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1.  Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias 
Scientific Reports  2015;5:11204.
Methyl-CpG-binding protein 2 (MeCP2) is an epigenetic regulator of gene expression that is essential for normal brain development. Mutations in MeCP2 lead to disrupted neuronal function and can cause Rett syndrome (RTT), a neurodevelopmental disorder. Previous studies reported cardiac dysfunction, including arrhythmias in both RTT patients and animal models of RTT. In addition, recent studies indicate that MeCP2 may be involved in cardiac development and dysfunction, but its role in the developing and adult heart remains unknown. In this study, we found that Mecp2-null ESCs could differentiate into cardiomyocytes, but the development and further differentiation of cardiovascular progenitors were significantly affected in MeCP2 deficiency. In addition, we revealed that loss of MeCP2 led to dysregulation of endogenous cardiac genes and myocardial structural alterations, although Mecp2-null mice did not exhibit obvious cardiac functional abnormalities. Furthermore, we detected methylation of the CpG islands in the Tbx5 locus, and showed that MeCP2 could target these sequences. Taken together, these results suggest that MeCP2 is an important regulator of the gene-expression program responsible for maintaining normal cardiac development and cardiomyocyte structure.
doi:10.1038/srep11204
PMCID: PMC4466896  PMID: 26073556
2.  Upregulated GABA Inhibitory Function in ADHD Children with Child Behavior Checklist–Dysregulation Profile: 123I-Iomazenil SPECT Study 
The child behavior checklist–dysregulation profile (CBCL–DP) refers to a pattern of elevated scores on the attention problems, aggression, and anxiety/depression subscales of the child behavior checklist. The aim of the present study was to investigate the potential role of GABA inhibitory neurons in children with attention deficit/hyperactivity disorder (ADHD) and dysregulation assessed with a dimensional measure. Brain single photon emission computed tomography (SPECT) was performed in 35 children with ADHD using 123I-iomazenil, which binds with high affinity to benzodiazepine receptors. Iomazenil binding activities were assessed with respect to the presence or absence of a threshold CBCL–DP (a score ≥210 for the sum of the three subscales: Attention Problems, Aggression, and Anxiety/Depression). We then attempted to identify which CBCL–DP subscale explained the most variance with respect to SPECT data, using “age,” “sex,” and “history of maltreatment” as covariates. Significantly higher iomazenil binding activity was seen in the posterior cingulate cortex (PCC) of ADHD children with a significant CBCL–DP. The Anxiety/Depression subscale on the CBCL had significant effects on higher iomazenil binding activity in the left superior frontal, middle frontal, and temporal regions, as well as in the PCC. The present brain SPECT findings suggest that GABAergic inhibitory neurons may play an important role in the neurobiology of the CBCL–DP, in children with ADHD.
doi:10.3389/fpsyt.2015.00084
PMCID: PMC4451796  PMID: 26082729
CBCL-dysregulation profile; iomazenil; GABA; ADHD
3.  High correlation between salivary cortisol awakening response and the psychometric profiles of healthy children 
Background
Cortisol awakening response (CAR) as an indicator of psychological stress and related physical and psychiatric diseases has attracted growing attention from researchers. Although CAR changes have been investigated extensively in children with behavioral and psychiatric disorders, the association between CAR and conventional psychometric scales for healthy children has not been reported. The aim of this study was to investigate the association between salivary CAR and subscales of Profiles of Mood States (POMS), a self-assessment questionnaire widely used to evaluate the temporal emotional states of healthy children.
Findings
This study included 18 healthy girls aged 13–16 years. Saliva was collected immediately on awakening, 30 min and 60 min after waking, and then at 2-hour intervals from 9 am to 5 pm. The current mood state, including depression, anxiety, fatigue, and other psychometric profiles were assessed using POMS. The magnitude of salivary CAR and the area under the concentration-time curve (AUC) for diurnal salivary cortisol were compared with the profiles. There were significant positive correlations between the magnitude of CAR and the POMS subscales for "Depression-Dejection", "Tension-Anxiety", "Fatigue", and "Confusion". No correlation was found between the AUC salivary cortisol level and the psychometric profiles.
Conclusions
Salivary CAR was associated with various mood states of healthy female children but diurnal salivary cortisol AUC was not. Salivary CAR may be a biomarker of the physical and mental condition of healthy female children.
doi:10.1186/1751-0759-8-9
PMCID: PMC3995602  PMID: 24625309
Cortisol awakening response; Hypothalamus-pituitary-adrenal axis; Saliva; Children
4.  The reliability and validity of the Questionnaire - Children with Difficulties (QCD) 
Background
The aim of this study was to evaluate the reliability and validity of the Questionnaire-Children with Difficulties (QCD), which was developed for the evaluation of children’s daily life behaviors during specified periods of the day.
Methods
The subjects were 1,514 Japanese public elementary and junior high school students. For the examination of reliability, Cronbach’s alpha was calculated to assess the internal consistency of the questionnaire. With regard to validity, correlation coefficients were calculated to examine whether QCD scores correlated with those of the ADHD-Rating Scale (ADHD-RS) and the Oppositional Defiant Behavior Inventory (ODBI).
Results
Cronbach’s alpha coefficient for the total score of the QCD was .876. The correlation coefficients of the QCD score with ADHD-RS and ODBI scores were -.514 and -.577, respectively.
Conclusions
The internal consistency and validity of the QCD were demonstrated. The QCD is a reliable and valid instrument for evaluating daily life problems for children during different time periods of the day.
doi:10.1186/1753-2000-7-11
PMCID: PMC3616960  PMID: 23537143
Adolescent; Child; Daily life; Questionnaire-Children with Difficulties (QCD); Reliability; Validity
5.  Functional near-infrared spectroscopy studies in children 
Psychosomatic and developmental behavioral medicine in pediatrics has been the subject of significant recent attention, with infants, school-age children, and adolescents frequently presenting with psychosomatic, behavioral, and psychiatric symptoms. These may be a consequence of insecurity of attachment, reduced self-confidence, and peer -relationship conflicts during their developmental stages. Developmental cognitive neuroscience has revealed significant associations between specific brain lesions and particular cognitive dysfunctions. Thus, identifying the biological deficits underlying such cognitive dysfunction may provide new insights into therapeutic prospects for the management of those symptoms in children. Recent advances in noninvasive neuroimaging techniques, and especially functional near-infrared spectroscopy (NIRS), have contributed significant findings to the field of developmental cognitive neuroscience in pediatrics. We present here a comprehensive review of functional NIRS studies of children who have developed normally and of children with psychosomatic and behavioral disorders.
doi:10.1186/1751-0759-6-7
PMCID: PMC3337812  PMID: 22433235
Development; Children; Cognitive neuroscience; Near-infrared spectroscopy

Results 1-5 (5)