Low Levels of Tyrosine Hydroxylase in the Lateral Nucleus of the Amygdala in Major Depression

Abstract

The lateral and basal nuclei of the amygdala receive dopaminergic projections from the ventral tegmental area and substantia nigra, and noradrenergic projections from the locus coeruleus (LC). Previously, we demonstrated postmortem indices of altered dopaminergic (amygdala) and noradrenergic (LC) neurochemistry in subjects with major depressive disorder (MDD). For example, decreased levels of dopamine transporter were observed in the amygdala in MDD, while concentrations of tyrosine hydroxylase (TH) were elevated in the LC in MDD. The present study investigated the quantitative distribution of TH in nuclei of the human amygdala from 5 control subjects, and measured amounts of TH in specific amygdaloid nuclei and the LC from 8-10 matched pairs of MDD and psychiatrically normal control subjects. Matched pairs included 3 females and 7 males (controls and MDD), average ages of 50±5 y (controls) and 51±5 y (MDD), average postmortem intervals of 16±2 h (controls) and 21±1 h (MDD), and average pH values of 6.58±0.08 (controls) and 6.59±0.09 (MDD). The lateral, basal, accessory basal, and central nuclei of the amygdala and the LC were punched from frozen sections of postmortem brain. TH-immunoreactivity was measured by quantitative Western blotting. In normal control subjects, TH levels in the LC were between 3000- and 4000-fold higher than TH levels in the nuclei of the amygdala. Within the amygdala, amounts of TH were highest in the basal and central nuclei, and lowest in the lateral nucleus. TH levels in the basal nucleus were highly variable across subjects. TH levels were significantly lower (-50%) in the lateral amygdaloid nucleus in MDD subjects as compared to control subjects. In contrast, TH levels in the LC were significantly higher (+75 %) in MDD subjects. This report is the first demonstration of altered TH levels in the human amygdala. The direction of change associated with MDD of TH in the lateral nucleus of the amygdala was opposite to that found in the LC. Whether abnormal amounts of TH in the amygdala are a result of altered dopaminergic or noradrenergic input to the amygdala requires further study