affective disorder

n.
A mental disorder characterized by a consistent, pervasive alteration in mood, and affecting thoughts, emotions, and behaviors.

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Definition

Affective disorders are psychiatric diseases with multiple aspects, including biological, behavioral, social, and psychological factors. Major depressive disorder, bipolar disorders, and anxiety disorders are the most common affective disorders. The effects of these disorders—such as difficulties in interpersonal relationships and an increased susceptibility to substance abuse—are major concerns for parents, teachers, physicians, and the community. Affective disorders can result in symptoms ranging from the mild and inconvenient to the severe and life-threatening; the latter account for more than 15% of deaths due to suicide among those with one of the disorders.

Major depressive disorder (MDD), also known as monopolar depression or unipolar affective disorder, is a common, severe, and sometimes life-threatening psychiatric illness. MDD causes prolonged periods of emotional, mental, and physical exhaustion, with a considerable risk of self-destructive behavior and suicide. Major studies have identified MDD as one of the leading causes of work disability and premature death, representing an increasingly worldwide health and economic concern.

Bipolar affective diseases are divided into various types according to the symptoms displayed: Type I (bipolar I, or BPI) and Type II (bipolar II or BPII) disease, cyclothymic disorder, and hypomania disorder. Other names for bipolar affective disease include manic-depressive disorder, cyclothymia, manic-depressive illness (MDI), and bipolar disorder. People with bipolar diseases experience periods of manic (hyper-excitable) episodes alternating with periods of deep depression. Bipolar disorders are chronic and recurrent affective diseases that may have degrees of severity, tending however to worsen with time if not treated. Severe crises can lead to suicidal attempts during depressive episodes or to physical violence against oneself or others during manic episodes. In many patients, however, episodes are mild and infrequent. Mixed states may also occur with elements of mania and depression simultaneously present. Some people with bipolar affective disorders show a rapid cycling between manic and depressive states.

Anxiety disorders are also common psychiatric disorders, and are considered one of the most under-treated and overlooked health problems. Among its common manifestations are panic syndromes, phobias, chronic generalized anxiety disorder, obsessive-compulsive disorder, and post-traumatic disorder. Anxiety disorders are important contributors to other diseases such as hypertension, digestive and eating disorders, and cardiac arrhythmia. Severe anxiety disorders often lead to tobacco addiction, alcohol abuse, and drug abuse.

Description

People with major depressive disorder (MDD) experience periods of at least two weeks of symptoms that often include sadness, emotional heaviness, feelings of worthlessness, hopelessness, guilt, anguish, fear, loss of interest for normal daily activities, social withdrawal, inability to feel pleasure, physical apathy, difficulty in concentrating, and recurrent thoughts about death. Changes in sleeping pattern, with insomnia during the night and hypersomnia (excessive sleep) during the day, chronic fatigue, and a feeling of being physically drained and immobile may also occur. Irritability and mood swings may be present, and loss of appetite or overeating are common features. In severe cases, MDD may last for months, with those affected experiencing profound despair and spending most of their time isolated or prostrate in bed, considering or planning suicide. Approximately 50% of MDD patients attempt suicide at least once in their lives.

In bipolar I disease (BPI), the manic episodes are severe, lasting from one week to three months or more if untreated, and often require hospitalization. Manic episodes are characterized by hyperactivity, feelings of grandiosity or omnipotence, euphoria, constant agitation, obsessive work or social activity, increased sexual drive, racing thoughts and surges of creativity, distractibility, compulsive shopping or money spending, and sharp mood swings and aggressive reactions, which may include physical violence against others. Depressive episodes may not occur in some BPI patients, but when present, the signs are similar to those of MDD and tend to last for months if untreated.

In bipolar II disease (BPII), milder and fewer manic episodes occur than for those people suffering from BPI, and at least one major depressive episode is experienced. BPII depression is the most common form of bipolar disease. Depressive episodes are usually more frequent than manic episodes, and can also last for extended periods if untreated.

