CACNA1C genotype explains interindividual differences in amygdala volume among patients with schizophrenia

Affective deficits are one common denominator of schizophrenia (SZ), bipolar disorder (BD) and obsessive compulsive disorder (OCD) with the amygdala indicated as one of the major structures involved in emotion regulation. Previous findings of differences in amygdala volume between healthy controls and patients with SZ, BD or OCD diverge with respect to the affected hemisphere, size and direction of the effect. Variability in the CACNA1C gene has been linked to BD, SZ as well as structural and functional variation in the amygdala in healthy people and patients with BD. We were interested to investigate whether amygdala volumes differ between hemispheres, diagnostic or genotype groups, and whether any interactive effects exist. We combined genotyping of SNP rs1006737 in CACNA1C with structural MRI measurements of relative gray matter (GM) amygdala volume in patients with SZ, BD or OCD as well as healthy controls (N _Total = 72). The CACNA1C genotype showed a significant effect on relative GM amygdala volume in patients with SZ. There was a significant left versus right relative GM amygdala volume decrease in patients with SZ or BD. The effects of hemisphere and diagnosis (controls vs. patients with SZ) on relative GM amygdala volume were genotype specific. Our data suggest that the CACNA1C genotype may account for some heterogeneity in the effects of hemisphere and diagnosis on amygdala volume when comparing patients with SZ and controls and point to disturbed Ca²⁺-signaling as a plausible mechanism contributing to the pathology in patients with SZ.     

CACNA1C rs1006737 genotype and bipolar disorder: Focus on intermediate phenotypes and cardiovascular comorbidity

Recently, multiple genome-wide association studies have identified a genetic polymorphism (CACNA1C rs1006737) that appears to confer susceptibility for BD. This article aims to summarize the existing literature regarding the impact of rs1006737 on functional and structural neuroimaging intermediate phenotypes. Twenty eight articles, representing 2486 healthy participants, 369 patients with BD and 104 healthy first-degree relatives of patients with BD, are incorporated. Multiple studies have demonstrated structural differences, functional differences associated with emotion-related and frontal-executive tasks, and/or differences in behavioral task performance in risk allele carriers (AA or AG). Results comparing participants with BD to health controls are generally less pronounced than within-group genetic comparisons. The review concludes with an integration of how cardiovascular comorbidity may be a relevant mediator of the observed findings, and proposes future directions toward optimized therapeutic use of calcium channel blockers in BD.     

Lack of association between a functional genetic variant of connexin 37 and ischemic stroke in a Taiwanese population

Introduction

Connexin 37, encoded by the GJA4 gene, protects against atherosclerosis. A recent study reported an association between polymorphism rs1764391 at GJA4 and ischemic stroke in a Chinese population. We aimed to replicate this result.

Materials and Methods

A total of 958 ischemic stroke patients and 2196 controls were enrolled for the study. All participants were Chinese residing in Taiwan. Logistic regression analysis with adjustment for traditional risk factors was used to estimate the genetic effect. We also performed stratification analyses by sex and stroke subtypes. Literature reviews were conducted for available genetic association studies investigating rs1764391 and cardiovascular phenotypes.

Results

We did not find any significant association for overall stroke (p = 0.87) or from any subset analyses. Eight studies addressing the associations between rs1764391 and cardiovascular phenotypes had a sample size greater than 1000. Including the present study, five out of the eight large-scale studies found no association.

Conclusions

GJA4 polymorphism is not associated with stroke risk in the Taiwanese population.     

Association of ADIPOQ gene polymorphisms and coronary artery disease risk: a meta-analysis based on 12 465 subjects

Introduction

Coronary artery disease (CAD) is one of the most common cardiovascular diseases and is a major cause of morbidity and mortality worldwide. Various researchers have investigated the role of ADIPOQ gene in the risk of CAD, yet their results have been inconsistent.

