Akemi Tomoda

Epigenetic studies of psychiatric and neurological disorders rely largely on peripheral tissues, yet where peripheral DNA methylation (DNAm) reflects the brain remains unclear. We generated a paired brain and peripheral DNAm dataset from 148 donors in three cohorts and combined it with five published cohorts for consensus brain–peripheral correlations. By cross-validation across cohorts, we defined brain epigenome shared sites (BrESS), more than 100,000 CpGs per tissue at which peripheral DNAm reproducibly predicts brain DNAm. BrESS lay at promoters active in both brain and periphery and in housekeeping genes, and most were not explained by genetic effects. BrESS did not contribute to the heritability of seven disorders, and CpGs from epigenome-wide association studies of these disorders were not enriched at BrESS. Peripheral DNAm reflects the brain mainly in a regulatory compartment shared across tissues, outside which disease signals largely lie, and BrESS separate peripheral signals attributable to the brain from others.

Smooth parent–child interaction is essential for children’s socioemotional development; however, the neural basis linking parent–child brain similarity to real-time interaction behavior remains unclear. This study examined whether mother–child similarity in resting-state functional connectomes was associated with eye contact during a cooperative task and the quality of their interaction. Resting-state functional magnetic resonance imaging (fMRI) data were obtained from school-aged children and their mothers. Region-of-interest (ROI)-to-ROI functional connectivity matrices were calculated. Mother–child functional connectome similarity was defined as the correlation between the mother’s and child’s connectivity profiles. Subsequently, the mother–child dyads completed a cooperative tabletop game, during which their interactions were video-recorded. Eye-contact behavior was coded, and interaction quality was assessed using the Interaction Rating Scale (IRS). Linear mixed-effects models revealed that greater mother–child functional connectome similarity was significantly associated with a higher eye-contact ratio, controlling for the child’s age, sex, socioeconomic status, and family-level clustering. Conversely, older age and male sex were associated with lower eye-contact ratios. Eye contact was positively associated with IRS scores. In addition, mediation analysis suggested a significant indirect effect of functional connectome similarity on interaction quality through eye contact. These findings indicate that similarity in intrinsic functional brain organization between the mother and child is reflected in observable reciprocal gaze behavior during face-to-face interaction. Furthermore, eye contact may serve as a behavioral pathway linking parent–child neural similarity to the quality of mother–child communication.

Background: Maternal bonding difficulties are an important yet under-recognized aspect of perinatal mental health, influencing both maternal well-being and child development. Although studies have examined postpartum depression and bonding impairment, few have investigated their longitudinal relationship within general pediatric settings in Japan. Methods: This single-center observational study analyzed data from 512 mother–infant dyads following delivery at a general hospital in Fukuoka, Japan. Maternal depressive symptoms and bonding were assessed at five days and one, two, and three months postpartum using the Edinburgh Postnatal Depression Scale (EPDS) and Mother-to-Infant Bonding Scale (MIBS), respectively. Latent growth models were estimated, and the resulting intercept and slope factor scores were subsequently subjected to Gaussian mixture-based clustering to identify trajectory-based subgroups. This analysis was conducted using an exploratory framework. The MIBS trajectory analyses were conducted on a subsample of 77 mothers with complete MIBS data, whereas the EPDS trajectory analyses used full information maximum likelihood-derived factor scores from 512 mothers. Results: In the linear mixed-effects model using all available paired observations, higher EPDS total scores were significantly associated with higher subsequent MIBS scores across the early postpartum period. Exploratory clustering of latent growth model-derived factor scores suggested three MIBS and four EPDS trajectory-based subgroups, characterized by different baseline levels and decreasing or persistent depressive symptom patterns. The EPDS total and subscale scores were also associated with MIBS scores. Because the MIBS trajectory analysis was based on a small, clinically selected, complete-case sample, subgroup-specific findings should be interpreted cautiously. Conclusions: Repeated EPDS and MIBS assessments in pediatric clinical practice may help characterize the associations between postpartum depressive symptoms and maternal bonding difficulties during the early postpartum period. Exploratory trajectory-based analyses suggested heterogeneous bonding-difficulty patterns, including a subgroup with increasing MIBS scores over the first three months postpartum. Further studies are required to determine whether such assessments can improve maternal and child outcomes.

