Effects of Paliperidone Palmitate on Healthcare Utilization and Costs for Patients with Schizophrenia: A Claim-based Mirror-image Study in South Korea

Objective@#Long-acting injectable (LAI) antipsychotics, such as paliperidone palmitate (PP), are known to improve treatment adherence in patients with schizophrenia, which can lead to reductions in relapse and hospitalization rates. However, relatively few studies have demonstrated the economic impact of LAIs, especially in Asian populations. @*Methods@#We conducted a claim-based mirror-image study to explore changes in healthcare utilization and associated costs, among 1,272 South Korean patients with schizophrenia (ICD-10-CM code F20), between the 1-year periods before and after the initiation of PP treatment. @*Results@#Patients accessed outpatient services more frequently after versus before starting PP treatment, with the number of prescription days increasing by 133.45 (p ＜ 0.0001) and the associated costs increasing by USD 1,497.15 (p ＜ 0.0001). The number of admission days was reduced by 11.33 after starting PP treatment (p ＜ 0.0001) and the associated costs were reduced by USD 1,220.75 (p ＜ 0.0001). However, admission cost savings were different according to patients’ oral drug compliance. The daily dosages for benztropine, procyclidine, and propranolol decreased, showing that there were fewer side-effects after PP-treatment (p ＜ 0.0001). @*Conclusion@#Although the high acquisition cost of PP has been regarded as an obstacle to its clinical use, our results imply that the high prescription costs for PP may be counterbalanced by the reduced admission costs associated with its use. Economic outcomes for patients treated with LAIs should be investigated further to help healthcare decision-makers and providers to determine the value of LAIs relative to other treatment medications.

Effects of an Online Imagery-Based Treatment Program in Patients with Workplace-Related Posttraumatic Stress Disorder: A Pilot Study

OBJECTIVE: We developed easily accessible imagery-based treatment program for patients with post-traumatic stress disorder (PTSD) related to workplace accidents and investigated the effects of the program on various PTSD related symptoms. METHODS: The program was based on an online platform and consisted of eight 15-min sessions that included script-guided imagery and supportive music. Thirty-five patients with workplace-related PTSD participated in this program 4 days per week for 4 weeks. Its effects were examined using self-report questionnaires before and after the take-home online treatment sessions. RESULTS: After completing the 4-week treatment program, patients showed significant improvements in depressed mood (t=3.642, p=0.001) based on the Patient Health Questionnaire-9 (PHQ-9), anxiety (t=3.198, p=0.003) based on the Generalized Anxiety Disorder seven-item (GAD-7) scale, and PTSD symptoms (t=5.363, p < 0.001) based on the Posttraumatic Stress Disorder Check List (PCL). In particular, patients with adverse childhood experiences exhibited a greater degree of relief related to anxiety and PTSD symptoms than those without adverse childhood experiences. CONCLUSION: The present results demonstrated that the relatively short online imagery-based treatment program developed for this study had beneficial effects for patients with workplace-related PTSD.

In-Depth Relationships between Emotional Intelligence and Personality Traits in Meditation Practitioners

OBJECTIVE: Meditation can elicit trait-like changes in psychological and social styles, as well as enhancement of emotional regulatory capacity. We investigated the relation between personality traits and emotional intelligence in meditation practitioners. METHODS: Seventy-two long-term practitioners of mind-body training (MBT) and 62 healthy comparative individuals participated in the study. The participants completed emotional intelligence questionnaires and the Myers-Briggs Type Indicator (MBTI). RESULTS: The MBT group revealed higher scores on all five emotional intelligence factors than did those in the control group, such as emotional awareness and expression, empathy, emotional thinking, emotional application, and emotional regulation (all p≤0.001). MBT practitioners also had higher scores on the intuition of perceiving function (t=−2.635, p=0.010) and on the feeling of the judging function (t=−3.340, p=0.001) of the MBTI compared with those in the control group. Only the MBT group showed a robust relationship with every factor of emotional intelligence and MBTI-defined intuitive styles, indicating that higher scores of emotional intelligence were related to higher scores for intuition. CONCLUSION: Emotional intelligence of meditation practitioners showed notable relationships with some features of personality trait. In-depth associations between emotional intelligence and personality traits would help to foster psychological functions in meditation practitioners.