Methods

To evaluate the association between ADIPOQ genetic polymorphisms and CAD risk, relevant studies published before October 2011 were identified by searching PubMed and EMBASE. Studies were selected using previously defined criteria. The strength of the relationship between the four single nucleotide polymorphisms (SNPs) of the ADIPOQ gene and CAD risk was assessed using odds ratios (ORs).

Results

A total of 12 465 subjects from 17 case-control studies were identified in the present study. Based on the relevant studies, it was determined that the risk of CAD was not associated with rs2241766 in any genetic model. Increased risk of CAD was associated with rs266729 in allele contrast (1.11, [1.03, 1.20]) and dominant genetic model (1.15, 95%CI: [1.05, 1.27]); increased risk of CAD was also associated with rs822395 in additive (1.63, 95%CI: [1.19, 2.22]) and recessive genetic model (1.71, 95%CI: [1.27, 2.30]). It was further determined that the rs1501299 polymorphism reduced the risk of CAD in the additive (0.80, 95%CI: [0.67, 0.94]) and recessive genetic model (0.81, 95%CI: [0.68, 0.95]). In the stratified analysis, significant associations were found in Asian subjects for rs266729 and in Caucasian subjects for rs1501299.

Conclusion

There is an association between ADIPOQ gene polymorphisms and CAD risk. Different SNPs of the ADIPOQ gene have different associations with CAD risk, and appear to increase risk in individuals of Asian ethnicity while decrease the CAD risk in Caucasians. However, the overall strength of association was mild to moderate.     

White matter hyperintensities in affected and unaffected late teenage and early adulthood offspring of bipolar parents: A two-center high-risk study

Background

White matter hyperintensities (WMHs) are among the most replicated neuroimaging findings in bipolar disorder (BD). It is not clear whether these lesions are an artifact of comorbid conditions, or whether they are directly associated with the disorder, or even represent biological risk factor for BD.

Methods

To test whether WMHs meet criteria for an endophenotype of BD, we conducted a high-risk design study and recruited 35 affected, 44 unaffected relatives of bipolar probands (age range 15-30 years), matched by age and sex with 49 healthy controls without any personal or family history of psychiatric disorders. The presence of WMHs was determined from Fluid Attenuated Inversion Recovery (FLAIR) scans acquired on a 1.5 Tesla scanner using a validated semi-quantitative scale.

Results

We found mostly low grade WMHs in all groups. The proportion of WMH-positive subjects was comparable between the unaffected high-risk, affected familial and control groups.

Conclusion

White matter hyperintensities did not meet criteria for an endophenotype of BD. Bipolar disorder in young subjects without comorbid conditions was not associated with increased rate of WMHs.     

Catechol-O-methyltransferase gene Val108/158Met polymorphism in bipolar disorder

Backgrounds

Although several studies have tested the association between bipolar disorder (BD) and the Val108 (H, high-activity allele)/158Met (L, low-activity allele) polymorphism of the catechol-O-methyltransferase (COMT) gene, most of the results showed no significant association. However, an association between the H or L allele and bipolar disorder (BD), particularly, between L allele and rapid-cycling form has been reported; it has also been suggested that the variation in the COMT gene modifies the course of BD and there is a tendency for the L allele amongst the female patients. In this study, the researchers aimed to evaluate the association between BD and COMT gene H/L polymorphism considering the influence of gender in a group of Turkish patients.

Method

One hundred and thirty-five BD patients (71 male and 64 female) and 171 controls were included. Polymerase chain reaction-based endonuclease digestion method was used.

Results

Genotypic distribution in patients and controls were in Hardy-Weinberg equilibrium. No significant difference was found in genotypic and allelic frequencies between patients and controls. However, female patients had H allele more frequently than male patients and female healthy controls. Females had more depressive and less manic episodes than males. Number of total episodes was associated with H allele in all patients.

Conclusion

Distribution of COMT genetic polymorphism was not significantly different between the patients and controls. However, it has been found an association of H allele with female patients and number of episodes among all patients.     

