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Depression and Disease Risk

What is depression?

Depression can range from a sinking of spirits to frank clinical mood disorders. Sadness is normal depression that we all get now and then. It is a reaction to adverse events and may be adaptive in that it allows us to withdraw from an energy-draining circumstance. Sadness related to the first two-postpartum weeks, to premenstrual phases, anniversary reactions, or holidays are within normal limits.

Reactive depression is a reaction to meaningful losses or separations (for example, death, divorce, emigration, loss of a relationship, natural disasters). What is commonly called grief is the normal manifestation of reactive depression. This includes autonomic nervous system hyperactivity, insomnia, anxiety, and inability to concentrate. A special type of reactive depression is anaclitic depression that occurs when an infant is separated from its mother. It is characterized by anorexia, listlessness, and withdrawal, and results in impaired physical, intellectual, and emotional development.

Paradoxical depression may occur after positive incidents. Elation, which is generally associated with success, is sometimes viewed as a defense against depression, and in some people, it may lead to mania, which is excessive. Mania is distinguished by a frenzy of psychomotor activity, euphoria, rapid speech, decreased need for sleep, grandiosity, poor judgment, and flight of ideas. Melancholy has been used in two ways. One way is a name for sluggish and uncomfortable thought processes and low spirits associated with other conditions. The other is a severe form of depression characterized by symptoms of clinical depression.

When sadness or grief is excessively intense and lasts significantly longer than is expected by the nature of the stressor, or when it occurs without the association of a stressor, it is diagnosed as clinical depression. In contrast to normal emotional reactions, there is significant crippling of physical or social functioning, and work ability. Clinical depression is one of the two basic affective components of mood disorders (the other is mania).

Mood disorders were previously known as affective disorders because anxiety and irritability are commonly involved. In 2003, it was estimated that in the USA some type of mood disorder will afflict 20% of all women and 12% of all men in their lifetime (4). Mood disorders are said to be the most prevalent of all psychiatric illnesses. They appear to represent 10% of all non-psychiatric consultations, 25% of all patients in mental facilities and 65% of all psychiatric outpatients (4). Most of these are unipolar major depressive disorder and its variants. Incidence of bipolar disease (mania and depression) in the general population may be about 4 to 5%. Bipolar disease is about equally distributed between the sexes, whereas twice as many women as men seem to have clinical depression. In bipolar disease, more women have predominately-depressive symptoms and men seem to have predominately-manic symptoms. Bipolar disease seems to have an increased incidence in higher socioeconomic classes. The onset of bipolar is usually in the teens through 30 (4).

Being female is the greatest known risk factor for unipolar depression (M). Almost twice as many women as men suffer from depression (1). Influences of sociocultural relationships and current and early experiences as well as family relationships may make a significant contribution to depression. Gender roles and beliefs can foster and perpetuate depression in both and men and women (2). The onset of unipolar disorders usually is in the ages of 20 to 50, (4).

It has been proposed that age, gender, race, socioeconomic status and birth cohort (a group of people born during the same period or time of year) may make a difference in depression in children. A meta-analysis was conducted on 310 samples out of 61,424 children aged 8 to 16 who responded to the Children’ Depression Inventory (CDI) ().Girls scored slightly lower in depression than boys until the age of 13 when they became higher and stayed higher. Boys CDI scores were unchanging except for a high score at age 12. Girls CDI scores remained unchanged from 8 to 11 and then increased between 12 and 16. No differences were seen between Blacks and Whites, and there were no apparent socioeconomic effects. But, Hispanic children registered significantly higher depression scores. There was no change in birth cohort scores in time for girls and a slight increase for boys. A marked longitudinal testing effect (improved performance by the repeated taking of the test) was evident.

Higher socioeconomic status as measured by income, education, and occupation is inversely related to hostility, depressive symptoms, and major depression ().

