Longitudinal association between smartphone ownership and depression among schoolchildren under COVID-19 pandemic.

Under the COVID-19 pandemic, concerns regarding prolonged screen time and mental health effects in children have increased. We examined the association of depression with smartphone ownership in school children at four time points: September 2019, July 2020, December 2020, and March 2021. The analysis revealed an interaction between group and time, indicating that depressive symptoms among smartphone owners were significantly more severe than in the other group. These results were clearer for fourth-year students, pointing that smartphone possession at younger ages may be a risk factor for mental health in the new lifestyle caused by the COVID-19 pandemic.

Atypical Sensory Processing Profiles and Their Associations With Motor Problems In Preschoolers With Developmental Coordination Disorder.

The aims of this study were to identify sensory processing profiles specific to preschoolers with DCD in a community sample and examine the association of sensory processing problems with motor coordination difficulties in these children. Sixty-three 5-year-old children with DCD and without other neurodevelopmental disorders and 106 age-matched typically developing children participated in this study. Sensory processing problems were assessed using the Sensory Profile. Our results demonstrated problems in wide sensory processing patterns (low registration, sensitivity and avoiding) and areas (auditory, vestibular, touch and oral) in children with DCD compared with typically developing children. Additionally, the association of problems in sensory processing patterns (sensitivity and avoiding) and areas (touch and auditory) with motor coordination difficulties were identified in children with DCD alone. Our findings indicate that sensory processing abnormalities may contribute to the pathophysiology of DCD, suggesting the importance of assessing sensory processing functions in children with DCD.

Prevalence of pathological and maladaptive Internet use and the association with depression and health-related quality of life in Japanese elementary and junior high school-aged children.

PURPOSE: Pathological Internet use has been predominantly studied in junior high/middle school-aged or older children; data from elementary/primary school-aged children, however, are scarce. The current study aimed to examine the prevalence of problematic Internet use, including pathological and maladaptive Internet use, in elementary and junior high school-aged children and the relationships between problematic Internet use and mental health problems and health-related quality of life. METHODS: The survey was conducted among children who attend national and public elementary and junior high schools in a medium-sized city in Japan; data were received from 3845 elementary school-aged and 4364 junior high school-aged children. RESULTS: Based on the Young's Diagnostic Questionnaire score, the prevalence of pathological and maladaptive Internet use was 3.6% and 9.4% and 7.1% and 15.8% in elementary and junior high school-aged children, respectively. The prevalence of problematic Internet use, including pathological and maladaptive Internet use, consistently increased from the 4th grade to the 8th grade. In addition, the prevalence sharply increased between the 7th grade and the 8th grade. Our study revealed that children with pathological and maladaptive Internet use exhibited more severe depression and decreased health-related quality of life than those with adaptive Internet use. CONCLUSIONS: Our results demonstrated that pathological Internet use is not uncommon even in elementary school-aged children and that those with pathological and maladaptive Internet use have severe mental health problems and decreased health-related quality of life, supporting the importance of providing these children with educational and preventive interventions against problematic Internet use and associated risk factors.

Vascular risk factors and the relationships between cognitive impairment and hypoperfusion in late-onset Alzheimer's disease.

OBJECTIVE: Our recent single-photon emission computed tomography (SPECT) study of patients with late-onset Alzheimer's disease (AD) revealed that regional cerebral blood flow (rCBF) was reduced in the frontal, temporal, and limbic lobes, and to a lesser degree in the parietal and occipital lobes. Moreover, these patients' scores on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) were significantly correlated with rCBF in some gyri of the frontal, parietal, and limbic lobes. Our present study aimed to understand how vascular factors and metabolic disease influenced the relationship between rCBF and ADAS-cog scores. METHODS: We divided late-onset AD patients into two groups according to their Hachinski Ischemic Score (HIS), low vascular risk patients had values of ≤4 (n=25) and high vascular risk patients had scores ≥5 (n=15). We examined rCBF using brain perfusion SPECT data. RESULTS: The degrees and patterns of reduced rCBF were largely similar between late-onset AD patients in both groups, regardless of HIS values. Cognitive function was significantly associated with rCBF among late-onset AD patients with low vascular risk (HIS≤4), but not among those with high vascular risk (HIS≥5). Furthermore, metabolic diseases, such as hypertension and diabetes mellitus, disrupted the relationships between hypoperfusion and cognitive impairments in late-onset AD patients. CONCLUSION: Factors other than hypoperfusion, such as hypertension and diabetes mellitus, could be involved in the cognitive dysfunction of late-onset AD patients with high vascular risk.

