Neurobiology of chronic mental diseases
The neurobiology of chronic mental diseases like schizophrenia or the recurrent affective disorders is still poorly understood. In schizophrenia, for example, acute and chronic symptoms are known; whereas the psychosis involves striatal hyperdopaminergia and can be treated by dopamine antagonists, the underlying pathology leading to these neurotransmitter changes and also the chronic, lifelong impairments of cognitive dysfunction are unknown and escape efficient pharmacotherapy.
A common feature of dysfunctional neurons is a disturbance in proteostasis which leads to the protein deposition and aggregation in the classical neurodegeneartive diseases. While chronic mental diseases are clearly no neurodegenerative diseases, the identification of subtle alterations in proteostasis may equally lead to subtle protein aggregates in the chronic mental diseases which then can serve as a handle to further investigate the molecular mechanisms of fundamental neuronal dysfunction.
Carsten Korth's laboratory has pioneered the notion of misfolded proteins in chronic mental diseases (Interview of International Innovation with Carsten Korth from July 2012 on Mental illness Research) by demonstrating that insoluble DISC1 protein occurs in post mortem brain tissue of patients with chronic mental disorders, and that disease associated polymorphisms increase the tendency of DISC1 to form oligomers (Leliveld, J Neurosci, 2008; Leliveld, 2009; Seshadri, PNAS 2010). Furthermore, cell invasiveness of DISC1 aggregates was demonstrated (Ottis, Biol Psychiatry 2011) indicating that certain psychiatric diseases might be classified as protein conformational diseases (OpenAccess Review: Korth, Prion 2012), and thus display overlap in disease pathomechanisms with neurodegenerative diseases. Using a novel technique of epitope discovery and an interdisciplinary approach, CRMP1 was identified as a candidate protein in chronic mental illnesses (Bader, Hum Mol Genet 2012).
Wolfgang Gaebel's research groups deal with several aspects of the neurobiology of chronic and acute mental disorders. One focus is on the elucidation of the types of functional neurocircuits of the brain and their disturbances in mental disorders like schizophrenia (“modular psychiatry”; Gaebel and Zielasek, 2011; Seitz et al., 2011). Another aspect of this research is the role of social cognitive alterations in patients with schizophrenia as measured with facial affect recognition tests, their neurophysiological correlates (Wölwer et al., 2011) and their amelioration with the help of novel psychotherapeutic regimens. To elucidate the basic mechanisms of the pathophysiology of side effects of neurotropic drugs, an animal research group uses behavioural tests and neuropathological approaches (von Wilmsdorff et al., 2010). Finally, in the field of the neurodegenerative disorders, a research group investigates the modeling of small neuronal networks in vitro using synchronous neuronal firing as the readout for studying the role of potentially neurotoxic amyloid proteins (Görtz et al., 2009). Other, more clinically oriented neuroscientific projects, deal with the early detection and early treatment of chronic mental disorders like schizophrenia and Alzheimer´s disease using detection of early forms of the disorders and MRI-investigations (Luckhaus et al., 2010).