Developmental Changes of Prefrontal Activation in Humans: A Near-Infrared Spectroscopy Study of Preschool Children and Adults

Previous morphological studies indicated that development of the human prefrontal cortex (PFC) appears to continue into late adolescence. Although functional brain imaging studies have sought to determine the time course of functional development of the PFC, it is unclear whether the developmental change occurs after adolescence to adulthood and when it achieves a peak because of the narrow or discontinuous range in the participant's age. Moreover, previous functional studies have not focused on the anterior frontal region, that is, the frontopolar regions (BA9/10). Thus, the present study investigated the developmental change in frontopolar PFC activation associated with letter fluency task by using near-infrared spectroscopy (NIRS), in subjects from preschool children to adults. We analyzed the relative concentration of hemoglobin (ΔHb) in the prefrontal cortex measured during the activation task in 48 typically-developing children and adolescents and 22 healthy adults. Consistent with prior morphological studies, we found developmental change with age in the children/adolescents. Moreover, the average Δoxy-Hb in adult males was significantly larger than that in child/adolescent males, but was not true for females. These data suggested that functional development of the PFC continues into late adolescence. Although the developmental change of the frontopolar PFC was independent of gender from childhood to adolescence, in adulthood a gender difference was shown

Neuroanatomical correlates of attention-deficit-hyperactivity disorder accounting for comorbid oppositional defiant disorder and conduct disorder

Aim: An increasing number of neuroimaging studies have been conducted to uncover the pathophysiology of attention-deficit-hyperactivity disorder (ADHD). The findings are inconsistent, however, at least partially due to methodological differences. In the present study voxel-based morphometry (VBM) was used to evaluate brain morphology in ADHD subjects after taking into account the confounding effect of oppositional defiant disorder (ODD) and conduct disorder (CD) comorbidity. Methods: Eighteen children with ADHD and 17 age-and gender-matched typically developing subjects underwent high-spatial resolution magnetic resonance imaging. The regional gray matter volume differences between the children with ADHD and controls were examined with and without accounting for comorbid ODD and CD in a voxel-by-voxel manner throughout the entire brain. Results: The VBM indicated significantly smaller regional gray matter volume in regions including the bilateral temporal polar and occipital cortices and the left amygdala in subjects with ADHD compared with controls. Significantly smaller regional gray matter volumes were demonstrated in more extensive regions including the bilateral temporal polar cortices, bilateral amygdala, right occipital cortex, right superior temporal sulcus, and left middle frontal gyrus after controlling for the confounding effect of comorbid ODD and CD. Conclusion: Morphological abnormalities in ADHD were seen not only in the regions associated with executive functioning but also in the regions associated with social cognition. When the effect of comorbid CD and ODD was taken into account, there were more extensive regions with significantly smaller volume in ADHD compared to controls.ArticlePSYCHIATRY AND CLINICAL NEUROSCIENCES. 64(4):394-402 (2010)journal articl

Neighborhood Social Cohesion and Dementia-Related Stigma Among Mothers of Adolescents in the Pre- and Current COVID-19 Period: An Observational Study Using Population-Based Cohort Data

BACKGROUND: Middle-aged adults may be the ideal target group for dementia-related stigma reduction interventions to encourage the utilization of services among those who may become family caregivers. Neighborhood social cohesion may diminish dementia-related stigma, particularly in terms of perceived public attitudes. The COVID-19 pandemic can further negatively impact perceived public stigma. OBJECTIVE: To investigate the association between neighborhood social cohesion and dementia-related stigma during the pre- and current COVID-19 period. METHODS: We employed a cross-sectional design using data from a large population-based cohort, the Tokyo Teen Cohort, in Japan. Overall, 2,469 mothers of 16-year-old adolescents self-completed a questionnaire comprising nine dementia-related stigma questions evaluating perceived public and personal attitudes. Neighborhood social cohesion was assessed using a five-item instrument. The participants were divided into two groups according to the time of assessment: prior to the pandemic’s onset (February 2019–March 2020) and during the pandemic (April 2020–July 2021). A multiple regression analysis of stigma was performed using neighborhood social cohesion as an independent variable, and caring experience, age, educational level, and working status as covariates. RESULTS: Personal and perceived public stigma were significantly lower in participants who perceived greater neighborhood social cohesion. However, level of personal and perceived public stigma did not differ between pre- and during the pandemic period. CONCLUSIONS: Neighborhood social cohesion may be a modifiable factor for dementia-related stigma. A localized intervention to enhance social cohesion in the neighborhood community would promote the utilization of services among those who may become family caregivers

The association between locus of control and psychopathology:A Cross-Cohort Comparison Between a UK (Avon Longitudinal Study of Parents and Children) and a Japanese (Tokyo Teen Cohort) Cohort

