Professor Dr. med. Christian Scharfetter

Department of Psychiatry, Psychotherapy and Psychosomatics

Psychiatric Hospital, University of Zurich

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Inflammatory Processes and Psychiatric Disorders

From the psychiatric point of view, it is most intriguing that active immune processes may be involved in the pathogenesis of major psychiatric disorders, as suggested by evidence from recent studies. Specifically, significant alterations of T-cell function, along with activation of the inflammatory response system, appear to be linked to treatment-resistant schizophrenia. Similar processes have also been reported for mood disorders in general. The abnormalities of CNS metabolism observed with functional psychoses and depression might, therefore, arise because genetically modulated inflammatory reactions damage the microvascular system of the brain, with the nature of the infectious agent being less important than the patients’ genetically influenced inflammatory response.

Chronically Elevated Poly-Reactive IgM Levels

The "natural" antibody IgM is in use, for example, as a standard diagnostic test for rheumatoid arthritis, but possesses a low specificity. Since the formation of chronically elevated poly-reactive IgM levels develops years before clinical symptoms occur [Nielen et al. 2006], a genetically predisposed aberrancy of the inflammatory response system has been linked to various complex diseases. In the field of psychiatric disorders, a population-based study of 7,704 patients with a diagnosis of schizophrenia and 192,590 control subjects without psychiatric history has revealed that a parental history of schizophrenia was associated with a 5-fold risk for autoimmune diseases, whereas a parental history of autoimmune diseases increased this risk only slightly, by a factor of 1.45 [Eaton et al. 2006]. More specifically, several antidepressants and antipsychotics show anti-inflammatory effects [e.g., Müller and Schwarz 2006, 2007], while a quantitative (R)-[11C]PK11195 positron emission tomography study demonstrated microglia activation in recent-onset schizophrenia [van Berckel et al. 2008].


Stassen HH, Szegedi A, Scharfetter C: Modeling Activation of Inflammatory Response System. A Molecular-Genetic Neural Network Analysis. BMC Proceedings 2007, 1 (Suppl 1): S61, 1-6
Stassen HH, Anghelescu IG, Hell D, Hoffmann K, Rujescu D, Scharfetter C, Szegedi A, Tadic A: Linking autoantibody formation to genetic vulnerability to psychiatric disorders and psychotropic drug response. Int J Neuropsychopharmacol. 2008; 11 (Suppl. 1): 101
Stassen HH, Hoffmann K, Scharfetter C: The Difficulties of Reproducing Conventionally Derived Results through 500k-Chip Technology. BMC Genet 2009; 3 Suppl 7: S66
Stassen HH, Braun S, Bridler R, Seifritz E, Weisbrod M: Inflammatory Processes and Schizophrenia: Evidence from a Twin Study. Eur Neuropsychopharmacology 2017; 27 Suppl 4: S934-S935
Braun S, Bridler R, Müller N, Schwarz MJ, Seifritz E, Weisbrod M, Zgraggen A, Stassen HH: Inflammatory Processes and Schizophrenia: Two Independent Lines of Evidence from a Study of Twins Discordant and Concordant for Schizophrenic Disorders. European Archives of Psychiatry and Clinical Neuroscience 2017; 267: 377-389
Stassen HH: Heterogeneity of schizophrenic disorders and link to chronically elevated IgM values. Neurology, psychiatry and brain research 2018; 29: 23-24


Inflammatory Processes and Psychiatric Disorders
Molecular-genetic Neural Nets can be used to connect multiple genetic factors, as observed in each individual patient, through a layer of gene products to a one-dimensional phenotype, for example, IgM level or time to response to treatment under consideration of interactions between gene products. The method of approach can easily be generalized to multidimensional phenotypes, for example, the syndrome patterns underlying schizophrenic or bipolar illness.
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