Effects of smartphone use with and without blue light at night in healthy adults: A randomized, double-blind, cross-over, placebo-controlled comparison.

Smartphones deliver light to users through Light Emitting Diode (LED) displays. Blue light is the most potent wavelength for sleep and mood. This study investigated the immediate effects of smartphone blue light LED on humans at night. We investigated changes in serum melatonin levels, cortisol levels, body temperature, and psychiatric measures with a randomized, double-blind, cross-over, placebo-controlled design of two 3-day admissions. Each subject played smartphone games with either conventional LED or suppressed blue light from 7:30 to 10:00PM (150 min). Then, they were readmitted and conducted the same procedure with the other type of smartphone. Serum melatonin levels were measured in 60-min intervals before, during and after use of the smartphones. Serum cortisol levels and body temperature were monitored every 120 min. The Profile of Mood States (POMS), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and auditory and visual Continuous Performance Tests (CPTs) were administered. Among the 22 participants who were each admitted twice, use of blue light smartphones was associated with significantly decreased sleepiness (Cohen's d = 0.49, Z = 43.50, p = 0.04) and confusion-bewilderment (Cohen's d = 0.53, Z = 39.00, p = 0.02), and increased commission error (Cohen's d = -0.59, t = -2.64, p = 0.02). Also, users of blue light smartphones experienced a longer time to reach dim light melatonin onset 50% (2.94 vs. 2.70 h) and had increases in body temperature, serum melatonin levels, and cortisol levels, although these changes were not statistically significant. Use of blue light LED smartphones at night may negatively influence sleep and commission errors, while it may not be enough to lead to significant changes in serum melatonin and cortisol levels.

Plasma catecholamine levels before and after paroxetine treatment in patients with panic disorder.

Catecholamines such as norepinephrine, epinephrine, and dopamine are closely related to the autonomic nervous system, suggesting that panic disorder may involve elevated catecholamine levels. This study investigated basal and posttreatment catecholamine levels in patients with panic disorder. A total of 29 patients with panic disorder and 23 healthy controls participated in the study. Panic disorder patients received paroxetine treatment for 12 weeks after clinical tests and examination had been conducted. We investigated the difference in basal levels of catecholamine and measured the changes in catecholamine levels before and after drug treatment in panic disorder patients. The basal plasma epinephrine (48.87±6.18 pg/ml) and dopamine (34.87±3.57 pg/ml) levels of panic disorder patients were significantly higher than those (34.79±4.72 pg/ml and 20.40±3.53 pg/ml) of the control group. However, basal plasma norepinephrine levels did not show statistically significant differences between patients and controls. After drug therapy, plasma catecholamine levels were nonsignificantly decreased and norepinephrine levels showed a tendency toward a decrease that did not reach significance. In conclusion, this study suggests the possibility of a baseline increase of plasma catecholamine levels and activation of sympathetic nervous systems in patients with panic disorder which may normalize after treatment with paroxetine.

Clinical characteristics of the respiratory subtype in panic disorder patients.

OBJECTIVE: Panic disorder has been suggested to be divided into the respiratory and non-respiratory subtypes in terms of its clinical presentations. The present study aimed to investigate whether there are any differences in treatment response and clinical characteristics between the respiratory and non-respiratory subtypes of panic disorder patients. METHODS: Among the 48 patients those who completed the study, 25 panic disorder patients were classified as the respiratory subtype, whereas 23 panic disorder patients were classified as the non-respiratory subtype. All patients were treated with escitalopram or paroxetine for 12 weeks. We measured clinical and psychological characteristics before and after pharmacotherapy using the Panic Disorder Severity Scale (PDSS), Albany Panic and Phobic Questionnaire (APPQ), Anxiety Sensitivity Index-Revised (ASI-R), State-Trait Anxiety Inventory (STAI-T, STAI-S), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D). RESULTS: The prevalence of the agoraphobia was significantly higher in the respiratory group than the non-respiratory group although there were no differences in gender and medication between the two groups. The respiratory group showed higher scores on the fear of respiratory symptoms of the ASI-R. In addition, after pharmacotherapy, the respiratory group showed more improvement in panic symptoms than the non-respiratory group. CONCLUSION: Panic disorder patients with the respiratory subtype showed more severe clinical presentations, but a greater treatment response to SSRIs than those with non-respiratory subtype. Thus, classification of panic disorder patients as respiratory and non-respiratory subtypes may be useful to predict clinical course and treatment response to SSRIs.

