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1.
Neuroimage ; 292: 120589, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38575041

Child maltreatment can adversely affect brain development, leading to vulnerabilities in brain structure and function and various psychiatric disorders. Among the various types of child maltreatment, neglect has the highest incidence rate (76.0%); however, data on its sole adverse influence on the brain remain limited. This case-control brain magnetic resonance imaging (MRI) study identified the changes in gray matter structure and function that distinguish neglected children with no other type of maltreatment (Neglect group, n = 23) from typically developing children (TD group, n = 140), and investigated the association between these structural and functional differences and specific psychosocial phenotypes observed in neglected children. Our results showed that the Neglect group had a larger right and left anterior cingulate cortex (R/L.ACC) and smaller left angular gyrus (L.AG) gray matter volume. The larger R/L.ACC was associated with hyperactivity and inattention. Resting-state functional analysis showed increased functional connectivity (FC) between the left supramarginal gyrus (L.SMG) in the salience network (SN) and the right middle frontal gyrus (R.MFG) simultaneously with a decrease in FC with the L.ACC for the same seed. The increased FC for the R.MFG was associated with difficulty in peer problems and depressive symptoms; a mediating effect was evident for depressive symptoms. These results suggest that the structural atypicality of the R/L.ACC indirectly contributes to the disturbed FCs within the SN, thereby exacerbating depressive symptoms in neglected children. In conclusion, exposure to neglect in childhood may lead to maladaptive brain development, particularly neural changes associated with depressive symptoms.


Brain , Child Abuse , Magnetic Resonance Imaging , Humans , Child , Male , Female , Child Abuse/psychology , Brain/diagnostic imaging , Brain/physiopathology , Brain/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Case-Control Studies , Connectome , Nerve Net/diagnostic imaging , Nerve Net/physiopathology
2.
Int J Methods Psychiatr Res ; 33(1): e2015, 2024 Mar.
Article En | MEDLINE | ID: mdl-38363207

OBJECTIVES: This study validated the Japanese version of the Attention-Deficit/Hyperactivity Disorder-Rating Scale-5 (ADHD-RS-5) and the Disruptive Behavior Disorders Rating Scale. We extended the ADHD-RS-5 by adding the oppositional defiant disorder and conduct disorder subscales to compare the two rating scales psychometrically. METHODS: We examined the internal consistency, test-retest reliability, construct validity and criterion validity of the two rating scales in 135 Japanese outpatients aged 6-18 years. RESULTS: The internal consistency and test-retest reliability were good for all the subscales of the two rating scales except for the conduct disorder subscale of the ADHD-RS-5 extended. Good construct validity was revealed by expected correlational patterns between subscales from the two rating scales and the Children Behavior Checklist. The criterion validity was good for all the subscales of the two rating scales rated by parents, while teacher-ratings revealed substantially lower predictive ability for all the subscales. Agreement between parent- and teacher-ratings of the two rating scales was generally moderate and using predictive ratings alone of both ratings showed the best predictive ability among the integration methods examined. CONCLUSION: The two rating scales have sound psychometric properties and will aid in screening and severity assessment of externalizing disorders in Japanese clinical settings.


Attention Deficit Disorder with Hyperactivity , Problem Behavior , Child , Humans , Attention Deficit Disorder with Hyperactivity/diagnosis , Psychometrics/methods , Reproducibility of Results , Japan , Outpatients , Psychiatric Status Rating Scales
3.
JMIR Res Protoc ; 12: e49828, 2023 Sep 19.
Article En | MEDLINE | ID: mdl-37725414

