Schizophrenia mainly occurs in puberty and adolescence, positive symptoms such as hallucinations and delusions, negative symptoms such as desire to motivation and emotion obsessive, cognitive impairment, etc. are observed, and many are related to chronic and recurrent course with a decline in social function. Schizophrenia is highly integrated in families, genome research focusing on its genetic factors was conducted. 108 risk loci were successfully identified by GWAS with large scale samples, and drug discovery based on these genes is expected. Advances in neuroimaging and neurophysiological research have also been remarkable, especially eye movement can be expected from objective auxiliary diagnostic methods. Furthermore, Measurement of cognitive decline could be an objective diagnostic method, as a measurement method is established for cognitive decline and the treatment method also changes depending on the presence or absence of cognitive decline. Although diagnostic methods are focused on intermediate phenotypes in this way, molecules / genes are necessary for development of therapeutic methods, and a translational approach is further expected.

View full abstract

Autism spectrum disorders (ASDs) arise during the early years of life with heterogeneous neurodevelopmental clinical conditions and are diagnosed based on DSM-5 criteria reflecting symptoms in social interaction, communication, repetitive behavior, and intense interests. Progress in understanding both the genetic and non-genetic etiology of ASDs has provided remarkable information in its potential neurobiological mechanisms, i.e. synaptic dysfunction, disrupted neuron-glia signaling, maternal immune activation and chronic neuroinflammation. With the early onset of ASDs, the intervention may occur at a very young age when the brain is under going the period of development and maturation. To reduce the unwanted effect to the developing brain, therapeutic intervention should be circuitry-specific. Combining genetic evidence, neuropathology, studies in animal studies, studies of human induced pluripotent stem cells models and clinical findings, more comprehensive translational research to develop an evidence-based theoretical framework for understanding ASDs and design more efficient and effective interventions is needed.

View full abstract

Activity-dependent synaptic plasticity is widely accepted to provide a cellular basis for learning and memory. Synaptic associativity could be involved in activity-dependent synaptic plasticity, because it distinguishes between local mechanisms of synaptic tags and cell-wide mechanisms that are responsible for the synthesis of plasticity-related proteins (PRPs) . An attractive hypothesis for synapse specificity of long-term memory (LTM) is synaptic tagging: synaptic activity generates a tag, which captures the PRPs derived outside of synapses. Here we show that neuropsin, a plasticity-related extracellular protease, is engaged in synaptic tag setting for late associativity in vitro and behavioral tag setting for LTM in vivo. First, we investigated about neuropsin dependent late associativity using electrophysiological technique. Neuropsin was involved in synaptic tagging during LTP at basal and apical dendritic inputs. Furthermore we next addressed whether a neuropsin was involved in behavioral tag setting. Behaviorally, weak training, which induces short-term memory (STM) but not LTM, can be consolidated into LTM by exposing animals to novel but not familiar environment 1 h before training. We found that neuropsin deficient mouse impaired such transformation STM into LTM. These results suggest neuropsin as a tag setting for synaptic plasticity and memory.

View full abstract

Many clinical and epidemiological researches have pointed out the importance of environmental factors, as well as genetic factors, in the etiology of psychiatric and neurodevelopmental disorders. Then, in late years, there is a growing number of animal studies focused on the environmental etiology of psychiatric illness. We have recently investigated the roles of juvenile environmental factors in the psycho-neurologic functions and the effects of maternal environment in the pre-and perinatal periods on the neurodevelopment of offspring. In this review, we summarize our findings on the improvement of psychobehavioral and neuroanatomical abnormalities by environmental factors and drug treatments during juvenile periods in the PACAP-KO mice, a schizophrenia animal model, and the prenatal valproate-exposed mice, an autism animal model, and further discuss the possibility of environmental regulation in the pathogenesis of psychiatric and neurodevelopmental disorders.

View full abstract

The clinical state of depression includes occurrence, response, acute phase, remission, relapse, and recurrence. It reminds us that their dynamic way is based on a neuroplastic change. In addition, ‘resilience’ is the suitable concept to study the prevention of depression and the condition of mild depression. In this review, I summarize the neuroplastic change, breakdown and modification by the nurturing environment of hypothalamic-pituitary-adrenocortical axis.

View full abstract

Patients with schizophrenia exhibit impairments in diverse cognitive functions, such as sensory processing, memory, attention, learning, reasoning, and executive function. These functions depend on neural networks formed by multiple brain regions, including areas of the cerebral cortex. Parvalbumin (PV) -expressing neurons represent one of the three separate subsets of cortical inhibitory neurons. Each PV neuron makes powerful, divergent inhibitory innervations on nearby pyramidal neurons and receives convergent excitatory inputs from pyramidal neurons. PV neurons are mutually connected through inhibitory synapses, forming homogenous interneuron networks. Recently developed optogenetics enabled targeted manipulations of PV neuron activities and successfully revealed roles of PV neurons. PV neurons are essential for the generation of neuronal oscillations, which enhance information processing within and between cortical areas in neural networks. During development and learning, PV neurons regulate neuronal plasticity through attenuation of their activities and resultant disinhibition of neural network. In the cortex of subjects with schizophrenia, lower expression levels of molecules that regulate excitability and neurotransmission of PV neurons have been observed in postmortem studies, indicating that alterations of PV neurons contribute to the cognitive deficits in schizophrenia, an idea supported by aberrant neuronal oscillations commonly observed in patients during various cognitive tasks. In order to test the involvement of PV neurons in the pathophysiology of cognitive deficits in schizophrenia, several mouse models, in which PV neurons were genetically manipulated to mimic their alterations in schizophrenia, has been created for analyses of their molecular, electrophysiological and behavioral phenotypes.

View full abstract

Based on the recent advances in genomic medicine, genome-wide association studies (GWASs) are now one of the main and basic technologies to detect susceptibility genes for complex disorders, including psychiatric disorders. This method also contributes the translational evidence between genomics and clinical medicine by detecting the related genes for treatment response or side effect caused by drugs, known as pharmacogenomics (PGx) . In this article, we review the recent findings of the GWASs and PGx for mood disorders and discuss with the future direction of the “mood disorder” genetics.

View full abstract