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Institute for Response-Genetics (e.V.)

Prof. Dr. Hans H. Stassen, Chairman

(Formerly Associated Institute of the University of Zurich)

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Mechanisms that Support and Maintain Health

A subject's vulnerability is typically compensated, at least in part, by resilience factors. The term «resilience» is used here as a broader concept than just neurogenesis, encompassing all those intrinsic/endogenous mechanisms that support and maintain health, thereby enabling subjects to cope with stressful situations. In fact, chronic stress can lead to serious health problems and can affect nearly every system of the human body, as suggested by physical, cognitive, affective and behavioral symptoms. For a certain percentage of the general population, chronic stress raises blood pressure, increases the risk of heart attack and stroke, suppresses the immune system, and affects the vulnerability to psychiatric disorders, such as anxiety, depression, or schizophrenia. As no more than 15% of people under chronic stress will develop a psychiatric disorder at some point, the term «resilience» not only suggests a certain mental robustness, but probably also indicates a certain auto-therapeutic capacity. All this is likely to include personality traits supporting or impeding social skills.

Genetic Factors linked to Resilience?

Given the convincing results of our Neural Net derived molecular-genetic model of vulnerability to psychiatric disorders, we also addressed the question of the extent to which the concept of «healthiness» can be quantified in a similar way and might be helpful in strengthening a person's «resilience». To this end, we used the sample of healthy controls (n=267) as the target population while all patients of our study (n=1,431) served as control population. In fact, as was the case with our vulnerability approach, our analysis revealed genotype patterns that exhibited unique characteristics in the healthy target populations when compared to the affected control population. However, unlike in the case of vulnerability, the contribution of each significant gene to discrimination was quite small, so that even with 18 genes that reached significance, no more than 46% of individuals were correctly classified, whereas 54% were labeled as "unknown" (a false-positive rate of "0" was part of the optimization criteria). A further complicating detail was the fact that the sample selection had a much greater influence than was the case with the patients.

This result made it clear that a "positive" definition of «healthiness» is difficult to accomplish, if not impossible, so that its usefulness for investigations into the nature of «resilience» is questionable. The "negative" definition of «healthiness», namely not having certain genotype patterns of the affected patients, does not help in this context either. As an alternative, we would like to draw attention to the results of our studies with more than 3,000 students on coping behavior under chronic stress, which revealed 2 personality traits showing a close link between basic coping behavior and mental health problems, across cultures and ethnicities. The respective scores allow an early detection of psychiatric risk cases, nota bene prior to the development of clinically relevant symptoms. Additionally, there are known rules for such risk cases (some 10% of the general population) that have proven to be very effective in preventing psychiatric disorders: (1) get enough sleep, (2) control consumption behavior, (3) do regular exercises to meet the "Recommendation for Adults" of the American Heart Association as to regular moderate-intensity cardio or aerobic exercise (e.g., going for a walk/hike, riding a bicycle, doing sports).



References

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. 2021, doi: 10.1007/s00406-021-01358-5 [epub ahead of print] [get the article]
Stassen HH, Bachmann S, Bridler R, Cattapan K, Herzig D, Schneeberger A, Seifritz E. Inflammatory Processes linked to Major Depression and 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 H, 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
Stassen HH, Braun S, Bridler R, Seifritz E, Weisbrod M: Inflammatory Processes and Schizophrenia: Evidence from a Twin Study. Eur Neuropsychopharmacology 2017; 27 Suppl 4: S934-S935
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. European Archives of Psychiatry and Clinical Neuroscience 2017; 267: 377-389 [get the article]
Braun S, Annovazzi C, Botella C, Bridler B, Camussi E, Delfino JP, Mohr C, Moragrega I, Papagno C, Pisoni A, Soler C, Seifritz E, Stassen HH: Assessing Chronic Stress, Coping Skills and Mood Disorders through Speech Analysis. A Self-Assessment "Voice App" for Laptops, Tablets, and Smartphones. Psychopathology 2016; 49(6): 406-419 [get the article]
Delfino JP, Barragán E, Botella C, Braun S, Bridler R, Camussi E, Chafrat V, Lott P, Mohr C, Moragrega I, Papagno C, Sanchez S, Seifritz E, Soler C, 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
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, Delfino JP, Kluckner VJ, Lott P, Mohr C: Vulnerabilität und psychische Erkrankung. Swiss Archives of Neurology and Psychiatry 2014; 165(5): 152-157
Bridler R, Orosz A, Cattapan K, Stassen HH: In Need of Psychiatric Help – Leave a Message after the Beep. Psychopathology 2013; 46(3): 201-205
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
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
Lötscher K, Stassen HH, Hell D, Bridler R: Community-based crisis home programme – cost-efficient alternative to psychiatric hospitalization. Nervenarzt 2009; 80(7): 818-826
Stassen HH, Anghelescu IG, Braun S, Hoffmann K, Rujescu D, Scharfetter C, Szegedi A, Tadic A: Vulnerability to major psychiatric disorders, response to treatment and medical comorbidity – shared genetic factors? Eur Neuropsychopharmacol. 2009; 19 (Suppl. 3): 262
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
Stassen HH, Scharfetter C: Vulnerability, resilience and response to psychotropic drugs: shared genetic factors? Am J Med Genetics 2006; 141: 707-708 2007; 68(8): 1195-1205
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
Scharfetter C, Stassen HH: Psychopathological concepts. Psychopathology 1995; 28: 8-12
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
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

 

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quantitative genetic profile
Genes code for proteins or RNA ("gene products") which may interact among each other or the immediate environment in a variety of ways, and influence the phenotype only after a cascade of intermediate steps. That is, genes act quantitatively.
Please note: even though subjects may exhibit considerable deviations from the "optimal" genetic profiles associated with biological systems, self-regulation keeps their systems as a whole entity in stable conditions, thus guaranteeing high failure tolerance.
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