“Endocrine and Immune Responses to Separation and Maternal Loss in Nonhuman Primates”

by Christopher L. Coe, Sandra G. Wiener, Leon T. Rosenberg, and Seymour Levine


found in The Psychobiology of Attachment and Separation, edited by Martin Reite and Tiffany Field

Academic Press, Inc, 1985 – Orlando

ISBN 0125867808

pp 163-199

“The conceptualization of the stress syndrome was based originally on the response to physical trauma, but subsequent research showed that psychological stimuli were also potent elicitors of autonomic and endocrine activation.  In particular, situations that contain elements of novelty, uncertainty, or conflict are strong evokers of physiological arousal.  These have been labeled as collative factors by Berlyne (1960, 1967), because in order to evaluate them, it is necessary to compare similarity and differences between stimulus elements (novelty) or between stimulus-evoked expectations (uncertainty).  Clearly, an infant’s perception of separation as threatening involves aspects of all three factors, and thus, we believe that it is only with a cognitive perspective that one can fully understand how an infant copes with the trauma of separation.  (Coe/eir/165)”

“Two other concepts are especially important for understanding the coping process, and both are related to the reduction of uncertainty about the environment or upcoming events (Levine & Coe, in press; Seligman, 1975).  These are predictability and controlPredictability is concerned with the amount and type of information available to the organism, whereas control involves the capacity to make active behavioral responses to alter or alleviate the aversive situation.  (Coe/eir/165)”

“Situations can be seen to vary along a continuum from highly certain and predictable (i.e. benign) to highly uncertain and unpredictable (i.e., stressful).  Because uncertainty is aversive, those factors or actions that enhance predictability and controllability will serve to reduce the stressfulness of a situation.  (Coe/eir/165)”

“The relevance of these concepts to the separation response is obvious, because this kind of disturbance represents a major loss of control and the onset of a highly unpredictable event for the infant…..  We have found that the concepts of control and predictability are particularly helpful for understanding the changing response of infants during prolonged separations or across repeated separation experiences.  (Coe/eir/165)”

++ separation studies on two primate species, squirrel monkey and rhesus macaque

“The relevance of these concepts to the separation response is obvious, because this kind of disturbance represents a major loss of control and the onset of a highly unpredictable event for the infant.  The importance of control is evident in the observation by Robertson and Robertson (1971) that even those infants who react violently to involuntary separations will still readily accept and make voluntary separations.  We have found that the concepts of control and predictability are particularly helpful for understanding the changing response of infants during prolonged separations or across repeated separation experiences.  (Coe/eir/165)”

“Both mothers and infants showed significant cortisol elevations over basal levels at each time point, and the infants’ adrenal response continued to increase while their behavioral agitation decreased.  (Coe/eir/169)”

“…we believe that the vocal response should be viewed as a malleable signaling behavior that functions primarily to elicit promixity [sic] seeking and caregiving from the mother.  (Coe/eir/171)”

“…we believe that the protest calling is an active attempt to elicit caregiving behavior and that a decline in vocalizations in the absence of reinforcement should be viewed as part of an adaptational process, and not necessarily as being indicative of a depressive state.  (Coe/eir/175)”

“A number of investigators have reported that the behavioral disturbance of separated monkey infants is considerably reduced and sometimes entirely ameliorated when they are left in the presence of a social group that is supportive (Dolhinow, 1980; Rosenblum & Kaufman, 1968).  These findings concur with studies on children that have shown that the separation response is less marked in the home environment and, conversely, that the reaction is more severe in unfamiliar places or when strangers are present (Kagan, 1974; Sroufe, Waters, & Maas, 1974).  In fact, some theorists have suggested that the fear evoked by separation in children is largely due to the manner and location of departure rather than to the actual breaking of contact (Robertson & Robertson, 1971).  (Coe/eir/171)”

“Maternal separation is clearly a traumatic and stressful event for infant monkeys, but throughout our research we have continually been impressed with their resiliency and capacity to cope with the separation experience.  (Coe/eir/175)”

“…pituitary-adrenal response.  In general, one tends to emphasize the deleterious physiological effects of adrenal activation.  However, these effects usually occur only after sustained cortisol elevations or at pharmacological levels.  Short-term activation can, in fact be extremely important for mobilizing the organism to deal with a stressful stiation. Coritcoids have diverse effects on body physiology serving to enhance energy mobilization by affecting glucose, fat, water, and ion regulation, and by generally slowing down growth and digestive processes (Cope, 1972; Lorenzen, 1969).  Corticoids serve to increase blood sugar concentrations and to mobilize fatty acids from fat depots [sic], and they have a number of anti-inflammatory and inhibitory effects on the immune system.  Moreover… the adrenocortical hormones may also be actively involved in shaping the coping behavior of a stressed organism….  (Coe/eir/182)”

