Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder

Background

In recent years, a role for the immune system in the pathogenesis of psychiatric diseases has gained increased attention. Although bipolar disorder appears to be associated with altered serum cytokine levels, a putative immunological contribution to its patho-physiology remains to be established. Hitherto, no direct analyses of cerebrospinal fluid (CSF) cytokines in patients with bipolar disorder have been performed.

Methods

We analyzed CSF cytokine concentrations in euthymic patients with diagnosed bipolar disorder type I (n = 15) or type II (n = 15) and healthy volunteers (n = 30) using an immunoassay-based protein array multiplex system.

Results

The mean interleukin (IL)-1β level (4.2 pg/mL, standard error of the mean [SEM] 0.5) was higher and the IL-6 level (1.5 pg/mL, SEM 0.2) was lower in euthymic bipolar patients than in healthy volunteers (0.8 pg/mL, SEM 0.04, and 2.6 pg/mL, SEM 0.2, respectively). Patients with 1 or more manic/hypomanic episodes during the last year showed significantly higher levels of IL-1β (6.2 pg/mL, SEM 0.8; n = 9) than patients without a recent manic/hypomanic episode (3.1 pg/mL, SEM 1.0; n = 10).

Limitations

All patients were in an euthymic state at the time of sampling. Owing to the large variety of drugs prescribed to patients in the present study, influence of medication on the cytokine profile cannot be ruled out.

Conclusion

Our findings show an altered brain cytokine profile associated with the manifestation of recent manic/hypomanic episodes in patients with bipolar disorder. Although the causality remains to be established, these findings may suggest a pathophysiological role for IL-1β in bipolar disorder.     

The Effectiveness of Cross-Tapering Switching to Ziprasidone in Patients with Schizophrenia or Schizoaffective Disorder

Objective

Switching antipsychotics is one useful therapeutic option when the treatment of schizophrenia encounters suboptimal efficacy and intolerability issues. This study aimed to investigate the efficacy and tolerability of cross-tapering switching to ziprasidone from other antipsychotics.

Methods

A total of 67 patients with schizophrenia or schizoaffective disorder were recruited in this 12-week, multicenter, non-comparative, open-label trial. Prior antipsychotics were allowed to be maintained for up to 4 weeks during the titration of ziprasidone. Efficacy was primarily measured using the 18-item Brief Psychotic Rating Scale (BPRS) at baseline, 4 weeks, 8 weeks, and 12 weeks. Efficacy was secondarily measured by the Clinical Global Impression-Severity (CGI-S) scale and the Global Assessment of Functioning (GAF) scale at each visit. Regarding the metabolic effects of switching to ziprasidone, weight, body mass index (BMI), waist-to-hip ratio (WHR), and lipid profile-including triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol levels-were measured at each follow-up visit.

Results

The BPRS scores were significantly improved at 12 weeks after switching to ziprasidone (F=5.96, df=2.11, p=0.003), whereas the CGI-S and GAF scores were not significantly changed. BMIs, WHRs, and TG levels were significantly decreased, with no significant changes in other lipid profiles.

Conclusion

Cross-tapering switching to ziprasidone is effective for patients with schizophrenia spectrum disorders. Beyond the efficacy of the procedure, favorable metabolic profiles show that switching to ziprasidone may be helpful for maintenance therapy over an extended period.     

A Preliminary Validity Study of the Cambridge Neuropsychological Test Automated Battery for the Assessment of Executive Function in Schizophrenia and Bipolar Disorder

Objective

Although the executive function subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) have been used to assess cognitive function in diverse psychiatric illnesses, few studies have verified the validity of this battery for Korean psychiatric patients. Therefore, this preliminary study evaluated the construct and concurrent validity of the executive function subtests of the CANTAB for Korean psychiatric patients by comparing it with subtests of the Computerized Neuropsychological Test (CNT).

Methods

Three subtests of the CANTAB and three subtests of the CNT were administered to 36 patients diagnosed with either schizophrenia or bipolar disorder. Subtests of the CANTAB included the Intra/Extra-Dimensional Set Shift (IED), Stockings of Cambridge (SOC), and Spatial Working Memory (SWM). Differences between groups on each subtest as well as correlations between the subtests of the CANTAB and the CNT were assessed.

