Social stress-associated depression in adult female cynomolgus monkeys (Macaca fascicularis)

Department of Pathology (Comparative Medicine), Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1040, USA.
Biological Psychology (Impact Factor: 3.4). 05/2005; 69(1):67-84. DOI: 10.1016/j.biopsycho.2004.11.006
Source: PubMed


This paper describes a behavior pattern in adult female cynomolgus monkeys that has several behavioral and physiological characteristics in common with human depression including reduced body fat, low levels of activity, high heart rate, hypothalamic-pituitary-adrenal (HPA) axis disturbances, and increased mortality. Under certain circumstances, this depressive behavior appears more common in socially stressed subordinate, than dominant, females. This is the first animal model of social stress-related depression in females and the first primate model of adult depression. It is important to have a female animal model of depression because women are more likely to experience a clinically significant depression than men, and depression in women is often associated with changes in reproductive system function. This model is particularly useful because these monkeys have menstrual cycles that are similar to those of women, and those that exhibit depressive behavior have relatively low levels of ovarian steroids. These monkeys may be a useful model of reproductive system-associated mood disorders in females.

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    • "fascicularis) increased the incidence of sitting with head down and apparent disinterest in the environment. In a separate study, this reaction was observed in adult female M. fascicularis during the course of 12 months of individual housing (Shively et al., 2005). Camus et al. (2013, 2014) observed depressivelike behavior in adult male rhesus and cynomolgus monkeys that had been singly housed for at least 9 months, though animals of both species displayed substantial inter-individual variability in susceptibility. "
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    ABSTRACT: Social isolation is a major risk factor for the development of depressive illness; yet, no practical nonhuman primate model is available for studying processes involved in this effect. In a first study, we noted that adult male rhesus monkeys housed individually indoors occasionally exhibited a hunched, depressive-like posture. Therefore, Study 2 investigated the occurrence of a hunched posture by adult males brought from outdoor social groups to indoor individual housing. We also scored two other behaviors-lying on the substrate and day time sleeping-that convey an impression of depression. During the first week of observation following individual housing, 18 of 26 adult males exhibited the hunched posture and 21 of 26 displayed at least one depressive-like behavior. Over 2 weeks, 23 of 26 males showed depressive-like behavior during a total of only 20 min observation. Further, the behavior during the first week was positively related to the level of initial response to a maternal separation procedure experienced in infancy. In Study 3, more than half of 23 adult males of a new sample displayed depressive-like behavior during 10 min of observation each of Weeks 7-14 of individual housing. The surprisingly high frequency of depressive-like behavior in Studies 2 and 3 may have been due to recording behavior via camera with no human in the room to elicit competing responses. These results suggest that a common animal husbandry procedure might provide a practical means for examining effects of social isolation on depression-related endpoints in a nonhuman primate. The findings also suggest that trait-like differences in emotional responsiveness during separation in infancy may predict differences in responsiveness during social isolation in adulthood.
    Frontiers in Behavioral Neuroscience 09/2014; 8:309. DOI:10.3389/fnbeh.2014.00309 · 3.27 Impact Factor
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    • "Estradiol and progesterone were assayed in serum collected at necropsy (Shively et al., 2005). Characteristics of the behavior and physiology of these animals have been described in detail elsewhere (Shively et al., 2005; 2008; 2009). "
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    ABSTRACT: The anterior hippocampus is associated with emotional functioning and hippocampal volume is reduced in depression. We reported reduced neuropil volume and number of glia in the dentate gyrus (DG) and cornu ammonis (CA)1 of the anterior hippocampus in behaviorally depressed adult female cynomolgus macaques. To determine the biochemical correlates of morphometric and behavioral differences between behaviorally depressed and nondepressed adult female monkeys, glial and synaptic transcripts and protein levels were assessed in the DG, CA3 and CA1 of the anterior hippocampus. Glial fibrillary acidic protein (GFAP) was increased whereas spinophilin and postsynaptic density (PSD)-95 protein were decreased in the CA1 of depressed monkeys. GFAP was reciprocally related to spinophilin and PSD-95 protein in the CA1. Gene expression of GFAP paralleled the protein changes observed in the CA1 and was inversely related to serum estradiol levels in depressed monkeys. These results suggest that behavioral depression in female primates is accompanied by astrocytic and synaptic protein alterations in the CA1. Moreover, these findings indicate a potential role for estrogen in modulating astrocyte-mediated impairments in synaptic plasticity.
    Neuroscience Letters 01/2014; 563. DOI:10.1016/j.neulet.2014.01.012 · 2.03 Impact Factor
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    • "The slumped body posture, characteristic of depressive-like individuals [54], was observed significantly more among wild-born animals. However whilst in this posture, both populations expressed a similar amount of inactivity. "
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    ABSTRACT: Adverse early-life experience might lead to the expression of abnormal behaviours in animals and the predisposition to psychiatric disorder (e.g. major depressive disorder) in Humans. Common breeding processes employ weaning and housing conditions different from what happens in the wild. The present study, therefore, investigated whether birth origin impacts the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 captive-born and 40 wild-born socially-housed cynomolgus macaques in farming conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence and hierarchical clustering analyses. We identified 10 distinct profiles (groups A to J) that significantly differed on several behaviours, body postures, body orientations, distances between individuals and locations in the cage. Data suggest that 4 captive-born and 1 wild-born animals (groups G and J) present depressive-like symptoms, unnatural early life events thereby increasing the risk of developing pathological symptoms. General differences were also highlighted between the captive- and wild-born populations, implying the expression of differential coping mechanisms in response to the same captive environment. Birth origin thus impacts the development of atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like symptoms. The use of unbiased behavioural observations might allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups.
    PLoS ONE 07/2013; 8(7):e67711. DOI:10.1371/journal.pone.0067711 · 3.23 Impact Factor
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