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Introduction Food insecurity is a major global contributor to developmental origins of adult disease. The allostatic load of maternal food uncertainty from variable foraging demand (VFD) activates corticotropin-releasing factor (CRF) without eliciting hypothalamic-pituitary-adrenal (HPA) activation measured on a group level. Individual homeostatic adaptations of the HPA axis may subserve second-order homeostasis, a process we provisionally term “social allostasis.” We postulate that maternal food insecurity induces a “superorganism” state through coordination of individual HPA axis response. Methods Twenty-four socially-housed bonnet macaque maternal-infant dyads were exposed to 16 weeks of alternating two-week epochs of low or high foraging demand shown to compromise normative maternal-infant rearing. Cerebrospinal fluid (CSF) CRF concentrations and plasma cortisol were measured pre- and post-VFD. Dyadic distance was measured, and blinded observers performed pre-VFD social ranking assessments. Results Despite marked individual cortisol responses (mean change = 20%) there was an absence of maternal HPA axis group mean response to VFD (0%). Whereas individual CSF CRF concentrations change = 56%, group mean did increase 25% (p = 0.002). Our "dyadic vulnerability" index (low infant weight, low maternal weight, subordinate maternal social status and reduced dyadic distance) predicted maternal cortisol decreases (p < 0.0001) whereas relatively “advantaged” dyads exhibited maternal cortisol increases in response to VFD exposure. Comment In response to a chronic stressor, relative dyadic vulnerability plays a significant role in determining the directionality and magnitude of individual maternal HPA axis responses in the service of maintaining a “superorganism” version of HPA axis homeostasis, provisionally termed “social allostasis.”

Recent studies have indicated a gene by environment interaction between serotonin transporter gene (5-HTTLPR) polymorphism and childhood abuse on depressive symptoms. In addition, persistent elevation of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentrations following early-life adversity has been posited to underlie the subsequent development of major depression. This pilot study tested the hypothesis that elevations of juvenile CSF CRF concentrations are, in part, determined by an interaction between polymorphisms of the 5-HTTLPR and early-life stress. Nine juvenile male bonnet macaques (Macaca radiata) had been raised under variable foraging demand (VFD) conditions, a nonhuman primate model of early-life stress, whereas nine subjects were normatively raised under LFD (low foraging demand) conditions. Genotyping revealed that four (44.4%) of the VFD-reared monkeys possessed at least one “s” allele whereas five VFD monkeys were of the l/l genotype. Of the nine LFD subjects, two (22%) had the s/l genotype and seven had the l/l genotype. A “juvenile” CSF sample was obtained at approximately three years of age. CSF CRF concentrations were elevated specifically in the VFD “s/s” and “s/l” allele group in comparison to each of the remaining three groups, indicating a gene by environment (GxE) interaction.

Background: Nonhuman primates have served as models for human cardiovascular (CV) and metabolic diseases. Recently, echocardiographic measurement of epicardial adipose tissue (EAT) thickness has been shown to be a reliable marker of visceral adiposity, and greater EAT is associated with increased CV risk, left ventricular (LV) hypertrophy, and metabolic syndrome. The objective of the present study was to determine EAT thickness in apparently healthy bonnet macaques and assess its relations with anthropometric and CV variables. Methods: Echocardiography was performed on 61 monkeys (41 females and 20 males, mean age 13.0 ± 4.7 years). EAT was measured on the right ventricular free wall in parasternal windows. Applanation tonometry was performed in 25 unselected monkeys using a SphygmoCor pulse wave system. Results: The mean EAT thickness was 2.4 ± 0.6 mm. EAT thickness was directly correlated with age (r = 0.26, P = 0.04), male gender (r = 0.47, P < 0.01), weight (r = 0.42, P < 0.01), crown–rump length (r = 0.45, P < 0.01), BMI (r = 0.38, P < 0.01), diastolic BP (r = 0.46, P = 0.01), and HR (r =−0.49, P < 0.01). EAT thickness also correlated with augmentation index (r = 0.42, P = 0.04), LV mass (r = 0.48, P < 0.01), and left atrial (LA) diameter (r = 0.26, P = 0.04). Intra- and interobserver coefficients of variation between measurements of EAT were 1.4% and 3.7%. On multivariate analysis adjusting for age, gender, weight, and CRL, EAT was independently related to age and weight (r2= 0.47, P < 0.01). Conclusion: This study found echocardiography to be a feasible and practical method to evaluate EAT in nonhuman primates. In bonnet macaques, EAT thickness correlates with LV and LA dimensions and augmentation index, and is independently related to age and weight. (ECHOCARDIOGRAPHY 2010;27:180-185)