Peripheral and Central Metabolites Affecting Depression, Anxiety, Suicidal Ideation, and Anger in Complex Regional Pain Syndrome Patients Using a Magnetic Resonance Spectroscopy: A Pilot Study

OBJECTIVE: This study investigated peripheral and central metabolites affecting depression, anxiety, suicidal ideation, and anger in complex regional pain syndrome (CRPS) patients. METHODS: Metabolite levels were determined in the right and left thalamus and insula, in 12 CRPS patients using magnetic resonance spectroscopy (MRS). RESULTS: There were positive correlations between valine (Val)/tNAA (N-acetylaspartate+N-acetylaspartylglutamate) and the anxiety, and a negative correlation between glutamine (Gln)/NAA and the depression. There were positive correlations between alanine (Ala)/Gln and the depression and suicidal ideation, between glutamate (Glu)/Gln and the depression and suicidal ideation, between N-acetylaspartylglutamate (NAAG)/Gln and the depression. There was a positive correlation between Ala/NAAG and the trait anger and a negative correlation between creatine (Cr)/N-acetylaspartate (NAA) and the trait anger. There was a negative correlation between Cr/Glx (Glu+Gln) and the trait anger. High hemoglobin and alkaline phosphatase were associated with low pain levels, but CO2 and chloride showed positive correlations with pain levels in CRPS patients. Peripheral glucose, CO2 and chloride were associated with depression, anxiety, anger and suicidal ideation. CONCLUSION: The specific central and peripheral metabolites were associated with psychological disorders including depression, anxiety, suicidal ideation and anger in CRPS patients, showing pathological interactions between a painful body and mind.

Effects of Cognitive-Behavioral Therapy on Empathy in Patients with Chronic Pain

OBJECTIVE: Cognitive-behavioral therapy (CBT) is effective in patients with chronic pain. However, the efficacy of CBT for impaired empathy has not been studied in this population. We investigated the effect of CBT on empathy in patients with chronic pain. METHODS: Patients with severe chronic pain were recruited. Empathy was assessed before and after CBT using the Interpersonal Reactivity Index (IRI). The patients underwent eight sessions over the course of 1 month conducted. Additional symptoms were assessed using the Short-Form McGill Pain Questionnaire (SF-MPQ), Beck Depression Inventory, Beck Anxiety Inventory, World Health Organization Quality of Life Scale Abbreviated Version, and the Scale for Suicide Ideation. RESULTS: A total of 26 participants were included. Pre-CBT pain severity assessed using the SF-MPQ was significantly correlated with the IRI-empathic concern subscale score (p=0.021), and the relationship remained significant after adjusting for sex, age, education level, and marital status. After CBT, the IRI-perspective-taking subscale scores (p=0.004) increased significantly and the IRI-personal distress subscale scores (p=0.013) decreased significantly in all participants. The SF-MPQ scores increased significantly (p=0.021). CONCLUSION: CBT improved empathy in patients with chronic pain independent of its effect on pain, suggesting that CBT is useful for improving interpersonal relationships in patients with chronic pain.

Effects of Mind-Body Training on Cytokines and Their Interactions with Catecholamines

OBJECTIVE: Mind-body training (MBT) may control reactions to stress and regulate the nervous and immune systems. The present study was designed to assess the effects of MBT on plasma cytokines and their interactions with catecholamines. METHODS: The study group consisted of 80 subjects who practice MBT and a control group of 62 healthy subjects. Plasma catecholamine (norepinephrine, NE; epinephrine, E; and dopamine, DA) and cytokine (TNF-alpha, IL-6, IFN-gamma, and IL-10) levels were measured, and the differences between the MBT and control groups and the interactions of cytokines with catecholamines were investigated. RESULTS: A significant increase in IL-10+IFN-gamma was found in females of the MBT group compared with controls. Also, a significant increase of IL-10 (anti-inflammatory cytokine) in the MBT group was shown in a specific condition in which TNF-alpha and IL-6 (pro-inflammatory cytokines) are almost absent (≤1 ng/L) compared with controls. In the MBT group, significant positive correlations were found between IL-10 and the NE/E ratio and between IL-10 and the DA/E ratio, whereas the control group did not show any such correlations. CONCLUSION: MBT may increase IL-10, under specific conditions such as a decrease of pro-inflammatory cytokines or E, which may regulate the stress response and possibly contribute to effective and beneficial interactions between the nervous and immune systems.

