Machine Learning and Bayesian Network Analyses Identifies Psychiatric Disorders and Symptom Associations with Insomnia in a national sample of 31,285 Treatment-Seeking College Students.

Background: A better understanding of the structure of relations among insomnia and anxiety, mood, eating, and alcohol-use disorders is needed, given its prevalence among young adults. Supervised machine learning provides the ability to evaluate the discriminative accuracy of psychiatric disorders associated with insomnia. Combined with Bayesian network analysis, the directionality between symptoms and their associations may be illuminated. Methods: The current exploratory analyses utilized a national sample of college students across 26 U.S. colleges and universities collected during population-level screening before entering a randomized controlled trial. Firstly, an elastic net regularization model was trained to predict, via repeated 10-fold cross-validation, which psychiatric disorders were associated with insomnia severity. Seven disorders were included: major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder, post-traumatic stress disorder, anorexia nervosa, and alcohol use disorder. Secondly, using a Bayesian network approach, completed partially directed acyclic graphs (CPDAG) built on training and holdout samples were computed via a Bayesian hill-climbing algorithm to determine symptom-level interactions of disorders most associated with insomnia [based on SHAP (SHapley Additive exPlanations) values)] and were evaluated for stability across networks. Results: Of 31,285 participants, 20,597 were women (65.8%); mean (standard deviation) age was 22.96 (4.52) years. The elastic net model demonstrated clinical significance in predicting insomnia severity in the training sample [R2 = .449 (.016); RMSE = 5.00 [.081]), with comparable performance in accounting for variance explained in the holdout sample [R2 = .33; RMSE = 5.47). SHAP indicated the presence of any psychiatric disorder was associated with higher insomnia severity, with major depressive disorder demonstrated to be the most associated disorder. CPDAGs showed excellent fit in the holdout sample and suggested that depressed mood, fatigue, and self-esteem were the most important depression symptoms that presupposed insomnia. Conclusion: These findings offer insights into associations between psychiatric disorders and insomnia among college students and encourage future investigation into the potential direction of causality between insomnia and major depressive disorder. Trial registration: Trial may be found on the National Institute of Health RePORTER website: Project Number: R01MH115128-05.

The transdiagnostic use of worry and rumination to avoid negative emotional contrasts following negative events: A momentary assessment study.

The contrast avoidance model (CAM) suggests that individuals with generalized anxiety disorder (GAD) are sensitive to a sharp increase in negative and/or decrease in positive affect. They thus worry to increase negative emotion to avoid negative emotional contrasts (NECs). However, no prior naturalistic study has examined reactivity to negative events, or ongoing sensitivity to NECs, or the application of CAM to rumination. We used ecological momentary assessment to examine effects of worry and rumination on negative and positive emotion before and after negative events and intentional use of repetitive thinking to avoid NECs. Individuals with major depressive disorder (MDD) and/or GAD (N = 36) or without psychopathology (N = 27) received 8 prompts/day for 8 days and rated items on negative events, emotions, and repetitive thoughts. Regardless of group, higher worry/rumination before negative events was associated with less increased anxiety and sadness, and less decreased happiness from before to after the events. Participants with MDD/GAD (vs. controls) reported higher ratings on focusing on the negative to avoid NECs and greater vulnerability to NECs when feeling positive. Results support the transdiagnostic ecological validity for CAM extending to rumination and intentional engagement in repetitive thinking to avoid NECs among individuals with MDD/GAD.

Association between Dissociative Symptoms and Morning Cortisol Levels in Patients with Post-traumatic Stress Disorder.