Stress is a risk factor for chronic illnesses such as obesity, type 2 diabetes, and hypertension and has been postulated to cause the metabolic syndrome via perturbation of the hypothalamo-pituitary-adrenal (HPA) axis. In our model of early-life stress (variable foraging demand [VFD]), food insecurity is imposed on monkey mothers for 16 weeks beginning when their nursing offspring are 3–5 months of age. Under VFD, food availability is never restricted, and the infant's growth is unaffected. VFD rearing does, however, cause a range of neurobiological abnormalities, including dysregulation of the HPA axis, manifested in abnormal cerebrospinal fluid cortisol and corticotropin-releasing factor levels. We previously reported spontaneous occurrence of metabolic syndrome in 14% of normally reared peripubertal bonnet macaques given ad libitum access to standard monkey chow. Here, we show that compared with normally reared monkeys, peripubertal VFD juveniles exhibit greater weight, BMI, abdominal circumference, and glucagon-like peptide-1 and decreased glucose disposal rates during hyperinsulinemic-euglycemic clamps. Our data suggest that early-life stress during a critical period of neuro development can result in the peripubertal emergence of obesity and insulin resistance.

Two experiments were conducted to examine the effectiveness of presenting brief video of conspecifics to socially housed bonnet macaques as a reward for performing a joystick task. Using a joystick, subjects tracked a moving target with the cursor on a computer monitor. In Exp. 1, subjects completed significantly more joystick trials for food reward than for video reward or no reward. Subjects also preferred viewing video of another group (Other Group Video) to receiving no reward or to viewing video of their own group (Own Group Video). In Exp. 2, subjects were given two reward conditions, video of a familiar social group or video of a new social group. Two monkeys contributed the vast majority of trials, and both responded more frequently when the reward was video of the new social group. Results of these two experiments suggest that viewing video of conspecifics may serve as an effective reward for at least some socially housed primates and suggests that novelty of the individuals depicted in the video is an important factor contributing to the reward value of video.

The two neuropeptides corticotropin-releasing-factor (CRF) and oxytocin (OT) may produce opposing behavioral effects — elevations of the former have been associated with anxiety and social vigilance and reductions of the latter with reduced social affiliation. We sought to test the hypothesis that, within the primate macaque genus, the more gregarious, affiliative, and affectively stable bonnet species ( Macaca radiata ) would exhibit lower cerebrospinal fluid (CSF) CRF and higher CSF OT concentrations in comparison to its close relative, the temperamentally volatile and socially distant pigtail ( Macaca nemestrina ). Cisternal CSF samples were obtained from young adult male and female pigtail and bonnet macaques, and CRF and OT concentrations were measured by radioimmunoassay. Pigtail macaques exhibited significantly higher concentrations of CSF CRF and significant lower concentrations of CSF OT than bonnet macaques. Results were not attributable to age or sex differences in group composition. When included together in a multiple regression, CRF and OT showed a multiple R of 0.76, accounting for more than half of the species variance. Although species differences in the bioeffectiveness of these peptides may possibly confound the observed biobehavioral relationships, in the absence of any existing data to that effect, the current findings appear in accordance with the hypothesis and consistent with previously reported species–typical behaviors observed in these macaques.

