Psychometric Properties of the Korean Version of Functioning Assessment Short Test in Bipolar Disorder.

Objective: The Functioning Assessment Short Test (FAST) is a relatively specific test for bipolar disorders designed to assess the main functioning problems experienced by patients. This brief instrument includes 24 items assessing impairment or disability in 6 domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. It has already been translated into standardized versions in several languages. The aim of this study is to measure the validity and reliability of the Korean version of FAST (K-FAST). Methods: A total of 209 bipolar disorder patients were recruited from 14 centers in Korea. K-FAST, Young Mania Rating Scale (YMRS), Bipolar Depression Rating Scale (BDRS), Global Assessment of Functioning (GAF) and the World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF) were administered, and psychometric analysis of the K-FAST was conducted. Results: The internal consistency (Cronbach's alpha) of the K-FAST was 0.95. Test-retest reliability analysis showed a strong correlation between the two measures assessed at a 1-week interval (ICC = 0.97; p < 0.001). The K-FAST exhibited significant correlations with GAF (r = -0.771), WHOQOL-BREF (r = -0.326), YMRS (r = 0.509) and BDRS (r = 0.598). A strong negative correlation with GAF pointed to a reasonable degree of concurrent validity. Although the exploratory factor analysis showed four factors, the confirmatory factor analysis of questionnaires had a good fit for a six factors model (CFI = 0.925; TLI = 0.912; RMSEA = 0.078). Conclusion: The K-FAST has good psychometric properties, good internal consistency, and can be applicable and acceptable to the Korean context.

Psychiatric comorbidities and quality of life in breast cancer patients undergoing radiation treatment: Risk and protective factors.

OBJECTIVE: The primary goal was to evaluate the prevalence of psychiatric comorbidities and changes in psychological distress levels among breast cancer patients receiving radiotherapy (RT). The secondary goal was to determine risk and protective factors for psychiatric comorbidities of these patients. METHODS: From June 2018 to November 2019, patients were recruited from the hospital, Department of Psychiatry. Patients completed baseline surveys after seeing their radiation oncologist and prior to the first treatment, which was scheduled to take place within 7 days (visit 1, baseline); visit 2 occurred within 7 days after RT completion, and visit 3 occurred at 6 weeks after RT completion. A total of 99 patients participated in the study at visit 1; 56 patients completed the study through visit 3. RESULTS: Although changes in psychiatric comorbidities and overall quality of life were observed in patients with breast cancer prior to, during, and after RT, the differences were not significant among visits. Patients diagnosed with psychiatric comorbidities after RT had exhibited risk factors at previous visits, including preexisting psychiatric comorbidities, functional deterioration, and more severe symptoms related to breast cancer. Based on the results, the psychological characteristics of optimism and resilience can be considered as protective factors for psychiatric comorbidities. CONCLUSIONS: The results suggest that early detection and follow-up of psychological distress and poor quality of life at the onset of RT are of paramount importance, and that psychosocial interventions to enhance protective factors (optimism and resilience) may be helpful.

Glucocorticoid Receptor Gene (NR3C1) Expression in the Pathogenesis of Depression in Cancer.

Background: This study aimed to compare the NR3C1 expression among cancer patients with major depressive disorder (cancer depression), cancer patients without major depressive disorder (cancer non-depression), and major depressive disorder patients without cancer (general depression), as a preliminary investigation of epigenetic changes in the glucocorticoid receptor gene. Methods: From May 2019 to November 2019, patients were recruited from the Department of Psychiatry, Cancer Center in Busan, Korea. For gene expression studies, primers were designed using the Primer3 web tool (http://frodo.wi.mit.edu/primer3), and amplification reactions were performed. Results: Expression levels of NR3C1 were lower in cancer depression and general depression than in cancer non-depression group. Given that we observed downregulation of the NR3C1 gene expression in depressive patients regardless of cancer status, it appears that methylation changes in NR3C1 may contribute to the pathophysiology of depression. Conclusion: The results of this study imply that the expression of NR3C1 may be decreased in major depressive disorder.

Differences in depressive and anxiety symptoms between cancer and noncancer patients with psychological distress.

BACKGROUND: Cancer patients are particularly vulnerable to psychological problems. The purpose of the present study was to compare differences in psychological difficulties, including depression and anxiety, between cancer patients and noncancer patients. This study assessed the differences in depressive and anxiety symptoms between patients with and without cancer. MATERIALS AND METHODS: Participants included 219 patients at The Cancer Center, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea, who reported depressive or anxiety symptoms between April 2014 and April 2016. Patients were categorized into cancer and noncancer groups based on medical histories showing a diagnosis of any type of cancer. The Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were used to evaluate psychological distress at each patient's first visit. Patients' charts were reviewed for clinical data, including BDI and BAI scores and duration of cancer treatment, and for demographic data such as age and sex. RESULTS: The results showed that patients in the cancer group experienced greater discomfort related to somatic symptoms; higher BDI subscale scores were related to work difficulties, insomnia, loss of appetite, somatic worries (fatigue), and loss of libido compared with patients in the noncancer group. The BAI subscale scores for fear of the worst happening, feeling unsteady, feeling terrified or afraid, a sense of choking, fear of dying, and feeling scared were higher in patients with than in those without cancer. CONCLUSION: High levels of depressive symptoms related to somatic discomfort and anxiety symptoms related to fear of cancer were associated with considerable psychological distress in patients with cancer diagnosis and treatment.

