J. Richard Jennings

Psychological stress and the progression of carotid artery disease

Background We examined the relation between cardiovascular reactivity (the response of the cardiovascular system to psychological stress) and the severity and progression of carotid atherosclerosis. Methods Using duplex ultrasonography, we measured the change in the area of all detectable plaques in the extracranial carotid arteries during 2 years. Cardiovascular reactivity was assessed by measuring changes in hemodynamics during a frustrating cognitive task (the Stroop Color Word Interference Task). Established risk factors for atherosclerosis were measured by interviewing patients, a physical examination, and blood assays for 351 subjects with a wide range of types of atherosclerotic disease. Results Atherosclerotic plaques were present in the carotid arteries of 273 (78%) subjects. In a forward stepwise multiple regression analysis, it was found that greater age (β = 0.46), a history of hypertension (β = 0.20), use of lipid level-lowering agents (β = 0.18), a longer history of smoking (β = 0.13), a larger cholesterol: high-density lipoprotein ratio (β = 0.13), a smaller change in heart rate during the task (β = −0.12), and a higher resting systolic blood pressure (SBP; β = 0.11) were associated significantly with a greater plaque area (R2 = 0.35). In 136 untreated subjects who were followed up for 2 years, a greater change in SBP during the task (b = 0.28), a higher total cholesterol: high-density lipoprotein ratio (β = 0.23), a shorter resting preejection period (β = −0.19), and a lower body mass index (β = −0.17) were significant predictors of the change in atherosclerosis, after controlling for age and initial plaque area in a stepwise multiple regression analysis (R2 = 0.24). Conclusions These results support the hypothesis that hemodynamic responses under conditions of mental stress may influence the progression of atherosclerosis.

A psychophysiological analysis of inhibitory motor control in the stop-signal paradigm

We examined two potential inhibitory mechanisms for stopping a motor response. Participants performed a standard visual two-choice task in which visual stop signals and no-go signals were presented on a small proportion of the trials. Psychophysiological measures were taken during task performance to examine the time course of response activation and inhibition. The results were consistent with a horse race model previously proposed to account for data obtained using a stop-signal paradigm. The pattern of psychophysiological responses was similar on stop-signal and no-go trials suggesting that the same mechanism may initiate inhibitory control in both situations. We found a distinct frontal brain wave suggesting that inhibitory motor control is instigated from the frontal cortex. The results are best explained in terms of a single, centrally located inhibition mechanism. Results are discussed in terms of current neurophysiological knowledge.

Exaggerated Blood Pressure Responses During Mental Stress Are Associated With Enhanced Carotid Atherosclerosis in Middle-Aged Finnish Men Findings From the Kuopio Ischemic Heart Disease Study

BACKGROUND Exaggerated cardiovascular reactivity to mental stress is hypothesized to increase atherosclerotic risk. We examined this hypothesis using cross-sectional data from the Kuopio Ischemic Heart Disease study, a population-based epidemiological sample. METHODS AND RESULTS 901 Eastern Finnish men from four age cohorts (age, 42 to 60 years) were administered a standardized testing battery to assess cardiovascular reactivity to mental stress. Ultrasound measures of intima-medial thickness (IMT) and plaque height from the common carotid arteries were used as noninvasive markers of atherosclerosis. Diastolic blood pressure (DBP) responses to mental stress were significantly associated with mean IMT (b=.021, P=.006), maximum IMT (b=.026, P=.013), and mean plaque height (b=.017, P=.041). Significant associations were also shown between stress-related systolic blood pressure (SBP) reactivity and mean IMT (b=.0151, P=.042). When examined separately by age, associations with IMT were significant only in the youngest half of the sample (age, 46 and 52 years, n=433; for mean IMT, DBP b=.033, P=.0002, SBP b=.0266, P=.003; for maximum IMT, DBP b=.039, P=.002, SBP b=.032, P=.011). Results remained significant in the younger subjects after adjustment for smoking, lipid profiles, fasting glucose, and resting blood pressure (b=.024, P=.011); results also remained significant in a subgroup of unmedicated younger subjects without symptomatic cardiovascular disease (n=135; for SBP reactivity, b=.031, P=.036; for DBP, b=.037, P=.007). CONCLUSIONS The tendency to show exaggerated pressor responses to mental stress is a significant independent correlate of atherosclerosis in this population sample of Finnish men. The effect does not appear to be accounted for by the confounding influence of other risk factors or preexisting clinical disease.