Background: An external locus of control (externality) is associated with poorer psychopathology in individualist cultures, but associations are reported to be weaker in collectivist cultures where an external style is less maladaptive. We investigated the prospective association between externality and psychotic-like experiences (PLE) and depressive symptoms (DS) and compared the strength of associations between a UK and a Japanese cohort. Method: Cross-cultural cohort study of a UK (Avon Longitudinal Study of Parents and Children) and a Japanese cohort (Tokyo Teen Cohort). Externality was assessed using the Children's Nowicki and Strickland Internal, External Scale and DS using the Short Moods and Feelings Questionnaire in both cohorts, PLE were assessed with the Psychosis-Like Experiences Questionnaire (ALSPAC), and the Adolescent Psychotic-Like Symptom Screener (TTC). Associations were investigated using multivariable regression models and bivariate regression models to compare the strength of associations. Results: Mean externality in both childhood and adolescence was higher in ALSPAC than in the TTC. Childhood externality was associated with PLE in late childhood and adolescence in both cohorts and adolescent externality was associated with PLE in young adulthood in the ALSPAC cohort. There was a more mixed pattern of association between externality and DS scores. There was little evidence of any differences in the strength of associations between externality and different psychopathologies, or between cohorts. In ALSPAC adolescent externality and early adult psychopathology were more strongly associated than childhood externality and adolescent and early adult psychopathology. There was no evidence that change in externality between childhood and adolescence was associated with new onset PLE or DS in early adulthood. Conclusion: An external locus of control is associated with poor mental health regardless of cultural context

Progressive and Interrelated Functional and Structural Evidence of Post-Onset Brain Reduction in Schizophrenia

Context: Progressive brain abnormalities in schizophrenia remain controversial. Evidence of interrelated progressive functional impairment would buttress the case for structural progression. Mismatch negativity (MMN) is reduced in chronic but not first-hospitalized schizophrenia and may index progressive structural changes. Objective: To determine whether MMN shows associations with underlying auditory cortex gray matter at first hospitalization and progressive reduction longitudinally. Design: Cross-sectional (first hospitalization) and longitudinal (1.5-year follow-up). Setting: A private psychiatric hospital. Participants: Protocol entrance: MMN and magnetic resonance imaging at first hospitalization in 20 subjects with schizophrenia, 21 subjects with bipolar disorder with psychosis, and 32 control subjects. Longitudinal electrophysiologic testing: MMN in 16 subjects with schizophrenia, 17 subjects with bipolar disorder, and 20 control subjects. Longitudinal electrophysiologic testing and magnetic resonance imaging: MMN and magnetic resonance imaging in 11 subjects with schizophrenia, 13 subjects with bipolar disorder, and 13 control subjects. At each time point, reported samples were group matched for age, handedness, and parental socioeconomic status. Interventions: Electrophysiologic testing and high-resolution structural magnetic resonance imaging. Main Outcome Measures: Mismatch negativity amplitude and Heschl gyrus and planum temporale gray matter volumes. Results: Initially, groups did not differ in MMN amplitude. Subjects with schizophrenia showed associations between MMN and Heschl gyrus (r=−0.52; P=.02) not present in the other groups. At longitudinal MMN testing, schizophrenia showed MMN reduction (P=.004). Only schizophrenia evinced longitudinal left hemisphere Heschl gyrus reduction (P=.003), highly correlated with MMN reduction (r=0.6; P=.04). Conclusions: At first hospitalization for schizophrenia, MMN indexed left hemisphere Heschl gyrus gray matter volume, consistent with variable progression of pre-hospitalization cortical reduction. Longitudinally, the interrelated progressive reduction of functional and structural measures suggests progressive pathologic processes early in schizophrenia. An active process of progressive cortical reduction presents a potential therapeutic target. Mismatch negativity may be a simple, sensitive, and inexpensive index not only of this progressive pathologic process but also of successful intervention

Being Praised for Prosocial Behaviors Longitudinally Reduces Depressive Symptoms in Early Adolescents: A Population-Based Cohort Study

BackgroundDepression is highly prevalent and causes a heavy burden in adolescent life. Being praised for prosocial behavior might be a preventive factor because both being praised and prosocial behavior are protective against depression. Here, we investigated the longitudinal relationship between being praised for prosocial behavior and depressive symptoms in adolescents.MethodsIn Tokyo Teen Cohort study (TTC), an ongoing prospective population-based cohort study, we collected 3,171 adolescents' data on self-reported experiences of being praised for prosocial behavior, depressive symptoms, and caregiver-evaluated prosocial behavior. Ten-year-old children were asked to freely describe answers to the question “What are you praised for?”. Only children who clearly answered that they were praised for their prosocial behavior were designated the “prosocial praise group.” The degree of depression at ages 10 and 12 was measured with the Short Mood and Feelings Questionnaire (SMFQ), a self-report questionnaire about depression. Objective prosocial behavior of the 10 year-old children was assessed by the Strength and Difficulty Questionnaire (SDQ). Multiple linear regression analysis was performed using the SMFQ score at age 12 as the objective variable and being praised for prosocial behavior as the main explanatory variable, and the SMFQ score at age 10 and the objective prosocial behavior at age 10 were included as confounders.ResultsDepressive symptoms (SMFQ scores) in the “prosocial praise group” were significantly lower than those in the other group both at age 10 (4.3 ± 4.4 vs. 4.9 ± 4.6, p < 0.001) and at age 12 (3.4 ± 4.2 vs. 4.0 ± 4.6, p < 0.01). In the single regression analysis, the children who reported being praised for prosocial behavior at age 10 had significantly lower depressive symptoms at age 12 (partial regression variable: −0.57, 95% confidence interval (CI) [−0.96, −0.17]). This association remained significant after adjusting for confounders, including baseline depressive symptoms (partial regression variable: −0.44, 95% CI [−0.80, −0.08]). Prosocial behavior alone was not associated with depressive symptoms.ConclusionsBeing praised for prosocial behavior rather than objective prosocial behavior at 10 years of age predicted lower depressive symptoms 2 years later. Praise for adolescents' prosocial behavior can be encouraged to prevent depression

