Comparison of the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depressive disorder

Objective

Only two-thirds of depressive patients respond to antidepressant treatment. In recent years, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we compared the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depression.

Subjects and methods

Twenty-four patients who met the DSM-IV criteria for major depressive disorder who did not at least two different classes of antidepressants were enrolled in the study. Nine were male and thirteen were female, and their ages ranged from 28 to 66 (mean ± SD = 39 ± 12) years. Patients were prescribed paroxetine (n = 11) or sertraline (n = 13) for 4 weeks. Then, those whose scores on the 17-item Hamilton Rating Scale for Depression (HAMD17) decreased below 50% received adjunctive therapy of aripiprazole for 4 weeks.

Results

Although the use of either combination treatment decreased the HAMD17 scores compared to the respective monotherapy, there was no significant difference in HAMD17 scores between the paroxetine plus aripiprazole group and sertraline plus aripiprazole group.

Conclusion

Aripiprazole augmentation therapy with paroxetine or sertraline was equally effective and tolerated in patients with refractory major depressive order.     

Neurotrophin-3 gene,intelligence, and selective attention deficit in a Korean sample with attention-deficit/hyperactivity disorder

Objective

Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a strong genetic component. Neurotrophin-3 (NTF3), which participates in the differentiation and survival of dopaminergic and noradrenergic neurons, has been identified as a factor in the development of ADHD. We investigated the relationships between ADHD and NTF3 gene polymorphism.

Methods

We conducted a case–control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 151 trios, and compared the intelligence quotient (IQ) and a continuous performance test (CPT) according to the genotype of two single-nucleotide polymorphisms (SNPs) (rs6332 and rs6489630) in the NTF3 gene.

Results

In the case–control and family-based analyses, NTF3 was not significantly associated with ADHD. However, in the ADHD probands, the subjects with AA genotype in the rs6332 SNP had significantly higher mean T-scores for commission errors on the CPT than did those with the AG genotypes (p = 0.045). The mean IQ of the ADHD probands who had the CC genotype of the rs6489630 SNP were higher compared with those who had the CT or TT genotype (p = 0.035). The mean T-score for response time on the CPT was higher in the subjects with TT genotype in the rs6489630 SNP compared to those with the CC or CT genotype, even after adjusting for the effect of IQ (p = 0.021).

Conclusions

These results provide preliminary evidence of an association between NTF3 and the intelligence and selective attention deficit in the Korean population.     

Validation of the Chinese Non-Motor Symptoms Scale for Parkinson's disease: Results from a Chinese pilot study

Objectives

To evaluate a Chinese version of the Non-Motor Symptoms Scale (NMSS) in Parkinson's disease (PD) as an instrument for measuring non-motor symptoms (NMSs) in Chinese patients with Parkinson's disease.

Methods

We conducted a psychometric analysis of the Chinese version of NMSS using a cross-sectional study of 126 patients with PD. The battery also included the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Hamilton Anxiety Scale (HAMA), and was conducted by neurologists.

Results

There were significant correlations between the NMSS and PSQI scores (rS = 0.63, P < 0.001), as well as the NMSS and ESS scores (rS = 0.38, P < 0.001). Furthermore, significant positive correlations between NMSS and GDS, NMSS and HAMA, and NMSS and disease duration were also observed. Importantly, the sleep/fatigue index of the NMSS significantly correlated with the PSQI and ESS findings, the mood/cognition index of the NMSS significantly correlated with the GDS and HAMA findings, and the attention/memory index of the NMSS significantly correlated with the MMSE findings.

Conclusion

The Chinese version of the NMSS can be considered a comprehensive, useful measure for NMS evaluation in Chinese PD patients.     

Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder

Objectives

Bipolar disorder is a severe mental disorder with prominent genetic etiologic factors. Dopaminergic dysfunction has been implicated in the pathogenesis of bipolar disorder, which suggests that the dopamine D3 receptor gene (DRD3) is a strong candidate gene. The brain-derived neurotrophic factor (BDNF) gene has been implicated in the etiology of bipolar disorder. We examined the association between the BDNF Val66Met and DRD3 Ser9Gly polymorphisms with two subtypes of bipolar disorder: bipolar-I and -II. Because BDNF regulates DRD3 expression (1), we also examined possible interactions between these genes.