Results

The schizophrenia group performed significantly more poorly on the IED and the Wisconsin Card Sorting Test (WCST) compared with the bipolar disorder group. Additionally, correlation analyses revealed a significant correlation between the IED and the WCST; a positive correlation between the SOC and the Trail Making Test, Part B and the Stroop test; and a significant correlation between the SWM and the Stroop test.

Conclusion

This study verified the construct and concurrent validity of the executive function subtests of the CANTAB for Korean psychiatric patients and suggests that the subtests of this battery would be useful and appropriate for assessing deficits in executive function in Korean clinical settings.     

Genetic Association Study of the Alpha 7 Nicotinic Receptor (CHRNA7) with the Development of Schizophrenia and Bipolar Disorder in Korean Population

Objective

CHRNA7 has been shown to be a strong candidate gene for schizophrenia and bipolar disorder. It is located on chromosome 15q13-q14, which is one of the replicated linkage spots for schizophrenia and bipolar disorder.

Methods

We conducted an association study to determine whether previous positive association is replicable in the Korean population. We included 254 patients with schizophrenia, 193 patients with bipolar disorder type I, 38 patients with bipolar disorder type II, 64 schizoaffective disorder patients, and 349 controls. All subjects were ethnically Korean. A total of 898 subjects were included, and genotyping was done for three single nucleotide polymorphisms (SNPs) of CHRNA7. These three intronic SNPs were rs2337506 (A/G), rs6494223 (C/T), and rs12916879 (A/G).

Results

There was only one marginally significant association; this association was between rs12916879 and bipolar disorder type I in the male subgroup. In both the allele and genotype distributions, we found a weak signal (Chi-squared=3.57, df=1, p=0.06 for allele, Chi-squared=7.50, df=2, p=0.02 for genotype) only. Unphased haplotype analysis could not provide additional support for this finding. No SNP was associated with schizophrenia or any other affected groups in this Korean sample. The associative finding is marginal and inconclusive.

Conclusion

We could not replicate positive association in other ethnic groups previously studied. This suggests possible heterogeneity in the genes associated with schizophrenia and bipolar disorders. Because of structural complexity of the CHRNA7 gene and the limited statistical power of this study, further genetic studies with more SNPs and larger samples covering various populations, along with more fine molecular exploration of the CHRNA7 gene structure, are required.     

Cortical folding in patients with bipolar disorder or unipolar depression

Background

Analysis of cortical folding may provide insight into neurodevelopment deviations, which, in turn, can predispose to depression that responds particularly poorly to medications. We hypothesized that patients with treatment-resistant depression would exhibit measurable alterations in cortical folding.

Methods

We computed hemispheric global sulcal indices (g-SIs) in T₁-weighted magnetic resonance images obtained from 76 patients and 70 healthy controls. We separately searched for anatomic deviations in patients with bipolar disorder (16 patients with treatment-resistant depression, 25 with euthymia) and unipolar depression (35 patients with treatment-resistant depression).

Results

Compared with healthy controls, both groups of patients with treatment-resistant depression exhibited reduced g-SIs: in the right hemisphere among patients with bipolar disorder and in both hemispheres among those with unipolar depression. Patients with euthymic bipolar disorder did not differ significantly from depressed patients or healthy controls. Among patients with bipolar disorder who were taking lithium, we found positive correlations between current lithium dose and g-SIs in both hemispheres.

Limitations

We cannot estimate the extent to which the observed g-SI reductions are linked to treatment resistance and to what extent they are state-dependent. Furthermore, we cannot disentangle the impact of medications from that of the affective disorder. Finally, there is interindividual variation and overlap of g-SIs among patients and healthy controls that need to be considered when interpreting our results.

Conclusion

Reduced global cortical folding surface appears to be characteristic of patients with treatment-resistant depression, either unipolar or bipolar. In patients with bipolar disorder, treatment with lithium may modify cortical folding surface.     

Polarity of the First Episode and Time to Diagnosis of Bipolar I Disorder

Objective

The current study explored the relationship between the polarity of the first episode and the timing of eventual diagnosis of bipolar I disorder, and associated clinical implications.