“Although the acute adrenal response may be adaptive for the separated infant, we have found that the prolonged cortisol elevations induced by sustained separations can adversely affect the immune system.  (Coe/eir/183)”

“In addition to determining that maternal loss has an adverse effect on the immune system of the separated infant, we have found that the availability of other social companions can have an ameliorative effect on the immunological consequences of separation.  (Coe/eir/183)”

“…we believe that the data convincingly show the applicability of stress and coping theory for understanding the infant’s response to separation.  (Coe/eir/192)”

“Discussions on the influence of the environment or prior experience have, therefore, focused primarily on the occurrence and intensity of a depressive phase.  Our data suggest instead that environmental and experiential factors exert an immediate influence on how the infant perceives the loss and on its behavioral options for dealing with the separation.  The infant’s response is not simply reactive in an emotional sense; its behavior reflects an active attempt to alter the aversive situation (i.e., coping).  (Coe/eir/193)”

“…the infant’s physiological responses indicated that total isolation was the more stressful condition…(Coe/eir/193)”

“We propose that, under normal conditions, it is proximity and contact with the mother that serve to modulate and reduce the infant’s fear and distress responses.  The aversiveness of involuntary separation is due not only to loss of the mother but also to exposure to an unfamiliar and threatening environment in the mother’s absence.  Because distress and alarm calls are the primary means through which primate infants elicit caregiving behavior, and they have had extensive experience with the efficacy of calling since birth, it is not surprising that separation evokes high levels of these calls.  We believe, therefore, that the vocalizations of the separated infant are best viewed as a type of signaling behavior designed to elicit proximity seeking on the part of the mother.  The stimuli of a proximal, but inaccessible, mother exacerbate the vocal response; conversely, the absence of the usual reinforcer for this response, the mother, results in a more rapid cessation of calling.  (Coe/eir/193)”

“Moreover, in coping theory, the vocal response provides the primary means through which the separated infant can exert some degree of control over the aversive situation.  Thus, the ineffectiveness of the vocal response in the total isolation condition may compound the already unpredictable and threatening aspects of the situation.  In keeping with a functional interpretation of the infant’s separation behavior, it is of interest that the agitated movement does not subside to the same degree or as rapidly as does the vocal response.  Under most circumstances, the infant’s agitated movement would probably provide the only means of reestablishing contact after its vocalizations failed to elicit retrieval by the mother.  (Coe/eir/194)”

“We have also been impressed by the resiliency of the primate infant in responding to maternal separation and have seen little evidence of the depressive behavior described in the literature.  In most of our studies, the infant’s behavioral response shifted from agitation to adaptation and acquiescence during repeated or prolonged separations.  Several factors may account for this difference regarding depressive behavior.  First it is an interpretation problem, because some investigators have viewed the absence of calling and movement as indicative of despair, rather than as an adaptation to the separation.  Second is a genetic factor…..Individual variation within a species also occurs….  A third source of variability is related to the separation and reunion paradigms used by different investigators.  Most studies reporting depression have examined the effects of traumatic and repeated separations where a sense of helplessness was invoked by imposing additional demands on the infant, or where the reunion environment was also disturbed (Kaufman & Stynes, 1978; Mineka, 1981; Suomi, Mineka, & DeLizio, 1983).  The effect of repeated separation seems to be the most debilitating when the reunion environment is not supportive, and in some studies, the long-term effects of separation may have occurred because the infants were reunited with other traumatized infants or in disturbed social groups (McGinnis, 1980).  Finally, many studies reporting depressive responses were conducted on infants reared without mothers (i.e. peer separations), and these (Coe/eir/194) infants are more vulnerable to depression than are mother-reared infants (Kraemer & McKinney, 1979; Suomi et al., 1983).  (Coe/eir/195)”

“In contrast to the cumulative and worsening reaction to separation described in many reports, we found that there was less and less overt evidence of behavioral distress across repeated or prolonged separations.  It should be reiterated, however, that prior to separation, our infants were reared normally.  The separation environment was comparatively benign, and a stable reunion environment was available during experiments on repeated separations…..  We have observed depressive behavior in only two situations.  In one case, the separated infant was placed in an unfamiliar social group to assess whether the effect of social buffering would generalize to all environments.  The depressive response in this situation falls under the category of imposing additional demands and threats upon the separated infant.  The second instance of depression occurred following pretreatment with metyrapone to block the adrenal response to separation.  This finding indicated that the increased cortisol secretion is critical for mobilizing the infant and adapting it to the trauma of separation.  Moreover, this finding suggests that disturbances of physiological homeostasis, such as sleep arrhythmia and altered temperature regulation, maybe the precipitating events leading to depressive responses in other studies (Reite et al., 1978).  (Coe/eir/195)”