Exposure of primate infants to adverse rearing conditions during the first half year of life can result in enduring behavioral, neuroendocrine, and immunologic abnormalities. However, the effects of differential rearing on cytokines, some of which can regulate immune and inflammatory responses and modulate activity of the central nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, are largely unexamined. The present study explored the relationship between circulating levels of transforming growth factor-beta 1 (TGF-beta 1) and cortisol in macaques reared either normally or under conditions of variable foraging demand (VFD). Under VFD rearing, for a period of 4 months, the infants' mothers intermittently had to expend more time and effort to obtain food than did the mothers of normally reared control subjects. Two years after cessation of the rearing experience, exposure to a moderate stressor (confinement in an unfamiliar room for 90 min) induced elevated levels of serum TGF-beta 1 and plasma cortisol in VFD-reared monkeys compared to normally reared controls. The correlation between TGF-beta 1 and cortisol levels was substantially higher in the normally reared subjects. Examination of the relationship between HPA axis and immune function will improve our understanding of the pathophysiological consequences of adverse rearing.

Adolescent bonnet macaques nursed as infants by mothers facing unpredictable requirements for food procurement (variable foraging demand, VFD) display persistent neurobiological disturbances. This study examined the long-term neurochemical and behavioral effects of adverse rearing initiated later in infancy than in previous cohorts of subjects to test the hypothesis that the timing of an early adverse experience would influence patterns of biobehavioral outcome. Cisternal cerebrospinal fluid (CSF) monoamine and corticotropin-releasing factor (CRF) concentrations were obtained from 20 bonnet macaques (11 VFD-reared and 9 normally reared controls) approximately 2 years after the end of differential rearing. VFD-reared primates displayed on multiple samplings significantly lower CSF CRF concentrations and higher CSF 5-hydroxyindoleacetic acid (5-HIAA) concentration compared to controls. In the VFD-reared, significant inverse correlations between CRF and all three monoamines were found (5-HIAA, 3-methoxy-4-hydroxyphenethyleneglycol and homovanillic acid), most prominently for 5-HIAA. In controls, but not VFD-reared subjects, CSF CRF was positively correlated with changes in "gregariousness" upon presentation of a fear stimulus. VFD-reared subjects displayed greater baseline hierarchical engagement than controls. In contrast to prior findings, in which rearing under VFD conditions at an earlier age led to increased CSF CRF compared with controls, CSF CRF was lower after later exposure to VFD rearing than in controls. Thus, the timing of exposure to VFD conditions early in life evidently determines whether CSF CRF was found to be elevated or decreased, within the context of increased serotonin metabolism, during the course of primate maturation.

Background: The authors previously reported elevated cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentrations in juvenile primates nursed by mothers undergoing experimentally imposed unpredictable foraging conditions in comparison to normally reared controls. The purpose of the present study was to determine if these changes would endure into young adulthood. Methods: Cisternal CSF samples were obtained from those unpredictably reared young adult primates who had been previously studied as juveniles and age-matched ad libitum normally reared controls. Samples were assayed for CSF CRF. Results: Concentrations of CSF CRF were significantly elevated in the unpredictably reared sample in comparison to the ad libitum-reared control group. A significant positive correlation was noted between juvenile and young adult CSF CRF values within the unpredictably reared cohort. Conclusions: Disturbances of maternal-infant attachment processes have an enduring impact on primate CRF function into young adulthood. The CRF elevations following unpredictable maternal foraging conditions appear traitlike in nature.

When primate infants are reared during the first half-year of life in an environment in which their mothers face uncertain requirements for food procurement (variable foraging demand [VFD]), long-lasting behavioral and neurodevelopmental consequences ensue, including increases in timidity and social subordinance as well as alterations in stress-related neuroendocrine profiles. We examined the nature and persistence of the effects of VFD rearing by exposing VFD-reared and normally reared adolescent bonnet macaques to a mild fear-provoking stimulus 2 years after the end of differential rearing. VFD-reared subjects at baseline were less gregarious than normally reared monkeys. VFDs also were considerably less responsive to the fear stimulus, and their behavior and affect returned to baseline levels more quickly than normally reared subjects. The extent and persistence of the sequelae of VFD rearing suggest parallels with predisposing factors in human anxiety disorders. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 39: 40–45, 2001

