Frances H. Gabbay

Triggers of myocardial ischemia during daily life in patients with coronary artery disease : Physical and mental activities, anger and smoking

OBJECTIVES This study assessed the potency of physical and mental activities and emotions (anger and anxiety) and smoking and other substance use as proximate triggers of ischemia in patients with coronary artery disease during daily life. BACKGROUND Myocardial ischemia occurs during a wide variety of activities in patients with coronary artery disease, but frequency and relative potency of physical and mental activities, smoking and use of caffeine and alcohol as triggers of ischemia during daily life have not been established. METHODS Patients (n = 63) with coronary artery disease and evidence of out-of-hospital ischemia kept a validated structured diary of physical and mental activities and psychologic states while undergoing ambulatory electrocardiographic monitoring for 24 to 48 h. RESULTS Ischemia occurred most frequently during moderately intense physical and mental activities. Patients spent the largest proportion of time engaged in low intensity physical and mental activities (p < 0.05), but the likelihood of ischemia was greatest during intense physical (p < 0.0001) and stressful mental activities (p < 0.03). The percentage of time in ischemia was elevated and approximately equivalent for high intensity physical and high intensity mental activities (5%) compared with 0.2% when patients were engaged in low intensity activities. Strenuous physical activity (e.g., effortful walking, p < 0.05) and the experience of intense anger were potent ischemic triggers, and heart rates at onset of ischemia increased with the intensity of physical and mental activity and with anger. Among smokers, ischemia was more than five times as likely when patients smoked than when they did not (during 24% vs. 5% of diary entries, p < 0.0001). Coffee and alcohol consumption were also related to ischemia (p < 0.05), but this association disappeared after controlling for concurrent cigarette smoking. CONCLUSIONS Triggers of ischemia in patients with coronary artery disease during daily life include not only strenuous exercise, but also activities involving low levels of exertion, such as anger and smoking. Mental activities appear to be as potent as physical activities in triggering daily life ischemia. Coffee and alcohol consumption are related to ischemia only by virtue of their associations with smoking.

D2 dopamine receptor Gene TaqI A1 and B1 restriction fragment length polymorphisms: Enhanced frequencies in psychostimulant-preferring polysubstance abusers

Several lines of evidence suggest that presence of a D2 dopamine receptor (DRD2) gene variant marked by TaqI restriction fragment length polymorphisms (RFLPs) might contribute to vulnerability to substance abuse. Psychostimulants display the most robust enhancement of dopamine activity in mesolimbic/mesocortical circuits important for behavioral reward. The present study tests the hypothesis that a DRD2 gene variant might be more prominent in polysubstance users who preferentially use psychostimulants than in addicts with preferential opiate use or in those with no drug preference. Polysubstance users with histories of heavy daily preferential psychostimulant use more often displayed one or two copies of the TaqI A1 (27/62 = 43.5% vs 33/119 = 27.7% for controls), and B1 (20/62 = 32.3% vs 23/119 = 19.8% for controls) markers at the DRD2 locus. DRD2 gene marker distributions in abusers with more prominent opiate use, or those with no history of drug preference, were similar to control genotypes. Psychostimulant-preferring drug users also reported earlier onset of psychostimulant use. Our data are consistent with the hypothesis that DRD2 gene variants marked by these polymorphisms may work, probably in concert with other genetic and environmental factors, to enhance vulnerability to psychostimulant abuse.

Circadian Variation of Ambulatory Myocardial Ischemia Triggering by Daily Activities and Evidence for an Endogenous Circadian Component

