Psychosocial factors predicting symptoms of depression and anxiety in allogeneic hematopoietic stem cell transplant recipients in Japan.

OBJECTIVE: We explored whether a patient's psychosocial background before allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict the occurrence of psychiatric symptoms during treatment and after hospital discharge. METHOD: Logistic regression analysis was performed using INTERMED, a scale that comprehensively evaluates psychological factors such as psychiatric history, current mental status, and coping skills, and social factors such as social participation status, relationships with others, and living environment, which were used as independent variables. The Center for Epidemiologic Studies Depression Scale was used to measure depression, while the Profile of Mood States was used to measure anxiety and other symptoms. Both measures were used as dependent variables and were administered upon clean room admission, during clean room stay, at clean room discharge, and at 3, 6, and 12 months after hospital discharge. RESULTS: Participants included 70 patients (45 males and 25 females, mean age 53.3 ± 12.3 years). Thirty-eight patients participated in the program for the entire period, up to 12 months after hospital discharge. The total score on the Japanese version of the INTERMED and psychological factor scores assessed at baseline were significant predictors of depressed mood on discharge; however, there were no significant predictors of scores on the Profile of Mood States. CONCLUSIONS: A comprehensive pretransplant evaluation of psychosocial background can help predict the appearance of psychiatric symptoms after allo-HSCT. In patients who are expected to develop psychiatric symptoms after allo-HSCT, it is important to consider early intervention by a specialist and close monitoring by a medical team.

Effective Tools to Predict Depression in Acute and Subacute Phase of Ischemic Stroke.

OBJECTIVE: Despite the high frequency of depression in the first year following stroke, few studies have predicted risk of depression after the acute and subacute stroke periods. The aim of this study was to identify, in the acute and subacute periods, measures that would predict major depression during the first year after stroke. METHODS: Study subjects were inpatients with ischemic stroke aged 20-85 years within 6 weeks of onset. Patients were evaluated at baseline and at 3, 6, 9, and 12 months. Patients were diagnosed with major depression using the Structured Clinical Interview for DSM-IV. The severity of depressive symptoms was measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Of the 152 potential patients who met inclusion criteria, 49 had follow-up evaluations; one patient with major depression in the acute and subacute periods was excluded from the analysis. Among the remaining 48 patients, the number of those with major depression during the first year of stroke onset was five (10.4%). Patients who developed major depression had significantly more depressive symptoms in the acute and subacute stroke phase as assessed by both the PHQ-9 and MADRS. Patients with PHQ-9 scores ≥9 in the acute and subacute stroke phases were significantly more likely to develop major depression in a chronic phase of stroke. CONCLUSIONS: The self-administered PHQ-9 can identify patients in the acute and subacute stroke periods who are at increased risk for developing major depression during the first year after stroke.

Aripiprazole in the real-world treatment for irritability associated with autism spectrum disorder in children and adolescents in Japan: 52-week post-marketing surveillance.

BACKGROUND: The purpose of this study was to evaluate the post-marketing safety and effectiveness of aripiprazole in treating irritability in pediatric patients (6-17 years) with autism spectrum disorder (ASD) in actual clinical sites of Japan. METHODS: In this post-marketing surveillance, patients were enrolled into the multicenter, prospective, non-interventional, observational study for 52 weeks, and were dosed with aripiprazole (1-15 mg/day) under daily clinical settings in Japan. RESULTS: In 510 patients, the continuation rate of aripiprazole treatment was 84.6% at day 168 (week 24) and 78.1% at day 364 (week 52). Adverse drug reactions (ADRs) occurred in 22.7% of patients (n = 116), and the most common ADRs were somnolence (9.4%), followed by weight increased (3.3%). At week 4, the mean change from baseline in the irritability subscale score for the Aberrant Behavior Checklist Japanese version (ABC-J) was - 5.7 ± 6.8 (n = 288). Based on multiple regression analysis, comorbid attention deficit and hyperactivity did not affect the ABC-J irritability subscale score at endpoint. At week 24, the mean change from baseline for the Strengths and Difficulties Questionnaire was - 3.3 ± 4.9 (n = 215) for the total difficulties score and 0.6 ± 1.7 (n = 217) for the prosocial behavior subscale score. CONCLUSIONS: Aripiprazole was well tolerated and effective in the long-term treatment of irritability associated with ASD in Japanese pediatric patients in the real-world clinical practice. TRIAL REGISTRATION: This surveillance was registered with Clinical Trial.gov (no. NCT03179787 ) on June 7, 2017 (retrospectively registered).

Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study.

We evaluated the efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents (6-17 years) with autism spectrum disorder (ASD) in a randomized, double-blind, placebo-controlled 8-week study in Japan. Patients received flexibly dosed aripiprazole (1-15 mg/day) or placebo. Ninety-two patients were randomized to placebo (n = 45) or aripiprazole (n = 47). Aripiprazole produced a significant improvement in the mean parent/caregiver-rated Aberrant Behavior Checklist Japanese Version irritability subscale score relative to placebo from week 3 through week 8. Administration of aripiprazole provided significantly greater improvement in the mean clinician-rated Clinical Global Impression-Improvement scores than placebo from week 2 through week 8. All patients randomized to aripiprazole completed the study, and no serious adverse events were reported. Three patients in placebo group discontinued. Aripiprazole was effective and generally safe and well-tolerated in the treatment of irritability associated with ASD in Japanese children and adolescents.

Prevention of post-stroke generalized anxiety disorder, using escitalopram or problem-solving therapy.

This study examined the efficacy of antidepressant treatment for preventing the onset of generalized anxiety disorder (GAD) among patients with recent stroke. Of 799 patients assessed, 176 were randomized, and 149 patients without evidence of GAD at the initial visit were included in this double-blind treatment with escitalopram (N=47) or placebo (N=49) or non-blinded problem-solving therapy (PST; 12 total sessions; N=53). Participants given placebo over 12 months were 4.95 times more likely to develop GAD than patients given escitalopram and 4.00 times more likely to develop GAD than patients given PST. Although these results should be considered preliminary, the authors found that both escitalopram and PST were effective in preventing new onset of post-stroke GAD.

Relationship between the plasma concentration of paliperidone and the clinical and drug-induced extrapyramidal symptoms in elderly patients with schizophrenia.

OBJECTIVE: We investigated the relationship between the plasma concentration of paliperidone (PAL) and clinical and drug-induced extrapyramidal symptoms (EPS) in elderly patients with schizophrenia. METHODS: In this study, 15 patients with schizophrenia receiving risperidone were switched to PAL and treated for 12 weeks. Their clinical symptoms were assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impression-Severity of Illness Scale. Their EPS were assessed using the Drug-induced EPS Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Scale at baseline and 12 weeks. Plasma concentrations were measured by the liquid chromatography-mass spectrometry/mass spectrometry method. RESULTS: The results revealed that there were significant correlations between the plasma concentration of PAL and improved Positive and Negative Syndrome Scale total, negative, and general psychopathology scores (p<0.05). However, the efficacy did not improve linearly with plasma level. No significant correlations were found between the PAL plasma concentration and the mean change from baseline in the Drug-induced EPS Scale total score, Barnes Akathisia Scale, or Abnormal Involuntary Movement Scale. CONCLUSIONS: The results of this research suggested that, in elderly patients, although none of an increased plasma concentration of PAL, a worsening of EPS, or an increase in prolactin level occurs, linear clinical efficacy may not be obtained.

The influence of switching from risperidone to paliperidone on the extrapyramidal symptoms and cognitive function in elderly patients with schizophrenia: a preliminary open-label trial.