There is increasing evidence for an important role of adverse early experience on the development of major psychiatric disorders in adulthood. Corticotropin-releasing factor (CRF), an endogenous neuropeptide, is the primary physiological regulator of the mammalian stress response. Grown nonhuman primates who were exposed as infants to adverse early rearing conditions were studied to determine if long-term alterations of CRF neuronal systems had occurred following the early stressor. In comparison to monkeys reared by mothers foraging under predictable conditions, infant monkeys raised by mothers foraging under unpredictable conditions exhibited persistently elevated cerebrospinal fluid (CSF) concentrations of CRF. Because hyperactivity of CRF-releasing neurons has been implicated in the pathophysiology of certain human affective and anxiety disorders, the present finding provides a potential neurobiological mechanism by which early-life stressors may contribute to adult psychopathology.

OBJECTIVE The authors determined the effects of antipanic treatment with fluoxetine on human growth hormone (GH) response to the alpha 2 agonist clonidine. METHOD Seventeen patients with panic disorder and 15 healthy volunteers were challenged with clonidine. Thirteen of the patients and 12 of the volunteers were given a second challenge with clonidine 12 weeks later. The patients received open fluoxetine and the healthy subjects received no treatment between challenges. Subjects with high baseline human GH levels (greater than 2 ng/ml) at the first and second challenges were excluded from further analysis. RESULTS The patients with panic disorder (N = 13 for the first challenge and N = 9 for the second) had significantly lower human GH responses to clonidine than the healthy subjects (N = 14 during the first challenge and N = 9 for the second) during both challenges, despite clinical improvement in eight of the nine patients at the time of the second challenge. CONCLUSIONS Blunted secretion of human GH in response to clonidine in patients with panic disorder persists despite clinical recovery.

A microchip that provided a unique identification number was injected into each forearm of all 8 members of a bonnet macaque (Macaca radiata) social group. The group was then given computer-controlled joystick tasks of increasing difficulty. The identification number of the arm used on each trial was input into the computer and used to determine individual performance and hand preference in more than 23,000 trials. Three subjects reversed hand preference as task difficulty was increased over time. All subjects exhibited nearly exclusive use of a single hand on the most difficult task; 6 used the right hand, and 2 used the left. Daily patterns of joystick activity for the group members differed somewhat from that of our individually housed monkeys.

Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) may be effective in treating depression. Parental verbal abuse has been linked to decreased fractional anisotropy (FA) of white matter and reduced FA correlated with depression and anxiety scores. Utilizing a nonhuman primate model of mood and anxiety disorders following disrupted mother-infant attachment, we examined whether adverse rearing conditions lead to white matter impairment of the ALIC. We examined white matter integrity using Diffusion Tensor Imaging (DTI) on a 3T-MRI. Twenty-one adult male Bonnet macaques participated in this study: 12 were reared under adverse [variable foraging demand (VFD)] conditions whereas 9 were reared under normative conditions. We examined ALIC, posterior limb of the internal capsule (PLIC) and occipital white matter. VFD rearing was associated with significant reductions in FA in the ALIC with no changes evident in the PLIC or occipital cortex white matter. Adverse rearing in monkeys persistently impaired frontal white matter tract integrity, a novel substrate for understanding affective susceptibility.

Nonhuman primates are commonly used in cardiovascular research. Increased arterial stiffness is a marker of subclinical atherosclerosis and higher CV risk. We determined the augmentation index (AI) using applanation tonometry in 61 healthy monkeys (59% female, age 1–25 years). Technically adequate studies were obtained in all subjects and required1.5±1.3minutes. The brachial artery provided the highest yield (95%). AI was correlated with heart rate (HR) (r=−0.65, P<.001), crown rump length (CRL) (r= 0.42,P= .001), and left ventricular (LV) mass determined using echocardiography (r=0.52, P<.001). On multivariate analysis, HR (P<.001) and CRL (P= .005) were independent predictors of AI (R2=0.46, P<.001). Body Mass Index (BMI) and AI were independent predictors of higher LV mass on multivariate analysis (P<.001andP=.03). In conclusion, applanation tonometry is feasible for determining AI. Reference values are provided for AI in bonnet macaques, in whom higher AI is related to HR and CRL, and in turn contributes to higher LV mass.