BACKGROUND: Individual face-to-face cognitive behavioral therapy is known to be effective for bulimia nervosa (BN). Since foods vary considerably between regions and cultures in which patients live, cultural adaptation of the treatment program is particularly important in cognitive behavioral therapy for BN. Recently, an internet-based cognitive behavioral therapy (ICBT) program was developed for Japanese women with BN, adapted to the Japanese food culture. However, no previous randomized controlled trial has examined the effectiveness of ICBT. OBJECTIVE: This paper presents a research protocol for strategies to examine the effects of guided ICBT. METHODS: This study is designed as a multicenter, prospective, assessor-blinded randomized controlled trial. The treatment groups will be divided into treatment as usual (TAU) alone as the control group and ICBT combined with TAU as the intervention group. The primary outcome is the total of binge eating and purging behaviors assessed before and after treatment by an independent assessor. Secondary outcomes will include measures of eating disorder severity, depression, anxiety, quality of life, treatment satisfaction, and working alliances. Treatment satisfaction and working alliances will be measured post assessment only. Other measures will be assessed at baseline, post intervention, and follow-up, and the outcomes will be analyzed on an intention-to-treat basis. RESULTS: This study will be conducted at 7 different medical institutions in Japan from August 2022 to October 2026. Recruitment of participants began on August 19, 2022, and recruitment is scheduled to continue until July 2024. The first participants were registered on September 8, 2022. CONCLUSIONS: This is the first multicenter randomized controlled trial in Japan comparing the effectiveness of ICBT and TAU in patients with BN. TRIAL REGISTRATION: University Hospital Medical Information Network UMIN000048732; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055522. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49828.

4.
Neuropsychopharmacology ; 48(11): 1690-1698, 2023 10.
Article En | MEDLINE | ID: mdl-37491674

Methylphenidate is a widely used and effective treatment for attention-deficit/hyperactivity disorder (ADHD), yet the underlying neural mechanisms and their relationship to changes in behavior are not fully understood. Specifically, it remains unclear how methylphenidate affects brain and behavioral dynamics, and the interplay between these dynamics, in individuals with ADHD. To address this gap, we used a novel Bayesian dynamical system model to investigate the effects of methylphenidate on latent brain states in 27 children with ADHD and 49 typically developing children using a double-blind, placebo-controlled crossover design. Methylphenidate remediated greater behavioral variability on a continuous performance task in children with ADHD. Children with ADHD exhibited aberrant latent brain state dynamics compared to typically developing children, with a single latent state showing particularly abnormal dynamics, which was remediated by methylphenidate. Additionally, children with ADHD showed brain state-dependent hyper-connectivity in the default mode network, which was also remediated by methylphenidate. Finally, we found that methylphenidate-induced changes in latent brain state dynamics, as well as brain state-related functional connectivity between salience and default mode networks, were correlated with improvements in behavioral variability. Taken together, our findings reveal a novel latent brain state dynamical process and circuit mechanism underlying the therapeutic effects of methylphenidate in childhood ADHD. We suggest that Bayesian dynamical system models may be particularly useful for capturing complex nonlinear changes in neural activity and behavioral variability associated with ADHD. Our approach may be of value to clinicians and researchers investigating the neural mechanisms underlying pharmacological treatment of psychiatric disorders.


Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Methylphenidate , Humans , Child , Methylphenidate/pharmacology , Methylphenidate/therapeutic use , Attention Deficit Disorder with Hyperactivity/psychology , Bayes Theorem , Brain , Nerve Net , Central Nervous System Stimulants/pharmacology , Central Nervous System Stimulants/therapeutic use
5.
BMJ Open ; 13(6): e070157, 2023 06 23.
Article En | MEDLINE | ID: mdl-37355265

