Sex Differences in COVID-19 Infection Fear in a Community Sample of Korean Adults Using Quantile Regression.

This study aims to explore the impact of distributional changes in coronavirus disease 2019 (COVID-19) infection fear with sex differences. A quota sampling strategy was followed and 483 Korean adults were surveyed in a community sample. Self-report questionnaires were used to assess COVID-19 infection fear, depressive symptoms, and general characteristics. Quantile regression was used to explore the regression relationship of COVID-19 infection fear and an individual's sex. There was a significant difference in COVID-19 infection fear (P = 0.001) and depression (P = 0.008) between the sexes - male and female. The differences between sexes at the 20th and 30th percentiles were significant (ß = 2.04, P = 0.006; ß = 1.5, P = 0.004, respectively). The results demonstrate that sex significantly predicts COVID-19 infection fear and women had significantly greater fear than men in the mild-level of COVID-19 infection fear.

The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP): Changes in preferred treatment strategies and medications over 16 years and five editions.

OBJECTIVES: The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) is based on expert consensus and has been revised five times since 2002. This study evaluated the changes in treatment strategies advocated by the KMAP-BP over time. METHODS: The five editions of the KMAP-BP were reviewed, and the recommendations of the KMAP-BP were compared with those of other bipolar disorder (BP) treatment guidelines. RESULTS: The most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP). Either MS or AAP monotherapy was also considered a first-line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. In general, although lithium and valproic acid were commonly recommended, valproic acid has been increasingly preferred for all phases of BP. The most notable changes over time included the increasing preference for AAPs for all phases of BP, and lamotrigine for the depressive and maintenance phases. The use of antidepressants for BP has gradually decreased, but still represents a first-line option for severe and psychotic depression. CONCLUSIONS: In general, the recommended strategies of the KMAP-BP were similar to those of other guidelines, but differed in terms of the emphasis on rapid effectiveness, which is often desirable in actual clinical situations. The major limitation of the KMAP-BP is that it is a consensus-based rather than an evidence-based tool. Nevertheless, it may confer advantages in actual clinical practice.

The Brain-Gut-Microbiome Axis in Psychiatry.

Beginning with the concept of the brain-gut axis, the importance of the interaction between the brain and the gastrointestinal tract has been extended to the microbiome with increasing clinical applications. With the recent development of various techniques for microbiome analysis, the number of relevant preclinical and clinical studies on animals and human subjects has rapidly increased. Various psychotic symptoms affect the intestinal microbiome through the hypothalamus-pituitary-adrenal gland axis. Conversely, the intestinal microbiome regulates the gastrointestinal tract environment and affects psychological factors by means of the microorganisms or their metabolites, either acting directly on the brain or through the synthesis of various neurotransmitters. This review discusses the clinical applicability of the brain-gut-microbiome axis and directions for improving psychological symptoms based on the studies published to date.

Clinical Evidence of Antidepressant Effects of Insulin and Anti-Hyperglycemic Agents and Implications for the Pathophysiology of Depression-A Literature Review.

Close connections between depression and type 2 diabetes (T2DM) have been suggested by many epidemiological and experimental studies. Disturbances in insulin sensitivity due to the disruption of various molecular pathways cause insulin resistance, which underpins many metabolic disorders, including diabetes, as well as depression. Several anti-hyperglycemic agents have demonstrated antidepressant properties in clinical trials, probably due to their action on brain targets based on the shared pathophysiology of depression and T2DM. In this article, we review reports of clinical trials examining the antidepressant effect of these medications, including insulin, metformin, glucagon like peptide-1 receptor agonists (GLP-1RA), and peroxisome proliferator-activated receptor (PPAR)-γ agonists, and briefly consider possible molecular mechanisms underlying the associations between amelioration of insulin resistance and improvement of depressive symptoms. In doing so, we intend to suggest an integrative perspective for understanding the pathophysiology of depression.