Diagnostic utility of worry and rumination: a comparison between generalized anxiety disorder and major depressive disorder.

AIM: Although previous reports have addressed worry and rumination as prominent cognitive processes in generalized anxiety disorder (GAD) and major depressive disorder (MDD) and their distinct correlation with anxious and depressive symptoms, the differential association of worry and rumination with the diagnosis of GAD and MDD remains unclear. The purpose of this study was to investigate the distinct features of worry and rumination in factor structure and their predictive validity for the diagnosis of GAD and MDD. METHODS: Four hundred and sixty-eight patients with GAD (n = 148) and MDD (n = 320) were enrolled and the diagnoses were confirmed with the Structured Clinical Interview for DSM-IV. Participants completed the Penn State Worry Questionnaire and Ruminative Response Scale and the severity of anxiety and depressive symptoms was assessed via clinician ratings. RESULTS: In joint factor analysis using the Penn State Worry Questionnaire and Ruminative Response Scale items, worry and rumination emerged as distinct factors. In logistic regression analyses, worry contributed to a higher probability of the diagnosis of GAD than rumination, as rumination did in MDD than worry. CONCLUSION: This is the first comprehensive study investigating the diagnostic utility of worry and rumination in a well-defined clinical sample of both GAD and MDD. Our results suggest that worry and rumination are distinct cognitive processes and play a differential role in the diagnosis of GAD and MDD, distinguishing them at the cognitive level.

The usefulness of the korean version of penn state worry questionnaire for screening generalized anxiety disorder: a receiver operating characteristic analysis.

OBJECTIVE: Excessive worry about minor matters and a state in which this worry is experienced as uncontrollable are known to be key symptoms of generalized anxiety disorder (GAD). Given the importance of pathological worry in GAD, the need for psychometrically sound measures of this construct has increased. The purpose of this study was to investigate the usefulness of the Korean version of Penn State Worry Questionnaire (K-PSWQ) for screening GAD. METHODS: Two hundred and forty six patients were initially screened, from which 102 GAD patients and 118 patients with anxiety disorder not otherwise specified (anxiety disorder NOS) were finally enrolled. Patients were diagnosed by a structured clinical interview for the DSM-IV Axis I. We also enrolled 114 control subjects who had no medical or psychiatric history. Pathological worry in both patients and control subjects were assessed at baseline using the PSWQ and we estimated optimal cutoff score by the receiver operating characteristic (ROC) analysis. RESULTS: We found that in the first ROC analysis, a score of 53 could simultaneously optimize sensitivity and specificity in order to discriminate GAD patients from control subjects. From the second receiver operating characteristic analysis, when both sensitivity and specificity were optimized, we can suggest a score of 61 as being the cutoff for differentiating GAD patients from patients with anxiety disorder NOS. CONCLUSION: The Korean version of PSWQ is a useful method for screening GAD patients, although ethnic and cultural differences may affect the cutoff score of PSWQ for GAD.

Improvement in subjective and objective neurocognitive functions in patients with major depressive disorder: a 12-week, multicenter, randomized trial of tianeptine versus escitalopram, the CAMPION study.