Race, culture, and socio-economic class have been variably associated with diagnosis of depression (, , , , , , ). Indeed, diagnosis and treatment of depression seems to vary significantly with the training of the diagnostician ().

As of 2002, almost 20% of all primary-care patients had symptoms of depression and needed additional assessment and education (3). Approximately 6% of primary care patients suffered from clinical depression and needed antidepressants or psychotherapy. Depression is projected to become the second leading cause of disability worldwide in the first decade of the 21st century.

Depression and suicide

A significant number of folks find their existence so depressing and unbearable that they can see no alternative but to terminate it. It has been said that although aggression appears to occur in all species, humans are the only species known to commit suicide. Some animals do take serious risks, or do not take good care of themselves, but this is not truly suicide.

According to the Merck Manual of Diagnosis and Therapy (4), depression is involved in more than 50% of all suicide attempts (4). Recognition and treatment of depression is vital. Every depressed person should be queried very carefully about suicidal thoughts. As of this writing, there appears to be no evidence that such a query would plant the idea in the depressed persons (4). At least 50% of persons committing suicide have seen their physician within the past few months, and more than 20% have received psychiatric care during the previous year (4).

Direct self-destructive suicidal behavior encompasses suicidal gestures, attempted suicide, and completed suicide. Suicidal gestures are suicidal plans and actions that are not likely to succeed and are often cries for help. They must be taken seriously and carefully evaluated especially because approximately 20% will try again within 1 year and 10% complete suicide (4). Attempted suicides are not fatal sometimes because the impulse was vague or ambivalent and the method chosen was of low lethal potential. It is said that they are often pleas for help, and the attempter may not die because of a real desire to live. Again, they must be taken very seriously. Sometimes suicide attempts are unsuccessful because of early discovery, and sometimes completed suicides may be unintentionally fatal due to miscalculation. Completed suicides result in death.

As of 2002, suicide is the second leading cause of death in adolescents (4), the third foremost cause of death for Americans ages 15 to 24, and the eighth foremost cause of death for all Americans (7). In the age group of 25 to 34 it accounts for 10% of all deaths, and 30% of causes of death in university students (4). In the 1990’s, male completed suicides increased more than two fold. For completed suicides, 70% are in people older than 40 years of age, and the incidence rises steeply in persons older than 65 years of age. People less than 40 years of age account for 65% of attempted suicides (4). In the USA, approximately 10% of 200,000 attempted suicides are completed. Attempted suicides account for 20% of all emergency room admissions and 10% of all regular medical admissions (4). In some American Indian tribes, the suicide rate is 5 times the national average. For physicians, it is the principle cause of death in those less than 40 years of age. For women physicians, the suicide rate is 4 times the matched national average (4). By medical specialty, the rate is highest among psychiatrists. Suicide is the cause of death in 15 to 25% of patients with untreated mood disorders. Unrecognized or inadequately treated depression is said to contribute to 50 to 70% of all completed suicides (4).

For every completed suicide, there are hundreds of thousands more who attempt to commit suicide. Urban and rural rates are about the same in the USA, but in Europe, the urban rate is higher than the rural.

Women attempt suicide 2 to 3 times more often than men do (4), but are less successful: men have a 3 to 4 times greater completed suicide rate than women.

Choice of the method is largely culturally determined. Ingestion of drugs is the most common vehicle used in suicide attempts (4). Two or more methods or a combination of drugs is used in approximately 20% of attempts (4).

About 1/6th of people who complete suicide leave notes. Notes in elderly folks generally refer to concern for those left behind. In adolescents, they usually express anger or vindictiveness. Most often, they refer to events that will follow and personal relationships. Notes are less frequent in attempted suicides, and auger future suicide attempts (4).

It is a daunting task even for the expert suicidologists to accurately predict who will attempt suicide (5, 6). Maris summarizes common factors that seem to predict suicide: more than one may be present at a given time (5, 7).