OBJECTIVE: This study was to evaluate the effects on clinical symptoms and cognitive function of switching the treatment of elderly patients with schizophrenia from risperidone to paliperidone (PAL). METHODS: This study was a 12-weeks, preliminary open-label trial. The subjects were 17 inpatients. Their extrapyramidal symptoms (EPS) were assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Scale (BAS), and their cognitive function was assessed using the Brief Assessment Cognition in Schizophrenia: Japanese language version (BACS-J), and their clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity of illness scale (CGI-S) at the 0 and 12 weeks. RESULTS: The DIEPSS and BAS significantly improved after switching from risperidone to PAL. Furthermore, improvement was found on AIMS. The mean change from baseline in z-score of the digit sequencing task was significantly increased. All items on the PANSS and CGI-S were not significant; however, changes in some cognitive function were correlated with changes in EPS. CONCLUSIONS: The results of this study suggest the possibility that switching elderly patients from risperidone to PAL may have improved pre-existing EPS, and may also have helped improve working memory.

Psychiatric Features of Children with Chronic Functional Constipation: Focusing on Individuals with Autism Spectrum Disorder.

PURPOSE: The present study aimed to assess the psychiatric characteristics of children with chronic functional constipation using the Aberrant Behavior Checklist-Japanese version and the Pervasive Developmental Disorders/Autism Society Japan Rating Scale, and to examine the frequency of autism spectrum disorder in children with chronic functional constipation. We also investigated differences in treatment duration between children with and without autism spectrum disorder. METHODS: Treatment outcomes were examined retrospectively for 55 participants (chronic functional constipation group: n = 30, mean age 3.4 years; control group: n = 25, mean age, 4.5 years). The association between chronic functional constipation and autism spectrum disorder was evaluated using multivariable logistic regression analysis. RESULTS: The mean Aberrant Behavior Checklist score and frequency of individuals with autism spectrum disorder were significantly higher in the chronic functional constipation group. After adjusting for age and sex, chronic functional constipation was significantly associated with autism spectrum disorder. In the chronic functional constipation group, the frequency of onset was significantly higher in children with autism spectrum disorder under 1 year of age. When treated, the mean duration of constipation was significantly longer in children with autism spectrum disorder. CONCLUSION: Pediatricians, pediatric surgeons, and child psychiatrists should work closely to ensure appropriate treatment of chronic functional constipation in children with autism spectrum disorder.

Incident apathy during the first year after stroke and its effect on physical and cognitive recovery.

OBJECTIVE: This prospective study examined the course of cognitive, physical, and social impairment among patients who developed apathy during the first year after stroke. METHODS: Patients diagnosed with apathy (N = 23) were compared with patients who had no apathy (N = 33) at initial, 3, 6, 9, and 12 months after stroke for severity of global cognitive impairment as measured by Mini-Mental State Examination, severity of impairment in activities of daily living (ADLs) as measured by Functional Independence Measure, and severity of impairment in social functioning as measured by Social Functioning Exam. RESULTS: A total of 41.1% of patients met diagnostic criteria for apathy during the first year after stroke. The mean time from stroke to onset of apathy was 3.8 (3.3 SD) months and the mean duration was 5.6 (2.3 SD) months. Using a linear mixed model, after controlling for age, initial severity of impairment, and major depression, patients in the apathy group had significantly less recovery in cognition (t(149) = -2.06; p = 0.0411) and ADLs (t(104) = -3.37; p = 0.0011) during the first year after stroke compared with nonapathic patients. CONCLUSION: Apathy is common after stroke and leads to less recovery in cognition and ADLs over the first year after stroke compared with similar nonapathic patients.

Prevention of poststroke apathy using escitalopram or problem-solving therapy.