INTRODUCTION: Neuroimaging studies on attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have demonstrated differences in extensive brain structure, activity and network. However, there remains heterogeneity and inconsistency across these findings, presumably because of the diversity of the disorders themselves, small sample sizes, and site and parameter differences in MRI scanners, and their overall pathogenesis remains unclear. To address these gaps in the literature, we will apply the travelling-subject approach to correct site differences in MRI scanners and clarify brain structure and network characteristics of children with ADHD and ASD using large samples collected in a multi-centre collaboration. In addition, we will investigate the relationship between these characteristics and genetic, epigenetic, biochemical markers, and behavioural and psychological measures. METHODS AND ANALYSIS: We will collect resting-state functional MRI (fMRI) and T1-weighted and diffusion-weighted MRI data from 15 healthy adults as travelling subjects and 300 children (ADHD, n=100; ASD, n=100; and typical development, n=100) with multi-dimensional assessments. We will also apply data from more than 1000 samples acquired in our previous neuroimaging studies on ADHD and ASD. ETHICS AND DISSEMINATION: The study protocol has been approved by the Research Ethics Committee of the University of Fukui Hospital (approval no: 20220601). Our study findings will be submitted to scientific peer-reviewed journals and conferences.


Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Adult , Humans , Child , Autism Spectrum Disorder/diagnostic imaging , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Cross-Sectional Studies , Magnetic Resonance Imaging , Brain , Multicenter Studies as Topic
6.
BMJ Open ; 13(4): e068547, 2023 04 19.
Article En | MEDLINE | ID: mdl-37076162

INTRODUCTION: Cognitive-behavioural therapy (CBT) consists of multiple treatment techniques for each treatment model and is tailored to the patient's characteristics. Randomised controlled trials (RCTs) have reported that CBT is effective for attention-deficit/hyperactivity disorder (ADHD); however, which CBT components are effective is unknown. In order to provide the best treatment technique, it is important to know which therapeutic component or combination thereof is more effective and what the specific effect size is. METHODS AND ANALYSIS: We will perform component network meta-analysis (cNMA). The search will include studies published from database inception up to 31 March 2022, in English. The electronic databases of MEDLINE (via PubMed), EMBASE, PsycINFO, ClinicalTrials.gov and Cochrane Library will be searched. We will systematically identify all RCTs in the treatment of ADHD between the ages of 10 and 60 years, comparing interventions composed of various CBT components with controlled interventions. We will perform pairwise and network meta-analysis with random effects to estimate summary ORs and standardised mean differences. We will assess the risk of bias in selected studies using the Cochrane risk of bias tool. ETHICS AND DISSEMINATION: Since we will review published papers, ethical approval is not required. The results from this cNMA will provide a panorama of the CBT-based ADHD studies. The results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022323898.


Attention Deficit Disorder with Hyperactivity , Cognitive Behavioral Therapy , Adolescent , Adult , Humans , Child , Young Adult , Middle Aged , Attention Deficit Disorder with Hyperactivity/drug therapy , Network Meta-Analysis , Meta-Analysis as Topic
7.
Brain Imaging Behav ; 17(4): 436-449, 2023 Aug.
Article En | MEDLINE | ID: mdl-37079157

This randomized controlled study examined neurological changes in socioemotional processing skills through parent training in caregivers of children with attention-deficit/hyperactivity disorder. Thirty mothers of children with attention-deficit/hyperactivity disorder were stratified into parent training and non-parent training groups. Functional magnetic resonance imaging was performed during the "Reading the Mind in the Eyes" test, and parenting difficulties were evaluated using the Parenting Stress Index and the Parenting Scale, twice (before and after parent training). Only mothers in the parent training group showed a significant decrease in Parenting Stress Index and Parenting Scale scores. They also demonstrated increased activity in the left occipital fusiform gyrus during the task of estimating emotions from facial pictures. We presumed that these changes might reflect the potential impact of enrollment in parent training in reducing stress, which might have increased activation of the fusiform gyrus.


