Research in Psychosomatic Medicine: Beginning to Set the Future Agenda

The recent approval of psychosomatic medicine (PM) as the newest psychiatric subspecialty by the American Board of Medical Specialties¹ was predicated, in significant part, on the public health significance of the field and on the existence of a well-developed body of knowledge to support its validity and activities. The continued growth of the evidence base is crucial to the future of the field and to improving the care of the patients who are its focus, thus leading to a reduction of the public health burden associated with their condition. In this article, we present a brief overview of the existing evidence base of PM in the context of its public health significance; we also provide some suggestions for its future development.

Examples of the evidence Because the PM evidence base is rich and varied, it cannot be fully covered in an article of this length. Nevertheless, the following examples serve to illustrate the current status and depth of the research. Psychiatric comorbidity is very common in patients with medical conditions, with a prevalence ranging from 20% to 67%. Patients in the general hospital have a higher rate of psychiatric disorders than community samples or patients in ambulatory primary care. Compared with community samples, depressive disorders in hospitalized medical patients are more than twice as common, major depression 2 to 3 times as common, substance abuse 2 to 3 times as common, and somatization disorder more than 10 times as common. Delirium occurs in 18% of hospitalized patients, a rate much higher than one would expect in the community. Similarly increased rates are seen in primary care and long-term care.

Psychiatric comorbidity has serious effects on physically ill patients and is often a risk factor for their medical conditions. It is well established that depression is both a risk factor and a poor prognostic factor in coronary artery disease. Psychiatric illness worsens cardiac morbidity and mortality in patients with a history of myocardial infarction, diminishes glycemic control in patients with diabetes, and decreases return to functioning in patients who have had a stroke. Mood and anxiety disorders compound the disability associated with stroke. In the context of neurodegenerative disease (eg, Parkinson or Alzheimer disease), depression, psychosis, and behavioral disturbances are significant predictors of functional decline, institutionalization, and caregiver burden.

Hospitalized patients with delirium are significantly less likely to improve in function than patients without delirium. Delirium is associated with worse outcomes after surgery, even after controlling for severity of physical illness.¹ Dialysis patients with psychiatric conditions experience more difficulties in adjusting to dialysis, such as placement of the shunt, dependence on a machine, multiple needle-sticks, and accepting the reality of blood circulating outside their bodies. Psychopathology adversely affects patients during the long wait for an organ transplant. After organ transplantation, relatively minor disruptions in compliance with immunosuppressant medication such as may be associated with depression, may result in graft rejection and death.

In addition, depression and other psychiatric disorders significantly impact quality of life and the ability of patients to adhere to treatment regiregimens. For example, psychiatric disorders are linked to nonadherence with antiretroviral therapy, adversely affecting the survival of patients with HIV infection. Psychiatric disorders worsen the prognosis and quality of life of patients with cancer. Psychiatric disorders are also linked to nonadherence to safe sex practices and to the use of sterile needles in HIV-infected injection drug users, leading to major public health implications.

With regard to clinical services, failure to identify, evaluate, diagnose, treat, or achieve symptom resolution of psychiatric morbidity in medical care settings results in significant adverse outcomes. Depression, dementia, and delirium,³ common psychiatric disorders found in hospitalized medical patients, are associated with higher medical care use, both in the hospital (more than 30% longer duration of hospitalization) and after discharge.

Although it is the treatment of choice, fewer than 1 in 5 patients with agitated delirium receive neuroleptic treatment in the hospital. When delirium is unrecognized and untreated in the hospital, patients are needlessly placed in nursing homes instead of being sent home.

Physically ill patients with depression whose condition is not diagnosed and who therefore do not start treatment while hospitalized have only an 11% chance of receiving treatment for depression in the next year. Untreated depression is associated with a higher need for medical services after hospital discharge and with higher morbidity and mortality in coronary disease, hypertension, diabetes, and stroke.²

Based on existing research findings, the presence of co-occurring physical and psychiatric disorders can be explained by an adverse bidirectional interaction.³ This model proposes that the seemingly disparate medical and psychiatric disease states are, in fact, integrally related in their causation and pathophysiology and, ultimately, should be treated together. Underlying risk factors, including genetic vulnerability, childhood adversity, maladaptive attachment, and adverse life events are associated with depression and biobehavioral risk of chronic disease. A recent editorial summarizing findings of a conference on depression in medical illness called for more research "to understand this bidirectional relationship and identify possible common pathogenic, mechanistic pathways that link depression and serious medical illness."⁴

Cardiovascular disease as a model

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 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.

References:

Drugs Mentioned in This Article

Memantine (Namenda)
Sertraline (Zoloft)

References

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3. Katon WJ. Clinical and health services relationships between major depression, depressive symptoms, and general medical illness. Biol Psychiatry. 2003;54:216-226.
4. Evans DL, Charney DS. Mood disorders and medical illness: a major public health problem. Biol Psychiatry. 2003;54:177-180.
5. Glassman AH, O'Connor CM, Califf RM, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002;288:701-709.
6. Berkman LF, Blumenthal J, Burg M, et al, for the Enhancing Recovery in Coronary Heart Disease Patients Investigators (ENRICHD). Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) randomized trial. JAMA. 2003;289:3106-3116.