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.     

Relationships between IGF-1, schizophrenia,and treatment of metabolic syndrome

Objectives

The use of atypical antipsychotic drugs in patients with psychiatric illness may result in dyslipidemia, hypertension, glucose intolerance, and abdominal obesity, which are together referred to as metabolic syndrome (MS). To investigate any correlations among insulin-like growth factor-1 (IGF-1), schizophrenia, and MS, we examined the metabolic profiles of patients with schizophrenia taking atypical antipsychotics.

Design

Patients with schizophrenia, their siblings, and controls participated in this study (N = 50 in each group). The Structured Clinical Interview for DSM-IV Axis 1 Disorders (SCID I) and the Brief Psychiatric Rating Scale (BPRS) were administered to patients, and SCID I was administered to patients' siblings. We drew blood to measure IGF-1 levels and to determine the metabolic profiles of all participants; we also conducted anthropometric measurements.

Results

There were no significant differences in IGF-1 levels between groups. By comparing IGF-1 levels with MS-related parameters, we found that IGF-1 levels were negatively correlated with triglyceride levels in the control group, and positively correlated with HDL levels in the patient group (Pearson's correlation: r = −0.291, P = 0.04, and r = 0.328, P = 0.02, respectively). Compared to their siblings, patients with schizophrenia had a significantly different body mass index, waist circumference, and insulin resistance, and showed a trend toward a difference in glucose levels (ANOVA: P = 0.004, P < 0.0001, P = 0.004, P = 0.072, respectively).

Conclusion

A correlation between IGF-1 and MS may significantly influence future therapeutic strategies for MS. In order to determine the role of IGF-1 in schizophrenia, comprehensive longitudinal studies with first-episode drug-naive patients are needed.     

Cutaneous perception thresholds of electrical stimulation methods: Comparison of tDCS and tRNS

Objective

Controlled blinded studies using transcranial electrical stimulation (tES) paradigms need a validated sham stimulation paradigm since an itching or tingling sensation on the skin surface under the electrode can be associated with current flow.

Methods

Here we investigated the skin perception thresholds of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) for current intensities ranging from 200 to 2000 μA and additional non-stimulation trials using a motor cortex–contralateral orbit montage in three different healthy subject groups: subjects naïve to tES methods, subjects with previous experience with these techniques and investigators, who use these methods in their research.

Results

Taking the whole sample into consideration the 50% perception threshold for both tDCS conditions was at 400 μA while this threshold was at 1200 μA in the case of tRNS. Anodal and cathodal tDCS are indistinguishable regarding sites of perception. Experienced investigators show a significantly higher anodal stimulation detection rate when compared to the naïve group, furthermore investigators performed significantly better than naïve subjects in non-stimulation discrimination.

Conclusions

tRNS has the advantage of higher cutaneous perception thresholds and lower response rates in when compared with tDCS. Further investigation in blinding methods (such as placebo itching) is warranted in order to improve sham control.

Significance

As tRNS has been shown to have similar aftereffects as anodal tDCS, this finding points to the application of tRNS as a possible alternative with a better blinding control.     

An exploratory model for G × E interaction on hippocampal volume in schizophrenia; obstetric complications and hypoxia-related genes

Background

Smaller hippocampal volume has repeatedly been reported in schizophrenia patients. Obstetric complications (OCs) and single nucleotide polymorphism (SNP) variation in schizophrenia susceptibility genes have independently been related to hippocampal volume. We investigated putative independent and interaction effects of severe hypoxia-related OCs and variation in four hypoxia-regulated schizophrenia susceptibility genes (BDNF, DTNBP1, GRM3 and NRG1) on hippocampal volume in schizophrenia patients and healthy controls.

Methods

Clinical assessment, structural MRI scans, and blood samples for genotyping of 32 SNPs were obtained from 54 schizophrenia patients and 53 control subjects. Information on obstetric complications was collected from original birth records.

