Psychological characteristics and emotional difficulties underlying school refusal in adolescents using functional near-infrared spectroscopy.

BACKGROUND: This study aims to explore the psychological characteristics, related emotional problems and potential NIR brain function mechanism of adolescents who refuse to attend school. METHODS: The study included 38 adolescents (12-18 years old) who were not attending school and 35 healthy controls (12-18 years old) who are attending school regularly. Participants completed (1) general demographics, (2) Eysenck Personality Questionnaire (EPQ), (3) Zung Self-Rating Depression Scale (SDS), (4) Zung Self-Rating Anxiety Scale (SAS), and (5) Symptom Checklist-90 (SCL-90). In addition to the clinical tests, participants completed functional near-infrared spectroscopy (fNIRS). Mental health, personality, and emotional state were evaluated in both groups to explore the differences and to understand the underlying mechanisms of school refusal during adolescence. RESULTS: Adolescents who did not attend school had higher neuroticism scores on the Eysenck Personality Questionnaire than healthy controls (p(FDR) < 0.001), introversion and concealment scores were lower than those of healthy controls (p(FDR) < 0.001), there was no significant difference in psychoticism scores between groups. SDS, SAS, SCL-90 scores and factor scores were higher than those of healthy control group (p(FDR) < 0.001), NIR functional brain imaging was different from healthy control group in the 12 and 27 channels (p(FDR) = 0.030, p(FDR) = 0.018), and no difference was found in the remaining channels (p(FDR) > 0.05). There were statistically significant differences in age and gender between the adolescents who refused school and the control group (p(FDR) < 0.001). CONCLUSION: School refusal adolescents are relatively introverted and sensitive and need more attention in daily life. Although the adolescents' emotional problems did not reach the diagnostic criteria of depressive disorder and anxiety disorder, their scores were still higher than those of the control group, suggesting that we should pay more attention to their emotional problems in order to better help them return to school. Using fNIRS, it was found that abnormalities in frontal lobe regions in adolescents with school refusal behaviors, which would contribute to early diagnosis and timely intervention of school refusal behaviors.

Add-On Intermittent Theta Burst Stimulation Improves the Efficacy of First-Episode and Recurrent Major Depressive Disorder: Real-World Clinical Practice.

Objective: Repetitive transcranial magnetic stimulation (rTMS) is an effective and evidence-based treatment for major depressive disorder (MDD). This retrospective study aimed to explore the efficacy of add-on iTBS treatment in MDD in real-world clinical practice. Methods: One hundred and fifty-nine inpatients with MDD in a general hospital were included in this study. These patients were treated with at least 8 sessions of iTBS, in addition to antidepressants and supportive psychotherapy. Symptoms of depression and anxiety were assessed with the Hamilton Depression Rating Scale (HDRS) and the Hamilton Rating Scale for Anxiety (HAMA) at baseline and after 2-4 weeks of treatment. The improvement degree of depressive and anxious symptoms was compared between the first-episode MDD (n=107) and recurrent MDD (n=52) groups. Results: Depressive and anxious symptoms were reduced significantly after the add-on iTBS treatment; the response and remission rates in the first-episode MDD group were 55.14% and 28.97%, which were 63.46% and 28.85% for the recurrent MDD group, respectively (P>0.05). The response rate and remission rate of anxiety in the first-episode MDD group was 64.13% and 57.45% for HAMA, and 66.67% and 62.50% for the recurrent MDD group (P>0.05). Conclusion: Our findings indicated that antidepressant and anti-anxiety efficacy of add-on iTBS treatment remains equivocal in real-world clinical practice, regardless of a first-episode depression diagnosis or recurrent depression.

Analysis of Whole Blood and Urine Trace Elements in Children with Autism Spectrum Disorders and Autistic Behaviors.