Validation of the Korean Version of the Depression in Old Age Scale and Comparison with Other Depression Screening Questionnaires Used in Elderly Patients in Medical Settings.

OBJECTIVE: The Depression in Old Age Scale (DIA-S) is a new screening tool for assessing depression in the elderly. The primary aims of this study were to describe the validation of the Korean version of the DIA-S (K-DIA-S) and to compare its validity with that of other depression screening questionnaires used in elderly outpatients in medical settings. METHODS: A total of 385 elderly outpatients completed the K-DIA-S and underwent the Mini International Neuropsychiatric Interview to diagnose depressive disorders. Other measures included the 15-item short form of the Geriatric Depression Scale (SGDS), the 9-item depression module of the Patient Health Questionnaire (PHQ-9), and the Montgomery-Asberg Depression Rating Scale (MADRS). Reliability and validity tests, an optimal cutoff point estimate, and receiver operating characteristic curve analysis were performed to investigate the diagnostic validity of the K-DIA-S. Areas under the curves (AUCs) for the K-DIA-S, SGDS, and PHQ-9 were compared statistically. RESULTS: The K-DIA-S showed good internal consistency and strong correlations with the SGDS (r = 0.853), PHQ-9 (r= 0.739), and MADRS (r= 0.772). The cut-off point of the K-DIA-S that can be recommended for screening depressive symptoms was a score of 4. For "any depressive disorder", the AUC (standard error) for the K-DIA-S was 0.896 (0.015), which was significantly larger than that for the PHQ-9 (p= 0.033). CONCLUSION: The present findings suggest that the K-DIA-S has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in elderly populations and medically ill patients.

The prevalence and diagnostic classification of mixed features in patients with major depressive episodes: A multicenter study based on the DSM-5.

OBJECTIVES: The purpose of this study was to evaluate the prevalence of mixed features using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and to examine how patients with mixed states would be classified using the DSM-5. METHODS: In total, 12 hospitals participated in this study, and data on the demographic characteristics and clinical diagnoses of patients treated between October 2013 and September 2016 were obtained. We reviewed the data for opposite-polarity symptoms according to the DSM-5 criteria and the research-based diagnostic criteria. RESULTS: Of the 859 patients included in the final analysis, the prevalence of mixed features in patients with major depressive episodes based on the DSM-5 remained low. Patients with major depressive disorder were more likely to be classified as experiencing anxious distress and/or a cluster-B personality disorder in mixed state patients not diagnosed with DSM-5 mixed features, whereas more mixed state patients with bipolar disorder were diagnosed with mixed features using the DSM-5. CONCLUSIONS: The prevalence of mixed features did not increase significantly when the DSM-5 was used, and patients with mixed states were more likely to be classified as having anxious distress and/or a cluster-B personality disorder in addition to mixed features.

Pharmacological Treatment of Major Depressive Episodes with Mixed Features: A Systematic Review.

We reviewed clinical studies investigating the pharmacological treatment of major depressive episodes (MDEs) with mixed features diagnosed according to the dimensional criteria (more than two or three [hypo]manic symptoms+principle depressive symptoms). We systematically reviewed published randomized controlled trials on the pharmacological treatment of MDEs with mixed features associated with mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). We searched the PubMed, Cochrane Library, and ClinicalTrials.gov databases through December 2017 with the following key word combinations linked with the word OR: (a) mixed or mixed state, mixed features, DMX, mixed depression; (b) depressive, major depressive, MDE, MDD, bipolar, bipolar depression; and (c) antidepressant, antipsychotic, mood stabilizer, anticonvulsant, treatment, medication, algorithm, guideline, pharmacological. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We found few randomized trials on pharmacological treatments for MDEs with mixed features. Of the 36 articles assessed for eligibility, 11 investigated MDEs with mixed features in mood disorders: six assessed the efficacy of antipsychotic drugs (lurasidone and ziprasidone) in the acute phase of MDD with mixed features, although four of these were post hoc analyses based on large randomized controlled trials. Four studies compared antipsychotic drugs (olanzapine, lurasidone, and ziprasidone) with placebo, and one study assessed the efficacy of combination therapy (olanzapine+fluoxetine) in the acute phase of BD with mixed features. Pharmacological treatments for MDEs with mixed features have focused on antipsychotics, although evidence of their efficacy is lacking. Additional well-designed clinical trials are needed.