Macaques are used in cardiovascular and metabolic research. We determined echocardiographic-derived reference values of left ventricular (LV) systolic and diastolic function in healthy adult bonnet macaques (Macaca radiata).Transthoracic echocardiography was performed during ketamine sedation in 83 (67% female) healthy monkeys (age 7-26 years).Technically adequate studies were obtained in all subjects and required 10.1 +/- 1.3 min of scanning time. Age correlated inversely with the following Doppler indices: E (r = -0.44, p0.001), E/A (r = -0.26, p = 0.02), E' (r = -0.45, p0.001, E'/A' (r = -0.44, p0.001), E/E' (r -0.25, p = 0.03), S' (r = -0.33, p = 0.003), Vp (r = -0.26, p = 0.049). LV mass was more strongly correlated with crown rump length (r = 0.72, p0.001) and body surface area (r = 0.70, p0.001) than with body mass index (r = 0.47, p0.001) and weight (r = 0.63, p0.001).This study demonstrates echocardiography is feasible for characterizing LV function. Age-related changes in Doppler indices in primates are similar to those in humans. LV mass is more closely related to fat-free mass indices. We provide reference values for LV systolic and diastolic function in adult bonnet macaques across the captive life span.

Among 250 laboratory-born bonnet macaques living in social groups and maintained on commercial monkey chow, we measured weight, crown-rump length, sagittal abdominal diameter (SAD), and fasting serum insulin, glucose, triglycerides, high-density lipoproteins, low-density lipoproteins, and total cholesterol. Body mass index (BMI = weight/crown-rump length(2)), and insulin resistance determined by the insulin/glucose ratio (IGR) and homeostasis model assessment, were measured. We defined the metabolic syndrome using a composite score based on morphometry, insulin resistance, and serum lipid levels, analogous to clinical criteria. Elevated BMI was associated with significantly greater SAD, insulin, IGR, homeostasis model assessment, and triglycerides. Among 120 adult monkeys aged 5-17 yr, males (n = 48) had higher BMI, SAD, insulin, and IGR levels than females, independent of age. Sixteen of 113 adult monkeys and five of 36 peripubertal subjects, aged 3-4 yr (14%), met our criteria for the metabolic syndrome, as did four of 12 monkeys, aged 20-28 yr. Markers of the metabolic syndrome are present by 3-4 yr of age in our colony and are observed across the life span in the absence of conventional obesifying interventions. Socially reared and housed bonnet macaques may provide a useful model for studying the pathogenesis, prevention, and treatment of the metabolic syndrome.

Seven bonnet macaques (Macaca radiata) with strong hand preferences in performing a computer-generated joystick task that required directing a cursor to contact a small stationary target on a monitor were given comparable experience with each hand on the task over a 5-week period. Hand use was randomly restricted to either only the left or only the right hand across trials by automatically inputting into a computer the unique identification numbers of microchips implanted in the forearms of each macaque. Subsequent presentation of a novel task requiring maintenance of contact between a cursor and a moving target revealed no performance difference between preferred and nonpreferred hands or between left and right hands on the basis of number of errors or time to complete the task. The findings suggest that the strong hand preference for these tasks does not derive from a performance advantage for the preferred hand.