Methods

Twelve years of clinical data from the medical records of 258 inpatients meeting DSM-III-R or DSM-IV criteria for bipolar I disorder were analyzed. Subjects were divided into two groups according to the polarity of the first episode: those with depressive polarity (FE-D), and those with manic polarity (FE-M). Comparisons were made between the two groups on variables associated with the timing of diagnosis and related outcomes.

Results

In population with bipolar I disorder, a significant longer time lapse from the first major mood episode to the confirmed diagnosis was associated with the FE-D group compared to the FE-M group [5.6 (±6.1) vs. 2.5 (±5.5) years, p<0.001]. FE-D subjects tended to have prior diagnoses of schizophrenia and major depressive disorder while FE-M subjects tended to have prior diagnoses of bipolar disorder and schizophrenia. A significantly higher rate of suicide attempts was associated with the FE-D group compared to the FE-M group (12.7 vs. 1.7%, p<0.001).

Conclusion

The results of this study indicate that first-episode depressive polarity is likely to be followed by a considerable delay until an eventual confirmed diagnosis of bipolar I disorder. Given that first-episode depressive patients are particularly vulnerable to unfavorable clinical outcomes such as suicide attempts, a more systematic approach is needed to differentiate bipolar disorder among depressed patients in their early stages.     

Rash in psychiatric and nonpsychiatric adolescent patients receiving lamotrigine in Korea: a retrospective cohort study

Objective

Lamotrigine is a widely used medication for psychiatric disorders and epilepsy, but the adverse effects of this drug in adolescent Korean patients have not yet been investigated. In the present study, we sought to compare the incidence and impact of lamotrigine-induced skin rashes and different pattern of adverse events in psychiatric and nonpsychiatric adolescent patients.

Methods

Using a retrospective cohort design, all of the charts were reviewed for adolescents (13 to 20 years old), treated with lamotrigine during the previous 2 years in the Child and Adolescent Psychiatric Clinic and Pediatric Neurologic Clinic of the Ulsan University Hospital in South Korea.

Results

Of the 102 subjects, 23 patients developed a skin rash. All of these rashes were observed within 7 weeks of the initiation of the lamotrigine therapy. Only one subject developed a serious rash, which was diagnosed as Stevens-Johnson syndrome. Although the psychiatric subjects were administered statistically lower doses of lamotrigine during weeks 1 through 5 and at week 12, the likelihood of developing a rash was not significantly different between the psychiatric and nonpsychiatric patients.

Conclusion

Careful dose escalation and close observation of side effects for the first 7 weeks of treatment is important. The present study reveals the tolerability of lamotrigine in an adolescent population, although a double-blind, controlled trial is needed to confirm these findings.     

Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder

Background

Patients with schizophrenia show elevated brain levels of the neuroactive tryptophan metabolite kynurenic acid (KYNA). This astrocyte-derived mediator acts as a neuroprotectant and modulates sensory gating and cognitive function. We measured the levels of KYNA in the cerebrospinal fluid (CSF) of patients with bipolar disorder and healthy volunteers to investigate the putative involvement of KYNA in bipolar disorder.

Methods

We obtained CSF by lumbar puncture from 23 healthy men and 31 euthymic men with bipolar disorder. We analyzed the samples using high-performance liquid chromatography.

Results

Patients with bipolar disorder had increased levels of KYNA in their CSF compared with healthy volunteers (1.71 nM, standard error of the mean [SEM] 0.13 v. 1.13 nM, SEM 0.09; p = 0.002. The levels of KYNA were positively correlated with age among bipolar patients but not healthy volunteers.

Limitations

The influence of ongoing drug treatment among patients cannot be ruled out. We conducted our study during the euthymic phase of the disease.

Conclusion

Brain KYNA levels are increased in euthymic men with bipolar disorder. In addition, KYNA levels increased with age in these patients. These findings indicate shared mechanisms between bipolar disorder and schizophrenia. Elevated levels of brain KYNA may provide further insight to the pathophysiology and progression of bipolar disorder.     

A combination of the korean version of the mini-mental state examination and korean dementia screening questionnaire is a good screening tool for dementia in the elderly

Objective

The aim of this study is to investigate whether a combination of the Korean version of the mini-mental state examination (K-MMSE) and the Korean dementia screening questionnaire (KDSQ) is better than the use of test alone when differentiating patients with dementia from those without dementia in Korea.