Introduction: Neurodevelopmental outcomes in late preterm (LP) children, born between 34 and 36 gestation weeks, remain unclear. This study aimed to examine behavioral, cognitive, and multimodal neuroimaging outcomes in children born late preterm compared with children born full term during early adolescence using data from the large U.S.-based Adolescent Brain Cognitive Development Study, with longitudinal mixed-effects models used as the primary analytic framework to evaluate group, timepoint, and group-by-timepoint effects. Methods: Participants aged 9–11 years at baseline were categorized into LP and full-term (FT; ≥40 weeks) groups. Outcomes included behavioral and emotional problems, cognitive function, structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI. Longitudinal mixed-effects models were used as the primary analyses, with Type III tests evaluating group, timepoint, and group-by-timepoint effects. False discovery rate correction was applied within predefined outcome families. Results: The longitudinal models showed no broad LP–FT differences or group-by-timepoint interactions in behavioral and emotional problems, most cognitive outcomes, cortical thickness, cortical surface area, or resting state functional MRI within-network connectivity. Structural MRI showed group effects in six regional brain volumes, without significant timepoint or group-by-timepoint effects. DTI showed the most prominent findings: significant group effects were observed in selected white matter tract, cortical and subcortical region of interest fractional anisotropy or mean diffusivity metrics, and significant group-by-timepoint interactions were observed in selected DTI metrics. Discussion: These findings suggest that late preterm birth is associated with subtle and regionally specific neuroimaging differences during early adolescence, particularly in DTI metrics.

Neurobiological mechanisms underlying child maltreatment perpetration remain poorly understood, and the role of immune dysregulation has rarely been examined. Here, we tested whether peripheral inflammatory signatures are linked to brain structural alterations in mothers who have perpetrated maltreatment, and whether such alterations mediate this link to perpetration. In this cross-sectional study integrating structural MRI and inflammatory proteomics, 16 mothers with histories of maltreatment perpetration and 145 age-matched control mothers underwent brain imaging; a subgroup (n = 52; 11 maltreatment, 41 control) also completed plasma proteomic profiling using the Olink Target 96 Inflammation panel. Whole-brain voxel-based morphometry revealed significantly reduced gray matter volume (GMV) in the right middle/inferior temporal gyri—a region implicated in social cognition and contextual interpretation—in the maltreatment group. Proteomic analysis identified 16 inflammation-related proteins differentially expressed between groups; among these, nine were significantly associated with GMV in this temporal region. Lower GMV was associated with higher levels of pro-inflammatory proteins (CCL20, IL-17C) and with lower levels of immune-regulatory and metabolic proteins (CXCL1, CXCL6, SIRT2, STAMBP, MCP-2, MCP-4, 4E-BP1). Mediation analyses revealed that both protein sets were indirectly associated with perpetration through this regional GMV, with opposing patterns of direct association. These findings suggest that peripheral immune imbalance—characterized by elevated inflammatory signaling and diminished immune-regulatory capacity—is linked to structural vulnerability in a temporal cortical region involved in social cognition, specifically in perpetrating mothers. This neuroimmune pathway may contribute to maladaptive interpretation of child signals during caregiving and represents a potential target for biomarker-informed preventive intervention.