“In spite of our comments on the infant’s active behavioral attempts to cope with separation, it should be emphasized that the physiological data indicate that maternal loss is an extremely stressful event for the young monkey..  (Coe/eir/195)”

“It is probably more important to end, however, not with the stress of separation, but rather with the modulating influence of social companions on the separation response.  In keeping with the current emphasis on the importance of social support in human studies, we have found that the presence of familiar social partners can largely ameliorate the separation response of primate infants.  The separated and distressed infant usually receives the most overt caregiving and solicitous behavior from a familiar adult female, but we have now found that the simple presence of other conspecifics can reduce the behavioral and physiological responses to maternal separation.  In fact, even the presence of other separated infants served to reduce the adrenal response to separation and, subsequently, the effect on complement proteins in a separated infant.  Thus, just as the response to loss indicates the importance of a mother-infant bond, we can also state that fear and stress reduction is an important benefit and function of social relationships in general.  (Coe/eir/196)”


It dawns on me this morning, 3-5-7 Monday, that what I am studying is the neurophysiology of isolation.  That is the starting point for where attachment comes from, the high levels of opioids that are in the system at birth and are supposed to be replaced through the process of interaction with humans by the lesser opioids.

It makes me wonder about the twilight sleep – increasing the levels of opioids prebirth by the administration of even MORE opioids.

But whatever happened and didn’t happen, the “intended” transfer of opioids to people, and hence attachment and affiliation, did not happen correctly with me.

If B-endorphin is the strongest opioid, from there our systems and brain are supposed to operate with the “lesser” ones activated through attachment processes.  The “single point of light” is supposed to essentially find its diminishment and division so that it manifests within many separate flames rather than one big one.  I don’t think that dispersion happened for me.  And instead of social relationships lessening my fear and stress, they increase it.

If mother never bonded with me, does that mean that I don’t even know what true separation is supposed to feel like, stress and all?  Is isolation my base-line, my fundamental state?  I know I can feel separation stress – like with my children, and certainly via my attachment to Ernie.  But I certainly do not feel called or driven to be around other people to get needs met the way I think humans are supposed to.

It is sort of a strange feeling to realize that human neurophysiology and neurochemistry is supposed to be designed so that we do not want to be alone and seek affiliation within the group.  It may well be, then, that this is the common ground I share with autistic people – the inability to experience the joy others do when in contact with other members of their species.

“Just the facts, Ma-am,” I look like a member of my species from the outside, but from the inside I lack the true capacity to affiliate – because that would be what attachment really means

If a secure attachment leads to an autonomous adult, does that mean that they do not need others to modulate their arousal and regulate their emotions because they have appropriately internalized those abilities?  That would mean, to me, that they can give, not get.  If a person’s system is geared to the original, singular, most powerful B-endorphin then does that state of essential isolation mean that they are essentially needy, or essentially self contained?

If they are self contained that means that their relationship with their species is not normal.  How does this all relate to the “safe brain” versus the “danger brain?”

We are then studying the neurochemistry of isolation, attachment, and separation, with autonomy being thrown somewhere in the mix.  Are we supposed to NEED other members of our species?  Like that medicine man told me, “Linda, you do not need people the way other people need people.”

I have to go to work now.


  1. We are working in a rodent model of maternal and littermate separation throughout artificial rearing, and we had found that these rats as juvenile and/or adults show behavioral and physiological disturbs. For example, they show deficit in: taking mother care toward their own pups, or foraing pups of juvenile or adult non-pregnant female in a sensitization paradigm, social learning, attention, male sexual behavior. Furthermore, they show an increased in: play-fighting behaviors as juvenile males, maternal aggression, locomotion, impulsive responses, etc. Interestingly, most of these negative alteration were prevented when pups isolated received tactile stimulations (using a brush), or companion of 1-2 pups same-age into the cup of isolation. The former results suggest us as for Hofer and many others, that these effects were due not only as a stressfull process during this critical period (postnatal preweaning period), also to a sensory and social deprivation process. Angel I. Melo

    • Interesting that you should mention all of this — I am just getting ready to do a renewed search about newborn sense of smell — grief among human newborns removed from their mothers even if then given adequate surrogate mothers.

      What university are you affiliated with?


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