Although many patients with major depressive disorder (MDD) complain of neurocognitive impairment, the effects of antidepressant medications on neurocognitive functions remain unclear. This study compares neurocognitive effects of tianeptine and escitalopram in MDD. Patients with MDD (N = 164) were randomly assigned in a 1:1 ratio to either tianeptine (37.5 mg/d) or escitalopram (10 mg/d) for 12 weeks. Outcome measures included clinical improvement, subjective cognitive impairment on memory and concentration, the Mini-Mental State Examination, the Continuous Performance Test, the Verbal Learning Test, and the Raven Progressive Matrices, assessed every 4 weeks. After 12 weeks, the tianeptine group showed significant improvement in commission errors (P = 0.002), verbal immediate memory (P < 0.0001), Mini-Mental State Examination (P < 0.0001), delayed memory (P < 0.0001), and reasoning ability (P = 0.0010), whereas the escitalopram group improved in delayed memory and reasoning ability but not in the other measures. Both groups significantly improved in subjective cognitive impairment in memory (P < 0.0001) and concentration (P < 0.0001). Mixed effects model repeated measures analyses revealed that the tianeptine group had a significant improvement in scores of commission errors (F = 6.64, P = 0.011) and verbal immediate memory (F = 4.39, P = 0.038) from baseline to 12 weeks, compared with the escitalopram group, after controlling for age, sex, education years, baseline scores, and changes of depression severity. The treatment of MDD with tianeptine led to more improvements in neurocognitive functions, especially in commission errors and verbal immediate memory, compared with escitalopram, after controlling for changes in depression severity. Both drugs improved subjective cognitive impairment of memory and concentration.

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 Tukey's 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 (ß = -0.187, p = 0.039), whereas VLDL was positively associated with the recent suicide status (ß = 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.

Follicle-stimulating hormone (FSH), current suicidal ideation and attempt in female patients with major depressive disorder.

Current suicidal ideation and attempts are more commonly found in female patients with major depressive disorder (MDD) than in males. However, little is known about the relationship between activity of female reproductive hormones and suicide. The study population consisted of 490 female MDD patients of age ≥18. They were assessed by the Mini-International Neuropsychiatric Interview. At the same visit, we measured blood Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol, progesterone, Adrenocorticotropic Hormone (ACTH), cortisol, thyroid hormones, and prolactin. Blood FSH showed a significant difference among female MDD patients with suicide attempt, those with ideation, and those without within the previous month. Post-hoc analysis also showed that FSH was significantly lower in MDD patients with suicide attempt and ideation than those without, whereas other hormones showed no differences between those with and without attempt. FSH was negatively associated with current suicidality scores after adjustment for age and education years in all age groups. FSH was significantly lower in those with current suicide ideation or attempt than those without in age 45 years or under, but not in other age groups. In conclusion, blood FSH is significantly lower in female MDD patients with current suicide attempt or ideation than those without, especially in age 45 years or under.

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.

Temperament affects sympathetic nervous function in a normal population.

OBJECTIVE: Although specific temperaments have been known to be related to autonomic nervous function in some psychiatric disorders, there are few studies that have examined the relationship between temperaments and autonomic nervous function in a normal population. In this study, we examined the effect of temperament on the sympathetic nervous function in a normal population. METHODS: Sixty eight healthy subjects participated in the present study. Temperament was assessed using the Korean version of the Cloninger Temperament and Character Inventory (TCI). Autonomic nervous function was determined by measuring skin temperature in a resting state, which was recorded for 5 minutes from the palmar surface of the left 5th digit using a thermistor secured with a Velcro® band. Pearson's correlation analysis and multiple linear regression were used to examine the relationship between temperament and skin temperature. RESULTS: A higher harm avoidance score was correlated with a lower skin temperature (i.e. an increased sympathetic tone; r=-0.343, p=0.004) whereas a higher persistence score was correlated with a higher skin temperature (r=0.433, p=0.001). Hierarchical linear regression analysis revealed that harm avoidance was able to predict the variance of skin temperature independently, with a variance of 7.1% after controlling for sex, blood pressure and state anxiety and persistence was the factor predicting the variance of skin temperature with a variance of 5.0%. CONCLUSION: These results suggest that high harm avoidance is related to an increased sympathetic nervous function whereas high persistence is related to decreased sympathetic nervous function in a normal population.

