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Highlights • GMA are present in psychiatric disorders with neurodevelopmental origin. • Motor dysfunction reflects vulnerability for the development of mental disorders. • This analysis will help promoting RDoC Motor System construct. Abstract Although genuine motor abnormalities (GMA) are frequently found in schizophrenia, they are also considered as an intrinsic feature of bipolar, obsessive-compulsive, and neurodevelopmental disorders with early onset such as autism, ADHD, and Tourette syndrome. Such transnosological observations strongly suggest a common neural pathophysiology. This systematic review highlights the evidence on GMA and their neuroanatomical substrates in bipolar, obsessive-compulsive, and neurodevelopmental disorders. The data lends support for a common pattern contributing to GMA expression in these diseases that seems to be related to cerebello-thalamo-cortical, fronto-parietal, and cortico-subcortical motor circuit dysfunction. The identified studies provide first evidence for a motor network dysfunction as a correlate of early neurodevelopmental deviance prior to clinical symptom expression. There are also first hints for a developmental risk factor model of these mental disorders. An in-depth analysis of motor networks and related patho-(physiological) mechanisms will not only help promoting Research Domain Criteria (RDoC) Motor System construct, but also facilitate the development of novel psychopharmacological models, as well as the identification of neurobiologically plausible target sites for non-invasive brain stimulation. [ABSTRACT FROM AUTHOR]

Schizophrenia is a severe behavioral syndrome of neurodevelopmental nature marked by primary or genuine motor abnormalities (GMA), which refer to spontaneous and medication-independent motor phenomena. Since motor dysfunction thus might be a consequence of events occurring during early childhood and adolescence, GMA can be detected in the period preceding manifest schizophrenia. However, the question whether motor system dysfunction might be a promising motor intermediate phenotype for schizophrenia remains unanswered. In this review, we systematically evaluate the evidence on GMA in healthy persons, individuals with schizotypal personality traits, persons at ultra-high risk for psychosis, and unaffected first-degree relatives of schizophrenia patients. What becomes evident is a continuum of GMA expression, which appears to be linked to abnormalities of cerebello-thalamo-cortical, fronto-parietal, and cortico-subcortical motor circuits. According to current evidence, motor dysfunction is a key aspect of the neurodevelopmental risk factor model of schizophrenia. Insights provided by this research will help promoting the RDoC Motor System construct and expand the clinical relevance of the motor domain in the period preceding manifest schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: Schizophrenia is a chronic, severe, and disabling brain disorder arising from the adverse interaction of predisposing risk genes and environmental factors. The psychopathology is characterized by a wide array of disturbing cognitive, emotional, and behavioral symptoms that interfere with the individual''s capacity to function in society. Contemporary pathophysiological models assume that psychotic symptoms are triggered by a dysregulation of dopaminergic activity in the brain, a theory that is tightly linked to the serendipitous discovery of the first effective antipsychotic agents in the early 1950s. In recent years, the availability of modern neuroimaging techniques has significantly expanded our understanding of the key mediator circuits that bridge the gap between genetic susceptibility and clinical phenotype. This paper discusses the pathophysiological concepts, molecular mechanisms and neuroimaging evidence that link psychosis to disturbances in dopamine neurotransmission. [Copyright &y& Elsevier]

Abstract: Recent clinical evidence for the effectiveness of new antipsychotic drugs that specifically target glutamate receptors has rekindled interest in the glutamatergic system regarding pathophysiology and treatment of schizophrenia. The glutamatergic hypothesis of schizophrenia was triggered by the clinical/behavioural observation that NMDA receptor antagonists can induce psychosis in humans and abnormal behaviour with schizophrenia-like symptoms in animals. Initial models focused on NMDA receptor hypofunction as a potential pathogenetic mechanism. More recent genetic and pharmacological studies revealed that malfunction of other components of the glutamatergic system might also be relevant in explaining specific symptoms of this complex disease. Here, we review mutant mouse models with relevance for schizophrenia. These rodent models, in which specific glutamate receptor subtypes or various components of their intracellular transduction machinery are genetically altered, permit a detailed dissection of the contribution of different components of the glutamate system in inducing schizophrenia-like behaviours. They may provide insight into the pathophysiology of schizophrenia and prove useful in the development of new therapeutics. [Copyright &y& Elsevier]