Eunchong Seo’s research while affiliated with Yonsei University Hospital and other places

Background: Social cognition, which ranges from recognizing social cues to intricate inferential reasoning, is influenced by environmental factors and epigenetic mechanisms. Notably, methylation variations in stress-related genes like brain-derived neurotrophic factor (BDNF) and the oxytocin receptor (OXTR) are linked to distinct social cognitive functions and exhibit sex-specific differences. This study investigates how these methylation differences affect social cognition across sexes, focusing on both perceptual and inferential cognitive levels. Methods: Social cognitive abilities were assessed using the Korean version of the Reading the Mind in the Eyes Test (K-RMET) and Brune’s story-based Theory of Mind tasks (ToM-PST). DNA methylation levels in BDNF and OXTR were analyzed for correlations with performance on these cognitive tasks in a cohort of male and female participants. A moderation model was applied to determine if sex moderates the relationship between social cognition and DNA methylation. Results: No significant overall correlation was found between social cognition and DNA methylation across participants. However, sex-specific correlations were identified, including a negative impact of BDNF methylation on K-RMET scores in males, and a similar effect of OXTR methylation on ToM-PST scores in females. Conclusions: The findings underscore the complex relationship between epigenetic modifications and social cognition, revealing sex-specific effects and highlighting the importance of considering sex in epigenetic studies of social cognition. This research contributes to understanding how epigenetic factors, influenced by sex, shape social cognitive processes and supports the need for sex-specific therapeutic approaches.

Objectives Hostile attribution bias is reportedly common from non-clinical population to those with serious mental illness, such as schizophrenia, and is known to be closely related to theory of mind (ToM). This study aimed to investigate whether ToM skills mediate the relationship among neurocognitive ability, personality traits, and attribution bias. Methods A total of 198 (101 females) non-clinical youths were recruited. To assess their neurocognitive ability and ToM skills, the participants were asked to complete Raven’s Standard Progressive Matrices (SPM) and the Korean version of the Reading the Mind in Eyes Test (K-RMET). To determine their personality traits, the Eysenck Personality Questionnaire (psychoticism) and interpersonal reactivity index (perspective taking) were used. To evaluate hostile attribution bias, the Ambiguous Intentions Hostility Questionnaire was administered. Path analysis and bias-corrected percentile bootstrap methods were used to estimate model fit and the parameters of the mediating effects. Results Based on model comparison, the best model characterized (1) two direct pathways from psychoticism and the K-RMET to hostility attribution bias and (2) three indirect pathways, wherein SPM, perspective taking, and psychoticism influenced hostile attribution bias through K-RMET. The final model fit indices were good [x²/df = 1.126; comparative fit index = 0.996; root mean square error of approximation = 0.026; standard root mean square residual = 0.026 and Akaike information criterion = 28.251] and the K-RMET fully mediated the association between SPM, perspective taking, psychoticism, and hostile attribution bias. Conclusion The main findings suggested that ToM skills, such as the RMET, play an important role in explaining the relationship among neurocognitive ability, personality traits, and hostile attribution bias. ToM skills and a remediation strategy may need to be developed to balance the enhanced hostility bias that underlies the paranoia.

The interplay between schizophrenia liability and environmental influences has been considered to be responsible for the development of schizophrenia. Recent neuroimaging studies have linked aberrant functional connectivity (FC) between the default-mode network (DMN) and the frontoparietal network (FPN) in the resting-state to the underlying neural mechanism of schizophrenia. By using schizotypy as the proxy for genetic-based liability to schizophrenia and methylation of brain-derived neurotrophic factor (BDNF) to represent environmental exposure, this study investigated the impact of the interaction between vulnerability and the environment on the neurobiological substrates of schizophrenia. Participants in this study included 101 healthy adults (HC) and 46 individuals with ultra-high risk for psychosis (UHR). All participants were tested at resting-state by functional magnetic resonance imaging, and group-independent component analysis was used to identify the DMN and the FPN. The Perceptual Aberration Scale (PAS) was used to evaluate the schizotypy level. The methylation status of BDNF was measured by pyrosequencing. For moderation analysis, the final sample consisted of 83 HC and 32 UHR individuals. UHR individuals showed reduced DMN-FPN network FC compared to healthy controls. PAS scores significantly moderated the relationship between the percentage of BDNF methylation and DMN-FPN network FC. The strength of the positive relationship between BDNF methylation and the network FC was reduced when the schizotypy level increased. These findings support the moderating role of schizotypy on the neurobiological mechanism of schizophrenia in conjunction with epigenetic changes.

Background Hair cortisol concentration (HCC) has received attention as a useful marker of stress, but evidence on associations between psychological factors and cortisol concentration is inconsistent. The purpose of this study was to investigate the sex differences in the relationship between cortisol concentration and psychological factors in healthy young adults. Methods A total of 205 (103 females, 102 males) healthy young adults participated. HCC and various stress-related psychological measures were compared between sexes. Multiple linear regression analyses were performed to assess associations between HCC and stress-related psychological measures for all participants and for each sex. Results The difference in HCC according to sex was not significant. The reported number of stressful life events in the past year, stress perception, depressive and anxiety-related symptoms, and emotion dysregulation were not different between sexes, either. The association between HCC and emotion dysregulation was significant in females but not males. Conclusion We observed a sex-specific association between HCC and psychological factors. Our findings may imply that HCC could be a useful biomarker of stress and stress-related emotion dysregulation in healthy young women.

