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Estrogens play important roles in uterine growth and homeostasis through estrogen receptors (ESR1 and ESR2). To address the role of ESR1-mediated tissue events in the murine uterus, we analyzed mice with a mesenchymal tissue-specific knockout of Esr1. Isl1-driven Cre expression generated Esr1 deletion in the uterine stroma and endometrium (Isl-Esr1KO). We showed that overall structure of the Isl1-Esr1KO mouse uterus developed normally, but estrogen responsiveness and subsequent growth were defective, suggesting that mesenchymal ESR1 is necessary for both epithelial and mesenchymal cell proliferation. Furthermore, RNA-seq analysis revealed that the majority of estrogen-induced genes were regulated by stromal ESR1. In control mice, E2 administration induced 9476 up-regulated differentially expressed genes (DEGs), whereas only 1801 up-regulated DEGs were induced by E2 in Isl1-Esr1KO mice. We further showed that stromal ESR1-regulated genes in the mouse uterus included several growth factors and cytokines, which are potential factors that regulate epithelial and stromal tissue interaction, and also genes involved in lipid homeostasis. Therefore, we infer that stromal ESR1 expression is indispensable for most estrogen actions in the mouse uterus and the current results provide new insights into estrogen-mediated homeostasis in female reproductive organs., (© 2023. The Author(s).)

The aim of the present study was to clarify the association between child abuse experiences and drug addiction severity among Japanese drug-dependent patients using the Addiction Severity Index-Japanese version (ASI-J). One hundred and eleven inpatients and outpatients with drug dependence participated in the study. Some of the questions on the ASI-J asked about lifetime experiences of abuse. A higher percentage of female participants experienced child abuse compared with male participants. Male participants who experienced child abuse (MEA) had a significantly higher severity of drug use than men who did not experience it (MNEA). Female participants who experienced child abuse (FEA) had significantly more serious problems in family/social relationships than female participants who did not experience it (FNEA). Patients in the MEA group were arrested less frequently for drug charges, experienced more serious problems with their fathers, and experienced more severe anxiety in their lifetime compared with the MNEA group. The FEA group experienced more serious troubles with their sexual partners, close friends, and families and experienced more severe psychiatric problems in their lifetime compared with the FNEA group. These results suggest gender differences in the problems experienced by drug-dependent patients with child abuse experiences, and gender-specific interventions may be more effective in treating their drug dependence.

We examined the influence of G-protein-activated inwardly rectifying K+ (GIRK) channel inhibition on relapse risk in Japanese alcohol-dependent inpatients. The participants included 11 patients who received GIRK inhibition treatment and 39 patients who did not receive GIRK inhibition treatment. The participants answered a questionnaire, including the Alcohol Relapse Risk Scale (ARRS) and a questionnaire about their experiences of stressful events 2 weeks after hospitalization (time 1) and completed follow-up questionnaires 45-60 days after the first rating (time 2). A significant interaction was found between group and time on positive expectancy for alcohol scores on the ARRS (F = 5.93, p = 0.02). The scores at time 2 were lower than that at time 1 in the GIRK inhibition treatment group (p = 0.004) but not in the non-GIRK inhibition treatment group. The results of the present study suggest that GIRK inhibition treatment may improve the positive expectancy for alcohol, a component of relapse risk. The present study suggests that the effects of GIRK inhibition treatment should be investigated further in future studies.

Objectives: Methamphetamine (MAP) is one of the most commonly abused drugs in Japan. Japan has experienced three major epidemics of MAP abuse. The characteristics of abusers have changed between the second and third epidemics; however, few epidemical studies have investigated these changes. The purpose of this study is to describe the differences in the characteristics of MAP abusers between the second and third epidemics., Methods: We surveyed the medical records of patients admitted to Tokyo Metropolitan Matsuzawa Hospital for MAP-related disorders between 1989 and 1993 (n=60; second epidemic group) and between 2004 and 2008 (n=119; third epidemic group). We compared patients' backgrounds and issues related to MAP abuse between the two groups., Results: Compared to the second epidemic group, more abusers in the third epidemic group were similar to the general population of young people in terms of education level and criminal activity; were on welfare; had dependence syndrome; smoked MAP; and co-abused legal drugs. In contrast, abusers who exhibited antisocial tendencies and injected MAP were more likely to be in the second epidemic group., Conclusions: We confirmed changes in the characteristics of MAP abusers between two of the three epidemics of MAP abuse in Japan. These findings suggested that the change of environments from the second epidemics of MAP abuse to the third one influenced the characteristics of MAP-related disorders. So, it is necessary to provide accurate and updated knowledge about MAP for the drug prevention to young people, and the treatment of dependence syndrome will become more important in the future.

