Cognitive deficits and psychopathology among former prisoners of war and combat veterans of the Korean conflict.

OBJECTIVE: This study was conducted to describe the long-term psychological and psychiatric sequelae of prisoner of war (POW) confinement against the backdrop of psychiatric evaluations of Korean conflict repatriates more than 35 years ago. METHOD: A group of 22 POWs and a group of 22 combat veteran survivors of the Korean conflict were compared on measures of problem solving, personality characteristics, mood states, and psychiatric clinical diagnoses by means of a battery of psychometric instruments and structured clinical interviews. RESULTS: Although the two groups were similar in background and personal characteristics, they differed in reports of life adjustment problems, complaints of physical distress, proficiency on cognitive tests, objectively measured personality characteristics, and assigned psychiatric diagnoses. CONCLUSIONS: Illustrated by a case report which describes the prolonged brutality of the Korean conflict POW experience for one individual, the results suggest that the psychiatric symptoms documented more than three decades ago have persisted in severity and chronicity. In addition to problems with cognitive deficits and complaints of bodily discomfort, most common among POW survivors were symptoms of suspiciousness, apprehension, confusion, isolation, detachment, and hostility.

Trauma-induced weight loss and cognitive deficits among former prisoners of war.

Former prisoners of war (POWs) from the Korean Conflict and WWII reporting confinement weight losses of greater than 35% (n = 60) and less than or equal to 35% (n = 113) and non-POW combat veterans (n = 50) were compared on WAIS-R and Wechsler Memory Scale (WMS) Logical Memory indices. High weight-loss POWs performed more poorly than combat veterans on Performance IQ, Arithmetic, Similarities, and Picture Completion subtests, Witkin-Goodenough Attention-Concentration Factor, and WMS Immediate and Delayed Recall and more poorly than low weight-loss POWs on Arithmetic, Attention-Concentration Factor, and the WMS immediate memory measure. Low weight-loss POWs and combat veterans differed only on WMS immediate memory. Findings support the Thygesen, Hermann, and Willanger (1970) hypothesis that severity of POW confinement stress reflected by trauma-induced weight loss is predictive of long-term compromise in cognitive performance.

Assessment of long-term psychosocial sequelae among POW survivors of the Korean Conflict.

Psychological and psychiatric assessments were performed among 20 prisoner-of-war (POW) Korean-Conflict survivors. Results revealed extraordinary biological and psychological abuse with weight losses exceeding 35% of preservice weights and long-term cognitive, emotional, and behavioral sequelae. The full range of posttraumatic stress disorder symptoms was seen in 90% to 100% of the cases with high prevalence of co-morbidity, specifically mood (75%), other anxiety (45%), and alcohol abuse (20%) disorders. Documented by clinical investigators at POW release and now more than 30 years later, symptoms of apprehensiveness, confusion, detachment, and depression reflect the persistence of psychiatric morbidity over time.

Stress induced analgesia plays an adaptive role in the organization of behavioral responding.

The data on ability of stressful or noxious stimuli to suppress the perception of pain was reviewed. The focus of this review has been the attempt to demonstrate that the emergent "Stress Induced Analgesia" (SIA) plays an adaptive role in the modulation of behavioral responding by organisms during periods of threat or danger to the organism. We have reviewed the experimental paradigms that normally used in these studies which point to the fact that the variables inducing SIA need not be actually aversive or even stressful. We also reviewed the data on the mechanisms of SIA and suggested that both opioid and nonopioid mechanisms are involved in the mediation of SIA and that these mechanisms are at least semiindependent and subject to differential conditioning. Finally, we have described a series of experiments carried out in our laboratory where the induction of SIA interacted with behavioral performance in an inverted U shape function, low levels of stress facilitated responding and learning while high levels disrupted responding. We argued that taken together, the effects of SIA seem to be highly adaptive in that it allowed animals to deal with a dangerous and threatening situation in a manner which increased the organism's chance of survival.

Mediation of serotonin-induced analgesia by the 5HT2 receptor in the pentobarbital anesthetized mouse model.

Serotonin can induce analgesia when injected directly into the brain, but analgesia after peripheral administration has been more difficult to show. The pentobarbital anesthetized mouse (PAM) model, developed to alleviate some of the problems involved in the measurement of tail flick latency, was used to assess the action of peripherally administered serotonin. Mice were anesthetized with about 65 mg/kg of sodium pentobarbital IP and their tail flick latencies measured while they were in stage III anesthesia. In these anesthetized mice, IP serotonin induced a significant analgesia that was much more robust than that found in awake mice. The analgesic effect was dose-dependent from 0.25 mg/kg to 10 mg/kg but was not blocked by the antiopiate naltrexone. Of several psychotropic agents tested, only amitriptyline, mianserin, and trazodone had significant effects on analgesia in the PAM model. The analgesic effect of serotonin was reproduced by the 5HT2 agonist DOI and totally blocked by the 5HT2 antagonist NPP. These results show the utility of the PAM model in studying nonopiate analgesia and suggest that the analgesic action of serotonin is mediated primarily through the 5HT2 receptor.

