Ensure delivery by adding featureseries@email.emedicine.com to your address book.

MAJOR DEPRESSIVE DISORDER: GENETICS, DETECTION, AND AN ASSOCIATION WITH CARDIAC COMORBIDITIES

Summary of the state of affairs

Major depressive disorder (MDD), also known as unipolar depression and clinical depression, is one of the most commonly encountered psychiatric disorders. While MDD is readily diagnosable and treatable, the condition is also associated with relatively high rates of attempted and completed suicides. In fact, most people who commit suicide are depressed. Annually, MDD affects between 5-10% of the American adult population (approximately 19 million people) (NAMI, 2006). A gender differential exists, with a lifetime incidence of 20% for women and 12% for men.Of specific importance to the practicing clinician, the prevalence of depression in a typical medical practice can be higher than 10% because of a higher prevalence in patients with significant medical comorbidities (Aronson, 2006).

Diagnostic criteria for MDD, as defined by the American Psychiatric Association, reflect the significance of both severity and duration of symptoms. Symptoms must not be caused by bereavement or substance abuse and must cause significant impairment in functioning. The key symptoms, which must be present for at least 2 weeks, include the following:

• Depressed mood
• Diminished interest or pleasure
• Significant weight loss or gain
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Fatigue or loss of energy
• Feelings of worthlessness
• Diminished ability to think or concentrate
• Recurrent thoughts of death, suicidal ideation, suicide attempt, or specific plan for suicide

Most patients with MDD respond to one of the various therapies currently available. Many classes of medications have proved effective, including tricyclics (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MOAIs), bupropion, and mood stabilizers such as lithium. Therapies focused on working with patients in the clinical setting, such as cognitive therapy, have also been effective.  Finally, a number of somatic therapies have been successful, including electroconvulsive therapy (ECT), magnetic seizure therapy (MST), and transcranial magnetic stimulation (TMS). 

Relationship of MDD, genetics, and treatment

Individual susceptibility to depression is influenced by genetic risk factors. The Swedish National Twin Study on Lifetime Major Depression (Kendler, 2006) reported this year that MDD is approximately 35% due to genetic influence and that women show significantly higher heritable lifetime susceptibility (42%) than do men (29%).  The mechanism of the observed genetic differential of depression in men versus women is thought to differ. Caspi et al (2003) demonstrated that environmental effects, such as life stress, variably affect patients depending on the genetic makeup of the specific individual. In this study, individuals who were homozygous for the long allele in the promoter region of the serotonin transporter (5-HTT) gene were relatively immune to serious losses, abuse, and other events that heralded the onset and influenced the severity of depression in individuals who inherited 1 or 2 short arm alleles of the same gene (Caspi, 2003).        

Detection

Because unrecognized MDD can lead not only to significant morbidity but also to an increased risk of suicide, apt attention must be paid to early detection. References suggest that MDD can have a delayed diagnosis or go undiagnosed in many clinical settings and primary care practices (Vuorilehto, 2006). A number of clinical diagnostics tools are available to assist the psychiatrist and the primary care physician to improve the detection of MDD in their patients. The Beck Depression Inventory (BDI) is a thoroughly validated and reliable test consisting of 21 items that look at the symptoms of depression and rate their severity (Beck, 2006). Two newer tests, self-administered by the patient, are the Patient Health Questionnaire (PHQ-9) and the Mental Health Inventory 5 (MHI-5). The PHQ-9 was adapted from the physician-provided Primary Care Evaluation of Mental Disorders (PRIME-MD) and consists of 9 items (Spitzer, 1999). The MHI-5 is a 5-item screening survey that can take patients less than 3 minutes to complete and provides a rapid self-assessment tool (Rumpf, 2001). Use of these tests can lead to detection of unrecognized psychiatric disorders and the initiation of clinical interventions. They can also be effective tools to monitor responses to treatment (Lowe, 2006).