Effects of Early Life Stress on Epigenetic Changes of the Glucocorticoid Receptor 17 Promoter during Adulthood.

Growing evidence suggests that early life stress (ELS) has long-lasting effects on glucocorticoid receptor (GR) expression and behavior via epigenetic changes of the GR exon 17 promoter. However, it remains unclear whether ELS regulates histone modifications of the GR exon 17 promoter across the life span. We investigated the effects of maternal separation (MS) on histone acetylation and methylation of GR exon 17 promoter in the hippocampus, according to the age of adults. Depression-like behavior and epigenetic regulation of GR expression were examined at young and middle adulthood in mice subjected to MS from postnatal day 1 to 21. In the forced swimming test, young adult MS mice showed no effect on immobility time, but middle-aged MS mice significantly increased immobility time. Young adult and middle-aged MS mice showed decreased GR expression. Their two ages showed decreased histone acetylation with increased histone deacetylases (HDAC5) levels, decreased permissive methylation, and increased repressive methylation at the GR exon 17 promoter. The extent of changes in gene expression and histone modification in middle adulthood was greater than in young adulthood. These results indicate that MS in early life causes long-term negative effects on behavior via histone modification of the GR gene across the life span.

Ginkgo biloba induced mood dysregulation: a case report.

BACKGROUND: Impairment of cognitive function as well as negative symptom is the major factor causing the decline of a patient's functioning in chronic stages of schizophrenia. However, until now, there were no definite treatment options that could effectively reduce the impairment. CASE PRESENTATION: We report a case of mood dysregulation associated with use of Ginkgo biloba in a patient with schizophrenia. After Ginkgo biloba was given, the patient experienced cluster symptoms of mood dysregulation including irritability, difficulty in controlling anger, agitation and restlessness. We estimated the possibility as "probable" according to Naranjo scale considering circumstantial evidence. CONCLUSIONS: This case suggests that Ginkgo biloba may have caused mood dysregulation in this patient. Although it is generally accepted as safe, more attention should be given to the adverse effect when treating with Ginkgo biloba.

Antidepressants and Mood Stabilizers: Novel Research Avenues and Clinical Insights for Bipolar Depression.

The concept of the bipolar-spectrum and of mixed features being a bridge between major depressive disorders and bipolar disorders (BDs) has become increasingly important in mood-disorder diagnoses. Under these circumstances, antidepressants (ADs) and mood stabilizers (MSs) should be used with caution in the treatment of major depressive episodes (MDEs) and to obtain long-term stability in BDs. Before treating MDEs, screening tools, specific symptom evaluation and medical history should be used to distinguish between bipolarity and mixed features in patients for whom AD monotherapy may present a risk. In these patients, a combination of ADs plus MSs or atypical antipsychotics is recommended, rather than AD monotherapy. Studies evaluating MSs for bipolar depression suggest that lamotrigine is the most reliable treatment and lithium has modest effects; there is a lack of clear evidence regarding the efficacy of valproate and carbamazepine. Recently, significant progress has been made with respect to the pathophysiology of mood disorders and the application of potential biomarkers. There is an opportunity to study novel drug mechanisms through the rediscovery of fast-acting drugs such as ketamine. It is anticipated that future research developments will involve the discovery of potential targets for new drugs and their application to personalized treatments.

Anxiety or agitation in mood disorder with mixed features: A review with a focus on validity as a dimensional criterion.