Background: Brain imaging studies of attention-deficit/hyperactivity disorder (ADHD) have produced inconsistent findings, partly due to measurement bias across magnetic resonance imaging (MRI) scanners in multi-site studies. In particular, developmental trajectories of functional brain networks in ADHD remain poorly understood. This study aimed to clarify age-related functional brain characteristics in children with ADHD by reducing scanner-related measurement bias using the traveling-subject (TS) harmonization approach.Methods: MRI data were collected from 220 typically developing (TD) children, and 110 children with ADHD across four scanners at multiple institutions. Functional parcellation was based on Yeo’s 7-network atlas, and within- and between-network functional connectivity and the amplitude of low-frequency fluctuations (ALFF) were calculated. Scanner-related measurement bias was corrected using the TS method. Results: Results showed significantly higher intrinsic connectivity within the dorsal attention network (DAN) in the ADHD group (β = 0.159, p = 0.006; FDR-corrected p = 0.040). A significant diagnosis-by-age interaction was observed, with age-related decreases in DAN connectivity present in the TD group but absent in the ADHD group. Additionally, children with ADHD exhibited increased ALFF within the limbic network (β = 0.121, p = 0.006; FDR-corrected p = 0.041). In contrast to the DAN, both ADHD and TD groups showed similar age-related decreases in limbic ALFF despite a significant diagnosis-by-age interaction. Conclusion: These findings suggest hyperconnectivity within the DAN and elevated intrinsic activity in the limbic network in children with ADHD, and atypical developmental trajectories of large-scale functional brain networks in children with ADHD in DAN.

Child maltreatment adversely affects brain development, resulting in vulnerabilities in brain structure and function connectivity, as well as various psychiatric disorders. However, the relationship between structural changes in auditory-related regions and auditory function remains unclear. Therefore, this study investigated the relationship between auditory frequencies associated with brain atypicality and child maltreatment. T1-weighted magnetic resonance imaging (MRI) and functional MRI were used to assess differences in gray matter volume (GMV) and functional connectivity (FC) in maltreated children (n = 19) compared to those of no maltreatment history (n = 38) participants. This case–control study focused on the left middle temporal gyrus (L.MTG), a key region in speech perception, and its connectivity with the right temporal pole (R.TP). Additionally, the study analyzed the relationship between these neural alterations and auditory thresholds at pivotal frequencies relevant to speech perception and measures of speech reception thresholds. Maltreatment-related neurodevelopmental adaptations affected GMV (L.MTG; P < 0.001 for peak level, family-wise error [FWE] corrected P = 0.038 for cluster level) and FC (L.MTG-R.TP; P < 0.001 for peak level, FWE corrected P = 0.013 for the cluster level), potentially influencing how abused children process auditory and emotional information. These alterations may have long-term consequences on speech perception, emotional recognition, and social communication. Elucidating these mechanisms will contribute to developing effective therapeutic strategies to improve social and emotional outcomes in maltreated individuals.

Background Maternal bonding difficulties represent an important yet under-recognized aspect of perinatal mental health, influencing both maternal well-being and child development. Although numerous studies have examined postpartum depression (PPD) and bonding impairment, few have investigated their longitudinal relationship within general pediatric settings in Japan. Methods This single-center retrospective cohort study analyzed data from 512 mother–infant dyads who delivered at a general hospital in Fukuoka, Japan. Maternal depressive symptoms and bonding were assessed at five days and one, two, and three months postpartum using the Edinburgh Postnatal Depression Scale (EPDS) and Mother-to-Infant Bonding Scale (MIBS), respectively. Growth Mixture Modeling (GMM) identified latent trajectories of EPDS and MIBS scores, and multinomial logistic regression examined background factors associated with poor bonding. Results GMM identified five latent classes for MIBS and four for EPDS. A subgroup characterized by persistently worsening bonding difficulties (MIBS Class 2: increased poor bonding) and increasing depressive symptoms (EPDS Class 1: increased depression) was observed. Approximately 70% of mothers in MIBS Class 2 also belonged to EPDS Class 1. Higher EPDS total, anxiety, and anhedonia scores in the early postpartum period predicted elevated MIBS scores at three months. Among background factors, refusal of public health nurse home visits and insufficient opportunities to consult with partners or others were significantly associated with poor bonding trajectories. In contrast, economic hardship and unmarried status were not significant predictors. Conclusions Persistent maternal emotional instability during the early postpartum period worsens bonding difficulties. Incorporating systematic screening with the EPDS and MIBS into pediatric clinical practice, together with empathic listening and early referral to mental health or social support services, may help identify high-risk mothers, and prevent subsequent child maltreatment.