ABSTRACT
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.
Subject(s)
Bullying , Crime Victims , Glutamic Acid , Gyrus Cinguli , Psychotic Disorders , Humans , Gyrus Cinguli/metabolism , Adolescent , Male , Female , Psychotic Disorders/metabolism , Glutamic Acid/metabolism , Bullying/psychology , Crime Victims/psychology , Longitudinal Studies , Child , Glutamine/metabolism , gamma-Aminobutyric Acid/metabolism , Proton Magnetic Resonance Spectroscopy/methods , Risk Factors , Schizophrenia/metabolism , Magnetic Resonance Spectroscopy/methodsABSTRACT
Adolescence is a critical period for psychological difficulties. Auditory mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are representative electrophysiological indices that mature during adolescence. However, the longitudinal association between MMN/ASSR and psychological difficulties among adolescents remains unclear. We measured MMN amplitude for duration and frequency changes and ASSR twice in a subsample (n = 67, mean age 13.4 and 16.1 years, respectively) from a large-scale population-based cohort. No significant longitudinal changes were observed in any of the electroencephalography indices. Changes in SDQ-TD were significantly associated with changes in duration MMN, but not frequency MMN and ASSR. Furthermore, the subgroup with higher SDQ-TD at follow-up showed a significant duration MMN decrease over time, whereas the subgroup with lower SDQ-TD did not. The results of our population neuroscience study suggest that insufficient changes in electroencephalography indices may have been because of the short follow-up period or non-monotonic change during adolescence, and indicated that the longitudinal association with psychological difficulties was specific to the duration MMN. These findings provide new insights that electrophysiological change may underlie the development of psychosocial difficulties emerging in adolescence.
Subject(s)
Electroencephalography , Evoked Potentials, Auditory , Humans , Adolescent , Evoked Potentials, Auditory/physiology , Acoustic Stimulation/methods , Auditory Perception/physiologyABSTRACT
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.
Subject(s)
Altruism , Birth Order , Brain/physiology , Amygdala/diagnostic imaging , Amygdala/growth & development , Amygdala/physiology , Birth Order/psychology , Brain/diagnostic imaging , Child , Emotional Intelligence/physiology , Female , Humans , Magnetic Resonance Imaging , Male , NeuroimagingABSTRACT
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= â207; 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.
Subject(s)
Breast Feeding , Corpus Striatum/diagnostic imaging , Gray Matter/diagnostic imaging , Prefrontal Cortex/diagnostic imaging , Adolescent , Child , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Organ Size/physiology , Retrospective Studies , Time FactorsABSTRACT
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= â3026; children's mean age 10.2 years) and GABA+/Glx ratio (N â= â99; children's mean age 11.4 years). There was a significant negative association between GABA+/Glx ratio and prosociality in both children (N â= â208) and parents (N â= â128). 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.
Subject(s)
Brain Chemistry/physiology , Intergenerational Relations , Social Behavior , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Female , Glutamine/metabolism , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/metabolism , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Mother-Child Relations , Parent-Child Relations , Personality , Puberty/physiology , Social Class , gamma-Aminobutyric Acid/metabolismABSTRACT
Social withdrawal may lead to mental health problems and can have a large impact on a life course, particularly among boys. To support adolescents with social withdrawal, an integrative understanding of the biological bases would be helpful. Social dominance, a possible opposite of social withdrawal, is known to have positive associations with testosterone levels. A previous study suggested that social withdrawal has a negative relationship with sexual maturity among adolescent boys. However, the relationship between social withdrawal and testosterone in adolescence is unknown. This study aimed to examine whether social withdrawal was negatively associated with testosterone levels in early adolescent boys. Salivary samples were collected from 159 healthy early adolescent boys (mean age [standard deviation]: 11.5 [0.73]) selected from participants of the "population-neuroscience study of the Tokyo Teen Cohort" (pn-TTC). Social withdrawal and confounding factors, such as the secondary sexual characteristics and their age in months, were evaluated by self-administered questionnaires completed by the primary parents. The degree of social withdrawal was assessed with the Child Behaviour Checklist (CBCL). Levels of salivary testosterone, and cortisol as a control, were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Logistic regression was conducted to examine the association between social withdrawal and testosterone levels. A higher risk of social withdrawal was associated with a lower salivary testosterone level after adjustment for age in months (odds ratio 0.55, 95 % confidence interval 0.33-0.94), and the association remained significant after adjusting for body mass index, the degree of anxiety/depression and pubertal stage. Thus, we found a negative relationship between social withdrawal and testosterone levels in early adolescent boys. These findings may help to clarify the biological foundations of and to develop support for social withdrawal.
Subject(s)
Adolescent Behavior/physiology , Child Behavior/physiology , Puberty/physiology , Social Behavior , Testosterone/metabolism , Adolescent , Child , Chromatography, Liquid , Cohort Studies , Humans , Hydrocortisone/metabolism , Male , Puberty/metabolism , Saliva/metabolism , Tandem Mass SpectrometryABSTRACT
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= â203, 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.
Subject(s)
Adolescent Behavior/physiology , Behavioral Symptoms/physiopathology , Gray Matter/anatomy & histology , Gyrus Cinguli/anatomy & histology , Puberty/physiology , Sexual Maturation/physiology , Adolescent , Age Factors , Child , Cohort Studies , Female , Gray Matter/diagnostic imaging , Gyrus Cinguli/diagnostic imaging , Humans , Magnetic Resonance Imaging , MaleABSTRACT
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.
Subject(s)
Brain/physiology , Frontal Lobe/physiology , Prefrontal Cortex/physiology , Social Behavior , Adolescent , Brain/diagnostic imaging , Brain Mapping , Child , Female , Frontal Lobe/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/physiology , Prefrontal Cortex/diagnostic imaging , Rest/physiology , gamma-Aminobutyric Acid/metabolismABSTRACT
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.
Subject(s)
Adolescent Behavior/physiology , Adolescent Development/physiology , Behavioral Symptoms/physiopathology , Brain/diagnostic imaging , Electroencephalography , Epigenesis, Genetic/genetics , Magnetic Resonance Imaging , Neuropsychological Tests , Adolescent , Adolescent Behavior/psychology , Behavioral Symptoms/epidemiology , Female , Humans , Longitudinal Studies , Male , Parents , Saliva , Tokyo/epidemiologyABSTRACT
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.