Objective: Patients with post-traumatic stress disorder (PTSD) showed inconsistencies in their cortisol level, an index of the hypothalamic-pituitary-adrenal axis function. This study examined the relationship between dissociation, childhood trauma, and morning cortisol levels in PTSD patients. Methods: This study included 69 (23 males and 46 females) patients and 82 (22 males and 60 females) healthy controls (HCs). Clinical assessments, including the Childhood Trauma Questionnaire (CTQ) and Peri-traumatic Dissociative Experiences Questionnaire scores, and morning cortisol levels were evaluated. The morning cortisol levels were compared between PTSD with high dissociation and low dissociation (PTSD-LD) groups. The effect of CTQ subtype on morning cortisol levels was analyzed. Results: The PTSD with high dissociation group showed significantly lower cortisol levels than that of the PTSD-LD and HC groups. A significant inverse correlation was found between cortisol levels and dissociation. A significant positive correlation was found between dissociation and physical abuse and sexual abuse scores. Morning cortisol levels showed a significant positive correlation with emotional abuse, emotional neglect, and physical neglect, respectively. There was no moderating or mediating effect of CTQ on the relationship between cortisol level and dissociation. Conclusion: These findings suggest that dissociation is a significant factor related to hypocortisolism in PTSD patients. Additionally, basal morning cortisol levels and dissociation scores were closely associated with childhood trauma.

Improved cognitive function in patients with major depressive disorder after treatment with vortioxetine: A EEG study.

INTRODUCTION: Vortioxetine has a positive effect on cognitive function in patients with major depressive disorder (MDD). This study aimed to examine the changes in cognitive function and EEG (spectral power and mismatch negativity (MMN)) in patients with MDD pre- and postvortioxetine treatment. METHODS: Thirty patients with MDD were included in the study. They were given vortioxetine (10-20mg po per day) for eight weeks. Depression and anxiety severities, social function (Korean version of the social adjustment scale (K-SAS)), and cognitive function (digit-symbol substitution Test (DSST), Korean version of the attentional control questionnaire (K-ACQ), and Korean version of the perceived deficits questionnaire for depression (K-PDQD)) were evaluated. Spectral power of EEG and MMN was also measured pre- and postvortioxetine treatment. RESULTS: Depression and anxiety severity, social function, and cognitive functioning significantly improved after vortioxetine treatment. Also, there was a significant decrease in the right central delta band and an increase in the right central beta 2 band following vortioxetine treatment. The changes in EEG spectral power were not related to changes in cognitive functions. Baseline MMN significantly predicted changes in DSST score after controlling for the baseline clinical variables. CONCLUSION: Vortioxetine treatment improved cognitive function and induced changes in EEG (decreased theta power and increased beta power) in patients with MDD. Our results suggest that greater negative MMN amplitude is associated with greater potential for cognitive improvement following vortioxetine treatment.

Prefrontal Functional Connectivity During the Verbal Fluency Task in Patients With Major Depressive Disorder: A Functional Near-Infrared Spectroscopy Study.

Deviations in activation patterns and functional connectivity have been observed in patients with major depressive disorder (MDD) with prefrontal hemodynamics of patients compared with healthy individuals. The graph-theoretical approach provides useful network metrics for evaluating functional connectivity. The evaluation of functional connectivity during a cognitive task can be used to explain the neurocognitive mechanism underlying the cognitive impairments caused by depression. Overall, 31 patients with MDD and 43 healthy individuals completed a verbal fluency task (VFT) while wearing a head-mounted functional near-infrared spectroscopy (fNIRS) devices. Hemodynamics and functional connectivity across eight prefrontal subregions in the two groups were analyzed and compared. We observed a reduction in prefrontal activation and weaker overall and interhemispheric subregion-wise correlations in the patient group compared with corresponding values in the control group. Moreover, efficiency, the network measure related to the effectiveness of information transfer, showed a significant between-group difference [t (71.64) = 3.66, corrected p < 0.001] along with a strong negative correlation with depression severity (rho = -0.30, p = 0.009). The patterns of prefrontal functional connectivity differed significantly between the patient and control groups during the VFT. Network measures can quantitatively characterize the reduction in functional connectivity caused by depression. The efficiency of the functional network may play an important role in the understanding of depressive symptoms.

