Pre-clinical evaluation of cysteamine bitartrate as a therapeutic agent for mitochondrial respiratory chain disease.

Cysteamine bitartrate is a US Food and Drug Administration-approved therapy for nephropathic cystinosis also postulated to enhance glutathione biosynthesis. We hypothesized this antioxidant effect may reduce oxidative stress in primary mitochondrial respiratory chain (RC) disease, improving cellular viability and organismal health. Here, we systematically evaluated the therapeutic potential of cysteamine bitartrate in RC disease models spanning three evolutionarily distinct species. These pre-clinical studies demonstrated the narrow therapeutic window of cysteamine bitartrate, with toxicity at millimolar levels directly correlating with marked induction of hydrogen peroxide production. Micromolar range cysteamine bitartrate treatment in Caenorhabditis elegans gas-1(fc21) RC complex I (NDUFS2-/-) disease invertebrate worms significantly improved mitochondrial membrane potential and oxidative stress, with corresponding modest improvement in fecundity but not lifespan. At 10 to 100 µm concentrations, cysteamine bitartrate improved multiple RC complex disease FBXL4 human fibroblast survival, and protected both complex I (rotenone) and complex IV (azide) Danio rerio vertebrate zebrafish disease models from brain death. Mechanistic profiling of cysteamine bitartrate effects showed it increases aspartate levels and flux, without increasing total glutathione levels. Transcriptional normalization of broadly dysregulated intermediary metabolic, glutathione, cell defense, DNA, and immune pathways was greater in RC disease human cells than in C. elegans, with similar rescue in both models of downregulated ribosomal and proteasomal pathway expression. Overall, these data suggest cysteamine bitartrate may hold therapeutic potential in RC disease, although not through obvious modulation of total glutathione levels. Careful consideration is required to determine safe and effective cysteamine bitartrate concentrations to further evaluate in clinical trials of human subjects with primary mitochondrial RC disease.

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.

Knowledge and Attitude of 851 Nursing Personnel toward Depression in General Hospitals of Korea.

Our study aimed to examine the knowledge and attitude of nursing personnel toward depression in general hospitals of Korea. A total of 851 nursing personnel enrolled at four university-affiliated general hospitals completed self-report questionnaires. Chi-square tests were used to compare the knowledge and attitude of registered or assistant nurses toward depression. In addition, binary logistic regression analysis was used to adjust for the following confounders: age-group and workplace. Registered and assistant nurses differed in their knowledge and attitude toward depression. The proportion of rational and/or correct responses were higher in registered nurses than assistant nurses for the following: constellation of depressive symptoms defined by DSM-IV (adjusted odds ratio [aOR], 3.876; P<0.001); suicide risk in depression recovery (aOR, 3.223; P=0.001) and psychological stress as a cause of depression (aOR, 4.370; P<0.001); the relationship between chronic physical disease and depression (aOR, 8.984; P<0.001); and other items. Our results suggest that in terms of the biological model of depression, the understanding of registered nurses is greater than that of assistant nurses. Moreover, specific psychiatric education programs for nursing personnel need to be developed in Korea. Our findings can contribute to the development of a general hospital-based model for early detection of depression in patients with chronic medical diseases.

Increased levels of plasma glial-derived neurotrophic factor in children with attention deficit hyperactivity disorder.

BACKGROUND: Recent evidence suggests that neurotrophic growth factor systems, including brain-derived neurotrophic factor, might be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Glial cell line-derived neurotrophic factor (GDNF) is from the transforming growth factor-ß family and is abundantly expressed in the central nervous system, where it plays a role in the development and function of hippocampal cells. To date, no association studies have been done between ADHD and GDNF. Thus, here we investigate the hypothesis that there are differences in plasma GDNF levels between children with ADHD and healthy controls. METHODS: Plasma GDNF levels were measured in 86 drug-naïve children with ADHD and 128 healthy children. The severity of ADHD symptoms was determined by scores on the Korean ADHD Rating Scale (K-ARS) in patients and healthy controls. RESULTS: The median plasma GDNF levels in ADHD patients was 74.0 (IQR: 23.4-280.1) pg/ml versus 24.6 (IQR: 14.5-87.3) pg/ml in healthy controls; thus the median plasma GDNF levels in ADHD patients were significantly higher than in healthy controls (Mann-Whitney U-test, P < 0.01). Plasma GDNF levels were correlated positively with K-ARS subscale scores (inattention, hyperactivity-impulsivity and total), determined by Spearman's correlation test in ADHD patients and healthy controls (r = 0.371, P < 0.01; r = 0.331, P < 0.01; and r = 0.379, P < 0.01, respectively). CONCLUSIONS: These findings suggest increased plasma GDNF levels in untreated ADHD patients. In addition, plasma GDNF levels had a significant positive correlation with inattention, hyperactivity-impulsivity and K-ARS total scores in ADHD patients and healthy controls. Further studies are required to determine the source and role of circulating GDNF in ADHD.

Long-term clinical outcomes of image-guided percutaneous coronary intervention in acute myocardial infarction from the Korea Acute Myocardial Infarction Registry.

Imaging modalities for percutaneous coronary intervention (PCI), such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), have increased in the current PCI era. However, their clinical benefits in acute myocardial infarction (AMI) have not been fully elucidated. This study investigated the long-term outcomes of image-guided PCI in patients with AMI using data from the Korean Acute Myocardial Infarction Registry. A total of 9,271 patients with AMI, who underwent PCI with second-generation drug-eluting stents between November 2011 and December 2015, were retrospectively examined, and target lesion failure (TLF) at 3 years (defined as the composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) was evaluated. From the registry, 2,134 patients (23.0%) underwent image-guided PCI (IVUS-guided: n = 1,919 [20.6%]; OCT-guided: n = 215 patients [2.3%]). Based on propensity score matching, image-guided PCI was associated with a significant reduction in TLF (hazard ratio: 0.76; 95% confidence interval: 0.59-0.98, p = 0.035). In addition, the TLF incidence in the OCT-guided PCI group was comparable to that in the IVUS-guided PCI group (5.3% vs 4.7%, p = 0.903). Image-guided PCI, including IVUS and OCT, is associated with favorable clinical outcomes in patients with AMI at 3 years post-intervention. Additionally, OCT-guided PCI is not inferior to IVUS-guided PCI in patients with AMI.

Preventive effect of aripiprazole once-monthly on relapse into mood episodes in bipolar disorder: A multicenter, one-year, retrospective, mirror image study.

BACKGROUND: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment. METHODS: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit. RESULTS: The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM. LIMITATIONS: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times. CONCLUSION: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.

Resveratrol has anabolic effects on disc degeneration in a rabbit model.

This study was done to evaluate whether injections of resveratrol, a natural compound found in the skin of grapes, had anabolic effects on degenerated intervertebral discs in a rabbit model. Two non-continuous lumbar discs were punctured in rabbits to induce disc degeneration. Four weeks and 6 weeks after puncture, the rabbits were treated by injections with dimethylsulfoxide (DMSO) or resveratrol. At 4, 8, and 16 weeks after initial injection, rabbits were sacrificed and the spine was extracted for magnetic resonance image (MRI), mRNA expression, and histological staining. Resveratrol treatment resulted in stronger signal intensity in T2-weighted images. MRI grade showed significantly lower in the resveratrol group than the DMSO group (P = 0.039). In the resveratrol group, aggrecan gene expression was significantly increased than that in the DMSO group at 16 weeks after injection (P = 0.027). MMP-13 mRNA levels in the resveratrol group were significantly decreased than those in the DMSO group at 8 and 16 weeks (P = 0.006 and P = 0.048, respectively). In hematoxylin and eosin stain, resveratrol-treated discs showed the features of regeneration. Histologic grade revealed improvement in resveratrol-treated discs, compared with DMSO-treated discs (P = 0.024). These anabolic effects on degenerated discs indicate that resveratrol is a promising candidate for treatment of degenerative disc disease.

Impact of intravascular ultrasound and final kissing balloon dilatation on long-term clinical outcome in percutaneous revascularization with 1-stent strategy for left main coronary artery stenosis in drug-eluting stent era.

BACKGROUND: It remains uncertain whether intravascular ultrasound (IVUS) use and final kissing balloon (FKB) dilatation would be standard care of percutaneous coronary intervention (PCI) with a simple 1-stent technique in unprotected left main coronary artery (LMCA) stenosis. This study sought to investigate the impact of IVUS use and FKB dilatation on long-term major adverse cardiac events (MACEs) in PCI with a simple 1-stent technique for unprotected LMCA stenosis. METHODS: Between June 2006 and December 2012, 255 patients who underwent PCI with 1 drug-eluting stent for LMCA stenosis were analyzed. Mean follow-up duration was 1663 ± 946 days. Long-term MACEs were defined as death, nonfatal myocardial infarction (MI) and repeat revascularizations. RESULTS: During the follow-up, 72 (28.2%) MACEs occurred including 38 (14.9%) deaths, 21 (8.2%) nonfatal MIs and 13 (5.1%) revascularizations. The IVUS examination and FKB dilatation were done in 158 (62.0%) and 119 (46.7%), respectively. IVUS use (20.3 versus 41.2%; log-rank P < 0.001), not FKB dilatation (30.3 versus 26.5%; log-rank P = 0.614), significantly reduced MACEs. In multivariate analysis, IVUS use was a negative predictor of MACEs [hazards ratio 0.51; 95% confidence interval (CI) 0.29-0.88; P = 0.017], whereas FKB dilatation (hazard ratio 1.68; 95% CI, 1.01-2.80; P = 0.047) was a positive predictor of MACEs. In bifurcation LMCA stenosis, IVUS use (18.7 versus 48.0%; log-rank P < 0.001) significantly reduced MACEs. In nonbifurcation LMCA stenosis, FKB dilatation showed a trend of increased MACEs (P = 0.076). CONCLUSION: IVUS examination is helpful in reducing clinical events in PCI for LMCA bifurcation lesions, whereas mandatory FKB dilatation after the 1-stent technique might be harmful in nonbifurcation LMCA stenosis.

Clinical correlates associated with the long-term response of bipolar disorder patients to lithium, valproate or lamotrigine: A retrospective study.

BACKGROUND: Although mood stabilizers such as lithium (LIT), valproate (VAL), and lamotrigine (LMT) appear to be efficacious treatments for bipolar disorder (BD) in research settings, the long-term response to these mood stabilizers in clinical practice is highly variable among individuals. Thus, the present study examined the characteristics associated with good or insufficient responses to long-term treatment with LIT, VAL, or LMT for BD. METHODS: This study retrospectively analyzed the medical records of patients who visited an outpatient clinic with a diagnosis of BD I or II. Data from patients who were treated with one of three mood stabilizing medications (LIT, VAL, or LMT) for more than 6 months were selected, and the long-term treatment responses were evaluated using the Alda scale. For the purposes of this study, two response categories were formed: insufficient response (ISR), including non-response or poor response (Alda total score ≤ 6), and good response (GR; Alda total score ≥ 7). RESULTS: Of the 645 patients included in the present study, 172 were prescribed LIT, 320 were prescribed VAL, and 153 were prescribed LMT for at least 6 months. A binary logistic regression analysis revealed that a diagnosis of BD II (odds ratio [OR], 8.868; 95% confidence interval [CI], 1.123-70.046; p = 0.038), comorbid alcohol/substance use disorder (OR, 4.238; 95% CI, 1.154-15.566; p = 0.030), and a history of mixed episodes (OR, 4.363; 95% CI, 1.191-15.985; p = 0.026) were significant predictors of LIT-ISR. Additionally, a depressive-predominant polarity significantly predicted LMT-GR (OR, 8.586; 95% CI, 2.767-26.644; p < 0.001). CONCLUSION: The present findings demonstrated that patients with a diagnosis of BD II, a comorbid alcohol/substance problem, or a history of mixed episodes were not likely to respond to LIT treatment. Additionally, LMT might be a better treatment choice for patients with a depressive-predominant polarity.

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.

Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD).

BACKGROUND: Recent reports have suggested a pathophysiological role of brain-derived neurotrophic factor (BDNF) in attention deficit-hyperactivity disorder (ADHD). We evaluated the plasma levels of BDNF in patients with ADHD. METHODS: Plasma BDNF levels were measured in 41 drug naive ADHD patients and 107 normal controls. The severity of ADHD symptoms was determined by patient scores on the ADHD rating scale (ARS) and the computerized ADHD diagnostic system (ADS). RESULTS: ANCOVA with age and gender as covariates showed that the mean plasma BDNF levels were significantly higher in ADHD patients than in normal controls (F=16.968, p<0.001). There were also significant differences in plasma BDNF levels of ADHD patients and those of normal controls for males and females (Mann-Whitney U-test, p=0.001 and 0.041, respectively). We also found a significant correlation between plasma BDNF levels and omission errors in ADS outcome-variable T-scores (p<0.001). CONCLUSIONS: Our study suggests that there is an increase of plasma BDNF levels in untreated ADHD patients, and that plasma BDNF levels had a significant positive correlation with the severity of inattention symptoms. Further studies are required to elucidate the source and role of circulating BDNF in ADHD.

Differences in Psychopathology between Offspring of Parents with Bipolar I Disorder and Those with Bipolar II Disorder: A Cross-Sectional Study.

OBJECTIVE: The aim of this study was to evaluate differences in psychopathology between offspring of parents with bipolar I disorder (BP-I) and those with bipolar II disorder (BP-II). METHODS: The sample included 201 offspring between 6 and 17 years of age who had at least one parent with BP-I or BP-II. The offspring were diagnostically evaluated using the Korean Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version. Psychopathology and Clinical characteristics were evaluated, including lifetime DSM-5 diagnoses, depression, and childhood trauma. Lifetime DSM-5 diagnoses were also compared between schoolchildren aged 6 to 11 years and adolescents aged 12 to 17 years. RESULTS: In lifetime DSM-5 diagnoses, offspring of parents with BP-I had significantly increased risk of developing MDD and BP-I than those with BP-II. Regarding clinical characteristics, ADHD rating scale and childhood trauma scale were significantly higher in offspring of parents with BP-I than that in those with BP-II. CONCLUSION: The present study supports that BP-I may be etiologically distinct from BP-II by a possible genetic liability. Our findings indicate that additional research related to bipolar offspring is needed to enhance understanding of differences between BP-I and BP-II.

The Association between Suicide Attempts and Toxoplasma gondii Infection.

OBJECTIVE: Chronic 'latent' infection by Toxoplasma gondii is common and most of the hosts have minimal symptoms or they are even asymptomatic. However, there are possible mechanisms by which T. gondii may affect human behavior and it may also cause humans to attempt suicide. This article aimed to investigate the potential pathophysiological relationship between suicide attempts and T. gondii infection in Korea. METHODS: One hundred fifty-five psychiatric patients with a history of suicide attempt and 135 healthy control individuals were examined with enzyme-linked immunoassays and fluorescent antibody technique for T. gondii seropositivity and antibody titers. The group of suicide attempters was interviewed regarding the history of suicide attempt during lifetime and evaluated using 17-item Korean version of Hamilton Depression Scale (HAMD), Columbia Suicide Severity Rating Scale (C-SSRS), State-Trait Anxiety Inventory (STAI) and Korean-Barratt Impulsiveness Scale (BIS). RESULTS: Immunoglobulin G antibodies were found in 21 of the 155 suicide attempters and in 8 of the 135 controls (p=0.011). The Toxoplasma-seropositive suicide attempters had a higher HAMD score on the depressed mood and feeling of guilt subscales and a higher total score than the seronegative suicide attempters. T. gondii seropositive status was associated with higher C-SSRS in the severity and lethality subscales. T. gondii IgG seropositivity was significantly associated with higher STAI-X1 scores in the suicide attempters group. CONCLUSION: Suicide attempters showed higher seroprevalence of T. gondii than healthy controls. Among the suicide attempters, the T. gondii seropositive and seronegative groups showed several differences in the aspects of suicide. These results suggested a significant association between T. gondii infection and psychiatric problems in suicidality.

Long-term Clinical and Radiological Outcomes after Central Decompressive Laminoplasty for Lumbar Spinal Stenosis.

OBJECTIVE: There are many technical modifications of decompressive lumbar laminectomy. The purpose of this study was to report long-term clinical and radiological outcomes of central decompressive laminoplasty (CDL), the corresponding author's own modification of lumbar laminectomy for lumbar spinal stenosis (LSS). METHODS: Among 100 patients who underwent CDL by a single surgeon between December 2010 and March 2014, 68 patients were included in this study. Mean follow-up time was 37.7 months. Clinical and radiological data were gathered prospectively and reviewed retrospectively. Clinical outcome was measured by using visual analog scale (VAS) for back/buttock and leg, and the Oswestry Disability Index (ODI). Radiological outcome was measured by neutral slippage percentage, dynamic slippage percentage, and dynamic intervertebral angel on sagittal X-ray. Outcomes after CDL were assessed by changes of clinical and radiological parameters from the baseline. Mixed effect model with random patients' effect as used to test for differences in the repeated measured clinical and radiological data. RESULTS: The patients had no serious complications with an uneventful recovery during the early postoperative period. In the early postoperative period, VAS scores for back/buttock and leg improved significantly and were kept with time (p<0.001). ODI also improved significantly during the postoperative follow-up period (p<0.001). The radiologic parameters were well maintained and showed no progression of instability. During the follow-up, a case of herniated disc at same level recurrence was noted after lifting trauma, and 2 adjacent foraminal stenosis needed additional surgery. CONCLUSION: CDL provides long-term pain relief and functional restoration without progression of radiological instability.

The Normalization of Brain ¹8F-fluorodeoxy-D-glucose Positron Emission Tomography Hypometabolism following Electroconvulsive Therapy in a 55-year-old Woman with Treatment-resistant Late Onset Depression: A Case Report.

Major depressive disorder, especially in later life, has heterogeneous clinical characteristics and treatment responses. Symptomatically, psychomotor retardation, lack of energy, and apathy tends to be more common in people with late-onset depression (LOD). Despite recent advances in psychopharmacologic treatments, 20% to 30% of patients with mood disorders experience inadequate responses to medication, often resulting in a trial of electroconvulsive therapy (ECT). However, the therapeutic mechanism of ECT is still unclear. By using ¹8F-fluorodeoxy-D-glucose positron emission tomography-computed tomography (¹8F-FDG PET/CT), we can obtain the status of brain metabolism in patients with neuropsychiatric disorders and changes during psychiatric treatment course. The object of this case report is evaluating the effect of ECT on brain metabolism in treatment-refractory LOD by PET/CT and understanding the mode of action of ECT. In this case report, we presented a 55-year-old female patient who suffered psychotic depression that was resistant to pharmacological treatment. Several antidepressants and atypical antipsychotics were applied but there was no improvement in her symptoms. The patient presented not only depressed mood and behaviors but also deficit in cognitive functions. We found decreased diffuse cerebral metabolism in her brain ¹8F-FDG PET/CT image. ECT resulted in amelioration of the patients' symptoms and another brain PET imaging 7 weeks after the last ECT course showed that her brain metabolism was normalized.

Screening for Depressive Disorder in Elderly Patients with Chronic Physical Diseases Using the Patient Health Questionnaire-9.

OBJECTIVE: We aimed to identify depressive symptom profiles that indicated the presence of depressive disorder and present optimal cut-off sub-scores for depressive symptom profiles for detecting depressive disorder in elderly subjects with chronic physical diseases including diabetes, chronic obstructive pulmonary disease/asthma, and coronary artery disease, using the Patient Health Questionnaire-9 (PHQ-9). METHODS: Two hundred and thirty-one elderly patients with chronic physical diseases were recruited consecutively from a university-affiliated general hospital in South Korea. RESULTS: Greater severities of all 9 depressive symptoms in the PHQ-9 were presented in those with depressive disorder rather than those without depressive disorder. A binary logistic regression modeling presented that little interest [adjusted odds ratio (aOR)=4.648, p<0.001], reduced/increased sleep (aOR=3.269, p<0.001), psychomotor retardation/agitation (aOR=2.243, p=0.004), and concentration problem (aOR=16.116, p<0.001) were independently associated with increased likelihood of having depressive disorder. Receiver operating characteristics (ROC) curve analysis presented that the optimal cut-off value of score on the items for little interest, reduced/increased sleep, psychomotor retardation/agitation and concentration problem (PHQ-9) for detecting depressive disorder was 4 with 61.9% of sensitivity and 91.5% of specificity [area under curve (AUC)=0.937, p<0.001]. CONCLUSION: Our findings suggested that the diagnostic weighting of little interest, reduced/increased sleep, psychomotor retardation/agitation, and concentration problem is needed to detect depressive disorder among the elderly patients with chronic physical diseases.

Efficacy and Tolerability of Generic Mirtazapine (Mirtax) for Major Depressive Disorder: Multicenter, Open-label, Uncontrolled, Prospective Study.

OBJECTIVE: Mirtax is a generic mirtazapine widely used since 2003. We conducted an open-label, uncontrolled 6-week study to evaluate the efficacy and safety of Mirtax for major depressive disorder (MDD). METHODS: Ninety three MDD patients with the diagnosis of MDD and 17-item Hamilton Depression Rating Scale (HDRS) score ≥14 were recruited. The HDRS, Montgomery-Åsberg Depression Rating Scale (MADRS), and the Clinical Global Impressions-Severity Scale (CGI-S) were administered at baseline, 1, 2, 4 and 6 weeks. Response (≥50% decrease in the HDRS or MADRS score), remission (absolute HDRS score ≤7 or MADRS score ≤10) and CGI-I score ≤2 were also calculated. Adverse event (AE) frequency and severity, weight, blood pressure, and pulse rate were checked to assess safety. RESULTS: The starting dosage was 11.5±6.4 mg/day, and the maintenance dosage was 23.1±9.4 mg/day. During 6 weeks, HDRS, MADRS and CGI-S scores decreased from 25.1±5.6 to 11.9±8.6 (mean change -13.1±8.3, p<0.001), from 30.2±6.3 to 13.73±10.40 (mean change -16.5±9.8, p<0.001), and from 5.0±0.8 to 2.5±1.3 (mean change -2.5±1.3, p<0.001), respectively. The percentages of responders, remitters by HDRS and patients with a CGI-I score ≤2 were 64.6%, 35.4% and 52.7%, respectively. Significant decreases in HDRS, MADRS and CGI-S scores were confirmed at week 1. The total rate of AEs was 32.3%; the most frequently reported AEs were sedation (4.3%) and constipation (4.3%). Weight was increased from 58.8±10.6 to 60.3±9.3 kg (mean change 0.7±1.7 kg, p=0.004). CONCLUSION: This study, as the first clinical trial of generic mirtazapine, demonstrated the efficacy and tolerability of Mirtax for MDD using a single treatment design.