Results

Severe OCs were related to hippocampal volume in both patients with schizophrenia and healthy control subjects. Of the 32 SNPs studied, effects of severe OCs on hippocampal volume were associated with allele variation in GRM3 rs13242038, but the interaction effect was not specific for schizophrenia. SNP variation in any of the four investigated genes alone did not significantly affect hippocampal volume.

Conclusions

The findings suggest a gene–environment (G × E) interaction between GRM3 gene variants and severe obstetric complications on hippocampus volume, independent of a diagnosis of schizophrenia. Due to the modest sample size, the results must be considered preliminary and require replication in independent samples.     

Resting brain perfusion in alcohol-induced psychotic disorder: A comparison in patients with alcohol dependence,schizophrenia and healthy controls

Introduction

Alcohol-induced psychotic disorder (AIPD), also known as alcohol hallucinosis, is a rare complication of alcohol abuse. The underlying pathophysiology is poorly understood, and the disorder needs to be differentiated from alcohol withdrawal delirium and schizophrenia. No brain-imaging studies in AIPD have been reported to date. Case reports of brain imaging in AIPD suggest possible dysfunction in the thalamus, basal ganglia, frontal lobes and cerebellum. Our aim was to prospectively compare resting brain perfusion (rCBF) in patients with AIPD, uncomplicated alcohol dependence, schizophrenia and healthy volunteers.

Methods

Single photon emission computed tomography (SPECT) was utilized to compare rCBF in patients with AIPD (n = 19), schizophrenia (n = 16), uncomplicated alcohol dependence (n = 20) and healthy volunteers (n = 19).

Results

Increased rCBF was demonstrated in the right calcarine area in patients with AIPD compared to healthy volunteers, with a trend towards increased rCBF to the frontal and temporal lobes and the right pallidum. Decreased left sided rCBF to the putamen, parietal, mid-frontal and mid-temporal lobes and heterogenous flow to the cerebellum were demonstrated in patients with AIPD when compared to patients with uncomplicated alcohol dependence. The left posterior cingulate and right cerebellum showed higher and lower rCBF respectively in patients with AIPD compared to patients with schizophrenia.

Conclusion

Our findings implicate the right occipital lobe and possibly the cerebellum in the pathogenesis of AIPD and have similarities with those previously reported in alcohol withdrawal. Reduced rCBF to the frontal lobes, thalamus and basal ganglia in AIPD as suggested in previous case reports could not be confirmed.     

Cortical sources of resting-state EEG rhythms are abnormal in naïve HIV subjects

Objective

The aim of the study was to test the hypothesis that cortical sources of resting-state electroencephalographic (EEG) rhythms show peculiar frequency/spatial features in naïve human subjects with human immunodeficiency virus (HIV) compared to healthy control subjects.

Methods

Resting-state eyes-closed EEG data were recorded in 18 naïve HIV subjects (15 males; mean age 39 years ± 2.0 standard error of mean, SEM) and in 18 age-matched cognitively normal subjects (15 males; 38.7 years ± 2.2 SEM). EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha1 (8–10 Hz), alpha2 (10–12 Hz), beta1 (13–20 Hz) and beta2 (20–30 Hz). Cortical EEG sources were estimated by normalised, low-resolution electromagnetic tomography (LORETA).

Results

Mini Mental State Evaluation (MMSE) score was lower in HIV (26.5 ± 0.7 SEM) than in healthy (29.2 ± 0.5 SEM) subjects (p < 0.05). Central and parietal delta sources showed higher amplitude in the HIV than in control subjects. Furthermore, topographically widespread, cortical sources of resting-state alpha rhythms were lower in amplitude in HIV subjects than in control subjects.

Conclusions

The present results suggest that topography and frequency of the cortical sources of resting-state EEG rhythms can distinguish groups of HIV and control subjects.

Significance

These results encourage future studies in an enlarged cohort of HIV subjects to test the hypothesis that the present methodological approach provides clinically useful information for an early detection of the effect of HIV infection on brain and cognitive functions.     

Relationship between inflammation and metabolic syndrome following treatment with paliperidone for schizophrenia

Objective

Metabolic syndrome and antipsychotic medications are associated with inflammation. This study investigated the relationship between inflammation and metabolic syndrome in patients with schizophrenia. It also examined the effects of paliperidone extended release (ER) treatment on metabolic parameters.

