Affiliations: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Note: [] Corresponding author. Andreas Meyer-Lindenberg, M.D. Ph.D. M.Sc., Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Square J5, 68159 Mannheim, Germany. Tel.: +49 0621 1703 2001; Fax: +49 0621 1703 2005; E-mail: [email protected]
Abstract: Schizophrenia is a frequent and highly heritable brain disorder that typically manifests around or after puberty and has a fluctuating course. Multiple lines of evidence point to a neurodevelopmental origin of the illness and suggest that its (post) pubertal manifestation is related to genetic and environmental risk factors that interfere with the structural and functional reorganization of neural networks at this time. Longitudinal structural neuroimaging studies point to a progressive reduction in gray matter volume in many brain regions in schizophrenia. It has been proposed that these neuroimaging observations reflect an enduring disturbance of experience-dependent synaptic plasticity arising from developmental abnormalities in key neural circuits implicated in schizophrenia, including dorsolateral prefrontal cortex and hippocampal formation. Recent work has identified genetic variants linked to neural plasticity that are associated with changes in these circuits. Furthermore, non-invasive interventions such as transcranial magnetic stimulation have been shown to impact some of these systems-level intermediate phenotypes, suggesting a modifiability of these core pathophysiological processes of schizophrenia that may be exploited by therapy.
Keywords: Schizophrenia, plasticity, neurodevelopment, functional magnetic resonance imaging, graph theory, rapid transcranial magnetic stimulation
