eMedicine Specialties > Psychiatry > Adult

Depression

Author: Ravinder N Bhalla, MD, Assistant Clinical Professor of Child Psychiatry, University of Medicine and Dentistry of New Jersey; Medical Director, Mental Health Clinic of Passaic; Consulting Staff, Christian Health Care Center
Coauthor(s): Pascale Moraille-Bhalla, MD, Medical Director, Outpatient Clinic of Hoboken University Medical Center; Staff Psychiatrist, Mental Health Clinic of Passaic; Sarah C Aronson, MD, Associate Professor, Departments of Psychiatry and Medicine, Case Western Reserve School of Medicine/University Hospitals of Cleveland
Contributor Information and Disclosures

Updated: May 26, 2009

Introduction

Background

Major depression, also known as unipolar depression, is one of the more commonly encountered psychiatric disorders. While many effective treatments are available, this disorder is often underdiagnosed and undertreated. Primary care providers should strongly consider the presence of depression in their patients; studies suggest a high prevalence of affective disorders among patients seeking medical attention in the office setting. Following is a case study.

A 30-year-old presented to her primary care doctor with symptoms of frequent headaches, insomnia, feeling overwhelmed, and have low energy. Examination was unremarkable and blood workup supported mild iron deficiency anemia. She returned after one month with improvement in anemia but worsening of symptoms stated earlier. A Physician Depression Questionaire (PDQ-9) revealed that for several weeks she was feeling sad and had little interest or pleasure in doing thing she used to enjoy. She also had suicidal thoughts occasionally and could not concentrate on tasks. She felt like a failure. There were no recognizable losses. She stated that in the past she had similar feelings, but they were less intense and lasted for shorter periods. She did not have any period of euphoria or overproductiviy. Her primary care physician prescribed antidepressants and referred her to a psychiatrist.

Pathophysiology

The underlying pathophysiology of major depressive disorder (MDD) has not been clearly defined. Clinical and preclinical trials suggest a disturbance in CNS serotonin (ie, 5-HT) activity as an important factor. Other neurotransmitters implicated include norepinephrine (NE) and dopamine (DA).¹

The role of CNS serotonin activity in the pathophysiology of major depressive disorder is suggested by the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder. Furthermore, studies have shown that an acute, transient relapse of depressive symptoms can be produced in research subjects in remission using tryptophan depletion, which causes a temporary reduction in CNS serotonin levels. Serotonergic neurons implicated in affective disorders are found in the dorsal raphe nucleus, the limbic system, and the left prefrontal cortex.

Clinical experience indicates a complex interaction between neurotransmitter availability, receptor regulation and sensitivity, and affective symptoms in major depressive disorder. Drugs that produce only an acute rise in neurotransmitter availability, such as cocaine, do not have the efficacy over time that antidepressants do. Furthermore, an exposure of several weeks' duration to an antidepressant is usually necessary to produce a change in symptoms. This, together with preclinical research findings, implies a role for neuronal receptor regulation over time in response to enhanced neurotransmitter availability.

All available antidepressants appear to work via 1 or more of the following mechanisms: (1) presynaptic inhibition of uptake of 5-HT or NE; (2) antagonist activity at presynaptic inhibitory 5-HT or NE receptor sites, thereby enhancing neurotransmitter release; or (3) inhibition of monoamine oxidase, thereby reducing neurotransmitter breakdown.²

Frequency

United States

Lifetime incidence of major depressive disorder is 20% in women and 12% in men. Prevalence is as high as 10% in patients observed in a medical setting.

International

Cultural influences on the presentation of depression can be significant. The practitioner should be aware of differences in the expression of psychological distress in patients from other countries or cultures. Some cultural patterns are mentioned in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR); for example, major depressive disorder may be expressed as fatigue, imbalance, or neurasthenia in patients of Asian origin.

Mortality/Morbidity

Major depressive disorder is a disorder with significant potential morbidity and mortality, contributing as it does to suicide, medical illness, disruption in interpersonal relationships, substance abuse, and lost work time.

• Suicide ranks as a leading cause of death in the United States, with a yearly rate of approximately 200,000 attempts. The number of completed suicides for 2005 was 32,000.
• Suicide continues to rank as the second leading cause of death in adolescents and represents 10-30% of deaths in those aged 20-35 years. Major depressive disorder plays a role in more than one half of all suicide attempts, while the death rate from suicide among those with affective disorders can exceed 15%. Firearms are the most frequent method used in completed suicides. Risk factors for suicide include (1) male sex; (2) age older than 55 years; (3) concurrent chronic medical illness; (4) social isolation (eg, divorced, widowed); (5) depression, especially with severe melancholic or delusional symptoms; (6) substance abuse or dependence; (7) family history of suicide and/or major depressive disorder; (8) command hallucinations; (9) access to firearms; and (10) white race.
• Studies also show that major depressive disorder contributes to higher mortality and morbidity in the context of other medical illnesses, such as myocardial infarction, and that successful treatment of the depressive episode improves medical and surgical outcomes.

Race

Depression is less common in the black population.

