Institute for Response-Genetics (e.V.)

Chairman: Prof. Dr. Hans H. Stassen

Psychiatric Hospital (KPPP), University of Zurich

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Zurich Family Study of Functional Psychoses

In a prospective family study ascertained through 269 index cases suffering from functional psychoses, 1501 first- and second-degree family members, and a 20-year follow-up along with the assessment of 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 long-term outcome.

Familial Syndrome Patterns

Specifically, we carried out a multivariate cluster analysis based on the 16-dimensional, quantitative syndrome vectors 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. We searched for "natural" groupings that equally showed up among the index cases and the affected first-degree relatives. The analysis revealed three "core" clusters which were similarly present in the two populations under investigation. These three clusters encompassed patients across diagnostic entities —that is, patients with a diagnosis of schizophrenia, schizoaffective disorder or bipolar illness. The striking similarity of quantitative syndrome patterns between index cases (n = 136) and affected first-degree relatives (n = 116), as revealed by the largest "core" cluster, is demonstrated in Figure 1.

Familial Aggregation Rather than Genetic Segregation

There are considerable inter-individual differences in the quantitative syndrome patterns within the population of index cases and the population of "affected" first-degree relatives. Specifically, within-family comparisons of syndrome patterns demonstrate that the familial aggregation of psychopathology syndromes does not follow a homotypic pattern, that is, the data of nuclear families ascertained through index cases with a clinical diagnosis of functional psychosis do not provide evidence for genetic segregation.