Attention influences sensory integration for postural control in older adults

This study investigated the influence of attention on the sensory integration component of postural control in young and older adults. Eighteen young and 18 older healthy subjects performed information-processing tasks during different postural challenge conditions. Postural conditions included seated, standing on a firm surface, standing on a sway-referenced floor, and standing on a sway-referenced floor while viewing a sway-referenced scene. During each condition, reaction time (RT) was measured during two simple and one inhibitory RT tasks. For the inhibitory task, the time required to inhibit an action was derived, termed the inhibitory time (IT). Performing a RT task was associated with increased postural sway in older subjects, but not in young subjects. The greatest influence of RT task on sway of older subjects was found during the sway-referenced floor/sway-referenced scene condition. Conversely, postural condition had an influence on RT task performance in both young and older subjects. The IT was increased in both young and older subjects only during the sway-referenced floor/scene condition. These results suggest that the sensory integration component of postural control in particular seems to require attention. Further, our data suggest that attentional processes related to inhibitory control are engaged when sensory integration requirements are high.

Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus

Chronic stress in non-human animals decreases the volume of the hippocampus, a brain region that supports learning and memory and that regulates neuroendocrine activity. In humans with stress-related psychiatric syndromes characterized by impaired learning and memory and dysregulated neuroendocrine activity, surrogate and retrospective indicators of chronic stress are also associated with decreased hippocampal volume. However, it is unknown whether chronic stress is associated with decreased hippocampal volume in those without a clinical syndrome. We tested whether reports of life stress obtained prospectively over an approximate 20-year period predicted later hippocampal grey matter volume in 48 healthy postmenopausal women. Women completed the Perceived Stress Scale repeatedly from 1985 to 2004; in 2005 and 2006, their hippocampal grey matter volume was quantified by voxel-based morphometry. Higher Perceived Stress Scale scores from 1985 to 2004 - an indicator of more chronic life stress - predicted decreased grey matter volume in the right orbitofrontal cortex and right hippocampus. These relationships persisted after accounting for age, total grey matter volume, time since menopause, use of hormone therapy, subclinical depressive symptoms, and other potentially confounding behavioral and age-related cerebrovascular risk factors. The relationship between chronic life stress and regional grey matter volume - particularly in the hippocampus and orbitofrontal cortex - appears to span a continuum that extends to otherwise healthy individuals. Consistent with animal and human clinical evidence, we speculate that chronic-stress-related variations in brain morphology are reciprocally and functionally related to adaptive and maladaptive changes in cognition, neuroendocrine activity, and psychiatric vulnerability.

Individual Differences in Stressor-Evoked Blood Pressure Reactivity Vary with Activation, Volume, and Functional Connectivity of the Amygdala

Individuals who exhibit exaggerated blood pressure reactions to psychological stressors are at risk for hypertension, ventricular hypertrophy, and premature atherosclerosis; however, the neural systems mediating exaggerated blood pressure reactivity and associated cardiovascular risk in humans remain poorly defined. Animal models indicate that the amygdala orchestrates stressor-evoked blood pressure reactions via reciprocal signaling with corticolimbic and brainstem cardiovascular-regulatory circuits. Based on these models, we used a multimodal neuroimaging approach to determine whether human individual differences in stressor-evoked blood pressure reactivity vary with amygdala activation, gray matter volume, and functional connectivity with corticolimbic and brainstem areas implicated in stressor processing and cardiovascular regulation. We monitored mean arterial pressure (MAP) and concurrent functional magnetic resonance imaging BOLD signal changes in healthy young individuals while they completed a Stroop color-word stressor task, validated previously in epidemiological studies of cardiovascular risk. Individuals exhibiting greater stressor-evoked MAP reactivity showed (1) greater amygdala activation, (2) lower amygdala gray matter volume, and (3) stronger positive functional connectivity between the amygdala and perigenual anterior cingulate cortex and brainstem pons. Individual differences in amygdala activation, gray matter volume, and functional connectivity with corticolimbic and brainstem circuits may partly underpin cardiovascular disease risk by impacting stressor-evoked blood pressure reactivity.

