Polyunsaturated fatty acids and risk of anorexia nervosa: A Mendelian randomization study.

PURPOSE: Observational studies have suggested that polyunsaturated fatty acids (PUFAs) decrease the risk of anorexia nervosa (AN). In the present study, we examined this hypothesis using a Mendelian randomization analysis. METHODS: We used summary statistics for single-nucleotide polymorphisms associated with plasma levels of n-6 (linoleic acid and arachidonic acid) and n-3 PUFAs (alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) and the corresponding data for AN from a genome-wide association meta-analysis of 72,517 individuals (16,992 diagnosed AN cases and 55,525 controls). RESULTS: None of the genetically predicted PUFAs were significantly associated with the risk of AN; odds ratios (95 % confidence interval) per 1 standard deviation increase in PUFA levels were 1.03 (0.98, 1.08) for linoleic acid, 0.99 (0.96, 1.03) for arachidonic acid, 1.03 (0.94, 1.12) for alpha-linolenic acid, 0.98 (0.90, 1.08) for eicosapentaenoic acid, 0.96 (0.91, 1.02) for docosapentaenoic acid, and 1.01 (0.90, 1.36) for docosahexaenoic acid. LIMITATION: Only two types of fatty acids (LA and DPA) can be used for pleiotropy tests using the MR-Egger intercept test. CONCLUSION: This study does not support the hypothesis that PUFAs decrease the risk of AN.

Association between maternal infertility treatment and child neurodevelopment: findings from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Miyagi and Iwate Prefectures, Japan.

OBJECTIVES: This study aimed to examine the association between infertility treatment and neurodevelopment in children at 2 and 3.5 years of age. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: The study population consisted of mother-child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Miyagi and Iwate Prefectures, Japan. Pregnant women were recruited in obstetric clinics or hospitals and their children were followed up by the questionnaire. OUTCOME MEASURES: The children's neurodevelopmental outcomes were assessed at 2 and 3.5 years of age using the Ages and Stages Questionnaire, third edition (ASQ-3), which consists of questions on five developmental domains. We performed a multivariate logistic regression analysis of the association between infertility treatment (including ovulation induction (OI), artificial insemination with husband's sperm (AIH) and assisted reproductive technology (ART)) and the clinical range of ASQ-3. RESULTS: Of 9655 mother-child pairs, 273 (2.8%) and 487 (5.0%) were conceived through OI/AIH and ART, respectively. The odds of having developmental delays at 2 years of age were higher in children conceived through OI/AIH (OR, 1.36; 95% CI 1.00 to 1.85) and ART (OR, 1.36; 95% CI 1.07 to 1.72) than in those conceived naturally. Additionally, OI/AIH and ART were significantly associated with communication (OR, 1.93; 95% CI 1.25 to 2.98) and gross motor (OR, 1.50; 95% CI 1.08 to 2.09) delays, respectively. There were no statistically significant differences in the odds of having developmental delays at 3.5 years of age in children conceived through OI/AIH (OR, 1.13; 95% CI 0.79 to 1.61) and ART (OR, 1.03; 95% CI 0.78 to 1.37). CONCLUSION: In this study, we found a significant association between infertility treatment and children's neurodevelopment at 2 years of age, whereas no statistically significant differences were found at 3.5 years of age.

How does social support modify the association between psychological distress and risk of suicide death?

BACKGROUND: Social support (SS) has been reported as a factor preventing suicide death, but whether this association is independent of mental status is unclear. The present study examined the effect modification of SS on the association between psychological distress status and risk of suicide death. METHODS: Follow-up data for 43,015 subjects participating in a prospective cohort study were analyzed. At baseline, the subjects were asked about SS and mental status with the Kessler six-item Distress (K6) Scale. A Cox model was used to estimate the multivariate-adjusted hazard ratios (HRs) of suicide death according to two levels of psychological distress (K6 ≤ 4, K6 ≥ 5). The HRs in each SS subtype (emotional and instrumental) were also calculated. RESULTS: There was a significant association between SS and a lower risk of suicide death in the stratum of K6 ≥ 5, with an HR of 0.58 (95% confidence interval, 0.35-0.96). On the other hand, the association with the K6 ≤ 4 strata was not significant. CONCLUSION: SS appears to be associated with a lower risk of suicide death only among participants with moderate or severe psychological distress. These results imply that early detection of psychological distress and provision of SS is important for preventing suicide death.