The relationship between trace elements and neurological development is an emerging research focus. We performed a case-control study to explore (1) the differences of 13 trace elements chromium (Cr), manganese (Mn), cobalt (Co), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), stannum (Sn), stibium (Sb), mercury (Hg), titanium (TI), and plumbum (Pb) concentration in whole blood and urine between autism spectrum disorder (ASD) children and their typical development peers, and (2) the association between the 13 trace elements and core behaviors of ASD. Thirty ASD subjects (cases) and 30 age-sex-matched healthy subjects from Baise City, Guangxi Zhuang Autonomous Region, China, were recruited. Element analysis was carried out by inductively coupled plasma-optical emission spectrometry. Autistic behaviors were assessed using Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Children Neuropsychological and Behavior Scale (CNBS). The whole blood concentrations of Mo (p = 0.004), Cd (0.007), Sn (p = 0.003), and Pb (p = 0.037) were significantly higher in the ASD cases than in the controls. Moreover, Se (0.393), Hg (0.408), and Mn (- 0.373) concentrations were significantly correlated between whole blood and urine levels in ASD case subjects. There were significant correlations between whole blood Sb (0.406), Tl (0.365), Mo (- 0.4237), Mn (- 0.389), Zn (0.476), and Se (0.375) levels and core behaviors of ASD. Although the mechanism of trace element imbalance in ASD is unclear, these data demonstrate that core behaviors of ASD may be affected by certain trace elements. Further studies are recommended for exploring the mechanism of element imbalance and providing corresponding clinical treatment measures.

A resting state fMRI study of major depressive disorder with and without anxiety.

BACKGROUND: The neurobiology of the Major depressive disorder (MDD) with anxiety is still unclear. The present study aimed to explore the brain correlates of MDD with and without anxiety in men and women during resting-state fMRI. METHODS: Two hundred and fifty-four patients with MDD (MDD with anxiety, N = 152) and MDD without anxiety, N = 102) and 228 healthy controls (HCs) participated in this study. We compared the fALFF(fractional amplitude of low-frequency fluctuations) and ReHo(regional homogeneity) of ACC(anterior cingulate cortex) and insula among these three groups. We also compared gender difference between MDD with anxiety and MDD without anxiety. RESULTS: We found that the fALFF values within the ACC and insula were significantly lower in MDD with anxiety compared to without anxiety and HCs. However, we did not find differences in ReHo values among the three groups. In women, we found significant differences in fALFF values between MDD with and without anxiety. These differences were not observed in men. CONCLUSIONS: It is possible that MDD with anxiety show less spontaneous BOLD-fMRI signal intensity within the ACC and insula compared to MDD without anxiety, especially in women. The fALFF within the ACC and insula can be a potential biomarker for severe MDD phenotype.

The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder.

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.

Associations among serum markers of inflammation, life stress and suicide risk in patients with major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) are at high risk for suicide. As the worst outcome of MDD and common self-concealment in patients with suicide risk, studies of biomarkers may provide useful tools for suicide prevention and treatment. METHODS: This study recruited 168 patients with MDD from the Objective Diagnostic Markers and Personalized Intervention in MDD patients (ODMPIM), including 50 patients with suicide risk. Based on previous evidence and hypothesis, 23 targeted serum biomarkers involving immune-inflammation, neurotrophins, hypothalamic-pituitary-adrenal (HPA) axis and metabolism, were measured. We used path analysis and principal components analysis (PCA) to clarify the associations among serum biomarkers, childhood adversities, adulthood life events, severity of depression and suicide risk. RESULTS: We identified that patients with suicide risk had a higher level of inflammatory markers in serum than patients without suicide risk (P < 0.001), especially chemokine (C-X-C motif) ligand 1 (CXCL-1). After using the Bonferroni correction, there were no differences in biomarkers related to neurotrophins, HPA-axis and metabolism. In addition, a higher proportion of patients with suicide risk had adulthood adversity (assessed by Life Events Scale) (P = 0.003). Intriguingly, path analysis demonstrated that the association between adulthood adversity and suicide risk mainly depended on severity of depression and inflammatory index. CONCLUSION: This study highlights the possible role of inflammation involved in suicide risk of MDD patients. Inflammatory markers have the potential for early identification and then reducing suicidal behaviors or becoming novel treatment targets in suicide risk management.

The association study of CLOCK gene polymorphisms with antidepressant effect in Chinese with major depressive disorder.

AIM: Major depressive disorder (MDD) is a common psychiatric disorder with a complicated pathogenesis and genetic predisposition. The objective of this article is to explore the relationship between the four SNPs of circadian locomotor output cycles kaput (CLOCK) gene (rs11932595, rs12504300, rs3805148, rs534654) and the efficacy of antidepressants. Materials & methods: This study enrolled a total of 600 patients, who met the DSM-V diagnostic criteria for MDD. All subjects were treated with single selective serotonin reuptake inhibitors. The HAMD17 and adverse reaction scale (TESS/UKU) were used to assess the efficacy of antidepressants and adverse effects. The PCR and DNA sequencing analysis were used to genotype loci of CLOCK gene. RESULTS: The antidepressants efficacy of subjects with rs11932595 AA genotype was significantly higher than those with GG+GA genotypes (p = 0.035). But this p-value was not significant after false discovery rate (FDR) adjustment. CONCLUSION: The variant of CLOCK gene may be associated with the efficacy of selective serotonin reuptake inhibitors in Chinese Han MDD patients.

