Ernest H. Friedman

Behavioral Correlates of Coronary Risk

Ernest H. Friedman, MD, Departments of Medicine and Psychiatry, Case Western Reserve University, 1831 Forest Hills Boulevard, Cleveland, OH 44112-4313 (USA) In their study of healthy Italian blue-collar workers, Sanavio et al. [1] find that the content-based Jenkins Activity Survey type A score failed to differentiate subjects who were defined as type Al, A2, and non-A by the structured interview (SI). The possible advantage of the SI in assessing both content and behavior is supported by a report that type A style but not content correlated to lower coronary risk in normal coronary-prone upper middle class Cleveland men [2]. It is also supported by SI studies demonstrating favorable survival among older type A subjects who scored the lowest in anger-hostility and depression [3], and fewer speech hesitation pauses 1 s or more in type A than in type B subjects rated by Rosenman [2], These findings’ prompt identifying cues for prevention or treatment programs [1] by monitoring the frequency and duration of pauses in dialog, 4.79 ± 2.48/min, 1.50 ± 0.33 s (mean ± standard deviation), which correlate with a 6-fold increase in the prevalence and incidence of coronary heart disease, p < 0.05, and mood, respectively. This method is supported by the reduction of blood pressure associated with longer, less recurrent pauses [4] manifested by pauses averaging 1.18 s at > 2/min and 1.93 s at 1/min, yielding a ratio 1.18/1.93 = 0.611 approximating the golden section 0.618 (range 0.5340.833), and the fact that even brief (1-5 s) spontaneous pauses in ongoing patterned behaviors are accompanied by an immediate decrease in 5-hydroxytryptamine neuronal activity to, or below, baseline levels. It is also supported by participatory matching of pauses in dialog at moderate arousal on the order of 1.40 s at 2 pauses/ min, a joint, mutually responsive rhythm [5], the effects of therapy (remission from depressive state) manifested by a decrease of about 25% in the average number of pauses in female patients from 7.89 to 5.88 pauses per 100 syllables, p < 0.05, about 32% in male patients from 7.58 to 5.12 pauses per 100 syllables, p < 0.05, about 59% decrease in mean pause duration from 1.94 to 1.14 s in female patients and 56% decrease from 1.80 to 1.01 s in male patients, p < 0.004 and p < 0.04, respectively [6], and the chronic influence of depression on coronary heart disease manifested by the highly significant correlation (0.67) between obvious depression scores in 1964 and 1974 Glostrup examinations [7], and (0.60, p < 0.01) between pause rates in 1965 and 1975 Cleveland examinations [2]. References Sanavio E, Bertolotti G, Vidotto G, Zotti AM: Neuroticism and type A behavior pattern in healthy Italian blue-collar workers. Psychother Psychosom 1996;65:145-149. Friedman EH, Sanders GG: Speech pattern analysis; in Webster JG (ed): Encyclopedia of Medical Devices and Instruments. New York, Wiley, 1988, pp 2642-2652. Carmelli D, Swan GE: The relationship of type A behavior and its components to all-cause mortality in an elderly subgroup of men from

Respiratory Patterns and Chronic Heart Failure

To the Editor: A primary rhythm in the central nervous system that entrains both heart rate, blood pressure, and ventilation1 is suggested by profound effects on angina through consciously focusing on breathing and intervening pauses; adaptation to stress manifested by slower, …