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.

Predictors of a Shorter Time to Hospitalization in Patients with Bipolar Disorder: Medication during the Acute and Maintenance Phases and Other Clinical Factors.

OBJECTIVE: The present study was conducted to compare the effects of pharmacological treatments during the acute and maintenance phases of mood episodes, sociodemographic, and clinical characteristics between a shorter time to hospitalization group (＜12 months) and a longer time to hospitalization group (≥12 months). METHODS: The discharge medication for the first hospitalization was considered the acute treatment and the medication used during the week prior to the second hospitalization at the outpatient clinic was considered the maintenance treatment. Additionally, the charts were reviewed to examine a variety of demographic and clinical characteristics. RESULTS: Patients in the shorter time to hospitalization group were more likely to be unmarried and/or unemployed, have had a previous hospital admission for a mood episode, and have used antidepressant during the acute phase than those in the longer time to hospitalization group. Patients in the shorter time to hospitalization group were also less likely to use olanzapine, serotonin-norepinephrine reuptake inhibitors, or mood stabilizer monotherapy as a maintenance treatment than were patients in the longer time to hospitalization group. CONCLUSION: Predictors for shorter time to hospitalization were associated with number of previous hospital admissions for a mood episode, being unmarried and/or unemployed, and antidepressant use during the acute phase.

Dose Trends of Aripiprazole from 2004 to 2014 in Psychiatric Inpatients in Korea.

OBJECTIVE: Although aripiprazole has been widely used to treat various psychiatric disorders, little is known about the adequate dosage for Asian patients in clinical practice. Hence, we evaluated the initial and maximum doses of aripiprazole from 2004 to 2014 to estimate the appropriate dosage for Korean psychiatric inpatients in clinical practice. METHODS: In this retrospective study, we reviewed the medical records of patients who were hospitalized in five university hospitals in Korea from March 2004 to December 2014. The psychiatric diagnosis according to the text revision of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition during index hospitalization and the initial and maximum doses of aripiprazole were evaluated. RESULTS: There were 74 patients in Wave 1 (2004-2006), 201 patients in Wave 2 (2007-2010), and 353 patients in Wave 3 (2011-2014). The initial doses of aripiprazole in all diagnostic groups were significantly lower in Wave 3 than in Wave 2. The maximum doses of aripiprazole in each diagnostic group were not significantly different among Waves 1, 2, and 3. CONCLUSION: The relatively low initial doses of aripiprazole documented in our study may reflect a strategy by clinicians to minimize the side effects associated with aripiprazole use, such as akathisia.

Associations between immune activation and the current severity of the "with anxious distress" specifier in patients with depressive disorders.

OBJECTIVE: Immune dysregulation may be linked with depressive disorders and in particular anxiety symptoms. This study compared the levels of immune factors, demographic and clinical characteristics of patients with depressive disorders between mild to moderate and moderate-severe to severe anxious distress groups. METHODS: This study included 177 patients diagnosed with a depressive disorder who were hospitalized between March 2012 and April 2015. The patients were categorized into mild to moderate and moderate-severe to severe anxious distress groups, based on the Hamilton Depression Rating Scale (HAM-D) scores on the Agitation and Anxiety-Psychic subscales. The charts of the patients were reviewed to evaluate immune factors, including C-reactive protein (CRP) and white blood cell levels, confounding factors, such as smoking, other general medical disorders and body mass index, and demographic and clinical characteristics, such as age, sex, total HAM-D scores, comorbidities, family history of mood disorders, suicidality, psychotic features and prescription patterns. RESULTS: The moderate-severe to severe group tended to have higher CRP and monocyte levels compared with the mild to moderate group. After adjusting for the HAM-D scores, patients with moderate-severe to severe anxious distress had a significantly greater trend toward significance for suicidality and a higher rate of antipsychotic use. CONCLUSION: High levels of anxiety symptoms may modulate the inflammatory response and course of illness, affecting treatment planning.

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.

Prevalence rates and clinical implications of bipolar disorder "with mixed features" as defined by DSM-5.