BIOBEHAVIORAL FACTORS IN SUDDEN CARDIAC DEATH

The authors examine the recent literature on psychological factors and sudden cardiac death and explore the mediating psychophysiological processes by which these variables may be associated. Direct evidence that psychosocial stressors and their correlates may be causally linked with sudden cardiac death in humans is not conclusive, but there is abundant convergent evidence that several physiological precursors of sudden death may be promoted by psychological challenge, especially in persons with coronary heart disease. The authors call for increased attention to the acute effects of psychological events on cardiovascular health.

Assessment of sexual function in depressed, impotent, and healthy men: Factor analysis of a brief sexual function questionnaire for men

We report a study of sexual function in outpatient men with major depressive disorder (n = 42), compared with healthy control men (n = 37) and a clinic sample complaining of erectile dysfunction (n = 13). A principal-components factor analysis of the Brief Sexual Function Questionnaire confirmed differences in the clinical dimensions of sexual activity/performance, interest, satisfaction, and physiological competence. The four factors accounted for 72% of the variance in the analysis. Acceptable test-retest reliability, construct validity, and concurrent validity (with the Derogatis Sexual Function Inventory and a self-report behavioral log) were demonstrated. Parallel observations with findings from previous nocturnal penile tumescence studies in these same men are discussed.

Exaggerated Blood Pressure Responses During Mental Stress Are Prospectively Related to Enhanced Carotid Atherosclerosis in Middle-Aged Finnish Men

Background—Hemodynamic reactions to mental stress may contribute to atherosclerosis. We previously observed cross-sectional relationships between blood pressure reactions to a standardized stress battery and carotid intima-media thickness (IMT) in the Kuopio Ischemic Heart Disease (KIHD) study. These are the first prospective results on this relationship. Methods and Results—Men from 4 age cohorts (42 to 60 years old at study onset) were challenged with a standardized mental stress battery, and heart rate and blood pressure reactions were assessed. Ultrasound measures of common carotid IMT were collected at this time and 7 years later as noninvasive markers of atherosclerosis. Data were collected from a sample of 756 men at both times. Systolic blood pressure reactions to mental stress at study onset were positively related to mean carotid IMT 7 years later (&bgr;=0.035, P=0.001, by blood pressure quartile, IMT=0.91, 0.93, 0.96, 1.00 mm) and to the progression of IMT (&bgr;=0.020, P=0.006, by blood pressure quartile, &Dgr;IMT=0.08, 0.09, 0.11, 0.11 mm). Similar significant relations were shown for maximal IMT and plaque height. Diastolic blood pressure responses were less strongly related to carotid IMT than were systolic responses. Heart-rate responses were unrelated. Adjustment for standard risk factors did not substantially reduce the relation between systolic blood pressure reactivity and the progression of mean carotid IMT (standardized &bgr;=0.059, P=0.026), maximal carotid IMT (standardized &bgr;=0.084, P=0.006), or plaque height (standardized &bgr;=0.093, P=0.008). Conclusions—The degree of systolic blood pressure reactivity to mental challenge is prospectively related to carotid IMT in middle-aged and older men, independent of known risk factors.

Reactive aggression in boys with disruptive behavior disorders: behavior, physiology, and affect.

This study examined responses to peer provocation in boys ages 9–13 years who met symptomatic criteria for ADHD-only, ODD/CD-only, comorbid ADHD/ODD/CD, or no diagnosis. Boys participated in a reaction-time game that included standardized verbal and behavioral provocation. Their behavioral, physiological, and affective responses to this task were measured. Results showed that groups did not differ following high levels of provocation because all boys behaved aggressively. However, following low provocation boys with comorbid ADHD/ODD/CD had higher levels of behavioral aggression, had greater heart rate acceleration, and were rated as angrier than all other boys. In addition, boys with comorbid ADHD/ODD/CD held a grudge longer than other children. Results suggest that boys with comorbid ADHD/ODD/CD are especially reactive to provocation from their peers.