In Japan, the target mental disorders of preventive strategies for suicide had been limited to be mood disorder, but recently drug abuse are known to be significant as a cause of suicide because some researches has found the association between substance use disorder and suicidal behavior in Japan. However, the preventive plans for suicide of drug abusers has not been developed yet. In this study we would like to examine the risk factors of suicide ideation in Japanese drug abusers. We analyzed the data of 445 drug addicts from the Nationwide Research of Drug Addiction Rehabilitation Centers by Tokyo DARC and compared many variables including demographic factors, drug use status, family history, psychopathologies, treatment and daily life satisfactions between people with suicide ideations and without ideations. It was found that 182 cases (43.8%) had suicide ideations in a recent month, and that addicts who had suicide ideations had significantly shorter abstinence time, higher prevalence of victimized experiences before 15 years age, and more mental symptoms such as insomnia, depression, and psychotic symptoms, and more tendencies to use prescribed psychotropic drug than those without suicide ideation. These results suggested that to prevent suicide of drug abusers, we should pay attention to family histories, insomnia and abstinence periods, and help them recovery from psychological damages caused by childhood trauma without inappropriate medications.

We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas.

The present study assessed problems in Japanese prisoners (inmates) who abused methamphetamine. Fifty-two male inmates were assessed in 2005-2007 using the Addiction Severity Index-Japanese version and compared with 55 male methamphetamine abusers in hospitals and recovery centers. The chi(2) and Mann-Whitney-Wilcoxon tests showed that the inmates had a significantly lower education level, more frequently had full-time jobs, had more experience living with a sexual partner, and more frequently had a history of juvenile delinquency and criminal records than patients. Although psychiatric symptoms, such as depression, anxiety, and hallucinations, were not common among inmates, suicidal behavior and trouble controlling violence were common in both groups.

Child abuse is known to correlate with drug abuse and interferes with recovery from substance-related disorders. To determine the prevalence and severity of child abuse among drug addicts, we conducted a nationwide cross-sectional survey of residents and outpatients at drug addiction rehabilitation centers (DARC) in Japan. A total of 445 participants gave informed consent and completed a self-reporting questionnaire. Sixty-eight percent of participants had experienced some kind of child abuse by the time they reached junior high school. The kinds of abuse experienced were physical (53.7%), psychological (60.4%), sexual (5.4%) abuse and neglect (24.5%). Comparison of female and male participants revealed that more female than male participants had experienced psychological (76.9% vs. 58.2%) and sexual (17.5% vs. 4.0%) abuse. Comparison of participants who had experienced some kind of child abuse ("Abused" group 68.3%) and those who had not experienced abuse ("Non-abused" group 24.3%) revealed that the "Abused" group was younger than the "Non-abused" group (35.7 SD9.0 vs. 39.7 SD10.8). Participants in the "Abused" group were found to have more severe psychological difficulties than those in the "Non-abused" group for the following: anxiety (73.0% vs. 61.1%), delusional atmosphere (48.0% vs. 28.7%), lack of energy (53.9% vs. 40.7%), ideas of persecution (48.7% vs. 29.6%), depression (62.2% vs. 43.5%) and suicidal ideation in the previous year (50.7% vs. 24.3%). The present results suggest that additional program that prepared to care the drug addicts who experienced child abuse and are experiencing suicidal ideation is needed. Furthermore, intervention for families with risk factors for child abuse should be developed in order to prevent the victim from suffering not only from post traumatic stress disorder but also from substance related disorders.

