Institute for Response-Genetics (e.V.)

Chairman: Prof. Dr. Hans H. Stassen

Psychiatric Hospital (KPPP), University of Zurich

IFRG Logo
IFRG Emblem
Trithemius

Active Immune Processes in Psychiatry

Active immune processes appear to be involved in the pathogenesis of major psychiatric disorders, as suggested by evidence from recent studies. The abnormalities of CNS metabolism observed with depressive or schizophrenic disorders might arise, at least to some extent, because genetically modulated inflammatory reactions damage the microvascular system of the brain. Central to this hypothesis is the patients' genetically influenced inflammatory response, while the initial triggering of the inflammatory reaction is less important, irrespective of whether being due to an endogenous or exogenous event.

Chronically Elevated Poly-Reactive IgM Levels

Interestingly, the between-subject variation of the "natural" antibody immunoglobulin M (IgM) has been found to possess a strong genetic component, while chronically elevated IgM levels typically develop years before the first clinical symptoms of the responsible disease occur as is the case, for example, with rheumatoid arthritis. Moreover, chronically elevated IgM levels appear to be related to a heritable malfunction in the inflammatory response system, as suggested by our study of 599 nuclear families (1,868 genotyped subjects) ascertained through index cases with a clinical diagnosis of rheumatoid arthritis.

Longitudinal Study of 279 Patients

In a longitudinal study of 279 patients with clinical diagnoses of depressive (ICD10 F3) or schizophrenic (ICD10 F2) disorders we aimed to estimate the amount of between-patient variance that is "explainable" by chronically elevated levels of the "natural" antibody immunoglobulin M (IgM). We relied on multi-layer neural nets (NNs) and machine learning in order to determine that initially unknown subgroup of psychiatric patients for whom aberrancies of the inflammatory response system are linked to the pathogenesis of their illness, and for whom the inflammatory response system may be a target for therapeutic intervention. Our analyses revealed a 22.5% subgroup of F2 patients and a 19.6% subgroup of F3 patients with highly significant correlations between IgM levels on the one hand, and the global schizophrenia and depression scores on the other. The NN models explained with 55.7% and 41.4% a major proportion of the observed between-patient variance while predicting response to treatment at low false-positive error rates of 5.6% and 11.4% [Stassen et al. 2021].

References

Stassen HH, Bachmann S, Bridler R, Cattapan K, Hartmann AM, Rujescu D, Seifritz E, Weisbrod M, Scharfetter C. Analysis of genetic diversity in patients with major psychiatric disorders versus healthy controls: A molecular-genetic study of 1698 subjects genotyped for 100 candidate genes (549 SNPs). Psychiatry Res. 2024; 333: 115720. doi: 10.1016/j.psychres.2024.115720 [get the article]
Greil W, de Bardeci M, Müller-Oerlinghausen B, Nievergelt N, Stassen HH, Hasler G, Erfurth A, Cattapan K, Rüther E, Seifert J, Toto S, Bleich S, Schoretsanitis G. Controversies regarding lithium-associated weight gain: case-control study of real-world drug safety data. Int J Bipolar Disord. 2023; 11(1): 34. doi: 10.1186/s40345-023-00313-8 [get the article]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Seifritz E. Polypharmacy in Psychiatry and Weight Gain: Longitudinal Study of 832 Patients Hospitalized for Depression or Schizophrenia, along with Data of 3,180 Students from Europe, the U.S., South America, and China. Eur Arch Psychiatry Clin Neurosci. 2023 [in press]
de Bardeci M, Greil W, Stassen H, Willms J, Köberle U, Bridler R, Hasler G, Kasper S, Rüther E, Bleich S, Toto S, Grohmann R, Seifert J. Dear Doctor Letters regarding citalopram and escitalopram: guidelines vs real-world data. Eur Arch Psychiatry Clin Neurosci. 2023; 273(1): 65-74 [get the article]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Hartmann AM, Rujescu D, Seifritz E, Weisbrod M, Scharfetter C: Genetic Factors involved in Non-Response to Antidepressant or Antipsychotic Drug Treatment and the Development of Side Effects? A molecular-genetic study of 902 patients over 4 weeks. Arch Psychiatry Clin Neurosci. 2023 [in preparation]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Herzig D, Schneeberger A, Seifritz E: Detailing the Effects of Polypharmacy in Psychiatry: Longitudinal Study of 320 Patients Hospitalized for Depression or Schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2022; 272(4): 603-619 [get the article]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Herzig D, Schneeberger A, Seifritz E. Inflammatory Processes linked to Major Depression and Schizophrenic Disorders and the Effects of Polypharmacy in Psychiatry: Evidence from a longitudinal Study of 279 Patients under Therapy. Eur Arch Psychiatry Clin Neurosci. 2021; 271(3): 507-520 [get the article]
Stassen HH: Heterogeneity of schizophrenic disorders and link to chronically elevated IgM values. Neurology, psychiatry and brain research 2018; 29: 23-24
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. Eur Arch Psychiatry Clin Neurosci. 2017; 267: 377-389 [get the article]
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
Stassen HH, Delfino JP, Kluckner VJ, Lott P, Mohr C: Vulnerabilität und psychische Erkrankung. Swiss Archives of Neurology and Psychiatry 2014; 165(5): 152-157
Stassen HH, Hoffmann K, Scharfetter C: The Difficulties of Reproducing Conventionally Derived Results through 500k-Chip Technology. BMC Genet Proc. 2009; 3 Suppl 7: S66
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, 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

 

vSpacer Chronically Elevated Poly-Reactive IgM Levels
Our study identified subgroups of F2/F3 patients exhibiting highly significant correlations between IgM levels and global schizophrenia & depression scores.
Hspacer
[ Mail to Webmaster ] k454910@ifrg.ch
rFrame