Relationship of neurocognitive ability, perspective taking, and psychoticism with hostile attribution bias in non-clinical participants: Theory of mind as a mediator.

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 [x 2/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 stress-vulnerability model on the path to schizophrenia: Interaction between BDNF methylation and schizotypy on the resting-state brain network.

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.

Sex-specific association of hair cortisol concentration with stress-related psychological factors in healthy young adults.

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.

Empathy and Theory of Mind in Ultra-High Risk for Psychosis: Relations With Schizotypy and Executive Function.

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.

Effect of Childhood Trauma on the Association Between Stress-Related Psychological Factors and Hair Cortisol Level in Young Adults.

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.

Shame and guilt in youth at ultra-high risk for psychosis.

OBJECTIVE: Feelings of shame and guilt have rarely been 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.

"Reading the Mind in the Eyes Test": Translated and Korean Versions.

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.

Reading the Mind in the Eyes Test: Relationship with Neurocognition and Facial Emotion Recognition in Non-Clinical Youths.

OBJECTIVE: The Reading the Mind in the Eyes Test (RMET) is a common measure of the Theory of Mind. Previous studies found a correlation between RMET performance and neurocognition, especially reasoning by analogy; however, the nature of this relationship remains unclear. Additionally, neurocognition was shown to play a significant role in facial emotion recognition. This study is planned to examine the nature of relationship between neurocognition and RMET performance, as well as the mediating role of facial emotion recognition. METHODS: One hundred fifty non-clinical youths performed the RMET. Reasoning by analogy was tested by Raven's Standard Progressive Matrices (SPM) and facial emotion recognition was assessed by the Korean Facial Expressions of Emotion (KOFEE) test. The percentile bootstrap method was used to calculate the parameters of the mediating effects of facial emotion recognition on the relationship between SPM and RMET scores. RESULTS: SPM scores and KOFEE scores were both statistically significant predictors of RMET scores. KOFEE scores were found to partially mediate the impact of SPM scores on RMET scores. CONCLUSION: These findings suggested that facial emotion recognition partially mediated the relationship between reasoning by analogy and social cognition. This study highlights the need for further research for individuals with serious mental illnesses.

Impaired Facial Emotion Recognition in Individuals at Ultra-High Risk for Psychosis and Associations With Schizotypy and Paranoia Level.

BACKGROUND: Patients with schizophrenia and individuals at ultra-high risk for psychosis (UHR) have been reported to exhibit impaired recognition of facial emotion expressions. This impairment has involved both inaccuracy and negative bias of facial emotion recognition. The present study aimed to investigate whether UHR individuals display both types of impaired facial emotion recognition and to explore correlations between these impairments and schizotypy, as well as paranoia levels, in these individuals. METHODS: A total of 43 UHR individuals and 57 healthy controls (HC) completed a facial emotion recognition task consisting of 60 standardized facial photographs. To explore correlations, we assessed schizotypy using the Revised Physical Anhedonia Scale and Magical Ideation Scale and paranoia level using the Paranoia Scale and persecution/suspicious item of the Positive and Negative Syndrome Scale in UHR individuals. RESULTS: Compared with HC, UHR individuals exhibited less accuracy for facial emotion recognition (70.6% vs. 75.6%, p=0.010) and a higher rate of "fear" responses for neutral faces (14.5% vs. 6.0%, p=0.003). In UHR individuals, inaccuracy was significantly correlated with schizotypy scores, but not with paranoia level. Conversely, "disgust" response for neutral faces was the only fear response correlated with paranoia level, and no threat-related emotion response correlated with schizotypy scores. DISCUSSION: UHR individuals exhibited inaccuracy and negative bias of facial emotion recognition. Furthermore, schizotypy scores were associated with inaccuracy but not with negative bias of facial emotion recognition. Paranoia level was correlated with "disgust" responses for neutral faces but not with inaccuracy. These findings suggest that inaccuracy and negative bias of facial emotion recognition reflect different underlying processes, and that inaccuracy may be a vulnerability marker for schizophrenia.

Reduced activation of the ventromedial prefrontal cortex during self-referential processing in individuals at ultra-high risk for psychosis.

OBJECTIVE: Defects in self-referential processing and perspective-taking are core characteristics that may underlie psychotic symptoms and impaired social cognition in schizophrenia. Here, we investigated the neural correlates of self-referential processing regardless of the perspective taken and third-person perspective-taking regardless of the target person to judge relevance in individuals at ultra-high risk for psychosis. We also explored relationships between alterations in neural activity and neurocognitive function and basic self ('ipseity') disorder. METHODS: Twenty-two ultra-high-risk individuals and 28 healthy controls completed a functional magnetic resonance imaging task. While being scanned, participants were asked to take a first-person perspective or to put themselves in their close relative's place thereby adopting a third-person perspective during judgments of the relevance of personality trait adjectives to one's self and a close relative. RESULTS: For self-referential (vs other-referential) processing, ultra-high-risk individuals showed less neural activity in the left ventromedial prefrontal cortex/medial orbitofrontal cortex, which was correlated with poor working memory performance. When taking a third-person perspective (vs first-person perspective), ultra-high-risk individuals showed more activity in the middle occipital gyrus. CONCLUSION: Taken together, our findings suggest that ultra-high-risk individuals already show aberrant neural activity during self-referential processing which may possibly be related to engagement of working memory resources.