BACKGROUND: The diagnostic validity of mixed features, excluding anxiety or psychomotor agitation in mood disorders, has not yet been fully examined. METHOD: PubMed and relevant English-language literature (regardless of year) were searched. Keywords were mixed or mixed state or mixed features or mixed episode and anxious or anxiety or agitation and bipolar disorder or depressive disorder or mood disorder or affective disorder. RESULTS: Most studies on anxiety or psychomotor agitation have included a significant correlation relevant to the "with mixed features" specifier, although it is common in both poles of mood episodes regardless of the predominant polarity. There is some confusion between the characteristic of classical mixed states and the definition of the mixed features specifier with the newly added anxious distress specifier in DSM-5, specifically, whether to include anxiety and agitation as significant characteristics. This change is of concern because a large proportion of patients with mixed features are now unspecified, and this may influence treatment planning and prognosis. CONCLUSIONS: The findings of our review suggest that anxiety and psychomotor agitation can be core symptoms in mood episodes with mixed features and important clinical clues for prediction of treatment effects and disease course.

Clinical assessment of bipolar depression: validity, factor structure and psychometric properties of the Korean version of the Bipolar Depression Rating Scale (BDRS).

BACKGROUND: The Bipolar Depression Rating Scale (BDRS) is a scale for assessment of the clinical characteristics of bipolar depression. The primary aims of this study were to describe the development of the Korean version of the BDRS (K-BDRS) and to establish more firmly its psychometric properties in terms of reliability and validity. METHODS: The study included 141 patients (62 male and 79 female) who had been diagnosed with bipolar disorder, were currently experiencing symptoms of depression, and were interviewed using the K-BDRS. Other measures included the Montgomery and Asberg Depression Scale (MADRS), the 17-item Hamilton Depression Scale (HAMD), and the Young Mania Rating Scale (YMRS). Additionally, the internal consistency, concurrent validity, inter-rater reliability, and test-retest reliability of the K-BDRS were evaluated. RESULTS: The Cronbach's α-coefficient for the K-BDRS was 0.866, the K-BDRS exhibited strong correlations with the HAMD (r = 0.788) and MADRS (r = 0.877), and the mixed symptoms score of the K-BDRS was significantly correlated with the YMRS (r = 0.611). An exploratory factor analysis revealed three factors that corresponded to psychological depressive symptoms, somatic depressive symptoms, and mixed symptoms. CONCLUSIONS: The present findings suggest that the K-BDRS has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in patients with bipolar disorder.

Current prescription pattern of maintenance treatments for bipolar patients in Korea: A focus on the transition from acute treatments.

AIMS: We examined prescription patterns in maintenance treatment for recovered bipolar patients and compared these with acute treatments. METHODS: Using retrospective methods, the bipolar patients in clinical recovery (Clinical Global Impression Bipolar Version score ≤ 2 for 6 months) after acute episode were selected. We reviewed differences between prescription patterns at remission and after a maintenance period of at least 6 months. RESULTS: A total of 340 bipolar disorder patients were selected. During the maintenance period, more than half of the patients (192, 56.5%) took a mood stabilizer (MS) + antipsychotic (AP) combination. Among the MS, valproate (149, 43.8%) was most prescribed, and lithium (98, 28.8%) was second, but as patients moved into maintenance treatment, lithium use decreased, and the use of lamotrigine (86, 25.3%) increased. Preferred AP were quetiapine (125, 36.8%), aripiprazole (67, 19.7%), risperidone (48, 14.1%), and olanzapine (39, 11.5%). The use of olanzapine in maintenance was greatly decreased compared with that during acute treatment (67, 19.7%). Most patients did not take an antidepressant (AD), but the proportion using one or more AD was increased during maintenance (17.9% to 30.3%), and bupropion (28, 8.2%) was the preferred AD. Doses were decreased in all drugs, but lamotrigine was maintained at a dose of 133.2 ± 68.5 mg/day. CONCLUSIONS: The most common prescription combination for bipolar maintenance treatment was MS + AP. The use of AP was decreased, whereas the use of AD in combination with MS and/or AP was increased. The doses of MS and AP were generally decreased during the maintenance periods, with the exception of lamotrigine.

Obesity and Its Potential Effects on Antidepressant Treatment Outcomes in Patients with Depressive Disorders: A Literature Review.

