Association of hair cortisol concentration with brain-derived neurotrophic factor gene methylation: The role of sex as a moderator.

Hair cortisol concentration (HCC) reflects the long-term activity of the hypothalamus-pituitary-adrenal (HPA) axis in response to stress. Brain-derived neurotrophic factor DNA methylation (BDNF DNAM) may affect HCC, and sex and Val66Met may contribute to this association. Thus, the aim of this study was to investigate the associations between HCC and Brain-derived neurotrophic factor (BDNF) DNAM, and the moderating effects of Val66Met and sex. We recruited 191 healthy young participants (96 women, mean age 23.0 ± 2.6 years) and collected body samples to evaluate HCC, and to determine BDNF DNAM and Val66Met genotypes. We analyzed the effects of BDNF DNAM, sex, and Val66Met on HCC. We also evaluated the associations between BDNF DNAM and HCC in groups separated by sex and genotypes. We found a marked association of BDNF DNAM with HCC across men and women. After dividing the data by sex, a positive correlation of HCC with BDNF DNAM was found only in women. There was no substantial moderation effect of Val66Met genotypes on the association between BDNF DNAM and HCC. Therefore, BDNF DNAM was found to have positive association with HCC only in healthy young women, indicating that sex moderates the association of BDNF DNAM with long-term HPA axis activity.

Impact of data extraction errors in meta-analyses on the association between depression and peripheral inflammatory biomarkers: an umbrella review.

BACKGROUND: Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-ß (IL-1ß), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof. RESULTS: Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1ß, are associated with depression. CONCLUSIONS: These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.

Theory of mind and hair cortisol in healthy young adults: the moderating effects of childhood trauma.

Background: Experiences of negative social interactions and childhood trauma (CT) can lead to aberrant hypothalamic-pituitary-adrenal functions. Poor theory of mind (ToM) ability is related to increased social stress levels; however, studies on the relationship between ToM and cortisol remain scarce. Objective: This study aimed to evaluate the relationship between ToM and the hair cortisol concentration (HCC) in healthy young adults considering the moderating role of CT. Method: A total of 206 healthy young adults were divided into two groups based on an experience of moderate-to-severe childhood trauma (CT+ and CT-). To determine whether CT moderated the relationship between ToM and HCC, moderation analysis was conducted controlling for age, sex, years of education, and scores of perceived stress, depression, and anxiety. Results: CT+ individuals reported higher subjective stress perception and depressive symptoms than CT- individuals, whereas anxiety-related symptoms, ToM, and HCC were not different between the groups. The experience of CT significantly moderated the relationship between ToM and HCC. The association between poorer ToM ability and higher HCC was significant only in CT+ group. Conclusion: CT is a moderator of the association between ToM and HCC, indicating the importance of CT in social cognition and the stress response.

Antecedentes: Las experiencias de interacciones sociales negativas y el trauma infantil (CT por sus siglas en inglés) pueden conducir a funciones hipotalámicas-pituitarias-adrenales aberrantes. La pobre capacidad de teoría de la mente (ToM por sus siglas en inglés) está relacionada con mayores niveles de estrés social; sin embargo, los estudios sobre la relación entre ToM y cortisol siguen siendo escasos.Objetivo: Este estudio tuvo como objetivo evaluar la relación entre ToM y concentración de cortisol en el cabello (HCC por sus siglas en inglés) en adultos jóvenes sanos considerando el papel moderador del CT.Método: Un total de 206 adultos jóvenes sanos se dividieron en dos grupos en función de una experiencia de trauma infantil de moderada a severa (CT+ y CT­). Para determinar si el CT moderaba la relación entre ToM y HCC, se realizó un análisis de moderación controlando la edad, sexo, años de educación y las puntuaciones de estrés percibido, depresión y ansiedad.Resultados: Individuos CT+ informaron una mayor percepción subjetiva de estrés y síntomas depresivos que los individuos CT­, mientras que los síntomas relacionados con ansiedad, ToM y HCC no fueron diferentes entre los grupos. La experiencia de CT moderó significativamente la relación entre ToM y HCC. La asociación entre una capacidad de ToM más pobre y un HCC más alto fue significativa solo en el grupo CT+.Conclusión: CT es un moderador de la asociación entre ToM y HCC, lo que indica la importancia del CT en la cognición social y la respuesta al estrés.

A nationwide cohort study of the association of benzodiazepines with SARS-CoV-2 infection and clinical outcomes.