CACNA1C SNP rs1006737 associates with bipolar I disorder independent of the Bcl-2 SNP rs956572 variant and its associated effect on intracellular calcium homeostasis

Objectives. Intracellular calcium (Ca²⁺) dyshomeostasis (ICDH) has been implicated in bipolar disorder (BD) pathophysiology. We previously showed that SNP rs956572 in the B-cell CLL/lymphoma 2 (Bcl-2) gene associates with elevated B lymphoblast (BLCL) intracellular Ca²⁺ concentrations ([Ca²⁺]_B) differentially in BD-I. Genome-wide association studies strongly support the association between BD and the SNP rs1006737, located within the L-type voltage-dependent Ca²⁺ channel α1C subunit gene (CACNA1C). Here we investigated whether this CACNA1C variant also associates with ICDH and interacts with SNP rs956572 on [Ca²⁺]_B in BD-I. Methods. CACNA1C SNP rs1006737 was genotyped in 150 BD-I, 65 BD-II, 30 major depressive disorder patients, and 70 healthy subjects with available BLCL [Ca²⁺]_B and Bcl-2 SNP rs956572 genotype measures. Results. SNP rs1006737 was significantly associated with BD-I. The [Ca²⁺]_B was significantly higher in BD-I rs1006737 A compared with healthy A allele carriers and also in healthy GG compared with A allele carriers. There was no significant interaction between SNP rs1006737 and SNP rs956572 on [Ca²⁺]_B. Conclusions. Our study further supports the association of SNP rs1006737 with BD-I and suggests that CACNA1C SNP rs1006737 and Bcl-2 SNP rs956572, or specific causal variants in LD with these proxies, act independently to increase risk and ICDH in BD-I.     

Distinguishing affective depersonalization from anhedonia in major depression and bipolar disorder

Background

Affective depersonalization has received limited attention in the literature, although its conceptualization may have implications in terms of identification of clinical endophenotypes of mood disorders. Thus, this study aims to test the hypothesis that anhedonia and affective depersonalization represent 2 distinct psychopathological dimensions and to investigate their clinical correlates in patients with major depressive disorder (MDD) and bipolar disorder (BD).

Methods

Using a data pool of 258 patients with mood and anxiety disorders, an item response theory-based factor analysis approach was carried out on 16 items derived from 2 clinical instruments developed in the Spectrum Project (the Structured Clinical Interview for Mood Spectrum and the Structured Clinical Interview for Derealization-Depersonalization Spectrum). Clinical correlates of these psychometrically derived dimensions were subsequently investigated in patients with BD or MDD.

Results

Using an item response theory-based factor analysis, a 2-factor solution was identified, accounting overall for the 47.0% of the variance. Patients with BD showed statistically significant higher affective depersonalization factor scores than those with MDD (Z = 2.215, P = .027), whereas there was no between-groups difference in anhedonia scores (Z = 0.825 P = .411). In patients with BD, age of onset of the disease correlated with affective depersonalization factor scores (ρ = −0.330, P = .001) but not with anhedonia factor scores (ρ = −0.097, P = .361).

Conclusions

Affective depersonalization and anhedonia seem to be 2 distinct psychopathological dimensions, although closely related, bearing the opportunity to identify patients with a specific profile for a better clinical and neurobiological definition.     

Association between Novelty Seeking of opiate-dependent patients and the catechol-O-methyltransferase ValMet polymorphism

Background

Candidate genes of the dopaminergic system have been reported as key elements in shaping human temperament. Catechol-O-methyltransferase (COMT) plays a vital role in dopamine inactivation, and the Val¹⁵⁸Met single nucleotide polymorphism (rs4680) in its gene has been recently associated with the Novelty Seeking (NS) temperament scale of the Temperament and Character Inventory in studies of healthy adults, as well as methamphetamine abusers.

Method

Our goal was to examine the association between temperament dimensions of the Temperament and Character Inventory and the COMT Val¹⁵⁸Met variation in a Hungarian sample of 117 heroin-dependent patients and 124 nondependent controls.

