Results of PM research in the context of cardiovascular disease (CVD) can be used as a model to illustrate developments in the broader PM research agenda as they relate to understanding mechanisms linking psychiatric morbidity to poorer medical outcomes, as well as the effect of treating psychiatric morbidity on medical outcomes. This model also provides an illustration of the challenges and the future directions in this line of investigation for PM research concerning other physical conditions.
A confluence of evidence suggests that major depression is a risk factor for CVD and poorer cardiac outcomes in patients with CVD. Even minimal elevation in depressive symptoms increases the risk of subsequent cardiac events and mortality. What are the mechanisms underlying this? There has been a great deal of research to find physiologic pathways that explain this link. One plausible mechanism points to dysregulation of the autonomic nervous system as playing a critical role. Decreased activity of the parasympathetic nervous system and increased activity of the sympathetic nervous system are associated with risk of myocardial ischemia, ventricular tachycardia, ventricular fibrillation, and sudden cardiac death in patients with CVD.
Patients with depression are more likely to exhibit autonomic dysfunction as evidenced by increased catecholamine levels, increased heart rate, decreased heart rate variability, baroreflex dysfunction, and higher variability in ventricular repolarization. Additional mechanisms to explain the relationship between depression and CVD include alterations in platelet function, immune system parameters, and behavioral risk factors. Although a number of physiologic parameters have been identified, a conclusive underlying mechanism remains elusive.
If depression adversely affects CVD outcomes, what is the benefit of treating depression to CVD outcomes? Some evidence suggests that treating depression in patients with CVD results in improved cardiac autonomic function. The use of selective serotonin reuptake inhibitors and psychological therapies has proved safe and effective in the treatment of depression in patients who have CVD.
The Sertraline(Drug information on sertraline) Antidepressant Heart Attack Trial (SADHART)5 was a landmark trial because it combined psychiatric, cardiovascular, and physiologic data. Its findings demonstrated a trend for an association between treatment with sertraline and decreased incidence of severe cardiac events. It should be noted, however, that patients treated with sertraline demonstrated decreased platelet and endothelial activation markers. This suggests that the benefit of sertraline may be achieved through its antiplatelet effects rather than through its effects on depression.
The Enhancing Recovery in Coronary Heart Disease (ENRICHD)6 trial, which used a tailored cognitive-behavioral intervention, did not show a relationship between psychotherapeutic treatment and recurrent cardiac events or all-cause mortality in the overall sample, although post hoc analyses demonstrated cardiac benefits among white males. However, a significant proportion of the participants across study arms were taking antidepressant medications, which may have significantly decreased the risk of nonfatal reinfarction or death. Further research is needed to identify the most effective treatments that improve both depression and cardiovascular outcomes by targeting their shared pathophysiology. Once identified, research examining the dissemination of these interventions will be warranted.Future research agenda
PM is now involved with a wide and ever-expanding spectrum of investigations looking at the relationship between physical and psychiatric illness. Important contributions have occurred in HIV/AIDS; cancer; transplantation; cardiac, neurologic, pulmonary, renal, and GI disease; and obstetrics-gynecology. In each of these areas, first-generation studies have identified the extent and nature of psychiatric morbidity associated with the most common diseases or hospitalization. More sophisticated second-generation cross-sectional, epidemiologic studies have established the prevalence rates of a broader range of psychiatric disorders in several medical conditions, as well as less common or newly proposed psychiatric syndromes, such as Alzheimer-associated affective disorder.
In some cases, a new body of research has extended our knowledge about genetic, neurochemical, and behavioral factors contributing to the development of psychiatric disorders among complex medically ill populations. This work has shown that many different mechanisms are involved. Examples include the relationship between the location of brain lesion after stroke and poststroke major depression, or between childhood sexual abuse and the later development of chronic pain syndromes. This has led to more rational intervention studies focused on reducing the rate of occurrence of these disorders, including successful programs that reduce postcardiotomy delirium and other forms of ICU delirium.
The future research agenda for PM will continue to revolve around these themes. The Table displays examples of the sorts of studies that are anticipated in the next few decades. They are grouped by type of study, with specific examples provided within each group. For brevity, the examples are focused on specific psychiatric or medical conditions, even though similar studies might be envisioned involving a range of psychiatric and medical conditions. As is evident, PM research will slowly move away from descriptive studies and focus increasingly on studies of mechanisms while continuing with key treatment studies, until mechanism studies lead to the development of "designer" therapies informed by better mechanistic understanding. There will, by necessity, beincreasing application of newer research methods from genetics, brain imaging, animal models, pharmacology, psychology, epidemiology, and clinical trials.
The major challenge for the field will be the funding of its research. This is especially true given the funding limitations faced by the NIH in the next few years. Increasingly, the field will have to connect with a broader spectrum of research funding through closer relationships with the pharmaceutical industry and investor philanthropy. A critical component of the ability to grow and sustain funding will be the ability of PM to work closely with the NIH, especially within the context of the NIH Roadmap for Medical Research that calls for clinical and translation research in areas of high significance to public health and that crosses traditional basic and clinical disciplines. Already, the Academy of Psychosomatic Medicine, the American Psychosomatic Society, and the American Psychiatric Association are working closely to articulate a systematic work plan for PM research and research capacity in the next decade and are seeking NIH funding to support the development of this work. In all, the next decade promises to be highly exciting for the PM research field.
Dr Lyketsos is a professor in the department of neuropsychiatry and the Memory Group at the Johns Hopkins University School of Medicine in Baltimore. Dr Alter is associate professor and director of policy and community outreach in the department of psychiatry at the Georgetown University Medical Center in Washington, DC.
The authors have indicated that they have no conflicts of interest.