Methods

Data were analyzed from schizophrenic patients who participated in a multi-center, open-label, non-comparative clinical trial. Anthropomorphic measurements (i.e., weight, waist circumference, and blood pressure) were assessed along with fasting laboratory values, including white blood cell (WBC) count, glucose, high-density lipoprotein, and triglycerides.

Results

Among the 225 patients at baseline, the group with the highest WBC count displayed a 5.9-fold risk for metabolic syndrome compared with that of the lowest group. An increase of 10³ WBCs/μL was associated with a 1.4-fold increased risk for metabolic syndrome. After 24 weeks of treatment with paliperidone ER, significant increases were observed in waist circumference and body weight. Changes in WBC count were positively correlated with changes in waist circumference.

Conclusions

Schizophrenic patients with high levels of inflammation should be carefully monitored for metabolic syndrome. Moreover, strategies to reduce inflammation and obesity may prevent metabolic syndrome in patients with schizophrenia who take atypical antipsychotic medication.     

Substance use disorders among treatment naïve first-episode psychosis patients

Objectives

To examine the prevalence of substance use among treatment naïve patients with first episode psychosis presenting to a psychiatry outpatient clinic in India.

Methods

The study sample consisted of 139 first episode treatment naïve patients with psychosis from in and around Bangalore, a city in South India. Self as well as informant-reported data on type, use and duration of substance use as well as the severity of psychotic symptoms were collected using structured instruments. Urine toxicology screen was also conducted for six common drugs of abuse. Breath alcohol analysis was performed in all patients.

Results

Acute and transient psychosis was the most common diagnosis (42.4%). Overall, 20% of the population reported current substance use disorder (excluding nicotine). Current alcohol dependence was diagnosed among 17.3%, whereas cannabis dependence in 3.6%. Life time as well as current use of cannabis was less than 6%. While one patient reported inhalant abuse none reported use of amphetamine or opioids. There was very high concordance between reported drug use and urine toxicology screen.

Conclusion

The use of illicit drugs is substantially less among first episode drug naïve patients with psychosis in an Indian urban clinical setting compared to rates reported from developed countries like North America, Canada and UK.     

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.     

The loudness dependence of the auditory evoked potential (LDAEP) in schizophrenia,bipolar disorder,major depressive disorder,anxiety disorder,and healthy controls

Background

Serotonergic dysfunction in schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, and healthy controls was evaluated by measuring the activity of the loudness dependence of the auditory evoked potential (LDAEP).

Methods

The 357 subjects who were evaluated comprised 55 normal controls, 123 patients with major depressive disorder, 37 with bipolar disorder, 46 with schizophrenia, 37 with panic disorder (PD), 31 with generalized anxiety disorder (GAD), and 28 with post-traumatic stress disorder (PTSD).

Results

LDAEP was significantly stronger in healthy controls than in patients with either bipolar disorder (p = 0.025) or schizophrenia (p = 0.008), and significantly stronger in patients with major depressive disorder than in those with bipolar disorder (p = 0.01) or schizophrenia (p = 0.03). LDAEP did not differ significantly between patients with major depressive disorder and healthy control subjects (p = 0.667), or between healthy control subjects and patients with anxiety disorder, including PD (p = 0.469), GAD (p = 0.664), and PTSD (p = 0.167).

Conclusion

The findings of the present study reveal that patients with major psychiatric disorders exhibit different strengths of LDAEP according to their serotonin-related pathology. Studies controlled for psychotropic medication, menstruation cycle, and smoking are needed.     

Deficient inhibition of return in chronic but not first-episode patients with schizophrenia

Background

Inhibition of return (IOR) has been tested in patients with schizophrenia with contradictory results. Some studies indicated that patients with schizophrenia have normal levels of IOR; however, other studies reported delayed or blunted IOR. Inconsistency in findings might be due to differences across studies in relevant aspects associated with disease, such as heterogeneity of the disorder, different medications, onset and severity of the illness. The present study was to explore different patterns of IOR in antipsychotic medication free first-episode schizophrenia and chronic schizophrenia.