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]
Moragrega I, Bridler R, Mohr C, Possenti M, Rochat D, Sanchez Parramon J, Stassen HH: Monitoring Mental Health and the Effects of Therapeutic Interventions through Self-Assessment Voice Analyses. Res Psychother. 2021, 24(3): 250-262 [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]
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]
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
Greil W, Zhang X, Stassen HH, Grohmann R, Bridler R, Hasler G, Toto S, Bleich S, Kasper S: Cutaneous adverse drug reactions to psychotropic drugs and their risk factors - a case-control study. Eur Neuropsychopharmacol. 2019; 29(1): 111-121 [get the article]
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]
Delfino JP, Barragán E, Botella C, Braun S, Camussi E, Chafrat V, Mohr C, Bridler R, Lott P, Moragrega I, Papagno C, Sanchez S, Soler C, Seifritz E, Stassen HH: Quantifying Insufficient Coping Behavior under Chronic Stress. A cross-cultural study of 1,303 students from Italy, Spain, and Argentina. Psychopathology 2015; 48: 230-239
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
Mohr C, Braun S, Bridler R, Chmetz F, Delfino JP, Kluckner VJ, Lott P, Schrag Y, Seifritz E, Stassen HH: Insufficient Coping Behavior under Chronic Stress and Vulnerability to Psychiatric Disorders. Psychopathology 2014; 47: 235-243
Stassen HH, Anghelescu IG, Angst J, Böker H, Lötscher K, Rujescu D, Szegedi A, Scharfetter C: Predicting Response to Psychopharmacological Treatment. Survey of Recent Results. Pharmacopsychiatry 2011; 44: 263-272
Kemp DE, Ganocy SJ, Brecher M, Carlson BX, Edwards S, Eudicone JM, Evoniuk G, Jansen W, Leon AC, Minkwitz M, Pikalov A, Stassen HH, Szegedi A, Tohen M, Van Willigenburg AP, Calabrese JR: Clinical value of early partial symptomatic improvement in the prediction of response and remission during short-term treatment trials in 3369 subjects with bipolar I or II depression. J Affect Disord. 2011; 130(1-2): 171-179
Lötscher K, Anghelescu IG, Braun S, Bridler R, Stassen HH: Polypharmacy in psychiatry: clinical practice versus empirical evidence. Eur Neuropsychopharmacol. 2010; 20 (Suppl. 3): 378-379
Stassen HH, Angst J, Hell D, Scharfetter C, Szegedi A: Is there a common resilience mechanism underlying antidepressant drug response? Evidence from 2848 patients. J Clin Psychiatry 2007; 68(8): 1195-1205
Stassen HH, Scharfetter C: Vulnerability, resilience and response to psychotropic drugs: shared genetic factors? Am J Med Genetics 2006; 141: 707-708
Stassen HH, Scharfetter C, Angst J: Functional Psychoses —Molecular-genetic Evidence for a Continuum. In: A. Marneros and H.S. Akiskal (eds) The overlap of affective and schizophrenic spectra. Cambridge University Press 2006; pp. 55-78
Stassen HH, Angst J, Scharfetter C: Genetik affektiver Störungen —der quantitative Ansatz syndrom-orientierter Modelle. In: M. Leuzinger-Bohleber, S. Hau, H. Deserno (hsg): Depression —Pluralismus in Praxis und Forschung, Vandenhoeck & Ruprecht, Göttingen, 2005, pp. 219-257
Stassen HH, Scharfetter C: Ethnische Zugehörigkeit und Vulnerabilität am Beispiel der Affektkrankheiten und Schizophrenien. Die Psychiatrie 2005; 2: 85-95
Stassen HH, Angst J, Scharfetter C, Szegedi A: Therapie mit Antidepressiva: Erfolg von genetischen Faktoren abhängig? Leading Opinions, Neurologie & Psychiatrie 2005; 6: 25-27
Angst J, Sellaro R, Stassen HH, Gamma A: Diagnostic conversion from depression to bipolar disorders: results of a long-term prospective study of hospital admissions. J Aff Disorders 2005; 84(2-3): 149-157
Stassen HH: Veränderungen der Sprechmotorik. In: T.Jahn (ed) Bewegungsstörungen bei psychischen Erkrankungen. Springer Heidelberg 2004: 107-125
Angst F, Stassen HH, Clayton PJ, Angst J: Mortality of patients with mood disorders: follow-up over 34 to 38 years. J Aff Disorders 2002; 68: 167-181
Angst J, Angst F, Stassen HH: Suicide risk in patients with major depressive disorder. J Clin Psychiatry 1999; 60,2: 57-62
Angst J, Stassen HH: Methodische Probleme der Prüfung von Antidepressiva. In: Stieglitz RD, Fähndrich E, Möller HJ (eds): Syndromale Diagnostik psychischer Störungen. Hogrefe, Göttingen 1998: 5-12
Stassen HH, Ragaz M, Reich T: Age-of-onset or age-cohort changes in the lifetime occurrence of depression? Psychiat Genetics 1997; 7: 27-34
Stassen HH, Schmid GB, Gross G, Angst J, Huber G: Prädiktoren des langfristigen Verlaufs schizophrener Erkrankungen. In: G. Huber (ed), Idiopathische Psychosen: Psychopathologie, Neurologie, Therapie. Schattauer, Stuttgart-New York, 1990: 95-104
Scharfetter C, Stassen HH: Psychopathological concepts. Psychopathology 1995; 28: 8-12
Angst J, Stassen HH, Gross G, Huber G, Stone MH: Suicide in affective and schizoaffective disorders. In: Marneros A. and Tsuang M.T. (eds) Affective and Schizoaffective disorders. Springer, Berlin-Heidelberg 1990: 168-185
Stassen HH, Scharfetter C, Winokur G, Angst J: Familial syndrome patterns in schizophrenia, schizoaffective disorder, mania and depression. Eur Arch Psychiatr Neurol Sci 1988; 237: 115-123
Stassen HH, Scharfetter C, Angst J: Morbid risks of subgroups of affective disorders: some methodological and empirical results. J Psychiat Research 1987; 21: 347-355
Angst J, Bänninger R, Nüsperli M, Scharfetter C, Stassen HH: Syndromale Gruppierungen endogener Psychosen in genetischer Sicht. In: Perspektiven der Schizophrenie-Forschung, ed: Pflug B., Foerster K., Straube E.; Fischer, Stuttgart New York, 1985: 25-38
Angst J., Scharfetter C, Stassen HH: Classification of Schizoaffective Patients by Multidimensional Scaling and Cluster Analysis. Psychiatria Clin 1983; 16: 254-264

 

 vSpacer Familial Syndrome Patterns
Striking similarity between mean quantitative syndrome patterns derived by averaging across index cases (n=136; green bars) and mean quantitative syndrome patterns derived by averaging across "affected" first-degree relatives (n=116; red bars), as revealed through multivariate cluster analysis of SSCL16 syndrome scores.
Please note: (1) there are considerable inter-individual differences in the quantitative syndrome patterns within the population of index cases and the population of "affected" first-degree relatives; (2) within-family comparisons of syndrome patterns demonstrate that the familial aggregation of psychopathology syndromes does not occur in a homotypic way, i.e., family data do not provide evidence for genetic segregation.
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