Accumulating evidence regarding clinical, neurobiological, genetic, and environmental factors suggests a bidirectional link between obesity and depressive disorders. Although a few studies have investigated the link between obesity/excess body weight and the response to antidepressants in depressive disorders, the effect of weight on treatment response remains poorly understood. In this review, we summarized recent data regarding the relationship between the response to antidepressants and obesity/excess body weight in clinical studies of patients with depressive disorders. Although several studies indicated an association between obesity/excess body weight and poor antidepressant responses, it is difficult to draw definitive conclusions due to the variability of subject composition and methodological differences among studies. Especially, differences in sex, age and menopausal status, depressive symptom subtypes, and antidepressants administered may have caused inconsistencies in the results among studies. The relationship between obesity/excess body weight and antidepressant responses should be investigated further in high-powered studies addressing the differential effects on subject characteristics and treatment. Moreover, future research should focus on the roles of mediating factors, such as inflammatory markers and neurocognitive performance, which may alter the antidepressant treatment outcome in patients with comorbid obesity and depressive disorder.

Can Atypical Antipsychotic Augmentation Reduce Subsequent Treatment Failure More Effectively Among Depressed Patients with a Higher Degree of Treatment Resistance? A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Atypical antipsychotic augmentation was demonstrated to be efficacious in treatment-resistant depression (TRD) in previous meta-analyses. We investigate whether there are differences in the effect size of atypical antipsychotic augmentation in major depressive disorder according to the degree of treatment resistance. METHODS: A comprehensive search of four databases identified 11 randomized controlled trials. The 11 trials, which included 3 341 participants, were pooled using a random-effects meta-analysis. RESULTS: Atypical antipsychotic augmentation of antidepressant therapy showed superior efficacy compared to antidepressant monotherapy in TRD in terms of both response and remission rates (response, risk ratio [RR] = 1.38, 95% confidence interval [CI] = 1.25 to 1.53; remission, RR = 1.62, 95% CI = 1.42 to 1.85). In addition, regarding response rates in the TRD trials, atypical antipsychotic augmentation exhibited significantly different effect sizes according to the degree of treatment resistance (TRD 1: RR = 1.24; TRD 2: RR = 1.37; TRD 2-4: RR = 1.58). In non-TRD trials, atypical antipsychotic augmentation failed to show superior efficacy over antidepressant monotherapy in terms of remission rates (RR = 0.89; 95% CI = 0.69 to 1.14). Atypical antipsychotic augmentation of antidepressant therapy exhibits greater effect size in patients with a higher degree of treatment resistance. CONCLUSIONS: This finding strengthens the rationale for considering atypical antipsychotic augmentation among depressed patients with multiple previous treatment failures in clinical practice. The efficacy of atypical antipsychotic augmentation for non-TRD seems to be different from that for TRD and, thus, further studies of non-TRD populations are needed.

THE VALIDITY OF THE MOOD DISORDER QUESTIONNAIRE FOR SCREENING BIPOLAR DISORDER: A META-ANALYSIS.

We conducted a meta-analysis to review the diagnostic accuracy of the Mood Disorder Questionnaire (MDQ) among patients with mood disorders. We used a bivariate random effects model to calculate summary sensitivity and specificity. Twenty-one studies were included. At the standard or modified cutoff value of 7, summary sensitivity was .62 and summary specificity was .85. When we pooled 11 studies including both patients with bipolar disorder (BD) and those with unipolar depression, the summary sensitivity was .76 and summary specificity was .81. However, among the six studies that excluded patients with known BD, the summary sensitivity was significantly reduced to .37 and summary specificity was .88. There were no significant differences on the diagnostic accuracy of the MDQ between studies from Eastern and Western countries after adjusting for various clinical correlates. The overall diagnostic accuracy of the MDQ was relatively good. However, when the MDQ is applied among patients with depression without previous diagnoses of BD, its sensitivity was significantly reduced. This suggests that when the MDQ is applied among this population, its optimal cutoff value should be adjusted to enhance its sensitivity.