Attention Deficit Disorder with Hyperactivity , Mothers , Female , Humans , Child , Mothers/psychology , Magnetic Resonance Imaging , Emotions , Parenting/psychology
8.
Dev Cogn Neurosci ; 60: 101209, 2023 04.
Article En | MEDLINE | ID: mdl-36791556

Although cannabis use during pregnancy is increasing widely, the effects of cannabis on developmental trajectories, such as whether its effects during pregnancy remain the same between time points or gradually increase, are unclear. This study aimed to examine whether cannabis use during pregnancy affects the process of change in cognition and brain volume. Data from two-time points measured longitudinally were analyzed. We used data from the Adolescent Brain and Cognitive Development Study. Participants included 11,876 children aged 9-11 years participated at baseline, and 10,414 participated at 2-year follow-up from 22 sites across the United States. We explored the associations between prenatal cannabis exposure and cognitive abilities and brain volumes developmental trajectories. Among 11,530 children with valid data for prenatal cannabis exposure, 10,833 had no prenatal cannabis use, and 697 had cannabis use during their pregnancy. There was a significant interaction between time points and cannabis use during pregnancy on visuo-perceptual processing ability (b = -0.019, p = .009) and intracranial volumes (b = -6338.309, p = .009). We found that the effects of exposure to cannabis during pregnancy are not uniform at all times and may gradually become more apparent and magnified as development progresses.


Cannabis , Prenatal Exposure Delayed Effects , Child , Pregnancy , Female , Humans , Adolescent , Cannabis/adverse effects , Cognition , Adolescent Development , Brain
9.
Int J Methods Psychiatr Res ; 32(4): e1957, 2023 Dec.
Article En | MEDLINE | ID: mdl-36593592

OBJECTIVE: The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) is a widely used semi-structured diagnostic interview in child and adolescent psychiatry. However, the psychometric properties of its updated version, the K-SADS-PL for DSM-5, have scarcely been examined, especially for criterion validity. This study was designed to examine the inter-rater reliability, criterion validity and construct validity of the K-SADS-PL for DSM-5 in 137 Japanese outpatients. METHODS: Two of 12 experienced clinicians independently performed the K-SADS interview for each patient in a conjoint session, and the resulting consensus diagnosis was compared with a "best-estimate" diagnosis made by two of eight experienced clinicians using all available information for the patient. RESULTS: The inter-rater reliability was excellent, as shown by κ > 0.75 for all disorders, with the exception of current separation anxiety disorder. The criterion validity was fair to good, as shown by κ > 0.40 for all disorders, with the exception of current and lifetime agoraphobia. The construct validity was also good, as shown by theoretically expected associations between the K-SADS-PL diagnoses and subscales of the child behavior checklist. CONCLUSION: The K-SADS-PL for DSM-5, now available in Japanese, generates valid diagnoses in child and adolescent psychiatry.


Schizophrenia , Child , Adolescent , Humans , Schizophrenia/diagnosis , Mood Disorders/diagnosis , Outpatients , Psychometrics , Reproducibility of Results , East Asian People , Psychiatric Status Rating Scales
10.
Article En | MEDLINE | ID: mdl-36717325

BACKGROUND: Methylphenidate, a first-line treatment for attention-deficit/hyperactivity disorder (ADHD), is thought to influence dopaminergic neurotransmission in the nucleus accumbens (NAc) and its associated brain circuitry, but this hypothesis has yet to be systematically tested. METHODS: We conducted a randomized, placebo-controlled, double-blind crossover trial including 27 children with ADHD. Children with ADHD were scanned twice with resting-state functional magnetic resonance imaging under methylphenidate and placebo conditions, along with assessment of sustained attention. We examined spontaneous neural activity in the NAc and the salience, frontoparietal, and default mode networks and their links to behavioral changes. Replicability of methylphenidate effects on spontaneous neural activity was examined in a second independent cohort. RESULTS: Methylphenidate increased spontaneous neural activity in the NAc and the salience and default mode networks. Methylphenidate-induced changes in spontaneous activity patterns in the default mode network were associated with improvements in intraindividual response variability during a sustained attention task. Critically, despite differences in clinical trial protocols and data acquisition parameters, the NAc and the salience and default mode networks showed replicable patterns of methylphenidate-induced changes in spontaneous activity across two independent cohorts. CONCLUSIONS: We provide reproducible evidence demonstrating that methylphenidate enhances spontaneous neural activity in NAc and cognitive control networks in children with ADHD, resulting in more stable sustained attention. Our findings identified a novel neural mechanism underlying methylphenidate treatment in ADHD to inform the development of clinically useful biomarkers for evaluating treatment outcomes.


