Institute for Response-Genetics (e.V.)Chairman: Prof. Dr. Hans H. StassenPsychiatric Hospital (KPPP), University of Zurich |
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Complex InterplayPsychiatric disorders, like other complex traits and illnesses, are most likely influenced by multiple genetic as well as multiple non-genetic factors. The magnitude of the genetic component depends on the severity of the underlying syndromes and may vary from 10-70%. There is no single "biogenic imbalance" that causes psychiatric disorders. Rather, the complex interplay between some of the organism's intrinsic, self-regulating subsystems, upon which the organism can "normally" rely, becomes distorted for whatever reasons. Sometimes induced by identifiable endogenous or exogenous triggers. This situation becomes immediately apparent in the case of monozygotic twins who share identical genomes but may remain discordant over a lifetime in terms of severe psychiatric disorders. Familial AggregationAll empirical evidence speaks against single causes underlying psychiatric disorders as these disorders aggregate in families, but do not segregate. That is, they do not follow simple Mendelian modes of inheritance. In particular, no homotypic diagnostic patterns can be detected, so that very diverse psychiatric diagnoses can be found among family members and offspring, largely independent of the diagnoses of index cases. Rather, available data suggest that an unspecific vulnerability that acts across clinical diagnoses best explains the observed psychiatric reality. This vulnerability is constantly modified by exogenous factors such as lifestyle, sports, diet, and consumption behavior, among others. In line with such a vulnerability model, our study of 2,008 patients hospitalized for major psychiatric disorders, along with 464 healthy controls, aimed at detecting possible links between vulnerability on the one hand, and multi-locus genotype patterns on the other. We relied on methods of Artificial Intelligence (AI) in combination with multi-layer Neural Nets (NNs) in order to optimally fit the vulnerability model to the observed data ("supervised learning").
International Databases
References
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. 2024; https://doi.org/10.1007/s00406-024-01767-2
(Epub ahead of print)
[get the article]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Hartmann AM, Rujescu D, Seifritz E, Weisbrod M,
Scharfetter C: Genetic Determinants of Antidepressant and Antipsychotic Drug Response:
A molecular-genetic study of 902 patients over 6 weeks. Psychiatry Res. 2024 [submitted for publication]
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]
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, 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]
Greil W, de Bardeci M, Seifert J, Bernegger X, Cattapan K, Stassen HH, Wagner AL, Sieberer M,
Grohmann R, Toto S: Treatment of depression: Are psychotropic drugs appropriately dosed in women
and in the elderly? Dosages of psychotropic drugs by sex and age in routine clinical practice.
Hum Psychopharmacol. 2022; 37(1): e2809
[get the article]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Herzig D, Schneeberger A, Seifritz E:
Inflammatory Processes linked to Major Depression & 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]
Pollak TA, Lennox B, Müller S, Benros ME, Prüss H, Tebartz van Elst L, Klein H, Steiner J,
Frodl T, Bogerts B, Tian L, Groc L, Hasan A, Baune BT, Endres D, Haroon E, Yolken R,
Benedetti F, Halaris A, Meyer J, Stassen HH, Leboyer M, Fuchs D, Otto M, Brown DA, Vincent A,
Najjar S, Bechter K: An international consensus on an approach to the diagnosis and
management of psychosis of suspected autoimmune origin: the concept of autoimmune psychosis.
Lancet Psychiatry 2020; 7(1): 93-108
Zhang M, Bridler R, Mohr C, Moragrega I, Sun N, Xu Z, Yang Z, Possenti M, Stassen HH:
Early Detection of the Risk of Developing Psychiatric Disorders: A Study of 461 Chinese University
Students under Chronic Stress. Psychopathology 2019; 52(6): 367-377
[get the article]
Bhake R, Kluckner V, Stassen HH, Russell GM, Leendertz J, Stevens K, Linthorst ACE,
Lightman S: Continuous Free Cortisol Profiles – Circadian Rhythms in Healthy Men.
J Clinical Endocrinology & Metabolism 2019; 104(12): 5935-5947
Stassen HH: Heterogeneity of schizophrenic disorders and link to chronically elevated IgM
values. Neurology, psychiatry and brain research 2018; 29: 23-24
Schnipper N, Hoffmann K, Kallinich T, Sperling K, Stassen HH: Image analysis of neutrophil
nuclear morphology: Learning about phenotypic range and its reliable analysis from patients
with Pelger-Huët-Anomaly and treated with Colchicine. Cytometry B Clin Cytom. 2017; 92(6): 541-549
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]
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. Neuropsychopharmacology
2016; 41: S414–S415
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
Drago A, Giegling I, Schäfer M, Hartmann AM, Friedl M, Konte B, Möller HJ, De Ronchi D, Stassen HH,
Serretti A, Rujescu D: AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with
haloperidol efficacy during acute treatment. Eur Neuropsychopharmacol. 2013; 23(8): 887-894
Giegling I, Balzarro B, Porcelli S, Schäfer M, Hartmann AM, Friedl M, Konte B, Krämer P, Möller HJ,
De Ronchi D, Stassen HH, Serretti A, Rujescu D: Influence of ANKK1 and DRD2 polymorphisms in
response to haloperidol. Eur Arch Psychiatry Clin Neurosci. 2013; 263(1): 65-74
Drago A, Giegling I, Schäfer M, Hartmann AM, Möller HJ, De Ronchi D, Stassen HH, Serretti A,
Rujescu D: No association of a set of candidate genes on haloperidol side effects.