Did Children in Single-Parent Households Have a Higher Probability of Emotional Instability during the COVID-19 Pandemic? A Nationwide Cross-Sectional Study in Japan.

The influence of public health measures against COVID-19 in Japan on child mental health by household type is unknown. This study aimed to investigate whether COVID-19 and the declaration of a state of emergency in Japan affected children's mental health between single-parent and two-parent households disproportionately. A large cross-sectional online survey was conducted from August to September 2020. The study included 3365 parents with children aged 0-14 years old who reported their children's mental status during the declared state of emergency. Emotional instability was reported dichotomously by parents. As the primary result, the probability of emotional instability was higher in single-parent households compared with that in two-parent households after adjustments for potential covariates; the adjusted prevalence ratio (95% CI) was 1.26 (1.07-1.49). Our findings suggest a disproportionate impact on children's mental health due to the pandemic.

Social Participation and Healthy Aging Among the Older Japanese: The Ohsaki Cohort 2006 Study.

BACKGROUND: Our study examined the association between social participation and healthy aging using a community-based cohort study among Japanese older adults. METHODS: This prospective study was conducted in Ohsaki City, Japan, and included 7226 participants aged ≥65 years at the baseline survey in 2006. We obtained information on frequency of participation in 3 types of community activities (ie, neighborhood activities, hobbies, and volunteer activities) at baseline. Exposure was measured by the number of types of community activities participated in and participants were categorized into 4 groups (ie, none, 1 type, 2 types, and 3 types). The primary outcome was healthy aging as assessed by a questionnaire survey conducted in 2017, and was defined as meeting the following 4 criteria: free of disability, free of depression, high health-related quality of life, and high life satisfaction. We used multiple logistic regression models to calculate the corresponding odds ratios and 95% confidence intervals. RESULTS: During 11 years of follow-up, 574 (7.9%) participants attained healthy aging. Compared with participants not participating in any activity, the multivariable-adjusted odds ratios (95% confidence intervals) were 1.90 (1.40, 2.59) for those participating in 1 type, 2.49 (1.84, 3.38) for 2 types, and 3.06 (2.30, 4.07) for 3 types (p for trend < .0001). Furthermore, for each type of community activity, a higher frequency of participation was related to higher probability of healthy aging. CONCLUSIONS: Our study suggests that social participation is associated with the promotion of healthy aging, and that the benefits were observed across different types of community activities.

Association between weight loss since the age of 20 years and the risk of suicide death: A population-based cohort study.

BACKGROUND: Past studies have demonstrated that body mass index (BMI) is inversely associated with the risk of suicide death. However, to our knowledge, no study has investigated the association between long-term weight change and the risk of suicide death. The purpose of this study was to investigate the association between weight change from the age of 20 years to middle or older age and the risk of suicide death in a population-based cohort. METHODS: We analyzed follow-up data for 41,746 participants aged ≥40 years and calculated percent weight change from age 20 years to that at the survey baseline (mean age: 61.2 years). A Cox model was used to estimate the multivariate-adjusted hazard ratios (HRs) for suicide death. RESULTS: The mean duration of follow up was 6.9 years, and suicide death was documented for 80 persons. Weight loss >5% (WL) was associated with a significantly higher risk of suicide death, with a multivariate-adjusted HR of 1.92 (95% confidence interval: 1.02-3.63). On the other hand, weight gain tended to be associated with a lower risk of suicide death. The significantly higher risk of suicide death observed among those showing WL did not change after excluding participants with a history of disease or psychological distress. LIMITATIONS: No information was given regarding the reasons for weight change and suicide death. CONCLUSIONS: The present results suggest that physicians should pay attention to individuals who lose weight from early adulthood because they could be at increased risk for suicide.

