Nuria Lanzagorta

Neurocognitive Endophenotypes for Bipolar Disorder Identified in Multiplex Multigenerational Families

CONTEXT Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, a strategy for identifying risk genes is to identify and map quantitative intermediate phenotypes or endophenotypes. OBJECTIVE To adjudicate neurocognitive endophenotypes for bipolar disorder. DESIGN All participants underwent diagnostic interviews and comprehensive neurocognitive evaluations. Neurocognitive measures found to be heritable were entered into analyses designed to determine which test results are impaired in affected individuals, are sensitive to the genetic liability for the illness, and are genetically correlated with affection status. SETTING Central valley of Costa Rica; Mexico City, Mexico; and San Antonio, Texas. PARTICIPANTS Seven hundred nine Latino individuals participated in the study. Of these, 660 were members of extended pedigrees with at least 2 siblings diagnosed as having bipolar disorder (n = 230). The remaining subjects were community control subjects drawn from each site who did not have a personal or family history of bipolar disorder or schizophrenia. MAIN OUTCOME MEASURE Neurocognitive test performance. RESULTS Two of the 22 neurocognitive variables were not significantly heritable and were excluded from subsequent analyses. Patients with bipolar disorder were impaired on 6 cognitive measures compared with nonrelated healthy controls. Nonbipolar first-degree relatives were impaired on 5 of these, and the following 3 tests were genetically correlated with affection status: Digit Symbol Coding Task, Object Delayed Response Task, and immediate facial memory. CONCLUSION This large-scale extended pedigree study of cognitive functioning in bipolar disorder identifies measures of processing speed, working memory, and declarative (facial) memory as candidate endophenotypes for bipolar disorder.

Overview of genetics and obsessive-compulsive disorder

This paper reviews the current state of research into the genetics of obsessive-compulsive disorder (OCD). Heredity has a major role in OCD etiology. This evidence comes from several methodological approaches such as family, twin, and segregation analysis studies. A major single gene effect as well as a polygenic hypothesis has been suggested based on segregation studies. In addition, candidate gene association and linkage analyses have shown not only one gene, but a few interesting genes and areas of the genome that may be relevant in OCD. In this search for genes, new definitions of the OCD phenotype have emerged, and some of them may be considered intermediate phenotypes between the gene effect and OCD-DSM-IV diagnosis. The phenotypic and genetic heterogeneity of OCD magnifies the challenge of locating susceptibility genes; at the same time, the identification of vulnerability genes will elucidate the identification of subtypes or dimensions of the disorder. Therefore research strategies that take advantage of clinical subtyping and that redefine the OCD phenotype in the context of genetic studies may potentially contribute to the nosology of OCD and ultimately pathophysiology. There is a lack of understanding about how genes and environment interact in OCD. However, there are some reports that will be discussed, which have attempted to evaluate how the environment contributes to OCD.

The role of brain‐derived neurotrophic factor (BDNF) Val66Met genetic polymorphism in bipolar disorder: a case–control study, comorbidities, and meta‐analysis of 16,786 subjects

The aim of this study was to evaluate the association of Val66Met brain‐derived neurotrophic factor (BDNF) polymorphism with bipolar disorder in (i) a meta‐analysis and (ii) a case–control study in a Mexican population. We also investigated the possible association of this polymorphism with clinical features.

Childhood, adolescent and adult age at onset and related clinical correlates in obsessive–compulsive disorder: a report from the International College of Obsessive–Compulsive Spectrum Disorders (ICOCS)