Relationships between cognitive impairment on ADAS-cog and regional cerebral blood flow using SPECT in late-onset Alzheimer's disease.

The aim of this study was to examine brain hypoperfusion and its relationship with cognitive dysfunction in late-onset Alzheimer's disease (AD). Forty patients with late-onset AD and not receiving acetylcholinesterase inhibitors were recruited from outpatient clinics. We examined cognitive function using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and brain perfusion using single-photon emission computed tomography, and analyzed classified gyrus level segments with three-dimensional stereotactic surface projection and the stereotactic extraction estimation method level 3. ADAS-cog subscales were grouped into three domains: language, memory, and praxis. Patients with late-onset AD showed an apparent reduction in regional cerebral blood flow (rCBF) with a z score >1.5 in the frontal, temporal, and limbic lobes, with lesser reduction in the parietal and occipital lobes. Although hypoperfusion in the orbital, rectal, and subcallosal gyri of the frontal lobe was prominent, rCBF in the inferior frontal gyrus of the frontal lobe was significantly correlated with ADAS-cog total and language and praxis subscale scores. The parahippocampal gyrus of the limbic lobe was also significantly correlated with the ADAS-cog total, language, and praxis subscale scores. Additionally, the cingulate of the limbic lobe was significantly related with ADAS-cog memory. In spite of lesser hypoperfusion, the posterior cingulate gyrus of the limbic lobe was significantly related with ADAS-cog total, language, and memory subscale scores. Further, each subdivision of ADAS-cog was found to be related with various brain regions.

Prevalence of sleep problems in Japanese preschoolers in a medium-sized city: Community-based survey using the Children's Sleep Habits Questionnaire.

Although the mean score of the Children's Sleep Habits Questionnaire (CSHQ) differs between countries, there are no normative data for the CSHQ of Japanese preschoolers based on a community sample. The aims of this study were therefore to present normative data for the CSHQ and determine the prevalence and characteristics of sleep problems in Japanese preschoolers. Parents or the primary caregiver of 482 preschoolers aged 4-5 years completed the CSHQ and the Strength and Difficulties Questionnaire. Approximately 80% of preschoolers scored above the cut-off for sleep disturbance on the CSHQ. In addition, co-sleeping was prevalent in Japanese preschoolers but the habit of co-sleeping contributed little to behavioral and emotional problems. Sleep problems appear to be prevalent in Japanese preschoolers based on the CSHQ, and could be associated with the Japanese sleep habit of co-sleeping.

Utility of the Neurobehavioral Cognitive Status Examination (COGNISTAT) in differentiating between depressive states in late-life depression and late-onset Alzheimer's disease: a preliminary study.

BACKGROUND: It is often difficult to differentiate between the depressive states seen in late-life depression and late-onset Alzheimer' disease (AD) in the clinical setting. METHODS: Thirty-four outpatients were recruited, all fulfilling the criteria of aged 65 years or above, scores of 14 or more on the Hamilton depression rating scale (HAM-D), and 26 or less on the Mini-Mental State Examination (MMSE). At the initial visit, they were administered the Neurobehavioral Cognitive Status Examination (COGNISTAT). At 1 month, a diagnosis of either senile depression (n = 24) or Alzheimer' disease (n = 10) was made. RESULTS: The COGNISTAT revealed that the late-life depression group showed significantly higher scores in orientation and comprehension subtests compared with the AD group. At the study endpoint (6 months after treatment), MMSE detected significant improvements in the late-life depression group (n = 15), but no changes in the late-onset AD group (n = 7). Scores for memory, similarities, and judgment on the second COGNISTAT were significantly improved in the depressed group, whereas calculation scores deteriorated significantly in the AD group. CONCLUSION: The COGNISTAT could prove useful in differentiating late-life depression from late-onset AD, despite similar scores on MMSE.

