From: Kofi on 12 Jul 2010 00:00
Unfortunately, the idea of using COX-2 inhibitors to treat schizophrenia
is likely to backfire given that both schizophrenia and COX-2 inhibitors
are associated with leaky gut. Just because something works in a
short-term study doesn't mean it's going to work well over the lifetime
of a patient.
Dialogues Clin Neurosci. 2009;11(3):319-32
The impact of neuroimmune dysregulation on neuroprotection and
neurotoxicity in psychiatric disorders--relation to drug treatment.
Muller N, Myint AM, Schwarz MJ.
Department of Psychiatry and Psychotherapy,
Ludwig-Maximilians-Universitat Munchen, Germany.
An inflammatory pathogenesis has been postulated for schizophrenia and
major depression (MD). In schizophrenia and depression, opposing
patterns of type-7 vs type-2 immune response seem to be associated with
differences in the activation of the enzyme indoleamine 2,3-dioxygenase
and in the tryptophan-kynurenine metabolism, resulting in increased
production of kynurenic acid in schizophrenia and decreased production
of kynurenic acid in depression. These differences are associated with
an imbalance in the glutamatergic neurotransmission, which may
contribute to an excessive agonist action of N-methyl-D-aspartate (NMDA)
in depression and of NMDA antagonism in schizophrenia. Regarding the
neuroprotective function of kynurenic acid and the neurotoxic effects of
quinolinic acid (QUIN), different patterns of immune activation may also
lead to an imbalance between the neuroprotective and the neurotoxic
effects of the tryptophan/kynurenine metabolism. The differential
activation of microglia cells and astrocytes may be an additional
mechanism contributing to this imbalance. The immunological imbalance
results in an inflammatory state combined with increased prostaglandin
E2 production and increased cyclo-oxygenase-2 (COX-2) expression. The
immunological effects of many existing antipsychotics and
antidepressants, however, partly correct the immune imbalance and the
excess production of the neurotoxic QUIN. COX-2 inhibitors have been
tested in animal models of depression and in preliminary clinical
trials, pointing to favorable effects in schizophrenia and in MD.