Cyclothymia disorder is less severe, but tends to be chronic with frequent mood swings and single episodes lasting for at least two years. In some individuals, cyclothymic disorder is the precursor to a progressive bipolar disease. In others, the cyclothymic disorder remains chronic.

Hypomania is a mild degree of mania, manifested as brief and mild episodes of inflated self-esteem and excitability, irritability, impatience, and demanding attitude. Those with hypomania often find it disturbing or impossible to relax or to remain idle. Feelings of urgency to work longer hours and accomplish several tasks simultaneously are common.

Demographics

MDD is a leading cause of suicide, with more than 100,000 attempts per year in the United States alone. Affective disorders account for more than 200,000 suicide attempts in the United States, with an estimated mortality rate of 15%. Affective disorders are, however, a worldwide problem, and there are no racial differences, though Caucasian and Japanese males have been shown to be at higher risk of committing suicide. Suicide due to affective disorders is the second leading cause of mortality in teenagers in the United States and, among young adults, it accounts for 10–30% of deaths.

Causes and symptoms

Cultural influences and social pressures in achievement-oriented societies are important risk factors in affective disorders symptoms. Wars, catastrophic events, severe economic recession, accidents, personal loss, and urban violence are other contributing or triggering factors. Alcohol and drug abuse have a direct impact on brain neurochemistry, as well as some diseases, medical interventions, and medications, constituting a risk factor as well. However, in most cases, alcoholism, tobacco use, and/or drug abuse are the clinical symptoms of an underlying affective disorder that is inherently predisposed to substance abuse. Adaptive neurochemical and structural brain changes occurring in childhood give rise to the symptoms of many affective disorders; the diseases tend to run in families, although specific genetic factors causing the diseases have not yet been identified. Malnutrition and nutritional deficiencies are also important triggering factors in many psychiatric and affective disorders, as well as brain contamination with toxic levels of heavy metals such as methyl-mercury, lead, and bismuth.

The age of onset of bipolar diseases varies from childhood to middle adulthood, with a mean age of 21 years. MDD onset is highly variable, due to the presence of different possible factors such as family history, traumatic childhood, hormonal imbalance or seasonal changes, medical procedures, diseases, stress, menopause, emotional trauma and affective losses, or economical and social factors such as unemployment or social isolation.

Children with one parent affected by MDD or bipolar disease are five to seven times more prone to develop some affective or other psychiatric disorder than the general population. Although an inherited genetic trait is also under suspicion, studies over the past 20 years, as well as ongoing research on brain development during childhood, suggest that many cases of affective disorder may be due to the impact of repetitive and prolonged exposure to stress on the developing brain. Children of bipolar or MDD parents, for instance, may experience neglect or abuse, or be required to cope in early childhood with the emotional outbursts and incoherent mood swings of adults. Many children of those with affective disorders feel guilty or responsible for the dysfunctional adult. Such early exposure to stress generates abnormal levels of toxic metabolites in the brain, which have been shown to be harmful to the neurochemistry of the developing brain during childhood.

The neurochemical effects of stress alter both the quantities and the baseline systems of substances responsible for information processing between neurons such as neurotransmitters and hormones. Moreover, the stress metabolites such as glucocorticoids cause atrophy and death of neurons, a phenomenon known as neuronal crop, which alters the architecture of a child's brain. Neurotransmitters have specific roles in mood and in behavioral, cognitive, and other physiological functions: serotonin modulates mood, satiety (satisfaction in appetite), and sleeping patterns; dopamine modulates reward-seeking behavior, pleasure, and maternal/paternal and altruistic feelings; norepinephrine determines levels of alertness, danger perception, and fight-or-flight responses; acetylcholine controls memory and cognition processes; gamma amino butyric acid (GABA) modulates levels of reflex/stimuli response and controls or inhibits neuron excitation; and glutamate promotes excitation of neurons. Orchestrated interaction of proper levels of different neurotransmitters is essential for normal brain development and function, greatly influencing affective (mood), cognitive, and behavioral responses to the environment.