Regional brain metabolism and treatment response in panic disorder patients: an [18F]FDG-PET study.

BACKGROUND: Panic disorder (PD) is a common and often chronic psychiatric condition that can lead to considerable disability in daily life. Using [(18)F]fluorodeoxyglucose-PET, we examined brain baseline glucose metabolism in PD patients in comparison with normal controls and the changes in glucose metabolism after 12 weeks of escitalopram treatment. METHODS: Fifteen patients with PD were compared to 20 normal controls using [(18)F]FDG-PET at baseline and brain metabolism after 12 weeks of escitalopram treatment was compared to pretreatment in the patient group using voxel-based statistical analysis and post hoc region-of-interest analysis. RESULTS: Patients with PD showed decreased metabolism in both the frontal, right temporal, and left posterior cingulate gyruses. After 12 weeks of escitalopram treatment, treatment responders showed metabolic increases in global neocortical areas as well as limbic areas whereas nonresponders did not. CONCLUSION: Abnormal neocortical function appears to be associated with the pathophysiology of PD and escitalopram exerts its therapeutic action by modulating brain activity at the level of the neocortex and limbic system, notably the amygdala and parahippocampal gyrus.

Psychological characteristics of early remitters in patients with panic disorder.

We aimed to examine whether anxiety sensitivity and agoraphobic fear could affect the time taken to remission after 24 weeks of open-label escitalopram treatment of patients with panic disorder (PD). We recruited 158 patients, and 101 patients completed the study. Clinical severity and psychological characteristics were assessed at baseline and 4, 12, and 24 weeks after the treatment, using the Clinical Global Impression-Severity (CGI-S), the Hamilton Rating Scales for Anxiety and Depression, the Anxiety Sensitivity Index-Revised (ASI-R), the Albany Panic and Phobia Questionnaire (APPQ), and the Panic Disorder Severity Scale (PDSS). Remission was defined as the absence of full panic attacks and PDSS scores of 7 or less. Completing patients were stratified according to the time taken to remit: early (n=20) and late (n=58) remission and non-remission groups (n=23). There were no significant differences among the three groups at baseline on the CGI-S and the PDSS mean scores. However, early remitters had significantly lower scores than late remitters and non-remitters on the ASI-R and APPQ. In conclusion, anxiety sensitivity and agoraphobic fear can affect the time to remission after pharmacotherapy, and clinicians should consider the psychological characteristics of PD patients in order to achieve an optimal response to pharmacotherapy.

Long-term Escitalopram Treatment in Korean Patients with Panic Disorder: A Prospective, Naturalistic, Open-label, Multicenter Trial.

OBJECTIVE: Panic disorder is characterized by recurrent panic attacks, persistent concerns about additional attacks, and worry about the implications of the attack or significant changes in behavior related to the attacks. We examined the efficacy of 24-week naturalistic, open-label escitalopram treatment in terms of the response and remission rates and functional disability in 119 adult Korean patients with panic disorder from 6 clinical centers in South Korea. METHODS: Clinical severity and functional impairment were assessed at baseline and at 4, 12, and 24 weeks after the treatment using the Panic Disorder Severity Scale and Sheehan Disability Scale. Ninety-six patients (80.7%) showed a treatment response, and 87 patients (73.1%) had attained remission after 24 weeks of escitalopram treatment. RESULTS: Continuous improvement in the Panic Disorder Severity Scale and Sheehan Disability Scale scores was found over the 24 weeks of treatment. CONCLUSION: These findings suggest that escitalopram treatment is very effective for panic disorder in terms of both response and remission rates and that long-term pharmacotherapy with escitalopram continuously improved panic symptoms and functional disability in Korean patients with panic disorder.

Underestimating the severity of bipolar depression: a comparison of the Hamilton Depression Rating Scale items.

