Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization.

Previous studies reported decreased glutamate levels in the anterior cingulate cortex (ACC) in non-treatment-resistant schizophrenia and first-episode psychosis. However, ACC glutamatergic changes in subjects at high-risk for psychosis, and the effects of commonly experienced environmental emotional/social stressors on glutamatergic function in adolescents remain unclear. In this study, adolescents recruited from the general population underwent proton magnetic resonance spectroscopy (MRS) of the pregenual ACC using a 3-Tesla scanner. We explored longitudinal data on the association of combined glutamate-glutamine (Glx) levels, measured by MRS, with subclinical psychotic experiences. Moreover, we investigated associations of bullying victimization, a risk factor for subclinical psychotic experiences, and help-seeking intentions, a coping strategy against stressors including bullying victimization, with Glx levels. Finally, path analyses were conducted to explore multivariate associations. For a contrast analysis, gamma-aminobutyric acid plus macromolecule (GABA+) levels were also analyzed. Negative associations were found between Glx levels and subclinical psychotic experiences at both Times 1 (n = 219, mean age 11.5 y) and 2 (n = 211, mean age 13.6 y), as well as for over-time changes (n = 157, mean interval 2.0 y). Moreover, effects of bullying victimization and bullying victimization × help-seeking intention interaction effects on Glx levels were found (n = 156). Specifically, bullying victimization decreased Glx levels, whereas help-seeking intention increased Glx levels only in bullied adolescents. Finally, associations among bullying victimization, help-seeking intention, Glx levels, and subclinical psychotic experiences were revealed. GABA+ analysis revealed no significant results. This is the first adolescent study to reveal longitudinal trajectories of the association between glutamatergic function and subclinical psychotic experiences and to elucidate the effect of commonly experienced environmental emotional/social stressors on glutamatergic function. Our findings may deepen the understanding of how environmental emotional/social stressors induce impaired glutamatergic neurotransmission that could be the underpinning of liability for psychotic experiences in early adolescence.

Birth order and prosociality in the early adolescent brain.

Birth order is a crucial environmental factor for child development. For example, later-born children are relatively unlikely to feel secure due to sibling competition or diluted parental resources. The positive effect of being earlier-born on cognitive intelligence is well-established. However, whether birth order is linked to social behavior remains controversial, and the neural correlates of birth order effects in adolescence when social cognition develops remain unknown. Here, we explored the birth order effect on prosociality using a large-scale population-based adolescent cohort. Next, since the amygdala is a key region for sociality and environmental stress, we examined amygdala substrates of the association between birth order and prosociality using a subset neuroimaging cohort. We found enhanced prosociality in later-born adolescents (N = 3160), and observed the mediating role of larger amygdala volume (N = 208) and amygdala-prefrontal functional connectivity with sex-selective effects (N = 183). We found that birth order, a non-genetic environmental factor, affects adolescent social development via different neural substrates. Our findings may indicate the later-born people's adaptive survival strategy in stressful environments.

Association between duration of breastfeeding based on maternal reports and dorsal and ventral striatum and medial orbital gyrus volumes in early adolescence.

Maternal breastfeeding has an impact on motor and emotional development in children of the next generation. Elucidating how breastfeeding during infancy affects brain regional structural development in early adolescence will be helpful for promoting healthy development. However, previous studies that have shown relationships between breastfeeding during infancy and cortical brain regions in adolescence are usually based on maternal retrospective recall of breastfeeding, and the accuracy of the data is unclear. In this study, we investigated the association between breastfeeding duration and brain regional volume in a population-neuroimaging study of early adolescents in Japan (N â€‹= â€‹207; 10.5-13.4 years) using voxel-based morphometry, which enabled us to analyze the whole brain. We evaluated breastfeeding duration as indexed by maternal and child health handbook records during infancy. The results showed a significant positive correlation between the duration of breastfeeding and gray matter volume in the dorsal and ventral striatum and the medial orbital gyrus. Post hoc exploratory analyses revealed that the duration of breastfeeding was significantly correlated with emotional behavior. Additionally, the volume in the medial orbital gyrus mediated an association between breastfeeding duration and emotional behavior. This is the first study to evaluate the effect of breastfeeding during infancy on regional brain volumes in early adolescence based on maternal and child health handbook records. Our findings shed light upon the importance of maternal breastfeeding for brain development related to emotional and motivational processing in early adolescence.

Neurometabolic underpinning of the intergenerational transmission of prosociality.