Anticholinergic use trends in 14,013 patients with schizophrenia from three national surveys on the use of psychotropic medications in China (2002-2012).

Our previous study demonstrated that there have been changes in the patterns of prescription antipsychotic use in China over the period from 2002 to 2012. The aim of this study was to evaluate whether time trends were present for the prescription of anticholinergic medications (ACMs) during the observation period. A total of 14,013 patients with schizophrenia treated in 45 psychiatric hospitals/centers nationwide were surveyed in 2002, 2006 and 2012. Basic socio-demographic and clinical characteristics and the prescription of psychotropic drugs were recorded using a standardized protocol and data collection procedure. The frequency of ACM prescription was 25.9% in the whole sample (29.5%, 21.6%, and 27.4% in 2002, 2006 and 2012, respectively). In addition, different temporal trends were observed across age groups. Multiple logistic regression analysis of the entire sample showed that ACM prescriptions were predicted by females, outpatients, patients receiving high doses of antipsychotic medication, select study years, benzodiazepine users, patients displaying extrapyramidal side effects, as well as antipsychotic prescription patterns. Although there was more widespread use of second-generation antipsychotics over the past decade, the frequency of ACM use only slightly decreased. How to use ACM appropriately is still a therapeutic issue that needs to foster evidence-based prescription practice.

Adjunctive antidepressant use in schizophrenia in China: A national survey (2002-2012).

OBJECTIVE: This study examined the pattern of adjunctive antidepressant use in schizophrenia patients and its demographic and clinical correlates in a nationwide survey in China. METHODS: Fourteen thousand and thirteen patients in 45 Chinese psychiatric hospitals or centers were interviewed (4,486 in 2002, 5,288 in 2006, and 4,239 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Chi-square test, independent-samples t test, Mann-Whitney U test, and multiple logistic regression analysis were used in data analyses. RESULTS: Antidepressant use was found in 5.2% of the study population with 4.6% in 2002, 4.3% in 2006, and 6.9% in 2012, respectively. A significant increase in use from 2006 to 2012 was found (p < .001). Multiple logistic regression analyses in the whole population revealed that patients receiving adjunctive antidepressants were more likely to be outpatients in tertiary referral centers (level-III hospitals) and who had an earlier age of onset, less severe global illness, but more depressive symptoms. They were less likely to receive first-generation antipsychotics but more likely to receive benzodiazepines (R2  = 0.255, p < .001). CONCLUSIONS: Despite an increasing trend, the frequency of antidepressant use in schizophrenia in China was considerably lower than in Western countries. The benefits and risks associated with concomitant use of antidepressants in schizophrenia need to be studied further.

Electroconvulsive Therapy in Schizophrenia in China: A National Survey.

OBJECTIVE: Little is known about electroconvulsive therapy (ECT) use in the treatment of schizophrenia in China. This study examined the frequency of ECT use, its trend between 2006 and 2012, and its independent demographic and clinical correlates in a nationwide survey in China. METHODS: A total of 5162 inpatients in 45 Chinese psychiatric hospitals/centers were interviewed (2696 in 2006 and 2466 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. RESULTS: Electroconvulsive therapy was used in 6.1% of the whole sample; 4.7% in 2006 and 7.7% in 2012 (P < 0.001) with wide interprovince variations. Multiple logistic regression analyses of the whole sample revealed that patients receiving ECT were more likely to be women, receive second-generation antipsychotics, treated in tertiary referral centers (level III hospitals), had a shorter illness duration, and more positive and depressive symptoms (R = 0.181; P < 0.001). CONCLUSIONS: Electroconvulsive therapy for schizophrenia has increased between 2006 and 2012 in China. Its percentage was higher than the figures reported in most other countries. Reasons for the substantial variations in the frequency of ECT across different provinces in China require further investigations.

Homotopic connectivity in drug-naïve, first-episode, early-onset schizophrenia.

