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Background Insomnia is a common disorder that affects a vast number of patients; the hyperarousal theory of insomnia postulates that patients with insomnia are physiologically activated not only at nighttime but also during the daytime. We aimed to investigate the differences in the resting-state functional connectivity (RSFC) of the thalamus with cortical areas between patients with insomnia disorder and healthy controls. Methods All participants completed clinical questionnaires and underwent portable polysomnography and resting-state fMRI. Results Patients in the insomnia group (n = 50) showed increased RSFC between the thalamus and right medial superior frontal area, bilateral middle temporal areas, left rectus and right parahippocampal areas compared with controls (n = 42) after controlling for age, sex and education level. Among the pairs that showed increased connectivity, several functional connections were negatively correlated with sleep efficiency, measured by polysomnography.Limitations: We used a small sample size. Conclusion We consider these results on increased thalamocortical hyperactivity in brain areas related to sensory functions as providing evidence for the hyperarousal theory of insomnia.

Objective Patients with breathing-related sleep disorder (BRSD) often complain of psychiatric symptoms such as depression in addition to snoring, excessive sleepiness, and disturbed sleep. However, the relationship between psychiatric symptoms and severity of sleep apnea in BRSD is controversial. We conducted this study to investigate the relationship between psychiatric symptoms and sleep electroencephalography (EEG) findings in BRSD patients using spectral analysis. Methods All participants underwent polysomnography and evaluation using Symptom Checklist-90-Revised (SCL-90-R) scale. We analyzed the absolute spectral power density values of standard EEG frequency bands in the participants (n = 169) with BRSD during the non-rapid eye movement (NREM) sleep period. We performed correlation analysis between the domain scores of SCL-90-R scale and the absolute values of the EEG frequency bands. Results Significant positive correlation was observed between the absolute spectral power density values in the slow oscillation band and the degree of paranoid ideation (r = 0.226, p = 0.028) and depression (r = 0.216, p = 0.044) in SCL-90-R. The multiple linear regression model showed that higher paranoid ideation domain score (B = 0.007, p = 0.020), younger age (B = -0.011, p < 0.001), and female sex (B = 0.213, p = 0.004) were associated with higher slow oscillation power during NREM sleep. Conclusion The results of the present study suggested a relationship between sleep EEG and psychiatric symptoms in patients with BRSD. This relationship needs to be validated with further studies.

Objective The response to antipsychotics in patients with schizophrenia is still unsatisfactory. Therefore, augmentation with other antipsychotics is common in clinical situations. The purpose of this study was to evaluate the improvement of psychiatric symptoms and side effects after amisulpride add-on therapy. Methods Forty patients with schizophrenia or schizoaffective disorder without treatment response to second-generation antipsychotics were included in this study. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Korean version of Calgary Depression Scale for Schizophrenia (CDSS) at baseline, 4 weeks, and 8 weeks after the addition of amisulpride. Results Among the 29 subjects who completed the 8-week study, 34.5% were responders according to PANSS total score. At week 8, the mean positive (p < 0.001), negative (p < 0.001), general (p < 0.001), and total (p < 0.001) PANSS scores and CDSS scores (p = 0.002) showed significant improvement compared to baseline. There was no increase in extrapyramidal side effects according to Simpson Angus Scale (p = 0.379) and Barnes Akathisia Rating Scale (p = 0.070) and no weight gain (p = 0.308) after the add-on treatment. Conclusion The addition of amisulpride for schizophrenia patients without therapeutic response to second-generation antipsychotics is considered an effective and safe treatment. This study's results suggested that augmentation of second-generation antipsychotics with amisulpride could be a useful option for patients with schizophrenia unresponsive to second-generation antipsychotics. Further studies investigating the efficacy of amisulpride add-on therapy using placebo control are necessary to confirm these results.

Subjective–objective discrepancy of sleep (SODS) might be related to the distorted perception of sleep deficit and hypersensitivity to insomnia-related stimuli. We investigated differences in brain activation to insomnia-related stimuli among insomnia patients with SODS (SODS group), insomnia patients without SODS (NOSODS group), and healthy controls (HC). Participants were evaluated for subjective and objective sleep using sleep diary and polysomnography. Functional magnetic resonance imaging was conducted during the presentation of insomnia-related (Ins), general anxiety-inducing (Gen), and neutral (Neu) stimuli. Brain reactivity to the contrast of Ins vs. Neu and Gen vs. Neu was compared among the SODS (n = 13), NOSODS (n = 15), and HC (n = 16) groups. In the SODS group compared to other groups, brain areas including the left fusiform, bilateral precuneus, right superior frontal gyrus, genu of corpus callosum, and bilateral anterior corona radiata showed significantly increased blood oxygen level dependent (BOLD) signal in the contrast of Ins vs. Neu. There was no brain region with significantly increased BOLD signal in the Gen vs. Neu contrast in the group comparisons. Increased brain activity to insomnia-related stimuli in several brain regions of the SODS group is likely due to these individuals being more sensitive to sleep-related threat and negative cognitive distortion toward insomnia.

