Unstable Maternal Environment, Separation Anxiety, and Heightened CO2 Sensitivity Induced by Gene-by-Environment Interplay

D'Amato, Francesca R. and Zanettini, Claudio and Lampis, Valentina and Coccurello, Roberto and Pascucci, Tiziana and Ventura, Rossella and Puglisi-Allegra, Stefano and Spatola, Chiara A. M. and Pesenti-Gritti, Paola and Oddi, Diego and Moles, Anna and Battaglia, Marco (2011) Unstable Maternal Environment, Separation Anxiety, and Heightened CO2 Sensitivity Induced by Gene-by-Environment Interplay. PLoS ONE, 6 (4). e18637. ISSN 1932-6203

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Background: In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO2 hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO2 through genetic control of sensitivity to the environment. Methodology: Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were crossfostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O2), CO2-enriched air (6% CO2), hypoxic air (10%O2), and avoidance of CO2-enriched environments. Results: Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO2-enriched air and heightened aversion towards CO2- enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO2 was present at 16–20, and 75–90 postnatal days, implying the trait’s stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO2 breathing was significantly higher (Bartlett x = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO2 increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals. Conclusions: A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO2 sensitivity and anxiety. Some non

Item Type: Article
Subjects: 500 Scienze naturali e Matematica
500 Scienze naturali e Matematica > 570 Scienze della vita; Biologia
Depositing User: PhD Roberto Coccurello
Date Deposited: 19 Dec 2016 13:53
Last Modified: 19 Dec 2016 13:53
URI: http://eprints.bice.rm.cnr.it/id/eprint/15484

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