Bung Nyun Kim

Prenatal Exposure to Phthalates and Infant Development at 6 Months: Prospective Mothers and Children’s Environmental Health (MOCEH) Study

Background: There are increasing concerns over adverse effects of prenatal phthalate exposure on the neurodevelopment of infants. Objectives: Our goal was to explore the association between prenatal di(2-ethylhexyl) phthalate and dibutyl phthalate exposure and the Mental and Psychomotor Developmental Indices (MDI and PDI, respectively) of the Bayley Scales of Infant Development at 6 months, as part of the Mothers and Children’s Environmental Health Study. Methods: Between 2006 and 2009, 460 mother–infant pairs from Seoul, Cheonan, and Ulsan, Korea, participated. Prenatal mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MBP) were measured in one urine sample acquired from each mother during the third trimester of pregnancy. Associations with log-transformed creatinine-corrected phthalate concentrations were estimated using linear regression models adjusted for potential confounders. Results: MDI was inversely associated with the natural log concentrations (micrograms per gram creatinine) of MEHHP [β = –0.97; confidence interval (CI), –1.85 to –0.08] and MEOHP (β = –0.95; CI, –1.87 to –0.03), and PDI was inversely associated with MEHHP (β = –1.20; CI, –2.33 to –0.08). In males, MDI was inversely associated with MEHHP (β = –1.46; CI, –2.70 to –0.22), MEOHP (β = –1.57; CI, –2.87 to –0.28), and MBP (β = –0.93; CI, –1.82 to –0.05); PDI was inversely associated with MEHHP (β = –2.36; CI, –3.94 to –0.79), MEOHP (β = –2.05; CI, –3.71 to –0.39), and MBP (β = –1.25; CI, –2.40 to –0.11). No significant linear associations were observed for females. Conclusions: The results suggest that prenatal exposure to phthalates may be inversely associated with the MDI and PDI of infants, particularly males, at 6 months.

Methylphenidate But Not Atomoxetine or Citalopram Modulates Inhibitory Control and Response Time Variability

BACKGROUND Response inhibition is a prototypical executive function of considerable clinical relevance to psychiatry. Nevertheless, our understanding of its pharmacological modulation remains incomplete. METHODS We used a randomized, double-blind, placebo-controlled, crossover design to examine the effect of an acute dose of methylphenidate (MPH) (30 mg), atomoxetine (ATM) (60 mg), citalopram (CIT) (30 mg), and placebo (PLAC) (dextrose) on the stop signal inhibition task in 24 healthy, right-handed men 18-35 years of age. Participants performed the task under each of the four drug conditions across four consecutive sessions. RESULTS Methylphenidate led to a reduction in both response time variability and stop-signal reaction time (SSRT), indicating enhanced response inhibition compared with all other drug conditions. Crucially, the enhancement of response inhibition by MPH occurred without concomitant changes in overall response speed, arguing against a simple enhancement of processing speed. We found no significant differences between ATM and PLAC, CIT and PLAC, or ATM and CIT for either response time variability or SSRT. CONCLUSIONS An acute dose of MPH but not ATM or CIT was able to improve SSRT and reduce response time variability in nonclinical participants. Improvements in response inhibition and response variability might underlie the reported clinical benefits of MPH in disorders such as attention-deficit/hyperactivity disorder.

A Short Review on the Current Understanding of Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a deficit in social behaviors and nonverbal interactions such as reduced eye contact, facial expression, and body gestures in the first 3 years of life. It is not a single disorder, and it is broadly considered to be a multi-factorial disorder resulting from genetic and non-genetic risk factors and their interaction. Genetic studies of ASD have identified mutations that interfere with typical neurodevelopment in utero through childhood. These complexes of genes have been involved in synaptogenesis and axon motility. Recent developments in neuroimaging studies have provided many important insights into the pathological changes that occur in the brain of patients with ASD in vivo. Especially, the role of amygdala, a major component of the limbic system and the affective loop of the cortico-striatothalamo-cortical circuit, in cognition and ASD has been proved in numerous neuropathological and neuroimaging studies. Besides the amygdala, the nucleus accumbens is also considered as the key structure which is related with the social reward response in ASD. Although educational and behavioral treatments have been the mainstay of the management of ASD, pharmacological and interventional treatments have also shown some benefit in subjects with ASD. Also, there have been reports about few patients who experienced improvement after deep brain stimulation, one of the interventional treatments. The key architecture of ASD development which could be a target for treatment is still an uncharted territory. Further work is needed to broaden the horizons on the understanding of ASD.

Associations between serotonin transporter gene (SLC6A4) methylation and clinical characteristics and cortical thickness in children with ADHD.

