DEFINING MDD

The American psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V)7  distinguishes mood disorders into categories that include Depressive and Re- lated Disorders (“unipolar depression” such as MDD, persistent depressive disorder [dysthymia], and seasonal affective disorder) and Bipolar and Related Disorders. Mood disorders may reflect various causes (see below)  and can be based on etiology, such as substance intake or a general medical condition. It is important to note that patients may have more than one mood disorder; for example, substance abuse may coexist with MDD or bipolar disorder. the National Institute of Mental Health (NIMH) sum- marizes facets of common mood disorders as follows:8

  • Major depression: Severe symptoms that interfere with the ability to work, sleep, study, eat, and enjoy life. An episode can occur only once in a person’s lifetime, but more often, a person has several episodes.
  • Persistent depressive disorder: A depressed mood that lasts for at least two years. A person diagnosed with  persistent depressive disorder may have episodes of major depression along with periods of less severe symptoms.

Some forms of depression that develop under unique circumstances include:

  • Psychotic depression, which occurs when a person has severe depression plus some form of psychosis, such as  having disturbing false beliefs or a break with reality (delusions), or hearing or seeing upsetting things that  others cannot hear or see (hallucinations).
  • Postpartum depression, which is estimated to affect 10-15% of women after giving birth, is more serious than the “baby blues” that many women experience after giving birth, when hormonal and physical changes and  the new responsibility of caring for a newborn can be overwhelming. 
  • Seasonal affective disorder (SAD), which is characterized by the onset of depression during the winter months, when there is less natural sunlight. The depression generally lifts during spring and summer.
  • Bipolar disorder, which can be delineated into different types, but is usually characterized by episodes of extreme low (depression) and high moods (mania or hypomania).

Depression is believed to result from a combination of genetic, biochemical, environmental, and psychological factors, suggesting a complex etiology that requires an integrative model for full understanding. Depression is 2-3 times more common in first-degree biological relatives than in the general population.9 Although genetic association studies of mood disorders have implicated specific candidate genes in MDD, the complexity of genetic effects in influencing the phenotype is not fully understood. While depressive episodes may be triggered by stressful situations (e.g.,  trauma, emotional issues, job loss), MDD may also manifest independent of any obvious triggers. Moreover, depression often coexists with other illnesses, including anxiety disorders, substance abuse, heart disease, HIV/AIDS, diabetes, cancer, and Parkinson’s disease.8  Comorbid depression often exacerbates these and other chronic conditions. For example, in persons with coronary disease, depressive symptoms are strongly associated with symptom burden, physical limitations, quality of life (QoL), and overall health.10  Depression has been linked with a higher rate of cardiovascular events11  and functional decline12  in persons with coronary disease and with worse QoL in asthma patients.13

On a molecular level, the serotonergic system has been postulat- ed to play a central role in MDD pathophysiology. the serotoner- gic pathway influences various neurotransmitter systems, including serotonin (5-Ht), dopamine, norepinephrine, glutamate, acetylcholine, histamine, and GABA, and it is involved in mood regulation, fear responses, sleep, appetite, and sexual behavior.14 the pivotal role of these neurotransmitters has shaped a “mono- amine deficiency” model of depression, in which depletion of serotonin, norepinephrine, epinephrine, and/or dopamine in the central nervous system is postulated to undergird the pathophysiology of MDD.15

There are fourteen types of 5-Ht receptors in the brain, each of which effects multiple  functions.14  The most widespread 5-Ht receptor is 5-Ht1A, which is a site of action of many antidepressant agents. All FDA-approved antidepressants act on neurotransmitter receptors with an aim to elevate the levels of these compounds in the brain, and their efficacy has generally supported the monoamine deficiency model. However, there is no evidence of a primary dysfunction in a specific monoamine system in individuals with depressive disorders,15  and it is common for patients to achieve symptom relief with one agent, while other drugs within the same class fail to produce a comparable effect.

Table 1 (below) lists DSM-V criteria for diagnosing MDD.

Patients with MDD may present with various combinations of the symptoms listed above, and severity and frequency vary among individuals. While several persistent symptoms in addition to low mood are required for a diagnosis of MDD, the NIMH notes that individuals who present a few (but distressing) symptoms may benefit from treatment of their “subsyndromal” depression.8

Table 1. DSM-V Criteria for Diagnosing MDD7
A.     Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.
  • Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful). (Note: In children and adolescents, can be irritable mood.)
  • Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation.)
  • Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. (Note: In children, consider failure to make expected weight gain.)
  • Insomnia or hypersomnia nearly every day.
  • Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).
  • Fatigue or loss of energy nearly every day.
  • Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).
  • Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).
  • Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

B   The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

C. The episode is not attributable to the physiological effects of a substance or to another medical condition.

D.  The occurrence of the major depressive episode is not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders.

E.  There has never been a manic episode or a hypomanic episode. Note: This exclusion does not apply if all of the manic-like or hypomanic-like episodes are substance-induced or are attributable to the physiological effects of another medical condition.

Note: Criteria A-C represent a major depressive episode. Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should also be carefully considered. This decision inevitably requires the exercise of clinical judgment based on the individual’s history and the cultural norms for the expression of distress in the context of loss.