PLoS One. 2012; 7(10): e44853
Giegling I, Drago A, Schäfer M, Hartmann AM, Sander T, Toliat MR, Möller HJ, De Ronchi D,
Stassen HH, Rujescu D, Serretti A: Lack of association between 71 variations located in
candidate genes and response to acute haloperidol treatment. Psychopharmacology 2011; 214(3):
719-728
Giegling I, Drago A, Dolzan V, Plesnicar BK, Schäfer M, Hartmann AM, Sander T, Toliat MR,
Möller HJ, Stassen HH, Rujescu D, Serretti A: Glutamatergic gene variants impact the clinical
profile of efficacy and side effects of haloperidol. Pharmacogenet Genomics. 2011; 21(4): 206-216
Gravemann S, Schnipper N, Meyer H, Vaya A, Nowaczyk MJM, Rajab A, Hofmann WK, Salewsky B,
Tönnies H, Neitzel H, Stassen HH, Sperling K, Hoffmann K: Dosage effect of zero to three
functional LBR-genes in vivo and in vitro. Nucleus 2010; 1(2): 1-12
Hoffmann K, Planitz C, Rüschendorf F, Müller-Myhsok B, Stassen HH, Lucke B, Mattheisen M,
Stumvoll M, Bochmann R, Zschornack G, Wienker TF, Nürnberg P, Reis A, Luft FC, Lindner TH: A
novel locus for arterial hypertension on chromosome 1p36 maps to a metabolic syndrome trait
cluster in the Sorbs, a Slavic population isolate in Germany. J Hypertens 2009; 27: 983-990
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
Tadic A, Rujescu D, Dahmen N, Stassen HH, Müller MJ, Kohnen R, Szegedi A: Association
Analysis between Variants of the Interleukin-1? and the Interleukin-1 Receptor Antagonist
Gene and Antidepressant Treatment Response in Major Depression. Neuropsychiatr Dis Treat
2008; 4(1): 269-276
Stassen HH, Angst J, Hell D, Scharfetter C, Szegedi A: Is there a common resilience mechanism
underlying antidepressant drug response? Evidence from 2'848 patients. J Clin Psychiatry 2007;
68(8): 1195-1205
Tadic A, Rujescu D, Müller MJ, Kohnen R, Stassen HH, Dahmen N, Szegedi A: A monoamine
oxidase B gene variant and short-term antidepressant treatment response. Prog
Neuropsychopharmacol Biol Psychiatry. 2007; 31(7): 1370-1377
Tadic A, Müller MJ, Rujescu D, Kohnen R, Stassen HH, Dahmen N, Szegedi A: The MAOA
T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in
major depression. Am J Med Genet B Neuropsychiatr Genet. 2007; 144(3): 325-331
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
Berger M, Stassen HH, Köhler K, Krane V, Mönks D, Wanner C, Hoffmann K, Hoffmann MM, Zimmer M,
Bickeböller H, Lindner TH: Hidden population substructures in an apparently homogeneous
population bias association studies. Eur J Hum Genetics 2006; 14: 236-244
Stassen HH, Angst J, Scharfetter C, Szegedi A: Therapie mit Antidepressiva: Erfolg von
genetischen Faktoren abhängig? Leading Opinions, Neurologie & Psychiatrie 2005; 6: 25-27
Szegedi A, Rujescu D, Tadic A, Müller MJ, Ralf Kohnen R, Stassen HH, Dahmen N: The
catechol-O-methyltransferase Val108/158Met-polymorphism affects short-term treatment response
to mirtazapine, but not to paroxetine in Major Depression. Pharmacogenomics 2005; 5(1): 49-53
Stassen HH, Bridler R, Hell D, Weisbrod M, Scharfetter C: Ethnicity-independent genetic basis
of functional psychoses. A Genotype-to-phenotype approach. Am J Med Genetics B 2004; 124:
101-112
Stassen HH, Hoffmann K, Scharfetter C: Similarity by state/descent and genetic vector spaces:
Analysis of a longitudinal family study. Genetic Analysis Workshop 13: Analysis of longitudinal
family data for complex diseases and related risk factors. BMC Genet 2003; 4, S59: 1-6
Stassen HH, Scharfetter C: Oligogenic approaches to the predisposition of asthma in ethnically
diverse populations. Genetic Analysis Workshop 12: Analysis of genetic and environmental factors
in common diseases. Genetic Epidemiology 2001; 21(1): 284-289
Hoffmann K, Stassen HH, Reis A: Genkartierung in Isolatpopulationen. Medizinische Genetik 2000;
12,4: 428-437
Stassen HH, Bridler R, Hägele S, Hergersberg M, Mehmann B, Schinzel A, Weisbrod M, Scharfetter C:
Schizophrenia and smoking: evidence for a common neurobiological basis?
Am J Med Genetics B 2000; 96: 173-177
Stassen HH and Scharfetter C: Integration of genetic maps by polynomial transformations.
Am J Med Genetics B 2000; 96: 108-113
Stassen HH, Begleiter H, Porjesz B, Rice J, Scharfetter C, Reich T: Structural decomposition of
genetic diversity in families with alcohol dependence. Genetic Analysis Workshop 11: Analysis
of genetic and environmental factors in common diseases. Genetic Epidemiology 1999; 17:
325-330
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The «Zurich Molecular Genetic Study of Psychiatric Vulnerability» encompasses 2,008 patients hospitalized for major psychiatric disorders along with 464 healthy controls. To date, 1,698 individuals of this study have been genotyped for 100 specifically selected polymorphic candidate genes with 681 informative SNPs.
We rely on methods of Artificial Intelligence in combination with multi-layer
Neural Nets in order to optimally fit vulnerability models to the observed data
("supervised learning").
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