Methods

We recruited 964 participants: 268 with bipolar-I, 436 with bipolar-II, and 260 healthy controls. The genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.

Results

Logistic regression analysis showed a significant main effect for the Val/Val genotype of the BDNF Val66Met polymorphism (P = 0.020), which predicted bipolar-II patients. Significant interaction effects for the BDNF Val66Met Val/Val genotype and both DRD3 Ser9Gly Ser/Ser and Ser/Gly genotypes were found only in bipolar-II patients (P = 0.027 and 0.006, respectively).

Conclusion

We provide initial evidence that the BDNF Val66Met and DRD3 Ser9Gly genotypes interact only in bipolar-II disorder and that bipolar-I and bipolar-II may be genetically distinct.     

Association of the manganese superoxide dismutase gene Ala–9Val polymorphism with clinical phenotypes and tardive dyskinesia in schizophrenic patients

Objective

Several recent studies that have investigated the genetic association between the manganese superoxide dismutase (MnSOD) gene Ala–9Val single-nucleotide polymorphism (SNP) and tardive dyskinesia (TD) have produced conflicting results. This study was to investigate whether this SNP was associated with clinical phenotypes and antipsychotic-induced tardive dyskinesia (TD) in schizophrenia in a genetically homogeneous Han Chinese inpatient population.

Methods

Genotyping was performed for the MnSOD gene Ala–9Val SNP in Chinese schizophrenia patients with (n = 176) and without TD (n = 346). The severity of TD was assessed using the abnormal involuntary movement scale (AIMS), and psychopathology using the Positive and Negative Syndrome Scale (PANSS).

Results

The frequencies of genotypes and alleles did not differ significantly between schizophrenic patients with and without TD (both p > 0.05). Also, there was no significant difference in the AIMS total score between the Val/Val and Ala allele carrier groups (p > 0.05). However, the PANSS negative symptom subscore was significantly higher in patients with Val/Val genotype (21.8 ± 7.3) than those with Ala alleles (20.1 ± 7.7) (t = 2.32, p = 0.03).

Conclusion

While the MnSOD gene Ala–9Val polymorphism did not play a major role in the susceptibility to TD in schizophrenic patients, it might be associated with negative symptoms of schizophrenia.     

Association of F11 polymorphism rs2289252 with deep vein thrombosis and related phenotypes in population of Latvia

Introduction

Deep vein thrombosis (DVT) has a strong inherited predisposition that is partly explained by the strong genetic risk factors such as mutations in factor V, prothrombin, antithrombin III, protein C and S genes. Only recently the first GWAS have been performed on DVT resulting in discovery of novel genetic variants, however, the information on the common polymorphisms predisposing to the risk of DVT is still scarce.

Materials and Methods

Here we selected six SNPs (rs5361 in SELE, rs2066865 in FGG, rs2227589 in SERPINC1, rs1613662 in GP6, rs13146272 in CYP4V2, rs2289252 in F11) reported to be associated with venous thrombosis conditions and studied the association of these common variants in selected case (n = 177) and control (n = 235) groups from population of Latvia. Genotyping was performed using TaqMan hybridization probe SNP genotyping assay.

Results

Patients with DVT had a significantly higher frequency of F11 rs2289252 polymorphism (p = 0.001; OR [95%CI] = 1.61 [1.20-2.14]). When stratified by recurrence of DVT the tendency was observed that the same SNP had higher OR value in group of DVT patients with repeated episodes of DVT compared to patients with single DVT episode (p = 0.009; OR [95%CI] = 2.27[1.22-4.21] and p = 0.009; OR [95%CI] = 1.52[1.11-2.08] respectively), but due to limited group of cases this finding should be replicated.

Conclusion

We conclude that F11 gene variant rs2289252 contribute to inherited forms of DVT incidence and correlation of other analysed SNPs should be explored in populations with greater sample size and associated with various thrombosis related traits.     

