Interaction of serotonin-related genes affects short-term antidepressant response in major depressive disorder

Background

Four serotonin-related genes including guanine nucleotide binding protein beta polypeptide 3 (GNB3), 5-hydroxytryptamine receptor 1A (HTR1A; serotonin receptor 1A), 5-hydroxytryptamine receptor 2A (HTR2A; serotonin receptor 2A), and solute carrier family 6 member 4 (SLC6A4; serotonin neurotransmitter transporter) have been suggested to be candidate genes for influencing antidepressant treatment outcome. The aim of this study was to explore whether interaction among these genes could contribute to the pharmacogenomics of short-term antidepressant response in a Taiwanese population with major depressive disorder (MDD).

Methods

Included in this study were 101 MDD patients who were treated with antidepressants, 35 of whom were rapid responders and 66 non-responders after 2 weeks of treatment. We genotyped four single nucleotide polymorphisms (SNPs), including GNB3 rs5443 (C825T), HTR1A rs6295 (C-1019G), HTR2A rs6311 (T102C), and SLC6A4 rs25533, and employed the generalized multifactor dimensionality reduction (GMDR) method to investigate gene–gene interactions.

Results

Single-locus analyses showed the GNB3 rs5443 polymorphism to be associated with short-term antidepressant treatment outcome (P-value = 0.029). We did not correct for multiple testing in these multiple exploratory analyses. Finally, the GMDR approach identified a significant gene–gene interaction (P-value = 0.025) involving GNB3 and HTR2A, as well as a significant 3-locus model (P-value = 0.015) among GNB3, HTR2A, and SLC6A4.

Conclusions

These results support the hypothesis that GNB3, HTR2A, and SLC6A4 may play a role in the outcome of short-term antidepressant treatment for MDD in an interactive manner. Future research with independent replication using large sample sizes is needed to confirm the functions of the candidate genes identified in this study as being involved in short-term antidepressant treatment response.     

Association of HLA-DR/DQ polymorphism with myasthenia gravis in Tunisian patients

Background and objective

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction. MG has been shown to be associated with many human leukocyte antigens (HLA) in different populations. The aim of this study was to investigate the probable association between HLA-DR/DQ alleles and MG in Tunisian patients.

Patients and methods

HLA DR/DQ genotyping was performed using polymerase chain reaction sequence-specific primers (PCR-SSP) with 48 MG patients and 100 healthy individuals serving as the control group.

Results

Myasthenia gravis in Tunisian patients was found to be associated with the following alleles (p_c denotes Bonferroni corrected probability values): HLA-DRB1*03 (p_c < 10⁻³), DRB1*04 (p_c = 0.005), DQB1*02 (p_c = 0.002) and, DQB1*03 (p_c = 0.007).

Conclusion

Our data demonstrated a new HLA-MG predisposition with DRB1*04. The DRB1*03, DRB1*04, DQB1*02, and DQB1*03 alleles also could be predisposing genetic factors for MG in the Tunisian population.     

Exercise training improves depressive symptoms in people with multiple sclerosis: Results of a meta-analysis

Objective

There is a high prevalence, yet under-treatment of depressive disorder and symptoms by conventional therapy in people with multiple sclerosis (MS). We conducted a meta-analysis examining the overall effect of exercise training on depressive symptoms in MS.

Methods

We searched PubMed for randomized controlled trials (RCT) of exercise training and depression as an outcome in samples with MS. There were 13 RCTs that met inclusion criteria and yielded data for effect size (ES) generation (Cohen's d). An overall ES was calculated using a random effects model and expressed as Hedge's g.

Results

The weighted mean ES was small, but statistically significant (Hedge's g = 0.36, SE = 0.09, 95% CI = 0.18–0.54, z = 3.92, p < .001) indicating the exercise training resulted in an improvement in depressive symptoms compared to control. The overall effect was not heterogeneous (Q = 16.46, df = 12, p = 0.17, I² = 27.08); and post-hoc, exploratory analyses only identified depression symptom scale as a potential moderator variable (p = 0.04).