The general anesthesia induced by various drugs differentially affects analgesia and its variability.

Responses to noxious stimuli in awake animals are not totally consensual but are influenced by environmental factors. We considered the possibility that the influence of the environment could be reduced by induction of general anesthesia. We, therefore, compared responses to nociceptive thermal stimuli by measuring tail flick latency, a spinal reflex, in anesthetized and awake mice. All anesthetics tested decreased the intraindividual variability in the measurement of response, suggesting that environmental factors may account for much of this variability in the awake mouse. Mice treated with pentobarbital showed a graded response to increasing levels of heat but were unresponsive to either morphine or naloxone. In mice anesthetized with pentobarbital, increases in latencies occurred only at very deep levels of anesthesia, while urethane nociceptive effect of ketamine was reversed by morphine. Thus, the various anesthetics could show differential effects towards opiate action. The decrease in statistical variability, the differential effects of general anesthetics on tail flick latency, and the distinctive effects of the different anesthetics on opiate action suggest that the anesthetized animal may be a useful tool in the study of nociception.

Differential activity of the endogenous antiopiate Tyr-MIF-1 after various intensities of stress.

Three forms of stress-induced analgesia (electric shock, forced water-swim and novelty) were used to examine the nature of the endogenous antiopiate system. It was hypothesized that a role of the antiopiate system may be to regulate the extent of antinociception within varying environments. The antiopiate properties of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), which were manifest by reduction of opiate analgesia in mice on a hot-plate, were best expressed within a defined range of intensities. In each of the 3 analgesic situations, pre-administration of Tyr-MIF-1 (0.1 mg/kg) resulted in an antinociceptive effect after low to moderate stress but not after more intense stress. These observations indicate that the antiopiate system can function differentially under various environmental conditions, thus ensuring that the organism's responses to its perception of the immediate environment are appropriate and specific.

Tyr-MIF-1 attenuates antinociceptive responses induced by three models of stress-analgesia.

Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), a biologically active brain peptide, has previously been shown to antagonize the analgesia induced by morphine. In this report experiments are described in which mice were tested on the hot-plate in three models of antinociception - shock, novel environment, and warm-water swim - after the administration of various doses of Tyr-MIF-1 without any exogenous opiates. The peptide reduced the antinociception produced by all three methods of inducing endogenous antinociception. These results add further support for the existence of peptides like Tyr-MIF-1 that act as opiate antagonists.

Existence of antiopiate systems as illustrated by MIF-1/Tyr-MIF-1.

Evidence is presented that the small peptides MIF-1/Tyr-MIF-1 are part of an endogenous antiopiate system that may function to balance the opiate system. We review the biological activity, behavioral activity, and functional effects of this proposed opiate antagonist system. In addition, we suggest, based on antinociceptive mechanisms, that the individual components of the antiopiate system might function differently from naloxone.

Stress-induced analgesia: adaptive pain suppression.

In this paper we have examined the phenomenon of stress-induced analgesia. We have described the procedures used to measure analgesia and have suggested that the tests can be designed not only to indicate changes in pain threshold but also to allow for the determination of the capacity to execute adaptive behavior. Aside from enabling the analysis of responses, tests that induce reflexive as well as nonreflexive behavior may have the capacity to separate the more complex aspects of pain such as the possible presence of two components of pain, sensory/discriminative and motivational/affective. These components may be of fundamental importance for any attempt to understand the biological significance of SIA. Our examination of the neurotransmitter and neuropeptide systems has revealed that they are affected by the same manipulations that induce SIA. These amines and perhaps peptides play an integral role in learning, motivation, and performance. We conclude that the functional advantage of a reduction of pain during stressful situations is significant because it allows the animal to react in threatening and perhaps critical situations as if there were no pain. Once the pain system is inhibited, other systems modulate and mediate adaptive responses that expedite the survival of the animal.

MIF-1 antagonizes warm-, but not cold-water stress-induced analgesia: dissociation from immobility.

Forced swimming in warm or cold water can lead to immobility and analgesia in mice. In this report we demonstrate that the peptide MIF-1 (Pro-Leu-Gly-NH2) was able to attenuate the analgesia induced by swimming in warm water, but not that induced by swimming in cold water. In addition, we show that the analgesia and the immobility may be differentially mediated since MIF-1 was able to reduce the immobility at doses different from those necessary to reduce the analgesia. These results confirm previous research indicating that MIF-1 may act as an anti-opiate and further demonstrate that MIF-1 affects analgesia induced by stress.