Association Between Symptoms of Patients With Heart Failure and Patient Outcomes Based on Electronic Nursing Records.

We examined the association between symptoms (ie, dyspnea and pain) and patient outcomes (ie, length of stay, 30-day readmission, and death in hospital) among patients with heart failure using EMRs. This was a descriptive study that was conducted from July 1, 2014, to November 30, 2017. Participants were 754 hospitalized patients with heart failure (mean age, 70.62 ± 14.78 years; male-to-female ratio, 1:1.1). Data were analyzed using descriptive statistics, χ2 tests, and logistic regression analyses. Patients' average length of stay was 8.92 ± 13.12 days. Thirty-two patients (4.2%) were readmitted, and 100 patients (13.3%) died during hospitalization. Two-thirds (67.7%) experienced dyspnea, and 367 (48.7%) experienced pain. Symptoms and ICU admission were significantly related to patient outcomes. In the regression analyses, dyspnea, pain, and ICU admission were significantly related to higher-than-average lengths of stay. Dyspnea and ICU admission were related to death in hospital. Information regarding patients' symptoms, which was extracted from records, was a valuable resource in examining the relationship between symptoms and patient outcomes. The use of EMRs may be more advantageous than self-reported surveys when examining patients' symptom and utilizing big data.

Empathy and Social Attribution Skills Moderate the Relationship between Temporal Lobe Volume and Facial Expression Recognition Ability in Schizophrenia.

OBJECTIVE: While impaired facial expression recognition has been closely associated with reduced temporal lobe volume in patients with schizophrenia, this study aimed at examining whether empathy and social attribution affect such a relationship. METHODS: A total of 43 patients with schizophrenia and 43 healthy controls underwent a facial expression recognition task (FERT) and magnetic resonance imaging. Basic empathy scale and the social attribution task-multiple choice were used to measure empathy and social attribution. RESULTS: Patients with schizophrenia showed significant positive correlations between the total temporal lobe volume and the FERT-accuracy (FERT-ACC). Diminished temporal lobe volume predicted the impaired facial emotion recognition ability. Both empathy and social attribution played roles as moderators of the path from the left amygdala volume, left fusiform gyrus volume, both sides of the superior temporal gyrus volume, and left middle temporal gyrus volume to the FERT-ACC. In contrast, empathy alone functioned as a moderator between the right fusiform gyrus volume, right middle temporal gyrus volume, and FERT-ACC. No significant interaction was found for healthy controls. CONCLUSION: Our results suggest that social cognition remediation training on empathy and social attribution, could buffer the negative effects of small temporal lobe volume on interpersonal emotional communication in patients with schizophrenia.

Prediction of Antidepressant Treatment Outcome Using Event-Related Potential in Patients with Major Depressive Disorder.

(1) Background: Prediction of treatment outcome has been one of the core objectives in clinical research of patients with major depressive disorder (MDD). This study explored the possibility of event-related potential (ERP) markers to predict antidepressant treatment outcomes among MDD patients; (2) Methods: Fifty-two patients with MDD were recruited and evaluated through Hamilton depression (HAM-D), Hamilton anxiety rating scale (HAM-A), and CORE. Patients underwent a battery of ERP measures including frontal alpha symmetry (FAA) in the low alpha band (8-10 Hz), mismatch negativity (MMN), and loudness-dependent auditory evoked potentials (LDAEP); (3) Results: During the eight weeks of study, 61% of patients achieved remission, and 77% showed successful treatment responsiveness. Patients with low FAA in F5/F6 demonstrated a significantly higher remission/response ratio and better treatment responsiveness (F (2.560, 117.755) = 3.84, p = 0.016) compared to patients with high FAA. In addition, greater FAA in F7/F8 EEG channels was significantly associated with greater melancholia scores (r = 0.34, p = 0.018). Other ERP markers lacked any significant effect; (4) Conclusions: Our results suggested low FAA (i.e., greater left frontal activity) could reflect a good treatment response in MDD patients. These findings support that FAA could be a promising index in understanding both MDD and melancholic subtype.