Effects of add-on tipepidine on treatment-resistant depression: an open-label pilot trial.

OBJECTIVE: Treatment-resistant depression is a challenging problem in the clinical setting. Tipepidine has been used as a non-narcotic antitussive in Japan since 1959. METHODS: We administered tipepidine to 11 patients with treatment-resistant depression. Tipepidine was given for 8 weeks as an augmentation. RESULTS: Tipepidine significantly improved depression scores on the Hamilton Rating Scale for depression. Add-on treatment with tipepidine significantly improved scores on the trail making test and Rey auditory verbal learning test. However, no changes were observed in blood concentrations of stress-related hormones (adrenocorticotropic hormone, cortisol, dehydroepiandrosterone sulphate) with tipepidine augmentation. CONCLUSION: Tipepidine might be a potential therapeutic drug for treatment-resistant depression.

School Social Capital Mediates Associations Between ASD Traits and Depression Among Adolescents in General Population.

Though autism spectrum disorder (ASD) traits are associated with depression, it is unclear if school social capital mediates their association. We examined whether school social capital mediates the association between ASD traits and depression, and moderation effect of sex on the mediation effect among adolescents in a general population sample (1750 males, 1779 females; equivalent 12-15 years old). The results of this study indicate that ASD traits are associated with depression among adolescents, and that this association is partly mediated by school social capital. Furthermore, the results of the moderated mediation analysis suggest that lower level of school social capital can lead to more increase level of depression for females than for males.

Trajectories of emotional and behavioral problems in school-age children with coordination difficulties and their relationships to ASD/ADHD traits.

BACKGROUND: Although research has demonstrated associations between motor coordination difficulties and psychological problems in school-age children, including emotional and behavioral problems, longitudinal changes in these problems in children with motor coordination difficulties are not fully understood. AIMS: The current study aimed to identify patterns in the trajectory of emotional and behavioral problems in school-age children with motor coordination difficulties, and to elucidate the effect of co-existing neurodevelopmental traits on the occurrence and course of these problems. METHODS AND PROCEDURES: Using the Developmental Coordination Disorder Questionnaire, 773 children were defined as cases with motor coordination difficulties and followed for 4 years, from 6 to 10 years of age. Emotional and behavioral problems were assessed using the Strengths and Difficulties Questionnaire completed by children's parents or guardians. OUTCOMES AND RESULTS: We identified four trajectory patterns of emotional and behavioral problems. Children with higher autism spectrum disorder and attention deficit hyperactivity disorder traits were more likely to be assigned to poor prognostic trajectory patterns. CONCLUSIONS AND IMPLICATIONS: Our findings emphasize the importance of assessing emotional and behavioral problems and co-existing neurodevelopmental traits in children with motor coordination difficulties in early elementary school.

Adverse childhood experiences: impacts on adult mental health and social withdrawal.

Background: Adverse childhood experiences (ACEs) have been found to negatively impact adult mental health outcomes. Numerous studies have highlighted on ACEs in family and community settings. However, few have examined the impact of ACEs in school settings, despite the potential influence on social participation. Hikikomori, characterized by severe social withdrawal, was first studied in Japan and has gained recognition in recent years. The present study aims to present the concept of ACEs specific to schools and investigate the impact of both school ACEs and traditional ACEs on adult mental health and Hikikomori. Methods: A total of 4,000 Japanese adults, aged 20-34, were recruited through an Internet survey form. All data were obtained in October 2021. Participants answered questions regarding their ACEs in the family (10 items), school ACEs (five teacher-related items and two bullying-related items), depressive/anxiety symptoms, and Hikikomori (remaining at home for more than 6 months). Results: A significant association with depressive/anxiety symptoms was shown in both ACEs and school ACEs. An increase of one point in the ACE scores was associated with a 24% increase in the risk of depressive/anxiety symptoms. School ACE scores also demonstrated a significant association with depressive/anxiety symptoms, with an increase of one point associated with a 44% increase in the risk of these symptoms. As for Hikikomori, a significant association was shown in the school ACEs only: a 29% increased risk of Hikikomori for every one-point increase in school ACE scores. Both school ACE scores for teacher-related and bullying-related factors revealed a significant association with Hikikomori; the rates of increased risk were 23 and 37%, respectively. Conclusion: These results suggest that school ACEs, rather than ACEs in the family, are associated with the risk of Hikikomori. School ACEs are important for social adaptation, and reducing traumatic experiences in school settings may have the potential to prevent problems in later life, specifically in terms of social participation.

