Pao-Yen Lin

Glycine Transporter I Inhibitor, N-methylglycine (Sarcosine), Added to Clozapine for the Treatment of Schizophrenia

BACKGROUND Agonists at the N-methyl-D-aspartate (NMDA)-glycine site (D-serine, glycine, D-alanine and D-cycloserine) and glycine transporter-1 (GlyT-1) inhibitor (N-methylglycine, or called sarcosine) both improve the symptoms of stable chronic schizophrenia patients receiving concurrent antipsychotics. Previous studies, however, found no advantage of D-serine, glycine, or D-cycloserine added to clozapine. The present study aims to determine the effects of sarcosine adjuvant therapy for schizophrenic patients receiving clozapine treatment. METHODS Twenty schizophrenic inpatients enrolled in a 6-week double-blind, placebo-controlled trial of sarcosine (2 g/day) which was added to their stable doses of clozapine. Measures of clinical efficacy and side-effects were determined every other week. RESULTS Sarcosine produced no greater improvement when co-administered with clozapine than placebo plus clozapine at weeks 2, 4, and 6. Sarcosine was well tolerated and no significant side-effect was noted. CONCLUSIONS Unlike patients treated with other antipsychotics, patients who received clozapine treatment exhibit no improvement by adding sarcosine or agonists at the NMDA-glycine site. Clozapine possesses particular efficacy, possibly related to potentiation of NMDA-mediated neurotransmission. This may contribute to the clozapines unique clinical efficacy and refractoriness to the addition of NMDA-enhancing agents.

Are omega-3 fatty acids antidepressants or just mood-improving agents? The effect depends upon diagnosis, supplement preparation, and severity of depression.

Are omega-3 fatty acids antidepressants or just mood-improving agents? The effect depends upon diagnosis, supplement preparation, and severity of depression

State-dependent decrease in levels of brain-derived neurotrophic factor in bipolar disorder: a meta-analytic study.

Evidence has suggested a role of brain-derived neurotrophic factor (BDNF) in the pathogenesis of bipolar disorder (BD). Recent studies have examined BDNF levels in BD patients, but showed inconsistent results. In current study, meta-analyses by random-effects model were performed to compare blood BDNF levels between BD patients and healthy controls, and examine patients based on different affective status (manic, depressed, or euthymic state). Fifteen studies from 10 citations were included into the analysis. Pooling of results from all studies indicated that, overall, patients with BD had a lower level of BDNF than healthy controls (p=1x10(-4)). But when separating these studies based on different affective status, it showed that the significance existed only when comparing patients in manic (p=0.0008) or depressed (p=0.02) state with controls, but not in euthymic state (p=0.25). In addition, BDNF level was significantly increased after pharmacological treatment of manic state (p=0.01). These findings indicate that BDNF levels are abnormally reduced in manic and depressed states of BD, and the reduced level in manic state increases after treatment. They suggest a role of blood BDNF level as a state-dependent biomarker of bipolar disorder.

Meta-analysis of the association of serotonin transporter gene polymorphism with obsessive–compulsive disorder

Evidence has supported a role for serotonin system dysfunction in the pathogenesis of the obsessive-compulsive disorder (OCD). Many studies examined the association between OCD and a functional polymorphism of the serotonin transporter gene promoter (5-HTTLPR) but yielded inconsistent results. Current study aimed to determine conclusively whether there is an association by using a meta-analytic method. Over 3000 subjects from 13 independent case-control association studies were included in the analysis. By using random effects model, data from these studies were pooled to compare the genotypes and allelic distribution of the 5-HTTLPR polymorphism between OCD patients and control subjects. In the analysis, OCD was found to be associated with the SS homozygous genotype (OR=1.21, p=0.04), but was inversely associated with the LS heterozygous genotype (OR=0.79, p=0.03). No association with the LL homozygous genotype or the allelic distribution was found. These results suggest that variations of the serotonin transporter gene influence the risk of OCD, but their functional roles in the pathogenesis of OCD need to be elucidated.