Background Suicide is a serious social and public health problem. Social stigma and prejudice reduce the accessibility of mental health care services for high-risk groups, resulting in them not receiving interventions and committing suicide. A suicide prediction model is necessary to identify high-risk groups in the general population. Methods We used national medical check-up data from 2009 to 2015 in Korea. The latest medical check-up data for each subject was set as an index point. Analysis was undertaken for an overall follow-up period (index point to the final tracking period) as well as for a one-year follow-up period. The training set was cross-validated fivefold. The predictive model was trained using a random forest algorithm, and its performance was measured using a separate test set not included in the training. Results The analysis covered 372,813 individuals, with an average (SD) overall follow-up duration of 1.52 (1.52) years. When we predicted suicide during the overall follow-up period, the area under the receiver operating characteristic curve (AUC) was 0.849, sensitivity was 0.817, and specificity was 0.754. The performance of the predicted suicide risk model for one year from the index point was AUC 0.818, sensitivity 0.788, and specificity 0.657. Conclusions This is probably the first suicide predictive model using machine learning based on medical check-up data from the general population. It could be used to screen high-risk suicidal groups from the population through routine medical check-ups. Future studies may test preventive interventions such as exercise and alcohol in these high-risk groups.

Purpose: This study aimed to review the history and examine the current service system of the Korea Counseling Center for Fertility and Depression (KCCFD) by analyzing the characteristics of its users, and to suggest measures to improve the system.Methods: Data on 883 infertile patients counseled through the KCCFD’s counseling service over the last 2 years were collected for a demographic analysis. The clinical information of 396 female subjects who received regular counseling after registration were analyzed to investigate factors influencing depression. Finally, a matching sample t-test was conducted to verify the effects of the counseling service.Results: The screening test showed that 50.7% of the infertile patients in our study were registered at our centers and received registered counseling. A total of 27.6% of the subjects was identified as being at high-risk for depression, and 71.3% of those at high-risk received registered counseling. The logistic regression analysis showed that being a homemaker, having a history of psychiatric disorder, and having undergone in vitro fertilization three or more times were significant factors that predict moderate or more severe depression. The female infertility patients who underwent counseling showed a significant decrease in depression, anxiety, general stress, and infertility stress.Conclusion: Screening tests need to be performed prior to assisted reproductive technology if any of the 3 risk factors is present. The rate of registered counseling, regular follow-up using psychological tests, and cross-linkages with affiliated agencies should serve as the metrics for the quality control of the counseling service. Early detection of individuals at high-risk for depression calls for an activated liaison among affiliated agencies and expanded regional centers.

The habenula (Hb) has been hypothesized to play an essential role in major depressive disorder (MDD) as it is considered to be an important node between fronto-limbic areas and midbrain monoaminergic structures based on animal studies. In this study, we aimed to investigate the differences in volume and T1 value of the Hb between patients with MDD and healthy control (HC) subjects. Analysis for the Hb volumes was performed using high-resolution 7-T magnetic resonance (MR) image data from 33 MDD patients and 36 healthy subjects. Two researchers blinded to the clinical data manually delineated the habenular nuclei and Hb volume, and T1 values were calculated based on overlapping voxels. We compared the Hb volume and T1 value between the MDD and HC groups and compared the volume and T1 values between the left and right Hbs in each group. Compared to HC subjects, MDD patients had a smaller right Hb volume; however, there was no significant volume difference in the left Hb between groups. In the MDD group, the right Hb was smaller in volume and lower in T1 value than the left Hb. The present findings suggest a smaller right Hb volume and left-right asymmetry of Hb volume in MDD. Future high-resolution 7-T MR imaging studies with larger sample sizes will be needed to derive a more definitive conclusion.

