|
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].
References
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
|
|
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.
|