Biologische Hypothesen zur Schizophrenie: Mögliche Einflüsse von Immunologie und Endokrinologie

Abstract

A great number of studies show biological alterations in patients with schizophrenia, but many of these data are conflicting. Schizophrenia is a vastly heterogeneous disorder, most likely not caused by one etiological factor, but rather due to a complex network of different, interacting pathogenic influences. Variable clinical pictures may reflect different etiological factors. In a comprehensive theory of the origin of schizophrenic disorders, genetic and environmental influences cause changes in neuronal development which result in functional alterations of different neurotransmitter systems. Immunological research in schizophrenia was initially based on the "infection hypothesis" which was triggered by observing schizophrenia-like psychoses after influenza pandemic. Numerous immunological studies focusing on antibodies against specific viruses, unspecific antibodies and different other immune-phenomena were carried out in schizophrenia patients. Although the variability of the results from these studies is strikingly high, subgroups of patients with schizophrenia show an activated inflammatory response system with increased levels of proinflammatory cytokines and acute phase proteins. Furthermore, some investigations find changing activities in the T-cell system with a shift of TH-1 to an increased TH-2 activity. Endocrinological factors which may play a relevant role in the etiopathogenesis of schizophrenia include sex hormones and all changes caused by stress or other influences which are directly related to the HPA-axis. Alterations of the immune and the endocrinological systems might be caused by environmental factors like infections or exogenous stress. Due to the intensive interaction between the central nervous system, the immune system and different hormones the "development of a pathology" like schizophrenia can be seen in an integrative but multifactorial fashion. The clinical manifestation, the severity and the course of the disease might then be modulated by genetic vulnerability, the time of the "primary insult" -- which could be an infection, or psychological stress -- and its neuronal localisation and intensity. Different compensatory and decompensatory mechanisms in later life very likely play a crucial role for the further course of the disorder.

Effects of Two Commonly Found Strains of Influenza A Virus on Developing Dopaminergic Neurons, in Relation to the Pathophysiology of Schizophrenia

“…A relationship between viral infections and the onset of psychosis has been suspected for a long time because schizophrenia-like psychoses occur after InfV pandemics. Even though the extent of the association remains controversial, some patients with schizophrenia show increased proinflammatory cytokines, acute phase proteins, and TH-2 activity [56]. Yet again, no clear mechanism for the contribution of these environmental events to inherited (genetic) risk of disease has been established, even assuming that infections could either initiate schizophrenia by direct brain lesion or by triggering an autoimmune response during the neurodevelopmental period on a genetically susceptible brain [55].…”

Die Bedeutung des TNF-α-Systems für Erkrankungen des Gehirns

“…Als gesichertes Wissen kann aus Sicht der Autoren angesehen werden, dass proinflammatorische Zytokine wie TNF-α an der Entstehung von neurodegenerativen und zerebrovaskulären Erkrankungen [1, 64 -67] und depressiven Störungen beteiligt sind [79,81,85]. Des Weiteren wurde mehrfach beschrieben, dass im Gegensatz dazu bei schizophrenen Patienten eher ein Ungleichgewicht zugunsten antiinflammatorischer Zytokine besteht [146]. Aufgrund der referierten Literatur gibt es eine gewisse Evidenz dafür, dass eine Anti-TNF-α-Medikation zu einer Verringerung der depressiven Symptomatik bei Patienten führt, die an rheumatoider Arthritis oder einer Psoriasis leiden [137,138] und dass der TNF-α-Blocker Etanercept möglicherweise zur Behandlung der AD geeignet ist [53].…”

Social Phobia Is Associated with Delayed Onset of Chickenpox, Measles, and Mumps Infections

“…Current topics include prenatal infections with Toxoplasma gondii , rubella, and other infectious diseases (2, 3) as risk factors for neurodevelopmental disorders and schizophrenia. Furthermore, a series of postnatal infectious agents was reported in association with schizophrenia/psychosis (4–6). The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) model also postulates a crucial role for autoantibodies against basal ganglia tissue appearing after infections with group A streptococci in the development of attention deficit hyperactivity disorder, Gilles de la Tourette syndrome, and obsessive–compulsive disorder (OCD) (7, 8).…”