Methods

Forty two patients with first-episode schizophrenia, 44 patients with chronic schizophrenia, and 38 healthy controls were included in the study. All subjects went through a covert orienting of attention task with seven stimulus onset asynchrony (SOA) intervals (400 ms, 500 ms, 600 ms, 700 ms, 800 ms, 1200 ms and 1500 ms).

Results

Compared with healthy controls, the magnitude and onset of IOR in first-episode patients with schizophrenia were intact. However, in patients with chronic schizophrenia, there was an attenuated cuing effect especially at SOA 700 ms; in addition, there was a robust IOR until at SOAs 800 ms or above. Moreover, the illness duration and the number of psychotic episodes were significantly correlated with the validity effect at SOAs 400 ms and 600 ms.

Conclusion

Our study suggests that deficient IOR presents in chronic but not in first-episode patients with schizophrenia. IOR deficit in schizophrenia may begin during the course of illness and deteriorate over the course of illness. Our findings are consistent with the neurodegenerative model of schizophrenia.     

Oxidative stress in tardive dyskinesia: Genetic association study and meta-analysis of NADPH quinine oxidoreductase 1 (NQO1) and Superoxide dismutase 2 (SOD2, MnSOD) genes

Introduction

Tardive dyskinesia (TD) is a potentially irreversible side effect of antipsychotic medication treatment that occurs in approximately 25% of chronically treated schizophrenia patients. Oxidative stress has been one of the proposed mechanisms influencing TD risk. Pae et al. (2004) originally reported a significant association between TD and the NADPH quinine oxidoreductase 1 (NQO1) gene Pro187Ser (C609T, rs1800566) polymorphism in Korean schizophrenia patients; however, subsequent studies have not consistently replicated these findings. Similarly, Hori et al. (2000) reported an association between TD and the Manganese superoxide dismutase SOD2 (MnSOD) gene Ala9Val (rs4880) polymorphism in a Japanese sample, but most research groups failed to replicate their positive findings.

Aims

We investigated the role of the NQO1 polymorphism Pro187Ser and SOD2 (Ala9Val) in a group of well-characterized schizophrenia patients (N = 223) assessed for TD. We also performed a meta-analysis of all the previously published TD studies, including data from our sample, on these polymorphisms, Pro187Ser (N = 5 studies) and Ala9Val (N = 9 studies).

Results

We did not observe a significant association of the Pro187Ser or Ala9Val polymorphism with TD occurrence or AIMS scores in our Caucasian and African American samples when analyzed independently. Meta-analysis did not reveal a significant association of the Pro187Ser/Ala9Val alleles or genotypes with TD occurrence.

Conclusions

Neither the NQO1 Pro187Ser nor the SOD2 Ala9Val appear to play a major role in TD risk, although additional polymorphisms should be tested before the role of NQO1 and SOD2 in TD can be completely excluded.     

Effects of risperidone on glucose metabolism in Chinese patients with schizophrenia: a prospective study

Background

While most of the second generation antipsychotic agents are associated with abnormal glucose metabolism, previous studies have shown that risperidone has relatively little effect upon blood glucose levels. This study aimed to explore the effect of risperidone on the glucose-regulating mechanism of patients with schizophrenia by using the oral glucose tolerance test (OGTT), measuring insulin and C-peptide levels.

Methods

Thirty inpatients with schizophrenia taking risperidone were studied. All the patients were given a simplified OGTT at baseline and six weeks after treatment. Plasma glucose, insulin, and C-peptide concentrations were measured at fasting, then 1 and 2 h after OGTT respectively. Other data, including demographic characteristics and plasma drug concentrations, were also recorded.

Results

(1) There was no significant increase in the proportion of patients demonstrating abnormal plasma glucose levels compared with baseline (p = 1.000, McNemar test); (2) risperidone was associated with elevated insulin concentrations (p = 0.013), C-peptide levels (p = 0.020), insulin/glucose ratio (p = 0.020) and BMI (p < 0.01); (3) no sex differences in glucose-related measures were observed.

