Parsing the neuroanatomy of schizophrenia to enhance the translational validity of preclinical models - a multidisciplinary perspective

People with schizophrenia can experience a range of symptoms, typically classified as positive (such as hallucinations, delusions), negative (such as avolition, anhedonia) or cognitive (such as attentional or working memory impairments). The accumulation of evidence from EEG, and structural and functional imaging, combined with post-mortem neurochemistry and pathology, has gradually focussed attention on altered function in a core neural circuitry as underlying the aetiology of schizophrenia. The principal circuits apparently fundamental to positive symptoms (e.g. auditory pathway, including auditory cortex) overlap with those apparently fundamental to negative/cognitive symptoms (e.g. ventral striatum, ventral tegmental area) at prefrontal cortex and reticular thalamus. This review summarises the various strands of evidence that lead to these conclusions, considers how this circuitry might be selectively affected according to our understanding of the causes of the disease, and then highlights how the knowledge of regionally-specific electrophysiological, imaging and neurochemical endophenotypes could be better exploited for translational purposes.