Attention Deficit Disorder with Hyperactivity , Methylphenidate , Humans , Child , Methylphenidate/pharmacology , Methylphenidate/therapeutic use , Brain , Reward , Cognition
11.
Sci Rep ; 12(1): 19601, 2022 11 15.
Article En | MEDLINE | ID: mdl-36379997

A large longitudinal study on the impact of the COVID-19 pandemic on mental health in children is limited. This large-scale longitudinal observational study examines the pandemic's effects on children's mental health while considering the effects of parental care styles. The Adolescent Brain Cognitive Development Study is a large-scale, longitudinal multicenter study in the United States. Of the 11,875 children aged 9-12 years in its database, 4702 subjects were selected for this study. The child behavior checklist and parental monitoring questionnaire (PMQ) were used to assess children's mental health and parental support styles, respectively. Data collected before and during the pandemic were compared. Withdrawn/depressed and attention problems significantly worsened during compared to before the COVID-19 pandemic (p < 0.001, withdrawn/depressed; 53.4 ± 5.7 to 53.7 ± 5.9, attention problems; 53.4 ± 5.4 to 53.6 ± 5.6). However, the T scores are in the normal range both before and during the crisis. Simple slope analysis found withdrawn/depressed problems and aggressive behavior worsened when the PMQ was 1 SD below the mean, and rule-breaking behavior was improved when the PMQ was 1 SD above the mean. While the COVID-19 pandemic exacerbated children's depressive symptoms and attention issues, the effects may be minor. Additionally, parental involvement serve as a protective factor for the child's mental health even during the pandemic.


COVID-19 , Mental Health , Child , Adolescent , Humans , Pandemics , COVID-19/epidemiology , Longitudinal Studies , Parents/psychology
12.
Front Psychiatry ; 13: 942936, 2022.
Article En | MEDLINE | ID: mdl-36081468

Background: The process of cultural adaptation of internet-based cognitive behavioral therapy (ICBT) programs for bulimia nervosa (BN) have rarely been reported despite the potential influence of cultural adaptation of psychosocial interventions on therapeutic response. Aim: This study aimed to illustrate development process of an ICBT program for Japanese women with bulimia nervosa (BN). Methods: A mixed methods approach was used to assess cultural adaptation of the prototype of an original ICBT program by using the Cultural Relevance Questionnaire (CRQ). Five women with BN and seven clinicians were interviewed using the CRQ. Results: Quantitative analyses were conducted to assess cultural adaptation of the prototype of the program and participants rated cultural adaptation as high. A qualitative analysis of the mixed method supported the culturally sensitive changes implemented. Conclusions: The results of this study show that a series of processes can make ICBT programs more culturally adapted.