BACKGROUND: The disconnection hypothesis of schizophrenia has been extensively tested in adults. Recent studies have reported the presence of brain disconnection in younger patients, adding evidence to support the neurodevelopmental hypothesis of schizophrenia. Because of drug confounds in chronic and medicated patients, it has been extremely challenging for researchers to directly investigate abnormalities in the development of connectivity and their role in the pathophysiology of schizophrenia. The present study aimed to examine functional homotopy - a measure of interhemispheric connection - and its relevance to clinical symptoms in first-episode drug-naïve early-onset schizophrenia (EOS) patients. METHODS: Resting-state functional magnetic resonance imaging was performed in 26 first-episode drug-naïve EOS patients (age: 14.5 ± 1.94, 13 males) and 25 matched typically developing controls (TDCs) (age: 14.4 ± 2.97, 13 males). We were mainly concerned with the functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) measured by voxel-mirrored homotopic connectivity (VMHC). RESULTS: Early-onset schizophrenia patients exhibited both global and regional VMHC reductions in comparison with TDCs. Reduced VMHC values were observed within the superior temporal cortex and postcentral gyrus. These interhemispheric synchronization deficits were negatively correlated with negative symptom of the Positive and Negative Syndrome Scale. Moreover, regions of interest analyses based on left and right clusters of temporal cortex and postcentral gyrus revealed abnormal heterotopic connectivity in EOS patients. CONCLUSIONS: Our findings provide novel neurodevelopmental evidence for the disconnection hypothesis of schizophrenia and suggest that these alterations occur early in the course of the disease and are independent of medication status.

Efficacy and safety of prolonged-release trazodone in major depressive disorder: a multicenter, randomized, double-blind, flexible-dose trial.

OBJECTIVE: To investigate the efficacy, safety, and clinical benefit of prolonged-release trazodone (Trittico) in the treatment of major depressive disorder (MDD). METHODS: In this study, 363 Chinese patients with MDD were randomized 1:1 to receive either prolonged-release trazodone (150-450 mg) or placebo treatment for 6 weeks. The primary efficacy measurement was the change of the 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of the study. The secondary efficacy measurements were the response and remission rates, the Clinical Global Impression - Improvement of Illness (CGI-I) score at the end of the study, and the change of the HAMD-14 total score and quality of sleep [evaluated by the Pittsburgh Sleep Quality Index (PSQI) scale] during the study period. RESULTS: The mean maximum daily dose was 273.11 mg for the trazodone group and 290.92 mg for the placebo group. At the end of the study, there was a significant difference between the two groups in the HAMD-17 change score (trazodone vs. placebo: -11.07 vs. -8.29, p < 0.001). Trazodone showed advantages at 1 week of treatment, and the effect lasted until the end of the study (week 6). The response and remission rates of the trazodone group were significantly higher than those in the placebo group (response rate: 59.6 vs. 37.2%, p < 0.001; remission rate: 35.5 vs. 22.2%, p = 0.005). The majority of the adverse reactions of trazodone were mild to moderate, and the most frequent adverse reactions (≥5%) were dizziness, dry mouth, somnolence, and nausea. CONCLUSIONS: Prolonged-release trazodone was more effective than placebo in MDD and was well tolerated.

Surface-based regional homogeneity in first-episode, drug-naïve major depression: a resting-state FMRI study.

BACKGROUND: Previous volume-based regional homogeneity (ReHo) studies neglected the intersubject variability in cortical folding patterns. Recently, surface-based ReHo was developed to reduce the intersubject variability and to increase statistical power. The present study used this novel surface-based ReHo approach to explore the brain functional activity differences between first-episode, drug-naïve MDD patients and healthy controls. METHODS: Thirty-three first-episode, drug-naïve MDD patients and 32 healthy controls participated in structural and resting-state fMRI scans. MDD patients were rated with a 17-item Hamilton Rating Scale for Depression prior to the scan. RESULTS: In comparison with the healthy controls, MDD patients showed reduced surface-based ReHo in the left insula. There was no increase in surface-based ReHo in MDD patients. The surface-based ReHo value in the left insula was not significantly correlated with the clinical information or the depressive scores in the MDD group. CONCLUSIONS: The decreased surface-based ReHo in the left insula in MDD may lead to the abnormal top-down cortical-limbic regulation of emotional and cognitive information. The surface-based ReHo may be a useful index to explore the pathophysiological mechanism of MDD.

Isoflurane preconditioning confers cardioprotection by activation of ALDH2.