Informal Caregiving in Adolescents from 10 to 16 Years Old: A Longitudinal Study Using Data from the Tokyo Teen Cohort

There is growing evidence of the impact of informal caregiving on adolescent mental health, and its role is often hidden unintentionally or intentionally, which may hamper early identification and support for young informal caregivers. However, the quantitative evidence regarding household factors relating to informal caregiving has mostly been based on cross-sectional findings. This study examines the longitudinal associations between household characteristics and the duration of informal caregiving in adolescents from 10 to 16 years of age. Child–household respondent pairs (n = 2331) from the Tokyo Teen Cohort in Japan were followed every 2 years from 10 to 16 years of age. Informal caregiving was assessed repeatedly based on the household respondent’s survey responses. Persistent caregiving was defined as daily caregiving at two or more waves. There were 2.2% of children who gave daily care at two or more waves. Cross-sectional associations with daily informal caregiving at each wave were found with girls, low household income, and cohabiting with grandparents. A significant association with persistent caregiving was found only in cohabiting with grandparents at 10 years of age after adjusting for sex, number of siblings, single parent, and household income. Our longitudinal examination highlighted cohabiting with grandparents as a preceding factor for persistent caregiving. Identification and support for young informal caregivers should be integrated into social care service systems for older adults. The mechanism of persistent caregiving requires clarification

Psychiatric intervention and repeated admission to emergency centres due to drug overdose

Self-harm, with or without suicidal intent, substantially increases the risk of future suicide and is known to be the strongest predictor of completed suicide. Furthermore, repetition of self-harm is common: 16% of patients who self-harmed were found to repeat a similar episode within 1 year. Repetition of self-harm increases the risk of completed suicide. One study found overdose to be the most prevalent type of suicide attempt that required admission, and approximately 80% of self-harm episodes have been reported to involve overdose. It is therefore necessary to prevent the repetition of self-harm by drug overdose. According to clinical guidelines on the management of self-harm published in 2004, it is recommended that every patient presenting to hospital with self-harm should undergo a psychosocial assessment by specialists before being discharged. Despite this recommendation, some studies have found that many patients, especially those with repeated self-harm did not actually receive such assessments. That would suggest that the guideline has not been widely used – possibly because it was not based on firm evidence. There is a lack of data on the influence of psychosocial assessments on preventing repetition of self-harm. Some studies have suggested that such assessments do have an influence, but they were based on a small sample size or on a small number of highly advanced institutions. The present study focused on patients with drug overdose who were admitted to emergency centres. Using a national in-patient database in Japan, it aimed to investigate whether psychiatric intervention before discharge was associated with reduced patient readmissions with drug overdose.UTokyo Research掲載「過量服薬による入院患者と精神科医による診察の関係」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/psychiatric-intervention-and-repeated-emergency-admission-due-to-drug-overdose.htmlUTokyo Research "Psychiatric intervention and repeated emergency admission due to drug overdose" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/psychiatric-intervention-and-repeated-emergency-admission-due-to-drug-overdose.htm

Effects of Metabotropic Glutamate Receptor 3 Genotype on Phonetic Mismatch Negativity

BACKGROUND: The genetic and molecular basis of glutamatergic dysfunction is one key to understand schizophrenia, with the identification of an intermediate phenotype being an essential step. Mismatch negativity (MMN) or its magnetic counterpart, magnetic mismatch field (MMF) is an index of preattentive change detection processes in the auditory cortex and is generated through glutamatergic neurotransmission. We have previously shown that MMN/MMF in response to phoneme change is markedly reduced in schizophrenia. Variations in metabotropic glutamate receptor (GRM3) may be associated with schizophrenia, and has been shown to affect cortical function. Here we investigated the effect of GRM3 genotypes on phonetic MMF in healthy men. METHODS: MMF in response to phoneme change was recorded using magnetoencephalography in 41 right-handed healthy Japanese men. Based on previous genetic association studies in schizophrenia, 4 candidate SNPs (rs6465084, rs2299225, rs1468412, rs274622) were genotyped. RESULTS: GRM3 rs274622 genotype variations significantly predicted MMF strengths (p = 0.009), with C carriers exhibiting significantly larger MMF strengths in both hemispheres compared to the TT subjects. CONCLUSIONS: These results suggest that variations in GRM3 genotype modulate the auditory cortical response to phoneme change in humans. MMN/MMF, particularly those in response to speech sounds, may be a promising and sensitive intermediate phenotype for clarifying glutamatergic dysfunction in schizophrenia