Low levels of the neurotransmitters serotonin and norepinephrine were found in people with affective disorders, and even lower levels of serotonin are associated with suicide and compulsive or aggressive behavior. Depressive states with mood swings and surges of irritability also point to serotonin depletion. Lower levels of dopamine are related to both depression and aggressive behavior. Norepinephrine synthesis depends on dopamine, and its depletion leads to loss of motivation and apathy. GABA is an important mood regulator because it controls and inhibits chemical changes in the brain during stress. Depletion of GABA leads to phobias, panic attacks, chronic anxiety pervaded with dark thoughts about the dangers of accidents, hidden menaces, and feelings of imminent death. Acute and prolonged stress, as well as alcohol and drug abuse, leads to GABA depletion. Acetylcholine depletion causes attention and concentration deficits, memory reduction, and learning disorders.

Chronic stress or highly traumatic experiences cause adaptive or compensatory changes in brain neurochemistry and physiology, in order to provide the individual with defense and survival mechanisms. However, such adaptive changes come with a high cost, in particular when they are required for an extended period such as in war zones, or other prolonged stressful situations. The adaptive chemicals tend to outlast the situation for which they were required, leading to some form of affective and behavioral disorder.

These adaptive neurochemical changes are especially harmful during early childhood. For instance, neglected or physically, sexually, or emotionally abused children are exposed to harmful levels of glucocorticoids (comparable to those found in war veterans) that lead to neuron atrophy (wasting) and cropping (reduced numbers) in the hippocampus region of the brain. Neuronal atrophy and crop often cause cognitive and memory disorders, anxiety, and poor emotional control. Neuronal crop also occurs in the frontal cortex of the brain's left hemisphere, leading to fewer nerve-cell connections with several other brain areas. These decreased nerve-cell connections favor epilepsy-like short circuits or microseizures in the brain that occur in association with bursts of aggressiveness, self-destructive behavior, and cognitive or attention disorders. These alterations are also seen in the brains of adults who were abused or neglected during childhood. Time and recurrence of exposure and severity of suffered abuse help determine the extension of brain damage and the severity of psychiatric-related disorders in later stages of life.

Diagnosis

Well-known sets of clinical characteristics associated with MDD, bipolar diseases, or anxiety disorders provide the physician the necessary data for an initial diagnosis of affective disorder. The psychiatrist analyzes the person's pattern of mood, behavioral, and cognitive symptoms, along with the family history and environmental-contributing factors.

Abnormal atrophy, or loss of volume, in the hippocampus and cortex areas of the brain are detectable on magnetic resonance imaging (MRI) and computed tomography (CT) scans. Postmortem neuropathological (brain tissue) analysis demonstrates reduced cells and/or neuron size reductions in several brain regions of those with affective disorders.

Treatment team

The treatment team for people with affective disorders is primarily the psychiatrist, a medical doctor specializing in mood diseases and chemistry of the brain. Psychologists may also provide counseling and behavioral strategies for coping with the illness. Nurses administer prescribed medicine, along with monitoring behavior and physical condition during acute phases of the illness in the hospital setting. Mental health nurses also support treatment plans for clients in the community and provide a ready link to the psychiatrist. Additional community resources may include school psychologists, counselors, and support groups for affected people, as well as their family.

Treatment

Psychotherapy alone is rarely sufficient for the treatment of affective disorders, as the existing neurochemical imbalance impairs the ability of a person with an affective disorder to respond. However, psychotherapy is important in helping to cope with guilt, low self-esteem, and inadequate behavioral patterns once the neurochemistry is stabilized and more normal levels of neurotransmitters are at work.