Association between Serotonin Transporter Gene Polymorphism and Eating Disorders: A Meta-Analytic Study

OBJECTIVE Compelling evidence has suggested a role for serotonin system dysfunction in the pathogenesis of eating disorders (EDs), including anorexia nervosa (AN) and bulimia nervosa (BN). Studies have examined the association between EDs and a functional polymorphism of the serotonin transporter gene promoter (5-HTTLPR). These studies have yielded inconsistent results. The present study aimed to determine conclusively whether there is an association by using a meta-analytic method. METHOD Data of over 2,000 participants from eight independent case-controlassociation studies were pooled by using a random effects model. RESULTS AN was found to be significantly associated with the S allele (p < .001) and S carrier (SS + LS) genotype (p = .007). However, BN was associated neither with the S allele (p = .49) nor with the S carrier genotype (p = .33). DISCUSSION These results suggested that the genetic variance of the serotonin transporter gene promoter contributed to the susceptibility of AN.

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.

Subtypes of Mild Cognitive Impairment Among the Elderly With Major Depressive Disorder in Remission

BACKGROUND Cognitive impairment in remitted late-life depression varies and might be associated with greater risk of dementia in some individuals. This study aimed to classify the subtypes of mild cognitive impairment (MCI) in late-life major depressive disorder in remission and to examine their clinical correlates and structural magnetic resonance imaging (MRI) features. METHODS Elderly patients with major depressive disorder in remission and elderly comparisons were examined by a comprehensive battery of cognitive tasks. Proposed diagnostic criteria were used for MCI classification, and the degree of brain atrophy and white matter hyperintensity on MRI were evaluated. RESULTS We found information-processing speed and memory were independent cognitive domains associated with late-life remitted major depressive disorder. Of the study cohort, 52.3% met the definition of MCI, including 28.5% with amnestic MCI (aMCI) and 23.8% with nonamnestic MCI (naMCI). A clinical correlate of aMCI was the late-onset of disorder (OR = 4.76; 95% CI = 1.57, 14.40) and of naMCI was a higher score on the Framingham stroke risk scale (OR = 1.39; 95% CI = 1.12, 1.72). The odds ratio of highest quartile of ventricular atrophy for aMCI compared to the comparisons was 3.65 (95% CI = 1.22, 10.96). CONCLUSIONS The central cognitive impairments among the elderly with major depressive disorder in remission were memory and information-processing speed, and over half of the subjects met the MCI diagnostic criteria. Different risk factors existed for the subtypes of aMCI and naMCI. Later-age onset of first episode and ventricular atrophy were associated with aMCI, whereas vascular risk factor were associated with naMCI. We suggest there were different pathogeneses between aMCI and naMCI in late-life major depressive disorder.

Age-associated decrease in serum glial cell line-derived neurotrophic factor levels in patients with major depressive disorder

BACKGROUND Many studies have supported the role of neurotrophic hypothesis in the pathophysiology of mood disorders. This study examined serum levels of glial cell line-derived neurotrophic factor (GDNF), one of the neurotrophic factors, in patients with major depressive disorder (MDD) at different disease states. METHODS The serum GDNF levels were measured in 55 patients with MDD (29 severe patients and 26 remitted patients) and 35 healthy controls by ELISA method. Severity of depressive symptoms was assessed using the 17-item Hamilton Rating Scale of Depression (HAM-D) (HAM-D >/= 19 for severe MDD, HAM-D </= 7 for remitted MDD). RESULTS MDD patients were found to have significantly lower serum GDNF levels than healthy controls (p<0.001). This decrease was significant in older-aged (p=0.003) and middle-aged (p=0.026) groups, but not in the younger-aged group. We found no difference in GDNF level between severe and remitted MDD patients. CONCLUSIONS In spite of some limitations, our results indicate an age-associated reduction in serum GDNF levels in patients with MDD, further supporting the role of the neurotrophic factor as a disease marker and a new target for developing antidepressant treatment.

Low-dose escitalopram for 2 days associated with corrected QT interval prolongation in a middle-aged woman: a case report and literature review

Prolongation of the corrected QT interval (QTc) on the electrocardiography is an important clinical condition because it increases the risk of torsade de pointes, a medical emergency that can cause sudden cardiac death. QTc prolongation can be induced by many drugs, including antipsychotics and tricyclic antidepressants (TCAs). Compared with TCAs, use of selective serotonin reuptake inhibitors (SSRIs) was less likely to cause severe cardiac adverse effects. Escitalopram, one of the SSRIs, has shown significant antidepressant efficacy and well tolerability. Here, we present one female patient showing QTc prolongation induced by low-dose (5 mg/day) treatment of escitalopram for 2 days. The QTc returned to normal soon after discontinuation of escitalopram. Clinicians should be cautious about cardiac effects when using a SSRI, even in a low dose.

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.