The volatile anesthetic, isoflurane, protects the heart from ischemia/reperfusion (I/R) injury. Aldehyde dehydrogenase 2 (ALDH2) is thought to be an endogenous mechanism against ischemia-reperfusion injury possibly through detoxification of toxic aldehydes. We investigated whether cardioprotection by isoflurane depends on activation of ALDH2.Anesthetized rats underwent 40 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups: untreated controls, isoflurane preconditioning with and without an ALDH2 inhibitor, the direct activator of ALDH2 or a protein kinase C (PKCε) inhibitor. Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide. Isolated neonatal cardiomyocytes were treated with hypoxia followed by reoxygenation. Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2. In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2. Activation of ALDH2 and cardioprotection by isoflurane were substantially blocked by the PKCε inhibitor. Activation of ALDH2 by mitochondrial PKCε plays an important role in the cardioprotection of isoflurane in myocardium I/R injury.

[Association between protein tyrosine phosphatase receptor type R gene and major depressive disorder].

OBJECTIVE: To explore the genetic association between protein tyrosine phosphatase receptor type R (PTPRR) gene polymorphism and major depressive disorder (MDD) and its endophenotype. METHODS: A total of 517 unrelated MDD patients and 455 unrelated healthy subjects were recruited in this study to detect 11 single nucleotide polymorphisms (SNPs) in the PTPRR locus. They all were of the Chinese Han origin. Genotyping of SNPs was performed by matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) -based genotyping approach. The UNPHASED program was applied to analyze the genotyping data. RESULTS: Of the 11 selected SNPs, no significant allelic and genotypic association was found between MDD patients and the normal controls (corrected P > 0.05). However, analysis of haplotypes showed that the three SNPs haplotype rs1398599 (C) -rs2175711 (A) - rs4489789 (T) (P = 0.0023, OR = 1.334, 95% CI = 1.104-1.612) and four SNPs haplotype rs11178391 (C) -rs1398599 (C) -rs2175711 (A)-rs4489789(T) (P = 0.0063, OR = 1.281, 95% CI = 1.059-1.549) were associated with increased risk of MDD. Quantitative trait analysis revealed that rs2203231 in the PTPRR locus had strong allelic and genotypic association with the raw score of long-term memory (P = 0.0038 for allelic association, P = 0.0024 for genotypic association), the scaled score of long-term memory (P = 0.0057 for allelic association, P = 0.0038 for genotypic association), the raw score of short-term memory (P = 0.0027 for allelic association, P = 0.0015 for genotypic association), and the scaled score of short-term memory (P = 0.0035 for allelic association, P = 0.002 for genotypic association) in MDD patients. CONCLUSION: The polymorphism of PTPRR gene rs2203231 may be associated with the impairment of long-term and short-term memories in MDD patients.

[Association study between Protein Kinase C gamma gene polymorphism and major depressive disorder].

OBJECTIVE: To explore the genetic association of PKCgamma gene rs3745406 polymorphism with major depressive disorder (MDD) and their clinical phenotypes. METHODS: A total of 453 Chinese Han MDD patients with an initial episode were recruited from our hospital. The symptomatic phenotypes of these cases were evaluated by HAMD. Polymerase chain reaction (PCR) and direct sequencing analysis were used to detect the genotype of rs3745406. Associations of allele, genotype and quantitative character were analyzed using the UNPHASED software. RESULTS: (1) The distributions of genotypes in both study and control samples were in a Hardy-Weinberg equilibrium (chi(2) = 1.46, P = 0.25); (2) No significant allelic and genotypic association was found in these samples (P > 0.05); (3) Further analyses revealed a significant association between rs3745406 locus and HAMD suicidal phenotypes (chi(2) = 4.746, P = 0.0360). CONCLUSION: The PKCgamma rs3745406 polymorphism is not significantly associated with MDD whereas it has a marked association with suicidal symptoms in MDD.

Association of BDNF Val66Met polymorphism with both baseline HRQOL scores and improvement in HRQOL scores in Chinese major depressive patients treated with fluoxetine.

OBJECTIVE: To explore the association of brain-derived neurotrophic-factor (BDNF) Val66Met polymorphism with both baseline health related quality of life (HRQOL) scores and improvement in HRQOL scores in Chinese major depressive patients treated with fluoxetine. METHODS: Patients with major depressive disorder (MDD) took fluoxetine (20 mg/day) for 6 weeks. The HRQOL was measured with the Medical Outcomes Study Short Form-36 (SF-36) at baseline and at 6th week. Patients were genotyped for Val66Met polymorphism of BDNF gene. RESULTS: There was a significant association between social function (SF) and BDNF Val66Met polymorphism, and patients with Met/Met genotype had better SF (compared with Val/Val P = 0.004; compared with Val/Met P = 0.005). A significant association was found between improvement in SF and BDNF Val66Met polymorphism, and patients with Met/Met genotype had poorer improvement in SF (compared with Val/Val P = 0.010; compared with Val/Met P = 0.001). Similar association was found between improvement in mental component summary (MCS) and BDNF Val66Met polymorphism, and patients with Met/Met genotype had poorer improvement in MCS (compared with Val/Val P = 0.066; compared with Val/Met P = 0.006). CONCLUSIONS: These results indicate that there may be association between BDNF Val66Met polymorphism and both baseline HRQOL (SF) scores and improvement in HRQOL (SF, MCS) scores in Chinese major depressive patients treated with fluoxetine.