OBJECTIVE: Apathy occurs frequently following stroke and prior studies have demonstrated the negative effect of apathy on recovery from stroke. This study was a secondary analysis examining the efficacy of escitalopram, problem-solving therapy (PST), or placebo administered for 1 year to prevent the onset of apathy among patients with recent stroke. METHODS: Patients within 3 months of an index stroke who did not meet DSM-IV diagnostic criteria for major or minor depression and who did not have a serious comorbid physical illness were enrolled. Patients were recruited from three sites: University of Iowa, University of Chicago, and Burke Rehabilitation Hospital. One hundred fifty-four patients without evidence of apathy at initial evaluation were included in the randomized controlled trial using escitalopram (10 mg patients ≤65 years; 5 mg patients >65 years) (N = 51) or placebo (N = 47) or non-blinded PST (12 total sessions) (N = 56) over 1 year. At 3, 6, 9, and 12 months, patients were assessed for diagnosis and severity of apathy using the Apathy Scale. RESULTS: Using a Cox proportional hazards model of time to onset of apathy, participants given placebo were 3.47 times more likely to develop apathy than patients given escitalopram and 1.84 times more likely to develop apathy than patients given PST after controlling for age, sex, cognitive impairment, and diabetes mellitus status (adjusted hazard ratio: 3.47, 95% CI: 1.79-6.73 [escitalopram group]; adjusted hazard ratio: 1.84, 95% CI: 1.21-2.80 [PST group]). CONCLUSION: Escitalopram or PST was significantly more effective in preventing new onset of apathy following stroke compared with placebo.

Study of the efficacy and safety of switching from risperidone to paliperidone in elderly patients with schizophrenia.

AIM: We investigated the clinical efficacy and safety of switching to paliperidone (PAL) in elderly schizophrenia patients receiving risperidone. METHODS: The subjects were 27 inpatients who had been diagnosed with schizophrenia according to the DSM-IV. The patient's clinical symptoms were assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impression-Severity of Illness Scale, and their safety was assessed using the Drug-induced Extrapyramidal Symptoms Scale, bodyweight, body mass index, and laboratory tests. We also investigated patient satisfaction using the Drug Attitude Inventory, a subjective outcome measure. RESULTS: No significant differences in clinical symptom improvement efficacy were seen between the PAL-switching group and the control group. The mean changes from baseline on the Drug-induced Extrapyramidal Symptoms Scale total score, Drug Attitude Inventory score, and prolactin level were significantly greater in the PAL-switching group than in the control group. Furthermore, patients with PAL needed less biperiden, even though they had similar risperidone-equivalent daily dosages to the control group. CONCLUSIONS: The results of this study suggest that switching elderly patients from risperidone to PAL may result in superior safety and patient satisfaction, and may also make it possible to reduce the dosage of biperiden.

Impact of Gut Microbiota on Host Aggression: Potential Applications for Therapeutic Interventions Early in Development.

Aggression in the animal kingdom is a necessary component of life; however, certain forms of aggression, especially in humans, are pathological behaviors that are detrimental to society. Animal models have been used to study a number of factors, including brain morphology, neuropeptides, alcohol consumption, and early life circumstances, to unravel the mechanisms underlying aggression. These animal models have shown validity as experimental models. Moreover, recent studies using mouse, dog, hamster, and drosophila models have indicated that aggression may be affected by the "microbiota-gut-brain axis." Disturbing the gut microbiota of pregnant animals increases aggression in their offspring. In addition, behavioral analyses using germ-free mice have shown that manipulating the intestinal microbiota during early development suppresses aggression. These studies suggest that treating the host gut microbiota during early development is critical. However, few clinical studies have investigated gut-microbiota-targeted treatments with aggression as a primary endpoint. This review aims to clarify the effects of gut microbiota on aggression and discusses the therapeutic potential of regulating human aggression by intervening in gut microbiota.

Clinical characteristics of child and adolescent psychiatric outpatients engaging in fireplay or arson: a case-control study.