BACKGROUND Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Additionally, environmental factors such as perinatal stress and early adversities contribute to the occurrence and severity of ADHD. Recently, DNA methylation has emerged as a mechanism that potentially mediates gene-environmental interaction effects in the aetiology and phenomenology of psychiatric disorders. Here, we investigated whether serotonin transporter gene (SLC6A4) methylation patterns were associated with clinical characteristics and regional cortical thickness in children with ADHD. METHOD In 102 children with ADHD (age 6-15 years), the methylation status of the SLC6A4 promoter was measured. Brain magnetic resonance imaging was obtained and ADHD symptoms were evaluated. RESULTS A higher methylation status of the SLC6A4 promoter was significantly associated with worse clinical presentations (more hyperactive-impulsive symptoms and more commission errors). Additionally, a negative correlation was observed between SLC6A4 methylation levels and cortical thickness values in the right occipito-temporal regions. CONCLUSIONS Our results suggest that the SLC6A4 methylation status may be associated with certain symptoms of ADHD, such as behavioural disinhibition, and related brain changes. Future studies that use a larger sample size and a control group are required to corroborate these results.

Increased Cortical Thickness in Professional On-Line Gamers

Objective The bulk of recent studies have tested whether video games change the brain in terms of activity and cortical volume. However, such studies are limited by several factors including cross-sectional comparisons, co-morbidity, and short-term follow-up periods. In the present study, we hypothesized that cognitive flexibility and the volume of brain cortex would be correlated with the career length of on-line pro-gamers. Methods High-resolution magnetic resonance scans were acquired in twenty-three pro-gamers recruited from StarCraft pro-game teams. We measured cortical thickness in each individual using FreeSurfer and the cortical thickness was correlated with the career length and the performance of the pro-gamers. Results Career length was positively correlated with cortical thickness in three brain regions: right superior frontal gyrus, right superior parietal gyrus, and right precentral gyrus. Additionally, increased cortical thickness in the prefrontal cortex was correlated with winning rates of the pro-game league. Increased cortical thickness in the prefrontal and parietal cortices was also associated with higher performance of Wisconsin Card Sorting Test. Conclusion Our results suggest that in individuals without pathologic conditions, regular, long-term playing of on-line games is associated with volume changes in the prefrontal and parietal cortices, which are associated with cognitive flexibility.

Differences in gray matter volume corresponding to delusion and hallucination in patients with schizophrenia compared with patients who have bipolar disorder

Background Although schizophrenia and bipolar disorder (BD) are classified as different disease entities, they share critical pathognomonic symptoms in terms of hallucination and delusion. Because the characteristics of clinical symptoms are not sufficient to differentiate schizophrenia from BD, several studies have applied brain imaging methods to provide biological evidence of differences. We compared gray matter (GM) volume differences in schizophrenia and BD patients and examined volumetric differences associated with hallucination and delusion in these two groups. Methods Ninety-three schizophrenia patients and 75 BD patients who were followed for at least 3 years in an outpatient department were recruited for this study. Magnetic resonance data from 71 schizophrenia patients and 44 BD patients were obtained using a 3.0 T scanner. Volumetric differences were analyzed using Matlab 8.0.0 and SPM8 software. Results The results showed that delusion symptoms were negatively correlated with GM volume within both frontal and both temporal cortices in the schizophrenia group and were negatively correlated with GM volume within the bilateral frontal cortices in the BD group. Hallucination symptoms were negatively correlated with GM volume within the bilateral frontal, bilateral temporal, and left parietal cortices in the schizophrenia group and were negatively correlated with GM volume within the bilateral frontal, right parietal, occipital, and insular cortices in the BD group. Conclusion Delusions in schizophrenia were correlated with GM volume in multiple brain regions, including the frontal, temporal, and parietal cortices, compared to those in patients with BD. Hallucination was associated with temporal lobe GM volume in patients with schizophrenia and with insular cortex GM volume in patients with BD.

Brain activity of adolescents with high functioning autism in response to emotional words and facial emoticons.