Hopelessness, cognitive rigidity. Feeling hopeless and helpless may be the strongest predictor of suicide.
Physical illness. Approximately 35% to 40% of people who commit suicide have significant physical disorders. Prominent among these are epilepsy, malignant neoplasms, gastrointestinal problems, or musculoskeletal problems (e.g., lower back pain, arthritis). Temporal lobe epilepsy may often be accompanied by brief but deep episodes of depression, and being on medication for epilepsy increases the risk.
Depressive diseases, mental illness especially schizophrenia and bi-polar disorder. Approximately 15% of those suffering with these mental illnesses and diagnosed with depression commit suicide.
Alcoholism, drug abuse. Approximately 25% of those committing suicide were intoxicated when they died. Merck says about 30% had consumed alcohol and 50% of these were intoxicated when they died. Merck also says that 10% of alcoholics committed suicide, and alcoholics are at higher risk even when sober. Alcohol reduces self-control and intensifies mood swings.
Suicide ideation, talk, preparation, religion. Almost 80% of people committing suicide give clues to their intentions. These clues include missing work or school, talking about death, giving away possessions, new wills or new or changed life insurance policies, or sexually acting out. Catholic countries have lower suicide rates than protestant countries. Beliefs in after life and prohibitions against suicide may make a difference.
Previous suicide attempts. Greatly increases risks of future attempts.
Isolation, living alone, sudden loss of external support. Greater suicide rates are seen in divorced, widowed, or single people compared to married. Rates are improved by almost any social interaction.
Older white males. Almost 70% of all completed suicides are by older white males. About 90% kill themselves on the first try.
Methods of committing suicide. Men generally choose more deadly methods than do women do. Guns are used by 63% of men and 39% of women. Women choose poison 27%. Men choose hanging 15%. Merck says 74% for men and 31% for women, for completed suicides but the disparity still applies. Overall, violent methods for attempted suicides are uncommon (4).
Family history of suicide. Approximately 11% of people committing suicide have at least one first degree relative who committed suicide.
Modeling of behavior. Reading or hearing about suicide increases rates. Adolescent suicide rates increase about 7% for up to 10 days after widely publicized suicides.
Stress and undesirable life events. Problems can trigger negative emotions such as shame, fear, and guilt, and diminish feelings of self worth.
Anger, irritability, and aggression. In addition to being depressed, most people who kill themselves are angry. Usually older people are angry at life not a specific individual.

To this list, the Merck Manual (4) adds that risk increases,

at personally significant anniversaries,
if the person is making detailed suicide plans, especially to avoid the risk of discovery,
near the end of or at the onset of depressive illnesses,
when agitation, restlessness, and anxiety are present,
when command hallucinations are present,
in someone with an impulsive, hostile personality,
when someone is taking a prescription drug that can cause severe depression (e.g., reserpine)

Depression and physical illness

In addition to being a risk factor for suicide, well-controlled studies have shown that symptoms of depression as well as the psychiatric illness of major depression are associated with increased risk of other serious illness (, , , , , , ). On the other hand, some studies have looked for but not found a linkage between negative emotions and malignancies (, ). When evaluating these or any studies, it is important to remember the principles discussed in the chapter: The Scientific Method of Investigation.

There are a few problems encountered with interpreting these results: notably, in the studies not showing linkage. Brief follow-up periods, small sample sizes, lack of control over other risky behavior such as alcohol abuse and smoking, low mortality, incomplete follow-up and lack of information on health status that may be premorbid are possibilities suggested by one set of reviewers (). It is has been asserted that the lack of positive findings may be due to failure to assess and control for alcohol and smoking, behaviors that have profound impact on a sundry of health problems (, )

Additionally, in performing their analyses, the non-linkage studies tended to lump together cancers that have disparate etiologies, and differing contributory genetic factors and life styles. With this diversity, correlations are difficult to find. As pointed out in Ershler and Keller in 2000 (), some cancers may have stronger relationships to emotions than others may. In addition, definitions of depression and analytical methods in these studies have sometimes been at odds with the studies that have shown correlations. Early work that did not show correlations with negative emotions, tended to rely on single assessments of depression with narrow time frames (). Indeed when Penninx et al. () subjected data from their own positive correlating study to this type of assessment, they did not see a correlation.