Conclusion

Risperidone treatment may be associated with alterations in glucose-regulating mechanisms in patients with schizophrenia.     

Tamoxifen induces resistance to activated protein C

Introduction

The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet.

Materials and Methods

Blood samples were collected prospectively from women with breast cancer before (n = 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally.

Results

APC sensitivity decreased by 41% (p = 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p = 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed.

Conclusions

This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors.     

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.     

Linguistic and psychometric validation of the Chinese version of the self-efficacy measures for sleep apnea questionnaire

Objectives

The self-efficacy measure for sleep apnea (SEMSA) questionnaire was shown to be an effective tool to assess adherence-related cognitions on continuous positive airway pressure (CPAP) therapy in obstructive sleep apnea (OSA) subjects. SEMSA helps to solicit fundamental information for formulating strategies to promote CPAP adherence for better treatment outcomes. The objective of our study was to perform a linguistic and psychometric evaluation of a Chinese version of the SEMSA (SEMSA-C).

Methods

Data were obtained from 100 subjects in a randomized controlled trial (RCT) on CPAP education. Subjects were newly diagnosed of OSA and naïve to CPAP therapy.

Results

A 26-item SEMSA-C was obtained by a rigorous linguistic validation process. Internal consistency was high with Cronbach α > 0.88. One-week test–retest intraclass correlation coefficient (ICC) ranged from 0.70 to 0.82. Principal component factor analysis identified three of the same hypothesized factors (perceived risks, outcome expectancies, and treatment self-efficacy) as in the original version. CPAP adherence was associated with outcome expectancies and treatment self-efficacy at 3-month assessment. Further, SEMSA-C demonstrated an improvement in self-efficacy after CPAP use.

Conclusions

SEMSA-C shows similar psychometric properties as the original English version. It is a reliable and responsive instrument to measure perceived risks, outcome expectancies, and treatment self-efficacy in Chinese subjects with OSA.     

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.     

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.     

Low molecular weight heparin-induced increase in chylomicron-remnants clearance,is associated with decreased plasma TNF-α level and increased hepatic lipase activity

Objective

The acute effect of heparin on lipoprotein clearance is well characterized. Yet, the effect of prolonged low-molecular-weight-heparin (LMWH) administration on post-prandial lipemia has remained so far unexplored. Recent reports suggest that LMWH could modify lipid and carbohydrate metabolism by diminishing TNFα-mediated inflammatory response. This, together with the known negative effect of TNF-α on insulin sensitivity, prompted us to hypothesize that LMWH would favorably affect post-prandial lipoprotein disposal.

Methods

Twenty four patients were given a vitamin A-fat loading meal at the end of 6-week enoxaparin treatment and after 3-month washout period. Post-prandial lipemia was assessed by measuring retinyl-palmitate (RP) during 8 hours following the meal. Insulin sensitivity index (ISI), plasma lipolytic activity and plasma TNF-α were measured.

Results

Enoxaparin did not impact fasting plasma lipids and lipoproteins levels. Enoxaparin increased RP clearance in the chylomicron remnant (CMR) fraction by 32% (P < 0.01). Additionally, enoxaparin decreased plasma TNF-α by 22% (P < 0.01), increased hepatic lipase (HL) activity by 81% (P < 0.01), along with a 2-fold increase in ISI (P < 0.01). The decrease in CMR correlated with the reduction in TNFα and the increase in ISI and HL activity (R = 0.48, -0.68, - 0.56, respectively, p < 0.05). Significant correlations were also found between the reduction in TNFα and both the increase in ISI and increase in HL activity (R = - 0.43, -0.54, respectively, P < 0.05).

Conclusions

The association of the effect on post-prandial metabolism, plasma TNFα level and HL activity during prolonged enoxaparin treatment may support the hypothesis that the beneficial outcome of enoxaparin may possibly be linked to anti-inflammatory and lipase-potentiating impact.