Objective: To demonstrate the usefulness of the Addiction Severity Index Japanese Version (ASI-J) in Japanese alcohol-dependent individuals. The ASI is a frequently used clinical and research instrument that measures severities in seven functional domains in people with substance abuse disorders., Methods: A total of 370 male inpatients with a history of alcohol dependence participated in the study. Forty-nine participants were excluded in the final analysis due to lack of reliability (i.e., patient misrepresentation or inability to understand). We used the ASI-J and a series of indexes that determined patient states during and post-treatment., Results: The correlations between ASI Composite Scores (CSs), which were calculated through a weighted formula and indicated the severity of each problem area, were significant but low in eight relations and not significant in 13 relations, indicating substantial independence of the problem areas. Significant differences were found in Family/Social CSs between abstinent and relapsed alcohol-dependent individuals. The questions of undesirable attitude were significantly related to the CSs of Employment, Drug use, Family/Social, and Psychiatric sections. Significant differences were observed in patient demographics, CS, and ASI Severity Rating (SR) and interviewer's subjective scoring between alcohol-dependent individuals and drug abusers. CSs in Japanese alcohol-dependent individuals were generally similar to corresponding CSs in individuals from other countries, with the exception of The Netherlands., Conclusions: This study demonstrated that the ASI-J is useful for understanding individual profiles of problems for each patient and planning customized treatment. The ASI-J served as a predictive tool for relapse and compliance to treatment afterward and was shown to be useful as a comparison tool in clarifying similarities and differences between substance abuser groups.

Objective: To develop and validate the Alcohol Relapse Risk Scale (ARRS) for Japanese alcohol-dependent individuals and to compare the features of relapse risk for alcohol-dependent individuals with those for stimulant abusers., Methods: The ARRS is a multidimensional self-rating scale consisting of 32 items based on the Stimulant Relapse Risk Scale (SRRS). Two hundred eighteen inpatients and outpatients with a history of alcohol dependence (181 males and 36 females) were recruited, provided informed consent, and were administered the ARRS. The Visual Analog Scale (VAS) for alcohol craving, current state of drinking, and data on relapse within 1 month after the rating were used for validation., Results: Exploratory factor analysis highlighted five factors: stimulus-induced vulnerability (SV), emotionality problems (EP), compulsivity for alcohol (CA), lack of negative expectancy for alcohol (NE), and positive expectancy for alcohol (PE). Cronbach's alpha coefficient for each of the subscales ranged from .55 to .90 and was .90 for the total ARRS, indicating their adequate internal consistency. SV, EP, CA, PE, and total ARRS were significantly correlated with the VAS and current drinking state, supporting their concurrent validity. SV and total ARRS were significantly correlated with relapse, suggesting that the ARRS is useful for predicting relapse risk in alcohol-dependent individuals, similar to the SRRS for stimulant abusers. Compared with stimulant abusers, alcohol-dependent individuals tended to express their desires related to relapse more honestly on the scales., Conclusions: The ARRS has multidimensional psychometric properties that are useful for assessing the various aspects of alcohol relapse risk.

Objective: To develop and validate a multidimensional measure of relapse risk for stimulants in Japanese drug abusers., Methods: A Stimulant Relapse Risk Scale (SRRS) was developed based on the Marijuana Craving Questionnaire and a discussion among three psychiatrists. We created 48 items after confirming the items including a variety of relapse risk, such as craving (expectancy, compulsivity, etc.) and emotionality problems. One hundred inpatients and outpatients with a history of stimulant abuse (71 males and 29 females) were recruited with informed consent, and were administered the SRRS. The Visual Analogue Scale for drug craving (VAS), Addiction Severity Index for Japanese (ASI-J), and data on relapse within 3 and 6 months after the rating were used for the validation., Results: Exploratory factor analysis highlighted five factors: anxiety and intention to use drug (AI), emotionality problems (EP), compulsivity for drug use (CD), positive expectancies and lack of control over drug (PL), and lack of negative expectancy for drug use (NE). These accounted for 48.3% of the total variance. Thirty of the 43 items were classified into the five subscales. Cronbach's alpha coefficient for each subscale ranged from .55 to .82, and was .86 for the total SRRS, indicating their adequate internal consistency. AI, CD, PL, and total SRRS were significantly correlated with the drug-use composite score of the ASI-J, supporting their concurrent validity. AI, PL, NE, and total SRRS were significantly correlated with relapse, implying their predictive validity., Conclusions: The SRRS has multidimensional psychometric properties useful for assessing the various aspects of stimulant relapse risk.