Impaired Empathic Abilities among Patients with Complex Regional Pain Syndrome (Type I)

OBJECTIVE: The aims of this study were to evaluate differences in empathic abilities between patients with complex regional pain syndrome (CRPS) Type I and healthy control subjects (HCs) and to assess correlations between empathic abilities and multidimensional aspects of pain. METHODS: Empathic ability was measured in 32 patients with CRPS Type I and in 36 HCs using the Interpersonal Reactivity Index (IRI). A comprehensive assessment of pain was conducted in the patient group using the West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Psychiatric symptoms were assessed using the Beck Depression and Anxiety Inventories (BDI and BAI), and quality of life was evaluated using the WHO Quality of Life (WHOQOL-BREF) questionnaire. RESULTS: Patients with CRPS showed impaired cognitive and emotional empathic abilities compared with HCs. Significantly lower levels of perspective taking and empathic concern and higher levels of personal distress on the IRI were exhibited by the patient group. Perspective taking and personal distress were associated with affective distress and poor quality of life in social contexts (BDI, BAI, and WHOQOL). However, empathic concern was positively correlated with pain severity and social support from others (WHYMPI). CONCLUSION: A tendency toward self-oriented distress in social cognition was exhibited among patients with CRPS Type I. Impaired empathic ability was shown to have potentially negative effects on subjective emotional outcomes and social performance in the lives of patients. Interventions to improve emotional awareness and theory of mind would be beneficial for enhancing social functioning in patients with CRPS Type I.

Effects of Mind-Body Training on Personality and Behavioral Activation and Inhibition System According to BDNF Val66Met Polymorphism

OBJECTIVE: It has been known that mind-body training (MBT) can affect personality and behavior system as well as emotional well-being, but different effects of MBT on them has not been reported according to BDNF genetic polymorphism. METHODS: Healthy subjects consisted of 64 subjects and the MBT group who practiced meditation regularly consisted of 72 practitioners. Participants completed neuroticism-extraversion-openness (NEO) Five-Factor Inventory and Behavioral Activation System/Behavioral Inhibition System (BAS/BIS) scales. All subjects were genotyped for the BDNF Val66Met polymorphism. RESULTS: In the same genotypes of the BDNF Val/Val+Val/Met group, MBT group showed the increased Extraversion (p=0.033) and the increased Openness to Experience (p=0.004) compared to the control group. Also, in the same Met/Met carriers, MBT group exhibited the increase of Extraversion (p=0.008), the reduction of Neuroticism (p=0.002), and the increase of Openness to Experience (p=0.008) compared to the control group. In the same genotypes of the BDNF Val/Val+Val/Met group, MBT group showed the decreased BAS-Reward Responsiveness (p=0.016) and the decrease of BIS (p=0.004) compared to the control group. In the BDNF Met/Met group, MBT group increased BAS-Fun Seeking (p=0.045) and decreased BIS (p=0.013) compared to the control group. CONCLUSION: MBT would differently contribute to NEO personality and BAS/BIS according to BDNF genetic polymorphism, compensating for different vulnerable traits based on each genotype.

Evaluating Carriers for Immobilizing Saccharomyces cerevisiae for Ethanol Production in a Continuous Column Reactor

We evaluated a more practical and cost-effective immobilization carriers for ethanol production using the yeast Saccharomyces cerevisiae. Three candidate materials-rice hull, rice straw, and sawdust-were tested for their cell-adsorption capacity and operational durability. Derivatizations of rice hull, rice straw, and sawdust with the optimal concentration of 0.5 M of 2-(diethylamino)ethyl chloride hydrochloride (DEAE . HCl) resulted in > 95% adsorption of the initial yeast cells at 2 hr for DEAE-rice hull and DEAE-sawdust and in only approximately 80% adsorption for DEAE-rice straw. In addition, DEAE-sawdust was found to be a more practical carrier for immobilizing yeast cells in terms of operational durability in shaking flask cultures with two different speeds of 60 and 150 rpm. Furthermore, the biosorption isotherms of DEAE-rice hull, -rice straw, and -sawdust for yeast cells revealed that the Qmax of DEAE-sawdust (82.6 mg/g) was greater than that of DEAE-rice hull and DEAE-rice straw. During the 404-hr of continuous column reactor operation using yeast cells immobilized on DEAE-sawdust, no serious detachment of the yeast cells from the DEAE-sawdust was recorded. Ethanol yield of approximately 3.04 g/L was produced steadily, and glucose was completely converted to ethanol at a yield of 0.375 g-ethanol/g-glucose (73.4% of the theoretical value). Thus, sawdust is a promising practical immobilization carrier for ethanol production, with significance in the production of bioethanol as a biofuel.