Effect of a financial incentive (shopping point) on increasing the number of daily walking steps among community-dwelling adults in Japan: a randomised controlled trial.

OBJECTIVE: The aim of this study was to investigate the effect of a financial incentive on the number of daily walking steps among community-dwelling adults in Japan. STUDY DESIGN: Two-arm, parallel-group randomised controlled trial. SETTING/PARTICIPANTS: We recruited physically inactive community-dwelling adults from Sendai city, Japan. Eligible participants were randomly allocated to an intervention or a wait list control group. Pedometers were used to assess the mean number of daily steps in three periods: baseline (weeks 1-3), intervention (weeks 4-6) and follow-up (weeks 7-9). INTERVENTION: The intervention group was offered a financial incentive (shopping points) to meet the target number of increased daily steps in the intervention period. MAIN OUTCOME MEASURES: The primary outcome was an increase in the mean number of daily steps in the intervention and follow-up periods compared with baseline. RESULTS: Seventy-two participants (69.4% women; mean age, 61.2±16.2 years; mean number of daily steps at baseline, 6364±2804) were randomised to the intervention (n=36) and control groups (n=36). During the intervention period, the increase in mean daily steps was significantly higher in the intervention group (1650, 95% CI=1182 to 2119) than in the control group (514, 95% CI=136 to 891; p<0.001). However, the difference between groups was not significant at follow-up after the incentives were removed (p=0.311). In addition, compared with controls, a significantly higher proportion of participants in the intervention group showed an increase in mean daily steps of ≥1000 (69.4% vs 30.6%, respectively; OR=5.17, 95% CI=1.89 to 14.08). There were no adverse effects from the intervention. CONCLUSIONS: The present results suggest that financial incentives are effective in promoting short-term increases in physical activity. TRIAL REGISTRATION NUMBER: UMIN000033276.

Emotional support (giving or receiving) and risk of incident dementia: The Ohsaki Cohort 2006 Study.

Previous studies have suggested that emotional support may promote cognition; however, the effects of giving or receiving emotional support on incident dementia remain unclear. Therefore, we sought to investigate the relationship between emotional support (giving or receiving) and incident dementia. In December 2006, we conducted a prospective cohort study of 31,694 Japanese individuals aged ≥65 years who lived in Ohsaki City, Miyagi Prefecture, Japan. A self-reported questionnaire including items on emotional support and lifestyle factors was distributed. After excluding those who did not provide consent or responses to all items, 13,636 eligible responses were analyzed for this study. According to responses of "yes" or "no" for emotional support, we made two categories for both giving (gave or did not give) and receiving (received or did not receive) emotional support. Furthermore, we combined giving and receiving emotional support into four categories ("giving = no & receiving = no", "giving = no & receiving = yes", "giving = yes & receiving = no", "giving = yes & receiving = yes"). Data on incident dementia were retrieved from the Long-term Care Insurance Database in which participants were followed up for 5.7 years. Using multivariate Cox proportional hazards models, we found that compared with participants who did not give emotional support to others, those who did give had a lower risk of dementia (multivariate-adjusted hazard ratio [HR]: 0.61 (95% confidence interval [CI]: 0.52, 0.71)). However, a nonsignificant relationship was observed for receiving emotional support. Additionally, compared to "giving = no & receiving = no" for emotional support, "giving = no & receiving = yes" showed a higher risk of dementia (multivariate-adjusted HR: 1.51 [95% CI: 1.07, 2.14]).

Randomised controlled trial of a financial incentive for increasing the number of daily walking steps: study protocol.

