We sometimes make boundedly rational decision- makings (altruistic behavior, moral judgment gamble etc.) , which is not accounted for by normative economic theories (e. g. expected utility theory) that assume that individuals are rational decision makers and have purely self- regarding preferences. These boundedly rational decision- makings are highly influenced by emotions. A leading alternative to the expected utility theory is the prospect theory. Central features of the prospect theory are non- linear probability weighting and loss aversion. We behaviorally estimated the degree of non- linearity of probability weighting, and the measured dopamine receptor density by positron emission tomography (PET) in healthy volunteers. We found that people with low D1 receptor density in the striatum showed more non- linear probability weighting (more pronounced overestimation of low probabilities and underestimation of high probabilities) . We also examined relationship between the degree of loss aversion and noradrenalin transmission by PET. Our finding was that individual with low norepinephrine transporter density in the thalamus tended to be more loss averse. Our approach may contribute to a better understanding of the role of neurotransmitters in emotional and boundedly rational decision- making in human. At the same time, understanding the molecular mechanism of extreme or impaired decision- making can con-tribute to the assessment and prevention of neuropsychiatric disorders.

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Cognitive Behavioral Therapy affects on cognitive and emotional dysfunction. Many evidence suggested Cognitive Behavioral Therapy is effective treatment for various psychiatric disorder. However, biological mechanism of action of Cognitive Behavioral Therapy is unclear. Recent neuroimaging study reported effect of Cognitive Behavioral Therapy on brain function. This article summarizes recent neuroimaging study for Cognitive Behavioral Therapy, and discusses biological mechanism of action of Cognitive Behavioral Therapy.

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We conducted a preliminary study to investigate the effects of a Neuropsychological Educational Approach to Cognitive Remediation (NEAR), one of the cognitive remediation therapies, on neurocognitive functions assessed by Japanese version of Brief Assessment of Cognition in Schizophrenia (BACS-J), and on prefrontal and temporal hemodynamic responses during working memory (WM) task (2-back, letter version) using 52-channel near-infrared spectroscopy (NIRS). We assessed sixteen patients with schizophrenia or schizoaffective disorder twice with an interval of six months. As previously reported, after NEAR, they showed significant improvement in four subcomponents of BACS-J, that is, verbal memory, motor speed, attention, executive functions along with composite score representing overall neurocognitive function. After NEAR, the patient group showed a significant increase in brain activation in bilateral cortical regions associated with working memory. In addition, the amount of enhancement in some cognitive subcomponents was positively correlated with the magnitude of an increase in hemodynamic response during WM task predominantly in right hemispheres. These findings suggest that neurocognitive deficits in schizophrenia and its related disorder, and their underlying neural dysfunction can be improved by NEAR.

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Two major therapeutic approaches, medication such as SSRI and cognitive behavior therapy (CBT), are taken for anxiety disorder. However, their efficacy is often not sufficient and has large individual difference. Some kind of biological background must underlie such individual difference. In this review, we discussed the issue from the two points of view, i. e., sensory gating measured as an event related potential of P50 and an animal model of fear conditioning/extinction paradigm. Impaired P50 response was observed in obsessive- compulsive disorder, which suggests disrupted sensory gating mechanism underlies the pathogenesis of anxiety disorders. Clinical strategies for effective fear extinction can be well simulated in the animal model, and cognitive enhancing agent such as D-cycloserine could be a candidate for newer approach in fear extinction learning.

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There is now ample evidence that selective serotonin reuptake inhibitors (SSRIs) and behavior therapy are highly effective methods for treatment of obsessive- compulsive disorder (OCD). It is, however, still unclear how these interventions improve the symptoms. A large number of recent neuroimaging studies using PET, SPECT and fMRI have found that abnormally high activities occur throughout the frontal cortex and subcortical structures in OCD and these hyperactivities were decreased after successful treatment using either SSRIs or behavioral therapy. In future, we should identify how each treatment repair the functional brain abnormalities in OCD. The evidence from recent neuroimaging studies also suggest that the orbitofronto- striatal model may not be sufficient to explain the brain basis of OCD and broader regions including dorsolateral prefrontal and posterior regions might involve pathophysiology of OCD. Furthermore, we should consider that OCD is heterogeneous and might have some different neural systems related to clinical factors. Neurobiological studies should be performed for development of treatment strategy with comprehension of OCD pathophysiology.

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[in Japanese]

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Multiple lines of evidence suggest that both genetic factor and environmental factor are associated with the onset of depression. Cohort studies are necessary for comprehensive investigation of interaction between genetic and environmental factor. However, in these studies, it is usually difficult to identify the stressor that may be important for of development of symptoms. This problem is less prominent in the study of if the postpartum depression where the relationship between stressor (i. e. pregnancy and childbirth), and development of the symptoms has already been established. Postpartum depression is suicide risk factor and affects mother’s Quality of life (QOL). In addition, maternal depression have a bad influence on the new- born child. Therefore, it’s imperative to establishment of an effective prevention and treatment protocols. In order to address these issues, we are performing prospective genome cohort study focused the pregnant woman who consulted obstetric service. At this point we have collected data from more than 600 women and we are expanding the number of participants In this article, we discuss the importance of the genome cohort study in depression research, and introduce a some of the data from our current research.

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An accurate population- based prospective cohort study of dementia was begun in 1985 in the town of Hisayama, Japan. To examine secular trends in the prevalence of dementia, four cross- sectional surveys were conducted among Hisayama residents aged 65 years or older in 1985, 1992, 1998, and 2005. The prevalence of Alzheimer’s disease (AD) significantly increased with time, while the prevalence of vascular dementia (VaD) decreased in the early period and then increased in late period. In a cohort study of incidence of dementia among Hisayama elder residents without dementia, the survival curve of dementia cases aged 65 to 89 years was significantly lower than that of age- and sex- matched control subjects randomly selected from those without incident dementia. We demonstrated that late- life hypertension was a significant risk factor for the development of VaD but not for AD, and people with mid- life hypertension were at an increasing risk of late- life onset of VaD regardless of late- life hypertension status. Meanwhile, we revealed the significant associations between glucose intolerance/diabetes and the risks of developing both VaD and AD. Additionally, elevating 2- hour postload glucose levels were closely associated with increased risk of VaD and AD.

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The Nagahama Study is a community - based long - term prospective cohort study co - organized by Kyoto University Graduate School of Medicine, Nagahama City in Shiga Prefecture and Zeroji Club, an NPO founded by citizens of Nagahama. The study was designed as a model case for the comprehensive understanding of health and disease in humans, through integrated analyses using information gathered from multiple omics studies in combination with life style and environment. It also aims to establish futuristic health promotion and the basis of personalized health care and disease treatment. More than ten clinical departments are involved in the project with a variety of target diseases such as COPD and asthma, cardiovascular diseases, ophthalmic diseases and periodontal diseases. The baseline study started in 2007, and a total of 115 biochemical and hematological traits have been measured from blood and urine samples. Self - administered questionnaire consisting of 742 questions were used to collect life style and environmental exposures as well as potential disease threats. The enrollment of 10,082 healthy residents was successfully finished in 2010. Genome- wide association study using SNP arrays was initiated in 2009 and, to date, approximately 4,000 DNA samples have been genome scanned and subjected to association analyses. Whole metabolome analysis is under way with GC- Mass spectrometry in collaboration with Shimazdu, a world- leading company of Mass spectrometry technology. A follow- up study planned every five years after the baseline survey will start this autumn to further accumulate health- related information and biological materials.

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