Sex

Major depressive disorder is diagnosed more commonly in women, with a prevalence twice that observed in men. In prepubertal children, boys and girls are affected equally.

Age

The incidence of clinically significant depressive symptoms increases with advancing age, especially when associated with medical illness or institutionalization. However, depression might not meet criteria for major depression because of somewhat atypical features of depression in elderly persons. Elderly persons experience more somatic complaints, cognitive symptoms, and fewer complaints of sad or dysphoric mood. Of particular importance is the increasing risk of death by suicide, particularly among elderly men. Rates in women and men are highest in those aged 25-44 years. For more information about childhood depression, see Mood Disorder: Depression.

Clinical

History

The DSM-IV-TR diagnostic criteria for a major depressive episode are as follows:

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• Atypical presentations
  • Patients with major depressive disorder may not initially present with a complaint of low mood, anhedonia, or other typical symptoms.
  • In the primary care setting, where many of these patients first seek treatment, the presenting complaints often can be somatic, such as fatigue, headache, abdominal distress, or change in weight. Patients may complain more of irritability than of sadness or low mood.
  • Elderly persons may present with confusion or a general decline in functioning.
  • Children with major depressive disorder may also present with initially misleading symptoms such as irritability, decline in school performance, or social withdrawal. Depression can occur in preschool children.³ René Spitz described what he called anaclitic depression in infants being raised in an orphanage.⁴ Childhood depression seems to be a more severe form of the same disorder in adults. Evidence-based treatment guidelines are limited. Of teenagers diagnosed with major depressive disorder, bipolar disorder is diagnosed in 50% of them as they grow into adulthood. Further research is needed in this area.
• The differential diagnosis in patients presenting with alterations in mood is extensive and should include consideration of the following:
  • Mood disorders secondary to CNS conditions: These include a broad range of physiologic and structural CNS processes that can produce changes in mood and behavior. Note that major depressive disorder can produce measurable cognitive deficits or a worsening of preexisting dementia. This decline in cognitive functioning, which, on formal testing, appears to arise from impaired concentration or motivation, is referred to as pseudodementia or, more currently, as dementia of depression and should remit with successful treatment of the depressive episode. Major depressive disorder does not cause focal neurologic signs. Such findings should prompt an evaluation for other organic syndromes.
  • Alzheimer disease: This disease and other degenerative and vascular dementias can be associated with affective symptoms. Mood disorders are very prominent in Parkinson disease, Huntington disease, multiple sclerosis, stroke, and seizure disorders.
  • Neoplastic lesions of the CNS: These lesions also can cause changes in mood and behavior before the onset of focal neurologic signs.
  • Inflammatory conditions: Conditions such as systemic lupus erythematosus (SLE) can produce a wide range of neuropsychiatric signs and symptoms, likely because of alterations in the blood-brain barrier and an autoimmune cerebritis.
  • Sleep disorders: Obstructive sleep apnea, especially, can cause significant medical and psychiatric symptoms and often is missed as a diagnosis. Patients, and, if necessary, their partners, should be interviewed regarding their sleep quality, daytime sleepiness, and snoring. Polysomnography can help make the diagnosis and guide treatment.
  • Infectious processes: These include syphilis, Lyme disease, and HIV encephalopathy, which can cause mood and behavior changes.
  • Pharmacologic agents: Substances that can produce changes in mood include antihypertensive medications (especially beta-blockers, reserpine, methyldopa, and calcium channel blockers); steroids; medications that affect sex hormones (eg, estrogen, progesterone, testosterone, gonadotropin-releasing hormone [GnRH] antagonists); H2 blockers (eg, ranitidine, cimetidine); sedatives; muscle relaxants; appetite suppressants; and chemotherapy agents (eg, vincristine, procarbazine, L-asparaginase, interferon, amphotericin B, vinblastine).
  • Endocrinologic disorders: Disorders involving the hypothalamic-pituitary-adrenal axis or thyroid are especially likely to produce changes in mood. These include Addison disease, Cushing disease, hyperthyroidism, hypothyroidism, prolactinomas, and hyperparathyroidism.
  • Substance use, abuse, or dependence: These can cause significant mood symptoms. This is especially true of alcohol, cocaine, amphetamines, marijuana, sedatives/hypnotics, and narcotics. Inhalant abuse also should be considered, particularly among young male patients. Other substance-related and psychiatric processes either can present with mood disturbance as the primary symptom or can occur together with major depressive disorder.
  • Axis I or II disorder: In cases in which another Axis I or II disorder is present, a careful psychiatric review of systems should elicit the alternative or additional diagnosis.
  • Seasonal affective disorder: Also known as SAD, this form of major depressive disorder shows a seasonal pattern of exacerbation and remission. SAD usually is treated with bright light therapy (BLT), with or without antidepressant medication.
  • Dysthymia: This mood disorder presents with low mood as a primary symptom. Dysthymia can predate a depressive episode. The symptoms of dysthymia alone do not meet criteria for major depressive disorder and must be present for at least 2 years.
  • Anxiety disorders: Patients with anxiety disorders are at higher risk for developing comorbid depression. In such patients, it is important to identify the anxiety disorder because they often require specific treatment approaches. Commonly encountered anxiety disorders include panic disorder, obsessive-compulsive disorder, generalized anxiety disorder, posttraumatic stress disorder, and phobia.
  • Eating disorders: People with eating disorders (EDs) also have a high rate of comorbid major depressive disorder and require specific treatment approaches. These disorders include bulimia, anorexia nervosa, and ED not otherwise specified. A large percentage of individuals in this last group have binge-eating disorder (BED), which, while not currently listed in the DSM-IV-TR as a specific diagnosis, constitutes most patients with EDs.
  • Personality disorders: Certain personality disorders (eg, borderline personality disorder) may present with mood changes as a prominent symptom. Remember that the presence of a personality disorder can be difficult to determine in the setting of acute affective symptoms. Many patients who are depressed who appear labile, demanding, or pathologically dependent look dramatically different once the depressive episode has been treated adequately.