The association of the JAK2 46/1 haplotype with non-splanchnic venous thrombosis

Background

The inherited JAK2 46/1 haplotype is strongly associated with the development of myeloproliferative neoplasms (MPNs), and its increased frequency has also been reported in splanchnic venous thrombosis (SVT). In the present study, the role of the JAK2 46/1 haplotype in non-splanchnic venous thrombosis (non-SVT) was investigated.

Methods and Results

We genotyped 438 patients with non-SVT, 226 patients with MPNs and 459 healthy controls for three single nucleotide polymorphisms (SNPs) which tag the JAK2 46/1 haplotype (rs12342421 G > C, rs12343867 T > C and rs10974944 C > G). We found statistically significant association of the rs12342421 GC + CC genotypes (OR = 1.40; p = 0.023) and the rs12343867 TC + CC genotypes (OR = 1.83; p = 7.02x10^- 5) with non-SVT. We also found that the CC haplotype of these two SNPs was associated with an increased risk of the disease (OR = 1.68; p = 0.009). Stratification analysis indicated that the observed association of the JAK2 46/1 haplotype with non-SVT was probably largely free of confounding effect of thrombophilic risk factors. In addition, we established a strong association of SNPs rs12342421 and rs10974944 and their CG haplotype with MPNs and with JAK2 V617F-positive MPNs.

Conclusions

This study provides statistical evidence that SNPs rs12342421 and rs12343867 are associated with an increased risk of non-SVT. Consistently, haplotypes of the SNPs were also associated with non-SVT risk, suggesting that inherited genetic variation in the JAK2 gene may play a role in the pathogenesis of non-SVT. Furthermore, the reported associations of the JAK2 46/1 haplotype with MPNs as well as with the occurrence of the JAK2 V617F mutation in MPNs were confirmed.     

A genetic schizophrenia-susceptibility region located between the ANKK1 and DRD2 genes

Background

The gene coding for the D2 dopamine receptor (DRD2) is considered to be one of the most pertinent candidate genes in schizophrenia. However, genetic studies have yielded conflicting results whereas the promising TaqIA variant/rs1800497 has been mapped in a novel gene, ANKK1.

Methods

We investigated eleven single nucleotide polymorphisms (SNPs) spanning the DRD2 and ANKK1 genes, using both a case–control association study comparing 144 independent patients to 142 matched healthy subjects, and a transmission disequilibrium test in 108 trios. This classical genetic study was coupled with a cladistic phylogeny-based association test of human variants, and with an interspecies evolution study of ANKK1.

Results

Case–control study, followed by a 108 trios family-based association analysis for replication, revealed an association between schizophrenia and the ANKK1 rs1800497 (p = 0.01, Odds Ratio = 1.5, 95% Confidence Interval = 1.1–2.2), and the intergenic rs2242592 (p = 2 · 10^− 4, OR = 1.8, 95%CI = 1.3–2.5). A significant SNP–SNP interaction was also found (p < 10^− 5, OR = 2.0, 95%CI = 1.6–2.5). The phylogeny-based association test also identified an association between both these polymorphisms and schizophrenia. Finally, interspecies comparison of the sequences from chimpanzee, orangutan, rhesus macaque and human species suggested specific involvement of ANKK1 in the human lineage.

Conclusions

Intergenic rs2242592 appears to be involved in the genetic vulnerability to schizophrenia, whereas the ANKK1 rs1800497 appears to have a modifying rather than causative effect. Finally, ANKK1 may be a specific human lineage-trait involved in a specific human disease, schizophrenia.     

Hopelessness, a potential endophenotpye for suicidal behavior, is influenced by TPH2 gene variants

Objectives

Hopelessness is one of the strongest risk factors for suicidal behavior but relevant genetic studies are poorly available. Tryptophan hydroxylase (TPH) is widely considered to be a good candidate for genetic association studies on depression and suicide, however, investigations on these complex, multifactorial phenotypes have resulted in conflicting data. We hypothesized that hopelessness could be a mediating phenotype between TPH2 gene, depression and suicidal behavior.