Conclusion

The cumulative evidence indicates that exercise training can yield a small, yet statistically significant and reliable reduction in depressive symptoms for people with MS.     

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.     

Lack of association between cerebral microbleeds and low serum cholesterol in patients with acute intracerebral hemorrhage

Background

The association of cerebral microbleeds (CMBs) with intracerebral hemorrhage (ICH) is well known and its relationship with low serum cholesterol in ICH patients might be of interest.

Methods

A total of 105 patients with ICH were evaluated. In all subjects cholesterol levels were measured after 12 h of fasting and gradient-echo magnetic resonance imaging (GE-MRI) was performed for detecting CMBs.

Results

CMBs were more common among patients with hypertension and leukoaraiosis (p = 0.008 and p = 0.001). Patients with and without CMBs did not differ according to total cholesterol, LDL cholesterol, triglycerides and HDL cholesterol levels.

Conclusion

In this study, 61% of Turkish ICH patients had CMBs, which was not associated with lipid profiles. Leukoaraiosis was independently associated with CMBs.     

Higher heart rate increments on head-up tilt in control subjects are not associated with autonomic dysfunction

Objective

To determine whether there is altered autonomic function associated with elevated heart rate increments on head-up tilt (HUT) in younger individuals.

Methods

A total of 149 subjects were enrolled in this study. Subjects underwent the autonomic reflex screen including HUT and completed the Autonomic Symptom Profile.

Results

Heart rate increment on HUT did not show a correlation with Composite Autonomic Severity Score (CASS) and the individual CASS scores were low (score 0/10, n = 103; score 1/10, n = 27; score 2/10, n = 1; score 3/10, n = 2). There was no correlation with multiple autonomic domains assessed by the Autonomic Symptom Profile. However, there were significant inverse correlations between heart rate increment and total COMPASS score including male sexual dysfunction (r = −0.318; p = 0.011; n = 64), bladder (r = −0.209; p = 0.014; n = 138), pupillomotor (r = −0.235; p = 0.006; n = 138) and male sexual dysfunction (r = −0.554; p < 0.0001; n = 64). These domains showed a positive correlation with age and a significant effect of age but not heart rate increment with regression analysis (except pupillomotor domain).

Conclusions

These results argue against a reduction in autonomic function underlying the higher heart rate increments seen on HUT in younger individuals.

Significance

These findings argue that the development of Postural Tachycardia Syndrome involves mechanisms that potentially occur independently of heart rate increment.     

Influence of sports climbing and yoga on spasticity,cognitive function,mood and fatigue in patients with multiple sclerosis

Objectives

Spasticity, cognitive impairment, depression and fatigue significantly reduce the quality of life in multiple sclerosis (MS) patients. To find out whether nonpharmalogical treatment approaches can reduce these symptoms we investigated effects of sports climbing (SC) and yoga on spasticity, cognitive impairment, mood change and fatigue in MS patients. Sports climbing (SC) and yoga are aerobic physical activities comprised a series of stretching techniques, implementation of which demands body control and planning of complex movements.

Materials and methods

20 subjects with relapsing–remitting or progressive MS, 26–50 years of age, with EDSS ≤ 6 and EDSS pyramidal functions score (EDSSpyr) > 2 were enrolled in a randomized prospective study. The participants were randomly divided into SC and yoga group. We evaluated spasticity, cognitive function, mood and fatigue before and after both programs, that lasted 10 weeks, with standardized assessment methods.

Results

There were no significant improvements in spasticity after SC and yoga. In the SC group we found a 25% reduction (p = 0.046) in EDSSpyr. There were no differences in executive function after the completion of both programs. There was a 17% increase in selective attention performance after yoga (p = 0.005). SC reduced fatigue for 32.5% (p = 0.015), while yoga had no effect. We found no significant impact of SC and yoga on mood.

Conclusions

Yoga and SC might improve some of the MS symptoms and should be considered in the future as possible complementary treatments.     

Epilepsy in children with periventricular leukomalacia

Objective

We aimed to analyze the development of epilepsy in a patient group with periventricular leukomalacia followed at a tertiary pediatric neurology center.