INTRODUCTION: Physical activity is one of the major modifiable factors for promotion of public health. Although it has been reported that financial incentives would be effective for promoting health behaviours such as smoking cessation or attendance for cancer screening, few randomised controlled trials (RCTs) have examined the effect of financial incentives for increasing the number of daily steps among individuals in a community setting. The aim of this study is to investigate the effects of financial incentives for increasing the number of daily steps among community-dwelling adults in Japan. METHODS AND ANALYSIS: This study will be a two-arm, parallel-group RCT. We will recruit community-dwelling adults who are physically inactive in a suburban area (Nakayama) of Sendai city, Japan, using leaflets and posters. Participants that meet the inclusion criteria will be randomly allocated to an intervention group or a waitlist control group. The intervention group will be offered a financial incentive (a chance to get shopping points) if participants increase their daily steps from their baseline. The primary outcome will be the average increase in the number of daily steps (at 4-6 weeks and 7-9 weeks) relative to the average number of daily steps at the baseline (1-3 weeks). For the sample size calculation, we assumed that the difference of primary outcome would be 1302 steps. ETHICS AND DISSEMINATION: This study has been ethically approved by the research ethics committee of Tohoku University Graduate School of Medicine, Japan (No. 2018-1-171). The results will be submitted and published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: UMIN000033276; Pre-results.

The association between emotional and instrumental social support and risk of suicide death: A population-based cohort study.

Suicide is an important public health issue and previous studies have suggested that social support can one preventive factor. However, the association between emotional and instrumental social support and suicide death has not been investigated in detail. The purpose of this study was to investigate the association between each type of social support and suicide death based on a population-based cohort study. We analyzed follow-up data for 47,223 subjects (aged ≥40 y) participating in a community-based, prospective cohort study. At the baseline, the subjects were asked five questions about social support. The end point of the study was suicide mortality, based on data from the National Vital Statistics. The Cox model was used to estimate the multivariate-adjusted hazard ratios of suicide death. In addition, stratified analysis was conducted to test the interaction of each type of social support with gender (male/female) and age (<65/≥65 y) separately. Among 320,880 person-years of follow-up, 90 cases of suicide death were documented. There were significant association between instrumental social support and lower risk of suicide death, and the hazard ratio was 0.60 (95% CI: 0.38-0.94). Emotional social support was also associated with a lower risk of suicide death, but not to a significant degree, and the hazard ratio was 0.70 (95% CI: 0.42-1.17). It is suggested that instrumental social support was significantly associated with a lower risk of suicide death, and emotional social support tended to be associated with a lower risk of suicide death.

Combined Healthy Lifestyle Behaviors and Disability-Free Survival: the Ohsaki Cohort 2006 Study.

BACKGROUND: Previous studies have suggested that a healthy lifestyle (HL) may prolong the years of life spent in good health. However, the impact of HL on disability-free survival (DFS) among the elderly is still uncertain. OBJECTIVE: To investigate the relationship between HL and DFS in the general elderly population. DESIGN: Prospective cohort study with a 10-year follow-up (2006-2016). PARTICIPANTS: 9910 community-dwelling elderly people (≥ 65 years). MAIN MEASURES: A HL index derived by summing the number of HL behaviors. Data on incident disability were retrieved from the public Long-term Care Insurance database. Multivariate-adjusted 50th percentile differences (PDs) in age at disability or death (months) and their 95% CIs were estimated with the Laplace regression model. KEY RESULTS: During the 10 years, 4562 disability or death events occurred. Participants who adhered to all three HL behaviors lived 17.1 (95% CI 12.7, 21.5) months longer without disability than those who adhered to zero or one. Each 1-point increase of the index score conferred 8.8 months additional life without disability. The tendency for the 50th PDs to increase with a higher HL index score did not differ according to age (< 75 or ≥ 75 years), sex, or the presence of chronic conditions (none, or ≥ 1 chronic condition). CONCLUSIONS: A combination of HL behaviors may substantially increase DFS, even for late-elderly (≥ 75 years), or elderly people with chronic conditions.

Psychological distress and completed suicide in Japan: A comparison of the impact of moderate and severe psychological distress.

