Ching-Kuan Wu

Monoamine oxidase A gene polymorphism and suicide: An association study and meta-analysis

BACKGROUND Abnormalities in brain monoamine transmission have been implicated in the pathogenesis of suicidal behavior. Studies examining the association between monoamine oxidase A (MAOA)-uVNTR polymorphism and suicide revealed inconsistent findings. This study aims to evaluate the possible association between the MAOA-uVNTR polymorphism and suicidal behaviors by examining our own subjects and conducting a meta-analytic review. METHODS 373 unrelated psychiatric patients (including 160 suicide attempters and 213 non-suicide attempters) were genotyped for the MAOA-uVNTR polymorphism. A meta-analysis was then performed by pooling data from seven case-control association studies by random effects model. RESULTS Our results indicate that there is no association between the MAOA-uVNTR polymorphism and suicide attempts in both genders. It also reveals that there is no association with violent suicide attempts. In the meta-analysis, there is no association between the polymorphism and suicidal behaviors. Also, there is no difference in the allelic distribution between psychiatric patients with and without suicidal behaviors. Limitations Our study was constrained by the insufficient information about environmental risk factors of suicide. CONCLUSIONS Our study is the first one to use meta-analysis in exploring the role of the MAOA-uVNTR polymorphism in suicidal behavior in psychiatric patients. No significant association was found in our study, suggesting MAOA-uVNTR polymorphism is unlikely to contribute significantly to suicide behavior. Further studies investigating the gene-environment interaction or focusing on the genetic risk factors of endophenotypes of suicidal behaviors are warranted.

Significantly lower nerve growth factor levels in patients with major depressive disorder than in healthy subjects: a meta-analysis and systematic review

Introduction Since its discovery several decades ago, nerve growth factor (NGF) has been found to play roles in different areas, such as neurology, endocrinology, and immunology. There is some evidence linking NGF and psychiatry, including the role of NGF in subjects’ response to stress, the alteration of NGF in different emotional states, and the penetration of NGF across the blood–brain barrier under specific conditions. There are many inconsistent findings regarding the differences in NGF in patients with major depressive disorder (MDD) at the present time. The aim of our study was to clarify whether NGF levels are different in MDD compared with healthy controls (HCs). Methods We conducted a thorough literature search and compared peripheral NGF levels between MDD and HC through meta-analysis, and investigated possible confounding variables through meta-regression. Results Seven studies were brought into the current meta-analysis comparing peripheral NGF in MDD and HCs. The main result was that the NGF levels were significantly lower in MDD than in HCs and that this had an inverse correlation with mean age and disease severity. In addition, meta-analysis of four articles found that the peripheral NGF levels did not change significantly before and after treatment. Conclusion Our study highlights the significant differences in peripheral NGF levels in patients with MDD. However, further exploration of the dynamic changes in peripheral NGF along with the disease course, and specific studies investigating the correlation of NGF in the peripheral and CNS environments are still needed.

Increased levels of vascular endothelial growth factor in patients with major depressive disorder: A meta-analysis

The regulation of neurotrophic factors plays an important role in the pathophysiology of major depressive disorder (MDD). Vascular endothelial growth factor (VEGF) has been shown to promote neurogenesis, neuroprotection, and influence synaptic transmission. Many studies have examined the VEGF levels in patients with depression, however the results have been inconsistent. In the current meta-analysis, we compared blood VEGF levels between MDD patients and control subjects (16 articles including 872 patients and 882 control subjects). The effect sizes of individual studies were synthesized using a random effect model. We found that the blood VEGF levels in the patients with MDD were significantly higher than those in the healthy controls (p<0.001), and the difference was negatively correlated with mean age (p=0.01). Other variables including proportion of female subjects, body mass index, severity of depression, duration of illness, and age at onset were not significantly correlated with the difference. Our results highlight that elevated blood VEGF levels may be a disease marker in patients with MDD. Further studies are needed to examine the relationship between VEGF levels in central and peripheral environments, and clarify the role of VEGF in the pathophysiology of MDD.

