Genetics of behavioural domains across the neuropsychiatric spectrum; of mice and men

Abstract

There is significant evidence for genetic factors in the susceptibility to anorexia nervosa (AN). Previously genetic variation in the estrogen receptor 2 gene (ESR2) has been studied, however no strong evidence of association with AN has been found. In the present study variation in the estrogen receptor 1 (ESR1) and ESR2 genes was examined. Estrogen receptors have been localised to areas of the brain involved in behaviour and regulation of food intake. The anorexic effects of estrogen are accentuated by stress and thus it is postulated that variation in the estrogen receptors may contribute to the genetic susceptibility to AN in females. A cohort of 170 female, Caucasian AN sufferers and 152 female controls were typed for dinucleotide repeat polymorphisms in both ESR1 and ESR2 and two further SNPs at each locus. Variation at ESR1 was not associated with AN. However an association was found at the ESR2 locus with the heterozygous genotype of the G1082A polymorphism and AN but not with any of the other ESR2 polymorphisms analysed. Analysis of haplotypes at ESR1 and ESR2 showed no significant evidence of association with AN suggesting that the variability in ESR2 alone may contribute to the genetic susceptibility to AN.

Targeting dynamic interplay among disordered domains or endophenotypes to understand complex neuropsychiatric disorders: Translational lessons from preclinical models

“…As explained in Table 1, endophenotypes represent objective quantifiable and inheritable biological or behavioral components of a disorder , which are present regardless of whether a specific disorder is active, and can be found in non-affected relatives of the patient at a higher rate than the general population (Cannon and Keller, 2006;LaPorte et al, 2008). This term is also related to (but different from) the term 'intermediate phenotype', often used to describe a quantitative trait that is between the genes and the disorder Kas et al, 2007;Walters and Owen, 2007).…”

“…Modeling human disorders using animal models from different (often evolutionarily distant) taxa-e.g., from humans to primates, rodents and fish (Bernier et al, 2014;Kas et al, 2007Kas et al, , 2011 …”

Best behaviour? Ontologies and the formal description of animal behaviour

“…However, many behaviours affected in disease states can be identified as equivalent in humans and model species at the level of the endophenotype, such as anxiety, arousal, cognition and social interaction. An ethological approach to identifying and assessing these basic behavioural building blocks is beginning to bear fruit (Gould and Gottesman 2006;Kas et al 2007Kas et al , 2011a. For example in modelling schizophrenia, anhedonia, asociality and avolition are at least theoretically accessible through behavioural assays in both humans and animals (Kas et al 2011a) and characteristics of autistic spectrum disorders, for example insistence on routine and resistance to change in tasks that involve reversal learning or set shifting, high anxiety and low socialization can be all assessed in mouse models (Bishop and Lahvis 2011;Amodeo et al 2012;Moy et al 2007;Naviaux et al 2014;Nestler and Hyman 2010).…”

Avances en enfoques multidisciplinarios y en diversas especies para el examen de la neurobiología de los trastornos psiquiátricos

“…Aunque los trastornos psiquiátricos muestran alteraciones en ciertos dominios conductuales, como déficits cognitivos, alteraciones motoras o anomalías de la sociabilidad, continúa existiendo la duda de cómo evaluar estas características en una población de pacientes y cómo estudiar su relevancia respecto a la etiología. Además, para estudiar de manera sistemática estas relaciones genotipo-fenotipo en un contexto genético y ambiental controlado, son muy necesarios paradigmas comparativos paralelos en animales (Kas et al, 2007(Kas et al, , 2009. Recientemente se han planteado varias iniciativas novedosas para abordar estas dificultades de la investigación translacional respecto a los trastornos psiquiátri-cos.…”