It has already been established that severe psychological distress is a major risk factor for completed suicide. However, the impact (population attributable fraction; PAF) of moderate psychological distress on completed suicide has not been clarified. The present study investigated the association between various severities of psychological distress and completed suicide. We analyzed follow-up data covering a 7.3-year period (2006-2014) for 43,473 adults (aged ≥ 40 years) participating in a community-based, prospective cohort study. Psychological distress was measured using the K6 psychological distress scale at the baseline. Participants were classified into three groups according to their K6 score (low: 0-4; moderate: 5-12; severe: 13-24). Completed suicide was determined from a Japanese national database. The Cox model was used to estimate hazard ratios (HRs) for completed suicide. The PAFs of moderate and severe psychological distress for completed suicide were also estimated. The multivariate-adjusted HRs (95% confidence interval) for completed suicide were 2.37 (1.49-3.78) among participants with moderate psychological distress, and 4.16 (2.13-8.15) among those with severe psychological distress, relative to those with low psychological distress (P for trend < 0.001). The PAF of the moderate group for completed suicide was 26.8%, whereas that of the severe group was 10.9%. Not only severe but also moderate psychological distress was significantly associated with an increased risk of completed suicide. The PAF of moderate psychological distress for completed suicide was larger than that of severe psychological distress. Public health actions for suicide prevention should focus on moderate as well as severe psychological distress.

Association between social participation and incident risk of functional disability in elderly Japanese: The Ohsaki Cohort 2006.

BACKGROUND: Although several longitudinal studies have examined the relationship between social participation and incident functional disability, the related mechanisms have remained unclear. The aim of this study was to examine the mechanisms linking social participation to incident functional disability. METHODS: We analyzed follow-up data for 11,992 older adults (≥65 years) participating in a community-based, prospective cohort study covering a 9-year period. At the baseline, the subjects were asked about three types of participation in community activities (volunteering, hobbies, and neighborhood associations) and the frequency of their participation. Data on incident functional disability were retrieved from the public Long-term Care Insurance database. The Cox model was used to estimate the multivariate-adjusted hazard ratios of incident functional disability. We then conducted mediation analysis to assess the magnitude of the mediating effect. RESULTS: Among 84,760 person-years of follow-up, there were 3,984 cases of incident functional disability. The hazard ratio was 0.79 (95% CI: 0.73-0.86) for participating in one type of activity, 0.82 (95% CI: 0.74-0.90) for two types of activity and 0.70 (95% CI: 0.64-0.77) for three types of activity in comparison with no participation in any activity. Among the estimated mediating effects, cognitive activity accounted for 9.3%, time spent walking for 8.3%, psychological state for 4.6%, and social support for 2.8% of the reduced risk of incident functional disability. CONCLUSION: The results of this population-based cohort study indicate that cognitive activity and time spent walking are important mechanisms linking social participation to incident functional disability.

Impaired white matter connectivity between regions containing mirror neurons, and relationship to negative symptoms and social cognition, in patients with first-episode schizophrenia.

In schizophrenia, abnormalities in structural connectivity between brain regions known to contain mirror neurons and their relationship to negative symptoms related to a domain of social cognition are not well understood. Diffusion tensor imaging (DTI) scans were acquired in 16 patients with first episode schizophrenia and 16 matched healthy controls. FA and Trace of the tracts interconnecting regions known to be rich in mirror neurons, i.e., anterior cingulate cortex (ACC), inferior parietal lobe (IPL) and premotor cortex (PMC) were evaluated. A significant group effect for Trace was observed in IPL-PMC white matter fiber tract (F (1, 28) = 7.13, p = .012), as well as in the PMC-ACC white matter fiber tract (F (1, 28) = 4.64, p = .040). There were no group differences in FA. In addition, patients with schizophrenia showed a significant positive correlation between the Trace of the left IPL-PMC white matter fiber tract, and the Ability to Feel Intimacy and Closeness score (rho = .57, p = 0.034), and a negative correlation between the Trace of the left PMC-ACC and the Relationships with Friends and Peers score (rho = remove -.54, p = 0.049). We have demonstrated disrupted white mater microstructure within the white matter tracts subserving brain regions containing mirror neurons. We further showed that such structural disruptions might impact negative symptoms and, more specifically, contribute to the inability to feel intimacy (a measure conceptually related to theory of mind) in first episode schizophrenia. Further studies are needed to understand the potential of our results for diagnosis, prognosis and therapeutic interventions.