Patients and methods

The study included 108 children aged between 2 and 8 years with radiologically proven periventricular leukomalacia who had been regularly observed at the Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Pediatric Neurology outpatient clinic between January 2006 and December 2011.

Results

Neonatal seizures were reported in 22 patients (20.3%), 14 of whom developed epilepsy. A significant correlation was found between neonatal seizures and prematurity and newborn asphyxia (p = 0.013 and p = 0.010, respectively). Epilepsy developed in 35 patients (32.4%), history of neonatal seizures and more severe loss of white matter, periventricular hyperintensity and corpus callosum involvement were found to be correlated with epilepsy (p = 0.001, p = 0.004, p = 0.016, and p = 0.004, respectively). The most common seizure pattern observed was generalized tonic clonic seizures (n = 13) and complex partial seizures (n = 11). Those with focal EEG findings had a significantly better neurodevelopmental and cognitive level than those with multifocal/generalized EEG findings (p = 0.024). Seizures continued with varying frequency in 14 epileptic patients (40%) despite antiepileptic treatment.

Conclusion

Almost a third of patients with periventricular leukomalacia develop epilepsy that can be intractable in substantial part. Neonatal seizures and severe MRI findings are important clues that can indicate the development of epilepsy in these patients.     

The relationship of chronic medical illnesses,poor health-related lifestyle choices,and health care utilization to recovery status in borderline patients over a decade of prospective follow-up

Background

The interaction of borderline personality disorder (BPD) with physical health has not been well characterized. In this longitudinal study, we investigated the long-term relationship of chronic medical illnesses, health-related lifestyle choices, and health services utilization to recovery status in borderline patients over a decade of prospective follow-up.

Method

264 borderline patients were interviewed concerning their physical health at 6-year follow-up in a longitudinal study of the course of BPD. This sample was then reinterviewed five times at two-year intervals over the next ten years. We defined recovery from BPD based on a Global Assessment of Functioning score of 61 or higher, which required BPD remission, one close relationship, and full-time competent and consistent work or school attendance. We controlled for potentially confounding effects of time-varying major depressive disorder.

Results

Never-recovered borderline patients were significantly more likely than ever-recovered borderline patients to have a medical syndrome, obesity, osteoarthritis, diabetes, urinary incontinence, or multiple medical conditions (p < 0.0063). They were also significantly more likely to report pack-per-day smoking, weekly alcohol use, no regular exercise, daily sleep medication use, or pain medication overuse (p < 0.0083). In addition, never-recovered borderline patients were significantly more likely than ever-recovered borderline patients to undergo a medical emergency room visit, medical hospitalization, X-ray, CT scan, or MRI scan (p < 0.0063).

Conclusions

Over a decade of prospective follow-up, failure to recover from BPD seems to be associated with a heightened risk of chronic medical illnesses, poor health-related lifestyle choices, and costly health services utilization.     

Mindfulness-based cognitive therapy for people with diabetes and emotional problems: Long-term follow-up findings from the DiaMind randomized controlled trial

Objective

The DiaMind trial showed beneficial immediate effects of mindfulness-based cognitive therapy (MBCT) on emotional distress, but not on diabetes distress and HbA_1c. The aim of the present report was to examine if the effects would be sustained after six month follow-up.

Methods

In the DiaMind trial, 139 outpatients with diabetes (type-I or type-II) and a lowered level of emotional well-being were randomized into MBCT (n = 70) or a waiting list with treatment as usual (TAU: n = 69). Primary outcomes were perceived stress, anxiety and depressive symptoms, and diabetes distress. Secondary outcomes were, among others, health status, and glycemic control (HbA_1c).

Results

Compared to TAU, MBCT showed sustained reductions at follow-up in perceived stress (p < .001, d = .76), anxiety (p < .001, assessed by HADS d = .83; assessed by POMS d = .92), and HADS depressive symptoms (p = .004, d = .51), but not POMS depressive symptoms when using Bonferroni correction for multiple testing (p = .016, d = .48). No significant between-group effect was found on diabetes distress and HbA_1c.

Conclusion

This study showed sustained benefits of MBCT six months after the intervention on emotional distress in people with diabetes and a lowered level of emotional well-being.