Factors Associated With Psychosocial Functioning and Outcome of Individuals With Recent-Onset Schizophrenia and at Ultra-High Risk for Psychosis.

Background: Patients with schizophrenia have impairments in social functioning and are readmitted to healthcare institutions frequently. Individuals at ultra-high risk (UHR) for psychosis already present poor social functioning; among those individuals, the conversion rate from the putative prodromal phase to overt psychosis is 20%-30% within 1-2 years. Here, we analyzed the factor structure of self-related variables and neuro- and socio-cognitive function, and investigated whether these factors were associated with psychosocial function and prognostic outcome in individuals with recent-onset schizophrenia (ROSPR) or at UHR for psychosis. Methods: We evaluated 60 individuals at UHR for psychosis, 47 individuals with ROSPR, and 71 healthy controls using a comprehensive neurocognitive test battery and self-reported attribution scales, self-esteem, resilience, aberrant subjective experiences of schizotypy (physical anhedonia, social anhedonia, magical ideation, and perceptual aberration), and basic symptoms. We assessed psychosocial function with the Quality of Life Scale (QLS). Results: Factor analysis of all subjects revealed a four-factor structure comprising social-cognitive bias, reflective self, neurocognition, and pre-reflective self factors. Multiple regression analysis at baseline revealed that the factor structure predicted QLS. In the UHR group, social-cognitive bias, reflective self, neurocognition, and negative symptoms were significant determinants, explaining 38.0% of total QLS score variance. In the ROSPR group, reflective self and negative symptoms were significant determinants, explaining 54.4% of total QLS score variance. During follow-up, 13 individuals at UHR for psychosis developed psychosis (cumulative prevalence: 31.2% ± 7.6% at 6 years), with neurocognition score at baseline remaining a significant predictor of conversion [χ2(1) = 4.009, p = 0.045; hazard ratio 0.56, 95% confidence interval 0.31-0.99, p = 0.048]. Five patients with schizophrenia were (re)admitted during follow-up (cumulative prevalence: 16.1% ± 7.1% at 6 years); no factor was found to predict (re)admission. Conclusion: Factor analysis revealed an intrinsic four-factor structure of social-cognitive bias, reflective self, neurocognition, and pre-reflective self. The four factors were associated with social functioning at baseline and prodrome-to-psychosis conversion during follow-up, indicating the clinical significance of the four-factor structure. These findings provide a framework for understanding schizophrenia.

Aberrant Tendency of Noncurrent Emotional Experiences in Individuals at Ultra-High Risk for Psychosis.

OBJECTIVE: This study aimed to investigate whether aberrant tendency of noncurrent emotion was present in individuals at ultra-high risk (UHR) for psychosis and to explore its associations with various clinical profiles. METHODS: Fifty-seven individuals at UHR and 49 normal controls were enrolled. The tendency of experiencing noncurrent emotion was assessed using various noncurrent emotional self-reported formats, including trait [Neuroticism and Extraversion of the Eysenck Personality Questionnaire], hypothetical (Chapman's Revised Physical and Social Anhedonia Scales), and retrospective [AnhedoniaAsociality Subscale of the Scale for the Assessment of Negative Symptoms (SANS)] measures. Self-related beliefs (Self-Perception Scale), clinical positive and negative symptoms (SA Positive Symptoms and SANS), psychosocial function (Global Functioning Scale: Role Function and Global Functioning Scale: Social Function) were also examined. RESULTS: Subjects at UHR for psychosis reported more trait unpleasant and less trait pleasant emotions, more hypothetical physical and social anhedonia, and more retrospective anhedonia than normal controls. In UHR, self-perception was correlated to trait unpleasant emotion and hypothetical physical and social anhedonia. Negative symptoms in UHR were associated with hypothetical physical anhedonia and retrospective anhedonia. Global social functioning was related to trait pleasant emotion, hypothetical physical and social anhedonia, and retrospective anhedonia. Neurocognitive function, positive symptoms, and global role functioning were not related with any noncurrent emotional experience measures in UHR. CONCLUSION: These findings suggest that the aberrant tendency of noncurrent emotional experience may be present at the 'putative' prodromal phase and are grossly associated with self-related beliefs and psychosocial functioning but not neurocognitive functioning.