Methods

Depressive phenotype and suicidal risk were investigated of 760 individuals from general population by Zung Self Rating Depression Scale (ZDS), Beck's Hopelessness Scale (BHS) and a detailed background questionnaire. All participants' DNA samples were genotyped for 7 tag SNPs in TPH2 gene. Generalized linear models were performed for single marker association studies and p-values were corrected by Bonferroni criteria. In haplotype analyses score tests were used and permutated p-values were computed.

Results

Four SNPs of TPH2 gene showed association with hopelessness but only rs6582078 had a significant effect on the BHS scores after Bonferroni's correction; GG individuals had significantly higher BHS scores, while GT and TT had intermediate and lower BHS scores respectively (p = 0.0047). Compared with other genotypes, homozygous GG individuals also had almost three times greater estimated suicidal risk, as did carriers of the AA genotype of rs6582078 (OR = 2.87; p = 0.005) and also of rs1352250 (OR = 2.86; p = 0.006). A risk and a protective haplotype of TPH2 gene were also identified in association with hopelessness. ZDS scores have not shown any association with TPH2 gene.

Conclusions

We found that hopelessness, with its allied increased suicidal risk was strongly associated with TPH2 gene variants in multiple tests. These findings suggest that TPH2 gene confers risk for suicidal behavior while hopelessness can be a potential endophenotype for suicidal vulnerability.     

Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism

Introduction

We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case–control study (n = 2753) from Sweden.

Materials and Methods

39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression.

Results

Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181).

Conclusions

It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.     

Double-blind placebo-controlled trial of pentoxifylline added to risperidone: Effects on aberrant behavior in children with autism

Background

There are several lines of evidence to indicate that the immune system plays an important role in the pathophysiology of autism. The objective of this study was to access the effects of pentoxifylline plus risperidone in the treatment of autistic disorder.

Methods

Forty children between the ages 4 and 12 years with a DSM IV-TR clinical diagnosis of autism were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to pentoxifylline + risperidone or placebo + risperidone for a 10-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/day, pentoxifylline was titrated to 600 mg/day. Patients were assessed at baseline and after 2, 4, 6, 8 and 10 weeks of starting medication. The measure of the outcome was the Aberrant Behavior Checklist-Community (ABC-C).

Results

The difference between the two protocols was significant as the group that received pentoxifylline had greater reduction in ABC-C subscale scores for Irritability, Lethargy/Social Withdrawal, Stereotypic Behavior, Hyperactivity/Noncompliance and Inappropriate Speech.

Conclusion

The results suggest that combination of atypical antipsychotic medications and pentoxifylline might have synergistic effects in treatment of behavioral problems of children with autism.     

Treatment of sleep disorders may improve fatigue in multiple sclerosis

Objective

In a previous polysomnographic cross-sectional study we found a significant relationship between sleep disorders and multiple sclerosis (MS) related fatigue. The purpose of this open follow-up observation was to compare the impact of treatment of sleep disorders on MS related fatigue measured with the Modified Fatigue Impact Scale (MFIS).

Methods

Non-randomized follow-up observation: treated versus untreated patients, subgroups according to compliance with sleep medical treatment recommendations (univariate, multivariate analysis, multiple logistic regression). 66 MS patients were followed after polysomnography, 49 patients with relevant sleep disorders and 17 without.

Results

Mean MFIS scores decreased from 41.2 to 26.2 (p = 0.025) in patients with good compliance (GC; n = 18), from 42.4 to 32.1 (p = 0.12) in patients with moderate compliance (MC; n = 12), and from 41.6 to 35.5 (p = 0.17) in non-compliant patients (NC; n = 17). Mean MFIS values increased in patients without sleep disorders from 22.9 to 25.4 (NSD; n = 12, p = 0.56). In multiple logistic regression, treatment of sleep disorders predicted decrease of MFIS-values (GC versus NSD odds ratio 13.4; p = 0.015; 95% confidence interval (CI) 1.7–107.2, MC versus NSD odds ratio 13.8; p = 0.028; 95% CI 1.3–143.3).

