| 1. |
- Baker, Maggie, et al.
(författare)
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Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 114:44, s. 11769-11774
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Tidskriftsartikel (refereegranskat)abstract
- Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to deter mine whether a gain-of-function nonsynonymous OXTR SNP inter acted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavior al differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.
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| 2. |
- Schwandt, Melanie L., et al.
(författare)
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Gene-Environment Interactions and Response to Social Intrusion in Male and Female Rhesus Macaques
- 2010
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 67:4, s. 323-330
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic factors interact with environmental stressors to moderate risk for human psychopathology, but sex may also be an important mediating factor. Different strategies for coping with environmental stressors have evolved in males and females, and these differences may underlie the differential prevalence of certain types of psychopathology in the two sexes. In this study, we investigated the possibility of sex-specific gene-environment interactions in a nonhuman primate model of response to social threat. Methods: Rhesus macaques (77 males and 106 females) were exposed to an unfamiliar conspecific. Using factor analysis, we identified three behavioral factors characterizing the response to social threat. Monkeys were genotyped for the serotonin transporter-linked polymorphism (5-HTTLPR), and the effects of genotype, early life stress, and sex on behavioral responses were evaluated. Results: Factor analysis produced five factors: High-Risk Aggression, Impulsivity/Novelty-Seeking, Gregariousness/Boldness, Harm Avoidance, and Redirected Aggression. Overall, males displayed higher levels of High-Risk Aggression and Gregariousness/Boldness than females. Levels of High-Risk Aggression in males carrying the s allele were significantly higher if they were also exposed to early adversity in the form of peer rearing. Conclusions: Our findings support those from studies in humans suggesting that males are more vulnerable to externalizing or aggression-related disorders. The results highlight the importance of interactions that exist among behavior, genes, and the environment and suggest that sex differences in vulnerability to psychopathology may be grounded in our evolutionary history.
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| 3. |
- Fahlke, Claudia, 1964, et al.
(författare)
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Platelet monoamine oxidase activity in a nonhuman primate model of type 2 excessive alcohol consumption
- 2002
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 159, s. 2107-2109
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Low platelet monoamine oxidase (MAO) activity is associated with "type 2 alcoholism." MAO activity is also affected by cigarette smoking. Since most alcoholics are smokers, it is difficult to evaluate the possible effect of platelet MAO activity on alcoholism independently of the effects of smoking, The authors investigated the relationship between platelet MAO activity and excessive alcohol consumption in rhesus macaques. Method: Platelet MAO activity and CSF metabolite concentrations were measured. The authors also investigated level of voluntary alcohol intake and social dominance rank. Results: Subjects with low platelet MAO activity consumed alcohol to excess, had low CSF 5-hydroxyindoleacetic acid concentrations, and were less competent socially. Conclusions: These findings show that nonhuman primates that exhibit type 2-like alcohol features display low platelet MAO activity and support the notion that platelet MAO activity is a biologic marker for central serotonergic activity. The results also challenge the hypothesis that low platelet MAO activity in type 2 alcoholism is simply an artifact of smoking.
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| 4. |
- Fahlke, Claudia, 1964, et al.
(författare)
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Rearing experiences and stress-induced plasma cortisol as early risk factors for excessive alcohol consumption in nonhuman primates
- 2000
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Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 24, s. 644-650
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this study was to assess the impact of early rearing and stress-induced rise of plasma cortisol collected during infancy as a biological predictors of adult alcohol consumption in nonhuman primates. Methods: Ninety-seven female and male rhesus macaques (Macaca mulatta) were investigated. They were reared for their first 6 months of life either without mothers or other adults but with constant access to same-aged peers (peer-reared), or as controls with their mothers (mother-reared). When subjects reached 6 months of age, they underwent a series of four sequential weeks of 4-day social separations. Blood was drawn 1 and 2 hr after initiation of the 4-day separation periods, and the plasma was assayed for plasma cortisol concentrations. When the subjects were young adults (approximately 50 months of age), they were tested for voluntary intake of alcohol for 1 hr per day, 4 days a week, during a period of 5 to 7 weeks under normal living conditions. Results: The social separation challenge increased infant plasma cortisol concentrations, with peerreared subjects exhibiting higher stress-induced cortisol concentrations than mother-reared animals. Subjects that responded to the social separation challenge with high cortisol levels consumed significantly more alcohol per kilogram of body weight as adults than subjects with a low cortisol response to the separation challenge, regardless of rearing condition. In addition, male and peer-reared subjects consumed significantly more alcohol than female and mother-reared subjects, respectively. Conclusions: These findings suggest that early rearing experiences, such as! adult absence, and high plasma cortisol concentrations early in life after a social separation stressor, are useful psychobiological predictors of future high alcohol consumption among nonhuman primates.
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| 5. |
- Simpson, Elizabeth A, et al.
(författare)
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Comments: Animal studies help clarify misunderstandings about neonatal imitation (vol. 40, articelID e400, 2017)
- 2017
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Ingår i: Behavioral and Brain Sciences. - : Cambridge University Press. - 0140-525X .- 1469-1825. ; 40
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Empirical studies are incompatible with the proposal that neonatal imitation is arousal driven or declining with age. Nonhuman primate studies reveal a functioning brain mirror system from birth, developmental continuity in imitation and later sociability, and the malleability of neonatal imitation, shaped by the early environment. A narrow focus on arousal effects and reflexes may grossly underestimate neonatal capacities.
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| 6. |
- Wargelius, Hanna-Linn, et al.
(författare)
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Platelet monoamine oxidase activity predicts alcohol sensitivity and voluntary alcohol intake in rhesus monkeys.
- 2010
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Ingår i: Upsala journal of medical sciences. - : Uppsala Medical Society. - 2000-1967 .- 0300-9734. ; 115:1, s. 49-55
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Tidskriftsartikel (refereegranskat)abstract
- Platelet monoamine oxidase B (MAO-B) has been proposed to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores on personality traits such as sensation seeking, monotony avoidance, and impulsiveness, as well as for vulnerability for alcoholism. In the present study, platelet MAO-B activity was analysed in 78 rhesus macaques, and its relation to voluntary alcohol intake and behaviours after intravenous alcohol administration was observed. Monkeys with low platelet MAO-B activity had low levels of 5-hydroxyindole acetic acid in cerebrospinal fluid and showed excessive aggression after alcohol administration. A novel finding was that animals with low platelet MAO-B activity showed less intoxication following alcohol administration. As we have shown previously, they also voluntarily consumed more alcohol. We here replicate results from studies on both humans and non-human primates, showing the utility of platelet MAO as a marker for risk behaviours and alcohol abuse. Furthermore, we link platelet MAO activity to alcohol sensitivity.
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