Risikofaktoren für die Entstehung und den Verlauf der Schizophrenie

Gemäß dem derzeitigen Wissen entsteht eine Schizophrenie multifaktoriell – und zwar durch kumulative Wirkung einzelner, für sich unterschwelliger Risikofaktoren. Diese Faktoren (u. a. genetische, psychosoziale, umweltbedingte, prä- und peripartale) ziehen strukturelle Gehirnveränderungen und Veränderungen einzelner Neurotransmittersysteme nach sich, die schließlich zum Vollbild der Schizophrenie führen.

Schizophrenia is a severe psychiatric disorder with lifetime prevalence about 1 %. Usually, the disorder starts during the adolescence, however it is estimated that around 30 % of first-onsets are beyond the age of 40. The incidence of males is a little bit higher in the adolescence, while from the age of 40 the incidence in females is higher. In this context, the pathogenesis and development of schizophrenia is a complex model of gene-environment interactions and is not, like it was postulated in the earlier “One-Hit” or “Two-Hit” models caused by exclusively one or two single events. The risk to develop schizophrenia is composed of a biological predisposition with multi-genetic risk factors and changes in the neurotransmitter system, immunological influence factors and psychosocial risk factors. Genetic risk factors, perinatal risk factors and complications during birth could increase the probability of the disease. Besides these early risk factors traumatic events during childhood and especially risk factors like cannabis abuse that occur during adolescence which is a sensitive phase in the brain development could influence onset, development and relapse risk of the disease. If timing and sum of the single risk factors interact, they can cause the disturbance of neuronal regeneration and lead to schizophrenia, but the whole interaction of this multifactorial process is still not fully understood.

Key words

multifactorial disorder - gene-environment interaction - timing and sum of risk factors

• Literatur

• 1 McGrath J, Saha S, Chant D. et al. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev 2008; 30: 67-76
• 2 Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987; 44: 660-669
• 3 Murray RM, Lewis SW. Is schizophrenia a neurodevelopmental disorder? Br Med J (Clin Res Ed) 1987; 295: 681-682
• 4 Fatemi SH, Folsom TD. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull 2009; 35: 528-548
• 5 Davis J, Eyre H, Jacka FN. et al. A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis. Neurosci Biobehav Rev 2016; 65: 185-194
• 6 Falkai P. , Hrsg. Praxishandbuch Schizophrenie. München: Urban und Fischer / Elsevier; 2016
• 7 Janoutova J, Janackova P, Sery O. et al. Epidemiology and risk factors of schizophrenia. Neuro Endocrinol Lett 2016; 37: 1-8
• 8 Saha S, Chant D, Welham J. et al. A systematic review of the prevalence of schizophrenia. PLoS Med 2005; 2: e141
• 9 Ripke S NB, Corvin A, Walters JT. et al. Biological insights from 108 schizophrenia-associated genetic loci. Nature 2014; 511: 421-427
• 10 Hasan A, Malchow B, Falkai P. et al. [The glutamate hypothesis of schizophrenia]. Fortschr Neurol Psychiatr 2014; 82: 447-456
• 11 Howes O, McCutcheon R, Stone J. Glutamate and dopamine in schizophrenia: an update for the 21st century. J Psychopharmacol 2015; 29: 97-115
• 12 Schmitt A, Malchow B, Hasan A. et al. The impact of environmental factors in severe psychiatric disorders. Front Neurosci 2014; 8: 19
• 13 Kendler KS, Ohlsson H, Sundquist J. et al. IQ and schizophrenia in a Swedish national sample: their causal relationship and the interaction of IQ with genetic risk. Am J Psychiatry 2015; 172: 259-265
• 14 Markham JA, Koenig JI. Prenatal stress: role in psychotic and depressive diseases. Psychopharmacol (Berl) 2011; 214: 89-106
• 15 Boydell J. Risk factors for schizophrenia. Expert Rev Neurother 2001; 1: 183-191
• 16 Cannon TD, van Erp TG, Rosso IM. et al. Fetal hypoxia and structural brain abnormalities in schizophrenic patients, their siblings, and controls. Arch Gen Psychiatry 2002; 59: 35-41
• 17 Gibson LE, Alloy LB, Ellman LM. Trauma and the psychosis spectrum: A review of symptom specificity and explanatory mechanisms. Clin Psychol Rev 2016; 49: 92-105
• 18 Corcoran CM, Smith C, McLaughlin D. et al. HPA axis function and symptoms in adolescents at clinical high risk for schizophrenia. Schizophr Res 2012; 135: 170-174
• 19 van Os J, Kenis G, Rutten BP. The environment and schizophrenia. Nature 2010; 468: 203-212
• 20 Cantor-Graae E, Selten JP. Schizophrenia and migration: a meta-analysis and review. Am J Psychiatry 2005; 162: 12-24
• 21 Vassos E, Agerbo E, Mors O. et al. Urban-rural differences in incidence rates of psychiatric disorders in Denmark. Br J Psychiatry 2016; 208: 435-440
• 22 Boden JM, van Stockum S, Horwood LJ. et al. Bullying victimization in adolescence and psychotic symptomatology in adulthood: evidence from a 35-year study. Psychol Med 2016; 46: 1311-1320
• 23 Stirling J. Schizophrenia and expressed emotion. Perspect Psychiatr Care 1994; 30: 20-25
• 24 Large M, Sharma S, Compton MT. et al. Cannabis use and earlier onset of psychosis: a systematic meta-analysis. Arch Gen Psychiatry 2011; 68: 555-561
• 25 Murray RM, Quigley H, Quattrone D. et al. Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis. World Psychiatry 2016; 15: 195-204
• 26 Bossong MG, Niesink RJ. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Prog Neurobiol 2010; 92: 370-385
• 27 Di Forti M, Marconi A, Carra E. et al. Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. Lancet Psychiatry 2015; 2: 233-238
• 28 Murray RM, Englund A, Abi-Dargham A. et al. Cannabis-associated psychosis: Neural substrate and clinical impact. Neuropharmacology 2017; 124: 89-104
• 29 Schoeler T, Petros N, Di Forti M. et al. Association between continued cannabis use and risk of relapse in first-episode psychosis: A quasi-experimental investigation within an observational study. JAMA Psychiatry 2016; 73: 1173-1179
• 30 Muller-Vahl KR, Emrich HM. Cannabis and schizophrenia: towards a cannabinoid hypothesis of schizophrenia. Expert Rev Neurother 2008; 8: 1037-1048