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.
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-complexvitamins, 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.
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).
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>.