Ethanol Production from Glycerol by the Yeast Pachysolen tannophilus Immobilized on Celite during Repeated-Batch Flask Culture

We investigated a novel process for production of ethanol from glycerol using the yeast Pachysolen tannophilus. After optimization of the fermentation medium, repeated-batch flask culture was performed over a period of 378 hr using yeast cells immobilized on Celite. Our results indicated that the use of Celite for immobilization of P. tannophilus was a practical approach for ethanol production from glycerol, and should be suitable for industrial ethanol production.

Risk Factors for Suicidal Ideation among Patients with Complex Regional Pain Syndrome

OBJECTIVE: Chronic pain frequently coexists with psychiatric symptoms in patients diagnosed with complex regional pain syndrome (CRPS). Previous studies have shown a relationship between CRPS and the risk of suicide. The purpose of this study was to assess risk factors for suicidal ideation in patients with CRPS. METHODS: Based on criteria established by the International Association for the Study of Pain, 39 patients diagnosed with CRPS Type 1 or Type 2 were enrolled in this study. Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD), and symptoms of pain were evaluated using the short form of the McGill Pain Questionnaire (SF-MPQ). Psychiatric symptoms were assessed in using the Structured Clinical Interview for DSM-IV Disorders (SCID-I, SCID-II), the HAMD, the Hamilton Anxiety Rating Scale (HAMA), the Global Assessment of Functioning Scale (GAF), and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Twenty-nine patients (74.4%) were at high risk and 10 (25.6%) were at low risk for suicidal ideation. Risk factors significantly associated with suicidal ideation included depression (p=0.002), severity of pain (p=0.024), and low scores on the GAF (p=0.027). No significant correlations were found between suicidal ideation and anxiety or quality of sleep. CONCLUSION: Significant risk factors for suicidal ideation in patients with CRPS include severity of pain, depressive symptoms, and decreased functioning. These results suggest that psychiatric evaluation and intervention should be included in the treatment of CRPS.

Symptomatic Hallucal Interphalangeal Sesamoid Bones Successfully Treated with Ultrasound-guided Injection: A Case Report

The hallucal interphalangeal sesamoid bone is usually asymptomatic, but it is not uncommon for it to be symptomatic in cases of undue pressure, overuse, or trauma. Even in symptomatic cases, however, patients often suffer for extended periods due to misdiagnosis, resulting in depression and anxiety that can steadily worsen to the extent that symptoms are sometimes mistaken for a somatoform disorder. Dynamic ultrasound-guided evaluations can be an effective means of detecting symptomatic sesamoid bones, and a simple injection of a small dose of local anesthetics mixed with steroids is an easily performed and effective treatment option in cases, for example, of tenosynovitis.

Impact of the BDNF Val66Met Polymorphism on Regional Brain Gray Matter Volumes: Relevance to the Stress Response

OBJECTIVE: Genetic imaging is used to investigate the mechanism by which genetic variants influence brain structure. In a previous study, a structural change of the dorsolateral prefrontal cortex was associated with symptom modulation in post-traumatic stress disorder patients. This study examined the effect of a polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF) on regional gray matter (GM) volumes and the correlations between the dorsolateral prefrontal GM volume and the stress level in healthy volunteers. METHODS: Sixty-one volunteers underwent genotyping for the BDNF Val66Met single nucleotide polymorphism (SNP) and completed the Stress Response Inventory (SRI). Magnetic resonance images were also acquired, and the effect of each subject's BDNF genotype and SRI subscore on his or her dorsolateral prefrontal GM volume was evaluated. RESULTS: The Val/Val homozygotes had significantly larger GM volumes in the prefrontal cortex and the precuneus, the uncus, and the superior temporal and occipital cortices than Met carriers. The Met homozygotes demonstrated a higher stress response in depression domain than Val/Val and Val/Met groups. A negative correlation between the middle frontal cortex GM volume and the SRI depression subscore was found. CONCLUSION: These findings indicate an interaction between genes and brain structure, and they suggest that differences in dorsolateral prefrontal GM volume related to the BDNF Val66Met SNP are associated with resilience to stressful life events, particularly in the dimension of emotion.

