Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.

Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.

Background General population survey data are presented on the lifetime prevalence of suicide attempts as well as transition probabilities to onset of ideation, plans among ideators, and attempts among ideators either with or without a plan. Risk factors for these transitions are also studied. Methods Data are from part II of the National Comorbidity Survey, a nationally representative survey carried out from 1990 to 1992 in a sample of 5877 respondents aged 15 to 54 years to study prevalences and correlates of DSM-III-R disorders. Transitions are estimated using life-table analysis. Risk factors are examined using survival analysis. Results Of the respondents, 13.5% reported lifetime ideation, 3.9% a plan, and 4.6% an attempt. Cumulative probabilities were 34% for the transition from ideation to a plan, 72% from a plan to an attempt, and 26% from ideation to an unplanned attempt. About 90% of unplanned and 60% of planned first attempts occurred within 1 year of the onset of ideation. All significant risk factors (female, previously married, age less than 25 years, in a recent cohort, poorly educated, and having 1 or more of the DSM-III-R disorders assessed in the survey) were more strongly related to ideation than to progression from ideation to a plan or an attempt. Conclusions Prevention efforts should focus on planned attempts because of the rapid onset and unpredictability of unplanned attempts. More research is needed on the determinants of unplanned attempts.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/205075/yoa8303.pdf

Prevalence of and risk factors for lifetime suicide attempts in the National Comorbidity Survey.

Advances in the conceptualization and measurement of life stress in the past 2 decades raise several questions concerning traditional diathesis— stress theories of psychopathology. First, comprehensive measures of life stress force investigators to become more precise about the particular stressful circumstances hypothesized to interact with diatheses. Second, the influence of the diathesis on a person's life is typically ignored, which results in several types of possible bias in the assessment of life stress. Finally, information is available on diatheses and stress for specific disorders to provide a foundation for more empirically based hypotheses about diathesis—stress interactions. This possibility is outlined for depression. Such an approach provides the basis for developing broader, yet more specific, frameworks for investigating diathesis—stress theories of psychopathology in general and of depression in particular.

Diathesis-stress theories in the context of life stress research: Implications for the depressive disorders.

People who are sensitive to social rejection tend to anxiously expect, readily perceive, and overreact to it. This article shows that this cognitive-affective processing disposition undermines intimate relationships. Study 1 describes a measure that operationalizes the anxious-expectations component of rejection sensitivity. Study 2 provides experimental evidence that people who anxiously expect rejection readily perceive intentional rejection in the ambiguous behavior of others. Study 3 shows that people who enter romantic relationships with anxious expectations of rejection readily perceive intentional rejection in the insensitive behavior of their new partners. Study 4 demonstrates that rejection-sensitive people and their romantic partners are dissatisfied with their relationships. Rejection-sensitive men's jealousy and rejection-sensitive women's hostility and diminished supportiveness help explain their partners' dissatisfaction.

https://www.ffri.hr/~ibrdar/komunikacija/seminari/Downey,%201996%20-%20Rejection%20Sensitivity%20for%20intimate%20relationsh.pdf

Implications of rejection sensitivity for intimate relationships.

OBJECTIVE: Risk factors for suicide attempts have rarely been studied comprehensively in more than one psychiatric disorder, preventing estimation of the relative importance and the generalizability of different putative risk factors across psychiatric diagnoses. The authors conducted a study of suicide attempts in patients with mood disorders, psychoses, and other diagnoses. Their goal was to determine the generalizability and relative importance of risk factors for suicidal acts across diagnostic boundaries and to develop a hypothetical, explanatory, and predictive model of suicidal behavior that can subsequently be tested in a prospective study. METHOD: Following admission to a university psychiatric hospital, 347 consecutive patients who were 14–72 years old (51% were male and 68% were Caucasian) were recruited for study. Structured clinical interviews generated axis I and axis II diagnoses. Lifetime suicidal acts, traits of aggression and impulsivity, objective and subjective severity of acute psycho...

https://ajp.psychiatryonline.org/doi/pdf/10.1176/ajp.156.2.181

Toward a clinical model of suicidal behavior in psychiatric patients.