Parent-child personality transmission can occur via biological gene-driven processes as well as through environmental factors such as shared environment and parenting style. We recently revealed a negative association between prosociality, a highly valued personality attribute in human society, and anterior cingulate cortex (ACC) γ-aminobutyric acid (GABA) levels in children at the age of 10 years. We thus hypothesized that prosociality would be intergenerationally transmitted, and that transmission would be underwritten by neurometabolic heritability. Here, we collected prosociality data from children aged 10 years and their parents in a large-scale population-based birth cohort study. We also measured ACC GABA+ and glutamate plus glutamine (Glx) levels in a follow-up assessment with a subsample of the participants (aged 11 years) using magnetic resonance spectroscopy. We analyzed the associations among children's and parents' prosociality and GABA+/Glx ratios. We also examined the effect of socioeconomic status (SES) and verbalized parental affection (VPA) on these associations. We found a significant positive parent-child association for prosociality (N â€‹= â€‹3026; children's mean age 10.2 years) and GABA+/Glx ratio (N â€‹= â€‹99; children's mean age 11.4 years). There was a significant negative association between GABA+/Glx ratio and prosociality in both children (N â€‹= â€‹208) and parents (N â€‹= â€‹128). Our model accounting for the effects of neurometabolic heritability on prosociality transmission fitted well. Moreover, in this model, a significant positive effect of VPA but not SES on children's prosociality was observed independently of the effect of neurometabolic transmission, while SES but not VPA was significantly associated with parental prosociality. Our results provide novel insights into the neurometabolic substrates of parent-child transmission of social behavior.

Smaller anterior subgenual cingulate volume mediates the effect of girls' early sexual maturation on negative psychobehavioral outcome.

Early-maturing girls are relatively likely to experience compromised psychobehavioral outcomes. Some studies have explored the association between puberty and brain morphology in adolescents, while the results were non-specific for females or the method was a region-of-interest analysis. To our knowledge, no large-scale study has comprehensively explored the effects of pubertal timing on whole-brain volumetric development or the neuroanatomical substrates of the association in girls between pubertal timing and psychobehavioral outcomes. We collected structural magnetic resonance imaging (MRI) data of a subsample (N â€‹= â€‹203, mean age 11.6 years) from a large-scale population-based birth cohort. Tanner stage, a scale of physical maturation in adolescents, was rated almost simultaneously with MRI scan. The Strengths and Difficulties Questionnaire total difficulties (SDQ-TD) scores were rated by primary parents some duration after MRI scan (mean age 12.1 years). In each sex group, we examined brain regions associated with Tanner stage using whole-brain analysis controlling for chronological age, followed by an exploration of brain regions also associated with the SDQ-TD scores. We also performed mediation analyses. In girls, Tanner stage was significantly negatively correlated with gray matter volumes (GMVs) in the anterior/middle cingulate cortex (ACC/MCC), of which the subgenual ACC (sgACC) showed a negative correlation between GMVs and SDQ-TD scores. Smaller GMVs in the sgACC mediated the association between higher Tanner stages and higher SDQ-TD scores. We found no significant results in boys. Our results from a minimally biased, large-scale sample provide new insights into neuroanatomical correlates of the effect of pubertal timing on developmental psychological difficulties emerging in adolescence.

Use of social networking sites and desire for slimness among 10-year-old girls and boys: A population-based birth cohort study.

OBJECTIVE: Desire for slimness (DS) is a well-established risk factor for eating disorders among adolescents, particularly girls. It is known that exposure to traditional media such as television can increase DS. However, the association between DS and the use of new media, such as social networking sites (SNS), adjusting for relevant potential confounders, has not been examined to-date. In this study, we assessed the relationship between DS and SNS use among early adolescent girls and boys, adjusting for body mass index (BMI), time spent watching television, and Internet use. METHOD: DS, SNS use, and confounding variables were assessed using self-report questionnaires and face-to-face interviews from a cross-sectional population-based survey of 4,478 10-year-old Japanese adolescents (2,100 girls and 2,378 boys). RESULTS: After adjusting for confounding variables, SNS use was associated with increased risk of DS among girls (odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.17-3.18, p = .010), but not among boys (OR = 1.07; 95% CI, 0.64-1.80, p = .786). DISCUSSION: Exposure to SNS was associated with an increased risk of DS among early adolescents, especially girls. Targeting SNS use in early adolescence seems a promising approach to prevention of DS and subsequent eating problems, particularly among girls.