Conclusions

Sleep medical treatment may improve MS related fatigue when patients adhere to treatment recommendations.     

The role of brain-derived neurotrophic factor (BDNF) gene variants in antipsychotic response and antipsychotic-induced weight gain

Background

Brain-derived neurotrophic factor (BDNF) has extensive effects on the nervous system including cell survival, differentiation, neuronal growth and maintenance, as well as cell death. Moreover, it promotes synaptic plasticity and interacts with dopaminergic and serotonergic neurons, suggesting an important role on the alteration of brain function with antipsychotic medications and induced weight gain in schizophrenia patients. The differential effects of BDNF gene variants could lead to changes in brain circuitry that would in turn cause variable response to antipsychotic medication. Therefore, we hypothesized that genetic variation in this candidate gene helps in explaining the inter-individual variation observed in antipsychotic drug treatment with respect to response and induced weight gain.

Method

We examined four single-nucleotide polymorphisms across the BDNF gene, including Val66Met (rs6265). Prospective BPRS change scores and weight change after six weeks were obtained from a total of 257 schizophrenia patients of European ancestry.

Results

The markers rs11030104 and Val66Met were associated with antipsychotic response (P = 0.04; 0.007, respectively). On the other hand, marker rs1519480 was associated with weight gain (P = 0.04). Moreover, a two-marker haplotype across rs6265 and rs1519480 was associated with weight change (P = 0.001). Results with Val66Met in response, and results with rs6265-rs1519480 haplotypes remained significant at the modified Bonferroni corrected alpha of 0.017.

Conclusion

BDNF genetic variants might play an important role in predicting antipsychotic response and antipsychotic-induced weight gain. However, replication in larger and independent samples is required.     

Who are at risk for thromboembolism after arthroplasty? A systematic review and meta-analysis

Background

Thromboembolism, including deep venous thrombosis and pulmonary embolism, is a grave threat to patients undergoing total joint replacement. Using a systematic review and meta-analysis we asked whether gene mutations or polymorphisms could be risk factors for thrombosis after arthroplasty.

Methods

We performed a comprehensive search of Medline, PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure (CNKI), and Google Scholar, and identified 19 studies detailing genetic investigations of patients with thromboembolism following joint replacement.

Results

Our meta-analyses included 5149 patients who underwent arthroplasty surgery. Significant associations with venous thromboembolism were identified for factor G1691A (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.03 - 1.94, p = 0.03), prothrombin G20210A (OR 2.16, 95% CI, 1.27- 3.69, p = 0.005), and MTHFR/C677T/TT (OR 2.36, 95% CI 1.03 - 5.42, p = 0.04) in Caucasian populations. No significant gene mutation was identified in Asian populations.

Conclusion

This study suggests a way to identify patients scheduled for arthroplasty who are at higher risk of thrombosis, enabling individualized treatment.     

Relationship Between ABCB1 Polymorphisms,Thromboelastography and Risk of Bleeding Events in Clopidogrel-Treated Patients With ST-Elevation Myocardial Infarction

Introduction

This study sought to investigate the relationship of polymorphisms in ABCB1 and the predictive value of thromboelastography (TEG) on bleeding risk in clopidogrel-treated patients with ST-elevation myocardial infarction (STEMI).

Methods

467 consecutive patients with STEMI undergoing percutaneous coronary intervention (PCI) were enrolled. Twenty tag single nucleotide polymorphisms (SNPs) selected from ABCB1 gene and CYP2C19*2, *3, *17 were detected by the ligase detection reaction. Platelet reactivity was assessed by TEG. The follow-up period was 12 months.

