RESUMO
We theorized the cognitive vulnerability factor featured in hopelessness theory [2] to be a novel endophenotype for depression. We investigated two possible genetic contributors to individual differences in cognitive vulnerability (and, in turn, depression): the BDNF gene and the COMT gene. Results showed that individuals (n=95) with the BDNF Val(66) genotype had significantly greater levels of cognitive vulnerability than individuals with a BDNF Met(66) genotype. In addition, among individuals with high levels of cognitive vulnerability, those with the Val(66) genotype were significantly more likely than participants with a Met(66) genotype to experience increases in depressive symptoms when faced with increased stress. The COMT gene was not associated with cognitive vulnerability or risk for depression. Results support the use of the cognitive vulnerability factor featured in hopelessness theory as an endophenotype associated with depression as well as the role of the BDNF gene in a cognitive subtype of depression.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Depressão/genética , Endofenótipos , Predisposição Genética para Doença/genética , Catecol O-Metiltransferase/genética , Transtornos Cognitivos/genética , Transtornos Cognitivos/psicologia , Depressão/psicologia , Genótipo , Humanos , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologiaRESUMO
The personality trait Openness/Intellect reflects the tendency to be imaginative, curious, perceptive, artistic, and intellectual-all characteristics that involve cognitive exploration. Little is known about the biological basis of Openness/Intellect, but the trait has been linked to cognitive functions of prefrontal cortex, and the neurotransmitter dopamine plays a key role in motivation to explore. The hypothesis that dopamine is involved in Openness/Intellect was supported by examining its association with two genes that are central components of the prefrontal dopaminergic system. In two demographically different samples (children: N = 608; adults: N = 214), variation in the dopamine D4 receptor gene (DRD4) and the catechol-O-methyltransferase gene (COMT) predicted Openness/Intellect, as main effects in the child sample and in interaction in adults.
RESUMO
We provide an illustration of an application of the elastic net to a large number of common genetic variants in the context of the search for the genetic bases of an endophenotype conceivably related to individual differences in learning. GABA concentration in the occipital cortex, a critical area for reading, was obtained in a group (n = 76) of children aged 6-10 years. Two extreme groups, high and low, were selected for genotyping with the 650Y Illumina array chip (Ilmn650Y). An elastic net approach was applied to the resulting SNP dataset; 100 SNPs were identified for each chromosome as "interesting" based on having the highest absolute value coefficients. The analyses highlighted chromosomes 15 and 20, which contained 55 candidate genes. The STRING partner analyses of the associated proteins pointed to a number of related genes, most notably, GABA and NTRK receptors.
Assuntos
Algoritmos , Dislexia/genética , Dislexia/fisiopatologia , Endofenótipos , Variação Genética/genética , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Genótipo , Modelos Genéticos , Polimorfismo de Nucleotídeo Único/genética , Ácido gama-Aminobutírico/metabolismo , Criança , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 20/genética , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Lobo Occipital/fisiopatologia , FenótipoRESUMO
A number of dopamine-related genes have been implicated in the etiology of violent behavior and conduct problems. Of these genes, the ones that code for the enzymes that influence the turnover of dopamine (DA) have received the most attention. In this study, we investigated 12 genetic polymorphisms in four genes involved with DA functioning (COMT, MAOA and MAOB, and DbetaH) in 179 incarcerated male Russian adolescents and two groups of matched controls: boys without criminal records referred to by their teachers as (a) "troubled-behavior-free" boys, n=182; and (b) "troubled-behavior" boys, n=60. The participants were classified as (1) being incarcerated or not, (2) having the DSM-IV diagnosis of conduct disorder (CD) or not, and (3) having committed violent or nonviolent crimes (for the incarcerated individuals only). The findings indicate that, although no single genetic variant in any of the four genes differentiated individuals in the investigated groups, various linear combinations (i.e., haplotypes) and nonlinear combinations (i.e., interactions between variants within and across genes) of genetic variants resulted in informative and robust classifications for two of the three groupings. These combinations of genetic variants differentiated individuals in incarceration vs. nonincarcerated and CD vs. no-CD groups; no informative combinations were established consistently for the grouping by crime within the incarcerated individuals. This study underscores the importance of considering multiple rather than single markers within candidate genes and their additive and interactive combinations, both with themselves and with nongenetic indicators, while attempting to understand the genetic background of such complex behaviors as serious conduct problems.