The evidence for the impact of benzodiazepine (BZD) use on infection or clinical outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited. We evaluated the association of BZD use with SARS-CoV-2 infection and the clinical outcomes of coronavirus disease 2019 (COVID-19) using a nationwide COVID-19 database from South Korea. This nationwide cohort study was performed using the COVID-19 database from the Health Insurance Review and Assessment Service of Korea, and SARS-CoV-2 positivity was investigated according to BZD use. SARS-CoV-2-positive adult patients were assessed in three groups, those who needed hospitalization, those with severe symptoms requiring intensive care, and those who died. A multivariate logistic regression model was used for all the analyses. After adjusting for potential confounding factors, there was no association between BZD use and SARS-CoV-2 positivity. SARS-CoV-2-positive patients with BZD use showed an increased risk of need for hospitalization from COVID-19 compared to those without BZD use (odds ratio [OR]: 1.33, 95% confidence interval [CI] 1.07-1.65). In addition, there was a higher risk for long-term users (OR: 2.64, 95% CI 1.08-6.47). Chronic BZD use contributed to a higher risk of the need for hospitalization among COVID-19 patients, whereas BZD use did not increase the risk of SARS-CoV-2 test positivity, severe outcomes, or mortality.

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.

Increased resting-state cerebellar-cortical connectivity in breast cancer survivors with cognitive complaints after chemotherapy.

Cognitive complaints after chemotherapy are common in breast cancer patients, but the neural bases for these complaints remain unclear. This pilot study explored resting-state functional connectivity (FC) as a marker of subtle cognitive changes in breast cancer patients who experience cognitive complaints. Chemotherapy-treated (n = 20, at least 6 months off therapy) and untreated (n = 17, disease-control) female breast cancer patients with cognitive complaints and healthy controls (n = 20) were recruited. The FC of the right dorsolateral prefrontal cortex was calculated, and any correlations between this FC and neuropsychological assessments were determined. Chemotherapy-treated patients with cognitive complaints displayed increased FC between the right dorsolateral prefrontal cortex and both the contralateral cerebellar lobule VII and the cerebellar vermis XI, compared to the disease-control and healthy-control groups, despite unimpaired neuropsychological performance. The increased FC was negatively correlated with executive function and attention in breast cancer survivors with cognitive complaints. Our pilot study findings provide evidence that cerebellar-cortical FC changes may be a pathophysiological basis for chemotherapy-related cognitive complaints. In addition, the FC changes have the potential to reflect minor or compensated cognitive function impairment in breast cancer patients.

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.

Deactivation of anterior cingulate cortex during virtual social interaction in obsessive-compulsive disorder.

Studies about social functioning in obsessive-compulsive disorder (OCD) are lacking, even though neuroimaging studies and metacognition evaluation results suggest abnormal neural responses during social interactions. This study examined neural responses of OCD patients during handshakes with a virtual avatar. Because of the nature of the handshaking task, we expected that OCD patients with predominantly contamination/washing symptoms (CON) would show different neural responses compared to healthy controls (HCs) and to disease-controlled (NCON) patients. Thirteen CON, 13 NCON, and 18 HC participants performed handshake tasks with clean or dirty virtual avatars while undergoing functional magnetic resonance imaging. During handshakes with a clean avatar, deactivation in the left anterior cingulate cortex was found in CON patients compared to NCON and HC subjects. This cortical deactivation also occurred with dirty-avatar handshakes, but the difference was significant only between the two OCD groups and HC patients. Deactivation in the left anterior cingulate cortex was correlated with both OCD symptom severity and social anxiety traits. This cortical deactivation in OCD, especially in CON patients, suggests that social dysfunction in OCD may be due to interactions between OCD symptoms and impairment in social cognition, including emotional processing.

Sex differences in the association between social relationships and insomnia symptoms.