Studies of social dysfunction in patients with autism spectrum disorder (ASD) have generally focused on the perception of emotional words and facial affect. Brain imaging studies have suggested that the fusiform gyrus is associated with both the comprehension of language and face recognition. We hypothesized that patients with ASD would have decreased ability to recognize affect via emotional words and facial emoticons, relative to healthy comparison subjects. In addition, we expected that this decreased ability would be associated with altered activity of the fusiform gyrus in patients with ASD. Ten male adolescents with ASDs and ten age and sex matched healthy comparison subjects were enrolled in this case-control study. The diagnosis of autism was further evaluated with the Autism Diagnostic Observation Schedule. Brain activity was assessed using functional magnetic resonance imaging (fMRI) in response to emotional words and facial emoticon presentation. Sixty emotional words (45 pleasant words +15 unpleasant words) were extracted from a report on Korean emotional terms and their underlying dimensions. Sixty emoticon faces (45 pleasant faces +15 unpleasant faces) were extracted and modified from on-line sites. Relative to healthy comparison subjects, patients with ASD have increased activation of fusiform gyrus in response to emotional aspects of words. In contrast, patients with ASD have decreased activation of fusiform gyrus in response to facial emoticons, relative to healthy comparison subjects. We suggest that patients with ASD are more familiar with word descriptions than facial expression as depictions of emotion.

Effect of Breastfeeding Duration on Cognitive Development in Infants: 3-Year Follow-up Study

We investigated the association between breastfeeding and cognitive development in infants during their first 3 years. The present study was a part of the Mothers’ and Children’s Environmental Health (MOCEH) study, which was a multi-center birth cohort project in Korea that began in 2006. A total of 697 infants were tested at age 12, 24, and 36 months using the Korean version of the Bayley Scales of Infant Development II (K-BSID-II). The use and duration of breastfeeding and formula feeding were measured. The relationship between breastfeeding and the mental development index (MDI) score was analyzed by multiple linear regression analysis. The results indicated a positive correlation between breastfeeding duration and MDI score. After adjusting for covariates, infants who were breastfed for ≥ 9 months had significantly better cognitive development than those who had not been breastfed. These results suggest that the longer duration of breastfeeding improves cognitive development in infants.

Prenatal, Perinatal and Infancy History of Autism Spectrum Disorder

Objectives:The purpose of this study was to evaluate the prenatal, perinatal, and infancy history of children with autism spectrum disorder (ASD) as compared to unaffected siblings (SIB) and typically developing children (TC). Methods:Subjects with ASD, their SIB, and TC were recruited. All subjects were assessed using both the Korean version of Autism Diagnostic Interview-Revised (K-ADI-R) and the Korean version of Autism Diagnostic Observation Schedule (K-ADOS) and were subsequently identified as affected or unaffected. Prenatal, perinatal, and infancy history was obtained from the primary caregivers and each facet was compared in those with ASD, the SIB, and the TC groups using SPSS ver. 17.0 (p<.05). Results:70 individuals with ASD (63 males, 87.94±37.8months), 53 SIB (27 males, 85.40±48.06 months), and 32 TC (19 males, 104.19±23.409 months) were analyzed. The ASD group showed significantly higher rates of insufficient vaccination as they aged age (χ 2 =15.54, p=.000). Among the scheduled vaccinations, the DPT vaccination (χ 2 =10.08, p=.006) was insufficient in ASD groups. The ASD group also showed higher rates of sleep disturbances from infancy. Differences in maternal/paternal age at conception, gestational age, and growth parameters at birth were not significantly difference among the three groups. Conclusion:These results do not support the previous controversies regarding the relationship between prenatal/ perinatal complications and ASD. However, these results indicate that perinatal and prenatal factors may contribute to the development of ASD.

Changing characteristics of the empathic communication network after empathy-enhancement program for medical students

The Empathy-Enhancement Program for Medical Students (EEPMS) comprises five consecutive weekly sessions and aims to improve medical students’ empathic ability, an essential component of humanistic medical professionalism. Using a graph theory approach for the Ising network (based on l1-regularized logistic regression) comprising emotional regulation, empathic understanding of others’ emotion, and emotional expressivity, this study aimed to identify the central components or hubs of empathic communication and the changed profile of integration among these hubs after the EEPMS. Forty medical students participated in the EEPMS and completed the Depression Anxiety Stress Scale-21, the Empathy Quotient-Short Form, the Jefferson Scale of Empathy, and the Emotional Expressiveness Scale at baseline and after the EEPMS. The Ising model-based network of empathic communication was retrieved separately at two time points. Agitation, self-efficacy for predicting others’ feelings, emotional concealment, active emotional expression, and emotional leakage ranked in the top 20% in terms of nodal strength and betweenness and closeness centralities, and they became hubs. After the EEPMS, the ‘intentional emotional expressivity’ component became less locally segregated (P = 0.014) and more directly integrated into those five hubs. This study shows how to quantitatively describe the qualitative item-level effects of the EEPMS. The key role of agitation in the network highlights the importance of stress management in preserving the capacity for empathic communication. The training effect of EEPMS, shown by the reduced local segregation and enhanced integration of ‘intentional emotional expressivity’ with hubs, suggests that the EEPMS could enable medical students to develop competency in emotional expression, which is an essential component of empathic communication.