Towards understanding the neural mechanism of behavioral phenotypes seen in psychiatric disorders

Patients with psychiatric disease are diagnosed by psychiatrists based on the information of non-quantitative objective parameters, including behavioral phenotypes. However, how any neural mechanism affects such behavioral phenotypes in patients is still unclear. Recent functional studies suggested the alteration in brain neural/network activity responds to subjected stimuli in some brain regions of psychiatric patients, indicating that excitatory/inhibitory (E/I) imbalance occurs in local neural circuits responsible for regional activities. Moreover, in human genetics, a large number of genetic variations, including single nucleotide variation (SNV) and copy number variation (CNV), have been found in psychiatric patients. Such variations must be causes of a psychiatric behavioral phenotype, while understanding of the relationship between genetic variations and neural mechanisms underlying psychiatric behavior remains poor due to the heterogeneity in genetic variations. Functional and molecular analyses with SNV and CNV suggest the mutations of synaptic genes might contribute to the abnormal neural activity due to synaptic dysfunction. To overcome the sparse knowledge of psychiatric neural phenotypes, we can choose two ways: one is to detect the abnormalities of neural function in animal models with the genetic variations found in human genetics, which means construct validity of an animal model, and another is to reproduce the behavioral phenotypes seen in psychiatric disorders by artificially controlling neural functions, referred to as face validity. Analyzing the neural activity in animal models with construct and face validities would help us understand the neural state in psychiatric patients.