Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutes–hours) and long period of time (days–weeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the lack of technologies with robustness, reversibility, and spatio-temporal control. Recently, we have demonstrated that our chemogenetic approach (eg, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) provides a reliable and robust tool for controlling genetically defined neural populations. Here we show how short- and long-term activation of dorsal raphe nucleus (DRN) serotonergic neurons induces robust behavioral responses. We found that both short- and long-term activation of DRN serotonergic neurons induce antidepressant-like behavioral responses. However, only short-term activation induces anxiogenic-like behaviors. In parallel, these behavioral phenotypes were associated with a metabolic map of whole brain network activity via a recently developed non-invasive imaging technology DREAMM (DREADD Associated Metabolic Mapping). Our findings reveal a previously unappreciated brain network elicited by selective activation of DRN serotonin neurons and illuminate potential therapeutic and adverse effects of drugs targeting DRN neurons

Characterization of the stanford integrated psychosocial assessment for transplant for heart, liver, and kidney transplant candidates in Japan

Abstract Background The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a comprehensive psychosocial assessment proven useful for predicting the outcomes of organ transplantation that is expected to be useful in Japan. However, the characteristics of organ-specific SIPAT scores for organ transplant recipient candidates in Japan are unclear and, to date, the SIPAT has not been properly utilized in clinical practice. The purpose of this study was to present basic data that can be used to establish the relation between SIPAT scores and post-transplantation psychosocial outcomes as well as organ-specific outcomes. Methods This study included 167 transplant recipient candidates (25 heart, 71 liver, and 71 kidney) who completed a semi-structured interview based on the Japanese version of SIPAT (SIPAT-J) prior to transplantation. The differences between organs in terms of SIPAT scores and differences in SIPAT scores based on demographic data were comparatively analyzed. Results The total SIPAT scores were higher for liver recipient candidates than for heart recipient candidates (P = .019). Regarding the subscales, SIPAT B (social support system) scores were higher for liver and kidney recipient candidates than for heart recipient candidates (P = .021), whereas SIPAT C (psychological stability and psychopathology) scores were higher for liver recipient candidates than for kidney recipient candidates (P = .002). Recipient candidates with a history of psychiatric treatment and those who were unemployed had higher SIPAT scores, regardless of the transplant organ, than recipient candidates without a history of psychiatric treatment and those who were employed (P < .001, P = .016, respectively). Conclusions There were notable differences in the total SIPAT-J and subscale scores among the liver, heart, and kidney recipient candidates. Each organ was associated with specific psychosocial issues that should be addressed before transplantation. Interventions such as information provision and patient education based on SIPAT assessment results for each organ may improve recipient post-transplant outcomes

Prevalence of Circadian Rhythm Sleep-Wake Disorder in Outpatients with Schizophrenia and Its Association with Psychopathological Characteristics and Psychosocial Functioning

The prevalence of circadian rhythm sleep-wake disorder (CRSWD) among patients with schizophrenia is not clear. The effect of comorbid CRSWD on such patients has also not been fully evaluated yet. Outpatients with schizophrenia in the maintenance phase who visited Tokyo Women’s Medical University Hospital between April 2018 and March 2019 participated in this study. The Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impressions–Severity Illness Scale (CGI-S), Global Assessment of Functioning (GAF), World Health Organization Disability Assessment Schedule II, Insomnia Severity Index (ISI), and Morningness–Eveningness Questionnaire (MEQ) were administered, and the patient responses with and without CRSWD were compared. Of the 105 patients with schizophrenia, 19 (18.1%) had CRSWD. There were trends toward higher BPRS and lower GAF scores in the CRSWD group than in the non-CRSWD group, although these did not reach statistical significance following a false discovery rate correction. Among the BPRS subitems, the anxiety scores were significantly higher in the CRSWD group than in the non-CRSWD group (p &lt; 0.01). CRSWD was highly prevalent among patients with schizophrenia in the maintenance phase. Comorbidities of CRSWD may affect psychopathological characteristics and psychosocial functioning

Effects of chronic haloperidol treatment on the expression of fear memory and fear memory extinction in the cued fear‐conditioned rats

Abstract Aim Impairments in emotional memory are frequently observed in several mental disorders, highlighting their significance as potential therapeutic targets. Recent research on the cued fear conditioning model has elucidated the neural circuits involved in fear memory processing. However, contradictory findings have been reported concerning the role of dopamine and the impact of dopamine D2 receptor (D2R) antagonists. There is notably limited knowledge regarding the clinical utility of chronic D2R antagonist treatments. This study aimed to uncover how such treatments affect fear memory processing. Methods We utilized a cued fear conditioning rat model and conducted chronic haloperidol treatment for 14 days. Subsequently, to investigate the effect of chronic haloperidol treatment on fear‐conditioned memory expression and extinction, we observed freezing behavior under exposure to a conditioned stimulus for 14 days. Results Chronic haloperidol treatment suppressed freezing time on the fear memory expression. In contrast, a single haloperidol administration enhanced the freezing time on fear memory expression and delayed extinction. Conclusion The results of this study suggest that chronic administration of antipsychotic drugs affects fear memory processing differently from single‐dose administration. This indicates that the effects of chronic D2R antagonist treatment are distinct from the nonspecific effects of the drugs. This study provides fundamental insights that may contribute to our understanding of therapeutic mechanisms for fear memory disorders related to D2R in the future

Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutes–hours) and long period of time (days–weeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the lack of technologies with robustness, reversibility, and spatio-temporal control. Recently, we have demonstrated that our chemogenetic approach (eg, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) provides a reliable and robust tool for controlling genetically defined neural populations. Here we show how short- and long-term activation of dorsal raphe nucleus (DRN) serotonergic neurons induces robust behavioral responses. We found that both short- and long-term activation of DRN serotonergic neurons induce antidepressant-like behavioral responses. However, only short-term activation induces anxiogenic-like behaviors. In parallel, these behavioral phenotypes were associated with a metabolic map of whole brain network activity via a recently developed non-invasive imaging technology DREAMM (DREADD Associated Metabolic Mapping). Our findings reveal a previously unappreciated brain network elicited by selective activation of DRN serotonin neurons and illuminate potential therapeutic and adverse effects of drugs targeting DRN neurons