Methods

The subjects (patients without dementia, 1120; patients with dementia, 908) were recruited from the Clinical Research Center for Dementia of South Korea. K-MMSE and KDSQ were used. Diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, fourth Edition. The weighted sum rule derived from logistic regression analysis was used for the combination of K-MMSE and KDSQ.

Results

On comparing the Area Under the Curve for each test using the method of Hanley and McNeil, the weighted sum was significantly greater than KDSQ or K-MMSE, and K-MMSE was significantly greater than KDSQ.

Conclusion

This study shows that when differentiating patients with dementia from those without dementia in Korea, a combination of K-MMSE and KDSQ achieved using the weighted sum method is better than either test performed alone. Further epidemiological studies in community-based settings are required before our results can be generalized to nonclinical samples.     

Correlates of Metabolic Abnormalities in Bipolar I Disorder at Initiation of Acute Phase Treatment

Objective

Treatment of bipolar patients is often complicated by metabolic abnormalities such as obesity, diabetes, and dyslipidemia. We therefore evaluated the prevalence of these abnormalities and their correlates, in bipolar I patients, at the time of commencement of pharmacological treatment for acute mood episodes.

Methods

The study cohort consisted of 184 bipolar I patients hospitalized for treatment of acute mood episodes. Socio-demographic and clinical variables were noted and metabolic parameters, including body mass index, fasting plasma glucose, fasting total cholesterol, and current treatment(s) for diabetes and/or dyslipidemia were measured before initiating medication(s).

Results

Fifty-six (30.4%) subjects met our criteria for obesity; 80 (43.5%) had hyperglycemia, with 8 (4.3%) receiving anti-diabetic medication; and 38 (20.7%) had hypercholesterolemia, with 2 (1.1%) receiving cholesterol-lowering agents. We found that male sex (χ²=5.359, p=0.021), depressed or mixed state versus manic state (χ²=4.302, p=0.038), and duration of illness (t=2.756, p=0.006) were significantly associated with obesity. Older age (t=3.668, p<0.001), later age of disease onset (t=2.271, p=0.024), and lower level of educational attainment (β=-0.531, p=0.001) were associated with hyperglycemia.

Conclusion

Our finding that metabolic abnormalities are prevalent when initiating acute pharmacological treatment in bipolar I patients indicates that these factors should be integrated into treatment plans at the onset of disease management.     

Titrating Optimal Dose of Osmotic-Controlled Release Oral Delivery (OROS)-Methylphenidate and Its Efficacy and Safety in Korean Children with ADHD: A Multisite Open Labeled Study

Objective

This study was aimed to determine effectiveness and tolerability of Osmotic-controlled Release Oral delivery (OROS) methylphenidate (MPH) and its optimal dose administered openly over a period of up to 12 weeks in drug naïve Korean children with ADHD.

Methods

Subjects (n=143), ages 6 to 18-years, with a clinical diagnosis of any subtype of ADHD were recruited from 7 medical centers in Korea. An individualized dose of OROS-MPH was determined for each subject depending on the response criteria. The subjects were assessed with several symptom rating scales in week 1, 3, 6, 9 and 12.

Results

77 of 116 subjects (66.4%) achieved the criteria for response and the average of optimal daily dose for response was to 30.05±12.52 mg per day (0.90±0.31 mg/kg/d) at the end of the study. Optimal dose was not significantly different between ADHD subtypes, whereas, significant higher dose was needed in older aged groups than younger groups. The average of optimal daily dose for response for the subjects aged above 12 years old was 46.38±15.52 per day (0.81±0.28 mg/kg/d) compared to younger groups (p<0.01). No serious adverse effects were reported and the dose did not have a significant effect on adverse effects.

Conclusion

Optimal mean dose of OROS-MPH was significantly different by age groups. Higher dose was needed in older aged groups than younger groups. Effectiveness and tolerability of OROS-MPH in symptoms of ADHD is sustained for up to 12 weeks.     