BACKGROUND: The Hamilton Depression Rating Scale (HDRS) is a clinician-rated instrument to assess the severity of depressive symptoms that does not account for the differences between bipolar (BP) and unipolar (UP) disorders. This study attempts to evaluate differences in the total scores of the HDRS, Beck Depression Inventory (BDI), and Global Assessment of Functioning (GAF) ratings of patients with bipolar II (BP-II) and UP depression. Each factor and item of the HDRS was compared between the two groups in order to identify specific symptoms. METHODS: 588 patients with bipolar II disorder (n=101) and major depressive disorder (n=487) were enrolled in this study. All participants completed the BDI and individually interviewed using HDRS. Each participant was also evaluated with regard to global functioning. RESULTS: The BP group scored lower on the total HDRS and all of the factors. The BP and UP groups did not differ in terms of BDI and GAF. With regard to the individual items of HDRS, the BP group scored lower on items associated with 'Depressed mood', 'Work and interest', 'Somatic, gastro', and 'Hypochondriasis'. LIMITATIONS: There was a significant age differences between the two groups. CONCLUSIONS: The results of this study suggest that the severity of bipolar depression may be less well-recognized by the HDRS due to the different presentations of depressive symptoms. Thus, the clinician should be careful not to underestimate the sincerity of patients' reports when evaluating depression.

Ruminative response in clinical patients with major depressive disorder, bipolar disorder, and anxiety disorders.

BACKGROUND: There is a growing interest in the transdiagnostic trait of rumination. However, few studies have directly examined the ruminative response in the diagnosis of disorders other than major depression, such as anxiety disorders and bipolar disorders. Even fewer studies have done so in a large, clinical sample. METHOD: Patients with major depressive disorder (MDD), bipolar disorder (BPD), panic disorder with/without agoraphobia (PD), and generalized anxiety disorder or obsessive-compulsive disorder (GAD/OCD) were compared using the Ruminative Response Scale (RRS), Hamilton Rating Scale for Depression (HAM-D), and Hamilton Rating Scale for Anxiety (HAM-A). RESULTS: The PD group displayed the lowest levels of rumination even when depression and anxiety symptoms were treated as a covariate. The BPD group displayed higher levels of rumination than the MDD group. CONCLUSIONS: A heightened ruminative response was not only found among individuals with MDD, but also among those with BPD and GAD/OCD; this might indicate ineffective thought control.

Relationship between Personality and Insomnia in Panic Disorder Patients.

OBJECTIVE: Panic disorder (PD) is frequently comorbid with insomnia, which could exacerbate panic symptoms and contribute to PD relapse. Research has suggested that characteristics are implicated in both PD and insomnia. However, there are no reports examining whether temperament and character affect insomnia in PD. Thus, we examined the relationship between insomnia and personality characteristics in PD patients. METHODS: Participants were 101 patients, recruited from 6 university hospitals in Korea, who met the DSM-IV-TR criteria for PD. We assessed sleep outcomes using the sleep items of 17-item Hamilton Depression Rating Scale (HAMD-17)(item 4=onset latency, item 5=middle awakening, and item 6=early awakening) and used the Cloninger's Temperament and Character Inventory-Revised-Short to assess personality characteristics. To examine the relationship between personality and insomnia, we used analysis of variance with age, sex, and severity of depression (total HAMD scores minus sum of the three sleep items) as the covariates. RESULTS: There were no statistical differences (p>0.1) in demographic and clinical data between patients with and without insomnia. Initial insomnia (delayed sleep onset) correlated to a high score on the temperamental dimension of novelty seeking 3 (NS3)(F(1,96)=6.93, p=0.03). There were no statistical differences (p>0.1) in NS3 between patients with and without middle or terminal insomnia. CONCLUSION: The present study suggests that higher NS3 is related to the development of initial insomnia in PD and that temperament and character should be considered when assessing sleep problems in PD patients.

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 disorder's 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.

Uncontrolled self-medication with venlafaxine in a patient with major depressive disorder.

