The evolutionary origin of psychosis

Abstract

Imagination, the driving force of creativity, and primary psychosis are human-specific, since we do not observe behaviors in other species that would convincingly suggest they possess the same traits. Both these traits have been linked to the function of the prefrontal cortex, which is the most evolutionarily novel region of the human brain. A number of evolutionarily novel genetic and epigenetic changes that determine the human brain-specific structure and function have been discovered in recent years. Among them are genomic loci subjected to increased rates of single nucleotide substitutions in humans, called human accelerated regions. These mostly regulatory regions are involved in brain development and sometimes contain genetic variants that confer a risk for schizophrenia. On the other hand, neuroimaging data suggest that mind wandering and related phenomena (as a proxy of imagination) are in many ways similar to rapid eye movement dreaming, a function also present in non-human species. Furthermore, both functions are similar to psychosis in several ways: for example, the same brain areas are activated both in dreams and visual hallucinations. In the present Perspective we hypothesize that imagination is an evolutionary adaptation of dreaming, while primary psychosis results from deficient control by higher-order brain areas over imagination. In the light of this, human accelerated regions might be one of the key drivers in evolution of human imagination and the pathogenesis of psychotic disorders.

Volume electron microscopy reveals 3D synaptic nanoarchitecture in postmortem human prefrontal cortex

“…Because whole, intact brains are typically obtained, postmortem sources also permit analysis of multiple brain regions from a single subject, as well as analysis of regions not typically obtained during neurosurgery. For example, the dorsolateral prefrontal cortex (DLPFC) is a higher-order, multi-modal association area 38,39 that is uniquely expanded in humans 40,41 , and is considered a key site of synaptic dysfunction in human-specific psychiatric disorders [42][43][44][45] . EM analysis of DLPFC obtained postmortem presents a unique opportunity to investigate synaptic and sub-synaptic impairments present in individuals with psychiatric disorders relative to individuals unaffected by brain disorders.…”