Neurometabolic and functional connectivity basis of prosocial behavior in early adolescence.

Human prosocial behavior (PB) emerges in childhood and matures during adolescence. Previous task-related functional magnetic resonance imaging (fMRI) studies have reported involvement of the medial prefrontal cortex including the anterior cingulate cortex (ACC) in social cognition in adolescence. However, neurometabolic and functional connectivity (FC) basis of PB in early adolescence remains unclear. Here, we measured GABA levels in the ACC and FC in a subsample (aged 10.5-13.4 years) of a large-scale population-based cohort with MR spectroscopy (MEGA-PRESS) and resting-state fMRI. PB was negatively correlated with GABA levels in the ACC (N = 221), and positively correlated with right ACC-seeded FC with the right precentral gyrus and the bilateral middle and posterior cingulate gyrus (N = 187). Furthermore, GABA concentrations and this FC were negatively correlated, and the FC mediated the association between GABA levels and PB (N = 171). Our results from a minimally biased, large-scale sample provide new insights into the neurometabolic and neurofunctional correlates of prosocial development during early adolescence.

Population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC): Cohort longitudinal study to explore the neurobiological substrates of adolescent psychological and behavioral development.

AIM: Adolescence is a crucial stage of psychological development and is critically vulnerable to the onset of psychopathology. Our understanding of how the maturation of endocrine, epigenetics, and brain circuit may underlie psychological development in adolescence, however, has not been integrated. Here, we introduce our research project, the population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC), a longitudinal study to explore the neurobiological substrates of development during adolescence. METHODS: Participants in the first wave of the pn-TTC (pn-TTC-1) study were recruited from those of the TTC study, a large-scale epidemiological survey in which 3171 parent-adolescent pairs were recruited from the general population. Participants underwent psychological, cognitive, sociological, and physical assessment. Moreover, adolescents and their parents underwent magnetic resonance imaging (MRI; structural MRI, resting-state functional MRI, and magnetic resonance spectroscopy), and adolescents provided saliva samples for hormone analysis and for DNA analysis including epigenetics. Furthermore, the second wave (pn-TTC-2) followed similar methods as in the first wave. RESULTS: A total of 301 parent-adolescent pairs participated in the pn-TTC-1 study. Moreover, 281 adolescents participated in the pn-TTC-2 study, 238 of whom were recruited from the pn-TTC-1 sample. The instruction for data request is available at: http://value.umin.jp/data-resource.html. CONCLUSION: The pn-TTC project is a large-scale and population-neuroscience-based survey with a plan of longitudinal biennial follow up. Through this approach we seek to elucidate adolescent developmental mechanisms according to biopsychosocial models. This current biomarker research project, using minimally biased samples recruited from the general population, has the potential to expand the new research field of population neuroscience.

Abnormal asymmetries in subcortical brain volume in early adolescents with subclinical psychotic experiences.

Subcortical structures may have an important role in the pathophysiology of psychosis. Our recent mega-analysis of structural magnetic resonance imaging (MRI) data has reported subcortical volumetric and lateralization alterations in chronic schizophrenia, including leftward asymmetric increases in pallidal volume. The question remains, however, whether these characteristics may represent vulnerability to the development of psychosis or whether they are epiphenomena caused by exposure to medication or illness chronicity. Subclinical psychotic experiences (SPEs) occur in some adolescents in the general population and increase the odds of developing psychosis in young adulthood. Investigations into the association between SPEs and MRI-measured volumes of subcortical structures in the general adolescent population would clarify the issue. Here, we collected structural MRI data in a subsample (10.5-13.3 years old) of a large-scale population-based cohort and explored subcortical volume and lateralization alterations related to SPEs (N = 203). Adolescents with SPEs demonstrated significant volumetric increases in the left hippocampus, right caudate, and right lateral ventricle, as well as a marginally significant increase in the left pallidum. Furthermore, adolescents with SPEs showed significantly more leftward laterality of pallidal volume than individuals without SPEs, which replicates our mega-analysis findings in chronic schizophrenia. We suggest that leftward asymmetries in pallidal volume already present in early adolescence may underlie the premorbid predisposition for developing psychosis in later life.

Disciplinary slapping is associated with bullying involvement regardless of warm parenting in early adolescence.