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder

Background

Previous magnetic resonance imaging (MRI) studies in young patients with bipolar disorder indicated the presence of grey matter concentration changes as well as microstructural alterations in white matter in various neocortical areas and the corpus callosum. Whether these structural changes are also present in elderly patients with bipolar disorder with long-lasting clinical evolution remains unclear.

Methods

We performed a prospective MRI study of consecutive elderly, euthymic patients with bipolar disorder and healthy, elderly controls. We conducted a voxel-based morphometry (VBM) analysis and a tract-based spatial statistics (TBSS) analysis to assess fractional anisotropy and longitudinal, radial and mean diffusivity derived by diffusion tensor imaging (DTI).

Results

We included 19 patients with bipolar disorder and 47 controls in our study. Fractional anisotropy was the most sensitive DTI marker and decreased significantly in the ventral part of the corpus callosum in patients with bipolar disorder. Longitudinal, radial and mean diffusivity showed no significant between-group differences. Grey matter concentration was reduced in patients with bipolar disorder in the right anterior insula, head of the caudate nucleus, nucleus accumbens, ventral putamen and frontal orbital cortex. Conversely, there was no grey matter concentration or fractional anisotropy increase in any brain region in patients with bipolar disorder compared with controls.

Limitations

The major limitation of our study is the small number of patients with bipolar disorder.

Conclusion

Our data document the concomitant presence of grey matter concentration decreases in the anterior limbic areas and the reduced fibre tract coherence in the corpus callosum of elderly patients with long-lasting bipolar disorder.     

Decreased cerebrospinal fluid secretogranin II concentrations in severe forms of bipolar disorder

Background

Bipolar disorder is a common psychiatric mood disorder that is defined by recurrent episodes of abnormally elevated mood and depression. Progressive structural brain changes in individuals with bipolar disorder have been suggested to be associated with defects in the secretion of neurotrophic factors. We sought to assess how the regulated secretory pathway in the brain is affected in patients with bipolar disorder by measuring chromogranin B and secretogranin II, which are 2 cerebrospinal fluid (CSF) biological markers for this process.

Methods

We measured the concentrations of chromogranin B (peptide 439–451) and secretogranin II (peptide 154–165) in the CSF of patients with well-defined bipolar disorder and healthy controls. The lifetime severity of bipolar disorder was rated using the Clinical Global Impression (CGI) scale.

Results

We included 126 patients with bipolar disorder and 71 healthy controls in our analysis. Concentrations of secretogranin II were significantly lower in patients with bipolar disorder type I than in healthy controls. The reduction was most pronounced in patients with high CGI scores (i.e., severe disease).

Limitations

The cross-sectional design of the current study limits the ability to pinpoint the causalities behind the observed associations.

Conclusion

This study shows that the CSF marker secretogranin II has the potential to act as a biological marker for severe forms of bipolar disorder. Our findings indicate that patients with bipolar disorder possess defects in the regulatory secretory pathway, which may be of relevance to the progressive structural brain changes seen in those with severe forms of the disease.     

Exploratory factor analysis and confirmatory factor analysis of the korean version of hypomania checklist-32

Objective

The Hypomania Checklist - 32 (HCL-32) is a self-assessment instrument developed by Angst et al. (2005) to identify bipolarity in the general population, as well as patients with unipolar depression. The principal objective of this study was to assess the factor structure of the Korean version of the HCL-32 for mood disorder patients, via exploratory factor analysis (EFA) and confirmatory factor analysis (CFA).

Methods

The Korean version of HCL-32 were evaluated in a sample of 608 mood disorder patients, including 210 bipolar disorder patients and 398 unipolar disorder patients, all of whom were diagnosed in accordance with either the Structured Clinical Interview of DSM-IV or Mini International Neuropsychiatric Interview They were divided randomly into two groups, and then the EFA was administered to group 1 and the CFA was administered to group 2.

Results

A 3-factor structure for the HCL-32 was generated, which explained 44% of the total variance from EFA. Factor 1, comprising 18 items, was designated as ''elated mood/increased energy''; factor 2, comprising 8 items, was designated as ''risk-taking behavior/irritability''; and factor 3, comprising 2 items, was designated as ''increased sexual activity''. Researchers confirmed the 3-factor solution derived from group 1 by the CFA.