Initial and Progressive Gray Matter Abnormalities in Insular Gyrus and Temporal Pole in First-Episode Schizophrenia Contrasted With First-Episode Affective Psychosis.

Although the insula and temporal pole (TP) of paralimbic regions are important in both affective and cognitive processing, it is not well known whether gray matter volume (GMV) abnormalities in these regions show post-onset progression and differentially affect first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients. To determine whether there are initial and progressive GMV deficits in insula and TP in FESZ and FEAFF (mainly manic) patients, their relative specificity to FESZ or FEAFF, and relationship to symptoms, we conducted a naturalistic study at first hospitalization for psychosis and follow-up ~1.5 years later. Initial 1.5T magnetic resonance imaging (MRI) scans and follow-up scans were on the same scanner. Twenty-two FESZ, 23 FEAFF, and 23 healthy control (HC) subjects were group matched for age, gender, parental socioeconomic status, and handedness. At first hospitalization, FESZ showed significantly smaller bilateral insular GMV compared with FEAFF, and smaller left TP GMV compared with FEAFF and HC. Moreover, on 1.5 years follow-up, FESZ showed progressive GMV decreases in bilateral insula compared with FEAFF and HC, and in TP GMV compared with HC. In contrast, FEAFF showed no progression. Progression of FESZ GMV in both insula and TP was inversely associated with changes in the overall Brief Psychiatric Rating Scale symptom score, indicating less improvement or worsening of symptoms.

Relationships between exploratory eye movement dysfunction and clinical symptoms in schizophrenia.

AIM: Many psychophysiological tests have been widely researched in the search for a biological marker of schizophrenia. The exploratory eye movement (EEM) test involves the monitoring of eye movements while subjects freely view geometric figures. Suzuki et al. (2009) performed discriminant analysis between schizophrenia and non-schizophrenia subjects using EEM test data; consequently, clinically diagnosed schizophrenia patients were identified as having schizophrenia with high probability (73.3%). The aim of the present study was to investigate the characteristics of schizophrenia patients who were identified as having schizophrenia on EEM discriminant analysis (SPDSE) or schizophrenia patients who were identified as not having schizophrenia on EEM discriminant analysis (SPDNSE). METHODS: The data for the 251 schizophrenia subjects used in the previous discriminant-analytic study were analyzed, and the demographic or symptomatic characteristics of SPDSE and SPDNSE were investigated. As for the symptomatic features, a factor analysis of the Brief Psychiatric Rating Scale (BPRS) rating from the schizophrenia subjects was carried out. RESULTS: Five factors were found for schizophrenia symptoms: excitement/hostility; negative symptoms; depression/anxiety; positive symptoms; and disorganization. SPDSE had significantly higher factor scores for excitement/hostility, negative symptoms and disorganization than SPDNSE. Furthermore, the BPRS total score for the SPDSE was significantly higher than that for the SPDNSE. CONCLUSION: SPDSE may be a disease subtype of schizophrenia with severe symptoms related to excitement/hostility, negative symptoms and disorganization, and EEM parameters may detect this subtype. Therefore, the EEM test may be one of the contributors to the simplification of the heterogeneity of schizophrenia.

Midbrain volume increase in patients with panic disorder.