13.
Neuroimage ; 257: 119332, 2022 08 15.
Article En | MEDLINE | ID: mdl-35640787

Methylphenidate is a widely used first-line treatment for attention deficit/hyperactivity disorder (ADHD), but the underlying circuit mechanisms are poorly understood. Here we investigate whether a single dose of osmotic release oral system methylphenidate can remediate attention deficits and aberrancies in functional circuit dynamics in cognitive control networks, which have been implicated in ADHD. In a randomized placebo-controlled double-blind crossover design, 27 children with ADHD were scanned twice with resting-state functional MRI and sustained attention was examined using a continuous performance task under methylphenidate and placebo conditions; 49 matched typically-developing (TD) children were scanned once for comparison. Dynamic time-varying cross-network interactions between the salience (SN), frontoparietal (FPN), and default mode (DMN) networks were examined in children with ADHD under both administration conditions and compared with TD children. Methylphenidate improved sustained attention on a continuous performance task in children with ADHD, when compared to the placebo condition. Children with ADHD under placebo showed aberrancies in dynamic time-varying cross-network interactions between the SN, FPN and DMN, which were remediated by methylphenidate. Multivariate classification analysis confirmed that methylphenidate remediates aberrant dynamic brain network interactions. Furthermore, dynamic time-varying network interactions under placebo conditions predicted individual differences in methylphenidate-induced improvements in sustained attention in children with ADHD. These findings suggest that a single dose of methylphenidate can remediate deficits in sustained attention and aberrant brain circuit dynamics in cognitive control circuits in children with ADHD. Findings identify a novel brain circuit mechanism underlying a first-line pharmacological treatment for ADHD, and may inform clinically useful biomarkers for evaluating treatment outcomes.


Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Methylphenidate , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Attention Deficit Disorder with Hyperactivity/drug therapy , Brain , Central Nervous System Stimulants/pharmacology , Child , Double-Blind Method , Humans , Magnetic Resonance Imaging
14.
Brain Dev ; 43(1): 55-62, 2021 Jan.
Article En | MEDLINE | ID: mdl-32741583

AIMS: The current study aimed to validate the relationship between sensory characteristics and sleep dynamics among children with autism spectrum disorder (ASD) using an actigraph, which is an objective assessment device used for sleep monitoring. METHODS: A total of 40 children (age range, 3-6 years) participated in this study (n = 20, with ASD and n = 20, age-matched children with typical development [TD]). We examined sleep dynamics using actigraph for 7 consecutive days, and the relationship between sleep parameters and sensory characteristics was analyzed using the Japanese Version of Sensory Profile (SP-J). RESULTS: Significant differences were observed in terms of activities per minute during sleep (p = 0.02), sleep efficiency (SE) (p = 0.005), and wake after sleep onset (WASO) (p = 0.02) between the two groups. In the ASD group, significant positive correlations were observed between activities per minute during sleep and low thresholds for Vestibular Sensory stimuli (p = 0.046) and Oral Sensory stimuli (p = 0.006) using the SP-J. Based on a multiple regression analysis, the activities per minute during sleep were associated with low thresholds for Oral Sensory stimuli (ß = 0.51, t = 2.29, p = 0.03), but not with other factors, in the ASD group. CONCLUSIONS: The current study showed that atypical Vestibular and Oral Sensory modulation may be a risk indicator for high activities during sleep among preschool children with ASD. Thus, whether the interventions for these sensory characteristics are effective in improving sleep quality, daytime activities, behaviors, and cognitive functions in this group of children must be considered.


Autism Spectrum Disorder/physiopathology , Sleep/physiology , Auditory Perception/physiology , Autism Spectrum Disorder/metabolism , Child , Child, Preschool , Female , Hearing/physiology , Humans , Japan , Male , Polysomnography , Sleep Wake Disorders/complications , Surveys and Questionnaires , Taste Perception/physiology , Vestibule, Labyrinth/physiology
15.
Mol Autism ; 11(1): 24, 2020 04 09.
Article En | MEDLINE | ID: mdl-32272970