Mental health status of children who use foreign languages at home in Japan.

Aim: Little is known about the mental health status of children in Japan whose roots are in foreign countries. The differences in language that are used every day may be a factor that makes adaptation difficult for these children. The aim of the present study, therefore, was to examine the mental health status of children who use foreign languages at home via a cross-sectional survey in a large cohort. Methods: The survey was conducted among children who attended public elementary and junior high schools in a large city in Japan. Data were received from 20,596 elementary school-aged (above 4th grade) and 19,464 junior high school-aged children. We compared mental health status evaluated by the Patient Health Questionnaire-4 in the group based on language usage at home (only Japanese, only foreign languages, and both languages). Results: We found that children who used foreign languages at home exhibited worse mental health status than children who used only Japanese at home. In addition, mental health status was slightly better among junior high school-aged children who used only foreign languages at home than among elementary school-aged children. This tendency was not observed in the group of children who used both languages at home. Conclusion: Our results suggest that children in Japanese society who use foreign languages at home have worse mental health, therefore there is a need for support for these children living in Japan.

Proline protects liver from D-galactosamine hepatitis by activating the IL-6/STAT3 survival signaling pathway.

The oral administration of proline, one of the non-essential amino acids, has been shown to effectively protect the liver from D-galactosamine (GalN)-induced liver injury and to improve the survival rate. The aim of this study was to investigate the mechanism of this protective action of proline. We paid particular attention to the effect of proline on inflammatory activation, regenerative response, and the associated signal transduction in the liver. Male Fischer rats received intraperitoneal injections of GalN (1.4 g/kg) with or without the oral administration of proline (2 g/kg) 1 h before GalN treatment. Liver pathology, plasma indices of inflammation, and the level of proliferative marker in the liver were monitored. The hepatic activation of interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)-3 pathway, which is downstream of tumor necrosis factor (TNF)-α/nuclear factor-κB, was also studied. GalN induced massive inflammatory expansion in the liver, leading to a high death rate (60 %) more than 72 h after the treatment. Proline administration significantly suppressed inflammatory infiltration in the live after 48 h, which was accompanied by depletion of plasma TNF-α, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase. The mRNA expression of histone H3, a marker of proliferation, was significantly upregulated in the liver of proline-treated animals. Furthermore, IL-6/STAT-3 pathway, an anti-inflammatory and regenerative signaling pathway, was strongly activated prior to these observations, with the upregulated expression of downstream genes. These results suggest that the tissue-protective mechanism of proline involves the early activation of IL-6/STAT-3 pathway in the liver, with subsequent activation of the regenerative response and suppression of massive inflammatory activation.

Somatostatin is involved in anorexia in mice fed a valine-deficient diet.

The ingestion of a valine (Val)-deficient diet results in a significant reduction of food intake and body weight within 24 h, and this phenomenon continues throughout the period over which such a diet is supplied. Both microarray and real-time PCR analyses revealed that the expression of somatostatin mRNA was increased in the hypothalamus in anorectic mice that received a Val-deficient diet. On the other hand, when somatostatin was administered intracerebroventricularly to intact animals that were fed a control diet, their 24-h food intake decreased significantly. In addition, Val-deficient but not pair-fed mice or those fasted for 24 h showed a less than 0.5-fold decrease in the hypothalamic mRNA expression levels of Crym, Foxg1, Itpka and two unknown EST clone genes and a more than twofold increase in those of Slc6a3, Bdh1, Ptgr2 and one unknown EST clone gene. These results suggest that hypothalamic somatostatin and genes responsive to Val deficiency may be involved in the central mechanism of anorexia induced by a Val-deficient diet.

Pharmacokinetics and cerebral distribution of glycine administered to rats.