Neurobiology of Anger-Hostility and Coronary Risk

Ernest H. Friedman, MD, Departments of Medicine and Psychiatry, Case Western Reserve University, 1831 Forest Hills Boulevard, Cleveland, OH 44112-4313 (USA) Ricci Bitti et al. [ 1] find that proneness to coronary heart disease is more significantly correlated with Aggressive Responding (p < 0.0001) than with Anger Arousal (p < 0.002). The neurobiologic features are suggested by reports linking disruption of brain stem cardiovascular control, cardiovascular reactivity in challenging tasks, and subclini-cal impairment of lung airways to dopamine abnormalities lateralized to the right hemisphere. This hypothesis is supported by optimal response organization at intermediate dopamine tone in a medial-frontalstriatal activation system, and by deactivation of the right hemisphere, a state marker of depression, promoting dominance of the left hemisphere associated with cardiac arrhythmia, vasoconstriction [2] and violence [3]. It is also supported by a neurochemical model underlying differences in reaction times between introverts and extroverts [2, 4, 5]. The fact that delay-dependent speeding of reaction time, indicating motor readiness, is abolished by depletion of dopamine [2, 6], prompts a multidisciplinary approach involving neuropharmacology and cardiovascular physiology [7] in investigations of particular components of anger-hostility [ 1 ] by monitoring behavioral correlates of asymmetric brain functions in emotionally charged dialog, reflecting properties of neu-ronal activity and firing. This method is supported by the correlation of the frequency and duration of speech hesitation pauses to 6-fold coronary heart disease and mood, respectively, by the blood pressure reduction effect of longer, less recurrent pauses [2] predictive of response to neuropharmacologic intervention [8], and by studies linking pause rate and variability of pause duration to the left and right hemisphere, respectively [2, 9]. It is also supported by reports suggesting temporal coding in the central nervous system manifested by the association of in-terspike intervals with specific behavioral events [10]. References Ricci Bitti PE, Gremigni P, Bertolotti G, Zotti AM: Dimensions of anger and hostility in cardiac patients, hypertensive patients, and controls. Psychother Psychosom 1995;64:162– 172. Friedman EH, Coyle CP, Santiago MC: Neurobiology of depressive symptoms (letter and reply). Arch Phys Med Rehabil 1995;76:1179. Friedman EH: Mania and paranoid psychosis (letter). Psychosomatics 1992;33:118-119. Ebstein RP, Novick O, Umansky R, Priel B, Osher Y, Blaine D, Bennett ER, Nemanov L, Katz M, Belmaker RH: Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nature Genet 1996;12:78-80.

Psychosocial Factors in Coronary Risk and Rehabilitation

The depressed mental state following myocardial infarction is considered to be the largest psychological barrier to rehabilitation. It has been recommended that the management of depression should begin by the third coronary care unit day. The most convenient practical focus for this is restoration of activity which is the most potent antidote known to combat mental distress of postcoronary convalescence. (Cassem and Hackett, 1973). Individual and group psychotherapy are prominent among other treatment modalities that have been employed during the immediate and long term postcoronary period.

Re: Pulse Pressure and Risk of Alzheimer Disease in Persons Aged 75 Years and Older

To the Editor: Qiu et al1 conclude that an increased pulse pressure, which is a clinical indication of large-artery stiffness and severe atherosclerosis, may increase the risk of Alzheimer disease (AD) and dementia. In addition, lower pulse pressure may increase the risk of AD and dementia through a deleterious …

Young survivors of myocardial infarction.