Association of brain-derived neurotrophic factor genetic Val66Met polymorphism with severity of depression, efficacy of fluoxetine and its side effects in Chinese major depressive patients.

BACKGROUND: Preclinical studies have shown that brain-derived neurotrophic factor (BDNF) may be involved in antidepressant action, and the BDNF gene has been suggested to be involved in the pharmacological treatment of major depressive disorder (MDD). In this study, the relationship between BDNF Val66Met polymorphism (Single Nucleotide Polymorphism Database ID: rs6265) and severity of depression, efficacy of fluoxetine and its side effects was tested in Chinese patients with MDD. METHODS: Patients with MDD took the oral selective serotonin reuptake inhibitor (SSRI) fluoxetine (20 mg/day) for 6 weeks. Its clinical efficacy and side effects were measured by the 17-item Hamilton Rating Scale for Depression and the Treatment-Emergent Symptoms Scale (TESS), respectively. The patients were genotyped for Val66Met polymorphism of the BDNF gene. RESULTS: In the multivariate regression analysis, there was no significant association between severity of depression and BDNF Val66Met polymorphism. There was no association between efficacy of fluoxetine and BDNF Val66Met polymorphism, but there was a marginal positive suggestion that heterozygous patients tended to have a better remission with fluoxetine in comparison with homozygous analogs. Insomnia and decreased sexual desire, side effects of fluoxetine, may have an association with the BDNF Val66Met polymorphism, and Met allele carriers showed a lower incidence of these side effects. CONCLUSIONS: These results indicate that there was a lack of association between severity of depression and BDNF Val66Met polymorphism in Chinese patients with MDD. The BDNF Val66Met polymorphism may play a major role in the efficacy and side effects of SSRI (fluoxetine) in Chinese patients with MDD.

[Association between copy number variants within metabotropic glutamate receptors 7 gene and schizophrenia].

OBJECTIVE: To investigate whether genomic copy number variants (CNVs), within metabotropic glutamate receptors 7 (GRM 7) gene are associated with schizophrenia. METHODS: We examined CNVs in conserved region of GRM7 using real time quantitative PCR among 180 Chinese schizophrenia cases and 33 normal controls. Products of real time quantitative PCR were sequenced bilaterally. RESULTS: Real time quantitative PCR found that a biallelic deletion existed at the 200 bps up-stream of exon 2 in a schizophrenia patient and a monoallelic deletion existed at this site in another 13 schizophrenia patients and a control subject. However, sequencing results showed a substitution of C to G at the 5bp up-stream of 3' end of reverse primer for real time PCR (GRM7-SV-1R). In addition, samples with this variant were exactly those having biallelic or monoallelic deletions, indicating that the results of the real time PCR were caused by the substitution variant at the 3' end of the primer rather than a bona fide genome deletion. CONCLUSIONS: Real-time quantitative PCR combined with sequencing can avoid false positive deletions and therefore is effective in detecting CNVs. According to our results, CNVs in GRM 7 gene is not associated with schizophrenia in the Han Chinese population. However, some potential rare CNVs may still have such relationship, and require further study.

[Association between monoamine oxidase A gene and major depression in Chinese Han population].

OBJECTIVE: To explore the association between monoamine oxidase A (MAOA) variable number tandem repeat (VNTR) polymorphism and major depression in Chinese Han population. METHODS: Polymerase chain reaction was used to genotype MAOA VNTR polymorphism. A total of 512 major depression patients and 566 normal controls were recruited in our study. These patients were also assessed using the 14-item Hamilton anxiety scale. RESULTS The allele frequency of MAOA VNTR was not significantly different between the male/female major depression patients and the normal controls. Compared with the normal controls, MAOA VNTR genotype was significantly more frequent in female major depression patients (P=0.002), but not in male patients (P=0.17). MAOA VNTR-L carrier was also associated with "fear" symptom in female patients (P=0.0056). CONCLUSION: MAOA gene is associated with the major depression in Chinese Han population, especially among female patients.