These considerations do not invalidate these studies; but it does show that circumspection is necessary when attempting to derive conclusions.

Depressed patients seem to be less likely to seek medical help and less likely to take prescribed medications (). They are more likely than nondepressed people are to smoke and are less likely to quit (). Nevertheless, increased mortality associated with depression especially in the elderly is only partly accounted for by bad health behaviors such as smoking, improper diet, alcohol consumption and lack of exercise (, , , ).

Depression and cancer

One of the better-known large studies is the Alameda County Study, a population based cohort of 6,848 people without cancer who were followed from 1965 to 1982 (, ). Age-adjusted and multivariate analyses showed an association between high levels of depressive symptoms at the beginning of the study and deaths from non-cancer causes, but no association with either cancer incidence or mortality. Women who were socially isolated had a significantly higher risk of dying from cancer of all sites and of smoking-related cancers. In men, social connections were not associated with cancer incidence or mortality; however, men who were socially isolated had significantly lower survival rates.

The Medical Outcomes Study that collected data from over 11,000 outpatients revealed that people who, when the research began, had a depressive disorder or who had depressive symptoms without a syndromal disorder had more pain, poorer physical, social, and role functioning, and perceived themselves to be in worse health than patients who were not chronically ill ().

In another study, people who were depressed at the beginning of the 6-year investigation had 73% greater risk for becoming disabled by the end of the 6 years (). Penninx () reported that chronically depressed mood was linked to a variety of cancers by a hazard ratio of 1.88. That is, after adjusting for demographics and risk factors, those persons with a depressed mood were 1.88 times more likely to have one of these cancers than was someone who was not depressed.

Depression and cardiovascular disease

Several appropriately controlled studies have shown that depression increases the risk of coronary heart disease (CHD), the number one killer in the USA, and the number one killer of women over 40. Indeed, CHD has a worse prognosis in women ().

There is convincing evidence for a psychological and social impact on CAD morbidity and mortality (). Five key variables have been identified as possible psychosocial risk factors: acute and chronic stress, hostility, depression, social support, and socioeconomic status.

Cohort studies on depression and CHD in initially healthy people were reviewed and subjected to meta-analysis (). MEDLINE (1966-2000) and PSYCHINFO (1887-2000) were searched along with bibliographies, and references of the review’s author. Eleven studies met rigorous inclusion criteria. The overall relative risk (RR) for CHD in depressed subjects was 1.64 (95% confidence interval (CI) = 1.29 - 2.08, p<0.001). Clinical depression was a stronger predictor for CHD (RR = 2.69, 95% CI = 1.63 – 4.43, p<0.001) than was depressed mood (RR = 1.49, 95% CI = 1.16 -1.92, p = 0.02). The studies author believes that there might be a dose-response effect.

One of the most telling depression/CHD studies is a prospective 13-year investigation (). People who suffered from major depression had 4.5 times the risk of having a heart attack compared to nondepressed persons. Depressed patients who had already had a heart attack were four-times more likely to die over the same time course (). Depressed people who had preexisting cardiovascular conditions were more likely to have more complications (). Originally, healthy but depressed people have an increased risk of 1.5 to 2.0 times for their first heart attack ().

One study () concluded that the risk of dying among depressed elderly women was as great as the danger conferred by other cardiovascular risk factors including smoking, hyperlipedemia, high blood pressure, diabetes, and obesity.

Depressed patients also have a higher than expected rate of sudden cardiovascular death. As more information is uncovered, it seems to some researchers that the association between depression and cardiovascular disease is inevitable. Up to 1/5th of patients with cardiovascular disease may have concomitant depression (). The 6-month post-MI-diagnosis cumulative mortality is higher in depressed patients. So, some scientists are looking at the possible benefits of antidepressants to decrease morbidity and mortality in depressed patients with cardiovascular disease ().