Does mirtazapine interfere with naturalistic diabetes treatment?

Mirtazapine is known to induce weight gain and possibly leads to exacerbation of diabetic profiles. However, many cases of diabetic patients, who complained of insomnia and depression, were treated with mirtazapine in the clinical situations. Thus, this study aimed to assess any negative effects that treatment with mirtazapine may incur in diabetic patients.This study included 33 patients enrolled in naturalistic diabetes treatment that had also been diagnosed with depression and prescribed mirtazapine for at least 6 months. Another 33 diabetic patients who had not taken any psychiatric medicines were included as a control group. Body mass index, fasting plasma glucose, HbA1c, total cholesterol, triglyceride levels, high-density lipoprotein, and low-density lipoprotein were assessed at baseline, 3 months, and 6 months.The dose of mirtazapine at baseline was 24.3 ± 14.0 mg/d in the mirtazapine group, and the 2 groups did not differ in any baseline characteristics except for total cholesterol levels. Body mass index increased in both groups, and the change in the mirtazapine group (1.0 ± 0.6 kg/m) was significantly greater than that in the control group (0.3 ± 0.4 kg/m, P < 0.001) at 6 months. Only the control group exhibited a decrease in fasting plasma glucose, whereas both groups showed a decrease in HbA1c, low-density lipoprotein, and total cholesterol, an increase in high-density lipoprotein, and no change in triglyceride levels. None of the differences between the groups were statistically significant.In conclusion, mirtazapine increased the weight gain of diabetic patients; however, other diabetic and lipid markers generally did not worsen during the 6-month treatment period. These results suggest that, at least in the short term, mirtazapine is safe for diabetic patients in a stable state and are undergoing appropriate diabetic treatment.

Anticonvulsants to treat post-traumatic stress disorder.

OBJECTIVE: We reviewed the existing literature on the efficacy of anticonvulsants in treating post-traumatic stress disorder. METHODS: We performed a literature search using PubMed, EMBASE and the Cochrane database on 30 September 2013. Randomized,controlled studies that investigated the efficacy of anticonvulsants for post-traumatic stress disorder were included in this review. Studies with retrospective designs, case reports and case series were excluded. RESULTS: A total of seven studies met the inclusion criteria for this review. Three studies used topiramate with negative findings regarding its efficacy. Two studies used divalproex, both of which failed to show superiority over placebo. One study used lamotrigine, with favourable results, and one study used tiagabine, with negative results. CONCLUSIONS: Future long-term studies with larger sample sizes are needed to investigate the clinical utility of anticonvulsants for posttraumatic stress disorder treatment.

The potential role of atypical antipsychotics in the treatment of panic disorder.

OBJECTIVE: Many studies have investigated the efficacy and tolerability of alternative pharmacotherapy for panic disorder. This study aims to provide a comprehensive review of the existing literature regarding the efficacy and tolerability of atypical antipsychotics for panic disorder. METHODS: We searched for relevant published articles using Medline, the Cochrane database, and EMBASE on 19 June 2013. Prospective studies that examined the efficacy and tolerability of atypical antipsychotics in the treatment of primary panic disorder or comorbid panic disorder (or symptoms) in other psychiatric disorders were included in this review. RESULTS: Seven prospective studies were included in this review. Among these, four were open-label studies for refractory panic disorder. Two of the seven included studies were randomized controlled trials among patients with panic symptoms comorbid with bipolar disorder. The remaining study was a randomized controlled trial for panic disorder or panic attack comorbid with major depression. Except one negative risperidone study, the reviewed studies showed the favorable efficacy results of atypical antipsychotics. CONCLUSIONS: Although the majority of the evidence regarding the efficacy of atypical antipsychotics in the treatment of panic disorder comes from small, open-label studies, this review suggests the potential role of atypical antipsychotics in treating panic disorder.

Potential role of anticonvulsants in the treatment of obsessive-compulsive and related disorders.