BACKGROUND: Elucidating developmental changes in the symptoms of autism spectrum disorder (ASD) is important to support individuals with ASD. However, no report has clarified the developmental changes in attention to social information for a broad age range. The aim of this study was to investigate the developmental changes in attention to social information from early childhood to adolescence in individuals with ASD and typically developed (TD) children. METHODS: We recruited children with ASD (n = 83) and TD participants (n = 307) between 2 and 18 years of age. Using the all-in-one-eye-tracking system, Gazefinder, we measured the percentage fixation time allocated to areas of interest (AoIs) depicted in movies (the eyes and mouth in movies of a human face with/without mouth motion, upright and inverted biological motion in movies showing these stimuli simultaneously, people and geometry in preference paradigm movies showing these stimuli simultaneously, and objects with/without finger-pointing in a movie showing a woman pointing toward an object). We conducted a three-way analysis of variance, 2 (diagnosis: ASD and TD) by 2 (sex: male and female) by 3 (age group: 0-5, 6-11, and 12-18 years) and locally weighted the scatterplot smoothing (LOESS) regression curve on each AoI. RESULTS: In the face stimuli, the percentage fixation time to the eye region for the TD group increased with age, whereas the one for the ASD group did not. In the ASD group, the LOESS curves of the gaze ratios at the eye region increased up to approximately 10 years of age and thereafter tended to decrease. For the percentage fixation time to the people region in the preference paradigm, the ASD group gazed more briefly at people than did the TD group. LIMITATIONS: It is possible that due to the cross-sectional design, the degree of severity and of social interest might have differed according to the subjects' age. CONCLUSIONS: There may be qualitative differences in abnormal eye contact in ASD between individuals in early childhood and those older than 10 years.


Attention , Autism Spectrum Disorder/psychology , Fixation, Ocular , Adolescent , Child , Child, Preschool , Female , Humans , Male , Social Behavior
16.
Cereb Cortex ; 30(7): 4238-4245, 2020 06 01.
Article En | MEDLINE | ID: mdl-32147718

Reactive attachment disorder (RAD) is associated with childhood maltreatment and affects approximately 1% of the general population. Recent data suggest that childhood maltreatment is associated with brain alterations in white and gray matter. However, the neural mechanisms of RAD-related brain alterations remain unknown. Herein, we evaluated the white matter pathways and gray matter volumes in 31 and 41 age-matched children with RAD and typical development (TD), respectively, by analyzing T1- and diffusion-weighted images. An increased fractional anisotropy (FA) and axial diffusivity in the anterior thalamic radiations (ATR) and an increased volume in the bilateral pallidum and right thalamus were observed in children with RAD compared with those with TD. Moreover, the volume of the thalamus was associated with increased ATR FA in children with RAD. Our study confirmed the existence of atypical neurodevelopment processes in the thalamus, pallidum, and ATR in children with RAD and highlighted an interdependent relationship between the alterations in the thalamus and ATR. These findings may help to improve our understanding of the comprehensive neural mechanisms of RAD.


Gray Matter/diagnostic imaging , Reactive Attachment Disorder/diagnostic imaging , Thalamus/diagnostic imaging , White Matter/diagnostic imaging , Adolescent , Brain/diagnostic imaging , Brain/pathology , Brain/physiopathology , Case-Control Studies , Child , Diffusion Tensor Imaging , Female , Gray Matter/pathology , Humans , Male , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Organ Size , Reactive Attachment Disorder/physiopathology , Reactive Attachment Disorder/psychology , Severity of Illness Index , Thalamus/pathology , White Matter/pathology , White Matter/physiopathology
17.
Transl Psychiatry ; 9(1): 332, 2019 12 09.
Article En | MEDLINE | ID: mdl-31819038

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share high rates of comorbidity, with the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition now acknowledging the comorbid diagnosis of ASD and ADHD. Although structural abnormalities in the prefrontal cortex, cerebellum, and basal ganglia occur in both ASD and ADHD, no structural studies have focused exclusively on patients with comorbid ASD and ADHD. We thus aimed to clarify the structural features and developmental changes in patients with comorbid ASD and ADHD in a relatively large sample from two sites. Ninety-two patients were age-matched to 141 typically developing (TD) controls (age range: 5-16 years) and assessed for volumetric characteristics using structural magnetic resonance imaging (i.e. surface-based morphometry). While there were no significant differences in prefrontal cortex, cerebellum, and basal ganglia volumes, patients with ASD and ADHD exhibited significantly lower left postcentral gyrus volumes than TD controls. We observed significantly lower postcentral gyrus volumes exclusively in children and preadolescents, and not in adolescents. Our findings suggest that abnormal somatosensory, attributed to delayed maturation of the left postcentral gyrus, leads to the core symptoms experienced by patients with comorbid ASD and ADHD.


