Associations of Clozapine Use With Psychosocial Functioning and Quality of Life in Patients With Schizophrenia: A Community-Based Cross-Sectional Study.

OBJECTIVE: More attempts have been made recently to improve psychosocial functioning and quality of life in patients with schizophrenia, due to their crucial role in long-term outcomes. Previous studies on the effects of clozapine on psychosocial functioning have been limited in terms of generalizability and application to clinical practice. This study examined the relationship of clozapine use with psychosocial functioning and quality of life in patients with schizophrenia in a real-world setting. METHODS: Data were obtained from a survey targeting community-dwelling patients with schizophrenia. The Behavior and Symptom Identification Scale (BASIS) and Satisfaction with Life Scale (SWLS) were administered to evaluate psychosocial functioning and quality of life, and patients were classified into Clozapine and Non-clozapine groups. Group differences were assessed using ANCOVA, with additional sensitivity analyses for participants on atypical antipsychotic medications only. RESULTS: Of 292 patients, the Clozapine group (n=34) had significantly better psychosocial functioning and quality of life than the Nonclozapine group (n=258), as demonstrated by their low BASIS score (F=4.651, df=1, 290, p=0.032) and high SWLS score (F=14.637, df=1, 290, p<0.001). Similar findings for psychosocial outcomes were observed in the analyses of the atypical antipsychotic subgroup (n=195). CONCLUSION: For optimal recovery in schizophrenia, restoration of impaired social functioning and enhanced satisfaction with life are essential. In this study, clozapine use was related to high levels of psychosocial functioning and quality of life in real-world settings. Further research on the causal relationship between clozapine use and psychosocial functioning is needed.

Serotonin Transporter and COMT Polymorphisms as Independent Predictors of Health-related Quality of Life in Patients with Panic Disorder.

There is growing evidence of poor health-related quality of life (HRQOL) in patients with panic disorder (PD). However, little is known about the factors affecting HRQOL in patients with PD. The authors examined whether 5-HTTLPR tri-allelic approach and Cathechol-O-methyltransferase (COMT) Val(158)Met polymorphism can predict HRQOL in patients with PD controlling for sociodemographic factors and disorder-related symptom levels. The sample consisted of 179 patients with PD consecutively recruited from an outpatient clinic and age- and gender ratio-matched 110 healthy controls. The SF-36 was used to assess multiple domains of HRQOL. Hierarchical multiple regression analysis was performed to determine the independent effect of the 5-HTTLPR and COMT Val(158)Met on the SF-36 in panic patients. Patients with PD showed lowered HRQOL in all sub-domains of the SF-36 compared to healthy controls. The 5-HTTLPR independently and additively accounted for 2.2% of variation (6.7% of inherited variance) of perceived general health and the COMT Val(158)Met independently and additively accounted for 1.5% of variation (5.0% of inherited variance) of role limitation due to emotional problems in patient group. The present study suggests that specific genetic polymorphisms are associated with certain domains of HRQOL and provides a new insight on exploring the factors that predict HRQOL in patients with PD.

Panic disorder and health-related quality of life: the predictive roles of anxiety sensitivity and trait anxiety.

Panic disorder (PD) is a very common anxiety disorder and is often a chronic disabling condition. However, little is known about the factors that predict health-related quality of life (HRQOL) other than sociodemographic factors and illness-related symptomatology that explain HRQOL in only small to modest degrees. This study explored whether anxiety-related individual traits including anxiety sensitivity and trait anxiety can predict independently HRQOL in panic patients. Patients with panic disorder with or without agoraphobia (N=230) who met the diagnostic criteria in the Structured Clinical Interview for DSM-IV were recruited. Stepwise regression analysis was performed to determine the factors that predict HRQOL in panic disorder. HRQOL was assessed by the 36-item Short-Form Health Survey (SF-36). Anxiety sensitivity was an independent predictor of bodily pain and social functioning whereas trait anxiety independently predicted all of the eight domains of the SF-36. Our data suggests that the assessment of symptomatology as well as individual anxiety-related trait should be included in the evaluation of HRQOL in panic patients.

Factors associated with treatment outcomes in mindfulness-based cognitive therapy for panic disorder.

