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.

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.

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.

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.

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.

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).

Iron Supplementation for Hypoferritinemia-Related Psychological Symptoms in Children and Adolescents.

BACKGROUND: Although some studies have described the association between serum ferritin levels and specific disorders in child and adolescent psychiatry, few have focused on mental status per se with low serum ferritin levels in children and adolescents. This study examined the effects of iron administration on psychological status of children and adolescents with reduced serum ferritin concentration. METHODS: This prospective study evaluated 19 participants aged 6-15 years with serum ferritin levels <30 ng/mL who visited a mental health clinic and received oral iron administration for 12 weeks. The participants were assessed using the Clinical Global Impression Severity (CGI-S), Profile of Mood States 2nd Edition Youth-Short (POMS), Center for Epidemiologic Studies Depression Scale (CES-D), and Pittsburgh Sleep Quality Index (PSQI). In addition to serum ferritin, blood biochemical values such as hemoglobin (Hb) and mean corpuscular volume (MCV) were examined. School attendance was recorded. RESULTS: The most prevalent physical symptoms were fatigability and insomnia. The CGI-S, PSQI, and CES-D scores decreased significantly following iron supplementation, whereas the scores of almost all POMS subscales improved significantly at week 12. No participant had hemoglobin levels <12 g/dL. Serum ferritin concentration increased significantly, whereas Hb and MCV remained unchanged. At baseline, 74% of the participants did not attend school regularly; this number improved to varying degrees by week 12. CONCLUSIONS: Serum ferritin levels would be preferable to be measured in children and adolescents with insomnia and/or fatigability regardless of psychiatric diagnoses or gender. Iron supplementation can improve the hypoferritinemia-related psychological symptoms of children and adolescents, such as poor concentration, anxiety, depression, low energy and/or irritability.

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).

Continuation rate for asenapine and brexpiprazole treatment in patients with schizophrenia.

INTRODUCTION: The current study sought to compare the treatment continuation rates of asenapine and brexpiprazole while specifically investigating the factors influencing this index and the clinical efficacy of brexpiprazole. METHODS: Retrospective study on patients with schizophrenia who were prescribed either asenapine (n = 73) or brexpiprazole (n = 136), as part of their routine medical care. RESULTS: The treatment continuation rates for asenapine and brexpiprazole were 19.0% and 38.6% at 52 weeks, with that of brexpiprazole found to be significantly higher than that of asenapine (p = .002). Moreover, age was found to be a significant factor affecting the treatment continuation rate for brexpiprazole (p = .03). Additionally, patients with a longer continuation duration had significantly lower Clinical Global Impression-Severity of Illness (CGI-S) scale scores compared to those who discontinued early (p = .04). The continuation rate was also significantly higher for those who began using the drug as outpatients compared to those first administered the drug as inpatients (p = .04). Furthermore, disease duration, CGI-S scale, and continuation duration significantly affected the clinical efficacy of brexipiprazole (p < .05 for all). CONCLUSIONS: The continuation rate for brexpiprazole increases as the age of the patient increases, as disease severity decreases, and if the patient first uses the drug as an outpatient. Shorter disease duration and longer drug administration may lead to improved clinical efficacy. These results suggest that brexpiprazole is an effective treatment option for maintenance therapy of schizophrenia.

Effect of gut microbiota early in life on aggressive behavior in mice.

Recent reports have indicated that gut microbiota modulates the responses to stress through the microbiota-gut-brain axis in mice, suggesting a connection between gut microbiota and brain function. We hypothesized that the gut microbiota early in life would have an effect on aggressiveness, and examined how gut microbiota affect aggressive behaviors in mice. BALB/c mice were housed in germ-free (GF) and ex-germ-free (Ex-GF) isolators. An aggression test was performed between castrated and a non-castrated mice at 8 weeks of age; the mice were allowed to confront each other for 10 min in strictly contamination-free environments. To evaluate aggressive behavior related to gut microbiota, we orally administered diluted Ex-GF mouse feces to the offspring of GF mice at 0, 6, and 10 weeks. GF mice showed more aggression than Ex-GF mice. Furthermore, GF mice who were administered feces of the Ex-GF group at 0-week-old were less aggressive than the GF mice. These findings suggested that the gut microbiota in the early stages of development was likely to have an effect on aggressiveness. Maintenance of healthy gut microbiota early in life can affect the mitigation of aggressive behavioral characteristics throughout the lifetime.