An association between depression and cardiac comorbidities

A positive correlation exists between depression and heart disease. Studies suggest that the incidence of acute myocardial infarction (AMI), as well as that of coronary artery disease (CAD), is increased in people with depression (NIMH, 2006). Furthermore, depression can often contribute to patient delays in seeking the necessary evaluation and treatment for the symptoms of AMI and unstable angina (Bunde, 2006). Individuals who have survived an AMI in the presence of depression have a death rate 3.5 times higher than survivors who don’t carry this psychiatric comorbidity (Brannon, 2004).

In addition to this relationship, a reverse relationship also exists, in which depression manifests as the most common emotional response of people who have experienced an AMI (Brannon, 2004). According to structured interviews, approximately 20% of AMI survivors have MDD (Thombs, 2006), and, once depression is diagnosed in these patients, the condition can negatively impact both the morbidity and mortality of AMI survivors (NIMH, 2006). In fact, CAD and AMI are not only linked to depression but are also associated with increased suicidal behavior (Artero, 2006). The development of MDD in patients who have CAD or are post-AMI should give additional impetus to the treating physician for early and aggressive treatment of MDD.  Recognizing and addressing post-AMI depression can enhance recovery and decrease the overall risk of cardiac death (Rumsfeld, 2005).

References

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (Text Revision) (DSM-IV-TR). 4th ed. Washington, DC: American Psychiatric Association; 2000.

Artero S, Astruc B, Courtet P, Ritchie K. Life-time history of suicide attempts and coronary artery disease in a community-dwelling elderly population. Int J Geriatr Psychiatry 2006;21:108-12.

Aronson SC. Depression. eMedicine.com [serial online]. 2005. Available at: http://www.emedicine.com/med/topic532.htm. Accessed  March 8, 2006.

Beck AT. Beck Depression Inventory (BDI). Available at: http://cps.nova.edu/~cpphelp/BDI.html. Accessed March 5, 2006.

Brannon L, Feist J. Health Psychology: An Introduction to Behavior and Health. 5th ed. Belmont, CA: Wadsworth/Thomson Learning; 2004.

Bunde J, Martin R. Depression and the prehospital delay in the context of myocardial infarction. Psychosom Med 2006;68:51-7.

Caspi A, Sugden K, Moffit T, et al. Influence of Life Stress on Polymorphism in the 5-HTT Gene. Science 2003;301(5631):386-9.

Kendler, K, Gatz, M, Gardner, C., Pedersen, N.  A Swedish national twin study of lifetime major depression. Am J Psychiatry 2006;163:109-14.

Kirchheiner J, Bertilsson L, Bruus H, et al. Individualized medicine-implementation of pharmacogenetic diagnostics in antidepressant drug treatment of major depressive disorders. Pharmacopsychiatry 2003;36 Suppl 3: S235-43.

Lowe B, Schenkel I, Carney-Dobbeling C, Gobel C. Responsiveness of the PHQ-9 to Psychopharmacological Depression Treatment. Psychosomatics 2006;47:62-7.

National Alliance on Mental Illness (NAMI). Major Depression. [NAMI Web site.]
Available at: http://www.nami.org/Template.cfm? Section=By_Illness&template=/ContentManagement/ContentDisplay.cfm&ContentID=7725. Accessed March 4, 2006.

National Institute of Mental Health (NIMH). Depression and Heart Disease. [NIMH Web site.] Available at: http://www.nimh.nih.gov/publicat/depheart.cfm. Accessed March 4, 2006.

Rumpf HJ, Meyer C, Hapke U, John U. Screening for mental health: validity of the MHI-5 using DSM-IV Axis psychiatric disorders as gold standard. Psychiatry Res 2001;105:243-53.

Rumsfeld JS, Jones PG, Whooley MA, et al. Depression predicts mortality and hospitalization in patients with myocardial infarction complicated by heart failure. Am Heart J 2005;150:961-7.

Spitzer RL, Koneke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: The PHQ primary care study. JAMA 1999;282:1737-44.

Thombs BD, Bass EB, Ford DE, et al. Prevalence of depression in survivors of acute myocardial infarction. J Gen Intern Med 2006;21(1):30-8.

Vuorilehto MS, Melartin TK, Isometsa ET. Suicidal behaviour among primary-care patients with depressive disorders. Psychol Med 2006;36:203-10.