Early detection of oppositional defiant behavior is warranted for timely intervention in children at risk. This study aimed to build a predictive model of persistent oppositional defiant behavior based on a machine learning algorithm.With nationwide cohort data collected from 2012 to 2017, a tree-based ensemble model, random forest, was exploited to build a predictive model for persistent oppositional defiant behavior. The persistent oppositional defiant behavior was defined by the presence of oppositional defiant behavior for all the five years. The area under the receiver operating characteristic curve (AUC), overall accuracy, sensitivity, specificity, and Matthew's correlation coefficients (MCC) were measured.Data of 1,323 children were used for building the machine learning-based predictive model. The baseline mean ± standard deviation month-age of the participants was 51.0 ± 1.2 months. The proportion of persistent oppositional defiant behavior was 0.98% (13/1323). In the hold-out test set, the overall accuracy, AUC, sensitivity, specificity, and MCC were 0.955, 0.982, 1.000, 0.954, and 0.417, respectively.Our study demonstrated that the machine learning-based approach is useful for predicting persistent oppositional defiant behavior in preschool-aged children.

Depression is a mental illness that causes significant disturbances in daily life. Depression is commonly associated with low mood, severe health problems, and substantial socioeconomic burden; hence, it is necessary to be able to detect depression earlier. We utilized the medical check-up cohort database of the National Health Insurance Sharing Service in Korea. We split the total dataset into training (70%) and test (30%) sets. Subsequently, five-fold cross validation was performed in the training set. The holdout test set was only used in the last step to evaluate the performance of the predictive model. Random forest algorithm was used for the predictive model. The analysis included 433,190 individuals who had a national medical check-up from 2009-2015, which included 10,824 (2.56%) patients in the depression group. The area under the receiver-operating curve was 0.849. Other performance metrics included a sensitivity of 0.737, specificity of 0.824, positive predictive value of 0.097, negative predictive value of 0.992, and accuracy of 0.780. Our predictive model could contribute to proactively reducing depression prevalence by administering interventions to prevent depression in patients receiving medical check-up. Future studies are needed to prospectively validate the predictability of this model.

The acute treatment duration for major depressive disorder (MDD) is 8 weeks or more. Treatment of patients with MDD without predictors of treatment response and future recurrence presents challenges and clinical problems to patients and physicians. Recently, many neuroimaging studies have been published on biomarkers for treatment response and recurrence of MDD using various methods such as brain volumetric magnetic resonance imaging (MRI), functional MRI (resting-state and affective tasks), diffusion tensor imaging, magnetic resonance spectroscopy, near-infrared spectroscopy, and molecular imaging (i.e., positron emission tomography and single photon emission computed tomography). The results have been inconsistent, and we hypothesize that this could be due to small sample size; different study design, including eligibility criteria; and differences in the imaging and analysis techniques. In the future, we suggest a more sophisticated research design, larger sample size, and a more comprehensive integration including genetics to establish biomarkers for the prediction of treatment response and recurrence of MDD.

Patients with simple snoring (SS) often complain of poor sleep quality despite a normal apnoea-hypopnoea index (AHI). We aimed to identify the difference in power spectral density of electroencephalography (EEG) between patients with SS and those with obstructive sleep apnoea (OSA). We compared the absolute power spectral density values of standard EEG frequency bands between the SS (n = 42) and OSA (n = 129) groups during the non-rapid eye movement (NREM) sleep period, after controlling for age and sex. We also analysed partial correlation between AHI and the absolute values of the EEG frequency bands. The absolute power spectral density values in the beta and delta bands were higher in the OSA group than in the SS group. AHI also positively correlated with beta power in the OSA group as well as in the combined group (OSA + SS). In conclusion, higher delta and beta power during NREM sleep were found in the OSA group than in the SS group, and beta power was correlated with AHI. These findings are microstructural characteristics of sleep-related breathing disorders.

Background Many studies have reported that selective serotonin reuptake inhibitors (SSRI) are associated with an increased risk of bleeding. Mirtazapine and bupropion, which commonly lack serotonin reuptake inhibition, have been recommended as alternatives for patients who are at risk for bleeding. However, the evidence for these recommendations is insufficient. Methods We conducted a systematic search, systematic review, and meta-analysis to investigate an evidence-based approach for the bleeding risks of mirtazapine and bupropion. From 1946 to May 2017, a total of 3981 studies were searched from PubMed, Embase, and the Cochrane Library. Among the studies, two independent reviewers selected studies per predefined eligibility criteria. Results A total of five meta-analyses were conducted. Patients taking mirtazapine were at a greater risk of gastrointestinal bleeding (OR = 1.17, 95% CI = 1.01–1.38) than those who did not take antidepressants. No differences were observed in the bleeding risk between mirtazapine and SSRI or between bupropion and SSRI. Limitations The number of studies included in the meta-analysis was small. Conclusion Our results suggest that it is premature to recommend mirtazapine and bupropion for patients who have a bleeding risk. More studies with larger sample sizes and longitudinal follow-ups are warranted.