Trial registration

Dutch Trial Register NTR2145, http://www.trialregister.nl.     

Plasma nitrite levels,total antioxidant status,total oxidant status,and oxidative stress index in patients with tension-type headache and fibromyalgia

Objectives

Tension-type headache (TTH) and fibromyalgia syndrome (FM) are worldwide seen chronic pain syndromes of unknown etiology. Despite the growing body of data on pathophysiology and generation mechanisms of pain; our knowledge on pain mechanisms in both FM and TTH is yet to be limited.

Patients and methods

We investigated the plasma nitrite levels, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) in 35 TTH, 33 FM patients and 31 healthy controls.

Results

The mean plasma nitrite levels and TAS levels were significantly low and OSI was found to be significantly high in TTH and FM groups compared to the control group (p = 0.001, p = 0.001, p = 0.001 and p = 0.001, respectively). The mean serum TOS levels were also significantly higher in FM group according to the control group (p = 0.034), but there was not a significant difference between TTH and control groups (p = 0.066).

Conclusion

These results indicated that; FM and TTH patients revealed higher oxidative stress index and lower total nitrite levels than healthy controls. We conclude that oxidative stress may have a role in the pathophysiological mechanisms of TTH and FM, although, whether it is the cause or the consequence, is not clear.     

Efficacy of postoperative anticoagulation therapy with enoxaparin for portal vein thrombosis after hepatic resection in patients with liver cancer

Backgrounds

Enoxaparin, low-molecular-weight heparin, has become a routine thromboprophylaxis in general surgery.

Study design

A retrospective cohort study was performed in 281 patients who underwent hepatic resections for liver cancers from 2011 to 2013. These patients were divided into two groups; an enoxaparin (-) group (n = 228) and an enoxaparin (+) group (n = 53). Short-term surgical results including venous thromboembolism (VTE) and portal vein thrombosis (PVT) were compared.

Results

In the enoxaparin (+) group, the patients’ age (65 vs. 69 years; p = 0.01) and BMI (22.9 vs. 24.4; p < 0.01) were significantly higher. According to the symptomatic VTE, symptomatic pulmonary embolism occurred in one patient (0.4%) in the enoxaparin (-) group, but the complication rate was not significantly different (p = 0.63). The complication rate of PVT was significantly lower in the enoxaparin (+) group (10 vs. 2%; p = 0.04). The independent risk factors for PVT were an operation time ≥ 300 minutes (Odds ratio 6.66) and non-treatment with enoxaparin (Odds ratio 2.49).

Conclusions

Postoperative anticoagulant therapy with enoxaparin could prevent PVT in patients who underwent hepatic resection for liver cancers.     

Optimism measured pre-operatively is associated with reduced pain intensity and physical symptom reporting after coronary artery bypass graft surgery

Objective

Optimism is thought to be associated with long-term favourable outcomes for patients undergoing coronary artery bypass graft (CABG) surgery. Our objective was to examine the association between optimism and post-operative pain and physical symptoms in CABG patients.

Methods

We assessed optimism pre-operatively in 197 adults undergoing CABG surgery, and then followed them up 6–8 weeks after the procedure to measure affective pain, pain intensity, and physical symptom reporting directly pertaining to CABG surgery.

Results

Greater optimism measured pre-operatively was significantly associated with lower pain intensity (β = − 0.150, CI = − 0.196 to − 0.004, p = .042) and fewer physical symptoms following surgery (β = − 0.287, CI = − 0.537 to − 0.036, p = .025), but not with affective pain, after controlling for demographic, clinical and behavioural covariates, including negative affectivity.

Conclusions

Optimism is a modest, yet significant, predictor of pain intensity and physical symptom reporting after CABG surgery. Having positive expectations may promote better recovery.     

Homocysteine,vitamin B12 and folate levels in Iranian patients with Multiple Sclerosis: A case control study

Background

Recently, homocysteine (Hcy), folate, and vitamin B12 have been proposed to have several roles on MS pathogenesis.

Objective

We performed this study to determine the role of serum levels of Hcy, vitamin B12, and folate in patients with relapsing remitting MS (RRMS) and compared them with healthy controls.

