Beatriz Camarena

Increased prevalence of the seven-repeat variant of the dopamine D4 receptor gene in patients with obsessive-compulsive disorder with tics

The polymorphism characterized by a varying number of 48 bp repeats (VNTR) in the dopamine D4 receptor (DRD4) gene was examined in 61 obsessive-compulsive disorder (OCD) probands with and without tics. Most of the OCD patients with tics showed at least one copy of the 7-fold variant compared to those affected subjects without tics (91 vs. 48%, respectively, Yates corrected chi2 = 5.54, P = 0.018). Similarly, a higher number of copies of this common variant were detected in the group of probands displaying tics compared to those OCDs without tics (Yates corrected chi2 = 4.66, P = 0.03). Our study suggests that the seven-repeat allele of the DRD4 gene could be a factor in the phenotypic variance of tics among OCD individuals.

Association study of the serotonin transporter gene polymorphism in obsessive–compulsive disorder

The hypothesis implicating the serotonergic system in the pathophysiology of obsessive-compulsive disorder (OCD) is supported by the therapeutic efficacy of selective serotonin reuptake inhibitors (SSRIs). Since SSRIs act on the serotonin transporter (5-HTT), it has been suggested that the 5-HTT gene (SCL6A4) could be a good candidate for OCD. The SCL6A4 gene has a 44-bp insertion/deletion polymorphism in its promoter region (5-HTTLPR). Previous studies have revealed an association between OCD and the l allele. We analysed the 5-HTTLPR polymorphic system in 115 Mexican OCD patients and 136 controls. No significant association was found between l allele and OCD (chi2 = 1.54, d.f. = 1, p = 0.21). Furthermore, we assessed alternative methods that employ family-based designs in a sample of 43 trios. Haplotype-based haplotype relative risk and transmission disequilibrium analysis did not show a preferential transmission of l allele to OCD probands. Our results indicate the need to analyse larger samples using family-based methods.

A family-based association study of the 5-HT-1Dβ receptor gene in obsessive-compulsive disorder

Abstract Pharmacological studies have shown that sumatriptan, a selective ligand of the serotonin 5-HT-1Dbeta autoreceptor, modifies obsessive-compulsive disorder (OCD) symptoms. The current study analysed the G861C polymorphism of the 5-HT-1Dbeta gene in a sample of 72 trios. Genotyping data were analysed using the Family-Based Association Test (FBAT). We did not replicate the previously reported linkage disequilibrium between the G861 variant and OCD. However, a quantitative trait analysis, assessing severity of OCD symptoms and defined as YBOCS score, confirmed the finding that subjects with a preferential transmission of the G861 variant showed higher YBOCS Obsession scores compared to patients carrying the C861 allele. These preliminary findings may indicate that the 5-HT-1Dbeta receptor gene could be involved in the severity of obsession symptoms in OCD. However, it is important to perform the replication of these findings in larger sample sizes of informative families.

μ opioid receptor gene as a candidate for the study of obsessive compulsive disorder with and without tics

Obsessive compulsive disorder (OCD) is a complex psychiatric disease characterized by recurring obsessions or compulsions that cause significant distress to the patient. The etiology of this disorder remains largely unknown, although a genetic component has been suggested. Many candidates genes have been evaluated based on a possible serotoninergic and dopaminergic brain dysfunction. We postulate the μ opioid receptor (MOR) gene as a candidate because some observations support a role of the opioid system in OCD. The opioid antagonist, naloxone, rapidly exacerbates OCD symptoms and the opioid agonist, tramadol, was reported to be effective in the treatment of some patients. We studied two single nucleotide polymorphisms (C17T and A118G) in 51 trios with OCD. Genotyping was analyzed with transmission desequilibrium test (TDT). The allelic variant +17T of the C17T polymorphism had a low frequency (1%) in our population that did not allow for statistic analysis. However, for the allelic variant +G of the A118G polymorphism we were able to performed statistical comparisons. Our results showed a trend toward significance (χ2 McNemar = 3.6, P = 0.065) for TDT in patients with comorbid tics. It is an interesting finding that should be tested in a larger sample of OCD patients with tics.

Severity of obsessive-compulsive symptoms is related to self-directedness character trait in obsessive-compulsive disorder.

OBJECTIVE The present study examined the psychobiological Temperament and Character model of personality on obsessive-compulsive disorder (OCD) patients, as well as the relation of temperament and/or character dimensions on the severity of obsessive-compulsive symptoms. METHODS Fifty-four subjects diagnosed with OCD, were assessed with the Temperament and Character Inventory, the Yale-Brown Obsessive-Compulsive scale and the Hamilton Rating Scales for depression and anxiety. RESULTS Compared with controls, OCD subjects displayed increased harm avoidance and lower self-directedness and cooperativeness. Low self-directedness and high Hamilton depression scores were associated with increased severity of obsessive-compulsive symptoms. CONCLUSION The Temperament and Character profile of OCD patients characterized in the present study was in agreement with previous reports using the same personality model and can be linked to some of their behavioral features. Furthermore, our data provides support of the influence that some personality traits may have on the severity of OCD symptoms.