AIM: Although recent studies suggest abnormalities of the cerebral cortex, limbic structures, and brain stem regions in panic disorder (PD), the extent to which the midbrain is associated with PD pathophysiology is unclear. The aim of this study was to investigate structural abnormalities of the midbrain using magnetic resonance imaging and to determine if there is a clinical correlation between midbrain volume and clinical measurements in patients with PD. METHODS: Thirty-eight patients with PD (PD group) and 38 healthy controls (HC group) participated in this study. The midbrain was measured with a manual tracing method with high spatial resolution magnetic resonance imaging. The Panic Disorder Severity Scale and Global Assessment of Functioning were used to examine the correlation between volume abnormality and clinical symptoms and functioning in the PD group. RESULTS: Relative midbrain volume was larger in the PD group than in the HC group. The relative volume of the dorsal midbrain was larger in the PD group, while the volume of the ventral midbrain was not. We found a significant positive correlation between relative dorsal midbrain volume and total Panic Disorder Severity Scale score, and a significant negative correlation between relative dorsal midbrain volume and Global Assessment of Functioning score in the PD group. CONCLUSIONS: Our findings suggest that the dorsal midbrain is associated with PD pathophysiology. The midbrain volume increase may reflect PD severity.

Serotonergic neurotransmission in the living human brain: a positron emission tomography study using [¹¹C]dasb and [¹¹C]WAY100635 in young healthy men.

The central serotonergic (5-HT) system is closely involved in regulating various mental functions such as mood and emotion. In this system, the serotonin transporter (5-HTT) and the 5-HT(1A) receptor play important roles in the pathophysiology and treatment of mood and anxiety disorders. However, only a few integrated databases have considered the intraindividual relationship between pre- and postsynaptic serotonergic transmission. In the present study, we constructed a database of 5-HTT and 5-HT(1A) receptors using positron emission tomography (PET) with [¹¹C]DASB and [¹¹C]WAY100635, respectively. Seventeen healthy young men participated in this study. After anatomic standardization of original images, BP(ND) was calculated on a voxel-by-voxel basis using reference tissue methods. The highest binding to 5-HTT was observed in the dorsal raphe nucleus, striatum, and thalamus; moderate binding, in the insula and cingulate cortex; and very low binding, in the cerebral neocortex. In contrast, the highest binding to 5-HT(1A) receptors was seen in the hippocampal regions, insula, neocortical regions, and dorsal raphe nucleus, and very low binding was found in the thalamus and basal ganglia. These distribution patterns were in agreement with those reported in human postmortem studies and previous PET investigations. In addition, exploratory analysis indicated significant negative correlations between the BP(ND) values with both radiotracers in certain regions of the brain, such as the cingulate, insula, and frontal, temporal and parietal cortices (Pearson's correlation, P < 0.05). These databases facilitate the understanding of the regional distribution of serotonergic neurotransmission function in the living human brain and the pathophysiology of various neuropsychiatric disorders.

Effect of risperidone on high-affinity state of dopamine D2 receptors: a PET study with agonist ligand [11C](R)-2-CH3O-N-n-propylnorapomorphine.

The increased proportion of the high-affinity state of dopamine D2/3 receptors (D2,high) is assumed to correlate with dopamine hypersensitivity, implying a relationship with psychotic symptoms observed in psychiatric disorders such as schizophrenia. [11C](R)-2-CH3O-N-n-propylnorapomorphine ([11C]MNPA), which has an agonistic property to dopamine D2 receptors (D2Rs), is expected to bind preferentially to D2,high. The occupancy of dopamine D2Rs by antagonists to receptors has not been investigated using [11C]MNPA. We compared dopamine D2R occupancies by risperidone, an antagonist to receptors, between [11C]MNPA and [11C]raclopride to confirm whether risperidone occupies D2,high and D2,low at almost identical proportions. PET studies were performed on 11 healthy men under resting condition and following oral administration of a single dose of risperidone (0.5-2.0 mg). Striatal receptor occupancy for each radioligand was calculated. The relationship between dose or plasma concentration of risperidone and dopamine D2R occupancy was calculated. Striatal dopamine D2R occupancies measured with [11C]MNPA and [11C]raclopride were 22-65% and 24-69%, respectively. In the striatum, ED50 values measured with [11C]MNPA and [11C]raclopride were 0.98 and 1.03 mg, respectively. The striatal ED50 values as calculated from plasma concentration were 9.15 ng/ml and 8.01 ng/ml, respectively. Almost identical occupancies and ED50 values were observed between the two radioligands, indicating that risperidone bound to D2,high and D2,low at almost identical proportions in a dose-dependent manner.