Antidepressants are known to have no significant ability to cause addiction. However, a recent study showed many individuals with mood disorders self-medicated with antidepressants to relieve symptoms. We report here a male physician, diagnosed five years ago with major depressive disorder, with insomnia, anxiousness, and chest heaviness. He began self-medicating with 150 mg of venlafaxine daily, without any monitoring. During his most recent severe depressive episode, he was taking up to 1,500 mg of venlafaxine daily. Without this medication, he experienced discontinuation syndrome, which included severe anxiety, chest heaviness, and breathing difficulty, and which he judged as indicating a more severely depressed state. He also experienced overdose symptoms, such as hypertension and tachycardia. He attempted suicide with drugs that he possessed. In conclusion, careful monitoring is needed when treating patients with venlafaxine, because its discontinuation syndrome is similar to symptoms of major depressive disorder, and suicidality may result from an overdose.

The positive and negative affect schedule: psychometric properties of the korean version.

OBJECTIVE: The Positive and Negative Affect Schedule (PANAS) was developed as a measure of positive affect (PA) and negative affect (NA). The aim here is to examine the factor structure and concurrent validity of the Korean version of the Positive and Negative Affect Schedule (K-PANAS) in a clinical sample in Korea. METHODS: K-PANAS was administered to a clinical sample in Korea. Internal consistency, test-retest reliability, and confirmatory factor analysis (CFA) were undertaken to examine the factorial structure and reliability of the K-PANAS. RESULTS: The reliability of K-PANAS is satisfactory. CFA showed that several of the models commonly used in Western populations provided an insufficient fit. The modified model provided a more adequate fit to the data. CONCLUSION: The authors demonstrate that the K-PANAS has adequate psychometric properties, and that findings obtained in the West using PANAS were partially replicated.

Changes in Cerebral Cortex and Limbic Brain Functions after Short-Term Paroxetine Treatment in Panic Disorder: An [F]FDG-PET Pilot Study.

OBJECTIVE: Panic disorder (PD) is a common and often chronic psychiatric illness, and serotonin-specific reuptake inhibitors (SSRIs) are the drugs of choice for the treatment of PD. Previous studies suggested the cerebral cortex and limbic brain structures played a major role in the development of PD, but the therapeutic effect of SSRIs on specific brain structures remains unclear in PD. We examined the changes in PD patients' glucose metabolism using the [(18)F] Fluorodeoxy-glucose-positron emission tomography (FDG-PET) before and after 12 weeks of paroxetine treatment. METHODS: We assessed the brain glucose metabolism of 5 PD patients, using the [(18)F]FDG-PET, and treated them with paroxetine (12.5-37.5 mg/day) for 12 weeks. Then, we compared before and after treatment PET images of the patients, using voxel-based statistical analysis and a post hoc regions of interest analysis. Furthermore, we measured the patients' clinical variables, including information from the Panic Disorder Severity Scale (PDSS), Clinical Global Impression for Severity (CGI-S), and Hamilton Anxiety Rating Scale (HAMA). RESULTS: After 12 weeks of paroxetine treatment, the patients showed significant clinical improvement in terms of PDSS, CGI-S and HAMA scores (12.8±1.8 vs. 3.8±2.3, 4.6±0.5 vs. 2.0±1.4, and 15.2±4.0 vs. 5.0±1.2, respectively; all p values<0.05). After treatment, patients' glucose metabolism increased significantly in global brain areas: the right precentral gyrus, right middle frontal gyrus, right amygdala, right caudate body, right putamen, left middle frontal gyrus, left precentral gyrus, left insula, left parahippocampal gyrus, and left inferior frontal gyrus (All areas were significant at uncorrected p<0.001 and cluster level corrected p<0.05). CONCLUSION: In these PD patients, cerebral cortex and limbic brain functions changed after short-term treatment with paroxetine. The therapeutic action of paroxetine may be related to altered glucose metabolism at both the cerebral cortex and limbic brain areas.