A psychoneuroimmunological perspective to Emil Kraepelins dichotomy

Norbert Müller, Markus J. Schwarz

The Kraepelinian classification of psychiatric disorders, in particular the dichotomy of dementia praecox and manic-depressive psychosis is under discussion since a long time. In recent years, not only new research in the fields of psychopathology and clinical outcome, but also findings of biological markers in the areas of neurophysiology, neuroendocrinology, psychoneuroimmunology, genetics, or psychopharmacology show a big overlap between both groups of disorders. This overlap of symptoms and markers of both disorders intensified the discussion and the proposals for new criteria for the classification of psychiatric disorders. By means of findings from the field of psychoneuroimmunology and inflammation it will be shown that different pathological mechanisms in depression and schizophrenia may lead to the same final common pathway of inflammation. These mechanisms include the immunological balance between type-1 and type-2 immune activation which influences the tryptophan-degradating enzyme indoleamine 2,3-dioxygenase (IDO) in the CNS in opposite ways, leading to an altered availability of tryptophan and serotonin, and a disturbance of the kynurenine metabolism with an imbalance in favor of the production of the NMDA-receptor agonist quinolinic acid in depression and of the NMDA-receptor antagonist kynurenic acid in schizophrenia. In both disorders, however, an increased production of prostaglandin E2 and increased expression of cyclo-oxygenase-2 reflect a slight inflammatory process taking place probably in different regions of the CNS. Albeit this common inflammatory pathway--inflammation is a general pathway of the body as answer to a lot of different noxae and pathogens--the Kraepelinian dichotomy is important with respect to pathological mechanisms and therapeutic approaches, not only for further research in understanding the exact pathological mechanisms but also for the development of preventive strategies in high risk individuals and in patients. Opposite pathways regarding the immune activation, the neurotoxic versus neuroprotective kynurenine metabolites and the agonistic versus antagonistic effects on the NMDA receptor and the glutamatergic neurotransmission show despite a possible therapeutic advantage of anti-inflammatory therapy in both disorders that the Kraepelinian dichotomy still has a significant value from a biologic-psychiatric point of view.