Results

By receiver operating characteristic curve analysis, the TEG platelet mapping assay value of ADP inhibition had the best predictive value of bleeding academic research consortium definition (BARC) ≥ 3b bleedings, yielding an area under the curve (AUC) of 0.707 (95% CI 0.662-0.749, p = 0.009; cut-off value > 93.4%). ADP inhibition can also predict BARC ≥ 3 bleedings with an AUC of 0.594 (95% CI 0.546-0.640, p = 0.05; cut-off value > 92.5%). After adjustment for established risk factors of bleeding including the gain of function CYP2C19*17 allele, age, female gender, renal function, the multivariable logistic regression model demonstrated that ADP inhibition > 92.5% (OR 2.247, 95%CI 1.082-4.665, P = 0.03), carriage of rs1045642 (OR 2.943, 95%CI 1.195-7.247, P = 0.019) and rs7779562 (OR 0.453, 95%CI 0.219-0.936, P = 0.032) were independent predictors of BARC ≥ 3 bleedings. These associations were validated in a second cohort of 504 STEMI patients.

Conclusions

In STEMI patients treated with clopidogrel after PCI, the ABCB1 tag SNP rs1045642 is associated with higher risk of bleedings while rs7779562 is associated with lower bleeding risk, and ADP inhibition in TEG has a predictive value of bleedings.     

Serum levels of platelet-derived growth factor BB homodimers are increased in male children with autism

Background

The neurobiological basis of autism remains poorly understood. To examine the role played by serum cytokines in brain development, we hypothesized that Platelet-Derived Growth Factor (PDGF) and Vascular Endothelial Growth Factor (VEGF) may be associated with pathophysiology of autism. In this study, we screened serum levels of these growth factors in young male subjects with autism.

Methods

We measured serum levels of PDGF subtypes and VEGF in the 31 male children with autism (6–19 years old) and 31 healthy age- and gender-matched subjects.

Results

The serum levels of PDGF-BB in male children with autism (N = 31, 5624.5 ± 1651.8 pg/mL [mean ± SD]) were significantly higher (two-tailed Student's t-test: p = 0.0188) than those of normal control subjects (N = 31, 4758.2 ± 1521.5 pg/mL [mean ± SD]). There was a significant and positive correlation (Pearson's r = 0.5320, p = 0.0010) between the serum levels of PDGF-BB and the Autism Diagnostic Interview-Revised (ADI-R) domain C scores, which represent stereotyped patterns of behavior in the children with autism. However, there were no marked or significant correlations between serum PDGF-BB levels and clinical variables, including the other ADI-R scores and Intellectual Quotient (IQ) scores by WAIS-R. There were no significant change and correlations with clinical variables in serum PDGF-AA, PDGF-AB, and VEGF levels in the children with autism.

Conclusions

Increased levels of serum PDGF-BB homodimers might be implicated in the pathophysiology of autism.     

Association between PAI-1 4G/5G Polymorphisms and osteonecrosis of femoral head: A Meta-analysis

Background

The polymorphism of the plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been correlated with susceptibility to osteonecrosis of the femoral head (ONFH), but study results are controversial. The aim of this study was to derive a more precise estimation of the relationship between the PAI-1 4G/5G Gene polymorphism and ONFH by performing a meta-analysis.

Methods

The meta-analysis was based on five eligible case-control studies involving 419 cases and 969 controls and summarized data indicating the association between PAI-1 polymorphism and risk of osteonecrosis of the femoral head. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to assess the strength of this association in the random-effects model or fixed-effects model.

Results

A significant association between PAI-1 4G/5G polymorphism and ONFH susceptibility was observed for 4G4G + 4G5G vs. 5G5G (OR = 1.766, 95% CI 1.279–2.437, P = 0.001), 4G/4G vs. 4G/5G + 5G/5G (OR = 2.050, 95% CI 1.581–2.657, P = 0.000), 4G/4G vs. 5G/5G (OR = 2.553, 95% CI 1.345–4.846, P = 0.004), and 4G vs. 5G (OR = 1.758, 95% CI 1.236–2.500, P = 0.002). No significant association between PAI-1 4G/5G polymorphism and ONFH susceptibility was observed for 4G/5G vs. 5G/5G (OR = 1.327, 95% CI 0.939–1.877, P = 0.109).

Conclusions

This meta-analysis suggested that 4G/5G polymorphism of the PAI-1 gene was a risk factor for ONFH. This study also suggests that the PAI-1 4G4G genotype may indicate a risk for ONFH.     

