RESUMEN
The etiology of mental disorders remains largely unclear. Complex interactions between genetic and environmental factors are key to the development of such disorders. Puerperal psychosis is the most extreme form of postnatal mood disorder in women. Similarly, parturition in the pig can trigger extreme behavioral disturbances, including maternal infanticide. In this study, we have used a targeted cDNA microarray approach using the pig as a model to understand the genes and genetic pathways that are involved in these processes. Two subtracted cDNA libraries from porcine hypothalamus were constructed, which were enriched for genes that were over-expressed and under-expressed in the aberrant behavioral phenotype, compared to the matched control. In addition to this, a normalized library was constructed from hypothalamus and pituitary samples taken from pigs in a variety of reproductive states. The libraries were partially sequenced and combined represented approximately 5,159 different genes. Microarray analysis determined differences in gene expression between hypothalamus samples from nine matched pairs of infanticidal versus control animals, using a common reference design. Microarray analysis of variance (MAANOVA) identified 52 clones as being differentially expressed (P Asunto(s)
Conducta Animal
, Perfilación de la Expresión Génica
, Trastornos Puerperales/genética
, Animales
, Animales Recién Nacidos
, Modelos Animales de Enfermedad
, Femenino
, Biblioteca de Genes
, Humanos
, Hipotálamo
, Recién Nacido
, Infanticidio
, Análisis de Secuencia por Matrices de Oligonucleótidos
, Hipófisis
, Porcinos
RESUMEN
Childbirth is a period of substantial rapid biological and psychological change and a wide range of psychotic disorders can occur ranging from mild 'baby blues' to severe episodes of psychotic illnesses. Puerperal psychosis is the most extreme form of postnatal psychosis, occurring in 1 in 1,000 births. In this study, we have used the pig as an animal model for human postnatal psychiatric illness. Our aim was to identify quantitative trait loci (QTL) associated with maternal (infanticide) sow aggression. This is defined by sows attacking and killing their own newborn offspring, within 24 hr of birth. An affected sib pair whole genome linkage analysis was carried out with 80 microsatellite markers covering the 18 porcine autosomes and the X chromosome, with the aim of identifying chromosomal regions responsible for this abnormal behavior. Analysis was carried out using the non-parametric linkage test of Whittemore and Halpern, as implemented in the Merlin software. The results identified 4 QTL mapping on Sus scrofa chromosomes 2 (SSC2), 10 (SSC10), and X (SSCX). The peak regions of these QTL are syntenic to HSA 5q14.3-15, 1q32, Xpter-Xp2.1, and Xq2.4-Xqter, respectively. Several potential candidate genes lie in these regions in addition to relevant abnormal behavioral QTL, found in humans and rodents.
Asunto(s)
Trastornos Psicóticos/genética , Trastornos Puerperales/genética , Sitios de Carácter Cuantitativo , Agresión , Animales , Conducta Animal , Mapeo Cromosómico , Modelos Animales de Enfermedad , Femenino , Trastornos Puerperales/psicología , Sus scrofaRESUMEN
Consistent, individual differences in the expression of maternal behaviour have been described in several species including the sheep. The neuroendocrine mechanisms underlying the onset of maternal behaviour in the sheep have been described, although the relationship between hormonal events and individual differences in behaviour has yet to be determined. In this study, we examined whether the individual differences in plasma estradiol, progesterone, oxytocin and cortisol concentrations were related to observed individual and breed differences in maternal behaviours in two breeds of sheep (Scottish Blackface and Suffolk) known to differ in maternal behavioural expression. Maternal estradiol concentration increased rapidly before parturition and was higher in Blackface ewes than Suffolk ewes. Plasma progesterone declined before parturition and was higher in Suffolk than Blackface ewes. Prepartum estradiol, but not progesterone, was related to individual differences in maternal grooming of the lamb. Plasma oxytocin did not differ between breeds in late gestation. There was a tendency for oxytocin to be higher in Blackface than Suffolk ewes immediately after birth. However, there were no significant relationships between prepartum or postpartum oxytocin and any maternal behaviours. Plasma cortisol was higher in Blackface than Suffolk ewes in the last days of pregnancy but rose in both breeds over the last 24 h before parturition and did not differ at delivery. Cortisol peripartum was negatively related to individual differences in maternal affiliative behaviours. These data suggest that estradiol, and potentially cortisol, may mediate individual differences in maternal behaviour in sheep.