ABSTRACT
Objective: In obsessive-compulsive disorder (OCD), symmetry-related symptoms may be important. Although clinical correlates of symmetry-related symptoms have been identified in OCD, few data exist on genetic associations. Animal studies indicate involvement of dopamine in symmetry-related behavior, suggesting this may be relevant to analogous symptoms in OCD. Alterations in dopamine may also reflect environmental influences. However, the association of symmetry-related symptomatology, early adversity, and polymorphisms in dopaminergic genes has not been investigated in OCD. Methods: Clinical information and polymorphisms in key dopaminergic genes were compared between OCD patients with primary symmetry symptoms and those without. Results: OCD patients with primary symmetry symptoms comprised 46.6% (n=210) of the sample (n=451), and were older (p < 0.01), had longer illness duration (p < 0.01), higher OCD severity scores (p = 0.01), and greater comorbidity (p < 0.01) than those without. In Caucasians (n=343), genotype frequency differed significantly between groups for ANKK1 rs1800497, with more OCD patients with symmetry symptoms being homozygous for the A2 (CC) genotype (χ2 = 7.296; p = 0.026). Conclusion: Symmetry symptoms have some distinct clinical features and may represent a marker of severity in OCD. However, clinical associations, in combination with the association found with the ANKK1 rs1800497 A2 variant, suggest that primary symmetry symptoms may represent a distinctive clinical and psychobiological profile.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Dopamine/genetics , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/genetics , Polymorphism, Genetic/genetics , Stress Disorders, Post-Traumatic/complications , Severity of Illness Index , Protein Serine-Threonine Kinases/genetics , Tandem Repeat Sequences/genetics , Depressive Disorder, Major/complications , Perfectionism , Genotype , Middle Aged , Obsessive-Compulsive Disorder/complicationsABSTRACT
El nivel de Dopamina en la Corteza Prefrontal se ha relacionado al desempeño de las Funciones Ejecutivas (FE). El objetivo de este estudio es explorar el efecto del polimorfismo funcional del gen COMT (Val/Val,Val/Met y Met/Met) en las FE de preescolares. Se utilizó la Batería Neuropsicológica de Funciones Ejecutivas para niños, y se extrajo el ADN genómico según metodología estándar (N=248) de 3 a 6 años de edad (M=4.6). Se estudiaron las frecuencias genotípicas del gen COMT y se realizó un análisis de varianza (ANOVA one-way) estableciendo diferencias significativas con una p<0.05. Los niños con el polimorfismo de baja actividad Met/Met puntúan significativamente mejor en relación a los niños con polimorfismo Val/Val en pruebas que requieren de Inhibición y los niños con el polimorfismo de alta actividad Val/Val resultan con un mejor rendimiento en pruebas relacionadas a MT, Planeación y Abstracción que los niños con polimorfismo Met/Met y Val/Met. Estos resultados parecen reflejar el papel de la enzima COMT como regulador de DA y que tanto el hipermetabolismo como el hipometabolismo tiene implicaciones importantes en las FE.
The level of DA in the prefrontal cortex has been related to the performance on executive functions (EF). The objective of this study was to explore the effect of the COMT polymorphism (Val/Val, Val/Met, Met/Met) in the performance of EF in a population of preschool children. All subjects were evaluated with a Neuropsychological Battery and genomic DNA was extracted according to standard methodology (N=248) from 3 to 6 years of age (M=4.6). We studied genotypic frequencies of the COMT gene and an analysis of variance (one-way ANOVA) with post hoc analysis, establishing significant differences at p<0.05. In Children with a low activity polymorphism Met/Met scored significantly better in relation to the children with polymorphism Val/Val in tests requiring inhibition and children with high activity polymorphism Val/Val had better performance on tests related to working memory, planning and abstraction that children with polymorphism Met/Met and Val/Met. These results seem to reflect the role of COMT enzyme as a regulator of DA and that both hypermetabolism and hypometabolism has important implications for the EF.
Subject(s)
Female , Child, Preschool , Child , Catechol O-Methyltransferase/genetics , Dopamine/genetics , Executive Function/physiology , Polymorphism, Genetic , Analysis of Variance , Cross-Sectional Studies , Genotype , Methionine/genetics , Valine/geneticsABSTRACT
Background: Worldwide diversity of alleles of D4 receptor gene (DRD4), linked to attention deficit hyperactivity disorder (ADHD), is mostly the result of length and single nucleotide polymorphisms in a 48-bp tandem repeat (VNTR). Alleles containing from two (2R) to eleven (11R) repeats have been identified. The most common are 4R, 7R and 2R. Aim: To study the association of ADHD risk with DRD4 genotypes in Chilean students. Subjects and Methods: ADHD risk data were obtained through the abbreviated Conner's Scale for School Teachers in 66 Aymara children (11 cases and 55 controls), 91 Rapa-Nui children (60 cases ad 31 controls) and 96 children from a mixed urban population from Santiago (51 cases and 45 controls). DNA extracted from saliva was amplified by polymerase chain reaction (PCR) to genotype the DRD4 VNTR. Results: The distribution of DRD4 alleles reveals that, beneath the 4R allele, 7R exhibits the second highest frequencies in Aymara and Santiago children. In Polynesian children, 2R ranks after 4R. A statistically significant association between ADHD risk and 2R/4R genotype was identified in Polynesian children (p < 0.05; odds ratio = 3.7). Conclusions: Different DRD4 genotypes are associated with ADHDphenotype in Chilean populations, probably as a consequence of their initial colonization history.
Subject(s)
Child , Humans , Attention Deficit Disorder with Hyperactivity/genetics , Dopamine/genetics , Indians, South American/genetics , /genetics , Alleles , Case-Control Studies , Chile , Gene Frequency , Genotype , Risk FactorsABSTRACT
The molecular mechanisms of the fact that more than 50% of the individuals with the same genetic make up [e.g. identical twins in schizophrenia] do not show the same psychiatric phenotype remained undefined in psychiatry. This along with the failure to find responsible genes with major effects in psychiatric disorders and lack of consistency of genetic association studies led to the current unanimous conclusion that, in addition to the genetic factors, environmental and epigenetic factors influence the functions of brain and the presentation of the symptoms in mental diseases. Here we reviewed the potential epigenetic dysregulations of genes related to dopaminergic [DAergic] system. A comprehensive genetic and epigenetic analysis of the DAergic and the interacting pathways such as serotoninergic and glutaminergic systems could help to understand the molecular bases of the differences in disease severity in individuals with similar or identical genetic make-up that can assist for the identification of novel targets with therapeutic and preventive applications