Behavioral support for an ACTH receptor in the CNS.

In this report we present a series of experiments which have led us to support the notion of the presence of an ACTH receptor in the CNS. A short intense heat-stress (hot-plate) applied to the paws of rats will temporarily reduce activity. During the course of experimentation we were able to eliminate a number of logical mediators. Neither adrenalectomy, adrenal-medullectomy, naloxone administration, nor alpha-MSH-(1-12) were able to affect the observed akinesia. Hypophysectomy, however, was able to abolish or mask the behavior and the reduction in activity could be reinstated by the administration of ACTH-(4-10) to hypophysectomised rats. These data support the notion that a short intense stressor can release ACTH and that this ACTH can be responsible for mediating the short term reduction in activity. In addition, the fact that ACTH-(4-10) has only minimal steroidogenic properties and was able to reinstate the behavior led us to speculate that these effects were of central origin. Furthermore, since naloxone was not capable of altering the behavior, the suggestion is that ACTH in this paradigm acted at a receptor site apart from the naloxone sensitive receptor. This site may in fact be an ACTH specific receptor.

Interactions between ACTH, morphine, and naloxone and their effects on locomotor behavior.

A series of behavioral experiments were performed to evaluate possible interactions between ACTH, morphine and naloxone with regard to locomotor activity in an open field. Manipulations included the administration of one of the drugs followed 30 min later by one of the other drugs. This allowed the examination of the effects of a drug on the ongoing behavior induced by the other drug. In two other experiments which differed in the time of day they were run, locomotor patterns as the result of the administration of combinations of the three drugs were examined for three hours. The results of the present experiments suggest a possible common mode of action of ACTH, opiate agonists and antagonists that was dependent on time of day and stress intensity.

Effects of heat-stress on behavior and the pituitary adrenal axis in rats.

Three experiments were performed in order to analyse the behavioral and biochemical correlates of four different intensities of the same stressor. In Experiment 1, rats were exposed to heat stress (hot-plate) of varying temperatures for 30 seconds. Activity was recorded in an open field immediately after stress for 30 minutes. The data revealed that the milder temperatures increased (21, 47, 52 degrees C), while the higher temperature (57 degrees C) decreased activity. Experiment 2 assessed the pituitary-adrenal response to the different temperatures by measuring levels of plasma corticosterone 30 minutes after stress. The four levels of hot-plate temperatures induced differential levels of corticosterone which may best be described as an inverted U-shaped function, with only the extreme temperature (57 degrees) inducing a significant elevation in levels of the steroid. Experiment 3 further manipulated the pituitary adrenal axis by administering dexamethasone 25 hr and 1 hr before stress and ACTH 15 min before stress. Both affected activity levels by depressing locomotion regardless of the stress intensity. These results are compared to other studies that have addressed the question of stress-induced activation and it is suggested that stress is not a unitary concept, but interacts with the performance of certain behaviors to produce both facilatory or inhibitory results.

ACTH1-39 but not naltrexone produces biphasic effects on locomotor activity.

Two experiments were conducted in order to investigate the effects of chronic ACTH and naltrexone treatment on motor activity in an open-field. In the first experiment, Wistar rats received two daily injections of either ACTH1-39-saline, naltrexone-saline, ACTH1-39-naltrexone or saline-saline for 24 consecutive days. Immediately following injections, motor activity was measured every fourth day. The results indicated that ACTH and naltrexone each had depressive effects on motor activity that did not dissipate over 24 days. In the second experiment, the procedure was similar to the first except that motor activity was measured at five hours postinjection. The results revealed that naltrexone by itself or in combination with ACTH had no observable effect on motor activity. ACTH was observed to have a stimulatory effect on motor activity that decreased over days and was not naltrexone reversible. The results are discussed in terms of different mechanisms underlying the effects of ACTH and naltrexone.

Opiate receptors may mediate the suppressive but not the excitatory action of ACTH on motor activity in rats.

Subcutaneous injections of adrenocorticotropin (ACTH) or of the opiate antagonist naltrexone produced a one (2.0 mg/kg) dpressed, whereas smaller doses of ACTH (50 micrograms/kg) and of naltrexone (0.125 and 0.25 mg/kg) stimulated motor activity in the open field test. Furthermore, naltrexone at a dose level that had no effect on motor activity blocked the suppressive effect of the high doses of ACTH but had no effect on the stimulating effect of the intermediate dose of ACTH. Finally, chronic naltrexone administration resulted in enhanced sensitivity to the suppressive but not to the stimulating effect of ACTH on motor activity. It is argued that opiate receptors may play a selective role in the effect of ACTH on motor activity. Such receptors may mediate the supressive effect of high doses of ACTH whereas other, naltrexone insensitive receptor systems may mediate the stimulating effect of ACTH on activity functions.