Developmental models, Mutant mouse models, Network dysfunction, Neuromotor abnormality, Psychological symptoms, Psychotic illness
The authors' studies were supported by Science Foundation Ireland Principal Investigator Grant 07/IN.1/B960.
Limitations in access to antipsychotic-naïve patients and in the incisiveness of studies that can be conducted on them, together with the inevitability of subsequent antipsychotic treatment, indicate an enduring role for animal models that can inform on the pathobiology of neuromotor abnormalities in schizophrenia and related psychotic illness. This review focusses particularly on genetically modified mouse models that involve genes associated with risk for schizophrenia and with mechanisms implicated in the neuromotor abnormalities evident in psychotic patients, as well as developmental models that seek to mirror the trajectory, phenomenology and putative pathophysiology of psychotic illness. Such abnormalities are inconsistent and subtle in mice mutant for some schizophrenia risk genes but more evident for others. The phenotype of dopaminergic and glutamatergic mutants indicates the involvement of these mechanisms, informs on the roles of specific receptor subtypes, and implicates the interplay of cortical and subcortical processes. Developmental models suggest a criticality in the timing of early adversity for diversity in the relative emergence of psychological symptoms vis-à-vis neuromotor abnormalities in the overall psychosis phenotype. These findings elaborate current concepts of dysfunction in a neuronal network linking the cerebral cortex, basal ganglia, thalamus and cerebellum. Both findings in model systems and clinical evidence converge in indicating that any distinction between 'psychomotor' and 'neuromotor' abnormality is artificial and arbitrary due to a unitary origin in developmentally determined systems/network dysfunction that underlies the lifetime trajectory of psychotic illness.
Waddington JL, O'Tuathaigh CM. Modelling the neuromotor abnormalities of psychotic illness: Putative mechanisms and systems dysfunction. 2017 Aug 31 [epub before print]
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Available for download on Saturday, September 01, 2018