Light therapy in the treatment of patients with bipolar depression: A meta-analytic study

Light therapy (LT) has been widely used in the treatment of seasonal affective disorder. Recently some evidence indicated that LT may play a role in bipolar depression, either as monotherapy or in combination with total sleep deprivation (TSD). However, the studies examining the treatment effect of LT in bipolar depression resulted in inconsistent findings. To clarify the role of LT in the disorder, we conducted a meta-analysis to compare the efficacy of LT in the treatment of bipolar depression. The results of individual studies were synthesized by a random effects model. Nine studies including 489 patients with bipolar depression were included in this current meta-analysis. We found that disease severity was significantly decreased after LT, in both with and without TSD, and with concomitant medication (p<0.001). Augmentation treatment with LT significantly decreased disease severity compared to treatment without LT (p=0.024). Our results highlight the significant efficacy of LT, either as monotherapy or in combination with TSD, in the treatment of bipolar depression. However, the detailed mechanism of LT still remains elusive. Further well-designed controlled trials are required to investigate the optimal intensity and frequency of LT in the treatment of bipolar depression.

Bone Mineral Density in Schizophrenia: An Update of Current Meta-Analysis and Literature Review Under Guideline of PRISMA.

AbstractNumerous reports have discussed bone mineral density (BMD) or the risk of osteoporosis in schizophrenia, but have yielded only controversial results.We conducted an update of meta-analysis to examine the overall change in BMD in patients with schizophrenia and the effect on BMD of different antipsychotic drugs.Electronic research through platform of PubMed.The inclusion criteria were as follows: articles with relevance to comparisons of BMD in patients with schizophrenia (SCHIZ) and healthy controls (HCs), or articles discussing comparisons of BMD in SCHIZ receiving prolactin-raising (PR) and prolactin-sparing (PS) antipsychotics; articles about clinical trials.In the current meta-analysis, we used the random-effect model to pool the results from 13 studies comparing BMD in SCHIZ and in HCs, and the results from 7 studies comparing BMD in patients receiving PR and PS.Our results revealed significantly lower BMD in SCHIZ than in HCs (P < 0.001). In the meta-regression, mean age of subjects modulated the difference in BMD between patients and control subjects (P < 0.001). In addition, the BMD in SCHIZ taking PR was significantly lower than in those taking PS (P = 0.006).Our study can only point to the phenomenon that BMD in SCHIZ is lower than that in HCs, and cannot reveal any possible pathophysiology or mechanism of this phenomenon. In addition, we could not rule out the possible effect of medication on BMD based on the results of the meta-analysis of comparison of BMD in SCHIZ receiving PR and PS.The main result of our meta-analysis suggests that BMD is significantly lower in SCHIZ than in HCs. Our study emphasizes the importance of further screening for the risk of osteoporosis in young-aged schizophrenic patients, especially those taking PR, which are in high risk of fracture.

Significantly Higher Peripheral Insulin-Like Growth Factor-1 Levels in Patients With Major Depressive Disorder or Bipolar Disorder Than in Healthy Controls: A Meta-Analysis and Review Under Guideline of PRISMA.

