Abstract
Psychiatric disorders represent a heterogeneous class of multifactorial mental diseases whose origin entails a pathogenic integration of genetic and environmental influences. Incidence of these pathologies is dangerously high, as more than 20% of the Western population is affected. Despite the diverse origins of specific molecular dysfunctions, these pathologies entail disruption of fine synaptic regulation, which is fundamental to behavioral adaptation to the environment. The synapses, as functional units of cognition, represent major evolutionary targets. Consistently, fine synaptic tuning occurs at several levels, involving a novel class of molecular regulators known as long non-coding RNAs (lncRNAs). Non-coding RNAs operate mainly in mammals as epigenetic modifiers and enhancers of proteome diversity. The prominent evolutionary expansion of the gene number of lncRNAs in mammals, particularly in primates and humans, and their preferential neuronal expression does represent a driving force that enhanced the layering of synaptic control mechanisms. In the last few years, remarkable alterations of the expression of lncRNAs have been reported in psychiatric conditions such as schizophrenia, autism, and depression, suggesting unprecedented mechanistic insights into disruption of fine synaptic tuning underlying severe behavioral manifestations of psychosis. In this review, we integrate literature data from rodent pathological models and human evidence that proposes the biology of lncRNAs as a promising field of neuropsychiatric investigation.