On the other hand, meta-analysis of 37 studies showed no effects of health education and stress management programs for CHD on coronary bypass surgery, depression or anxiety (). However, they did show a 34% reduction in cardiac mortality, 29% reduction in MI recurrence, and significant (p<0.025) positive effects on cholesterol, blood pressure, body weight, smoking, eating habits, and physical exercise. They also showed that those programs that were the most successful in decreasing MI recurrence and cardiac mortality were those that were the most successful in modifying the risks (systolic blood pressure, smoking, exercise, and emotional distress).

The constellation of the so-called type D distressed personality style and social inhibition show predictive value for 10-year cardiac morbidity and mortality (, ). The tendency to experience negative emotions suppress emotional expression of these emotions in social interactions is a hallmark of the type D (). In a study of 337 patients who were followed for 5 years, after controlling for age, gender and biomedical risk factors, stress (p = 0.011) and type D (p = 0.001) were shown to be related to the risk of experiencing a major adverse cardiac event (). It seems that type D personality is an independent predictor of negative cardiac events after controlling for current stress symptoms.

Depression and old age

In elderly folks 71 or older, initial symptoms of depression were predictive of greater physical decline over their next 4 years (). Women who had been or are depressed are at greater risk for osteoporosis (). In elderly men, baseline depression was associated with increased risk of physical decline over their next 3 years (). Depressed diabetics were less compliant with dietary and other glycemic controls (). For a variety of diseases, rehabilitation was less effective in depressed people (). And in older hospitalized patients, depression is associated with increased adverse drug reactions ().

Depression was also an independent risk factor for all causes of death in hospitalized patients ().

Epidemiology and diagnosis of depression in the elderly is sometime problematic, differing greatly depending on definition and population being studied (). Higher amount of depression are often seen in venues where comorbid physical illnesses are more common. Prevalence of depressive symptoms and major depressive disorders in community dwelling units are said to be 15% and 1-3% respectively. Depression associated factors include female gender, pharmaceuticals, alcohol and other substance abuse, family history, and medical conditions such as cancer, heart disease, stroke, Alzheimer’s disease. It is sometimes difficult to recognize depression in the elderly because they often deny their symptoms, or they may have comorbid somatic problems or anxiety, or are cognitively impaired.

In community housing, chronic strain, rumination and low sense of being in control were more common in women than in men and seemed to mediate a greater prevalence of depression ().

Minor depression as well as major depression in the elderly can have adverse health consequences (). For older men, both minor and major depression can increase the risk of dying, whereas for older women only major depression increases the risk of dying ().

Depression and pathophysiology

Pain perception is altered in folks with major depression (). In 16 patients with major depression, absolute pain perceptions thresholds were increased over age-matched and gender matched controls. However, the relative pain perception thresholds were significantly reduced. This reduction was negatively correlated with anxiety and positively correlated with anxiety. The researchers suggest this increase in relative perception of pain may be due to anxiety and decreased coping in depressed patients.

Cortisol and catecholamines are frequently elevated in depressed or anxious persons, and growth hormone is often depressed (). Elevated catecholamines in acute stress can be beneficial but in chronic stress, they can result in immune down-regulation. As important as long-term changes in hormone levels are, the possible effects upon circadian and ultradian rhythms may be equally important (, , ). Clinical depression is well documented to be associated with elevated levels of cortisol in the blood ().

Major depression may be thought of as a manifestation of a dysfunctional stress response syndrome (, ). There may be important genetic factors at work. In adolescents, baseline sleep-related growth hormone levels were predictive of subsequent depression (). First-degree relatives of people suffering with depression have significantly depressed HPA responses relative to controls ().

