Early social deprivation in nonhuman primates: long-term effects on survival and cell-mediated immunity.

BACKGROUND: Early differential social experience of non-human primates has resulted in long-term alterations in behavior and neurobiology. Although brief maternal separation has been associated with changes in immune status, the long-term effects on survival and immune function of prolonged early social deprivation are unknown. METHODS: Survival rates were examined in rhesus monkeys, half of which had been socially deprived during their first year of life. Repeated measures of immune status were tested in surviving monkeys (18-24 years old). Peripheral blood T, B, and natural killer lymphocytes, macrophages, and monocytes were measured by flow cytometry. Functional cellular immune activity measures included T-cell proliferative responses to mitogens (concanavalin and phytohemagglutinin), T-cell memory response to tetanus toxoid antigen, T-cell-dependent B-cell proliferative responses to mitogen (PWM) and natural killer cell cytotoxic activity. RESULTS: Despite identical environments following isolation, early social deprivation resulted in a significantly decreased survival rate, males being particularly vulnerable to early death. Early social deprivation was associated with a decrease in the ratio of helper to suppressor T cells, and a significant increase in natural killer cell number and in natural killer cell activity in the surviving monkeys. No differences in T- or B-lymphocyte proliferation following mitogen or tetanus toxoid antigen stimulation were observed. CONCLUSIONS: Prolonged early social deprivation of non-human primates profoundly affected mortality and resulted in lifelong effects on cell-mediated immune status.

Social deprivation of infant rhesus monkeys alters the chemoarchitecture of the brain: I. Subcortical regions.

Rhesus monkeys (Macaca mulatta) reared during the first year of life without social contact develop persistent stereotyped movements, self-directed behaviors, and psychosocial abnormalities, but neurobiological mechanisms underlying the behaviors of socially deprived (SD) monkeys are unknown. Monkeys were reared in total social deprivation for the first 9 months of life; control monkeys were reared socially (SR) with mothers and peers. Subjects were killed at 19-24 yr of age. Because the behaviors of SD monkeys are reminiscent of changes in striatal or amygdalar function, we used immunocytochemistry for substance P (SP), leucine-enkephalin (LENK), somatostatin, calbindin, and tyrosine hydroxylase (TH) to evaluate qualitatively and quantitatively patterns of neurotransmitter marker immunoreactivity within subcortical regions. In SD monkeys, the chemoarchitecture of the striatum was altered. Neuronal cell bodies and processes immunoreactive for SP and LENK were depleted markedly in patch (striosome) and matrix regions of the caudate nucleus and putamen; the average density of SP-immunoreactive neurons was reduced 58% relative to SR monkeys. Calbindin and TH immunoreactivities were diminished in the matrix of caudate and putamen of SD monkeys. TH-immunoreactive neurons, but not cresyl violet-stained neurons, in the substantia nigra pars compacta were decreased (43%) in SD monkeys. Peptide-immunoreactive terminals were reduced in the globus pallidus and substantia nigra in SD monkeys. The nucleus accumbens was the least affected of striatal regions. Striatal somatostatin immunoreactivity wa qualitatively and quantitatively similar in SD and SR monkeys. Several regions, for example, bed nucleus of the stria terminalis, amygdala, and basal forebrain magnocellular complex, that were in the same sections and are enriched in these markers did not appear altered in SD monkeys, suggesting a regional specificity for vulnerability. The altered chemoarchitecture of some basal ganglia regions in adult monkeys that experienced social deprivation as infants suggests that the postnatal maturation of neurotransmitter phenotypes in some structures is influenced by social environment. Abnormal motor and psychosocial behaviors resulting from this form of social/sensory deprivation may result from alterations in peptidergic and dopaminergic systems within the basal ganglia.

Associative processes in differentially reared rhesus monkeys (Macaca mulatta): blocking.

Nine isolate and 6 socially reared adult rhesus monkeys were examined in a standard blocking procedure. A tone was paired with a startle stimulus (US) during Phase 1. A tone-light compound CS was paired with a US during Phase 2. In Phase 3, the light was presented alone to test for blocking. Results showed that learning about the light was blocked in social controls, but not in isolates. These data suggest isolates processed information atypically, in that they developed an association to a redundant cue. A second group of isolates (n = 3) underwent the identical procedures. However, conditioned reactions to the tone were extinguished before testing. Test responding was significantly reduced in this group, that is, blocking was obtained. These data suggest the within-compound association developed during Phase 2 mediated the isolate blocking deficit. Together, these findings imply long-term intellectual consequences of early social impoverishment. Such deficits may be mediated by alterations in central dopamine systems.

Rehabilitation. Psychology's greatest opportunity?

