Posted by Netch on November 13, 2009, at 9:44:39
In reply to Chronic Infection May Spawn Depression (Article), posted by southernsky on November 8, 2009, at 16:02:03
"Evidence exists of a link between IDO activity and mood. In serotonergic nerve terminals tryptophan is hydroxylated before conversion to serotonin (5HT). Lower levels of serotonin in the brain are associated with depressed mood. Tryptophan availability limits de novo synthesis of serotonin and tryptophan depletion has been associated with depressive symptoms in patients with remitted major depressive disorder, resulting in a disturbance of mood in subjects with a family history of affective illness.
Given the proposed role of IDO in maintaining pregnancy, the linkage between IDO activity and mood may be relevant to postpartum depression. Typically this phenomenon occurs within a few days after delivery until the tenth day postpartum. An association has been noted between Kyn/Trp ratio and the severity of depressive symptoms in the early puerperium, suggesting that an increased degradation of typtophan relates to the occurrence of postpartum blues. Conversely, a decrease in Kyn/Trp ratioes has been reported in women with stable mood after delivery.
Some evidence exists that inflammatory changes in the brain that may be associated with IDO1 expression are pathological features of both depression and dementia. Pathological changes have been associated with a reduction in the neuroprotective components of the kynurenine pathway (e.g. kynurenic acid) and an increase in the neurodegenerative components (e.g. 3-hydroxykynurenine acid and quinolinic acid). These changes are postulated to cause neuronal damage and predispose chronically depressed patients to dementia. In Alzheimer's patients, plasma Kyn/Trp ratioes have been observed to correlate with the degree of cognitive deficit. Also, immunohistochemical analysis suggests that IDO1 is abundant in the brains of Alzheimer's patients compared to controls. Similarly, relative elevations in Kyn/Trp ratio have been found in plasma from patients with Huntington's or Parkinson's disease compared to controls. Notably, depressive symptoms affect up to 50% of Alzheimer's patients, 41% of Huntington's patients, and 40% of Parkinson's patients.
Further support for a link between IDO1 elevation and depressed mood are found in patients with autoimmune diseases, where symptoms have been associated with increased tryptophan catabolism. Enhanced tryptophan degradation was found in systemic lupus erythromatosus, rheumatoid arthritis, sarcoidosis, and a mouse model of multiple sclerosis. It has also been noted that a higher proportion of patients infected with Hepatitis C virus (HCV) have lower serum tryptophan concentrations and depression relative to healthy volunteers."http://atlasgeneticsoncology.org/Genes/IDO1ID40973ch8p11.html
poster:Netch
thread:924979
URL: http://www.dr-bob.org/babble/20091107/msgs/925583.html