Conclusion

The primary findings of this study were the replication and confirmation of the 3-factor structure in Korean mood disorder patients; our results were consistent with previous EFAs.     

Rapid antipsychotic response with ziprasidone predicts subsequent acute manic/mixed episode remission

Objective

To assess rapid antipsychotic efficacy with oral ziprasidone monotherapy in bipolar acute manic/mixed episodes with psychotic features, and predictive value of rapid antipsychotic response for subsequent acute manic/mixed episode remission.

Methods

Pooled analysis of two 3-week, randomized, double-blind, placebo-controlled trials of ziprasidone (40-160 mg/d) in inpatients with bipolar I disorder, and a current manic or mixed episode, with (n = 152) or without (n = 246) psychotic features. Psychosis improvement was evaluated by change in SADS-C psychosis score (sum of delusions, hallucinations, and suspiciousness items). Rapid antipsychotic response (?50% decrease in SADS-C psychosis score by Day 4) and acute manic episode response and remission (endpoint ?50% MRS decrease, and a MRS score ? 12, respectively) were analyzed.

Results

Significantly greater antipsychotic effects were observed by Day 4 with ziprasidone treatment (vs. placebo) and the magnitude of improvement increased significantly with time, in all subjects, in the subgroup of all psychotic subjects, and psychotic subjects with low baseline agitation (p < 0.05). Rapid antipsychotic response predicted subsequent acute manic episode remission independent of ziprasidone or placebo treatment received (p < 0.001, ROC AUC = 0.71) with significant improvement in accuracy of MRS remission prediction when compared to models using early changes in MRS score alone (p = 0.01).

Limitations

Post hoc analysis, use of 3 SADS-C psychosis items to assess psychosis.

Conclusions

The predictive value of rapid (Day 4) improvement in psychotic symptoms for subsequent (Day 21) remission of acute manic/mixed symptoms may facilitate enhanced therapeutics, in view of the current practice of brief hospitalization for patients with acute manic/mixed episodes with psychotic features.     

Association between Serotonin-Related Polymorphisms in 5HT2A, TPH1, TPH2 Genes and Bipolar Disorder in Korean Population

Objective

The aim of the present study was to examine the association between serotonin-related gene polymorphisms and bipolar disorder in the Korean population. In addition, we sought to explore the relationship between the clinical characteristics of bipolar patients and serotonin-related gene polymorphisms.

Methods

Inpatients with bipolar disorder (n=103) and control subjects (n=86) were genotyped for 5HT2A 1438A/G, tryptophan hydroxylase 1 (TPH1) 218 A/C, and TPH2 703G/T. We divided patients with bipolar disorder into two groups according to the presence of psychotic symptoms. The severity of their symptoms was measured using the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS).

Results

There were no significant differences in the genotype distributions or allelic frequencies in the three serotonergic polymorphisms between patients with bipolar disorder and normal controls. There were significant differences in genotype distributions and allele frequencies of the 5-HT2A -1438A/G polymorphism between the psychotic mania group and the non-psychotic mania group (genotype: χ²=7.50, p=0.024; allele: χ²=5.92, p=0.015). However, after Bonferroni correction this signifact difference disappeared. We did not find significant differences in the genotype distributions or allelic frequencies in the TPH1 218 A/C and TPH2 703G/T polymorphisms between the psychotic mania group and non-psychotic mania group.

Conclusion

We failed to found the statistically significant association between three polymorphisms and bipolar disorder. However, there was a trend towards association between 5-HT2A -1438A/G polymorphism and psychotic symptom in bipolar disorder. Future research should seek to clarify this association.     

Simultaneous Comparison of Efficacy and Tolerability of Second-Generation Antipsychotics in Schizophrenia: Mixed-Treatment Comparison Analysis Based on Head-to-Head Trial Data

Objective

Second-generation antipsychotics have been repeatedly shown to be superior to placebo. However, the comparative efficacy among these drugs has not been systematically evaluated. In this study, we used Mixed Treatment Comparison (MTC) procedures to elucidate the comparative efficacy and tolerability of second-generation antipsychotics.