Rehabilitation is one of the fastest growing areas in the health industry. Supported by several key pieces of legislation, psychologists have established themselves as integral health care providers in rehabilitation. Although psychologists have benefited from legislated membership in rehabilitation, most individual psychologists and the psychological associations have failed to recognize the importance of public policy for the practice of psychology. Escalating health care costs have resulted in major revisions in the manner in which health insurers reimburse treatment. Medicare, the major federal health insurance provider, increasingly has been viewed as a model for the provision of all health care. The historic exclusion of psychologists from Medicare has limited the scope of psychologists' practice and the growth of professional psychology. The recent inclusion of psychologists in Medicare improves but does not solve practice and policy issues confronting psychology. Knowledge of national health policy formulation and greater participation by psychologists in health policy is necessary to secure the scope of professional practice most psychologists expect.

Long-term effects of early social isolation in Macaca mulatta: changes in dopamine receptor function following apomorphine challenge.

The hypothesis that early social isolation results in long-term alterations in dopamine receptor sensitivity was tested using older adult rhesus monkeys. Isolated and control monkeys were challenged with apomorphine (0.1 and 0.3 mg/kg), and the drug effects on spontaneous blink rate, stereotyped behavior, and self-injurious behavior were quantified using observational measures. Monoamine metabolites were quantified from cisternal CSF by HPLC-EC, prior to pharmacological challenge. Isolated and control monkeys did not differ in CSF concentrations of HVA, 5-HIAA, or MHPG. At the higher dose, apomorphine significantly increased the rate of blinking, the occurrence of whole-body stereotypies, and the intensity of stereotyped behavior (as measured by observer ratings) in isolated monkeys. The frequency of occurrence of self-injurious behavior was too low to allow for meaningful comparisons. These significant differences in response to apomorphine challenge support the hypothesis that long-term or permanent alterations in dopamine receptor sensitivity, as assessed by drug challenge, are a consequence of early social deprivation.

Associative processes in differentially reared monkeys (Macaca mulatta): sensory preconditioning.

Past research has indicated that with regard to performance in formal learning test situations, early socially isolated rhesus monkeys display atypical reactions to noxious stimuli, deficits in response inhibition, slower adaptation to reinforcement contingencies, and lower performance on oddity tasks. Twelve adult rhesus monkeys (Macaca mulatta), 6 who had been reared in total isolation for the first 9 months of life 19 years earlier, and 6 socially reared, were tested in a sensory preconditioning paradigm. In phase I, two neutral stimuli (S1-S2) were paired in contiguous fashion; in phase II the S2 stimulus was conditioned to elicit a startle response; and in phase III the S1 stimulus was presented to assess whether an association between the two stimuli had been formed during the initial phase. Instead of a deficit, isolate subjects showed significantly more response transfer during phase III as compared to the controls. The superior performance displayed by isolates is viewed as resulting from a slower habituation to S1-S2 stimuli during preconditioning along with the perseveration of responses during testing. These findings support the notion that atypical cognitive processing across a lifespan is a consequence of early social impoverishment.

Effect of age on cisternal cerebrospinal fluid concentrations of monoamine metabolites in nonhuman primates.

There are conflicting reports of the effects of aging on human neurotransmitter systems as estimated by monoamine metabolite concentrations in cerebrospinal fluid (CSF). These discrepancies may be due to sampling site, age or sex of the subjects or other variables that affect CSF metabolite determinations. Cisternal CSF concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenyl-ethylene glycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), major metabolites of dopamine, norepinephrine and serotonin, respectively, were measured in rhesus monkeys (Macaca mulatta) of two age groups. Concentrations of HVA and MHPG were significantly lower in the older group of monkeys, whereas no changes in 5-HIAA were found. This supports the hypothesis that brain catecholamine concentrations decline with age.

Development of social behavior in an adult total isolate rhesus monkey (Macaca mulatta).

A 12-year-old female total isolate rhesus monkey was pretested with age mates and subsequently housed for 20 weeks with an infant "therapist" monkey. Daily observations during that period revealed a 24-fold increase in the probability of social behavior. Self-directed behaviors also increased significantly. Disturbance behaviors (self-slapping, self-biting, bizarre limb movements, etc.) remained unchanged. Although problems obviously exist in cross-species generalization, and are here considered, these results emphasize the importance of early therapeutic intervention as well as the need for a more comprehensive approach to both social and disturbance behaviors if the treatment of adults is to be as successful as the treatment of immature isolate subjects.

Acquisition and extinction of an operant response in differentially reared rats.

Rats reared in either socially isolated or control environments were trained to bar press for food on a variable interval schedule of reinforcement, beginning at 125 days of age for 37 consecutive days. Following this phase the subjects were tested for response persistence during an extinction test. Next, the subjects were compared on measures of spontaneous recovery and the rate of response reacquisition when the reinforcement contingencies were once again reinstated. Though no differences were discerned between the groups on measures of acquisition, maintenance, and reacquisition, isolated rats emitted many more responses than the controls during extinction testing.