Results

Case-control analysis did not show any significant difference in allele or genotype distributions. However, dimensional approach revealed an association between the COMT Val¹⁵⁸Met and NS (P = .01): both controls and opiate users with Met/Met genotypes showed higher NS scores compared to those with the Val allele. The NS scores are also significantly higher among opiate users; however, no interaction was found between group status and COMT genotype.

Conclusion

Association of the COMT polymorphism and NS temperament scale has been shown for heroin-dependent patients and controls regardless of group status.     

Serotonin receptor HTR1A and HTR2C variants and personality traits in suicide attempters and controls

Introduction

Serotonin has been extensively studied in relation to both personality features and suicidal behaviours.

Objective

In this study, we considered the association between the serotonin receptor 1A (HTR1A) and 2C (HTR2C) SNPs and personality traits, as measured by the Temperament and Character Inventory (TCI), in a sample of suicide patients and healthy volunteers.

Methods

The SNPs considered were, for HTR1A rs1423691, rs878567 and rs6295, and for HTR2C rs547536, rs2192372, rs6318, rs2428707, rs4272555 and rs1801412. The sample was composed of three groups: two German samples, consisting of a healthy control group of 289 subjects (42.6% males, mean age: 45.2 ± 14.9) and a psychiatric patient group of 111 suicide attempters (38.7% males, mean age: 39.2 ± 13.6), and an Italian sample, composed of 64 mood disorder patients (35.9% males, mean age: 43.0 ± 14.8). In the German samples all the SNPs were investigated, while in the Italian sample only the HTR1A rs6295 and the HTR2C rs6318 SNPs were considered.

Results

Controlling for sex, age and educational level, single markers and haplotypes were not or only marginally associated with personality dimensions.

Conclusions

Our study does not support the role of HTR1A and HTR2C gene variants on personality traits in both healthy volunteers and mood disorder patients.     

Combined cis-regulator elements as important mechanism affecting FXII plasma levels

Introduction

Factor XII (FXII) deficiency is a recessive Mendelian trait due to mutations in the F12 gene. There is no bleeding associated with FXII deficiency, but FXII deficiency has been reported to be associated with risk of thrombosis in some studies.

Material and Methods

We examined the functional effect of two naturally-occurring mutations in two Spanish FXII deficient families: a C/G substitution at position -8, and a C/T substitution at position -13. Both mutations were located on a putative HNF4 binding site of F12 gene promoter. We also analyzed the F12 C46T polymorphism (rs1801020), associated with a decrease in the FXII levels, which also segregated in both families. A fragment containing each one of both -8 and -13 mutations, was cloned 5′ of a reporter gene. We compared the in vitro expression of these constructs to the wild type expression.

Results

Our analyses confirm that the -8C/G and the -13C/T mutations decreased expression levels, demonstrating that both mutations are involved in the observed FXII deficiency. In addition, electrophoretic shift analyses suggest that they alter the union of nuclear proteins to the promoter. Coinheritance of these mutations with the C46T polymorphism, result in a significant genotype-phenotype correlation.

Conclusions

We have identified two naturally-occurring mutations in the F12 promoter that drastically reduce FXII levels. Knowing rare genetic alterations in the F12 gene, together with the C46T common variant, may yield further understanding about the genetic architecture of FXII levels, which may have a role in the risk of thrombosis.     

Human amygdala responses during presentation of happy and neutral faces: correlations with state anxiety

Background

Previous functional imaging studies demonstrating amygdala response to happy facial expressions have all included the presentation of negatively valenced primary comparison expressions within the experimental context. This study assessed amygdala response to happy and neutral facial expressions in an experimental paradigm devoid of primary negatively valenced comparison expressions.

Methods

Sixteen human subjects (eight female) viewed 16-sec blocks of alternating happy and neutral faces interleaved with a baseline fixation condition during two functional magnetic resonance imaging scans.

