Median raphe serotonergic neurons projecting to the interpeduncular nucleus control preference and aversion

不快感を誘発するセロトニン神経を発見 --セロトニン神経の多様性が明らかに--. 京都大学プレスリリース. 2022-12-23.Appropriate processing of reward and aversive information is essential for survival. Although a critical role of serotonergic neurons in the dorsal raphe nucleus (DRN) in reward processing has been shown, the lack of rewarding effects with selective serotonin reuptake inhibitors (SSRIs) implies the presence of a discrete serotonergic system playing an opposite role to the DRN in the processing of reward and aversive stimuli. Here, we demonstrated that serotonergic neurons in the median raphe nucleus (MRN) of mice process reward and aversive information in opposite directions to DRN serotonergic neurons. We further identified MRN serotonergic neurons, including those projecting to the interpeduncular nucleus (5-HTMRN→IPN), as a key mediator of reward and aversive stimuli. Moreover, 5-HT receptors, including 5-HT2A receptors in the interpeduncular nucleus, are involved in the aversive properties of MRN serotonergic neural activity. Our findings revealed an essential function of MRN serotonergic neurons, including 5-HTMRN→IPN, in the processing of reward and aversive stimuli

Utility of TEMPS-A in differentiation between major depressive disorder, bipolar I disorder, and bipolar II disorder.

BACKGROUND:The association between temperament characteristics and mood disorders has gained much attention in recent years. The Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A) is a self-rating scale measuring 5 affective temperament dimensions. In this study, we aimed to clarify whether each affective temperament of TEMPS-A is a differentiating factor between major depressive disorder (MDD), bipolar I disorder (BD-I), and bipolar II disorder (BD-II), and analyzed the utility of TEMPS-A in their differential diagnosis in a clinical setting. METHODS:A total of 346 patients (MDD, n = 176; BD-II, n = 112; BD-I, n = 58) filled out TEMPS-A. To assess the patients' mood state at the time of temperament assessment, Patient Health Questionnaire-9 (PHQ-9) and Young Mania Rating Scale (YMRS) were also conducted. RESULTS:Multivariate logistic regression analysis demonstrated that cyclothymic and anxious temperament scores were significant factors differentiating the diagnosis of BD-I and BD-II from the diagnosis of MDD, and hyperthymic temperament score was a specific factor for the differential diagnosis of BD-I versus the diagnosis of BD-II. LIMITATIONS:All of the patients included in our study received treatment in large general hospitals. Because the nature of the present study was cross-sectional, some MDD subjects in this study might have unrecognized BD-I/BD-II. CONCLUSIONS:Cyclothymic and anxious temperament scores assessed by TEMPS-A might enable differentiation between MDD and BD, and hyperthymic temperament score on TEMPS-A might be useful in distinguishing between BD-I and BD-II

Neuroticism mediates the association between childhood abuse and the well-being of community dwelling adult volunteers

Abstract Background Previous studies reported that the experience of maltreatment in childhood reduces subjective well-being in adulthood and that neuroticism is negatively associated with subjective well-being. However, the interrelationship between childhood maltreatment, adult life events, neuroticism, and subjective well-being has not been analyzed to date. Methods A total of 404 adult volunteers provided responses to the following questionnaires: 1) Childhood Abuse and Trauma Scale, 2) Life Experiences Survey, 3) Neuroticism Subscale of the Shortened Eysenck Personality Questionnaire-Revised, and 4) Subjective Well-Being Inventory. The path model was used to analyze possible interrelationships among these parameters. Results The effect of childhood abuse on subjective well-being was indirect and was mediated by neuroticism. The effect of neuroticism on the negative, but not positive, change score on the Life Experiences Survey was significant. The indirect effect of neuroticism on subjective well-being was not significant via either negative or positive change scores. Conclusions This study demonstrated that age, subjective social status, neuroticism, and negative and positive life events were significantly associated with subjective well-being. Furthermore, using path analysis, we demonstrated the mediating role of neuroticism in the indirect effect of childhood abuse on subjective well-being

Identification of the simultaneous use of multiple hypnotics as a risk factor for falls in hospitalized patients by a matched case-control study.

AimThe risk of falls owing to simultaneous use of multiple hypnotics has not been clarified. The aim of this study was to assess the association between the simultaneous use of 2 hypnotics and the occurrence of falls in hospitalized patients.MethodsA matched case-control study was conducted at Tokyo Medical University Hospital in Tokyo, Japan, utilizing data from medical records. Cases were 434 hospitalized patients who experienced falls during their hospital stay between January 2016 and December 2016, and controls were 434 hospitalized patients without falls, individually matched by age, sex, and clinical department. The outcome was the occurrence of an in-hospital fall. The associations between the use of 1 hypnotic and falls, and between the use of 2 hypnotics and falls were assessed by conditional logistic regression analyses. The main multivariable conditional logistic regression model was adjusted for potential risk factors, including the use of other classes of psychotropics (antipsychotics, antidepressants, and anxiolytics), in addition to patient characteristics.ResultsThe main multivariable conditional logistic regression analyses showed that the simultaneous use of 2 hypnotics (odds ratio [OR] = 2.986; 95% confidence interval [CI], 1.041-8.567), but not the use of a single hypnotic (OR = 1.252; 95% CI, 0.843-1.859), was significantly associated with an increased OR of falls.ConclusionThe simultaneous use of 2 hypnotics is a risk factor for falls among hospitalized patients, whereas the use of a single hypnotic may not

Depressive rumination and trait anxiety mediate the effects of childhood victimization on adulthood depressive symptoms in adult volunteers.

BackgroundPrior studies have reported that childhood victimization experiences substantially augment the risk of depression and suicide in adulthood. Several of our previous studies suggested that childhood experiences of victimization interact with the quality of parenting experienced in childhood, childhood experiences of abuse, neuroticism, and other factors to influence depressive symptoms in adulthood. In this study, it was hypothesized that "childhood victimization" worsens "trait anxiety" and "depressive rumination", and that "trait anxiety" and "depressive rumination" are mediators that worsen "depressive symptoms in adulthood".Subjects and methodsThe following self-administered questionnaires were completed by 576 adult volunteers: Patient Health Questionnaire-9, State-Trait Anxiety Inventory form Y, Ruminative Responses Scale, and Childhood Victimization Rating Scale. Statistical analyses were performed by Pearson correlation coefficient analysis, t-test, multiple regression analysis, path analysis, and covariance structure analysis.ResultsPath analysis demonstrated that the direct effect was statistically significant for the paths from childhood victimization to trait anxiety, depressive rumination, and depressive symptom severity. Moreover, the indirect effect of childhood victimization on depressive rumination mediated by trait anxiety was statistically significant. The indirect effects of childhood victimization on depressive symptom severity mediated by trait anxiety and depressive rumination were statistically significant. Furthermore, the indirect effect of childhood victimization on depressive symptom severity mediated by both trait anxiety and depressive rumination was statistically significant.ConclusionsWe found that childhood victimization directly and adversely influenced each of the above factors, and indirectly worsened adulthood depressive symptoms with trait anxiety and depressive ruminations as mediating factors. The present study is the first to clarify these mediation effects. Therefore, the results of this study suggest the importance of preventing childhood victimization and the importance of identifying and addressing childhood victimization in patients with clinical depression