We reviewed the extant literature to evaluate the current evidence regarding the efficacy and safety of anticonvulsants in the treatment of obsessive-compulsive and related disorders. Relevant literature was accessed using the Cochrane database, embase and PubMed on 29 October 2013. Prospective studies examining the efficacy of anticonvulsants in obsessive-compulsive and related disorders were included. Case reports, case series, and retrospective studies were excluded. A total of 10 studies were included in this review. The studies of obsessive-compulsive disorder, except for two negative studies, showed favorable efficacy results of anticonvulsants. In one study on body dysmorphic disorder, levetiracetam showed favorable efficacy. In two lamotrigine studies for pathologic skin-picking, the efficacy findings were inconsistent. In one trichotillomania study, topiramate had reduced hair-pulling symptoms. Despite limited evidence, our review suggests that anticonvulsants have a potential role in the treatment of obsessive-compulsive and related disorders.

One-year rehospitalization rates of patients with first-episode bipolar mania receiving lithium or valproate and adjunctive atypical antipsychotics.

AIM: We compared the 1-year rehospitalization rates of first-episode bipolar manic patients who were discharged while being treated with lithium or valproate in combination with an atypical antipsychotic. METHODS: We investigated the rehospitalization status of first-episode bipolar manic patients who were discharged between 1 January 2003 and 31 December 2010 while they were taking lithium or valproate in combination with aripiprazole, olanzapine, quetiapine, or risperidone. Rehospitalization rates during a 1-year period after discharge were compared between the group receiving lithium plus an atypical antipsychotic and the group receiving valproate plus an atypical antipsychotic using the Kaplan-Meier method. A Cox regression model was used to analyze covariates hypothesized to affect time to rehospitalization. RESULTS: The rehospitalization rate was 17.3% during the 1-year follow-up period. We found significant differences in the rehospitalization rates of patients in the lithium (23.1%) and the valproate (13.3%) groups using the Kaplan-Meier formula. According to Cox proportional hazards regression analysis, higher Clinical Global Impression-Bipolar Version-Severity score at discharge (P = 0.005) and lithium treatment (P = 0.055) contributed to the risk of rehospitalization. CONCLUSION: Treatment with valproate and an atypical antipsychotic can be more effective than treatment with lithium and an atypical antipsychotic in preventing rehospitalization during the 1 year after hospitalization due to a first manic episode in patients with bipolar I disorder. Higher Clinical Global Impression-Bipolar Version-Severity scores at discharge also negatively affected rehospitalization rates.

Defining "High Recurrence" of Depressive Episodes for Predicting Diagnostic Conversion from Major Depressive Disorder to Bipolar Disorder: A 5-year Retrospective Study.

Objective: This study determined the threshold for recurrent depressive episodes that predicted conversion from major depressive disorder (MDD) to bipolar disorder (BD). Methods: We retrospectively reviewed the medical records of 296 patients diagnosed with MDD for a minimum of 5 years in two university hospitals. We examined their the Diagnostic and Statistical Manual of Mental Disorders, 5th edition diagnoses and detailed clinical information at the initial admission and yearly assessments after discharge to establish the threshold for recurrent depressive episodes indicating a risk of diagnostic conversion from MDD to BD. Optimal cut-offs were derived using receiver operating characteristic (ROC) curves. Results: ROC curve analysis revealed that more than four recurrent depressive episodes was indicative of potential diagnostic conversion from MDD to BD (area under the curve, 0.604; sensitivity, 0.353; specificity, 0.855; positive predictive value, 0.421; negative predictive value, 0.816). Conclusion: These findings suggest that the best predictor of conversion from MDD to BD is more than four recurrent depressive episodes. Our findings have the potential to enhance diagnostic accuracy and treatment efficiency. To validate our results, longitudinal prospective studies are necessary.

Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials.

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials [DB-RCTs]) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over six months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.