Ernest H. Friedman, MD, Departments of Medicine and Psychiatry, Case Western Reserve University, 1831 Forest Hills Boulevard, Cleveland, OH 44112-4313 (USA), Tel. 216 681-5200, Fax 216 761-7053 In a study of psychological differences between young male and female survivors of myocardial infarction (MI), Uuskula [1] confirms the importance of subclinical affective symptomatology in the prodromal phase of myocardial infarction and in the definition of recovery. Females suffer considerably more frequently from fatigue and exhaustion in the prodromal period of MI. Women develop a higher level of cognitive-worry, sub-scale score of anxiety; they are more irritable and less able to relax. Neurobiologic features are suggested by reports linking rumination and subclinical impairment of lung airways in panic disorder with dopamine abnormalities lateralized to the right hemisphere, in which the metabolic rate is higher for women. This hypothesis is supported by optimal response organization at intermediate dopamine tone in a medial-frontal-striatal activation system, the concept of cellular tone, and deactivation of the right hemisphere, a state marker of depression, promoting left-hemisphere dominance associated with cardiac arrhythmia and vasoconstriction [2-4]. These observations prompt finding the optimum treatment and psychosocial rehabilitation course for young occupationally active patients with first acute MI [1, 5] and mental stress-induced left ventricular dysfunction predictive of adverse cardiac events [ 1 ‚ 6], by monitoring behavioral correlates of asymmetrical brain functions, reflecting properties of neuronal activity and firing. This method is supported by the correlation of rate and variability in duration of speech hesitation pauses with the left and right hemisphere, respectively [7], the role of the right prefrontal cortex in the discrimination of duration [8] and the association of the reduction of blood pressure with longer, less recurrent pauses predictive of response to neuropharmacologic intervention [7] alleviating depressive symptoms and that recovery from depression was associated with changes in coping style, such that patients relied less on inappropriate emotion-focused coping strategies [2], It is also supported by profound effects on angina pectoris through consciously focusing attention on breathing and intervening pauses, and adaptation to stress manifested by slower, deeper breathing contributing to 6.5-fold reduction in mortality [6]. References Uuskula M: Psychological differences between young male and female survivors of myocardial infarction. Psychother Psychosom 1996;65: 327-330. Friedman EH: Neurobiology of psychosocial factors in peptic ulcer (letter). J Clin Gastroenteroll996;22:165. Friedman EH: Neurobiologic characteristics of umbilical artery lactate levels (letter). Am J Obstet Gynecol 1996;175:236-237.

The Neurobiology of Stereotypies

Ernest H. Friedman, MD, 1831 Forest Hills Blvd., E. Cleveland, OH 94112-4313 (USA) The neurobiology of stereotypies in sows during chronic stress [ 1 ] is suggested by women’s sudden onset of catatonia and disordered gaze, and compulsive ruminations preceding oculogyric crises [2] linked to inefficient cortical circuits and abnormalities of dopa-mine subserving alcohol-seeking behavior [3], coronary-risk (CHD) [4], gastroprotection [5, 6], and mood [7–9]. This hypothesis is supported by the association of specific frontal asymmetries with certain immune functions [ 10] and by chronic stress leading to a reduced immune response [1] decreasing mucosal resistance to infection [11, 12]. These findings suggest that low dopamine may have a role in the inverse relation of tongue playing, a stereotypy, with stomach wall (pyloric) ulcers in veal calves as a result of the absence of roughage (grass, hay, straw) the calves need to develop rumination [1]. The fact that delay-dependent speeding of reaction time, reflecting motor readiness, is abolished by depletion of dopamine [13], suggests evaluating cognitive consequences of dopamine agonism and antagonism at intermediate dopamine tone in a medial-frontal-striatal ‘activation’ system underlying response organization [14] during treatment of the brain-gut axis [5] by monitoring speech hesitation and switching pauses analyzed on a time-base by a microcomputer. Remote data acquisition [13] is a precise, unambiguous method to facilitate further research of gender disparities in CHD [15–20] and to develop a more general picture of the way individuals cope with chronic stressors [1]. This strategy is supported by the concept of cellular tone [21] and by participatory matching of pauses in dialogs at intermediate arousal, a joint, mutually responsive rhythm. It also is supported by the correlation of the frequency and duration of hesitation pauses to CHD and mood, respectively, and by a causal link between a personally relevant, emotionally arousing speaking task and myocardial ischemia of a similar magnitude as exercise [22]. References Wiepkema PR, Schouten WGP: Stereotypies in sows during chronic stress. Psychother Psychosom 1992; 57:194–199. Gambert SR, Gupta KL, Friedman EH, Aronson MK, Ooi WL, Frish-man W, Masur DM: Women and dementia (letters and reply). Neurology 1991:41:461–462. Cloninger CR: Neurogenetic adaptive mechanisms in alcoholism. Science 1987;236:410–416. Svebak S, Knardahl S, Nordby H, Aakvaag A: Components of type A behavior pattern as predictors of neuroendocrine and cardiovascular reactivity in challenging tasks. Person individ Diff 1992;13:733–744. Glavin GB: Dopaine and gastroprotection: The brain-gut axis. Dig Dis Sci 1991;36:1670–1672.