Introduction Patients with insomnia frequently experience sleep/insomnia-related anxiety; this anxiety has been associated with hyperarousal. We investigated the underlying brain function changes in patients with insomnia during emotional task performance that induced sleep/insomnia-related anxiety. Methods Functional magnetic resonance imaging (fMRI) was performed during emotional task performance in healthy individuals and patients with insomnia who met the diagnostic criteria of insomnia disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and had chronic insomnia for more than 6 months. The participants underwent fMRI scanning during three types of emotional task performance—insomnia-anxiety task, reading sentences that cause insomnia-related anxiety; general-anxiety task, reading sentences that cause anxiety for everyone; and neutral task, reading neutral sentences that do not cause emotional anxiety. The images obtained from fMRI and blood oxygen level-dependent (BOLD) signal changes were compared between patients with insomnia and healthy controls. Interim analysis was performed with the data of 13 patients with insomnia and 9 controls. Results The brain activity in the left anterior cingulate was higher during insomnia-anxiety task performance than that during general-anxiety task performance in the insomnia group (voxel-wise uncorrected p < 0.05; cluster size, 100). In the insomnia group, the brain activity during insomnia-anxiety task performance was not lower in any brain area than that during general-anxiety task performance. Conclusion We show that patients with chronic insomnia experience sleep anxiety related with hyperarousal in the left anterior cingulate area. Additional subject recruitment and re-analysis are needed to confirm the findings of this interim analysis. Support This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03032431).

Background: Mental disorders play an important role both in clinical courses and recidivism among juvenile offenders. In view of the public health, prevalence of the mental disorders among the population is most fundamental element for planning strategy and establishing budget. Methods: A systematic search was conducted in the Embase, PubMed, PsycInfo, Web of Science, and Google scholar for studies reporting the prevalence rate of mental disorders in May 2018. Systematic review and meta-analysis was conducted to identify prevalence of mental disorders. Findings: A total 51,209 (32,616 boys and 8,393 girls) juvenile offenders from 90 studies in the 27 countries were included. The mean prevalence rate of any mental disorder was 0.791 (95% CI 0.786-0.796). The mean number of mental disorders per person was 2.1 in boys and 3.0 in girls. Boys (0.669 (95% CI 0.663-0.674)) had a higher prevalence rate than girls (0.530 (95% CI 0.515-0.546)). Depressive disorder (0.343 (95% CI 0.325-0.361)) vs 0.131 (95% CI 0.126-0.137)), bipolar disorder (0.374 (95% CI 0.349-0.399)) vs 0.163 (95% CI 0.157-0.170)), and posttraumatic stress disorder (0.243 (95% CI 0.225-0.261)) vs 0.083 (95% CI 0.781-0.882)), were more common in girls than in boys. The prevalence of psychotic disorder 0.060 (95% CI 0.056-0.064) was 30-fold higher than that in the general population. Interpretation: Mental disorders are substantially high among juvenile offenders. Active evaluation and intervention for the mental health are warranted particularly in offending girls. Funding: None. Declaration of Interest: We declare no competing interests.

Background: Magnesium (Mg2+), an endogenous N-methyl-D-aspartate receptor antagonist, has received increased attention recently because of its role in the pathophysiology of and treatment response in depression. However, whether Mg2+ level is decreased in depression is not firmly established. We aimed to conduct a systematic review and meta-analysis to help making consensus for the association between Mg2+ levels and depression.Methods: A systematic search was conducted in the electronic database resources PubMed and Embase. After a careful selection of relevant studies, a meta-analysis using the random effects model was conducted in each measuring source, such as serum, plasma, and cerebrospinal fluid (CSF).Results: A total of 18 studies were included in this study. Among 11 studies that measured Mg2+ in the serum, Mg2+ level was lower in patients with depression than in controls (weighted mean difference = −.088, 95% confidence interval = −.164 to −.012). In the sensitivity analysis by removin...

