Signs of mood and anxiety disorders in chimpanzees.

BACKGROUND: In humans, traumatic experiences are sometimes followed by psychiatric disorders. In chimpanzees, studies have demonstrated an association between traumatic events and the emergence of behavioral disturbances resembling posttraumatic stress disorder (PTSD) and depression. We addressed the following central question: Do chimpanzees develop posttraumatic symptoms, in the form of abnormal behaviors, which cluster into syndromes similar to those described in human mood and anxiety disorders? METHODOLOGY/PRINCIPAL FINDINGS: In phase 1 of this study, we accessed case reports of chimpanzees who had been reportedly subjected to traumatic events, such as maternal separation, social isolation, experimentation, or similar experiences. We applied and tested DSM-IV criteria for PTSD and major depression to published case reports of 20 chimpanzees identified through PrimateLit. Additionally, using the DSM-IV criteria and ethograms as guides, we developed behaviorally anchored alternative criteria that were applied to the case reports. A small number of chimpanzees in the case studies met DSM-IV criteria for PTSD and depression. Measures of inter-rater reliability, including Fleiss' kappa and percentage agreement, were higher with use of the alternative criteria for PTSD and depression. In phase 2, the alternative criteria were applied to chimpanzees living in wild sites in Africa (n = 196) and chimpanzees living in sanctuaries with prior histories of experimentation, orphanage, illegal seizure, or violent human conflict (n = 168). In phase 2, 58% of chimpanzees living in sanctuaries met the set of alternative criteria for depression, compared with 3% of chimpanzees in the wild (p = 0.04), and 44% of chimpanzees in sanctuaries met the set of alternative criteria for PTSD, compared with 0.5% of chimpanzees in the wild (p = 0.04). CONCLUSIONS/SIGNIFICANCE: Chimpanzees display behavioral clusters similar to PTSD and depression in their key diagnostic criteria, underscoring the importance of ethical considerations regarding the use of chimpanzees in experimentation and other captive settings.

Response to LPS in female offspring from sows treated with cortisol during pregnancy.

Prenatal stress has been shown to program responsiveness of the hypothalamus-pituitary-adrenal axis (HPA-axis) and behavior in offspring. In pig husbandry, sows are exposed to stressful conditions during gestation. Previously, cortisol treatment of pregnant sows has been shown to alter stress responsiveness and immunological parameters in their piglets. In the present study, we explored whether cortisol treatment of pregnant sows affects the offspring's response to an inflammatory stimulus. Sows were treated orally with cortisol either during the first, second, or third period of gestation, or received a placebo during this period. At 8 weeks of age, female offspring were injected intravenously with lipopolysaccharide (LPS). Offspring of sows that received cortisol during the first and third period of gestation showed a higher fever response to LPS. Cortisol treatment of sows during gestation did not affect offspring's response to LPS with regard to their cortisol response. LPS-induced sickness behavior, which was measured as the latency time in a human approach test, appeared to recover more quickly in offspring from sows that received cortisol during the second period of gestation. These results suggest that prenatal cortisol exposure programs responsiveness to inflammatory stimuli in female piglets.

Cortisol administration to pregnant sows affects novelty-induced locomotion, aggressive behaviour, and blunts gender differences in their offspring.

Several behavioural effects of prenatal stress are reported in literature, and these seem to depend, among other factors, on the gender studied and the period of gestation in which prenatal stress is applied. In the present study, oral administration of hydrocortisone-acetate (HCA) to 41 pregnant sows was used as a model for prenatal stress, since corticosteroids are considered a key mediator in the effects of prenatal stress. HCA was orally administered to pregnant sows during three periods of gestation: 21-50 (period 1, P1, n = 10), 51-80 (period 2, P2, n = 10) and 81-110 (period 3, P3, n = 10) days after insemination (term 115 days). Control sows (n = 11) received vehicle from 21 to 110 days after insemination. Between days 9 and 48 after birth, treatment effects on male and female piglet behaviour were determined in the home pen and in four different behavioural tests. During the backtest, no gender differences were observed in vocalisations in HCA-piglets, while control males vocalised more than control females. In the home pen at 14 days of age, HCA-piglets spent less time in social interactions than control piglets. During the novel environment test, P1- and P3-piglets walked more than control piglets, but this was not observed during the novel object test, four days later. At weaning, P2- and P3-piglets performed less individual play. Prior to mixing with an unfamiliar piglet (male piglets only), HCA-piglets had lower salivary cortisol concentrations than control piglets, but no difference was observed after mixing. P1-, P2-, and P3- piglets had fewer non-aggressive encounters, and P2-piglets continued fighting longer than control piglets. The present study demonstrates that elevated maternal cortisol concentrations during gestation affect piglet behaviour, and effects do differ between male and female piglets. In addition, effects depend on the period of cortisol administration.