Prefrontal Asymmetry during Cognitive Tasks and its Relationship with Suicide Ideation in Major Depressive Disorder: An fNIRS Study.

Reduced oxygenation changes in the prefrontal cortex during cognitive tasks have been reported in major depressive disorder (MDD). However, prefrontal asymmetry during cognitive tasks and its relation to suicide ideations have been less frequently examined in patients with MDD. This study investigated prefrontal asymmetry and its moderating effect on the relationship between depression severity and suicidal ideation in MDD patients during cognitive tasks. Forty-two patients with MDD and 64 healthy controls (HCs) were assessed for changes in oxygenated and deoxygenated hemoglobin (Hb) in the prefrontal cortex using functional near-infrared spectroscopy (fNIRS) during the verbal fluency task (VFT), Stroop task, and two-back task. Depression, anxiety, and suicide ideation were measured through self-report questionnaires. Relatively smaller left oxy-Hb changes during VFT, but not during the Stroop or two-back tasks, were found in MDD patients compared with HCs. Furthermore, prefrontal asymmetry during VFT moderated the effect of depression severity on suicide ideation, and was significantly and positively correlated with suicide ideation in patients with MDD. Specifically, relatively greater left oxy-Hb changes were associated with greater suicide ideation. These findings suggest fNIRS-measured prefrontal asymmetry as a potential biomarker for MDD and for the assessment of suicidal risk in patients with MDD.

The moderating effect of heart rate variability on the relationship between alpha asymmetry and depressive symptoms.

Electroencephalographic (EEG) research has suggested relatively reduced brain activity in the left frontal and right posterior region trait-markers of depression. However, inconsistent results have been reported. Based on previous studies reporting the heart rate variability (HRV) as an index of emotional regulation, this study makes a novel investigation of the role of heart rate variability (HRV) as a moderator in the relationship between frontal and parietal alpha asymmetry and depression. Resting EEG (eyes open) was recorded in 38 patients with MDD and 34 healthy subjects. Frontal and parietal alpha asymmetries were calculated at total (8-12 Hz), high (10-12 Hz), and low (8-10 Hz) alpha frequency bands. Three vagally mediated HRV (vmHRV) components (LF, HF, and the LF/HF ratio) were calculated in the frequency domain. Relatively greater right parietal alpha activity significantly predicted the severity of depression only when HF was low (or the LF/HF ratio was high) at low alpha frequency band. The interaction effect of parietal alpha asymmetry and vmHRV remained significant after including anxiety score as a covariate. No moderation effect of vmHRV was found for frontal sites and other frequency bands, as well as healthy subjects. These findings suggest that vmHRV moderates the association between parietal alpha asymmetry at low frequency band and depression for MDD patients. We suggest that the interaction between parietal alpha asymmetry and vmHRV may be a biomarker of MDD.

Self-Forgiveness Moderates the Effects of Depression on Suicidality.

OBJECTIVE: Not all depressive individuals are suicidal. An increasing body of studies has examined forgiveness, especially self-forgiveness, as a protective factor of suicide based on that suicide is often accompanied by negative self-perceptions. However, less has been studied on how different subtypes of forgiveness (i.e., forgiveness-of-self, forgiveness-of-others and forgiveness-of-situations) could alleviate the effects of depression on suicide. Hence, this study examined forgiveness as a moderator of depression and suicidality. METHODS: 305 participants, consisted of 87 males and 218 females, were included in the study. The mean age was 41.05 (SD: 14.48; range: 19-80). Depression, anxiety, and forgiveness were measured through self-report questionnaires, and suicidal risk was measured through a structuralized interview. Moderations were examined through hierarchical regression analyses. RESULTS: Depression positively correlated with suicidality. RESULTS: of the hierarchical regression analysis indicated forgiveness as a moderator of depression on suicidality. Further analysis indicated only forgiveness-of-self as a significant moderator; the effects of forgiveness-of-others and forgiveness-of-situation were not significant. CONCLUSION: These findings suggest that forgiveness-of-self is essential in reducing of the effects of depression on suicidality. It is suggested that self-acceptance and the promotion of self-forgiveness should be considered as an important factor when developing suicide prevention strategies.