AbstractAn increasing amount of research has focused on insulin-like growth factor-1 (IGF-1) because of multiple neurotrophic effects, including neurogenesis, remyelination, and synaptogenesis. In addition, IGF-1 can mediate an antidepressant effect in patients with major affective disorder, and its levels in the cerebrospinal fluid have been found to vary with antidepressant treatment. Furthermore, it has been proven to crossover the blood–brain barrier, with a reciprocal feedback loop being the central effect. However, recent studies have reported inconclusive findings about the role of IGF-1 in major affective disorder.The aim of the current study was to conduct a thorough meta-analysis of changes in peripheral IGF-1 levels in patients with major depressive disorder (MDD) or bipolar disorder (BD). We conducted a thorough literature search and compared peripheral IGF-1 levels in patients with MDD or BD and in healthy controls, and investigated clinical variables through meta-regression.Electronic research was conducted through platform of PubMed.We used inclusion criteria as clinical trials discussing comparisons of peripheral IGF-1 protein levels in patients with MDD or BD and those in healthy controls.We analyzed the cases from 9 studies with the random-effect model.The main finding was that peripheral IGF-1 levels in the patients were significantly higher than in the healthy controls (P < 0.001), with a significant inverse association with duration of illness (P = 0.03). In meta-analysis comparing peripheral IGF-1 levels in patients with BD or MDD before and after treatment, there was no significant change in peripheral IGF-1 levels after treatment (P = 0.092).The small numbers of studies and lack of correlation data with growth hormone in current studies are the main limitations of this meta-analysis.Our results indicated that peripheral IGF-1 levels may not be an indicator of disease severity, but may be a disease trait marker or an indicator of cognition. However, further investigations on the correlation between cognitive function and peripheral IGF-1 levels are needed to explore the role of IGF-1 in the pathophysiology of MDD and BD.

Significant treatment effect of adjunct music therapy to standard treatment on the positive, negative, and mood symptoms of schizophrenic patients: a meta-analysis

BackgroundMusic therapy (MT) has been used as adjunct therapy for schizophrenia for decades. However, its role is still inconclusive. A recent meta-analysis demonstrated that MT for schizophrenic patients only significantly benefits negative symptoms and mood symptoms rather than positive symptoms. In addition, the association between specific characteristics of MT and the treatment effect remains unclear. The aim of this study was to update the published data and to explore the role of music therapy in adjunct treatment in schizophrenia with a thorough meta-analysis.MethodsWe compared the treatment effect in schizophrenic patients with standard treatment who did and did not receive adjunct MT through a meta-analysis, and investigated the clinical characteristics of MT through meta-regression.ResultsThe main finding was that the treatment effect was significantly better in the patients who received adjunct MT than in those who did not, in negative symptoms, mood symptoms, and also positive symptoms (all p < 0.05). This significance did not change after dividing the patients into subgroups of different total duration of MT, amounts of sessions, or frequency of MT. Besides, the treatment effect on the general symptoms was significantly positively associated with the whole duration of illness, indicating that MT would be beneficial for schizophrenic patients with a chronic course.ConclusionsOur meta-analysis highlights a significantly better treatment effect in schizophrenic patients who received MT than in those who did not, especially in those with a chronic course, regardless of the duration, frequency, or amounts of sessions of MT. These findings provide evidence that clinicians should apply MT for schizophrenic patients to alleviate disease severity.

Significantly Higher Prevalence Rate of Asthma and Bipolar Disorder Co-Morbidity: A Meta-Analysis and Review Under PRISMA Guidelines.

AbstractAsthma and bipolar disorder (BD) are 2 distinct diseases that share similar pathophysiology. This study aimed to determine their relationship thorough a meta-analysis of articles on their comorbidity rate.The aim of the study is to examine the overall prevalence rate of BD in asthmatic patients and of asthma in BD patients compared to healthy controls.Electronic research of PubMed and ClinicalTrials.gov was performed.Articles discussing the prevalence rate of BD in patients with/without asthma and the prevalence rate of asthma in those with/without BD, as well as clinical trials in humans and case-controlled trials or cohort studies, were all included. Case reports or series and nonclinical trials were excluded.Through a random-effects model, a meta-analysis of the results of 4 studies comparing the prevalence rate of BD in patients with/without asthma, and in 6 studies comparing the prevalence rate of asthma in subjects with/without BD were performed.There were significantly higher prevalence rates of BD in asthmatic patients than in healthy controls (P < 0.001) and of asthma in BD patients than in healthy controls (P < 0.001). Only the patients mean age significantly modulated the odds ratio of the prevalence rate of asthma in BD patients (slope = 0.015, P < 0.001).Only 10 studies were included and most were cross-sectional studies. The possible confounding effect of medication on BD or asthma onset was not investigated. Any possible etiology of the comorbidity was also not determined.This meta-analysis highlights the importance of the significantly high comorbid rate of BD and asthma, and the positive association with age. Special attention must be given to the comorbidity of asthma and BD, especially in older patients.