Volumetric differences in the pituitary between drug-naïve and medicated male patients with obsessive–compulsive disorder

Objective

Obsessive–compulsive symptoms are induced or aggravated by stress, and the pituitary is a key component of the hypothalamic-pituitary-adrenal axis. We examined pituitary volume in drug-naïve and medicated male patients with obsessive–compulsive disorder (OCD).

Methods

Volumetric magnetic resonance imaging studies were conducted on 62 male control subjects, medicated male patients (N = 50) and drug-naïve male patients (N = 12) with OCD.

Results

Pituitary volume was significantly smaller in drug-naïve patients with OCD (464.97 ± 55.82 mm³) compared to medicated patients (577.84 ± 129.11 mm³, P = 0.004) and control subjects (543.04 ±113.70 mm³, P = 0.027), and no difference between control subjects and medicated patients (P = 0.174).

Conclusion

The results indicate that drug-naïve male patients with OCD exhibit decreased pituitary volume. This finding suggests that dysregulation of the HPA axis in OCD may influence pituitary volume. In addition, the increased pituitary volume in medicated patients may reflect the effect of drugs on the pituitary.     

Subjective well-being,but not subjective mental functioning shows positive associations with neuropsychological performance in schizophrenia-spectrum disorders

Objective

To assess the association of subjective quality of life as measured by the Subjective Well-being under Neuroleptic Treatment questionnaire (SWN-K) with neuropsychological functioning; to address interactions with the SWN-K domain mental functioning as a measure of subjective cognitive dysfunction; and to examine the interaction of subjective well-being and psychopathology ratings.

Methods

Forty-five patients diagnosed with schizophrenia spectrum disorder (SSD) were assessed regarding subjective well-being (SWN-K), neuropsychological impairment, and psychopathology (Brief Psychiatric Rating Scale; BPRS).

Results

After controlling for multiple comparisons, SWN-K total score showed significant positive correlations with concentration/attention (r = .498), working memory (r = .537), verbal memory (r = .522), and global cognition (r = .459). No correlations of SWN mental functioning and neuropsychological impairment remained significant after Bonferroni correction. Correlations between SWN-K subscales and neuropsychological functioning were generally positive, indicating higher subjective well-being in patients with better neurocognition. In multivariate analyses, global cognition was a significant predictor (p = .011), accounting for 19.7% of SWN total score variance. Adding BPRS total score as predictor (p = .054) explained an additional 6.9% of SWN-K variance. Linear regression analyses with SWN-K mental functioning as dependent variable did not yield statistically significant models.

Conclusion

Subjective well-being and objective neuropsychological functioning show only moderate associations and can be seen as largely independent parameters. In particular, subjective mental functioning cannot serve as a proxy for objective neuropsychological testing.     

Serum brain-derived neurotrophic factor predicts responses to escitalopram in chronic posttraumatic stress disorder

Introduction

Some studies have found that antidepressants increase serum brain-derived neurotrophic factor (BDNF) levels in patients with major depression and the expression of BDNF mRNA in limbic structures of rats.

Objectives

This study addressed whether the SSRI escitalopram increases serum BDNF levels in subjects with PTSD and whether BDNF levels are associated with treatment response.

Methods

Medically healthy male subjects (N = 16) with chronic PTSD completed a 12 week open-label trial of flexible dose (5–20 mg/day) escitalopram monotherapy. BDNF levels were obtained at baseline, and at weeks 4, 8 and 12.

Results

PTSD symptoms significantly declined over the course of the 12 week escitalopram treatment. Despite a substantial improvement in PTSD symptoms, there was virtually no change in BDNF levels over time. Nevertheless, mean BDNF levels across the trial were strongly correlated with the slope of PTSD symptoms over the 12 weeks (r = 0.58, p = 0.018). Lower mean BDNF was associated with a greater decrease in PTSD symptoms over the course of the trial.

Conclusions

PTSD subjects with low BDNF levels demonstrated the largest treatment response from an agent with putative neurotrophic effects.