Pessimism may be associated with immune perturbations and possibly worse control over HPV infections and greater risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ black women co-infected with HPV (). Lower levels of NK cell cytotoxicity and CD8 T cell percentages were seen in these women who had the highest amount of pessimism.

Effects of depression on morbidity and mortality in HIV disease and immune reactions have been reviewed in 2003 (). In general the function of killer lymphocytes is altered in depression. NK cell activity is decreased, CD8 T cells are less effective, and increased viral load is common

Weight Gain and Risk of Insulin Resistance Syndrome

When people get depressed, they often tend to overeat. Is there anything wrong with this? Yes. Obesity and overweight as well as weight gain from early adulthood to middle age are associated with increased risk of the insulin resistance syndrome (). The insulin resistance syndrome is the triad of hypertension, hyperinsulinemia, and dyslipidemia. In a population-based study of 2,272 eastern Finnish men, every increase of 5% over their weight at age 20 was associated with almost a 200% increased risk for the insulin resistance syndrome by middle age. And compared to men who were within 10% of their weight at age 20, men with an increase of 10-19%, 20-29% and > 30% were respectively 3.0, 4.7, and 10.6 times more likely to have the insulin resistance syndrome by middle age.

Psychological Interventions for Depression

Although depressed patients are highly treatable and should expect excellent results, studies in the 1990s have shown that detection and treatment rates are low in primary care settings: the place where patients are most likely to seek help. Many people who are treated for depression relapse within one year (1). Experts who treat depression find that therapy with depressed clients can often be frustrating because their hold on life is so fragile that it is easily broken (2).

Yet, there is hope provided by the encouraging success of the Partners in Care Program.

The Partners in Care (PIC) program is a real world, integrated program aimed at improving care for depression. The program is based upon two evidence-based medicine programs conducted at 46 medical clinics, within 6 diverse nonacademic managed care plans in 5 states representing the West, Midwest and the East. Approximately 27,000 people were screened for depression and 1,350 eligible patients agreed to participate. Almost one third of these were Mexican-American (an understudied depression-prone group). The two programs share much of the same materials, but one directed resources toward supporting medication treatment while the other directed resources toward supporting psychotherapy. Nevertheless, both of the programs encouraged care providers to take into account patient preferences when designing treatment. Overall, both programs were equally successful. So, patients can choose either program. If they want to, they can also integrate parts of the not-chosen program into their treatment.

Among patients not initially treated for depression, the patients in the PIC group were almost twice as likely to enroll in treatment within the first six-months of follow-up, as were patients in the care-as-usual group. Patients in the PIC group were 10% more likely to be less clinically depressed and report better quality of life than the usual-care group. The folks in the PIC group were significantly more likely to remain employed than those in the usual-care group, which is important for maintaining health insurance.

PIC includes support for assessment, treatment choice, patient self-management, and case management by mental health workers. PIC helps clinicians focus more costly treatment on those who need it and provide appropriate care for those who only have depressive symptoms. PIC program materials have all the tools necessary for putting the program into place. PIC has training materials, guidelines to help care providers, pamphlets and videos to educate patients and manuals for patients in therapy. For more information, visit www.rand.org/health/pic.products.

Non-Medline References

Nichols M and Schwartz R. Family Therapy: Concepts and methods (4th edition) Boston: Allyn and Bacon.1998.
Papp, P. Listening to the system. Family Therapy Networker, January/February, 52-58, 1997
RAND: Partners in Care: Hope for those who struggle with hope.
The Merck Manual of Diagnosis and Therapy 17th Ed. Merck, 1999.
Maris, R. Introduction. Suicide and life threatening behavior, Vol. 21(1), Spring, 1-17, 1991.
Motto, J. An integrated approach to estimating suicide risk. Ibid, 74-89.
Gagliardi J., Lapidus J, Guise RW, Vickers MI. Study Guide for Marriage and Family Therapy National Licensing Examination. Family Solutions Institute, 2001. Jamaica Plain, MA


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