PURPOSE: Although the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for panic disorder (PD) has been studied previously, data on the predictors of treatment outcomes in MBCT for PD are scarce. MATERIALS AND METHODS: Eighty patients with PD were screened to analyze treatment outcomes such as MBCT completion, treatment response, and remission after undergoing MBCT for PD. Sociodemographic characteristics, comorbid personality disorders, and baseline medication doses were examined. The study administered the Panic Disorder Severity Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale and Anxiety Sensitivity Inventory-Revised to patients at baseline and at eight weeks. RESULTS: Sixty-five participants were enrolled in the present study. Comorbid personality disorder was significantly associated with MBCT non-completion. We found that anxiety sensitivity (AS) improvement after an eight week MBCT program was a statistically significant factor associated with treatment response. Using logistic regression analysis, AS improvement after MBCT showed significant association with PD remission after MBCT. CONCLUSION: Comorbid personality disorders of participants could be a potential predictor of MBCT non-completion. Furthermore, AS improvement after MBCT may predict treatment response and remission after MBCT for PD. However, better designed studies with a larger number of patients are needed to confirm our findings.

Serotonergic genes (5-HTT and HTR1A) and separation life events: gene-by-environment interaction for panic disorder.

BACKGROUND: The polymorphisms of serotonergic genes (5-HTTLPR and HTR1A rs6295) and separation life events have been studied to find an association with panic disorder, respectively. However, there are no studies that have yet evaluated the interaction effect between serotonergic genes and separation life events for panic disorder. METHODS: For this study, 194 panic disorder patients and 172 healthy controls were included for genotyping and environmental factor analysis. Separation life events were assessed using the Stressful Life Events Scale and clinical interviews. To evaluate the potential endophenotypes of panic disorder, the Anxiety Sensitivity Index-revised (ASI-R), harm avoidance in the Temperament and Character Inventory (HA), and neuroticism in the Eysenck Personality Questionnaire (neuroticism) scales were administered. RESULTS: For 5-HTTLPR and HTR1A rs6295, there was no significant main effect of each genotype on panic disorder alone. However, the number of separation life events and their interaction with 5-HTTLPR showed a statistically significant effect on panic disorder. In addition, the interaction between 5-HTTLPR and the number of separation life events significantly affected the HA for potential endophenotypes. CONCLUSION: This study could suggest the effect of the interaction between 5-HTTLPR and separation life events on panic disorder and its potential endophenotype.

Comparison of panic disorder with and without comorbid major depression by using brain structural magnetic resonance imaging.

BACKGROUND: Strong lifetime and current comorbidity occur between panic disorder and depression. However, no study has examined the influence of comorbid depression on brain structural characteristics in panic disorder patients. We aimed to compare gray matter (GM) volume and white matter (WM) connectivity in panic disorder patients with and without depression. METHODS: Twenty-one panic disorder patients without comorbid major depression (PD-D) and seventeen panic disorder patients with major depression (PD+D) were investigated. The Panic Disorder Severity Scale (PDSS) and Beck Depression Inventory (BDI) were assessed for all subjects. Voxel Based Morphometry 5 toolbox and Tract-Based Spatial Statistics were used. RESULTS: Compared to the PD-D group, GM volumes of patients with PD+D were significantly increased in a cluster located across the left cingulate gyrus, right medial frontal gyrus, and left paracentral lobule. Clinical symptom severity such as PDSS and BDI scores showed positive correlation with GM volumes in the PD+D group. Of the highlighted regions, the left posterior cingulate gyrus demonstrated both a GM volume difference between the groups and a positive correlation of GM volume with symptom severity in the PD+D group. Fractional anisotropy values were significantly higher across almost all the WM tracts in the PD+D group compared to the PD-D group. CONCLUSION: Alteration of GM volume and WM connectivity was associated with comorbid depression in panic disorder patients in this study. These findings suggest that distinct structural characteristics may be related to comorbid depression occurring in the context of panic disorder.

The effects of the catechol-O-methyltransferase val158met polymorphism on white matter connectivity in patients with panic disorder.

