Depression Affects the Patient’s Brain, Body, and Social System

The study of mood disorders over the last decade has improved our understanding of depression in clinically meaningful ways. We tend to think about mood disorders as primarily emotional illnesses. Certainly so, but research is dissolving the boundaries between the brain and the body (see Depression, Pain, and Comorbid Medical Conditions). It can now be said with confidence that mood disorders are inflammatory disorders, too, or at least disorders with significant pro-inflammatory effects. There is strong evidence of a bidirectional impact of the brain on the body and vice versa. Neuroendocrine disruption in the CNS is not isolated to emotional symptomatology; the impact of this brain-body unity is far-reaching. People are whole and must be assessed and treated holistically. People are also connected in social systems, which are themselves impacted by the health of their members.

Physical symptoms are a prominent part of the experience of mood disorders, and mood symptoms often accompany physical illnesses. Conditions often comorbid with depression include obesity, type 2 diabetes, and chronic pain, among others, which leads to several questions:

• Why did the comorbidity of cardiovascular illness and depression in the Nurses’ Health Study result in a doubling of the relative mortality risk over the presence of cardiovascular illness alone?
• Why is depression so common in those suffering from rheumatoid arthritis?
• Why should interferon-alpha (INF-α), used to treat chronic hepatitis C, have adverse effects that include severe major depression?
• Why is major depression an ominous comorbidity in acute myocardial infarction and such a strong predictor of early mortality?

The brain-body connection and the effect of inflammatory mediators such as INF-α, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), among others, may provide answers to these questions.

The search is on for a biomarker that will allow clinicians to track the biochemical presence of major depression and permit treatment to biological remission. Such remission would promote functional wellness and hopefully reduce or extinguish the negative additive health risks resulting from depressive illness.

Until that search is fruitful, clinicians must focus on treatment to symptomatic remission. This is best accomplished by an active approach to management and the use of a validated metric for assessment of symptoms. One would never treat hypertension without measuring blood pressure or treat diabetes without measuring HgbA1c. There are established goals for the treatment of hypertension and diabetes based upon the reduction of risk for morbidity and mortality. By analogy, the utility and necessity of measuring depressive symptoms by some validated metric seems obvious. The goal of symptomatic treatment of depression is to extinguish symptoms completely. Remission is foundational for functional restoration and wellness—both of the individual and his or her social system.

An example of a social system is a mother and her family. One of the most powerful findings to come from the STAR*D studies of major depression documented the effects of residual depressive symptomatology on the children of mothers in the study. Remission of maternal major depression was found to have significant positive effects on the children studied. This seemingly obvious finding nevertheless reminds us that one way to improve the health of children is to target the mental health of mothers. Those of us in family practice who are moving to patient-centered medical homes (PCMH) would do well to consider maternal mental health as a chronic illness condition in meeting the 2011 PCMH standards for inclusion of a behavioral health focus.

The future of depression management may be brightest with the integration of mental health services into the primary care setting. Not mere co-location, the integration of primary care and mental health care is an active, team-based approach that honors the realities and pace of the busy primary care office. While the focus on depressive illness is enhanced through the use of a case manager, patient registry, validated metric tools, and consultation with a mental health expert, the primary care clinician’s principal role as team leader in care decisions is preserved. The IMPACT model, developed and researched by Jϋrgen Unϋtzer and colleagues at the University of Washington, is perhaps the best example of this team approach.

Financial disclosure:Dr Manning has been a consultant for Eli Lilly, Pearson, AstraZeneca, PamLab, Takeda, and Lundbeck and has been a member of the speakers/advisory boards for Eli Lilly and AstraZeneca. ​