Results

Within the ventral amygdala, a negative correlation between happy versus neutral signal changes and state anxiety was observed. The majority of the variability associated with this effect was explained by a positive relationship between state anxiety and signal change to neutral faces.

Conclusions

Interpretation of amygdala responses to facial expressions of emotion will be influenced by considering the contribution of each constituent condition within a greater subtractive finding, as well as 1) their spatial location within the amygdaloid complex; and 2) the experimental context in which they were observed. Here, an observed relationship between state anxiety and ventral amygdala response to happy versus neutral faces was explained by response to neutral faces.     

CACNA1C polymorphism and brain cortical structure in bipolar disorder

BackgroundThe CACNA1C gene encodes the 1C subunit of L-type voltage-gated calcium channels and has been associated with several psychiatric syndromes — including bipolar disorder — in many genome-wide association studies. Experimental and clinical studies have reported changes with respect to behaviour and biomarkers in risk allele carriers, corroborating the essential role of the CACNA1C gene in neurons, during development and in the mature brain. However, the association of this gene with regional cortical thickness has not been evaluated in patients with bipolar disorder.MethodsUsing magnetic resonance imaging, we measured the average cortical thickness of 68 brain regions in 87 patients genotyped for the single-nucleotide polymorphism rs1006737 in CACNA1C.ResultsWe found associations with the mean thickness of several cortical areas: the left lateral orbitofrontal and rostral anterior cingulate cortices, as well as other parts of the frontal and parietal cortices.Limitations: This cross-sectional cohort study could not fully differentiate correlation from causation.ConclusionThe CACNA1C polymorphism rs1006737 is associated with the mean thickness of cortical brain areas that have been shown to be altered in bipolar disorder.     

Early infantile manifestations of incontinentia pigmenti mimicking acute encephalopathy

Objective

We retrospectively reviewed six patients with incontinentia pigmenti (IP) who had encephalopathic manifestations during early infancy.

Methods

We enrolled six patients who met the following criteria from the mailing list of the Annual Zao Conference: (1) diagnosis of IP; (2) encephalopathic manifestations with reduced consciousness and clusters of seizures by 6 months of age; and (3) no evidence of central nervous system infection or metabolic derangement.

Results

The onset of the encephalopathic events was within the first 2 months of life in all but one patient. All had clusters of focal clonic seizures. The duration of seizures was typically 5 min. The seizures ceased within 5 days in all patients. Various degrees of reduced consciousness were observed in association with the frequent seizures. Diffusion-weighted imaging during the acute phase showed reduced water diffusion in the subcortical white matter, corpus callosum, basal ganglia, thalami, and internal capsule in two patients. Scattered subcortical white matter lesions were observed on fluid-attenuated inversion-recovery images in two patients.

Conclusions

The encephalopathic manifestations in patients with incontinentia pigmenti were characterized by seizure clusters and reduced consciousness, albeit of relatively short duration. Magnetic resonance imaging abnormalities were predominant in the subcortical areas in most patients.     

P11 expression and PET in bipolar disorders

Background

Bipolar disorder (BD) is a common mental disorder, subdivided into BD-I and BD-II. Currently, few biomarkers differentiate BD-I from BD-II. However, it is suggested that peripheral blood mononuclear cell (PBMC) mRNA levels of p11 and positron emission tomography (PET) might be potential biomarkers for BD.

Methods

Healthy controls (HCs), BD-I, and BD-II patients in remission (n = 20 in each group) underwent a resting PET study with the radiotracer [¹⁸F]-2-deoxy-2-fluoro-d-glucose (¹⁸F-FDG). PBMC p11 mRNA levels were determined by quantitative real-time PCR.