Methods

Seven antipsychotics were selected based on the availability of the relevant data. Data were gathered from a series of review article published by the Cochrane Collaboration. Six outcome measures were analyzed: 1) percentage of no clinically important response as defined by the original authors, 2) PANSS total score change from baseline to endpoint, 3) percentage of akathisia, 4) percentage of antiparkinson medication use, 5) percentage of total body weight increase more than 7%, and 6) percentage of drop-out due to any reasons.

Results

All the second-generation antipsychotics included in this study showed fairly similar efficacy but widely different tolerability. In terms of efficacy, amisulpride, clozapine and olanzapine were ranked higher than aripiprazole, quetiapine and ziprasidone. Clozapine and olanzapine were superior in terms of akathisia and extrapyramidal symptom risk, but, far more prone to induce clinically important weight gain.

Conclusion

Using MTC methodology, we could line up the second generation antipsychotics according to their hierarchical superiority in terms of efficacy and tolerability. Though the wide overlap among the confidence intervals and the inconsistency between the direct and indirect comparison results may limit the validity of these results, it may still allow the important insights into the relative merits of the available drugs.     

Medical Findings in Women with Anorexia Nervosa in a Korean Population

Objective

Eating disorders are a common clinical problem among young women in Asian countries. The aim of this study is to determine the medical effects of anorexia nervosa (AN) in the Korean population.

Methods

We comprehensively investigated medical complications including haemodynamic, haematologic, endocrine, and bone density abnormalities in 67 Korean women with AN, together with 194 healthy Korean women of comparable age with a cross-sectional design.

Results

In AN, 36.9% were anaemic, 50.8% were leukopenic, 35.5% were hypoproteinemic, 7.9% were hypokalemic, 9.5% had increased alanine aminotransferase, 6.3% were hyperbilirubinemia, 14.5% were hypercholesterolemia, 14.8% had decreased triiodothyronine. Osteopenia at any one site was identified in 43.3% and an additional 13.4% had osteoporosis. The lowest-ever body mass index was the main determinant of bone mineral density.

Conclusion

Our data in Korean patients with AN show high frequencies of laboratory abnormalities for medical complications. This study emphasizes the importance of recognizing AN as a medical risk in young Korean women.     

Mapping vulnerability to bipolar disorder: a systematic review and meta-analysis of neuroimaging studies

Background

Although early interventions in individuals with bipolar disorder may reduce the associated personal and economic burden, the neurobiologic markers of enhanced risk are unknown.

Methods

Neuroimaging studies involving individuals at enhanced genetic risk for bipolar disorder (HR) were included in a systematic review. We then performed a region of interest (ROI) analysis and a whole-brain meta-analysis combined with a formal effect-sizes meta-analysis in a subset of studies.

Results

There were 37 studies included in our systematic review. The overall sample for the systematic review included 1258 controls and 996 HR individuals. No significant differences were detected between HR individuals and controls in the selected ROIs: striatum, amygdala, hippocampus, pituitary and frontal lobe. The HR group showed increased grey matter volume compared with patients with established bipolar disorder. The HR individuals showed increased neural response in the left superior frontal gyrus, medial frontal gyrus and left insula compared with controls, independent from the functional magnetic resonance imaging task used. There were no publication biases. Sensitivity analysis confirmed the robustness of these results.

Limitations

As the included studies were cross-sectional, it remains to be determined whether the observed neurofunctional and structural alterations represent risk factors that can be clinically used in preventive interventions for prodromal bipolar disorder.

Conclusion

Accumulating structural and functional imaging evidence supports the existence of neurobiologic trait abnormalities in individuals at genetic risk for bipolar disorder at various scales of investigation.     

Ischemic Neuropathy Associated with Livedoid Vasculitis

Background

Livedoid vasculitis is a chronic dermatological problem with an unclear etiology. Clinical findings are petechiae with painful ulcers in both lower extremities, which heal to become hyperpigmented and porcelain-white satellite lesions. There are only a few reported cases of livedoid vasculitis presenting in combination with peripheral neuropathy.

Case Report

We report the first case of a Korean patient presenting with mononeuritis multiplex combined with livedoid vasculitis, which was confirmed by electrophysiological and pathological studies.

Conclusions

Our report supports the possible vaso-occlusive etiology of livedoid vasculitis in multifocal ischemic neuropathy.