Summary.-Two groups of bonnet macaque (Maraca radiato) mother-infant dyads were exposed to 12 wk. of a variable foraging demand paradigm for the mothcrs beginning when the infants were approximately 18 weeks of age. For the nursery group, infants were required to remain in a nursery within the mothers' living area during the entire treatment period. Testing of the dyads of both groups in a novel room subsequent to the differential rearing experience showed that only the inhnts required to remain within the nursery exhibited an increase in motor engagement of the novel environment over the first hour of exposure, possibly reflecting greater security of ;lttachment in these nursery infants. We previously demonstrated that a foraging task for bonnet macaque (Maraca radiata) mothers that varies benveen easy and difficult for 2-wk. blocks (variable foraging demand) during early infant development results in reduced motor engagement of a novel environment by the infants in subsequent testing and suggests a reduced security of attachment by comparison to infants reared by mothers with a low foraging demand (2, 3). To clarlfy mechanisms in this effect, we also developed a contact-permissive-mesh nursery that allows us to operationalize when mothers have made themselves available to their infants for grooming, huddling, etc., i.e., at the nursery, and permits us to provision the infants selectively, thereby buffering them from the direct effects of the foraging demands (4). The present goal was to assess how nursery rearing might modb the impact of variable foraging demand on infants' behavioral patterns in a novel environment subsequent to the experimental rearing condition. The nursery rearing might increase the effects because dyadic interactions would have to be negotiated through mesh, and mother would be physically unavailable during the necessary periods of task engagement. However, because the nursery rearing allows mothers to choose when to make themselves physically available to their infants, they may be psychologitaUv available at the same time. Concordance of physical and psychological availabilities may be I11ghc.r the more positive the overall quality of dyadic interactions with a lesser Wtelihood of hsrr~cl~on or rejection. This in turn would promote more secure infant development and mitigate the effects of variable foraging demand.

Background: Central noradrenergic (NA) dysregulation has provided a major theoretical framework for understanding the pathogenesis of panic disorder (PD). Using clonidine, an α2-adrenergic receptor agonist, as a probe of NA function, we investigated the hypothesis that the antipanic efficacy of the selective serotonin reuptake inhibitors may be associated with normalization of a putatively dysregulated NA system. Methods: We report further analyses on data from 17 subjects with PD and 16 healthy volunteers who underwent measurement of the plasma NA metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) immediately before and after oral clonidine administration. Thirteen patients with PD were rechallenged after 12 weeks during open fluoxetine hydrochloride treatment using the same clonidine paradigm; 13 healthy volunteers were rechallenged at 12 weeks, not having received treatment between challenges. Results: Patients with PD, compared with healthy volunteers, have markedly elevated plasma MHPG volatility during the first clonidine challenge. Volatility describes the magnitude of within-subject plasma MHPG oscillatory activity as assessed by the root of the mean square successive difference. A greater degree of clinical global improvement was predicted by a greater magnitude of basal MHPG reduction with fluoxetine treatment. Antipanic response to fluoxetine was accompanied by a significant decrease of MHPG volatility to volunteer levels. Volunteer MHPG volatility remained unchanged from the first to second clonidine challenge. Conclusions: Further evidence is provided for the hypothesis of NA dysregulation in PD as reflected by elevations of within-subject plasma MHPG volatility during clonidine challenge. Effective selective serotonin reuptake inhibitor—antipanic treatment in this clinical sample was paralleled by normalization of dysregulated NA function.

In this paper the authors examine the interrelationship of both the noradrenergic (NA) system and the hypothalamic-pituitary-adrenal (HPA) axis and its implications for panic disorder (PD). Seventeen PD patients and 16 healthy volunteers were challenged orally 12 weeks apart with the α2-agonist clonidine (13 healthy volunteers and 12 patients repeated the challenge). Between challenges, PD patients were treated with fluoxetine, with 10 of 12 improving at least moderately. Both during the acute phase of the illness and during the phase of pharmacological improvement, patients demonstrated a greater percentage of reductions of plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and plasma cortisol during clonidine challenge. We used correlational matrices to examine the relationship between the NA system, as reflected by plasma MHPG, and the HPA axis, as reflected by plasma cortisol measures. Healthy volunteers exhibited multiple significant “couplings” between either baseline or maximal decrease (Δmax) of plasma MHPG, with either baseline or Δmax plasma cortisol measures both within the first and second challenges and between the first and second challenges. In contrast, PD patients demonstrated “uncoupling” of the NA system and the HPA axis, with no significant correlations observed between either baseline and/or maximal decrease (δmax) measures of MHPG with the same cortisol measures for either the first or second challenge. The same uncoupling was observed for NA/HPA correlations between the first and second challenges. These data suggest that the hyperresponsivity to clonidine in PD patients persists during fluoxetine treatment. They also raise the possibility that an uncoupling of the NA system and the HPA axis may be a feature of PD patients, even following clinically significant improvement. The authors suggest suboptimal NA regulation of the HPA axis in PD patients, with pathophysiological implications particularly prominent during periods of stress-induced activation of the two systems.

