Abstract
The left and right hemispheres of the brain in most individuals are structurally and functionally specialized, but a significant minority displays an atypical variation in brain laterality specialization. Determining the biological basis of laterality specialization is essential for understanding the etiology of schizophrenia and bipolar disorder because they are often more prevalent in individuals with atypical brain laterality. These disorders are thought to be caused by contributions from hundreds of genes with small effects combined with environmental factors. However, lacking convincing evidence, the precise etiology of psychosis remains unknown. We have argued that chromosome 11 translocations associated with psychosis found in three families provide the only convincing evidence for the genetic etiology of psychosis. The paradoxes we try to resolve here concern the fact that the translocation breakpoints for chromosome 11 lie far apart, covering 40% length of the q arm, and the translocation associated psychoses is only 50% penetrant in each family. The selective chromatid segregation model has been proposed as a mechanism for the asymmetric cell division that initiates a cascade of gene regulation events in offspring cells to develop brain laterality in embryogenesis. The translocations we propose might cause random segregation of its sister chromatids to explain the result of 50% penetrance. We submit that errors in this system may explain the unique condition of these families. Here we review studies of model organisms that provide support to the model to explain brain laterality and psychosis development. We suggest that atypical brain laterality genetics predisposes carriers to develop general cases of psychoses due to developmental errors
Highlights
It is clear that schizophrenia and bipolar disorders result from anomalies in brain laterality development
We have previously argued that no convincing evidence exists in support of a genetic etiology for psychosis, other than that of the three
The major model for body laterality development postulates the distribution of morphogen gradients across the embryo, but it has remained a controversial model, despite decades of research, due to a lack of convincing evidence supporting it [16]
Summary
Because centromeres of chromosomes with translocations (Figure 1) would randomly segregate chromatids since RGHT1 factor does not function on them, 50% of the translocation carriers will develop symmetrical brain hemispheres, causing psychosis. This segregation mechanism proposes an epigenetic gene regulation process that deliberately generates asymmetric cell division of a specific cell during the period when brain laterality is initially established in embryogenesis.
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