Attention Deficit Disorder with Hyperactivity/pathology , Autism Spectrum Disorder/pathology , Cerebral Cortex/pathology , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Attention Deficit Disorder with Hyperactivity/epidemiology , Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/epidemiology , Cerebral Cortex/diagnostic imaging , Child , Child, Preschool , Comorbidity , Female , Humans , Magnetic Resonance Imaging , Male
18.
Cereb Cortex ; 29(9): 3902-3911, 2019 08 14.
Article En | MEDLINE | ID: mdl-30508034

The catechol-O-methyltransferase (COMT) gene is associated with frontal cortex development and the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, how the COMT gene impacts brain structure and behavior in ADHD remains unknown. In the present study, we identify the effect of COMT on cortical thickness and surface area in children with ADHD and children with typically developing (TD) using a machine learning approach. In a sample of 39 children with ADHD and 34 age- and IQ-matched TD children, we found that cortical thickness and surface area differences were predominantly observed in the frontal cortex. Furthermore, a path analysis revealed that a COMT genotype affected abnormal development of the frontal cortex in terms of both cortical thickness and surface area and was associated with working memory changes in children with ADHD. Our study confirms that the role of COMT in ADHD is not restricted to the development of behavior but may also affect the cortical thickness and surface area. Thus, our findings may help to improve the understanding of the neuroanatomic basis for the relationship between the COMT genotype and ADHD pathogenesis.


Attention Deficit Disorder with Hyperactivity/genetics , Attention Deficit Disorder with Hyperactivity/pathology , Catechol O-Methyltransferase/genetics , Cerebral Cortex/pathology , Adolescent , Child , Genotype , Humans , Magnetic Resonance Imaging , Male , Organ Size , Polymorphism, Single Nucleotide
20.
Sci Rep ; 7(1): 4850, 2017 07 07.
Article En | MEDLINE | ID: mdl-28687733

The cerebellum, although traditionally considered a motor structure, has been increasingly recognized to play a role in regulating executive function, the dysfunction of which is a factor in attention-deficit/hyperactivity disorder (ADHD). Additionally, catechol-O-methyltransferase (COMT) polymorphism has been reported to be associated with executive function. We examined whether the cortico-cerebellar executive function network is altered in children with ADHD and whether COMT polymorphism is associated with the altered network. Thirty-one children with ADHD and thirty age- and IQ-matched typically developing (TD) controls underwent resting-state functional MRI, and functional connectivity of executive function-related Crus I/II in the cerebellum was analysed. COMT Val158Met genotype data were also obtained from children with ADHD. Relative to TD controls, children with ADHD showed significantly lower functional connectivity of the right Crus I/II with the left dorsolateral prefrontal cortex. Additionally, the functional connectivity of children with ADHD was modulated by COMT polymorphism, with Met-carriers exhibiting significantly lower functional connectivity than the Val/Val genotype. These results suggest the existence of variations, such as ethnic differences, in COMT genetic effects on the cortico-cerebellar executive function network. These variations contribute to heterogeneity in ADHD. Further neuroimaging genetics study might lead to the development of fundamental therapies that target ADHD pathophysiology.


Attention Deficit Disorder with Hyperactivity/genetics , Catechol O-Methyltransferase/genetics , Cerebellum/physiopathology , Executive Function , Genetic Variation , Nerve Net/physiopathology , Prefrontal Cortex/physiopathology , Attention Deficit Disorder with Hyperactivity/physiopathology , Catechol O-Methyltransferase/metabolism , Child , Female , Genotype , Humans , Magnetic Resonance Imaging , Male
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