BACKGROUND: We investigated the increase in the prevalence of bipolar disorder with mixed features following the replacement of DSM-IV-TR criteria with DSM-5 criteria. Additionally, we examined the clinical implications of the use of "with mixed features" as a specifier with bipolar disorder. METHOD: We retrospectively reviewed medical charts from 2003 to 2013. A total of 331 patients diagnosed with bipolar disorder using the DSM-IV TR were enrolled and categorized into four groups: manic/hypomanic with mixed features, manic/hypomanic without mixed features, depressed with mixed features, and depressed without mixed features. These classifications were made in accordance with the DSM-5 definition of bipolar disorder "with mixed features." Changes in the prevalence, demographic and clinical characteristics were compared among the groups. RESULTS: The prevalence rates of mixed features were significantly different when using the DSM-5 criteria vs. the DSM-IV-TR criteria. Patients with mixed features had a younger age of onset, younger age at hospitalization, more frequent hospitalizations for mixed episodes, and greater suicide risk compared with patients without mixed features. LIMITATIONS: Retrospective study may have resulted in under diagnosis of mixed states. CONCLUSIONS: An approximately three-fold greater risk for mixed features was observed in patients with bipolar disorder when using the DSM-5 criteria than when using the DSM-IV-TR criteria. The additional patients may represent patients with sub-syndromal mixed features and could indicate that patients with mixed features are underdiagnosed.

Thyroid functioning in patients with bipolar disorder with mixed features.

We compared the prevalence of thyroid dysfunction in patients with bipolar disorder with and without mixed features by measuring of thyroid function test. We reviewed the medical charts between 2005 and 2013. These results did not show a significant difference in the association between thyroid dysfunction and the mixed features.

A diagnosis of bipolar spectrum disorder predicts diagnostic conversion from unipolar depression to bipolar disorder: a 5-year retrospective study.

BACKGROUND: The major aims of this study were to identify factors that may predict the diagnostic conversion from major depressive disorder (MDD) to bipolar disorder (BP) and to evaluate the predictive performance of the bipolar spectrum disorder (BPSD) diagnostic criteria. METHODS: The medical records of 250 patients with a diagnosis of MDD for at least 5 years were retrospectively reviewed for this study. RESULTS: The diagnostic conversion from MDD to BP was observed in 18.4% of 250 MDD patients, and the diagnostic criteria for BPSD predicted this conversion with high sensitivity (0.870) and specificity (0.917). A family history of BP, antidepressant-induced mania/hypomania, brief major depressive episodes, early age of onset, antidepressant wear-off, and antidepressant resistance were also independent predictors of this conversion. LIMITATIONS: This study was conducted using a retrospective design and did not include structured diagnostic interviews. CONCLUSIONS: The diagnostic criteria for BPSD were highly predictive of the conversion from MDD to BP, and conversion was associated with several clinical features of BPSD. Thus, the BPSD diagnostic criteria may be useful for the prediction of bipolar diathesis in MDD patients.

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.

A reevaluation of the possibility and characteristics in bipolar mania with mixed features: a retrospective chart review.

The aim of the present study was to reevaluate the feasibility of diagnosing a mixed features behind bipolar mania and to elucidate the clinical characteristics, treatment response, and course of the illness throughout a 12-month follow-up. The subjects (n=171) were inpatients diagnosed with bipolar I disorder, manic, between 2003 and 2010 and were classified into three groups: "mania" (n=67), "mania with probable mixed features" (n=79), and "mania with definite mixed features" (n=25). Diagnoses were in accordance with the Cincinnati criteria, which include the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision characteristics for a major depressive episode, except for agitation and insomnia. The charts of subjects were retrospectively reviewed for demographic and clinical characteristics prior to the index episode, clinical data regarding the index episode, and treatment courses over a 12-month follow-up period. Subjects in the mania with definite mixed features were more likely to be young at admission, to be female, to have a familial affective loading, and to have a history of suicidality relative to the mania. The results of the present study suggest the need for regular assessment of symptoms associated with both polarities during an episode in routine practice.

Mixed-state bipolar I and II depression: time to remission and clinical characteristics.

BACKGROUND: We compared the time to achieve remission and the clinical characteristics of patients with bipolar depressive mixed state and those with bipolar depressive non-mixed state. METHODS: The subjects (N=131) were inpatients diagnosed between 2006 and 2012 with bipolar I or II disorder, depression and were classified into the following three groups: "pure depressive state" (PD, n=70), "sub-threshold mixed state" (SMX, n=38), and "depressive mixed state" (DMX, n=23). Diagnosis of a DMX was in accordance with Benazzi's definition: three or more manic symptoms in a depressive episode. The subjects' charts were retrospectively reviewed to ascertain the time to achieve remission from the index episode and to identify other factors, such as demographic and clinical characteristics, specific manic symptoms, and pharmacological treatment, that may have contributed to remission. RESULTS: The time to achieve remission was significantly longer in the DMX (p=0.022) and SMX (p=0.035) groups than in the PD group. Adjustment for covariates using a Cox proportional hazards model did not change these results. Clinically, subjects with a DMX were more likely to have manic symptoms in the index episode, especially inflated self-esteem and psychomotor agitation than those in the PD. LIMITATIONS: We investigated only inpatients and therefore could not comment on outpatients. CONCLUSIONS: These findings showed that sub-syndromal manic symptoms in bipolar depression had different clinical characteristics and a more severe illness course, including a longer time to achieve remission, than did a pure depressive state.