Panic disorder, which is found in about 1.5 percent of the population at some time in their lives, includes recurrent episodes of sudden, unpredictable, intense fear accompanied by symptoms such as palpitations, chest pain, and faintness. Panic attacks, which do not meet these diagnostic criteria fully, are two to three times more prevalent. Since panic symptoms can mimic those of other medical disorders, patients with these symptoms use medical services frequently. To determine the risk of suicidal ideation and suicide attempts in panic disorder and attacks, we studied a random sample of 18,011 adults drawn from five U.S. communities. Subjects who had panic disorder, as compared with other psychiatric disorders, had more suicidal ideation and suicide attempts, with an adjusted odds ratio for suicide attempts of 2.62 (95 percent confidence interval, 1.83 to 3.74). The odds ratio was 17.99 (95 percent confidence interval, 12.18 to 26.58) when the group with panic disorder was compared with subjects who had no psychiatric disorder. Twenty percent of the subjects with panic disorder and 12 percent of those with panic attacks had made suicide attempts. These results could not be explained by the coexistence of major depression or of alcohol or drug abuse. We conclude that panic disorder and attacks are associated with an increased risk of suicidal ideation and suicide attempts. Physicians working in general medical settings and emergency departments should be alert to this problem.

Suicidal Ideation and Suicide Attempts in Panic Disorder and Attacks

Data from the Epidemiologic Catchment Area study showed that a lifetime Diagnostic Interview Schedule/DSM-III diagnosis of panic disorder was associated with pervasive social and health consequences similar to or greater than those associated with major depression. These consequences included subjective feelings of poor physical and emotional health, alcohol and other drug abuse, increased likelihood of suicide attempts, impaired social and marital functioning, financial dependency, and increased use of psychoactive medications, health services, and the hospital emergency department for emotional problems. Comorbidity of panic disorder with major depression, agoraphobia, and alcohol or other drug abuse did not explain these findings. The social and health consequences of panic disorder (quality of life) should be considered, as risks and benefits of currently available acute and maintenance treatments are evaluated. Clinical trials of panic disorder, whether of drugs or behavioral treatment, should include quality of life assessments as outcome measures. Long-term prospective studies based on clinical samples of patients with panic disorder are indicated to relate the illness more precisely to social morbidity.

Quality of Life in Panic Disorder

• One hundred nineteen patients who met specific criteria for atypical depression completed six weeks of double-blind, randomly assigned treatment with phenelzine sulfate, imipramine hydrochloride, or placebo. The overall response rates were 71% with phenelzine, 50% with imipramine, and 28% with placebo. Phenelzine was widely superior to placebo and also showed superiority to imipramine. Phenelzine superiority appeared even greater after an additional six-week continuation phase. Imipramine was only moderately effective in this atypical depressive sample. Unexpectedly, the superiority of either phenelzine or imipramine to placebo was largely confined to patients in subsets of the study sample who were prospectively judged to also have a history of spontaneous panic attacks and/or show hysteroid dysphoric features. This is consonant with some but not other recent findings and requires replication. Overall, the concept of atypical depression as a subtype that is preferentially responsive to monoamine oxidase inhibitors is supported.

Antidepressant Specificity in Atypical Depression

• Sixty patients meeting specific criteria for atypical depression completed six weeks of double-blind, randomly assigned treatment with phenelzine sulfate, imipramine hydrochloride, or placebo. The overall response rates were 67% with phenelzine, 43% with imipramine, and 29% with placebo. At week 6, phenelzine was superior to placebo on many measures, while the superiority of imipramine to placebo was confined to several variables. Phenelzine was superior to imipramine on the interpersonal sensitivity and paranola factors of the 90-Item Hopkins Symptom Checklist, with trends toward superiority on several other measures, while imipramine was not differentially superior on any measure. Atypical depressive patients with a history of spontaneous panic attacks and hysteroid dysphoric patients both showed extremely low rates of response to placebo and high rates of response to phenelzine. Conversely, those without panic or hysteroid dysphoric features responded equally to all three treatments. Responders to phenelzine also had greater platelet monoamine oxidase inhibition while receiving drug therapy than did nonresponders. Completion of the 120-patient sample will allow more detailed analyses.

Phenelzine v Imipramine in Atypical Depression: A Preliminary Report

Follow-up studies of psychiatric patients with panic disorder have shown an abnormally high mortality rate in men due to cardiovascular and cerebrovascular events. The authors report that in the New Haven portion of the Epidemiologic Catchment Area program the risk for stroke in persons with lifetime diagnoses of panic disorder was over twice that in persons with other psychiatric disorders or no psychiatric disorder. After adjustments for demographic differences between groups, the risk was even higher. While the results should be interpreted cautiously because of the small sample and absence of medical examinations, these findings are consistent with clinical studies showing an association between panic disorder and cardiovascular/cerebrovascular events.

Jeffrey S. Markowitz

Papers

Suicidal Ideation and Suicide Attempts in Panic Disorder and Attacks

Quality of Life in Panic Disorder

Antidepressant Specificity in Atypical Depression

Phenelzine v Imipramine in Atypical Depression: A Preliminary Report

Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey.