Bum-Hee Yu

Effect of CPAP treatment on mood states in patients with sleep apnea

Sleep apnea can lead to marked psychological distress including some mood symptoms. Previous studies on continuous positive airway pressure (CPAP) treatment usually reported significant improvement in mood symptoms in patients with sleep apnea, but most of them did not consider the placebo effect of CPAP. We examined the effect of CPAP treatment on mood states by employing both CPAP treatment and placebo CPAP. Twenty five men and nine women with sleep apnea underwent two successive nights of polysomnography (PSG) during hospitalization. The Profile of Mood States (POMS) was administered to measure mood states. Patients were randomly assigned to either CPAP treatment group or placebo CPAP group. After 7 days of CPAP use at home, all patients were re-hospitalized to undergo one more night of nocturnal PSG with their assigned treatment (CPAP treatment or placebo CPAP). They also had a repeat evaluation of mood by completing the POMS. Only patients on CPAP treatment improved significantly in apnea index, respiratory disturbance index, and mean oxygen saturation. However, both CPAP treatment group and placebo CPAP group showed significant improvement in mood states. In conclusion, the effect of CPAP treatment on mood symptoms in apneic patients could be a placebo effect. CPAP treatment may be effective in improving mood states only in patients who have severe depressive symptoms secondary to sleep apnea.

Serum lipids, recent suicide attempt and recent suicide status in patients with major depressive disorder.

OBJECTIVE Major depressive disorder (MDD) is associated with suicide. Although several studies have reported its association with low serum lipid, few studies have investigated relationships between current suicidality and lipid profiles, comparing with other blood measures in MDD patients. METHODS The study population consisted of 555 subjects with MDD who were ≥ 18 years old, evaluated by the Mini International Neuropsychiatric Interview (MINI) with the suicidality module. At the evaluation visit, we measured serum lipid profiles including total cholesterol, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very low-density lipoprotein (VLDL), and blood measures such as fasting glucose, total protein, albumin, blood urea nitrogen, creatinine, thyroid hormones, red and white blood cells, platelet count, hemoglobin, and hematocrit. RESULTS Recent attempters who had attempted suicide within the past month showed significantly lower TG and higher HDL levels than lifetime and never attempters, using Tukeys post-hoc analysis. Recent attempters exhibited lower TG and higher HDL than those with recent suicide ideation and wish to self-harm and those without previous attempt. Linear regression analysis revealed that TG was negatively associated with current suicidality scores (β = -0.187, p = 0.039), whereas VLDL was positively associated with the recent suicide status (β = 0.198, p = 0.032) after controlling for age and sex. There were no significant differences between the groups in terms of other serum lipid profiles and blood measures. CONCLUSIONS Low serum TG, high HDL and VLDL levels are associated with recent suicide attempt or recent suicide status in patients with MDD.

Psychological States and Lymphocyte β-Adrenergic Receptor Responsiveness

There is a complex interplay between psychological states and biochemical factors. β-Adrenergic receptor responsiveness is altered in some patients with depression and anxiety disorders, but the relation between various psychological states and receptor function in a normal population is unknown. We measured lymphocyte β-adrenergic receptor density (Bmax), sensitivity (cAMP ratio), the Profile of Mood States (POMS), and Spielberger State–Trait Anxiety Inventory (STAI) in 39 hypertensives and 81 normotensives. We examined correlations between log normalized receptor variables and psychological states. Log Bmax showed negative correlations with age and with POMS tension-anxiety, depression-dejection, and anger-hostility. Log cAMP ratio did not show significant correlations with POMS and STAI ratings. In step-wise multiple regression analyses, 36% of the variance in Bmax was accounted for by POMS tension-anxiety, and age. Our study suggests that increased POMS tension-anxiety was highly associated with down-regulation of β-adrenergic receptors, even in subjects who do not have psychiatric illness. Numerous psychological states could be associated with changes of β-adrenergic receptor responsiveness in a normal population.

Development of an LC–MS/MS method for the simultaneous determination of 25 benzodiazepines and zolpidem in oral fluid and its application to authentic samples from regular drug users

A simple and reliable analytical method was established and validated for the simultaneous determination of 25 benzodiazepines and zolpidem in oral fluid obtained using the Quantisal™ collection device. The samples were prepared by liquid-liquid extraction with ethyl acetate and analyzed using liquid chromatography-tandem mass spectrometry. The validation parameters included limits of detection and quantification (LOD and LOQ), linearity, accuracy and precision, selectivity, recovery, matrix effects and process efficiency. To investigate the variables associated with collection of oral fluid, drug stability and drug recovery in/from the collection device were also determined. The LOD ranged from 0.01 ng/ml to 0.5 ng/ml and the LOQ ranged from 0.1 ng/ml to 0.5 ng/ml. The results of the intra- and inter-day precision and accuracy were satisfactory, i.e., <10% for precision and within ± 10% for accuracy at a low (LOQ of each analyte) and high concentrations (5 ng/ml). In addition, all analytes were stable under the storage condition of below -20°C for 1 month. Drug recoveries from the collection device were more than 80% (81-95%) except those of clonazepam and flunitrazepam, which were unstable in oral fluid. The developed method was successfully applied to authentic oral fluid specimens obtained from psychiatric patients who take benzodiazepines or zolpidem regularly. As a result, alprazolam, clonazepam, diazepam, flunitrazepam, flurazepam, lorazepam, zolpidem and/or their metabolites were detected at 1-18 h after intake of these drugs. This study will be useful for the analysis of oral fluid samples collected in forensic toxicological cases.

Lymphocyte Subsets and Mood States in Panic Disorder Patients

This study was conducted to examine lymphocyte subset counts and mood states in panic disorder patients. Twenty patients with panic disorder and 20 age- and gender-matched normal healthy subjects were recruited for the study. We used the Spielberger State (STAIS) & Trait (STAIT) Anxiety Inventory, Hamilton Depression Rating scale (HAMD) and Hamilton Anxiety Rating scale (HAMA) to measure mood states in all subjects. Lymphocyte subsets counts were made by flow cytometry. Panic patients showed significantly higher scores for anxiety and depression than normal subjects. Panic patients showed no differences in terms of the numbers of immune cells, as compared with normal healthy subjects, other than a lower proportion of T suppressor cells and a higher T helper cell/T suppressor cell ratio. HAMA and STAIS scores were common factors that could predict T cell numbers and proportions, T helper cell numbers, and natural killer cell proportions in panic disorder patients. We suggest that anxiety levels are related to the T-cell population in panic disorder patients and that quantitative immune differences may reflect altered immunity in this disorder.

The Genetic Basis of Panic Disorder

Panic disorder is one of the chronic and disabling anxiety disorders. There has been evidence for either genetic heterogeneity or complex inheritance, with environmental factor interactions and multiple single genes, in panic disorders etiology. Linkage studies have implicated several chromosomal regions, but no research has replicated evidence for major genes involved in panic disorder. Researchers have suggested several neurotransmitter systems are related to panic disorder. However, to date no candidate gene association studies have established specific loci. Recently, researchers have emphasized genome-wide association studies. Results of two genome-wide association studies on panic disorder failed to show significant associations. Evidence exists for differences regarding gender and ethnicity in panic disorder. Increasing evidence suggests genes underlying panic disorder overlap, transcending current diagnostic boundaries. In addition, an anxious temperament and anxiety-related personality traits may represent intermediate phenotypes that predispose to panic disorder. Future research should focus on broad phenotypes, defined by comorbidity or intermediate phenotypes. Genome-wide association studies in large samples, studies of gene-gene and gene-environment interactions, and pharmacogenetic studies are needed.

Effect of Biofeedback-assisted Autogenic Training on Headache Activity and Mood States in Korean Female Migraine Patients

Biofeedback with or without combined autogenic training is known to be effective for the treatment of migraine. This study aimed to examine the effect of biofeedback treatment on headache activity, anxiety, and depression in Korean female patients with migraine headache. Patients were randomized into the treatment group (n=17) and monitoring group (n=15). Mood states including anxiety and depression, and psychophysiological variables such as mean skin temperature of the patients were compared with those of the normal controls (n=21). We found greater treatment response rate (defined as ≥50% reduction in headache index) in patients with biofeedback-assisted autogenic training than in monitoring group. The scores on the anxiety and depression scales in the patients receiving biofeedback-assisted autogenic training decreased after the biofeedback treatment. Moreover, the decrease in their anxiety levels was significantly related to the treatment outcome. This result suggests that the biofeedback-assisted autogenic training is effective for the treatment of migraine and its therapeutic effect is closely related to the improvement of the anxiety level.

Increased cholesterol levels after paroxetine treatment in patients with panic disorder.

Abstract: Panic disorder (PD) is associated with an increased cardiovascular risk. We examined serum cholesterol and plasma catecholamine levels in PD before and after paroxetine treatment. The serum cholesterol and plasma catecholamine levels were not different between the PD patients and control subjects before the treatment. However, the levels of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were significantly increased in the 28 PD patients after 3 months of paroxetine treatment, whereas the body mass index and plasma catecholamine levels were unchanged. Paroxetine should be used cautiously for PD patients who have overt or covert cardiovascular disorders.

Reliability and validity of the self-report version of the Panic Disorder Severity Scale in Korea

Background: The self‐report version of the Panic Disorder Severity Scale (PDSS‐SR) has been developed recently and has demonstrated good psychometric properties. However, there is no cross‐cultural evaluation of this scale. The purpose of this study was to confirm the reliability and validity of the PDSS‐SR in Korean subjects. Methods: We studied 148 patients with principal DSM‐IV diagnoses of panic disorder who underwent formal structured diagnostic assessment and the PDSS interview. The participants completed self‐report measures including the PDSS‐SR, Anxiety Sensitivity Index‐Revised, Albany Panic and Phobia Questionnaire, Beck Depression Inventory, Beck Anxiety Inventory, and Spielberger State–Trait Anxiety Inventory‐Trait Version. Results: The PDSS‐SR had a single‐factor structure, with all seven items having salient loadings. Cronbachs α for the PDSS‐SR was .88 and intraclass correlation coefficient was .71 between PDSS‐SR and PDSS. Also, the scale showed excellent 1‐day test–retest reliability and demonstrated significant correlation with other anxiety‐related measures. In addition, the PDSS‐SR was sensitive to change with pharmacological treatment. Conclusions: The findings of this study strongly support the reliability and validity of the PDSS‐SR. It is expected that this scale will be helpful in clinical settings and research protocols in Korea. Depression and Anxiety, 2009.

Changes in lymphocyte subsets after short-term pharmacotherapy in patients with panic disorder

Panic disorder is associated with a high frequency of comorbid immunological diseases, such as allergies and asthma, although the psychoneuroimmunology of panic disorder is relatively unexplored. The objective of this study was to determine whether panic patients have different immunological findings compared with normal healthy subjects and whether changes in immune function are associated with short-term pharmacotherapy. We also examined whether immunological variables were associated with clinical severity and serum catecholamine levels. Patients with panic disorder (n=26) and healthy control subjects (n=26) were recruited for this study. All patients were treated with paroxetine for 3 months. We measured the lymphocyte subsets, psychopathological characteristics and serum catecholamine (norepinephrine and epinephrine) levels. Panic patients did not differ initially from control subjects in peripheral lymphocyte phenotypic markers. After drug therapy, however, percentages of circulating CD3+, CD4+ and CD8+ T lymphocytes were significantly increased, while the percentage of CD19+ B lymphocytes was significantly decreased in the patients. The difference in the percentage of CD8+ T lymphocytes before and after treatment was negatively correlated with pretreatment Global Clinical Impression scores. The lymphocyte subsets were not significantly associated with serum catecholamine levels in panic patients. In conclusion, panic patients showed increased CD3+, CD4+ and CD8+ T lymphocyte proportions and a decreased B lymphocyte proportion after 3 months of drug therapy. This finding suggests that pharmacological treatment may affect immune function in panic patients.