BACKGROUND: Fireplay and arson incidents among children and adolescents have gained attention because of their potentially severe consequences and societal impacts. Understanding the underlying psychiatric characteristics of individuals engaging in fireplay or arson is crucial for early identification and targeted intervention. However, there is a lack of research conducted in clinical psychiatric populations in this context. This study compared the clinical characteristics of child and adolescent psychiatric outpatients who engaged in fireplay or arson with those without such behaviors. METHODS: A retrospective case-control study was conducted using data collected from patients who visited the Department of Child and Adolescent Psychiatry at Kohnodai Hospital, National Center for Global Health and Medicine in Japan, between April 2014 and March 2022. Medical records were checked to see if the patient had practically committed behaviors that corresponded to fireplay or arson. The case group was identified using this process. After identifying the case and control groups, sex, diagnosis, antisocial behavior, abuse history, and children-to-parent violence were assessed and compared by careful review of medical records. RESULTS: The study identified 64 patients who engaged in fireplay or arson, representing approximately 1.1% of the total 5,587 patients (case group). The median age of the patients' first fire-related behavior was 13 years (range, 6-18 years). In the case group, 14.1% of the cases involved arson, resulting in substantial damage. Of the remaining 5523 patients, 2268 patients had datasets for the first consultation (control group). The most prevalent diagnosis in the case group was attention-deficit hyperactivity disorder (ADHD), present in 57.8% of the cases. The study revealed a significant association between fire-related behaviors and ADHD as well as antisocial behavior. Gender differences were observed, with boys being more likely to engage in fireplay or arson than girls. CONCLUSIONS: This study suggests that clinicians and mental health professionals should closely consider male sex, ADHD, and antisocial behaviors as potential risk factors for fire-related behaviors. Monitoring the case group for the development of psychiatric disorders, including the use of illegal drugs, is recommended to prevent future arson incidents.

Prescribing Patterns in Child and Adolescent Outpatient Psychiatry: A Retrospective Cohort Study of Prescriptions in the First Year.

OBJECTIVE: Recently, excessive and off-label prescribing of psychotropic drugs for children and adolescents have become a problem. Child and adolescent psychiatric patients receive treatment in many departments and department-specific psychotropic drug use has not been analyzed. We surveyed prescriptions for child and adolescent psychiatric outpatients during their first year of treatment. METHODS: The participants were 302 patients, 15 years or younger, who made their first visit to the outpatient psychiatry department of Tokai University Hospital from September 1, 2015 to September 1, 2016. Prescription details and patient profiles were retrospectively investigated using medical records. RESULTS: Medication was prescribed for 20.9% of patients (63/302) with the prescription rate increasing with age. Psychotropic drugs were prescribed for 15.6% of patients (48/302), with attention-deficit/hyperactivity disorder (ADHD) medications being most frequently prescribed (20 cases). Other than psychotropic drugs, iron pills (25 cases) and herbal medicines (21 cases) were prescribed frequently. CONCLUSIONS: The pharmacotherapy and psychotropic prescription rates were low. This may be due to the use of non-pharmacological interventions and the lack of inpatient facilities. With the publication of guidelines for pharmacotherapy in child psychiatry in Japan, measuring the patterns of psychotropic drug prescription in children and adolescents is important, and would make treatment more transparent.

A Case of Nocturnal Enuresis Associated with Attention-deficit/hyperactivity Disorder Successfully Treated with Guanfacine Monotherapy.

Nocturnal enuresis (NE) is a syndrome associated with abnormal nocturnal urine production, urination mechanism, and sleep arousal. NE is strongly associated with attention-deficit/hyperactivity disorder (ADHD), and it has been reported that NE occurs in approximately 30% of children with ADHD. There have been several reports on the efficacy of atomoxetine as treatment for NE with ADHD, while the efficacy of guanfacine is still limited. We report our experience of treating an 10-year-old girl with NE with ADHD with a single dose of guanfacine. The patient first visited our hospital because of difficulty concentrating, restlessness at home and school, and nocturnal incontinence. She was diagnosed with NE with ADHD based on a review of her personal history from her mother. Her NE symptoms improved with guanfacine monotherapy (1 mg/day. The patient weighed 28 kg).