Changes in Effective Connectivity According to Working Memory Load: An fMRI Study of Face and Location Working Memory Tasks

OBJECTIVE: The functional strategic mechanisms in the brain during performing visuospatial working memory tasks, especially tasks with heavy load, are controversial. We conducted the functional magnetic resonance imaging (fMRI) while sixteen subjects were performing face- and location-matching n-back tasks to examine causal relations within the frontoparietal networks. METHODS: We applied a sophisticated method, the structural equation modeling (SEM), to the fMRI data. The imaging data were analyzed by extracting the task-related eigenseries using the principal component analysis (PCA) and then by applying a form of data-driven model called the automated search method. RESULTS: The SEM analyses revealed a functional shift of network connectivity from the right to the left hemisphere with increasing load in the face-matching n-back tasks while the location-matching tasks required bilateral activation. In the locating matching n-back tasks, a pattern of parallel processing was observed in the left phonological loop and the right inferior parietal regions. Furthermore, object working memory-related activities in the left hemisphere reliably contributed to performance of both the face- and location-matching 2-back tasks. CONCLUSION: Our results are consistent with previous reports in terms of demonstrating parallel and distributed information processing during performing working memory tasks with heavy loads. Our results additionally suggest a dynamic shift between the fast imagery circuit (right hemisphere) and the stable verbal circuit (left hemisphere), depending on task load.

Altered Brain Activation in Ventral Frontal-Striatal Regions Following a 16-week Pharmacotherapy in Unmedicated Obsessive-Compulsive Disorder

Recent studies have reported that cognitive inflexibility associated with impairments in a frontal-striatal circuit and parietal region is a core cognitive deficit of obsessive-compulsive disorder (OCD). However, few studies have examined progressive changes in these regions following clinical improvement in obsessive-compulsive symptoms. To determine if treatment changes the aberrant activation pattern associated with task switching in OCD, we examined the activation patterns in brain areas after treatment. The study was conducted on 10 unmedicated OCD patients and 20 matched controls using event-related functional magnetic resonance imaging. Treatment improved the clinical symptoms measured by the Yale-Brown Obsessive Compulsive Scale and behavioral flexibility indicated by the switching cost. At baseline, OCD showed significantly less activation in the dorsal and ventral frontal-striatal circuit and parietal regions under the task-switch minus task-repeat condition compared with controls. After treatment, the neural responses in the ventral frontal-striatal circuit in OCD were partially normalized, whereas the activation deficit in dorsal frontoparietal regions that mediate shifting attention or behavioral flexibility persisted. It is suggested that altered brain activation in ventral frontal-striatal regions in OCD patients is associated with their cognitive flexibility and changes in these regions may underlie the pathophysiology of OCD.

The Effect of Repeated Virtual Nicotine Cue Exposure Therapy on the Psychophysiological Responses: A Preliminary Study

OBJECTIVE: Smoking related cues may elicit smoking urges and psychophysiological responses in subjects with nicotine dependence. This study aimed to investigate the effect of repeated virtual cue exposure therapy using the surround-screen based projection wall system on the psychophysiological responses in nicotine dependence. METHODS: The authors developed 3-dimensional neutral and smoking-related environments using virtual reality (VR) technology. Smoking-related environment was a virtual bar, which comprised both object-related and social situation cues. Ten subjects with nicotine dependence participated in 4-week (one session per week) virtual cue exposure therapy. Psychophysiological responses [electromyography (EMG), skin conductance (SC), and heart rate] and subjective nicotine craving were acquired during each session. RESULTS: VR nicotine cue elicited greater psychophysiological responses and subjective craving for smoking than did neutral cue, and exposure to social situation cues showed greater psychophysiological responses in SC and EMG than did object-related cues. This responsiveness decreased during the course of repeated therapy. CONCLUSION: The present study found that both psychophysiological responses and subjective nicotine craving were greater to nicotine cue exposure via projection wall VR system than to neutral cues and that enhanced cue reactivity decreased gradually over the course of repeated exposure therapy. These results suggest that VR cue exposure therapy combined with psychophysiological response monitoring may be an alternative treatment modality for smoking cessation, although the current findings are preliminary.

