Clinical syndromes

The most common form of affective disorder is a major depressive episode. The episode is defined by a pervasively depressed or low mood (which is experienced most of the day over a period of 2 weeks or longer) and at least four associated symptoms affecting sleep, appetite, hedonic capacity, interest, and behavior.

Major depressive episodes have several clinical forms. Melancholia is a severe episode characterized by anhedonia, marked anorexia with weight loss, early morning awakening, observable motor disturbances (extreme slowing, or retardation, or pacing and stereotypic agitated behaviors), and diurnal mood variation (mood is worse in the morning). See Anorexia nervosa

Common among young patients, especially women, is a milder syndrome historically referred to as atypical depression. Atypical depression is characterized by intact mood reactivity (one's spirits can go up or down in response to day-to-day events) and reverse symptoms: oversleeping, overeating, or gaining weight. Significant anxiety symptoms, including phobias and panic attacks, also are common in atypical depression.

A more chronic, insidious form of depression known as dysthymia “smolders” at a subsyndromal level (that is, there are three or four daily symptoms) for at least 2 years. Dysthymia often begins early in life and, historically, has been intertwined with atypical and neurotic characteristics.

A manic episode is heralded by euphoric or irritable mood and at least four of the following: increased energy, activity, self-esteem, or speed of thought; decreased sleep; poor judgment; and risk-taking. About one-half of manic episodes are psychotic. The delusions of mania typically reflect grandiose or paranoid themes. Most people who have manic episodes also experience recurrent depressive episodes.

The term bipolar affective disorder has largely replaced the old term manic-depression, although both names convey the cyclical nature of this illness. The classical presentation (which includes full-blown manic episodes) is known as type 1 disorder. The diagnosis of bipolar type 2 disorder is used when there are recurrent depressive episodes and at least one hypomania. The diagnosis of cyclothymia is used when neither hypomanias nor depressions have reached syndromal levels.

Two variations of bipolar episodes are increasingly recognized. A mixed episode is diagnosed when the symptoms of mania and depression coexist. The term rapid cycling is used when there have been four or more episodes within a time frame of 1 year.

A number of affective disorders follow a seasonal pattern. A pattern of recurrent fall/winter depressions (also known as seasonal affective disorder) has generated considerable interest because it may be treated with bright white light, which artificially lengthens the photoperiod.

Literally all forms of affective disorder can be caused by general medical illnesses and medications that affect brain function (such as antihypertensives, hormonal therapies, steroids, and stimulant drugs). The diagnosis “mood disorder associated with a general medical condition” is applied to these conditions.

Pathophysiology

The affective disorders have diverse biopsychosocial underpinnings that result, at least in part, in extreme or distorted responses of several neurobehavioral systems. The neurobehavioral systems of greatest relevance regulate a person's drives and pursuits, responses to acute stress, and capacity to dampen or quiet pain or distress.

Although there is considerable evidence that affective disorders are heritable, vulnerability is unlikely to be caused by a single gene. It is likely that some combination of genes conveys greater risk and, like an amplifier, distorts the neural signals evoked by stress and distress. See Behavior genetics, Human genetics

Research permits several firm conclusions about brain neurochemistry in stress and depression. Acute stress mobilizes the release of three vital brain monoamines–serotonin, norepinephrine, and dopamine—as well as glucocorticoids such as cortisol. Sustained and unresolvable stress eventually depletes the neurotransmitters (cortisol levels remain high), inducing a behavioral state of learned helplessness. Severe depression, especially recurrent episodes of melancholia, affects the brain similarly.

Psychosocial and neurobiologic vulnerabilities, no doubt, intersect. For example, harsh early maltreatment, neglect, or other abuses can have lasting effects on both self-concept and brain responses to stress.

Epidemiology

The lifetime rates of affective disorders are increasing, with an earlier age of onset. The onset of major depression most often occurs in the late 20s to mid-30s; dysthymia and bipolar disorder typically begin about a decade earlier. However, no age group is immune to an affective disorder. Vulnerability is not related to social class or race, although the affluent are more likely to receive treatment.

Treatment

Most episodes of dysthymia and major depressive disorder respond to treatment with either psychotherapy or antidepressant medication, either singly or in combination. Many experts now recommend the newer forms of psychotherapy, including cognitive behavior therapy and interpersonal therapy, because they have been better studied than more traditional psychoanalytic therapies and because they have been found to be as effective as medications.

Nearly 30 antidepressant medications are available worldwide, with most falling into three classes: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase reuptake inhibitors (MAOIs). Most classes of antidepressants enhance the efficiency of serotonin or norepinephrine neurotransmission. Antidepressants are not habit-forming and have no mood-elevating effects for nondepressed people. See Psychopharmacology, Psychotherapy

Acute manic episodes are usually treated with either lithium salts or divalproex sodium. Psychotic symptoms and severe agitation sometimes warrant the acute use of antipsychotic drugs. Although psychotherapy does not have a major role in the acute treatment of mania, it may help people come to terms with their illness, cope more effectively with stress, or curb minor depressive episodes.

When pharmacotherapies are not effective, the oldest proven treatment of the affective disorders, electroconvulsive therapy (ECT), still provides a powerful alternative. Today, ECT is a highly modified and carefully monitored treatment that has little in common with its depictions in the movies. Nevertheless, confusion and transient amnesia are still problems.