The utility of current diagnostic entities for genetic studies seems limited, since
psychiatric diagnoses incompletely cover the patients’ prodromal phase, age-of-onset,
severity of illness, long-term course, and impairment. In particular, psychiatric diagnoses
do not offer much information about a patient’s response to treatment and prognosis.
Quantitative, syndrome-oriented approaches to psychopathology extend the DSM-IV or ICD-10
phenotype definitions by replacing the dichotomy of the diagnostic schema by dimensional
quantities. These quantities allow one to assess intra-familial patterns of psychopathology
that do not reach diagnostic significance. Our syndrome-oriented approach to psychopathology
includes 16 syndromes and leads to a representation of psychopathology patterns via
16-dimensional quantitative "syndrome vectors" that are extracted from the DIGS and SSCL16
rating instruments.
In a prospective family study of 269 index cases suffering from functional psychoses,
350 affected first- and second-degree relatives, a 20-year follow-up of the index cases, and
105 offspring of the index cases, we applied a multivariate syndrome-oriented approach to
psychopathology in order to derive a quantitative measure of the severity of illness and to
partition the population into "natural" subgroups. Our main interest was focused on: (1) the
question of increasing severity of psychoses across generations (anticipation), (2) the
question of differences in the severity of psychoses depending on whether the illness has
been transmitted by the maternal or paternal side (genomic imprinting), and (3) the question
of age-of-onset shifts toward earlier onset of psychoses in successive birth cohorts (secular
trends). Structural analyses revealed clearly distinguishable subgroups of patients
characterized by differences in the familial aggregation of syndromes and in the longterm
outcome [Stassen et al. 1988; Scharfetter and Stassen 1995; Scharfetter et al. 1999, 2002].
We carried out multivariate cluster analysis based on the 16-dimensional, quantitative syndromes
derived from the 269 index cases with a diagnosis of functional psychosis, on the one hand, and
from the 350 first-degree relatives who exhibited psychopathologic features in our quantitative
SSCL-16 syndrome scores, on the other. Our search for "natural" groupings revealed three "core"
clusters which were similarly present in the two populations under investigation. There was
Striking similarity between mean quantitative syndrome patterns derived by averaging across
index cases and mean quantitative syndrome patterns derived by averaging across "affected"
first-degree relatives. Despite this striking similarity on the group level, within-family
comparisons of syndrome patterns demonstrate that the familial aggregation of syndromes does not
occur in a homotypic way, i.e., family data do not provide evidence for genetic segregation.
This finding is specifically supported by twin samples ascertained through co-twins suffering
from schizophrenic disorders, where highly significant deviations from the mz:dz ratio of 2
indicate the existence of strong non-linearities in the genetic predisposition to functional
psychoses.
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)
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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. Eur Arch Psychiatry Clin Neurosci. 2024.
doi: 10.1007/s00406-024-01918-5 (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. 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
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, 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, 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, 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