Abstract Objective: Many studies suggest that age at onset (AAO) is an important factor for clinically differentiating patients with juvenile and adult onset of obsessive–compulsive disorder (OCD). The present international study aimed to assess the prevalence of different AAO groups and compare related socio-demographic and clinical features in a large sample of OCD patients. Methods: A total of 431 OCD outpatients, participating in the ICOCS network, were first categorised in groups with childhood (≤12 years), adolescent (13–17 years) and adult-onset (≥18 years), then in pre-adult and adult onset (≥18 years) and their socio-demographic and clinical features compared. Results: Twenty-one percent (n = 92) of the sample reported childhood onset, 36% (n = 155) adolescent onset, and 43% (n = 184) adult onset. Patients with adult onset showed a significantly higher proportion of females compared with the other subgroups (χ2 = 10.9, p< 0.05). Childhood- and adolescent-onset patients had been more frequently treated with cognitive behavioural therapy (CBT), compared to adult-onset patients (χ2 = 11.5; p < 0.05). The pre-adult- versus adult-onset analysis did not show any additional significant difference. Conclusions: The present international multicentre study confirms that OCD onset occurs more frequently before adult age, with approximately one out of five patients showing childhood onset. Pre-adult onset was associated with higher rate of CBT, while adult onset was more prevalent in females.

Cigarette smoking in patients with obsessive compulsive disorder: A report from the International College of Obsessive Compulsive Spectrum Disorders (ICOCS)

Obsessive compulsive disorder (OCD) showed a lower prevalence of cigarette smoking compared to other psychiatric disorders in previous and recent reports. We assessed the prevalence and clinical correlates of the phenomenon in an international sample of 504 OCD patients recruited through the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) network. Cigarette smoking showed a cross-sectional prevalence of 24.4% in the sample, with significant differences across countries. Females were more represented among smoking patients (16% vs 7%; p<.001). Patients with comorbid Tourettes syndrome (p<.05) and tic disorder (p<.05) were also more represented among smoking subjects. Former smokers reported a higher number of suicide attempts (p<.05). We found a lower cross-sectional prevalence of smoking among OCD patients compared to findings from previous studies in patients with other psychiatric disorders but higher compared to previous and more recent OCD studies. Geographic differences were found and smoking was more common in females and comorbid Tourettes syndrome/tic disorder.

Prevalence of suicide attempt and clinical characteristics of suicide attempters with obsessive-compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS)

OBJECTIVE Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients. METHODS A total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearsons chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable. RESULTS 14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables. CONCLUSIONS Our international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.

Association between obesity and the brain-derived neurotrophic factor gene polymorphism Val66Met in individuals with bipolar disorder in Mexican population

Background The brain-derived neurotrophic factor (BDNF) has been considered as an important candidate gene in bipolar disorder (BD); this association has been derived from several genetic and genome-wide studies. A polymorphic variant of the BDNF (Val66Met) confers some differences in the clinical presentation of affective disorders. In this study, we evaluated a sample population from Mexico City to determine whether the BDNF (rs6265) Val66Met polymorphism is associated with the body mass index (BMI) of patients with BD. Methods This association study included a sample population of 357 individuals recruited in Mexico City. A total of 139 participants were diagnosed with BD and 137 were classified as psychiatrically healthy controls (all individuals were interviewed and evaluated by the Diagnostic Interview for Genetic Studies). Genomic DNA was extracted from peripheral blood leukocytes. The quantitative polymerase chain reaction (qPCR) assay was performed in 96-well plates using the TaqMan Universal Thermal Cycling Protocol. After the PCR end point was reached, fluorescence intensity was measured in a 7,500 real-time PCR system and evaluated using the SDS v2.1 software, results were analyzed with Finetti and SPSS software. Concerning BMI stratification, random groups were defined as follows: normal <25 kg/m2, overweight (Ow) =25.1–29.9 kg/m2, and obesity (Ob) >30 kg/m2. Results In the present work, we report the association of a particular BMI phenotype with the presence of the Val66Met allele in patients with BD (P=0.0033 and odds ratio [95% confidence interval] =0.332 [157–0.703]), and correlated the risk for valine allele carriers with Ow and Ob in patients with BD. Conclusion We found that the methionine allele confers a lower risk of developing Ow and Ob in patients with BD. We also confirmed that the G polymorphism represents a risk of developing Ow and Ob in patients with BD. In future studies, the haplotype analysis should provide additional evidence that BDNF may be associated with BD and BMI within the Mexican population.