Re: Interhemispheric Asymmetries of Motor Cortex Excitability in the Postacute Stroke Stage

To the Editor: Cicinelli and others1 report that intracortical inhibition was reduced in affected hemispheres and normal in the unaffected hemispheres of stroke patients. Neurobiological features are suggested by 2.5- to …

Neurobiology of Disruptive Nocturnal Behavior

Bliwise et all report that Parkinson’s disease (PD) patients were more likely than Alzheimer’s disease patients to exhibit disruptive nocturnal behavior. The role of neurotransmitter abnormalities is suggested by gaze and thought disorders (e.g., compulsive ruminations preceding oculogyric crises), linked to inefficient cortical circuits and dopamine abnormalities lateralized to the right hemisphere.2 This hypothesis is supported by a report that inhibition of the right hemisphere promotes dominance of the left hemisphere3 subserving violence.4 It is also supported by optimal response organization at intermediate dopamine tone in a medial-frontal-striatal activation system, and by diurnal variation of serotonergic-mediated inhibition of dopamine5 controlling periodic leg movements’ and wakefulness manifested by a reduction of reaction time and gap frequency These findings suggest that circadian timing of asymmetric brain functions may be a reason that PD patients demonstrate a greater likelihood of disruptive nocturnal behavior. 1

Neurobiology of Rhinitis

Ernest H. Friedman, MD, 1831 Forest Hills Blvd, East Cleveland, OH 44112-4313 (USA) In their survey of psychosomatic aspects of otorhinolaryngology, Lamparter and Schmidt [1] report that some patients with rhinitis experience even the physiologic nasal cycle as bothering (unilaterally ‘obstructed’ nose). The neurobiology is suggested by unilateral naris closure leading to a reduction of dopa-mine (DA) [2] lateralized to the right hemisphere [3]. It is also suggested by left nostril breathing improving nonverbal performance [4]. This hypothesis is supported by optimal response organization at intermediate DA tone in a medial-frontal-striatal activation system [3] and by operant conditioning of the activity of a CA1 pyramidal cell in a slice of dorsal hippocampus with local injections of DA. The DA reinforcement function showed a sharp peak at 1 mJlí and fell of abruptly when this optimal concentration was either halved or doubled [5]. It is also supported by studies linking DA to affect, mood, induction of breathing, vasospasm, and wakefulness manifested by a reduction of reaction time and gap frequency [3, 6]. The fact that delay-dependent speeding of reaction time, indicating motor readiness, is abolished by depletion of DA, suggests monitoring speech hesitation and switching pauses [3] in the evaluation and treatment of cases such as a 9-year-old girl who showed a coincidence of sinusitis and modified behavior characterized by withdrawal, depression, fear; these symptoms disappeared together with the sinusitis [1]. This method is supported by profound effects on angina pectoris by attention to breathing and intervening pauses [4]. It is also supported by the blood pressure lowering effect of longer, less recurrent pauses of 1+s, 1.50 ± 0.33 s(x ± SD)and by the association of pauses of 2+ s with prearticulatory repair [7] and competitive and courtship activity [18]. These findings tend to confirm powerful isomorphisms between mind and body and the existence of deep and lawful mental structures governing human cognitive and emotional functioning reflecting properties of neuronal activity and firing [9]. References Lamparter U, Schmidt HU: Psychosomatic medicine and otorhinolaryngology. Psychother Psychosom 1994;61:25-40. Brunjes PC: Unilateral naris closure and olfactory system development. Brain Res Rev 1994; 19:146-160. Friedman EH: Handling of anger and ischemic stroke in women (letter). Stroke 1994;25:521. Jella SA, Shannahoff-Khalsa DS: The effects of unilateral forced nostril breathing on cognitive performance. Int J Neurosci 1993;73:61-68. Stein L, Xue BG, Belluzzi JD: Cellular targets of brain reinforcement systems. Ann NY Acad Sci 1993; 702:41-60. Friedman EH, Nathanielsz PW: Neurobiology of fetal breathing (letter and reply). Am J Obstet Gynecol 1993;169:1361-1362.