Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation.

The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep.

Temporal placement of a nap for alertness: contributions of circadian phase and prior wakefulness.

Napping can enhance alertness during sustained wakefulness, but the importance of the temporal placement of the nap between days and within the circadian cycle remains controversial. To resolve these issues, a between-groups study was conducted with 41 healthy, young adults permitted a 2-h nap at one of five times during a 56-h period otherwise devoid of sleep. Naps were placed 12 h apart, near the circadian peak (P) or trough (T), and were preceded by 6, 18, 30, 42, or 54 h of wakefulness. Visual reaction time (RT) performance, Stanford Sleepiness Scale (SSS) ratings, and sublingual temperature were assessed every few hours throughout the 56 h, which took place in an environment free of time cues. All groups displayed a circadian-modulated decline in RT measures and increases in SSS functions as sleep loss progressed. A nap placed at any time in the protocol improved RT performance, particularly in the lapse domain, but not SSS ratings. Comparisons within groups of circadian temperature cycles for the first versus second day of the protocol indicated that early naps (P6, T18, P30) tended to prevent the mean drop in temperature across days. The earlier naps (P6, T18) yielded more robust and longer lasting RT performance benefits, which extended beyond 24 h after the naps, despite the fact that they were comprised of lighter sleep than later naps. Circadian placement of naps (P vs. T) did not affect the results on any parameter. In terms of temporal placement, therefore, napping prior to a night of sleep loss is more important for meeting subsequent performance demands than is the circadian placement of the nap. SSS ratings suggest that the napper is not aware of these performance benefits. Because the longest lasting RT gains followed early naps, which were composed of less deep sleep than later naps, napping during prolonged sleep loss may serve to prevent sleepiness more readily than it permits recovery from it.

Shock controllability and opioid substrates of escape performance and nociception: differential effects of peripherally and centrally acting naltrexone.

Rats exposed to inescapable shock exhibited analgesia and a significant impairment of shock-escape learning in a shuttle box situation 24 hr later. In contrast, rats exposed to escapable shock or to no shock displayed neither effect. Naltrexone (10 mg/kg) significantly reduced the analgesia and completely eliminated the escape deficit in inescapably shocked rats but induced hyperalgesia, coupled with a marked deterioration of escape performance, in escapably shocked and nonshocked rats. The same dose of quaternary naltrexone, which has low ability to cross the blood-brain barrier, had no effect on either the antinociception or the escape deficit produced by inescapable shock, although it also induced escape impairment and hyperalgesia in rats preexposed to escapable shock or to no shock. A second experiment demonstrated that both the escape interference and the antinociceptive consequences of prior inescapable shock could be reduced partially by a much lower dose (1 mg/kg) of naltrexone but 50 times this amount of quaternary naltrexone was still without effect. These results imply that the consequences of exposure to inescapable shock are mediated by activation of central opioid processes whereas naltrexone-induced effects in escapably shocked and nonshocked animals may be peripherally mediated. The relevance of these findings to the possible role of nociception in escape performance is discussed.

Interaction of Pavlovian conditioning with a zero operant contingency: chronic exposure to signaled inescapable shock maintains learned helplessness effects.

In four experiments we used triads, consisting of escapable-shock (ES), yoked inescapable-shock (IS), and no-shock (NS) rats, to investigate the effect of the interaction between Pavlovian contingencies and a zero operant contingency (i.e., uncontrollability) upon subsequent shock-escape acquisition in the shuttle box. After exposure to 50 signals and shocks per session for nine sessions, interference with shuttle box escape acquisition for IS rats was a monotonically increasing function of the percentage of signal-shock pairings during training (Experiment 1), with 50% pairings producing little or no impairment. Without regard to signaling, ES rats performed as well as NS rats. Experiment 2 demonstrated that our training and test conditions led to substantial and equal impairment in IS rats preexposed for one session to 100% or 50% signal-shock pairings or to unsignaled shocks. In Experiment 3, chronic exposure to 100% signaled inescapable shocks resulted in impairment only if the signal (light) was present during the shuttle box test. The continuous presence of the signal during the test contrasted with its discrete (5-s) presentation during training and suggested that an antagonistic physiological reaction rather than a specific competing motor response had been conditioned. Experiment 4 provided evidence for possible conditioned opioid mediation by demonstrating contemporaneous stress-induced analgesia and shock-escape impairment in IS rats chronically exposed to 100%, but not to 50%, signal-shock pairings, and the elimination of both analgesia and escape interference by the opiate antagonist naltrexone. Thus, chronic exposure to uncontrollable shocks appears to maintain the impairment produced by acute exposure only if the shocks are adequately signaled.