Significant treatment effect of add-on ketamine anesthesia in electroconvulsive therapy in depressive patients: A meta-analysis.

Add-on ketamine anesthesia in electroconvulsive therapy (ECT) has been studied in depressive patients in several clinical trials with inconclusive findings. Two most recent meta-analyses reported insignificant findings with regards to the treatment effect of add-on ketamine anesthesia in ECT in depressive patients. The aim of this study is to update the current evidence and investigate the role of add-on ketamine anesthesia in ECT in depressive patients via a systematic review and meta-analysis. We performed a thorough literature search of the PubMed and ScienceDirect databases, and extracted all relevant clinical variables to compare the antidepressive outcomes between add-on ketamine anesthesia and other anesthetics in ECT. Total 16 articles with 346 patients receiving add-on ketamine anesthesia in ECT and 329 controls were recruited. We found that the antidepressive treatment effect of add-on ketamine anesthesia in ECT in depressive patients was significantly higher than that of other anesthetics (p<0.001). This significance persisted in both short-term (1-2 weeks) and moderate-term (3-4 weeks) treatment courses (all p<0.05). However, the side effect profiles and recovery time profiles were significantly worse in add-on ketamine anesthesia group than in control group. Our meta-analysis highlights the significantly higher antidepressive treatment effect of add-on ketamine in depressive patients receiving ECT compared to other anesthetics. However, clinicians need to take undesirable side effects into consideration when using add-on ketamine anesthesia in ECT in depressive patients.

Significant Effect of Valproate Augmentation Therapy in Patients With Schizophrenia: A Meta-analysis Study.

AbstractValproate is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproate augmentation therapy in schizophrenia. Previous meta-analysis showed inconsistent findings because of limited literature at that time.The aim of this study is to update the newer published data by conducting a meta-analysis of clinical efficacy of valproate augmentation therapy in patients with schizophrenia or schizoaffective disorder.Data sources include electronic research through platform of PubMed.Study eligibility criteria, participants, and interventions were as follows: the inclusion criteria included articles discussing comparisons of the treatment effect in schizophrenic patients treated with antipsychotic augmented with valproate and antipsychotics with/without placebo; articles on clinical trials in humans. The exclusion criteria were case reports or series and nonclinical trials. We compared the effect between antipsychotic treatment with valproate augmentation and antipsychotic monotherapy.Data from clinical trials were pooled by random-effects model, and possible confounding variables were examined through meta-regression and subgroup analysis. Data from 11 articles including 889 patients were included into current meta-analysis.We found patients treated with antipsychotics with valproate augmentation showed significantly more improvement in total psychopathology than those treated with antipsychotics only (P = 0.02). Results from open trials, but not from randomized controlled trials (P = 0.20), showed significant improvement (P = 0.01). In addition, the significance only persisted in the studies conducted with a shorter treatment duration (P < 0.001) rather than longer treatment duration (P = 0.23). There is no difference in the dropout rate between valproate augmentation and antipsychotic treatment only (P = 0.14).We could not perform a detailed meta-analysis for every category of antipsychotics, long-term effect, and safety profiles of valproate augmentation therapy in maintenance treatment, safety in pregnant patients, and subtype of schizophrenia.Our meta-analysis highlights the significantly better treatment effect with valproate augmentation therapy in patients with schizophrenia or schizoaffective disorder, and provides important evidence for supporting the practice of valproate augmentation therapy in these patients.