INTRODUCTION: Bullying among adolescents can cause depression and suicidality. Identifying the risk factors for bullying in early adolescence, when its prevalence tends to increase, would assist in its prevention. Although certain parenting styles are known to be associated with bullying, the association of slapping as a parental disciplinary practice with early adolescent bullying is not sufficiently understood. Furthermore, little is known about how warm parenting modifies this association although slapping and warm parenting are not mutually exclusive. The aim of this study was to investigate the association of slapping with the experience of early adolescent bullying--categorized in terms of victims, bullies, and bully-victims--while considering how warm parenting modifies this association. METHODS: This study used data from the Tokyo Early Adolescence Survey, a cross-sectional survey of 4478 children aged 10 from the general population. Data were collected from both children and their primary parent using self-administered questionnaires and face-to-face interviews. Responses from 4326 participants with no missing data were usable for the current analysis (mean age,  10.2 ±â€¯0.3 years; 53 % boys). RESULTS: Frequent and occasional slapping was associated with increased odds of youth being identified as bullies or bully-victims, even after adjusting for warm parenting. The likelihood of being victims, bullies or bully-victims increased as the frequency of slapping increased. CONCLUSION: Disciplinary slapping was associated with increased odds of bullying in early adolescence, regardless of whether warm parenting was present or not.

Enuresis and Hyperactivity-Inattention in Early Adolescence: Findings from a Population-Based Survey in Tokyo (Tokyo Early Adolescence Survey).

BACKGROUND: Enuresis (9% at age 9.5) negatively affects children's psychosocial status. Clinically-diagnosed enuresis (2% at the age) is associated with hyperactivity-inattention, and common neural bases have been postulated to underlie this association. It is, however, unclear whether this association is applicable to enuresis overall among the general population of early adolescents when considered comorbid behavioral problems. We aimed to examine whether enuresis correlates with hyperactivity-inattention after controlling for the effects of other behavioral problems. METHODS: Participants were 4,478 children (mean age 10.2 ± 0.3 years old) and their parents from the Tokyo Early Adolescence Survey (T-EAS), a population-representative cross-sectional study conducted in Tokyo, Japan conducted from 2012 to 2015. Children's enuresis and behavioral problems, including hyperactivity-inattention (as measured by the Strength and Difficulties Questionnaire), were examined using parent-reporting questionnaires. Multivariate linear regression was used to explore whether enuresis predicts hyperactivity-inattention. RESULTS: The hyperactivity-inattention score was significantly higher in the enuretic group than the non-enuretic group (enuretic: M (SD) = 3.8 (2.3), non-enuretic: M (SD) = 3.0 (2.1), Hedge's g = 0.39, p < .001). This association remained significant even after controlling for other behavioral problems and including sex, age, intelligence quotient (IQ), low birth weight and parents' education (ß = .054 [95% CI: .028-.080], p < .001). CONCLUSIONS: Enuresis was independently associated with hyperactivity-inattention in early adolescents among general population even when other behavioral problems were considered. These results suggest that, as with clinically-diagnosed cases, enuresis may predict need for screening and psychosocial support for hyperactivity-inattention.

Enterolithiasis in a cat.

An 8-year-old female Persian cat was brought in for evaluation of chronic vomiting. The presence of opaque enteric foreign bodies and intestinal obstruction along with azotaemia, hyperphosphataemia, moderate anaemia and peritoneal fluid were revealed following appropriate diagnostic work-up. Exploratory laparotomy confirmed jejunoileal dilation, ileocaecal stenosis, and numerous foreign objects in the jejunoileum. These foreign objects and ileocaecal stenosis were surgically removed, and intestinal resection and anastomosis was performed. The patient recovered favourably. Analysis revealed that the foreign objects were composed of calcium phosphate and calcium carbonate. Intestinal inflammation and stenosis secondary to enterolithiasis may have developed following ingestion of cat litter or a previous unrelated surgical intervention. We were unable to delineate the inciting pathogenesis in this particular case.

A case of protein-losing enteropathy treated with methotrexate in a dog.

A 9-year-old female Pug was presented to us with chronic diarrhea. Hematologic findings indicated severe hypoproteinemia and hypoalbuminemia, and endoscopy revealed severe edema of the duodenal mucosa. Based on these results and on additional histopathological findings, we made a diagnosis of protein-losing enteropathy caused by lymphocytic-plasmacytic enteritis with lymphangiectasia. The dog was initially treated with prednisolone and cyclosporine. This treatment regimen was not effective. However, when methotrexate was substituted for cyclosporine, progress was obtained and the diagnosis was confirmed.