Methods

We recruited 75 RRMS patients and 75 subjects as controls with the same age and sex. Homocysteine was measured using fluorimetric high-performance liquid chromatography. Plasma folate and vitamin B12 levels were measured through ion-capture method.

Results

Mean plasma levels of vitamin B12, folate, and Hcy in cases were 342.64 ± 210.66 pg/ml, 9.74 ± 4.77 ng/ml, and 22.73 ± 11.63 μM/L, respectively, which showed significant difference in comparison with the controls. In addition, there were significant correlations between mean serum Hcy levels and duration of disease (r = 0.2, p = 0.05) and treatment with interferon (r = 0.21, p = 0.01). In cases, Hcy level was higher among those on β interferon (24.56 ± 11.87 vs. 19.71 ± 10.75, p = 0.01).

Conclusions

We concluded that serum levels of vitamin B12 and folate decreased in RRMS patients, but Hcy levels increased significantly. It seems necessary to conduct prospective trials to determine whether the treatment with supplements and correct biomarker levels in the early stage of the disease can change the course of the disease. We recommend regular checking of the serum level of Hcy in patients who use disease-modifying drugs.     

The impact of mood episodes and duration of illness on cognition in bipolar disorder

Objective

A number of studies showed cognitive impairment in bipolar patients but few researches have studied the impact of mood episodes or duration of illness on neuropsychological functioning.

Methods

Cognitive functioning was examined in 110 bipolar 1 outpatients with different mood state (mania, major depression, mixed episode and euthymia). The neuropsychological battery included The Visual Search Test, Trail Making Test, Corsi Test, Frontal Assessment Battery (FAB), Cognitive Estimation Task (CET) and Tower of London and it assessed attention, memory and executive/planning functions. Failures in the different cognitive tests were compared between groups using χ² tests with Bonferroni's corrections. Finally a binary logistic regression was performed in order to find an eventual association between age and duration of illness and CET bizarreness.

Results

All the symptomatic patients (manic, depressed, mixed) failed more frequently The Visual Search Test in comparison with euthymics (χ² = 9.882, df = 3, p = 0.017, phi = 0.30; rate of failures: manic patients 32.2%, depressed patients 30.6%, euthymics 0%, mixed patients 18.2%). CET was performed worse by manic and euthymic patients (χ² = 10.086, df = 3, p = 0.015, phi = 0.31; rate of failures: manic patients 46.4%, depressed patients 22.9%, euthymics 52.1%, mixed patients 18.2%). Finally, a longer duration of illness was found to be predictive of more bizarreness at CET (OR = 1.06, p = 0.01).

Conclusions

Bipolar patients present impairment in different cognitive domains even in euthymic phases. Frontal dysfunction might be associated with a long duration of illness as shown by number of bizarreness at CET in chronic bipolar patients.     

Distinctive correlations of sociotropy and autonomy with working models of the self and other

Background

Beck's cognitive theory of depression postulates personality vulnerability factors termed sociotropy and autonomy, which are accompanied by characteristic interpersonal styles. Meanwhile, Bartholomew contends that negative working models of the self and other built through insecure attachment relationships are externalized as distinctive interpersonal styles. The present study examined the relationships of sociotropy and autonomy with the self- and other-models, and attempted to promote understanding of the two personality traits from an attachment perspective.

Methods

The subjects were 510 healthy Japanese medical students or hospital staffs. Sociotropy and autonomy were assessed by the Sociotropy–Autonomy Scale, and working models of the self and other were evaluated by the Relationship Scales Questionnaire.

Results

The sociotropy score was correlated negatively with the self-model score (β = −0.52, p < 0.001) and positively with the other-model score (β = 0.11, p < 0.01). The autonomy score was correlated positively with the self-model score (β = 0.10, p < 0.05) and negatively with the other-model score (β = −0.33, p < 0.001).

Limitations

It may be risky to generalize the present results to general populations or other ethnic groups.

Conclusions

The present study suggests that both sociotropy and autonomy are associated with attachment insecurity, but the marked difference in their correlation patterns with the self- and other-models leads to the distinctive interpersonal styles of the two personality orientations.     

