13 age-matched c ontrol subjects having no Axis I psychiatric diagnosis. Most of the major d epressive subjects died as a result of suicide. Methods: Protein from sections cut through multiple rostro-caudal levels of LC was transferred to Immobilon-P membrane, immunoblotted for TH, and quan tified autoradiographically. Results: The distribution of TH-immunoreactivity (TH-ir) along the rostro-c audal axis of the LC was uneven and was paralleled by a similar uneven dist ribution of neuromelanin-containing cells in both major depressive and psyc hiatrically normal control subjects. Amounts of TH-ir in the rostral, middl e and caudal levels of the LC from major depressive subjects were significa ntly higher than that of matched control subjects. There were no,significan t differences in the number of noradrenergic cells at any particular level of the LC comparing major depressive subjects to control subjects. Conclusions: Elevated expression of TH in the LC in major depression implie s a premortem overactivity of these neurons, or a deficiency of the cognate transmitter, norepinephrine. (C) 1999 Society of Biological Psychiatry.