The Human Microbiome Project revealed that the human microbiome comprised about 10¹⁴ bacteria. It has become clear that intestinal microbiota plays an important role not only in metabolism but also in defense against infection and differentiation of host immune cells, and systemic diseases including neuropsychiatric disorders are associated with dysbiosis. Probiotics as therapeutic methods for restoration of intestinal microbiota do not show sufficient efficacy because the number of bacteria administered is too small compared to the whole intestinal bacterial flora. To solve this problem, fecal microbiota transplantation (FMT) was developed. In clinical studies of FMT for recurrent Clostridium difficile infection, FMT treated group was overwhelmingly inhibited in relapse compared with antibiotic therapy group. Previous reports showed the efficacy of FMT for functional gastrointestinal disorders and autism. Searching for adaptive diseases of FMT is being pursued and protocols including the frequency and method of administration are being studied. Although no serious adverse event associated with FMT have been reported so far, problems such as transmission of unknown infectious diseases, complications of the whole work and invasion to patients remain. Continuous efforts are required to ensure that treatment strategies based on human wisdom develop as preemptive therapy.

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Due to the development of metagenomics technology allowing for the analysis of the gut microbial genes exhaustively, a growing attention has been paid to the field of the gut microbiota for mental disorder over the last decade. However, a few clinical studies have been conducted to investigate the association between the gut microbiota and depression. In Japan, only one study demonstrated a significant difference in two bacterial counts in the gut in patients with depression compared to healthy subjects. Thus, further research is clearly needed to examine microbiota profiles in depression. To this aim, we conducted a systematic computerized literature search of MEDLINE, PubMed, EMBASE, PsycINFO and Cochrane library. The reference lists of the identified original articles and reviews were also searched manually for additional studies. Of the initial search of 95 records including nine records through other sources, the title and abstract of 65 studies were reviewed. We finally selected nine studies that examined the characteristics of gut microbiota in patients with depression : six are cross sectional studies and three are conducted with an intervention. I have summarized the current status in the field by using this systematic review.

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Interest in the microbiota‐gut‐brain axis, in which the intestine and the brain interact with each other via the microbiome and its metabolites, is rapidly growing. Autism spectrum disorder (ASD) is one of the most reported microbiota‐related disorders in the neuropsychiatric field. In ASD, differences in specific bacterial species and/or diversity (dysbiosis) as compared to healthy controls have been previously reported. Fecal Microbiota Transplantation (FMT) , for the purpose of restoring dysbiosis, has been noted as a novel treatment option for ASD. In this paper, we introduce up‐to‐date observational and intervention studies regarding the microbiota‐gut‐brain axis, and discuss future prospects, such as the possibility of therapeutic application and understanding the pathology of ASD through microbiome studies. There are no potential conflicts of interest to disclose.

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Delusional thoughts are common symptoms in patients with dementia. Delusions reduce the individual well‐being of the dementia sufferer and increase the burden of caregiver, therefore, early detection and adequate intervention on delusions is clinically important. According to previous reports and our data, many factors seem to be involved in the development of delusions in dementia. They include dementia type, severity of dementia, type of delusions such as misidentification delusions or persecutory delusions, cortical lesions such as frontal lobe or limbic system involvement, psychosocial factors such as loss experience, and so on. In terms of dementia type, 61% of patients with DLB had some delusions, whilst the prevalence of delusion in FTLD was extremely low. The different prevalence of delusions among different type of dementia suggests that some neurobiological factors may be associated with development of delusions in dementia. In addition, factor analysis revealed that delusions were classified under the same category as hallucinations in DLB. These results suggest that the disturbance of neuron systems such as dopamine or acetylcholine might be involved in delusions. On the other hand, FTLD may have resistance to delusions because of mild disturbances of dopamine neurons and severe frontal symptoms such as loss of empathy. It is important to take those factors into consideration in the management of delusions in patients with dementia.

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Auditory hallucination and thought disorder are main symptoms in patients with schizophrenia. These symptoms could profoundly affect the neural basis of social communications as well as various behaviors in daily life, i.e., by the appearance of auditory hallucination of some deeply pessimistic content, if the patient misattributes that it was real because he/she could not differentiate between auditory hallucination and real conversation, it could have a significant impact on daily life. However, it has not been fully verified how social communications are impaired, and whether cerebral function changes or not. In the current article, according to several items of evidence based on functional MRI, I will introduce our findings regarding impairment of the neural basis of auditory hallucination, and I will discuss cerebral dysfunction in relation to the appearance of auditory hallucination from the viewpoint of cognitive impairment of attractiveness prosody.

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The mechanism for auditory hallucinations of schizophrenia is not simple ; however, it seems important to investigate brain structures and functions related to psychotic symptoms. We will review findings of our structural and functional studies associated with auditory hallucinations. For the brain imaging study, the subregions of the lateral temporal lobe were measured by the manual drawing method. Compared to patients with no hallucinations, individuals with auditory hallucinations showed significantly reduced left superior temporal gyrus (STG) , left middle temporal gyrus and left inferior temporal gyrus. Therefore, it is suggested that left hemisphere gray matter volume reductions are dominant (especially STG) in patients with auditory hallucinations. In the P50m study, there was a significant positive correlation between the left P50m gating ratio and the auditory hallucinatory score (ρ=0.44, p=0.04) . More specifically, patients with more severe auditory hallucinations showed more affected filtering functions to human voices. Furthermore, in the auditory steady state response (ASSR) study, there was a significant negative association between the left ASSR power to 80 Hz‐clicks and the severity of auditory hallucinations (ρ=‐0.50, p=0.04) . Thus, patients with 80 Hz‐ASSR deficits may have more severe auditory hallucinations. Brain imaging and neurophysiological efforts will be important to understand the pathophysiology of schizophrenia.

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To study molecular basis for specialization of cortical architectures in primates, we have searched for genes differentially expressed among neocortical areas of macaque monkeys by restriction landmark cDNA screening (RLCS) . In the present study, we found that SLIT1, a member of axon guidance molecules, is enriched in the prefrontal cortex (PFC) . In situ hybridization analysis revealed that SLIT1 mRNA is mainly distributed in the middle layers of most cortical areas, highest in the PFC but fainter in primary sensory areas, lowest in V1. Other SLITs (SLIT2 and SLIT3) mRNAs exhibited modest specificity in the PFC, while the receptor, Roundabouts (ROBO1 and ROBO2) , mRNAs were widely distributed in the cortex. From late fetal to early postnatal days, SLIT1 mRNA was abundantly expressed in layers IV and VI throughout neocortex (except for V1) . The downregulation of the expression occurs initially in the sensory areas and follows in the association areas around postnatal days 60, and the prefrontal‐enriched pattern was established due to by the area‐and laminar‐specific reduced expression. These results suggest that the roles of SLIT1 are altered from the developmental to matured cortex to maintenance the prefrontal circuits in primates.

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