To explore behavioral patterns in bonnet macaque mother-infant dyads under environmental challenge, the motivation of infants to contact their mothers during a 1-hr foraging period was manipulated in two ways. First, sessions were given in which the infants were separated from their mothers for 3 hr prior to the foraging period. Second, sessions were given in which the infants were allowed access to food prior to the foraging period, thereby presumably reducing their motivation to separate from mother to seek food for themselves during the foraging period. Neither manipulation resulted in heightened conflict within the dyads. Separation of the infants prior to the foraging period did result, in general, in mothers forfeiting foraging task engagement to attend to their infants. The extent to which a mother exhibited this pattern correlated with her level of foraging effectiveness.

Background: In an earlier study, infant primates were nursed by mothers randomly assigned to variable foraging demand (VFD) or nonvariable foraging conditions (non-VFD). A group of grown VFD-reared subjects demonstrated elevations of cisternal cerebrospinal fluid (CSF) corticotropin-releasing factor concentrations and decreased CSF cortisol levels vs non-VFD counterparts. To further characterize neurobiological sequelae of disturbed early rearing, CSF concentrations of serotonin, dopamine, and norepinephrine metabolites (5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenethyleneglycol [MHPG], respectively) and of somatostatin were determined. Methods: Second CSF taps were obtained from the previously studied cohort of 30 subjects and from 28 agematched ad libitum‐reared control subjects. Relevant assays were performed. Results: All neurochemicals assayed except MHPG were elevated in the VFD-reared compared with non-VFD subjects. In the VFD group, statistically significant positive correlations between corticotropin-releasing factor and each neurochemical was found, except for MHPG. In the non-VFD subjects, no significant correlations with corticotropin-releasing factor were observed. No effect of age was evident. Conclusions: Reducing the predictability of maternal foraging demand during early rearing was associated with elevations of cisternal somatostatin and of serotonin and dopamine metabolite concentrations in grown offspring. The corticotropin-releasing factor elevations reported previously were positively correlated with all the elevated CSF parameters of the current study. The findings support the notion that adverse early rearing experiences in primates have longstanding and complex effects on a range of neurochemicals relevant to emotional regulation. Replication in prospective age-controlled studies is warranted. Arch Gen Psychiatry. 1998;55:473-477

A group of twelve bonnet macaques (Macaca radiata) raised in partial social isolation from birth to adulthood expressed moderate-to-severe behavioral disturbance as a function of their early rearing environments. The range of these behavioral function of their early rearing environments. The range of these behavioral abnormalities in this species are described for the first time. In order to assess the role of the current environment on their behavior, the animals as a group were required to obtain all of their food from a foraging device presenting two levels of difficulty. The therapeutic effect of the imposed foraging task was dependent upon the individual's status in the dominance hierarchy. Low- and high-ranking animals responded positively and became more social (338% above baseline levels) and showed lower levels of specific abnormal behaviors (nearly 75% lower). Mid-ranking animals responded negatively and became less social (89% lower), while their levels of abnormal behavior dramatically increased (200% higher).

Differential handling of male and female infants by their mothers and differential behavior of male and female infants independent of maternal behavior is a critical research issue with significant implications for understanding human development. This report describes mother-infant interaction in the squirrel monkey as a function of the infant's sex in a variety of laboratory environments. In a complex social environment, males move away from their mothers at a younger age than do females. The mothers then attempt to keep the males physically close. This maternal effort at continuing mother-son closeness is not successful, indicating greater infant-activated autonomy in the male.

The physiological and behavioral factors underlying the annual reproductive cycle of the squirrel monkey were evaluated under controlled laboratory conditions. Mating activity following the formation of two social groups served to synchronize the reproductive phases during the subsequent year of observation. Changes in male and female reproductive status were assessed during four designated phases: breeding, pregnancy, lactation and fatting. Behavioral and somatic changes in gonadectomized subjects, living in the social groups, were also evaluated. The variations in behavior and physiology across the year were considered in terms of factors constraining the timing of the natural reproductive pattern.