Cognitive styles and life events interact to predict bipolar and unipolar symptomatology.

This study examined the interaction of cognitive style (as assessed self-report and information-processing battery) and stressful life events in predicting the clinician-rated depressive and manic symptomatology of participants with Research Diagnostic Criteria lifetime diagnoses of bipolar disorder (n = 49), unipolar depression (n = 97), or no lifetime diagnosis (n = 23). Bipolar and unipolar participants' attributional styles, dysfunctional attitudes, and negative self-referent information processing as assessed at Time 1 interacted significantly with the number of negative life events that occurred between Times 1 and 2 to predict increases in depressive symptoms from Time 1 to Time 2. Within the bipolar group, participants' Time 1 attributional styles and dysfunctional attitudes interacted significantly, and their self-referent information processing interacted marginally, with intervening life events to predict increases in manic symptoms from Time 1 to Time 2. These findings provide support for the applicability of cognitive vulnerability-stress theories of depression to bipolar spectrum disorders.

The Temple-Wisconsin Cognitive Vulnerability to Depression Project: lifetime history of axis I psychopathology in individuals at high and low cognitive risk for depression.

The authors tested the cognitive vulnerability hypotheses of depression with a retrospective behavioral high-risk design. Individuals without current Axis I diagnoses who exhibited either negative or positive cognitive styles were compared on lifetime prevalence of depressive and other disorders and the clinical parameters of depressive episodes. Consistent with predictions, cognitively high-risk participants had higher lifetime prevalence than low-risk participants of major and hopelessness depression and marginally higher prevalence of minor depression. These group differences were specific to depressive disorders. The high-risk group also had more severe depressions than the low-risk group, but not longer duration or earlier onset depressions. The risk group differences in prevalence of depressive disorders were not mediated by current depressive symptoms.

Opiate antagonists overcome the learned helplessness effect but impair competent escape performance.

Rats exposed to inescapable shocks exhibited deficiencies in learning to escape shock in a novel situation 24 hours later (learned helplessness). Opiate antagonists (naloxone or naltrexone) blocked the learned helplessness effect, allowing efficient escape performance on the subsequent test. In contrast, these drugs impaired the performance of rats pretrained with escapable shocks and animals with no previous exposure to shock. Both effects occurred at small doses and increased substantially with higher doses. The results suggest a significant role for endogenous opiates in the induction of learned helplessness as well as in the acquisition of efficient escape behavior.

Reduction of learned helplessness by central administration of quaternary naltrexone.

Prior research has established that escape impairment resulting from prior inescapable shock (IS) could be reversed by the peripheral administration of the opiate antagonist naltrexone (NTX), but not the quaternary form of naltrexone (QNTX), which when systemically administered, does not readily pass the blood-brain barrier. As it was unclear whether the failure of systemically administered QNTX to reduce shuttle escape deficits following exposure to IS could be attributed to reasons other than the restricted access of QNTX to receptor sites in the brain, rats were affixed with chronic indwelling ventricular cannulae to allow direct brain administration of QNTX. The present experiment found a significant attenuation of the escape deficit produced by prior inescapable shock following the intracerebroventricular (ICV) administration of QNTX (10 micrograms/rat). These data provide further evidence of a mediational role for central opiate receptors in the expression of escape interference following inescapable shock.

Evaluating hypnotic memory enhancement (hypermnesia and reminiscence) using multitrial forced recall.

Two experiments investigated whether hypnosis enhances memory retrieval per se or merely increases a person's willingness to report recollections. Both experiments assessed immediate and delayed (i.e., 1 week) recall for pictorial stimuli. In Experiment 1, following an initial waking baseline recall, subjects of high or low hypnotic ability completed a series of recall trials conducted either in hypnosis or in the walking condition. The classic hypermnesia effect was obtained, but with no supplemental contribution of hypnosis. In Experiment 2, hypnosis was introduced only after 6 waking-recall trials. Hypnosis again failed to enhance retrieval of new correct items, although it increased the production of new incorrect recall among hypnotizable individuals. The findings provide no evidence for alleged hypermnesic properties of hypnosis.

Depressogenic cognitive styles: predictive validity, information processing and personality characteristics, and developmental origins.