STUDY OBJECTIVES: Social relationships are an understudied factor affecting insomnia. In particular, these effects have not been evaluated in the context of sex differences. In this study, we investigated differences between sexes with regard to the association between insomnia symptoms and social relationships. METHODS: We used data from 2681 middle-aged adults (aged 40-64 years; females, 68.8%) from the Cardiovascular and Metabolic Diseases Etiology Research Center project. Insomnia symptoms were defined as difficulty with sleep induction or maintenance ≥3 nights per week. We assessed social network size and bridging potentials as indicators of social relationships. Social network size is a quantitative measure of the size of social relationships, and bridging potential is a qualitative indicator of the diversity and independence of these relationships. Multivariate regression analysis controlling for confounding factors was performed to evaluate associations between social relationships and insomnia symptoms. RESULTS: Smaller social network size was significantly associated with sleep induction (adjusted odds ratio = 0.866, P = .015) and sleep maintenance (adjusted odds ratio = 0.862, P = .015) difficulties, but only in men. Poor bridging potential was also associated with sleep induction (adjusted odds ratio = 0.321, P = .024) and maintenance (adjusted odds ratio = 0.305, P = .031) difficulties only in men. For women, social relationship variables were not significantly associated with insomnia symptoms. CONCLUSIONS: The association between insomnia symptoms and social relationships varied by sex, as noted by statistical analyses accounting for covariates affecting insomnia symptoms. These results suggest that qualitative assessments of social relationship variables should be considered in clinical practice, since these variables can be interpreted differently for men and women.

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.

Changes in resting-state brain connectivity following computerized cognitive behavioral therapy for insomnia in dialysis patients: A pilot study.

OBJECTIVE: Insomnia is prevalent among dialysis patients and affects their mortality. Although cognitive behavioral therapy for insomnia (CBTi) is recommended, attending regular face-to-face CBTi sessions is a major challenge for patients. We evaluated the effectiveness of a self-directed computerized CBTi (cCBTi) in dialysis patients, and investigated changes in resting-state brain connectivity and inflammatory cytokines following cCBTi. METHOD: Thirty-five patients undergoing maintenance hemodialysis or peritoneal dialysis who had insomnia were screened for participation in the study, with 17 participants included in the final analyses. A self-directed cCBTi protocol accessed via tablet computer during dialysis or at home was developed and applied. Information about sleep, anxiety, depression, laboratory data, and resting-state functional magnetic resonance imaging data was obtained 3-5 days before and after cCBTi. RESULTS: cCBTi improved sleep quality, and this was correlated with increased resting-state brain connectivity between the default-mode network and the premotor/dorsolateral prefrontal cortex. The decrement of interleukin-1ß levels were correlated with improved sleep quality and increased brain connectivity after cCBTi. CONCLUSION: Our pilot study findings suggest that cCBTi is effective for dialysis patients with insomnia, and the therapeutic effects of cCBTi are related to changes in brain functional connectivity and inflammatory cytokines.

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.

Correction: Population-based dementia prediction model using Korean public health examination data: A cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0211957.].

Cox Proportional Hazard Regression Versus a Deep Learning Algorithm in the Prediction of Dementia: An Analysis Based on Periodic Health Examination.

BACKGROUND: With the increase in the world's aging population, there is a growing need to prevent and predict dementia among the general population. The availability of national time-series health examination data in South Korea provides an opportunity to use deep learning algorithm, an artificial intelligence technology, to expedite the analysis of mass and sequential data. OBJECTIVE: This study aimed to compare the discriminative accuracy between a time-series deep learning algorithm and conventional statistical methods to predict all-cause dementia and Alzheimer dementia using periodic health examination data. METHODS: Diagnostic codes in medical claims data from a South Korean national health examination cohort were used to identify individuals who developed dementia or Alzheimer dementia over a 10-year period. As a result, 479,845 and 465,081 individuals, who were aged 40 to 79 years and without all-cause dementia and Alzheimer dementia, respectively, were identified at baseline. The performance of the following 3 models was compared with predictions of which individuals would develop either type of dementia: Cox proportional hazards model using only baseline data (HR-B), Cox proportional hazards model using repeated measurements (HR-R), and deep learning model using repeated measurements (DL-R). RESULTS: The discrimination indices (95% CI) for the HR-B, HR-R, and DL-R models to predict all-cause dementia were 0.84 (0.83-0.85), 0.87 (0.86-0.88), and 0.90 (0.90-0.90), respectively, and those to predict Alzheimer dementia were 0.87 (0.86-0.88), 0.90 (0.88-0.91), and 0.91 (0.91-0.91), respectively. The DL-R model showed the best performance, followed by the HR-R model, in predicting both types of dementia. The DL-R model was superior to the HR-R model in all validation groups tested. CONCLUSIONS: A deep learning algorithm using time-series data can be an accurate and cost-effective method to predict dementia. A combination of deep learning and proportional hazards models might help to enhance prevention strategies for dementia.