Association study of MAO-A and DRD4 genes in schizophrenic patients with aggressive behavior.

Genes involved in dopamine neurotransmission are interesting candidates to be analyzed in schizophrenia and aggressive behavior. Therefore, we analyzed the functional polymorphisms of the dopamine receptor D4 (DRD4) and monoamine oxidase A (MAO-A) genes in a sample of 71 schizophrenic patients assessed with the Overt Aggression Scale to measure aggressive behavior. CLUMP analysis of the DRD4 48-bp repeat-exon III polymorphism in schizophrenic patients showed significant differences between the aggressive behavior and the nonaggressive groups (T1 = 18.77, d.f. = 6, p = 0.0046; T3 = 6.54, p = 0.0195). However, analysis of the promoter polymorphism of the MAO-A gene revealed no significant association between aggressive and nonaggressive patients. Finally, analysis of Overt Aggression Scale dimensions exhibited significant differences for the DRD4 and MAO-A genes. Our preliminary findings suggest that the DRD4 and MAO-A genes may be involved in aggressive schizophrenic patients.

The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder

INTRODUCTION Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. METHODS 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. RESULTS Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. LIMITATIONS The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. CONCLUSIONS Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment.

Family-Based Association Study between the Monoamine Oxidase A Gene and Obesity: Implications for Psychopharmacogenetic Studies

Family studies have reported that obesity has a strong heritable component. It has been suggested that a neurotransmitter dysfunction could be involved in mental disorders and obesity; therefore, candidate genes in psychiatric disorders could be a risk factor for obesity. We investigated the association between the monoamine oxidase A (MAO-A) gene and obesity. Fifty obese subjects and their parents were included in the study. Two polymorphisms designated EcoRV and upstream variable number tandem repeats of the MAO-A gene were analysed using polymerase chain reaction. For analysis of the families, the transmission disequilibrium test (TDT) was applied. The TDT analysis of the EcoRV polymorphism showed in obese subjects with a body mass index (BMI) ≧35 kg/m2 a preferential transmission of the low activity-related allele (χ2TDT = 8.0, p = 0.005). Our findings may provide evidence of a candidate gene involved in obese subjects with a BMI ≧35 kg/m2.

Prediction of the time-course pattern of remission in depression by using clinical, neuropsychological, and genetic variables

BACKGROUND The prediction of remission in pharmacologically-treated MDD patients has been scarcely studied. The goal of our work is to study the possible effect of clinical variables, neuropsychological performance, and the 5HTTLPR, the rs25531 of the SLC6A4 gene, and the val108/58Met of the COMT gene polymorphisms on the prediction of the speed of remission in MDD patients. METHODS Seventy-two depressed patients were genotyped according to the aforementioned polymorphisms and were clinically and neuropsychologically assessed before a 12-week fluoxetine treatment. RESULTS From this original sample 51 patients were considered as remitters at the end of week 12. Thirteen out of those showed a rapid response pattern, 24 showed an oscillating response pattern, and 14 showed a slow response pattern. The following variable combination is capable of showing a statistically significant relationship with the pattern of remission of patients with MDD: initial Hamilton score, age at first depressive episode, AG and GG alleles of the val108/58Met COMT polymorphism, Stroop PC, and SWM Strategy. LIMITATIONS We have a slightly small sample size, which came to prominence during the data analysis since we were working with 3 subgroups. In this study, the placebo effect has not been controlled. DISCUSSION Our data suggest that the patients with MDD who remit after a 12-week treatment with fluoxetine show one of the following time-course patterns: a rapid symptomatic improvement, or a slow or oscillating pattern of remission. A combination of clinical, neuropsychological, and genetic variables allows us to predict these response patterns.

Association study between BDNF gene variants and Mexican patients with obsessive–compulsive disorder

Obsessive-compulsive disorder (OCD) is a psychiatric disorder whose etiology is not yet known. We investigate the role of three variants of the BDNF gene (rs6265, rs1519480 and rs7124442) by single SNP and haplotype analysis in OCD Mexican patients using a case-control and family-based association design. BDNF gene variants were genotyped in 283 control subjects, 232 OCD patients and first degree relatives of 111 OCD subjects. Single SNP analysis in case-control study showed an association between rs6265 and OCD with a high frequency of Val/Val genotype and Val allele (p=0.0001 and p=0.0001, respectively). Also, genotype and allele analysis of rs1519480 showed significant differences (p=0.0001, p=0.0001; respectively) between OCD and control groups. Haplotype analysis showed a high frequency of A-T (rs6265-rs1519480) in OCD patients compared with the control group (OR=2.06 [1.18-3.59], p=0.0093) and a low frequency of haplotype A-C in the OCD patients (OR=0.04 [0.01-0.16], p=0.000002). The family-based association study showed no significant differences in the transmission of any variant. Our study replicated the association between BDNF Val66Met gene polymorphism and OCD. Also, we found a significant association of rs1519480 in OCD patients compared with a control group, region that has never been analyzed in OCD. In conclusion, our findings suggest that BDNF gene could be related to the development of OCD.