BACKGROUND The morning peak in myocardial ischemia has been related to diurnal variations in physical and mental activities and to postural changes upon awakening. This study assesses (1) the effects of exogenous activity triggers at different times of the day and (2) the contribution of an endogenous (ie, activity- and posture-independent) circadian vulnerability for ambulatory ischemia. METHODS AND RESULTS Sixty-three stable coronary artery disease patients underwent ambulatory ECG monitoring and completed a structured diary assessing physical and mental activities. During 2519 hours of observation, a morning increase in ischemia coincided with increases in physical and mental activities, and an evening decrease in ischemia coincided with a decline in activities. During the morning, ischemic versus ischemia-free periods were more likely to occur with high levels of physical activity (P < .001). High physical activity triggered ischemia to a lesser but still significant extent (P < .05) in the afternoon but not in the evening (P = NS). High levels of mental activity triggered ischemia significantly during the morning (P < .04) and evening (P < .04) but not in the afternoon. When a residualized score procedure was used to correct ischemic time for each patients simultaneously measured activities, for hourly heart rates, or for activity-related heart rate fluctuations, the circadian variation in ischemia was still observed (P < .001), with a peak at 6 AM. A significant increase in ischemia occurred immediately after awakening (P < .05), but activity-adjusted increases in morning ischemia persisted (P < .05) for 2 hours after awakening. CONCLUSIONS Exogenous factors (physical and mental activities) are most potent as triggers of ischemia during the morning hours, and the postural change after awakening contributes to the morning increase in ischemia. There is also evidence for an endogenous, activity-independent circadian influence on ischemic susceptibility that is independent of exogenous factors and that sustains the increase in ischemia upon awakening.

Evidence for a new late positive ERP component in an attended novelty oddball task

In attended novelty oddball tasks, rare nontarget stimuli can elicit two late positive ERP components: P3a and P300. In passive oddball tasks, P300 is not elicited by these stimuli. In passive tasks, however, P3a is accompanied by another positive component, termed eP3a, which may have evaded detection in attended oddball tasks because of its spatiotemporal overlap with P300. To address this, temporal-spatial principal components analysis was used to quantify ERPs recorded in attended three-tone and novelty oddball tasks. As expected, novel stimuli elicited both P3a and P300. The analysis also identified a third component, evident in novelty ERPs as an inflection on the leading edge of P3a. This component has the same antecedent conditions as P3a, but is earlier and more centrally distributed. Its spatiotemporal characteristics suggest that it may be the eP3a component recently described in passive oddball tasks.

Family history of alcoholism and response to amphetamine: sex differences in the effect of risk.

BACKGROUND Individuals at risk for alcoholism exhibit an enhanced stimulant response to alcohol. It is not known whether individuals at risk also exhibit a heightened sensitivity to other drugs with stimulant properties. METHODS Healthy young men and women each received, in separate sessions, placebo and 10 mg of d-amphetamine in counterbalanced order. Stimulant and sedative subjective effects were recorded before and three times after capsule administration using the Biphasic Alcohol Effects Scale. The sample comprised 19 family-history-positive (FHP; 58% women) and 53 family-history-negative (FHN; 51% women) participants. RESULTS As compared with placebo, amphetamine increased ratings of stimulation in the sample as a whole. In addition, the ratings revealed an enhanced, as well as a protracted, stimulant response to amphetamine among FHP men, as compared with FHN men: for FHP men, ratings of stimulation made 3 and 6 hr after amphetamine administration were greater than baseline ratings. Moreover, in FHP men, the effect of amphetamine, as compared with placebo, was most evident 6 hr after capsule administration. In contrast, despite a dose x hour interaction in FHN men, post hoc comparisons revealed no differences between the baseline and any of the postamphetamine measurements or between amphetamine and placebo ratings at any of the time points. Among women, the drug effect did not differentiate the family-history groups. CONCLUSIONS Consistent with previous research on alcohol, high-risk men exhibited a heightened stimulant response to amphetamine. Thus, for men, sensitivity to the stimulant properties of drugs may be an endophenotype for alcoholism. Whereas the present results suggest that women at risk do not exhibit an enhanced stimulant response to amphetamine, further study is needed, including evaluation at various points in the menstrual cycle.

Brain potential indices of novelty processing are associated with preference for amphetamine.