Second-Generation Antipsychotic Drugs for Children and Adolescents.

The effectiveness and safety of antipsychotics have not been fully established in children and adolescents. Many antipsychotics approved for use in adults are prescribed off-label to children and adolescents. We investigated the effectiveness and tolerability of antipsychotics for children and adolescents with schizophrenia and bipolar disorder. A literature review of the empirical evidence regarding the use of antipsychotics, particularly second-generation antipsychotics, in children and adolescents showed that these drugs were safe and effective for this population. Antipsychotics were similarly effective for treatment of schizophrenia and bipolar disorder in children and adolescents. When prescribing antipsychotics to this population, clinicians should consider adverse events and the discontinuation rate in treated patients. However, the current evidence shows a lack of consensus regarding the use of antipsychotics in children and adolescents.

Metabolomics profile of Japanese female patients with restricting-type anorexia nervosa.

In this study, the serum metabolic profiles of 10 female patients with restricting type anorexia nervosa (ANR) were compared to those of 10 age-matched healthy female controls. While the levels of amino acids were lower among the patients than among the controls, the levels of uremic toxins, including p-cresyl sulfate (PCS), indole-3-acetic acid, and phenyl sulfate, were higher in ANR patients. The serum PCS levels correlated positively with the abundance of the Clostridium coccoides group or the C. leptum subgroup in the feces of patients, but not in those of controls. Collectively, these results indicate that the serum metabolic profiles of patients with ANR differ from those of healthy women in terms of both decreased amino acid levels and increased uremic toxins. Gut microbes including C. coccoides or C. leptum may be involved in such an increase in uremic toxins.

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.

Suicide Leap of an 11-Year-Old Girl with Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) has been linked with risk of suicide, and several cases of suicide attempts by adolescents with ASD have been reported. However, there is scant research on therapeutic approaches to prevent suicide re-attempts by children with ASD who have already attempted suicide. We report our experience of treating an 11-year-old girl with adjustment disorder comorbid with ASD who was transported to our hospital after sustaining injuries from the suicide leap. Initially, she was diagnosed with adjustment disorder brought on by poor interpersonal relationships at school, and, upon reviewing the patient's personal history, her underlying ASD characteristics became apparent. To prevent a re-attempt, it was crucial to reduce her risk factors and enhance her protective factors. To reduce her risk factors, we manipulated the environmental factor that triggered the patient's suicide attempt. In addition, to reinforce her protective factors, we intervened in the parent-child relationship and addressed her hesitation to ask for help, which we identified as a predisposing factor since early childhood. Over the course of her treatment, she did not exhibit suicidal ideation or re-attempt suicide.

Reconsideration of Periodic Psychosis of Adolescence.

The condition of periodic psychosis of adolescence based on the clinical features of recurrent depressive symptoms, sub-stupor, and psychotic symptoms whose features return to a normal state within 2 weeks with no residual symptoms has been often seen during adolescence. However, international recognition of periodic psychosis of adolescence is low and the condition is not recognized as an independent disease in ICD-10 or DSM-5. We presented a case report of a depressive episode central to periodic psychosis of adolescence in a 16-year old female. The symptoms presented in the case correspond to the DSM-5 classification of premenstrual dysphoric disorder. However, a diagnosis of periodic psychosis of adolescence was made due to the presence of clinical features of victim mentality, increased irritability, suicidal ideations, and changes in consciousness over short periods of time and sub-stupor. This report was focused on the medical treatment of the episode of periodic psychosis of adolescence with the aim of verifying its current significance.

The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice.

Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.