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Early life stress (ELS) is a risk factor for anxiety, mood disorders and alterations in stress responses. Less is known about the long-term neurobiological impact of ELS. We used [(18)F]-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) to assess neural responses to a moderate stress test in adult monkeys that experienced ELS as infants. Both groups of monkeys showed hypothalamic-pituitary-adrenal (HPA) axis stress-induced activations and cardiac arousal in response to the stressor. A whole brain analysis detected significantly greater regional cerebral glucose metabolism (rCGM) in superior temporal sulcus, putamen, thalamus, and inferotemporal cortex of ELS animals compared to controls. Region of interest (ROI) analyses performed in areas identified as vulnerable to ELS showed greater activity in the orbitofrontal cortex of ELS compared to control monkeys, but greater hippocampal activity in the control compared to ELS monkeys. Together, these results suggest hyperactivity in emotional and sensory processing regions of adult monkeys with ELS, and greater activity in stress-regulatory areas in the controls. Despite these neural responses, no group differences were detected in neuroendocrine, autonomic or behavioral responses, except for a trend towards increased stillness in the ELS monkeys. Together, these data suggest hypervigilance in the ELS monkeys in the absence of immediate danger., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Non-human primates have been used to model psychiatric disease for several decades. The success of this paradigm has issued from comparable cognitive skills, brain morphology, and social complexity in adult monkeys and humans. Recently, interest in biological psychiatry has focused on similar brain, social, and emotional developmental processes in monkeys. In part, this is related to evidence that early postnatal experiences in human development may have profound implications for subsequent mental health. Non-human primate studies of postnatal phenomenon have generally fallen into three basic categories: experiential manipulation (largely manipulations of rearing), pharmacological manipulation (eg drug-induced psychosis), and anatomical localization (defined by strategic surgical damage). Although these efforts have been very informative each of them has certain limitations. In this review we highlight general findings from the non-human primate postnatal developmental literature and their implications for primate models in psychiatry. We argue that primates are uniquely capable of uncovering interactions between genes, environmental challenges, and development resulting in altered risk for psychopathology.

Individuals with anxiety disorders often do not respond to safety signals and hence continue to be afraid and anxious. Consequently, it is important to develop paradigms in animals that can directly study brain systems involved in learning about, and responding to, safety signals. We previously developed a discrimination procedure in rats of the form AX+/BX-, where cues A and X presented together are paired with an aversive stimulus and cues B and X presented together predict the absence of an aversive stimulus. The present experiment adapted this procedure to the fear-potentiated startle paradigm in rhesus monkeys.

In experiment 1, we assessed the role of the primate amygdala and hippocampus in the acquisition of learned fear measured with fear-potentiated startle. Three groups of six rhesus monkeys were prepared with bilateral ibotenic acid lesions of the amygdaloid complex and the hippocampus or were sham operated. Selective ibotenic acid lesions of the amygdala, but not the hippocampus, blocked the acquisition of fear-potentiated startle. In experiment 2, we assessed the role of the primate amygdala in the expression of fear-potentiated startle. Surprisingly, animals that sustained amygdala damage after they successfully learned fear-potentiated startle expressed normal fear-potentiated startle, despite a complete amygdala lesion based on magnetic resonance imaging assessments. These results suggest that although the amygdala is necessary for the initial acquisition of fear-potentiated startle, it is not necessary for the retention and expression of fear-potentiated startle. These findings are discussed in relation to the role of the amygdala in emotional learning and in cross-species comparisons of emotional behavior.

Communication is essential to members of a society not only for the expression of personal information, but also for the protection from environmental threats. Highly social mammals have a distinct characteristic: when conspecific animals are together, they show a better recovery from experiences of distress. This phenomenon, termed 'social buffering', has been found in rodents, birds, non-human primates and also in humans. This paper reviews classical findings on social buffering and focuses, in particular, on social buffering effects in relation to neuroendocrine stress responses. The social cues that transmit social buffering signals, the neural mechanisms of social buffering and a partner's efficacy with respect to social buffering are also detailed. Social contact appears to have a very positive influence on the psychological and the physiological aspects of social animals, including human beings. Research leading towards further understanding of the mechanisms of social buffering could provide alternative medical treatments based on the natural, individual characteristics of social animals, which could improve the quality of life.

Mother-reared (MR) and nursery-reared (NR) male rhesus monkeys exhibit profound and persistent differences in social and emotional behavior. Compared to MR animals, NR monkeys show reduced reciprocal social behaviors and increased agonistic behavior and high levels of stereotypy. Cerebrospinal fluid oxytocin (CSF OT) in NR monkeys was significantly reduced compared to MR monkeys measured at 18, 24, and 36 months of age. Correlations between OT and individual social behavioral profiles measured across rearing conditions also revealed a significant association between OT and the expression of affiliative social behaviors including allogrooming and reciprocal intermale mounting at each age examined. In contrast, CSF vasopressin levels did not differ according to rearing history, but did correlate with fearful behaviors independent of rearing history. Differential rearing was not associated with differences in basal or stress-related plasma cortisol, although these levels did progressively decline as monkeys matured. MR but not NR monkeys were able to use a social companion to buffer their response to a stressor, but OT levels did not appear to be sensitive to the presence of a social companion in either group. These results are consistent with earlier reports from studies of rodents suggesting an important role for central OT pathways in the development of social affiliation.

Monogamous social organization is characterized by selective affiliation with a partner, high levels of paternal behaviour and, in many species, intense aggression towards strangers for defence of territory, nest and mate. Although much has been written about the evolutionary causes of monogamy, little is known about the proximate mechanisms for pair bonding in monogamous mammals. The prairie vole, Microtus ochrogaster, is a monogamous, biparental rodent which exhibits long-term pair bonds characterized by selective affiliation (partner preference) and aggression. Here we describe the rapid development of both selective aggression and partner preferences following mating in the male of this species. We hypothesized that either arginine-vasopressin (AVP) or oxytocin (OT), two nine-amino-acid neuropeptides with diverse forebrain projections, could mediate the development of selective aggression and affiliation. This hypothesis was based on the following observations: (1) monogamous and polygamous voles differ specifically in the distribution of forebrain AVP and OT receptors; (2) AVP innervation in the prairie vole brain is sexually dimorphic and important for paternal behaviour; (3) central AVP pathways have been previously implicated in territorial displays and social memory; and (4) central OT pathways have been previously implicated in affiliative behaviours. We now demonstrate that central AVP is both necessary and sufficient for selective aggression and partner preference formation, two critical features of pair bonding in the monogamous prairie vole.