Schizophrenia, neurodevelopment and corpus callosum

Abstract

The Zeitgeist favors an interpretation of schizophrenia as a condition of abnormal connectivity of cortical neurons, particularly in the prefrontal and temporal cortex. The available evidence points to reduced connectivity, a possible consequence of excessive synaptic pruning in development. A decreased thalamic input to the cerebral cortex appears likely, and developmental studies predict that this decrease should entail a secondary loss of both longand short-range cortico-cortical connections, including connections between the hemispheres. Indeed, morphological, electrophysiological and neuropsychological studies over the last two decades suggest that the callosal connections are altered in schizophrenics. However, the alterations are subtle and sometimes inconsistent across studies, and need to be investigated further with new methodologies.

The impact of asymmetrical light input on cerebral hemispheric specialization and interhemispheric cooperation

“…Deficits may only emerge when information of one hemisphere is not sufficient to solve a cognitive problem. These results suggest that cognitive impairments as observed in developmental or psychiatric disorders might also be only fully comprehensible by an understanding of abnormal interhemispheric communication systems, although genetic and/or environmental factors may primarily cause aberrations of intrahemispheric circuits 6,7 .…”

“…Accordingly, even profoundly lateralized cognitive functions, such as speech processing, benefit from efficient interhemispheric communication 2 . On the other hand, developmental disorders like autism 3 , dyslexia 4 or schizophrenia 5 are characterized by untypical cerebral lateralization patterns as well as structural peculiarities of the corpus callosum that are related to cognitive impairments [6][7][8][9][10] . Although several studies suggest a relationship between functional lateralization and structural organization of commissural systems, for example 11,12 , the functional and developmental relationships remain controversial 13 .…”

Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia

“…42 The pathophysiological symptoms of schizophrenia suggest a potential dysfunction in several brain regions that may also include neuronal and synaptic connections to temporal and frontal cortical regions, which are involved in higher cognitive functions, such as language and working memory. 43,44 In addition, MRI and post-mortem histopathological studies have revealed structural abnormalities in these cortical regions. 45,46 Interestingly, expression studies in mice showed a markedly reduced expression of PLXNA2 in the neocortex after birth, suggesting an important role in the development of neuronal connection patterns, especially in regions of the cortex.…”

Expression of disrupted in schizophrenia 1 (DISC1) protein in the adult and developing mouse brain indicates its role in neurodevelopment

“…Interestingly, cortex and hippocampus are regions strongly implicated in the pathophysiology of schizophrenia. [35][36][37][38] It was previously reported that density of neurons can be significantly reduced in certain layers of the cortex of schizophrenics. For example, schizophrenic subjects showed a significant decrease in density of nonpyramidal neurons in layer II and pyramidal neurons in layer IV of the anterior cingulated cortex.…”