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.