Neuroimaging Studies of Chronic Pain

The evolution of brain imaging techniques over the last decade has been remarkable. Along with such technical developments, research into chronic pain has made many advances. Given that brain imaging is a non-invasive technique with great spatial resolution, it has played an important role in finding the areas of the brain related to pain perception as well as those related to many chronic pain disorders. Therefore, in the near future, brain imaging techniques are expected to be the key to the discovery of many unknown etiologies of chronic pain disorders and to the subjective diagnoses of such disorders.

The Reliability and Validity of the Korean Version of the Structured Interview for Prodromal Syndrome

OBJECTIVE: The Structured Interview for Prodromal Syndrome (SIPS) from Yale University is intended to diagnose prodromal syndrome of psychosis and to measure the severity of prodromal symptoms. Here, a Korean version of SIPS is presented, and its reliability, validity, and factor structures are examined using a representative Korean sample. METHODS: The Korean version of SIPS was administered to 40 participants over a period of 1 year. The inter-rater reliability and internal consistency of the SIPS were then evaluated. In addition, its factor structure was investigated using principal-axis factor analysis. Concurrent validity was explored using Pearson correlation coefficients with the Positive and Negative Syndrome Scale (PANSS). RESULTS: Of the 40 subjects, 12.5% developed psychotic disorders during the 1-year follow-up period. Inter-rater reliability was good (intra-class correlations=0.96), and internal consistency was acceptable (Cronbach's alpha=0.83). A three-factor resolution displayed the best simple structure and accounted for 52.6% of all item variance. Factors 1 and 2 showed strong correlations with negative symptoms and cognitive dysfunction, respectively, on the PANSS. Factor 3 was not correlated with any factor on the PANSS. CONCLUSION: The Korean version of SIPS is a reliable instrument for the assessment of prodromal symptoms in subjects and may be used to evaluate prodromal psychosis.

Gender Difference in the Prodromal Symptoms of First-episode Schizophrenia

To investigate the gender difference of early symptoms appearing before the onset of the psychotic symptoms in patients with first-episode schizophrenia, we reviewed the medical records of 63 patients (38 males, 25 females), who were hospitalized for first-episode schizophrenia. The frequency and duration of prodromal and psychotic symptoms, Clinical Global Impression scale scores, Global Assessment of Functioning (GAF) scale scores at admission, and other clinical characteristics were recorded for all patients. Overall, the most common prodromal symptoms were attenuated positive symptoms (89%), followed by mood symptoms (86%). Negative symptoms were the most common in male patients (97.4%), whereas attenuated positive symptoms were the most common in female patients (84%). Male patients demonstrated more frequent negative, cognitive, and obsessive-compulsive symptoms than female patients did and also showed a tendency of having negative symptoms for the longer period. Correlational analysis showed a significant negative correlation between the duration of negative symptoms and GAF scores at admission in male patients. Our findings suggest that different patterns of prodromal symptoms between male and female begin before the onset of the psychosis. Further prospective studies should be needed.

Cognitive Assessment in Complex Regional Pain Syndrome Patients

BACKGROUND: Complex regional pain syndrome (CRPS) is characterized by severe neuropathic pain and disability, which can result in psychological and behavioral dysfunction. The goal of the present study was to evaluate neurocognitive disability, and to assess the relationship between clinical variables and neuropsychological features in CRPS patients. METHODS: We investigated the neuropsychological features of 15 CRPS I patients. The neuropsychological tests that we made comprised of a full intelligence quotient, memory quotient, trail-making test A, trail-making test B (TMT-B), and MMPI (Minnesota multiphasic personality inventory). RESULTS: The results showed severe disability in performance on TMT-B. There was no significant correlation between specific cognitive variables and MMPI scales. CONCLUSIONS: Decreased performance on TMT-B which shows mental flexibility in the prefrontal lobe exists independently from depressive disorders in CRPS patients.