Screening Tool for Anxiety Disorders: Development and Validation of the Korean Anxiety Screening Assessment.

OBJECTIVE: This study evaluated the psychometric properties of the Korean Anxiety Screening Assessment (K-ANX) developed for screening anxiety disorders. METHODS: Data from 613 participants were analyzed. The K-ANX was evaluated for reliability using Cronbach's alpha, item-total correlation, and test information curve, and for validity using focus group interviews, factor analysis, correlational analysis, and item characteristics based on item response theory (IRT). The diagnostic sensitivity and specificity of the K-ANX were compared with those of the Beck Anxiety Inventory (BAI) and Generalized Anxiety Disorder 7-item scale (GAD-7). RESULTS: The K-ANX showed excellent internal consistency (α=0.97) and item-total coefficients (0.92-0.97), and a one-factor structure was suggested. All items were highly correlated with the total scores of the BAI, GAD-7, and Penn State Worry Questionnaire. IRT analysis indicated the K-ANX was most informative as a screening tool for anxiety disorders at the range between 0.8 and 1.6 (i.e., top 21.2 to 5.5 percentiles). Higher sensitivity (0.795) and specificity (0.937) for identifying anxiety disorders were observed in the K-ANX compared to the BAI and GAD-7. CONCLUSION: The K-ANX is a reliable and valid measure to screen anxiety disorders in a Korean sample, with greater sensitivity and specificity than current measures of anxiety symptoms.

ERP investigation of attentional disengagement from suicide-relevant information in patients with major depressive disorder.

BACKGROUND: Previous studies suggest the presence of attentional bias towards suicide-relevant information in suicidal individuals. However, the findings are limited by their reliance on behavioral measures. This study investigates the role of difficulty in disengaging attention from suicide-relevant stimuli using the P300 component of event-related potentials (ERPs). METHODS: Forty-four adults with Major Depressive Disorder (MDD) were administered the spatial cueing task using suicide-relevant and negatively-valenced words as cue stimuli. Disengagement difficulty was measured using reaction time and P300 during invalid trials. RESULTS: P300 amplitudes at Pz were higher in suicide-relevant compared to negatively-valenced word condition on invalid trials for participants with low rates of suicidal behavior. However, no such difference was found among participants with high rates of suicidal behavior. P300 amplitudes for suicide-relevant word condition were negatively correlated with "lifetime suicide ideation and attempt" at Pz. No significant results were found for the reaction time data, indicating that the ERP may be more sensitive in capturing the attentional disengagement effect. LIMITATIONS: The groups were divided according to Suicidal Behaviors Questionnaire-Revised (SBQ-R) total score. Neutral stimulus was not included as cue stimuli. Most participants were under medication during the experiment. CONCLUSIONS: Our results indicate that patients with MDD and low rates of suicidal behavior show difficulty in disengaging attention from suicide-relevant stimuli. We suggest that suicide-specific disengagement difficulties may be related to recentness of suicide attempt and that acquired capability for suicide may contribute to reduced disengagement difficulties.

The Influence of Traditional Culture and the Interpersonal Psychological Theory on Suicide Research in Korea.

Korea has the highest suicide rate amongst the OECD countries. Yet, its research on suicidal behaviors has been primitive. While the Interpersonal Psychological Theory of Suicide has gained global attention, there has only been a few researches, which examined its applicability in Korea. In this article, we review the previous studies on suicide and examine the association between the Interpersonal Psychological Theory of Suicide and traditional Korean culture, with an emphasis on Collectivism and Confucianism. We propose that pathways to suicide might vary depending on cultural influences. Clinical implications and suggestions for future research will be discussed.