Obsessive-compulsive disorder in the elderly: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS)

INTRODUCTION Obsessive-compulsive disorder (OCD) is a highly disabling condition, with frequent early onset. Adult/adolescent OCD has been extensively investigated, but little is known about prevalence and clinical characterization of geriatric patients with OCD (G-OCD≥65years). The present study aimed to assess prevalence of G-OCD and associated socio-demographic and clinical correlates in a large international sample. METHODS Data from 416 outpatients, participating in the ICOCS network, were assessed and categorized into 2 groups, age<vs≥65years, and then divided on the basis of the median age of the sample (age<vs≥42years). Socio-demographic and clinical variables were compared between groups (Pearson Chi-squared and t tests). RESULTS G-OCD compared with younger patients represented a significant minority of the sample (6% vs 94%, P<.001), showing a significantly later age at onset (29.4±15.1 vs 18.7±9.2years, P<.001), a more frequent adult onset (75% vs 41.1%, P<.001) and a less frequent use of cognitive-behavioural therapy (CBT) (20.8% vs 41.8%, P<.05). Female gender was more represented in G-OCD patients, though not at a statistically significant level (75% vs 56.4%, P=.07). When the whole sample was divided on the basis of the median age, previous results were confirmed for older patients, including a significantly higher presence of women (52.1% vs 63.1%, P<.05). CONCLUSIONS G-OCD compared with younger patients represented a small minority of the sample and showed later age at onset, more frequent adult onset and lower CBT use. Age at onset may influence course and overall management of OCD, with additional investigation needed.

Effect of the polymorphism BDNF rs6265 G/A in Mexican outpatient children with autism spectrum disorders

Introduction. The study of autistic spectrum disorders (ASD) at the genetic level is extremely important to understand their origin. In Mexico, there are few works addressed from this perspective. Objective. We investigated the role of the Brain Derived Neurotrophic Factor ( BDNF ) gene variant rs6265 G/A for single nucleotide polymorphism analysis in Mexican children with ASD using a case-control association design. Method. We made a pilot study by case-control analysis adjusting by gender, age, and ancestry. Results. Our study found no association between the BDNF rs6265 gene polymorphism and ASD [ p = .419, OR = 1.597 (.514, 4.967)]. Discussion and conclusion. Worldwide, the results of case-control association studies with the rs6265 of BDNF are controversial and do not always replicate. This may be due to the ethnicity of our population and additional factors not studied in the present work. Our study suggests that the SNP rs6265 is not contributing for ASD susceptibility in Mexican population.

EXPLORING SOCIODEMOGRAPHIC AND CLINICAL CORRELATES OF OLDER ADULTS WITH OBSESSIVE-COMPULSIVE DISORDER: A REPORT FROM THE INTERNATIONAL COLLEGE OF OBSESSIVE-COMPULSIVE DISORDERS (ICOCS)

. Introduction Obsessive compulsive disorder (OCD) is a chronic and disabling condition, often showing an early onset (1). OCD has been extensively studied in adults, adolescents, and children, but a critial gap remains in the clinical characterization of older patients (2). The present study was aimed to assess prevalence of geriatric OCD (G-OCD ≥ 65 years) and associated sociodemographic and clinical correlates of geriatric OCD in a large international sample of OCD patients. Methods Data of 416 outpatients recruited by different OCD Clinics worldwide, participating in the International College of Obsessive-compulsive Spectrum Disorders (ICOCS) network (3), were assessed and first categorized into 2 groups, age Results Patients with G-OCD represented a significant minority of the overall sample (n=24, 6% of the total sample vs age When the whole sample was divided on the basis of the median age (age Conclusions The present international multicenter study revealed a significantly lower rate of patients with age ≥ 65 years compared to patients younger than 65 years. Patients with G-OCD showed a significantly higher age at onset and rate of adult onset compared to non-geriatric patients. Moreover, in G-OCD patients CBT was less frequently utilized. Subgroups divided on the basis of the median age of the sample showed that the age ≥ 42 years group had a significantly later onset of illness and higher rate of adult onset and female gender.