Background In contrast to the previous studies reporting that most suicides occur among people with mental disorders, recent studies have reported various rates of mental disorders in suicide in different geographical regions. We aimed to comprehensively investigate the factors influencing the variation in the prevalence of mental disorders reported among suicide victims. Method The authors searched Embase, Medline, Web of Science, and the Cochrane Library to identify psychological autopsy studies reporting the prevalence of any mental disorders among suicide victims. A meta-regression analysis was conducted to identify the potential effects of geographical regions, the year of publication, measurements of personality disorder, measurements of comorbidity, and the ratio of females on the prevalence of mental disorders in addition to examining the heterogeneity across studies. Results From 4475 potentially relevant studies, 48 studies met eligibility criteria, with 6626 suicide victims. The studies from East Asia had a significantly lower mean prevalence (69.6% [95% CI=56.8 to 80.0]) than those in North America (88.2% [95% CI=79.7–93.5]) and South Asia (90.4% [95% CI=71.8–97.2]). The prevalence of any mental disorder decreased according to the year of publication (coefficients=−0.0715, p Limitations Substantial heterogeneities were identified within all subgroup analyses. Conclusions The prevalence of mental disorders among suicide cases seemed relatively low in the East Asia region, and recently published studies tended to report a lower prevalence of mental disorders. The link between the risk factors and suicide in the absence of a mental disorder should be examined in different geographical and sociocultural contexts.

An increasing amount of evidence indicates that d-serine, a potent and selective endogenous coagonist of the N-methyl-d-aspartate receptor (NMDAR), is efficacious in the treatment of schizophrenia. Although the therapeutic efficacy of d-serine supplementation is based on the d-serine deficit and NMDAR hypofunction hypothesis, it has not been confirmed whether d-serine levels are decreased in patients with schizophrenia compared to healthy controls. We searched the following electronic databases: Embase, Ovid Medline, and the Cochrane Library. A total of 20 studies were included in our meta-analysis. Serum d-serine levels were significantly decreased in patients with schizophrenia (standardized mean difference (SMD)=-1.008, 95% CI=-1.827 to -0.190). In the meta-regression analysis, male gender was positively correlated with serum d-serine levels (coefficient=0.190, 95% CI=0.070 to 0.311). d-Serine therapy combined with antipsychotics significantly improved negative (SMD=-0.319, 95% CI=-0.576 to -0.061) and positive (SMD=-0.211, 95% CI=-0.413 to -0.009) symptoms in patients with schizophrenia. Our results suggest that decreased d-serine availability may justify combining d-serine therapy with antipsychotics in patients with schizophrenia. However, clinical methodological heterogeneity across studies should be considered a major limitation of this analysis.

The purpose of the present study was to examine the relationship between age and dopamine D(2) receptor availability in striatal subdivisions of young and middle-aged healthy subjects using high-resolution positron emission tomography (PET) with [(11)C]raclopride to better characterize the nature of age-related decrements in striatal D(2) receptor availability. Twenty-four healthy volunteers completed 3-Tesla magnetic resonance imaging and high-resolution [(11)C]raclopride PET scans. The analyses using linear and exponential models revealed that age had a significant negative correlation with D(2) receptor availability in the post-commissural putamen (postPU) and that D(2) receptor binding in the postPU decreased significantly more with age than in the ventral striatum, suggesting subregional differences in age-related changes in D(2) receptor binding. The postPU, which belongs to the sensorimotor striatum, may be particularly vulnerable to the effects of age in young and middle-aged subjects.

We examined the relationship between antipsychotic-associated mental side effects and dopamine D2 receptor occupancy in striatal subdivisions using high-resolution positron emission tomography with [11C]raclopride to better characterize the neurochemical mechanism underlying these adverse effects. Twenty-one patients with schizophrenia receiving stable doses of antipsychotics and 24 age- and sex-matched healthy controls completed 3-Tesla magnetic resonance imaging and high-resolution positron emission tomography scans with [11C]raclopride to measure D2 receptor binding potential (BP ND) in the striatum. The D2 receptor BP ND was obtained using a Logan plot, and receptor occupancy was calculated as the percentage reduction of receptor BP ND with drug treatment relative to baseline. The data obtained from age- and sex-matched healthy controls were used as an estimate of the patients' baseline, as previously proposed. Antipsychotic-associated mental side effects were measured with the Liverpool University Neuroleptic Side Effect Rating Scale. The whole striatal D2 receptor occupancy ranged from 54% to 95%. The analysis revealed that the Liverpool University Neuroleptic Side Effect Rating Scale score had significant positive associations with D2 occupancy in the precommissural dorsal caudate, postcommissural caudate, and ventral striatum. The results suggest that mental side effects of antipsychotics are associated with D2 receptor blockade in the associative and limbic subdivisions of the striatum, which are considered to play a crucial role in cognition and reward motivation.