In this article we report on the reliable production of several features of panic attacks following subcutaneous administration of sodium lactate to nonhuman primates. Unrestrained monkeys were evaluated by an observer without knowledge of the subjects' treatment with either sodium lactate or a dextrose control solution. The lactate produced temporally circumscribed episodes of agitation, wariness, and motor responses, normally elicited under stressful or threatening conditions. In an initial pharmacological intervention, we found that pretreatment with imipramine blocked the response to lactate. The further development of this model offers promise for the systematic examination of etiological factors in susceptibility to lactate induction of panic attacks, the physiological basis of the response, and new modes of treatment of panic disorder.

During tests of sexual behavior which permitted multiple ejaculations, male bonnet and pigtail macaques were found to differ on a number of traditionally defined behavioral parameters. Although pigtail tests were terminated by a more stringent criterion, they were longer in duration and more ejaculations were recorded than in the bonnet tests. Pigtail males required relatively more intromissions for initial ejaculations and somewhat fewer on successive ejaculations. Bonnets, on the other hand, generally ejaculated on the first mount of a test and then exhibited increased numbers of intromissions to successive ejaculations. Although both species exhibited increases in successive postejaculatory intervals, the changes were more gradual for the pigtails.

Developmental weight gain was traced in two species of macaque, Macaca radiata and Macaca nemestrina. Some similarities in growth patterns between the two species were observed. Spontaneous obesity in bonnet macaques was observed, and growth curves of these specimens were compared with those of normal animals.

Twelve juvenile bonnet macaques (Macaca radiata), 6 males and 6 females, were presented with color videotape recordings of 3 types of social stimuli. The stimulus animals, all unfamiliar adult conspecifics, consisted of a passive female, a passive male, and a threatening male. Subjects were observed in the presence of their mother and 1 other juvenile-mother dyad. The juveniles showed the highest scores for contact with mother when presented with the threatening male stimulus. Similarly, subjects lipsmacked significantly more to the male threatening male stimulus than to either the passive male or female. The female stimulus was approached significantly more than either the passive or threatening male. Results suggest that juvenile macaques will respond to social stimuli presented through color video recordings in a socially appropriate manner. This technique provides a new tool in the investigation of social perception in nonhuman primates.

Sustained physical contact between animals characterizes bonnet but not pigtail monkey groups. This pattern encourages maternal permissiveness and enhances social orientation in infants. Moreover, pigtail infants show depression and behavioral debilitation after maternal loss, whereas bonnets are often adopted by others and suffer minimal affective and behavioral changes.

The hormonal basis of the ‘fatted’ phenomenon in squirrel monkeys was investigated by gonadectomy and androgen treatment of adult males and females. Significant correlations were found between testis weight and body weight and between testis weight and the sharp reductions in body weight that occurred following gonadectomy. of the males. Females lost little, if any weight, following gonadectomy. Androgen treatment of male castrates resulted in increased body size, weight and physical appearance, closely approximating the condition reported to occur in normal males during the mating season. Female castrates responded to androgen treatment with an analogous development of‘fattedness.’ The data suggest that the ‘fatted’ condition observed seasonally in the field is regulated by fluctuations in endogenous androgen levels of males and that females share that characteristic responsiveness to androgen.

Two groups of squirrel monkeys (Saimiri sciurea) containing a male and four females each were studied before, during and after the temporary introduction of strange females. Social relations were generally characterized by minimal individual distance, an almost complete lack of social grooming and selective tail placements during huddling. Contrary to most experience with old-world species, introduction of the stranger produced no destructive aggressive encounters; social exploration, genital display and brief manual attacks directed at the stranger were relatively high initially but rapidly dissipated. Characteristic behaviours of group members including their resting postures and their frequency of huddling was disrupted immediately after introduction but rapidly returned to normal by the third day. Strangers then huddled as often as the original group members.