There is no question that genes are the cornerstones of our organism. Ultimately, even
such complex phenomena like affective reactions can be linked to genes as the driving source
in the background. However, the gene products for which genes code represent only intermediate
stages on the long way from genotype to observed phenotype. Genes must not be viewed as
isolated factors but, rather, are interacting with each other and with the organism's
environment in a variety of ways, for example, as described by the theory of dynamic systems
with many degrees of freedom, where none of the underlying factors, in isolation, is either
necessary or sufficient for the development of the phenotype. To a large extent, self-regulating
dynamic systems display robust error-tolerance in such a way that temporary,
intermediate or long-term deficiencies or excesses in one or another factor — induced
through exogenous or endogenous influences — can easily be compensated by the other
factors of the system.
Like all complex traits and illnesses, psychiatric disorders are influenced by multiple genes
as well as multiple non-genetic factors. The genetic component's magnitude correlates with
the severity of underlying syndromes and may vary from 10-70%. There is no single
"biogenic imbalance" that causes psychiatric disorders. Rather, the complex interplay between
several self-regulating, intrinsic/endogenous subsystems, upon which the organism can "normally"
rely, becomes distorted, for whatever reasons. This situation is evident in monozygotic
twins who share identical genomes but remain discordant over a lifetime for severe psychiatric
disorders, such as schizophrenia, schizoaffective disorders, bipolar illness or major depression.
There may even exist different pathways to the phenotype in ethnically diverse populations,
although prevalences are very similar worldwide across ethnicities.
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
Stassen HH and Scharfetter C: Integration of genetic maps by polynomial transformations.
Am J Med Genetics B 2000; 96: 108-113
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
Hoffmann K, Stassen HH, Reis A: Genkartierung in Isolatpopulationen. Medizinische Genetik 2000;
12,4: 428-437
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
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, 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
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, 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
Tadic A, Rujescu D, Muller 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, Muller 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
Tadic A, Rujescu D, Dahmen N, Stassen HH, Muller 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, Hoffmann K, Scharfetter C: The Difficulties of Reproducing Conventionally Derived
Results through 500k-Chip Technology. BMC Genet Proc. 2009; 3 Suppl 7: S66
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
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
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
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
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, 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