Increased xanthine oxidase in the thalamus and putamen in depression

Abstract

A growing body of literature suggests persistent and selective structural changes in the cortico-limbic-thalamic-striatal system in patients with recurrent depressive disorder (DD). Oxidative stress is thought to play a key role in these processes. So far, the main scientific focus has been on antioxidant enzymes in this context. For the first time, this proof of concept study examines the activity of the free radicals producing the enzyme, xanthine oxidase (XO), directly in the cortico-limbic-thalamic-striatal system of patients with recurrent depression. The activity of XO was ascertained in the cortico-limbic-thalamic-striatal regions in post-mortem brain tissue of patients with recurrent depressive episodes and individuals without any neurological or psychiatric history (7/7). We measured the XO activity in following brain areas: hippocampus, regio entorhinalis, thalamus, putamen and caudate nucleus. In this study, we report a significant increase of XO activity in the thalamus and the putamen of patients with depression. Our findings contribute to the growing body of evidence suggesting that oxidative stress plays a pivotal role in certain brain areas in recurrent depressive disorder.

Depression uncouples brain hate circuit

“…Elevated dopamine D2 receptor binding 36 and increased oxidative stress 37 have also been reported in the putamen of depressed patients, and stroke patients with damage to this region can show depressive symptoms. 38 Altered functioning of the insular cortex has been found in a number of psychiatric disorders, including depression.…”

DNA Damage in Major Psychiatric Diseases

“…In a human study on gene expression profiles in cells from autopsies of the frontal cortex, MDD was associated with molecular signs of inflammation, apoptosis and oxidative stress (Shelton et al 2011). Also, there are reports related to increased plasma levels of peroxides and xanthine oxidase (Herken et al 2007, Maes et al 2010) and increased xanthine oxidase activity in post-mortem brain tissue of patients with recurrent depression (Michel et al 2010). Furthermore, oxidative stress impacts telomere stability and functions to damage telomeric DNA, rendering the cell susceptible to apoptosis (Opresko et al 2005, Zhang et al 2007).…”

Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder

“…XO is a widely distributed enzyme involved in later stages of purine catabolism, which catalyzes the oxidation of hypoxanthine to xanthine and of xanthine to uric acid, both reactions with potential to generate O 2 ●− and H 2 O 2 [49]. A recent post-mortem study found increased XO activity in the thalamus and putamen patients with recurrent MDD [35]. …”

“…Michel et al (2010) showed increased XO activity in the thalamus and putamen of seven individuals with an ante-mortem diagnosis of recurrent MDD (age range = 61–93 y.o.). Four of these subjects received SSRI and one was medicated with clomipramine in the 6 months before death, while two of them were not antidepressant treatments [35]. These results suggest increased ROS production in brain samples of depressive patients due to increased XO activity.…”