Results

Comparing BD patients to HCs, normalized glucose metabolism (NGM) was higher in the hippocampus, parahippocampus, and amygdala, but lower in the anterior cingulate cortex (aCC), medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), insula and thalamus. Compared to BD-II, BD-I had hypometabolism of glucose in the aCC, bilateral middle and inferior gyrus, insula and striatum, and hypermetabolism of glucose in the left parahippocampus. PBMC p11 mRNA was over-expressed in both BD-I and BD-II, although there was no significant difference in its expression levels between BD-I and B-II patients. Further, there were significant positive correlations between PBMC p11 mRNA and NGM in the mPFC, aCC, left insula, bilateral orbitofrontal cortex (OFC), and left middle, inferior and superior temporal gyri. Also, PBMC p11 mRNA was positively correlated to the number of depressive episodes in BD patients, especially in BD-I patients.

Discussion

This study demonstrates that PBMC p11 mRNA expression is associated with neural activation in the brain of BD patients and warrants a larger translational study to determine its clinical utility.     

Heart rate variability in bipolar mania and schizophrenia

Background

Autonomic nervous system (ANS) dysfunction and reduced heart rate variability (HRV) have been reported in a wide variety of psychiatric disorders, but have not been well characterized in bipolar mania. We recorded cardiac activity and assessed HRV in acutely hospitalized manic bipolar (BD) and schizophrenia (SCZ) patients compared to age- and gender-matched healthy comparison (HC) subjects.

Method

HRV was assessed using time domain, frequency domain, and nonlinear analyses in 23 manic BD, 14 SCZ, and 23 HC subjects during a 5 min rest period. Psychiatric symptoms were assessed by administration of the Brief Psychiatric Rating Scale (BPRS) and the Young Mania Rating Scale (YMRS).

Results

Manic BD patients demonstrated a significant reduction in HRV, parasympathetic activity, and cardiac entropy compared to HC subjects, while SCZ patients demonstrated a similar, but non-significant, trend towards lower HRV and entropy. Reduction in parasympathetic tone was significantly correlated with higher YMRS scores and the unusual thought content subscale on the BPRS. Decreased entropy was associated with increased aggression and diminished personal hygiene on the YMRS scale.

Conclusion

Cardiac function in manic BD individuals is characterized by decreased HRV, reduced vagal tone, and a decline in heart rate complexity as assessed by linear and nonlinear methods of analysis. Autonomic dysregulation is associated with more severe psychiatric symptoms, suggesting HRV dysfunction in this disorder may be dependent on the phase of the illness.     

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls

Background

Similar patterns of subcortical brain abnormalities and neurocognitive dysfunction have been demonstrated in schizophrenia and bipolar disorder, with more extensive findings in schizophrenia. It is unknown whether relationships between subcortical volumes and neurocognitive performance are similar or different between schizophrenia and bipolar disorder.

Methods

MRI scans and neuropsychological test performance were obtained from 117 schizophrenia or 121 bipolar spectrum disorder patients and 192 healthy control subjects. Using the FreeSurfer software, volumes of 18 selected subcortical structures were automatically segmented and analyzed for relationships with results from 7 neurocognitive tests.

Results

In schizophrenia, larger left ventricular volumes were related to poorer motor speed, and bilateral putamen volumes were related to poorer verbal learning, executive functioning and working memory performance. In bipolar disorder, larger left ventricular volumes were related to poorer motor speed and executive functioning. The relationship between left putamen volume and working memory was specific to schizophrenia. The relationships between left inferior lateral ventricles and motor speed and between right putamen volumes and executive functioning were similar in schizophrenia and bipolar disorder, and different from healthy controls. The results remained significant after corrections for use of antipsychotic medication. Significant structure-function relationships were also found when all subjects were combined into one group.

Conclusion

The present findings suggest that there are differences as well as similarities in subcortical structure/function relationships between patients with schizophrenia or bipolar disorder and healthy individuals. The observed differences further suggest that ventricular and putamen volume sizes may reflect severity of cognitive dysfunction in these disorders.     

Childhood trauma history differentiates amygdala response to sad faces within MDD

Objective

Heightened amygdala reactivity to aversive stimuli in major depression is regarded as a core feature of the underlying physiology but individual differences in amygdala response may also arise secondary to persistent changes in limbic function during early neurodevelopment relative to stressors such as childhood trauma. We sought to determine whether heightened amygdala response is a core feature of depression or a general risk factor for psychopathology secondary to early life stress.