BACKGROUND: The catechol-O-methyltransferase (COMT) gene val158met polymorphism (rs4680) has been found to be associated with various psychiatric phenotypes including panic disorder. Considering the probable genetic influence of COMT on the pathogenesis of panic disorder and white matter connectivity, the present study investigated white matter connectivity using diffusion tensor imaging in relation to the COMT genotype in panic disorder. METHODS: Twenty-six patients with panic disorder and twenty-six age- and gender-matched healthy controls participated in this study. Brain magnetic resonance scans and genotype analysis for COMT rs4680 were conducted. Panic Disorder Severity Scale, Albany Panic and Phobia Questionnaire, and Anxiety Sensitivity Inventory-Revised were assessed. Tract-based spatial statistics (TBSS) were used for image analysis. RESULTS: There was no significant difference in white matter analysis between panic disorder and healthy controls. However, TBSS analysis showed increased fractional anisotropy (FA) in posterior thalamic radiation, posterior and superior corona radiata, superior longitudinal fasciculus, and sagittal stratum, all located in the right hemisphere in COMT AA/AG genotype group compared to GG genotype in panic disorder. Voxelwise correlational analysis revealed the symptom severity scores are correlated with the FA in white matter tracts that previously showed significant group differences between AA/AG and GG genotypes in COMT AA/AG genotype group, while no significant correlation was found in GG genotype group. LIMITATIONS: The sample size in each group was small, hence, further studies with larger numbers of patients are needed to confirm our findings. CONCLUSIONS: These data suggested that COMT rs4680 could affect the white matter connectivity in panic disorder.

The Effects of 5-HTR1A Polymorphism on Cingulum Connectivity in Patients with Panic Disorder.

OBJECTIVE: Serotonin-1A receptors (5-HTR1A) is suggested to be involved in the etiology of several psychiatric disorders including panic disorder (PD). A few imaging studies have suggested the alterations of the cingulum bundle in PD. The objective of this study is to examine the structural changes of cingulum related to the 5-HTR1A polymorphism rs6295 in the patients with PD. METHODS: Thirty-two right-handed patients with PD [11 men, 21 women; 40.34±13.17 (mean±SD) age] who met the diagnostic criteria in Structured Clinical Interview for DSM-IV were examined by means of MRI at 3 Tesla. We divided the patients with PD into CC genotype group and non CC genotype group (GG/CG genotype group) of the 5-HTR1A rs6295 polymorphism to compare the cingulum white matter connectivity. RESULTS: Tract-based spatial statistics showed significantly increased fractional anisotropy (FA) values in cingulate gyrus process of left cingulum in 5-HTR1A CC genotype compared to GG/CG genotype in PD. Significant positive correlations were shown between the Albany Panic and Phobia Questionnaire (APPQ) interoceptive fear subscale scores, the Anxiety Sensitivity Inventory-Revised fear of publicly observable anxiety reaction subscale scores and FA values of cingulate gyrus process of left cingulum in 5-HTR1A rs6295 GG/CG genotype group. In CC genotype group, APPQ total, APPQ agoraphobia subscale and APPQ social phobia subscale scores also showed significant positive correlations with FA values of hippocampal process of right cingulum. CONCLUSION: This preliminary study suggests that 5-HTR1A polymorphism may be associated with the cingulum white matter connectivity in PD.

The Tolerability of Mirtazapine Augmentation in Schizophrenic Patients Treated with Risperidone: A Preliminary Randomized Placebo-controlled Trial.

OBJECTIVE: Some patients with schizophrenia may need mirtazapine augmentation to improve negative and cognitive symptoms. However there have been a few studies about the tolerability of mirtazapine augmentation to antipsychotics such as akathisia, extrapyramydal symptoms, weight gain, and body mass index (BMI). METHODS: This study was an eight-week double-blind, randomized controlled trial (RCT) of mirtazapine augmentation to risperidone. Twenty-one stabilized participants diagnosed with schizophrenia and undergoing treatment with risperidone were randomized to adjunctive treatment with mirtazapine (15 mg/day for the first two weeks, 30 mg/day for the next six weeks) or placebo. Eleven patients were assigned to the mirtazapine group, and nine patients were given placebo. RESULTS: There was no significant difference between the mirtazapine and placebo groups with respect to Barnes Akathisia rating Scale (BAS) and Sympsom-Angus Scale (SAS). However, the mirtazapine group exhibited a statistically significant increase in weight and BMI (p<0.05). CONCLUSION: These results suggest that mirtazapine augmentation can be tolerable in schizophrenic patients treated with risperidone; however, we should pay attention to the weight gain with mirtazapine. Our results should be replicated in a large-scale lengthy trial.