Two of the major cognitive theories of depression, the theory of Beck [Beck, A. T. (1967). Depression: clinical, experimental and theoretical aspects. New York: Harper & Row. and Beck, A. T. (1987) Cognitive models of depression. Journal of Cognitive Psychotherapy: an International Quarterly, 1, 5-37] and the hopelessness theory [Abramson, Metalsky, & Alloy, (1989) Hopelessness depression: a theory-based subtype of depression. Psychological Review, 96, 358-372], include the hypothesis that particular negative cognitive styles increase individuals' likelihood of developing episodes of depression, in particular, a cognitively mediated subtype of depression, when they encounter negative life events. The Temple-Wisconsin Cognitive Vulnerability to Depression (CVD) project is a two-site, prospective longitudinal study designed to test this cognitive vulnerability hypothesis, as well as the other etiological hypotheses of Beck's and the hopelessness theories of depression. In this article, based on CVD project findings to date, we review evidence that the hypothesized depressogenic cognitive styles do indeed confer vulnerability for clinically significant depressive disorders and suicidality. In addition, we present evidence regarding moderators of these depressogenic cognitive styles, the information processing and personality correlates of these styles and the possible developmental antecedents of these styles. We end with a consideration of future research directions and the clinical implications of cognitive vulnerability to depression.

Childhood maltreatment and college students' current suicidal ideation: a test of the hopelessness theory.

Few studies have examined the relation between childhood maltreatment and adult suicidality within the context of a coherent theoretical model. The current study evaluates the ability of the hopelessness theory of depression's (Abramson, Metalsky, & Alloy, 1989) etiological chain to account for this relation in a sample of 297 undergraduates. Supporting the model, emotional, but not physical or sexual, maltreatment was uniquely related to average levels of suicidal ideation across a 2.5-year follow-up. Further, students' cognitive styles and average levels of hopelessness partially mediated this relation. Although these results cannot speak to causality, they support the developmental model evaluated.

Duration-reduction of avoidance sessions as negative reinforcement.

Five rats were exposed to a shock-postponement procedure in which responses on each of two levers initially had equivalent effects. After an initial training sequence that ensured at least some responding on each lever, an additional consequence was made conjointly operative on the previously less-preferred lever for each animal. Each response on this lever continued to postpone shock, but also reduced the session duration by one minute. The conjoint contingencies were operative until, through session-shortening responses and the passage of time, the session was scheduled to end in two minutes; during the final two minutes the session-shortening contingency was disabled while the shock-postponement contingency continued to be operative on both levers. When responding shifted to a predominance on the session-shortening lever, the conjoint contingency was shifted to the other lever; for four of the five rats this reversal was followed by two additional reversals. Two of the rats' responding showed clear, strong, and unambiguous sensitivity to the session-shortening contingency. The responding of two others was also systematically controlled by that contingency, but the effects were less clearcut. The fifth animal showed an initial shift when session-shortening was introduced, but its subsequent behavior proved insensitive to reversals of procedure. The results clearly indicate a sensitivity of behavior to events on a time scale quite distinct from that of immediate consequences. They also support an interpretation of avoidance sessions, considered in their entirety, as events whose contingent relationship to behavior can affect that behavior-even in the absence of stimuli that delineate those relationships. Finally, these results support an interpretation of aversively based conditioning within a broader context, analogous to the "open versus closed economy" interpretation of appetitively controlled behavior.

Memory liabilities associated with hypnosis: does low hypnotizability confer immunity?

Retrospective analyses of data from the authors' program of research on hypnosis and memory are presented, with special emphasis on effects observed among low hypnotizable individuals. In Experiment 1, participants completed seven forced-recall trials in an attempt to remember a series of pictures that had been shown 1 week earlier. For half the participants, the middle five trials were carried out using hypnotic procedures; the remaining participants performed all recall attempts in a motivated waking condition. Hypnosis failed to enhance correct recall for either high or low hypnotizable participants beyond the hypermnesia and reminiscence effects associated with repeated retrieval attempts over time. However, whereas high hypnotizable participants produced substantial numbers of confident recall errors (i.e., intrusions) independent of the use of hypnosis, low hypnotizable participants exposed to hypnotic procedures reported significantly more intrusions than their counterparts in the waking condition. In Experiment 2, participants were asked to identify whether specific recollections, reported during two forced-interrogatory recall tests conducted 1 week earlier, had originated in the first or second of those tests. A general bias to misattribute previously reported recollections to the first of two recall occasions was observed; however, the effect was greatest among low hypnotizables who had undergone the second recall attempt in hypnosis. The findings imply that highly hypnotizable individuals are not unique in their vulnerability to distortions of memory induced by hypnotic techniques. Individuals of lesser hypnotic capacity also manifest memory alterations when exposed to such procedures.

Self-hypnosis training as an adjunctive treatment in the management of pain associated with sickle cell disease.