Lower birth weight and attenuated adrenocortical response to ACTH in offspring from sows that orally received cortisol during gestation.

Prenatal stress is known to affect several offspring characteristics, but its effects depend among other factors on the period of gestation in which it is applied. In the present study, oral administration of hydrocortisone-acetate (HCA) was used to elevate cortisol concentrations in pregnant sows to levels also observed after psychological stress. HCA was administered during three different periods of gestation (115 days in pigs): period 1: 21-50 (P1, n = 10), period 2: 51-80 (P2, n = 10) and period 3: 81-110 (P3, n = 10) days after insemination. Control sows (n = 11) received vehicle from 21-110 days after insemination. When P1-, P2- and P3-sows did not receive HCA, they also received vehicle. During gestation, weekly saliva samples were taken from the sows to determine salivary cortisol concentrations. Treatment effects on sow, litter and piglet characteristics were determined. In addition, two female piglets per litter were subjected to an ACTH-challenge test at 6 weeks of age to determine the adrenocortical response to ACTH. Pigs were slaughtered at 6 months of age and slaughter weight, back fat thickness and percentage of lean meat were analysed. During the period of treatment with HCA, salivary cortisol concentrations were increased in P1-, P2- and P3-sows compared to control sows (P < 0.01). The total number of piglets born per litter did not differ among treatment groups (P > 0.30), but pooled HCA-litters had a higher percentage of live born piglets (P < 0.05) and fewer mummies than control litters (P < 0.05). Gestation length did not differ among treatment groups (P = 0.21), but did affect treatment effects on birth weight. Overall, HCA-piglets weighed less at birth, and remained lighter until weaning (P < 0.05). The salivary cortisol concentrations after i.m. injection of ACTH (2.5 IU/kg) were lower in P1- and P3-piglets compared to control piglets. At slaughter, HCA-treatment indirectly decreased lean meat percentage and increased back fat thickness. In conclusion, elevated peripheral cortisol concentrations in pregnant sows affect both litter characteristics and piglet physiology, the latter depending on the period of gestation during which concentrations were elevated. Underlying mechanisms require further investigation.

Evaluation of oral administration of cortisol as a model for prenatal stress in pregnant sows.

OBJECTIVE: To design a treatment that increases plasma corticosteroid concentrations to mimic prenatal stress in pregnant sows. ANIMALS: 24 pregnant sows. PROCEDURE: Sows were assigned to 1 of 4 treatment groups; treatment consisted of twice-daily oral administration of a placebo or 20, 60, or 180 mg of hydrocortisone acetate (HCA)/sow from 7 to 11 weeks of gestation. Blood and saliva samples for determination of cortisol concentrations were obtained hourly on treatment days 3 and 25 and twice weekly for the remainder of the treatment period. The WBC, neutrophil, and lymphocyte counts and concentrations of interleukin (IL)-2 and IL-4 were determined on 4 days during treatment. Litter characteristics were recorded. RESULTS: Plasma and salivary cortisol concentrations were significantly increased in sows that received 60 or 180 mg of HCA (0.30 to 0.37 mg/kg and 0.95 to 1.15 mg/kg, respectively), compared with control sows. Except for the second day of treatment, the number of WBCs and the IL-2:IL-4 ratio did not differ among treatment groups. The neutrophil-to-lymphocyte ratio was significantly higher in sows that received 180 mg of HCA. Gestation duration was significantly shorter in sows that received 180 mg of HCA. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of 60 mg of HCA is suitable to increase plasma and salivary cortisol concentrations in pregnant sows in a controlled manner to concentrations comparable to concentrations detected after psychologic stressors. This model seems to be suitable to study the effects of increased maternal corticosteroid concentrations on young pig behavior, physiologic variables, and development.