Understanding of the devastating effects of stress in the brain of highly stressed or abused children made evident the need of medication as well as psychotherapy in early intervention. Administration of clonidine, a drug that inhibits the fight-or-flight response, and of other medications—or GABA supplementation—that interfere with levels of glucocorticoids in the brain can prevent both harmful neurochemical and architectural changes in the child's central nervous system. Family and parental therapy is also crucial in order to reduce the presence of emotional stressors in the child's life.

Teenagers and adults suffering from affective disorders may benefit from prescribed antidepressant medications that reduce symptoms. Recent studies have shown that antidepressants also encourage neuron cells in certain areas of the brain to mature, thus protecting the number of neurons in this area and preventing stress-induced neuronal crop. Lithium is beneficial to some bipolar and MDD patients, and also shows a protective effect against several neural injuries.

Antidepressants that inhibit the fast removal (i.e., reuptake) of serotonin from the receptors in neurons and that regulate norepinephrine concentrations in the neuronal networks of the brain are very effective in mood stabilization. After a few days of medication, symptoms often recede. Nutrient supplementation, especially with B-complex vitamins, GABA, and essential amino acids, optimizes the synthesis of neurotransmitters and important neuropeptides, which are important for balanced neuro-chemistry in the central nervous system.

Recovery and rehabilitation

Helping individuals with an affective disorder to recognize their particular symptoms and mood states is essential for recovery and rehabilitation. With recognition, a person may seek additional treatment during recurring episodes early enough to deter the harmful consequences of the disease.

Clinical trials

As of early 2004, the National Institute of Mental Health (NIMH) is offering several clinical trials for adults and children with many types of affective disorders. People may participate at the institute's main facility in Bethesda, Maryland, or at several locations throughout the United States. Further information and updates may be found at the NIMH clinical trials web site.

Prognosis

Because affective disorders are usually long-term, cyclic conditions, ongoing treatment should be considered to prevent or modulate episodes of depression, mania, or severe anxiety. With preventative drug therapy, most people with affective disorders can expect to experience stabilization of their moods and anxiety, and can maintain an active role in work and social settings. Without treatment, daily activities and work are usually difficult to maintain within the cycles of mood disturbances, and social isolation, drug abuse, and suicide are often long-term consequences.

Resources

BOOKS

DePaulo, Jr., J. Raymond, and Leslie Alan Horvitz. Understanding Depression: What We Know and What You Can Do about It. New York: John Wiley & Sons, Inc., 2002.

Masters, Roger D., and Michael T. McGuire. The Neurotransmitter Revolution. Carbondale, IL: Southern Illinois University Press, 1994.

Mondimore, Francis Mark. Bipolar Disorder: A Guide for Patients and Families. Baltimore: The Johns Hopkins University Press, 1999.

PERIODICALS

Teicher, Martin H. "Wounds that Won't Heal—The Neurobiology of Child Abuse." Scientific American (March 2002): 68–75.

Vogel, G. "Depression Drugs' Powers May Rest on New Neurons." Science 301, no. 757 (2003).

OTHER

National Institute of Mental Health. For the Public. January 3, 2004 (March 30, 2004). http://www.nimh.nih.gov/publicat/index.cfm.

ORGANIZATIONS

National Institute of Mental Health. 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663. (301) 443-4513 or (866) 615-6464; Fax: (301) 443-4279. nimhinfo@nih.gov. http://www.nimh.nih.gov.

Depression and Related Affective Disorders Association (DRADA). 2330 West Joppa Rd., Suite 100, Lutherville, MD 21093. (410) 583-2919. drada@hmi.edu. http://www.drada.org/Facts/general.html.

Sandra Galeotti

A group of psychiatric conditions, also known as mood disorders, characterized by disturbances of affect, emotion, thinking, and behavior. Depression is the most common of these disorders, and about 10–20% of those affected also experience manic episodes. The affective disorders are not distinct diseases but are psychiatric syndromes that likely have multiple or complex etiologies.

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 also 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 also 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 also 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. See also Electroconvulsive therapy.

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Disorders of mood or emotions such as over-anxiety and depression.

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