A cohort of patients with sickle cell disease, consisting of children, adolescents, and adults, who reported experiencing three or more episodes of vaso-occlusive pain the preceding year, were enrolled in a prospective two-period treatment protocol. Following a 4-month conventional treatment baseline phase, a supplemental cognitive-behavioral pain management program that centered on self-hypnosis was implemented over the next 18 months. Frequency of self-hypnosis group straining sessions began at once per week for the first 6 months, became biweekly for the next 6 months, and finally occurred once every third week for the remaining 6 months. Results indicate that the self-hypnosis intervention was associated with a significant reduction in pain days. Both the proportion of "bad sleep" nights and the use of pain medications also decreased significantly during the self-hypnosis treatment phase. However, participants continued to report disturbed sleep and to require medications on those days during which they did experience pain. Findings further suggest that the overall reduction in pain frequency was due to the elimination of less severe episodes of pain. Non-specific factors may have contributed to the efficacy of treatment. Nevertheless, the program clearly demonstrates that an adjunctive behavioral treatment for sickle cell pain, involving patient self-management and regular contact with a medical self-hypnosis team, can be beneficial in reducing recurrent, unpredictable episodes of pain in a patient population for whom few safe, cost-effective medical alternatives exist.

Mood congruence and depressive deficits in memory: a forced-recall analysis.

Two experiments examined the contribution of reporting biases to mood-congruent recall patterns and diminished levels of recall frequently associated with depressed mood states. In Experiment 1, participants classified as dysphoric (n = 14) or nondepressed (n = 21) on the basis of scores on the Beck Depression Inventory and the Profile of Mood States made self-referential judgements regarding a series of affectively valenced words. Subsequently they were given an unexpected forced-recall test, which encouraged guessing to meet the output requirement (i.e. 40 responses) of the test. Nondepressed subjects confidently reported more positive words than dysphoric subjects, but the latter produced significantly more correct guesses of words that were positively valenced. Similar findings were obtained in Experiment 2, in which dysphoric (n = 40) and nondepressed subjects (n = 40) performed both self-referent and orthographic judgements of affectively valenced words, followed by either a free- or forced-recall test. The findings suggest that positive and negative trait words were adequately encoded in memory, but, consistent with cognitive theories of depression, their accessibility to retrieval was differentially limited. In addition, however, the results implicate an important contribution of diminished motivation and/or conservative report criterion in the manifestation of depression-related biases and deficits in recall.

Suicidality and cognitive vulnerability to depression among college students: a prospective study.

Using a behavioral high-risk two-site prospective design, we tested the cognitive vulnerability hypotheses about suicidality. Consistent with prediction, the high cognitive risk (HR) participants were more likely than the low cognitive risk (LR) participants to exhibit suicidality, measured by both structured diagnostic interview and questionnaire self-report, during the 2 1/2 year prospective follow-up period. Moreover, when the prospective period was examined as a whole, the mediation hypothesis derived from the cognitive theories was strongly supported. Hopelessness appeared to mediate the obtained relationship between cognitive vulnerability and suicidality. Finally, the obtained relationship between cognitive vulnerability and suicidality was not mediated by other hypothesized risk factors for suicidality not specified in the cognitive theories, such as past suicidality, personal history of depressive disorders, borderline and antisocial personality dysfunction, and parental history of depression.

Psychosocial and immune effects of self-hypnosis training for stress management throughout the first semester of medical school.

This study was a 19-week prospective conducted to determine the effectiveness of a self-hypnosis/relaxation intervention to relieve symptoms of psychological distress and moderate immune system reactivity to examination stress in 35 first-year medical students. Twenty-one subjects were randomly selected for training in the use of self-hypnosis as a coping skill and were encouraged to practice regularly and to maintain daily diary records related to mood, sleep, physical symptoms, and frequency of relaxation practice. An additional 14 subjects received no explicit training in stress-reduction strategies, but completed similar daily diaries. Self-report psychosocial and symptom measures, as well as blood draws, were obtained at four time points: orientation, late semester, examination period, and postsemester recovery. It was found that significant increases in stress and fatigue occurred during the examination period, paralleled by increases in counts of B lymphocytes and activated T lymphocytes, PHA-induced and PWM-induced blastogenesis, and natural killer cell (NK) cytotoxicity. No immune decreases were observed. Subjects in the self-hypnosis condition reported significantly less distress and anxiety than their nonintervention counterparts, but the two groups did not differ with respect to immune function. Nevertheless, within the self-hypnosis group, the quality of the exercises (ie, relaxation ratings) predicted both the number of NK cells and NK activity. It was concluded that stress associated with academic demands affects immune function, but immune suppression is not inevitable. Practice of self-hypnosis reduces distress, without differential immune effects. However, individual responses to the self-hypnosis intervention appear to predict immune outcomes.