A behavioral drug preference procedure was used to identify two groups of healthy individuals. One group preferred 10 mg of d-amphetamine over placebo (Choosers) and the other preferred placebo (Nonchoosers). In separate sessions, participants were administered placebo, 10, and 15 mg of d-amphetamine, and event-related brain potentials (ERPs) were recorded while participants performed two 3-stimulus oddball tasks. The effect of d-amphetamine on P3a, an ERP index of the orienting response, differed between groups: In Choosers, target stimuli elicited P3a after d-amphetamine but not after placebo; in Nonchoosers, the drug had no effect on P3a. Moreover, two group differences were evident after placebo and were unaffected by d-amphetamine. (1) N100 was larger in Nonchoosers than in Choosers, suggesting that Nonchoosers were more attentive than Choosers to the physical features of the stimuli. (2) The reorienting negativity (RON) elicited by targets in both tasks and by rare nontargets in a novelty oddball task (i.e., novel sounds) was larger in Nonchoosers than in Choosers. This suggests that Nonchoosers more effectively refocused attention on the task after distraction. It is hypothesized that these processing differences reflect a group difference in the balance between midbrain dopamine function and ascending cholinergic influences. The findings have implications for vulnerability to addiction and illustrate the promise of ERPs in parsing elemental phenotypes.

Behavioral Triggers of Silent and Symptomatic Myocardial Ischemia

Behavior and Myocardial Ischemia. Recent ambulatory electrocardiography studies reveal that myocardial ischemia out‐of‐hospital exhibits features that may not be evident during controlled exercise testing. Specifically, out‐of‐hospital ischemia: (1) is more frequently asymptomatic or silent; (2) occurs during a wide variety of mental, as well as physical, activities; (3) is triggered at relatively low heart rate elevations compared to exercise; (4) exhibits a circadian rhythm; and (5) exhibits variability over time. This article reviews recent field and laboratory research suggesting that behavioral factors, including mental stress, may contribute to the typical features of myocardial ischemia out‐of‐hospital.

The role of endocannabinoid function in posttraumatic stress disorder: Modulating the risk phenotype and rendering effects of trauma

Posttraumatic stress disorder (PTSD) is a debilitating consequence of trauma in military and civilian settings. Substantial evidence implicates endocannabinoid function in three dimensions associated with risk for the disorder and in the etiology of essential symptoms. Negative (fear-avoidance) and positive (approach-reward) systems, and a dispositional dimension of control, modulate risk for PTSD and rely heavily on endocannabinoid function. Moreover, animal models associate an exaggerated fear response, characteristic of PTSD, with compromised endocannabinoid signaling, while plasticity in the same system renders effects of trauma in early life, fundamentally altering the stress response. Further implicating the endocannabinoid system, PTSD often co-occurs with cannabis use. Cannabis appears to alleviate negative affect states and symptoms of PTSD, possibly by normalizing endocannabinoid function. While this diverse evidence recommends the endocannabinoid system as a therapeutic target, it also reveals complexities that complicate efforts to develop such therapies. Scientific analysis of endocannabinoid function in PTSD will facilitate these efforts, while also informing a developing discussion on medical and recreational use of marijuana.

A quiet voice: Roland Clark Davis and the emergence of psychophysiology

The 50th anniversary of the founding of the Society for Psychophysiological Research (SPR) provides an occasion to look back at the history of the Society and its founders. In particular, it is fitting to consider the life and work of the Chair of the Organizing Board, Roland Clark Davis, in the context of this anniversary. This examination reveals threads that connect psychophysiology to its roots in physiology and psychology and to efforts early in the last century to move psychology further into the realm of the empirical sciences. It also reveals a portrait of a quiet man who helped to weave those threads into a new discipline. With a gentle but insistent voice, Davis called upon his colleagues in the young field to eschew a rush to judgment—by retrofitting psychophysiological data to existing theories or prematurely espousing new theories— and instead apply the new tools of an emerging discipline thoughtfully and systematically toward the goal of empirical discovery. This year also marks the 50th anniversary of Davis’s untimely death. He died on February 23, 1961, at the age of 59, just as an informal network of psychophysiologists was coalescing into the organization that is now SPR.