Cognitive impairment and optic nerve axonal loss in patients with clinically isolated syndrome

Objective

To investigate cognitive impairment, to assess optical nerve axonal loss, and to determinate whether there is correlation between optical nerve axonal loss and cognition impairment in Clinically Isolated Syndrome (CIS).

Methods

Fifteen CIS patients and 15 controls were submitted to Wechsler memory scale, Rey Auditory Verbal Learning, Rey Complex Figure, Paced Auditory Serial Addition, Digit Span, verbal fluency, stroop color, D2, and Digit Symbol tests. CIS patients were evaluated by optical coherence tomography (OCT) (23 eyes).

Results

CIS patients had worse performance in Paced Auditory Serial Addition Test (PASAT) 2 seconds (P = 0.009) and fluency tests (P = 0.0038). Optical nerve axonal loss was found more frequently in eyes with previous optic neuritis (ON) (85.7%) than in those without previous ON (21.7%) (P = 0.0146). There were no significant correlations between optical nerve axonal loss and cognitive findings.

Conclusions

CIS patients had worse cognitive performance than controls. OCT can detect axonal loss resulting from optical neuritis and subclinical axonal loss in eyes without previous optical neuritis. Optical nerve axonal loss was not correlated with cognition.     

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.     

Less favorable neurological recovery after acute stroke in patients with hypercholesterolemia

Objectives

We aimed to investigate the effect of hypercholesterolemia on recovery after acute ischemic stroke.

Methods

Data of 3048 patients admitted for acute ischemic stroke from January to December 2009 were collected from the Stroke Registry in the Chang Gung Healthcare System. Baseline characteristics of patients with and without hypercholesterolemia were compared. The association of hypercholesterolemia with neurological severity and recovery was analyzed using multivariate logistic regression. The patients were then divided on the basis of age for subgroup analysis.

Results

The number of patients with and without a history of hypercholesterolemia was 474 (15.6%) and 2574 (84.4%), respectively. Univariate analysis showed that patients with hypercholesterolemia had a lower National Institutes of Health Stroke Scale (NIHSS) score on admission (p = 0.004). However, during hospitalization, these patients displayed less improvement in their NIHSS score (p = 0.002). These results remained significant in multivariate logistic regression analysis (p < 0.001 and p = 0.002, respectively). Subgroup analysis showed a similar association for hypercholesterolemia in both younger (age < 70) and older (age ≥ 70) age groups.

Conclusions

Acute ischemic stroke in patients with hypercholesterolemia was correlated with reduced severity on admission and less favorable recovery during hospitalization, regardless of age.     

Association analysis of GRM2 and HTR2A with methamphetamine-induced psychosis and schizophrenia in the Japanese population

Background

Abnormalities in glutaminergic neural transmission have been suggested to be involved in the pathogenesis of schizophrenia. A recent study reported that alterations in the 5-HT2A–mGluR2 complex may be involved in neural transmission in the schizophrenic cortex. In addition, methamphetamine-induced psychosis is thought to be similar to schizophrenia. Therefore, we conducted a case-control study with Japanese samples (738 schizophrenia patients, 196 methamphetamine-induced psychosis patients, and 802 controls) to evaluate the association and interaction between GRM2, HTR2A and schizophrenia.

Methods

We selected three ‘tagging SNPs’ in GRM2, and two biologically functional SNPs in HTR2A (T102C and A1438G), for the association analysis.

Results

We detected a significant association between methamphetamine-induced psychosis and GRM2 in a haplotype-wise analysis, but not HTR2A. We did not detect an association between GRM2 or HTR2A and schizophrenia. In addition, no interactions of GRM2 and HTR2A were found in methamphetamine-induced psychosis or schizophrenia. We did not detect any novel polymorphisms in GRM2 when we performed a mutation search using methamphetamine-induced psychosis samples.

Conclusion

Our results suggested that GRM2 may play a role in the pathophysiology of methamphetamine-induced psychosis but not schizophrenia in the Japanese population. A replication study using larger samples or samples of other populations will be required for conclusive results.