Physical

No physical findings are specific to major depressive disorder. Diagnosis lies in the history and the mental status examination.

• Appearance and affect
  • Most patients with major depressive disorder present to their physician with a normal appearance.
  • In patients with more severe symptoms, a decline in grooming and hygiene can be observed, as well as a change in weight. Patients may show psychomotor retardation, which is manifest as a slowing or loss of spontaneous movement and reactivity. Together with this, major depressive disorder often produces a flattening or loss of reactivity in the patient's affect (ie, emotional expression).
  • Psychomotor agitation or restlessness also can be observed in some patients with major depressive disorder.
• Mood and thought process
  • Patients report a dysphoric mood state, which may be expressed as sadness, heaviness, numbness, or sometimes irritability and mood swings. They often report a loss of interest or pleasure in their usual activities, difficulty concentrating, or loss of energy and motivation. Their thinking often is negative, frequently with feelings of worthlessness, hopelessness, or helplessness. While it is not uncommon for patients with major depressive disorder to show ruminative thinking, it is important to evaluate each patient for evidence of psychotic symptoms because this affects initial management.
  • Psychosis, when it occurs in the context of unipolar depression, usually is congruent in its content with the patient's mood state; for example, the patient may experience delusions of worthlessness or some progressive physical decline. Symptoms of psychosis should prompt a careful history evaluation to rule out a history of bipolar disorder, schizophrenia or schizoaffective disorder, substance abuse, or organic brain syndrome.
• Cognition and sensorium: Patients with major depressive disorder often complain of poor memory or concentration. Most commonly, no significant deficits are found on cognitive examination. If present, such findings may represent pseudodementia; however, they may indicate an underlying dementia or other organic brain syndrome and should be investigated. The level of consciousness (ie, sensorium) should be normal. A fluctuating or depressed sensorium suggests delirium, and the patient should be evaluated for organic contributors.
• Speech: Speech may be normal, slow, monotonic, or lacking in spontaneity and content. Pressured speech should suggest mania, while disorganized speech should prompt an evaluation for psychosis. Racing thoughts could also be an indication of mania or hypomania.
• Thought content, suicidality, and homicidality
  • The thought content of patients who are depressed usually is consistent with their dysphoric mood. Patients often report feeling overwhelmed or inadequate, helpless, worthless, or hopeless.
  • Thought content always should be assessed for hopelessness, suicidal ideation, or homicidal/violent ideation or intent.
  • A history of suicide attempts or violence is a significant risk factor for future attempts, and this should be noted in the history.
  • Hallucinations and delusions, including command hallucinations, could be part of presentation. These are usually mood congruent but could be mood incongruent. These psychotic elements, especially command hallucinations, are associated with increased suicidal and homicidal actions.
  • Depression screening tests such as PDQ-9 and Mood Disorder Questionnaire (MDQ) could be used easily in a primary care setting to screen for depression and bipolar disorder. The Hamilton and the Beck Depression inventory could also be similarly useful but are more detailed and time consuming.

Causes

The specific cause of major depressive disorder is not known. As with most psychiatric disorders, major depressive disorder appears to be multifactorial in its origin.

• Biological contributors
  • Genetic susceptibility plays a role in the development of major depressive disorder. Individuals with a family history of affective disorders (7%), panic disorder, and alcohol dependence (8%) carry a higher risk for major depressive disorder.
  • Certain neurologic illnesses increase the risk of major depressive disorder. Examples include Parkinson disease, stroke, multiple sclerosis, and seizure disorders.
  • Exposure to certain pharmacologic agents also increases the risk; medications such as reserpine or beta-blockers, as well as abused substances such as cocaine, amphetamine, narcotics, and alcohol are associated with higher rates of major depressive disorder.
  • Chronic pain, medical illness, and psychosocial stress also can play a role in both the initiation and maintenance of major depressive disorder. The psychological component of these risk factors is discussed below. However, neurochemical hypotheses point to the deleterious effects of cortisol and other stress-related substances on the neuronal substrate of mood in the CNS.
• Psychosocial contributors: While major depressive disorder can arise without any precipitating stressors, stress and interpersonal losses certainly increase risk. Psychodynamic formulations find that significant losses in early life predispose to major depressive disorder over the lifespan of the individual, as does trauma, either transient or chronic.

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