High doses of glycine have been reported to improve negative schizophrenic symptoms, suggesting that ingested glycine activates glutamatergic transmission via N-methyl-D-aspartate (NMDA) receptors. However, the pharmacokinetics of administered glycine in the brain has not been evaluated. In the present study, the time- and dose-dependent distributions of administered glycine were investigated from a pharmacokinetic viewpoint. Whole-body autoradiography of radiolabeled glycine was performed, and time-concentration curves for glycine and serine in plasma, cerebrospinal fluid (CSF), and brain tissues were obtained. Furthermore, pharmacokinetic parameters were calculated. For a more detailed analysis, the amount of glycine uptake in the brain was evaluated using the brain uptake index method. Radiolabeled glycine was distributed among periventricular organs in the brain. Oral administration of 2 g/kg of glycine significantly elevated the CSF glycine concentration above the ED50 value for NMDA receptors. The glycine levels in CSF were 100 times lower than those in plasma. Glycine levels were elevated in brain tissue, but with a slower time-course than in CSF. Serine, a major metabolite of glycine, was elevated in plasma, CSF, and brain tissue. Glycine uptake in brain tissue increased in a dose-dependent manner. Time-concentration curves revealed that glycine was most likely transported via the blood-CSF barrier and activated NMDA receptors adjacent to the ventricles. The pharmacokinetic analysis and the brain uptake index for glycine suggested that glycine was transported into brain tissue by passive diffusion. These results provide further insight into the potential therapeutic applications of glycine.

The association of social capital with depression and quality of life in school-aged children.

Social capital is an important factor that affects mental health. The purpose of this study was to examine the relationship between social capital and depression and between social capital and quality of life (QoL) in children in elementary and junior high school and to examine how this relationship differs in relevant patterns at both the individual- and school-level. The study was conducted in all elementary and junior high schools in a single municipality; the subjects consisted of 3,722 elementary school and 3,987 junior high school students (aged from 9 to 15). A multilevel linear mixed effect model analysis revealed that all three subscales of social capital were associated with depression and QoL at the individual-level: The school social capital at the individual-level showed the strongest association with depression and QoL. We also found that some of social capital at the school-level was associated with depression and QoL. An interactive effect was observed between educational stage (elementary and junior high) and some of social capital subscales. Specifically, the inverse association between school social capital and depression was stronger among the junior high students, while the positive association between school and neighborhood social capital and QoL was stronger among the elementary students. These interactions suggest that social capital impacts depression and QoL differently in elementary and junior high students. These findings suggest that the degree of association of social capital domains differs in mental health among the educational stage.

Trajectories of Adaptive Behaviors During Childhood in Females and Males in the General Population.

Little is known about the trajectory patterns and sex differences in adaptive behaviors in the general population. We examined the trajectory classes of adaptive behaviors using a representative sample and examined whether the class structure and trajectory patterns differed between females and males. We further explored sex differences in neurodevelopmental traits in each latent class. Participants (n = 994) were children in the Hamamatsu Birth Cohort for Mothers and Children (HBC Study)-a prospective birth cohort study. Adaptive behaviors in each domain of communication, daily living skills, and socialization were evaluated at five time points when participants were 2.7, 3.5, 4.5, 6, and 9 years old using the Vineland Adaptive Behavior Scales-Second Edition. Parallel process multigroup latent class growth analysis extracted sex-specific trajectory classes. Neurodevelopmental traits of children at age 9, autistic traits, attention deficit hyperactivity disorder (ADHD) traits, and cognitive ability were examined for females and males in each identified class. A 4-class model demonstrated the best fit. Moreover, a 4-class model that allowed for differences in class probabilities and means of growth parameters between females and males provided a better fit than a model assuming no sex differences. In the communication domain, females scored higher than their male counterparts in all four classes. In the daily living skills and socialization domains, the two higher adaptive classes (Class 1: females, 18.6%; males, 17.8%; Class 2: females, 48.8%; males, 49.8%) had similar trajectories for males and females, whereas in the two lower adaptive behavior classes (Class 3: females, 27.5%; males, 29.4%; Class 4: females, 5.1%; males, 3.0%), females had higher adaptive scores than their male counterparts. In Class 4, females were more likely to have autistic and ADHD traits exceeding the cutoffs, while males were more likely to have below-average IQ. Different trajectories in females and males suggest that adaptive skills may require adjustment based on the sex of the child, when standardizing scores, in order to achieve better early detection of skill impairment.