The Addiction Severity Index (ASI) is a frequently used clinical and research instrument that collects data from substance abusers in seven problem areas: medical, employment, alcohol, drug use, legal, family-social functioning, and psychiatric status. In each area, the ASI provides a composite score and severity rating that estimate the seriousness of the problem and the client's need for treatment. In the present study, we investigated the reliability and validity of the Japanese version of the ASI (ASI-J). One hundred and eleven subjects with a history of drug abuse were interviewed with a test battery including the ASI with informed consent. This revealed that: (a) the problem areas were independent of each other, underscoring the need for multidimensional assessment, (b) the inter-rater correlation of severity ratings in each area ranged from 0.68 to 0.99, and Cronbach's alpha coefficient for the items used for the composite score in each area ranged from 0.57 to 0.86, indicating their reliability with the exception of the drug and employment areas, and (c) several composite scores were significantly correlated with the drug craving levels assessed by a visual analogue scale, the abstinence period, mental health, and/or relapse, supporting their concurrent and predictive validity. These results suggest that the ASI-J has acceptable reliability and validity.

The number of reported child abuse cases is on the increase in Japan. This report describes the testing of an approach to prevention based on a key question: "Do you find any of your children irritating?" The study employed a focus group and a survey. The focus group consisted of 13 mothers who had been severely abusive to their children and were undergoing individual psychotherapy in Tokyo. The survey included 1,538 mothers living with at least one child less than 6 years of age in metropolitan Tokyo. The survey questionnaire asked about mothers' attitudes toward their children and about details and frequency of possibly abusive behavior for their children. All 13 mothers of the focus group reported the experience of feeling their children irritating. They talked extensively and provided many details of their feelings. Of the survey mothers, 3.6% reported feeling their children irritating and showed high scores of abusive behavior. There was a difference in attribution of source of the irritation between these mothers and focus-group mothers. We conclude that the question on irritability is effective in eliciting mothers' feelings and behavior, especially for providing public health nurses with an opportunity for intervention in child abuse.

The relationships between postpartum depression and demographic characteristics, social support, marital relationship, negative and passive acceptance of the mother role, and parenting behavior were examined in 215 mothers who live in Tokyo, Japan, and who have a child less than 1 year old. Social support from husbands or friends and marital relationship were found to be significantly related to the Edinburgh Postnatal Depression Scale (EPDS) score. Although negative and passive acceptance of the mother role was also related to the EPDS score and neglectful parenting behavior, it was not found to be related to aggressive parenting behavior. The correlation between EPDS score and neglectful or aggressive parenting behavior was also significant, with aggressive parenting behavior more strongly related to the EPDS score.

Objective: The aim of this study was to examine the effects of prelesioned peripheral nerve grafts on central nerve regeneration compared with the freshly transected peripheral nerve grafts in the dorsal funiculus of the rat spinal cord., Methods: The experimental paradigm consisted of ligating the common peroneal nerve at the midthigh level for 7 days, while the adjacent tibial nerve was left intact. Numerous Schwann cells appeared accompanying regenerating axons in the proximal stump of the ligated nerve. The proximal stumps of the ligated (prelesioned) common peroneal nerve and the intact (untreated) tibial nerve were excised as one tissue block and autografted into the dorsal funiculi of the upper cervical cord. The graft was placed so that the prelesioned common peroneal nerve was positioned on the left dorsal funiculus and the untreated tibial nerve was positioned to the right of the midsagittal plane. Nerve regeneration was examined by light and transmission electron microscopy 1 to 16 weeks after grafting, comparing the effectiveness of prelesioned and untreated nerve grafts., Results: Numerous regenerating axons were observed in the caudal border of both grafts 1 to 2 weeks after grafting. Astrocyte proliferation was suppressed in the prelesioned grafts compared to the untreated grafts. Four to 16 weeks later, the number of regenerating axons was approximately 10-fold as large in the prelesioned grafts as in the untreated grafts. The regenerating axons were myelinated by Schwann cells. Astrocytic glial scar formation was inconspicuous in the prelesioned grafts, whereas it was prominent in the untreated grafts. Schwann cells were contiguous with astrocytes along regenerating axons, forming a continuous conduit from the central to peripheral nerve microenvironments for the outgrowth of regenerating axons., Conclusion: The prelesioned peripheral nerve graft is more effective than the untreated graft in suppressing astrocytic scar formation and in supporting the outgrowth of regenerating axons in the dorsal funiculus of rat spinal cord.