Professor Dr. med. Christian Scharfetter

Dept. of Psychiatry, Psychotherapy & Psychosomatics

Psychiatric Hospital, University of Zurich

IFRG Logo
IFRG Emblem
Trithemius

Psychiatric Genetics, Genetic Epidemiology

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.

Psychiatric Disorders

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.

References

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

 

vSpacer Complex Interplay — Rather than Predetermined Fate
Within-pair concordances in mz twins for quantitative traits, such as "finger ridge count", "body height", "shoe size", "body weight", and "brain-wave patterns". Distributions are approximately normal with means ranging between 0.99 (finger ridge count) and 0.65 (body weight) for the above traits. Means and standard deviations provide information about (1) the magnitude of the genetic component, and (2) their "norm of variation" [Lykken and Stassen: data of 1,300 dz and 1,434 mz twin pairs].
For schizophrenia syndromes we found a within-pair concordance of 0.55 in mz twins.
Hspacer
[ Mail to Webmaster ] k454910@ifrg.ch
rFrame