In the diagnostic criteria of DSM‐5, schizophrenia and autism spectrum disorder (ASD) are distinguished as different psychiatric disorders based on clinical symptoms. However, recent epidemiological and clinical studies have pointed out the existence of a continuum between the two disorders. Genomic studies have identified many cross‐disorder variants involved in the pathogenesis of both disorders. Among others, low frequency genomic copy number variations (CNVs ; including deletions and duplications) , such as 22q11.2 deletion, 15q11.2‐q13.1 duplication, and 3q29 deletion, have been reported to be involved in both schizophrenia and ASD. In‐depth analyses of CNV data have also found the similarities in pathological mechanisms of both disorders. In future studies, the relationship between schizophrenia and ASD may be clarified by following clinical symptoms from childhood to adulthood in subjects with these CNVs. In addition, neurobiological analyses using CNV‐based animal models and patient‐derived iPS cells are expected to elucidate the neural basis of both disorders.

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Psychiatric disorders are complex and common diseases that display familial aggregation, multifactorial inheritance, and clinical and genetic heterogeneity. Cognitive functions, brain structures, and personality traits are useful intermediate phenotypes to reduce these heterogeneity. Because genetic factors are involved in the disorders of intermediate phenotypes as well as in psychiatric disorders, it is assumed that there is a common genetic basis between psychiatric disorders and intermediate phenotypes. Large‐scale genome‐wide association studies (GWAS) have been conducted for various psychiatric disorders and intermediate phenotypes, and many related genomic loci have been identified. In contrast to GWAS, which attempt to identify more strongly related genomic loci, polygenic risk score and LD score regression analyses use genome‐wide genetic polymorphism information to examine the common genetic basis between psychiatric disorders and between psychiatric disorders and intermediate phenotypes. In this article, we introduce our studies on the genetic commonalities and disease specificities among psychiatric disorders and between psychiatric disorders and intermediate phenotypes using these analysis techniques.

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The core feature of PTSD is memory and cognitive symptoms such as re‐experiencing symptoms of traumatic memory. Regarding biological abnormalities of PTSD, inflammation has recently attracted attention. Supporting this, we have reported cognitive problems and increased inflammation in Japanese patients with PTSD. Meanwhile, genetic factors are shown to contribute to the development of PTSD by twin studies and others. Genetic factors also contribute to cognition and inflammation. It can therefore be hypothesized that the genetic factors involved in the vulnerability of PTSD would affect intermediate phenotypes including cognition and inflammation, thereby increasing the risk of developing this disorder. However, such possibilities have been understudied. We have conducted research projects that encompass clinical and psychological assessments, cognitive experiments, blood inflammatory marker measurements, and blood DNA and RNA analyses in PTSD patients and healthy controls, with the aim of elucidating the pathogenesis and pathophysiology of PTSD. In this paper we will discuss the pathogenesis of PTSD based primarily on the latest findings from our research project.

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Post Traumatic Stress Disorder (PTSD) is a psychiatric disorder associated with traumatic memories. Fear memory is a representative model of traumatic memories. Since fear memory is observed across species from insects to higher animals, including humans, biological basis to regulate fear memory are thought to be shared by humans and other animals. Therefore, findings from studies to understand fear memory processes using rodents have been applied to facilitate the development and improvement of PTSD treatment methods. In particular, the treatments that shortens prolonged exposure (PE) therapy, an effective psychotherapy for PTSD, have been devised. From these backgrounds, my group continues to develop novel treatments for PTSD using hippocampal neurogenesis enhancers that promote fear memory forgetting. In this review, I will introduce our approach to developing a treatment for PTSD based on biological mechanisms involved in fear memory processes, the findings in my group and clinical trials based on these research findings.

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Although stressful events predispose individuals to psychiatric disorders, such as post‐traumatic stress disorder (PTSD) and depression, not all people who encounter a stressful life experience have an onset, suggesting that gene‐environment interactions (GxE) determine disease risk. A growing evidence has implicated that stress‐induced aberrant synaptic and structural plasticity may be key underlying mechanisms of stress susceptibility. Recent studies have provided key insights into the biological significance of the regulation of gene expression in synaptic plasticity and behavioral response to chronic stress. The ventral hippocampus (vHPC) is vulnerable to damage from a variety of psychosocial stressors and aberrant structural and functional changes in this brain structure have been implicated in stress‐related psychiatric disorders. However, little is known about the role of transcription mechanisms within the vHPC in chronic stress‐induced aberrant neuronal plasticity and behavioral changes. Herein, I focus on causal and mechanistic evidence implicating altered functions of the vHPC in the establishment and the maintenance of stress resilience and susceptibility.

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In spite of the rapid progress of science, the diagnosis of psychiatric disorders is still based on a list of symptoms, and there are still no biomarkers that can be clearly visualized as other physical disorders. This is especially true for schizophrenia, which is still a mystery. On the other hand, recent studies have provided consistent evidence that the pathological basis of schizophrenia is related to abnormalities in gamma oscillation, a rhythmic activity with higher frequency of neural oscillation in the brain. The gamma oscillation can be measured relatively easily by electroencephalography (EEG) and magnetoencephalography (MEG) and is one of the best indicators to visualize the ever‐changing brain activity with high temporal resolution. Furthermore, basic research has also elucidated its generation mechanism, making it suitable for translational research. Thus, gamma oscillation is the best candidate as a functional indicator to visualize the varied and abnormal brain and psychotic phenomena in schizophrenia. In this review, we tried to discuss how to visualize the psychotic phenomena of schizophrenia based on gamma oscillation and how to elucidate the pathophysiology of schizophrenia and develop new treatment methods.

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