Research Group 'Psychiatric Genetics', Head: Prof. Dr. Hans H. Stassen

Department of Psychiatry, Psychotherapy and Psychosomatics

Psychiatric Hospital, University of Zurich


Age-of-onset and Age-cohort Changes in the Lifetime Occurrence of Depression?

Shifts towards Earlier Onset of Major Depression

In a re-investigation of the NIMH Psychobiology of Depression data, we have studied the question of shifts towards earlier onset together with the question of steadily increasing lifetime risk of major depression in successive birth-cohorts. Using a contingency-table approach, it turned out that inhomogeneities with respect to successive birth-cohorts exclusively showed up in the neighborhood of principally unobservable combinations of the variables under investigation. Standard approaches to testing independence in cross-classified data, such as the quasi-independence model, yielded highly significant results.

Log-Linear Model

However, through the definition of a log-linear model with weights which replaces the "discrete" truncation of the quasi-independence approach by a "smoothed" truncation, it was possible to fully explain the observed age-of-onset shifts, thus supporting the hypothesis that age-of-onset and birth-cohort are independent.

Generational Changes in the Lifetime Risk of Depression?

With respect to the question of generational changes in the lifetime risk of depression this independence implied that such changes should occur at equal rates across all ages of onset. The analysis yielded significantly larger cohort sizes for the two youngest birth cohorts, a fact which might be interpreted as an indication of increasing environmental impacts on the genetically predisposed vulnerability during recent years. However, our cross-sectional survey data were, by design, not an optimal basis for a reliable assessment of changes in the lifetime risk of depression, because the risk estimate derived from affected-only survey data corresponds to the probability that a depressive belongs to a certain birth-cohort and is only loosely related to the lifetime risk of this cohort (which is the probability that a person belonging to a certain birth-cohort develops depression).

Likely the Result of a Statistical Artifact

We therefore conclude, firstly, that method effects are likely to explain a major portion of secular trends thus far reported in the literature, and, secondly, that there appears to be no clear necessity to include changing environmental effects into quantitative genetic modelling.


Angst J., Scharfetter C, Stassen HH: Classification of Schizoaffective Patients by Multidimensional Scaling and Cluster Analysis. Psychiatria Clin 1983; 16: 254-264
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
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
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
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, 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
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
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
Angst J, Angst F, Stassen HH: Suicide risk in patients with major depressive disorder. J Clin Psychiatry 1999; 60,2: 57-62
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
Stassen HH: Veränderungen der Sprechmotorik. In: T.Jahn (ed) Bewegungsstörungen bei psychischen Erkrankungen. Springer Heidelberg 2004: 107-125
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, Angst J, Scharfetter C, Szegedi A: Therapie mit Antidepressiva: Erfolg von genetischen Faktoren abhängig? Leading Opinions, Neurologie & Psychiatrie 2005; 6: 25-27
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: 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, 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, Scharfetter C: Vulnerability, resilience and response to psychotropic drugs: shared genetic factors? Am J Med Genetics 2006; 141: 707-708
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

Manlio Bacosi (1921-1998): Winter — seeking shelter from a dark, cold, and threatening world (oil on canvas).
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