Objective: While recent studies have found deficits in theory of mind (ToM) skills in individuals at ultra-high risk (UHR) for psychosis, empathic tendencies in these subjects remain unclear. The presence of high schizotypy and compromised executive functions, which are found in UHR individuals, would affect ToM skills and empathic tendencies. We investigated the ToM skills and empathic tendencies of UHR individuals and examined their relationship with schizotypy and executive function. Methods: This study included 28 UHR individuals and 28 age- and sex-matched healthy controls. All participants completed a self-reported empathic scale (Interpersonal Reactivity Index) and the Wisconsin Schizotypy Scales. Additionally, the ToM Picture Stories Task and Wisconsin Card Sorting Test were conducted. Results: UHR individuals showed a trend toward lower self-reported empathic tendencies; however, there were no differences in ToM skills between the two groups. Of the four subscales of the IRI, only empathic concern showed a significant difference between the two groups. Empathic concern was inversely associated with negative schizotypy. Conclusion: Our findings suggest that UHR individuals show relatively preserved cognitive empathy but compromised emotional empathy. Furthermore, in UHR individuals, the empathic concern subscale of the IRI was associated with negative schizotypy, while ToM skills were related to positive schizotypy and executive function.

Objective: Relationship between hair cortisol concentration (HCC) and stress-related psychological measures are inconclusive, possibly due to overlooked heterogeneity regarding childhood trauma and a lack of comprehensive research on stress-related psychological factors. This study aims to compare young adults without history of childhood trauma to young adults who experienced childhood trauma using HCC and various stress-related psychological factors, as well as investigate the impacts of childhood trauma on the association between HCC and stress-related psychological measures. Methods: A total of 206 young, healthy adults were recruited. We divided participants into two groups depending on whether or not they had suffered moderate-to-severe childhood trauma (CT+ and CT-) and compared HCC and various stress-related psychological measures between groups. Using multiple linear regression analyses, we assessed the associations between HCC and stress-related psychological measures for each group. Results: We found no difference between the groups in HCC or the reported number of stressful life events in the past year; however, CT+ individuals reported higher stress perception, more depressive and anxiety-related symptoms, and more difficulties in emotion regulation than CT- individuals. HCC was associated with emotion dysregulation among the CT- individuals, but not among the CT+ individuals. Conclusion: These findings suggest that history of childhood trauma should be considered in studies using HCC as a biomarker for stress in young adults. Furthermore, HCC might be a useful biomarker of stress and stress-related emotion dysregulation in individuals without moderate-to-severe childhood trauma.

Objective: The Reading the Mind in the Eyes Test (RMET) was developed by using Caucasian eyes, which may not be appropriate to be used in Korean. The aims of the present study were 1) to develop a Korean version of the RMET (K-RMET) by using Korean eye stimuli and 2) to examine the psychometric properties of the Korean-translated version of the RMET and the K-RMET. Methods: Thirty-six photographs of Korean eyes were selected. A total of 196 (101 females) healthy subjects were asked to take the Korean- translated version of the RMET and K-RMET. To assess internal consistency reliability, Cronbach's alpha coefficients were computed, and test-retest reliability was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman plots. Confirmatory factor analysis (CFA) and item analysis were also conducted. Results: Internal consistency, measured by Cronbach's alpha, was 0.542 for the Korean-translated version of the RMET, and 0.540 for the K-RMET. Test-retest reliability (n=25), measured by the ICC, was 0.787 for the Korean-translated version of the RMET, and 0.758 for the K-RMET. In CFA, the assumed single and 3-factor model fit indices were not good in the both types of RMETs. There was difficulty in discrimination in nine items of the Korean-translated version of the RMET and 10 items of the K-RMET. Conclusion: The psychometric properties of both the Korean-translated version of the RMET and the K-RMET are acceptable. Both tests are applicable to the clinical population, as well as the general population in Korea.

Objective Feelings of shame and guilt have rarely bee investigated in people at ultra-high risk (UHR) for psychosis. We aimed to outline differences in shame and guilt in relation to empathy and theory of mind (ToM) in young people, particularly those at UHR for psychosis. Methods First, 166 young healthy controls were assessed for their proneness to shame and guilt using the Test of Self-Conscious Affect, empathy and its four subdomains (perspective taking, fantasy, empathic concern, and personal distress) using the Interpersonal Reactivity Index (IRI), ToM using the ToM picture stories task, and neurocognitive performance using the Raven's Standard Progressive Matrices (SPM). Next, we evaluated shame and guilt in 24 UHR individuals comparing them to 24 age- and sex-matched healthy controls. Finally, we explored relationships for shame and guilt in relation to empathy and ToM in the UHR individuals. Results In the healthy youth, a regression analysis showed fantasy and personal distress in IRI to be significant determinants of shame, while perspective taking and empathic concern in IRI, ToM, and SPM were independent predictors of guilt. Meanwhile, compared to the healthy controls, individuals with UHR exhibited higher levels of shame, which was associated with increased personal distress. Discussion Our findings showed that four subdomains of empathy, ToM, and neurocognition were differentially associated with shame and guilt in healthy young people. Given the correlation between excessive feelings of shame and high levels of the personal distress dimension of empathy in UHR for psychosis, redressing the tendency to focus on self-oriented negative emotions upon witnessing distress of others could possibly reduce self-blame or self-stigma of help-seeking individuals.