Method

Twenty unipolar depressed patients with and without a history of significant early life trauma and 16 healthy comparison subjects underwent functional MRI in a cross-sectional study comparing neural response to sad and neutral faces.

Results

We observed a robust positive correlation between physical abuse and right amygdala response. A much weaker relationship with other forms of abuse and neglect was also found, suggesting differences between abuse subtypes and amygdala response. Group differences in amygdala response suggest heightened reactivity was not characteristic of persons with depression in general but was true primarily in those with a significant history of abuse.

Conclusion

These findings suggest the relationship between childhood trauma and risk for depression is mediated by heightened amygdala response but varies by abuse type. Preliminary evidence for two distinct depression phenotypes based on trauma history was also supported, consistent with differential etiology.     

Impact of obsessive-compulsive disorder comorbidity on the sociodemographic and clinical features of patients with bipolar disorder

Background

In this study, our aim is to determine the prevalence rates of obsessive-compulsive disorder (OCD) comorbidity and to assess the impact of OCD comorbidity on the sociodemographic and clinical features of patients with bipolar disorder (BD).

Methods

Using the Yale-Brown Obsessive Compulsive Scale Symptom Checklist and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-IV/Clinical Version on bipolar patients, 2 groups, BD with OCD comorbidity (BD-OCD) and BD without OCD comorbidity, were formed. These groups were compared for sociodemographic and clinical variables.

Results

Of 214 patients with BD, 21.9% of them had obsession and/or compulsion symptoms and 16.3% had symptoms at the OCD level. Although there was no statistically significant difference between the frequency of comorbid OCD in BD-I (22/185, 11.9%) and BD-II (3/13, 23.1%) patients, but OCD was found to be significantly high in BD not otherwise specified (10/16, %62.5) patients than BD-I (P < .001) and BD-II (P = .03). Six patients (17.1%) of the BD-OCD group had chronic course (the presence of at least 1 mood disorder episode with a duration of longer than 2 years), whereas the BD without OCD group had none, which was statistically significant. There were no statistically significant differences between BD-OCD and BD without OCD groups in terms of age, sex, education, marital status, polarity, age of BD onset, presence of psychotic symptoms, presence of rapid cycling, history of suicide attempts, first episode type, and predominant episode type.

Limitations

Main limitation of our study was the assessment of some variables based on retrospective recall.

Conclusions

Our study confirms the high comorbidity rates for OCD in BD patients. Future studies that examine the relationship between OCD and BD using a longitudinal design may be helpful in improving our understanding of the mechanism of this association.     

Lack of association between TLR4 Asp299Gly polymorphism and atherosclerosis: evidence from meta-analysis

Introduction

Toll like receptor 4 (TLR4) expression was found to increase markedly in human atherosclerotic lesions, notably on macrophages and endothelial cells. TLR4 Asp299Gly polymorphism was associated with a blunted receptor activity and a subsequently diminished inflammatory response, and may subsequently reduce atherosclerosis (AS) risk. However, the results of molecular epidemiological studies remained inconsistent.

Materials and methods

The PubMed, CNKI databases were searched for all articles available. The OR corresponding to the 95% confidence interval (95% CI) was used to assess the association between TLR4 Asp299Gly polymorphism and risk of AS.

Results

15 case-control studies with 9,989 cases and 6,746 controls were available for this analysis. For control subjects, G allele frequency of TLR4 Asp299Gly polymorphism was ranging from 0.045 to 0.085. The G allele and the AG/GG genotypes were not associated with significantly risk of AS (OR = 1.02, 95% CI = 0.83 - 1.26 for G versus A and OR = 0.96, 95% CI = 0.80 - 1.15 for AG/GG versus AA, respectively) by random effects model.

Conclusion

These findings indicated that TLR4 Asp299Gly polymorphism may not play a role in AS development.