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DEPRESSION |
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Life
is full of emotional ups and downs. But when the "down" times
are long lasting or interfere with your ability to function, you may be
suffering from a common, serious illness-depression. Clinical depression
affects mood, mind, body, and behavior. Research has shown that in the
United States about 19 million people-one in ten adults-experience
depression each year, and nearly two-thirds do not get the help they
need.9 Treatment can alleviate the symptoms in over 80
percent of the cases. Yet, because it often goes unrecognized,
depression continues to cause unnecessary suffering.
Depression
is a pervasive and impairing illness that affects both women and men,
but women experience depression at roughly twice the rate of men.1
Researchers continue to explore how special issues unique to
women-biological, life cycle, and psycho-social-may be associated with
women's higher rate of depression.
No
two people become depressed in exactly the same way. Many people have
only some of the symptoms, varying in severity and duration. For some,
symptoms occur in time-limited episodes; for others, symptoms can be
present for long periods if no treatment is sought. Having some
depressive symptoms does not mean a person is clinically depressed. For
example, it is not unusual for those who have lost a loved one to feel
sad, helpless, and disinterested in regular activities. Only when these
symptoms persist for an unusually long time is there reason to suspect
that grief has become depressive illness. Similarly, living with the
stress of potential layoffs, heavy workloads, or financial or family
problems may cause irritability and "the blues." Up to a
point, such feelings are simply a part of human experience. But when
these feelings increase in duration and intensity and an individual is
unable to function as usual, what seemed a temporary mood may have
become a clinical illness. Evidence
from neuroscience, genetics, and clinical investigation demonstrate that
depression is a disorder of the brain. Modern brain imaging technologies
are revealing that in depression, neural circuits responsible for the
regulation of moods, thinking, sleep, appetite, and behavior fail to
function properly, and that critical neurotransmitters – chemicals
used by nerve cells to communicate – are out
of balance. Genetics research indicates that vulnerability to
depression results from the influence of multiple genes acting together
with environmental factors. Studies of brain chemistry and of mechanisms
of action of antidepressant medications continue to inform the
development of new and better treatments. In the past decade, there have
been significant advances in our ability to investigate brain function
at multiple levels. THE
TYPES OF DEPRESSIVE ILLNESS
SYMPTOMS
OF DEPRESSION AND MANIA
A thorough diagnostic
evaluation is needed if three to five or more of the following symptoms
persist for more than 2 weeks (1 week in the case of mania), or if they
interfere with work or family life. An evaluation involves a complete
physical checkup and information gathering on family health history. Not
everyone with depression experiences each of these symptoms. The
severity of the symptoms also varies from person to person.
Depression
Mania
CAUSES
OF DEPRESSION
Genetic Factors
There is a risk for developing
depression when there is a family history of the illness, indicating
that a biological vulnerability may be inherited. The risk is somewhat
higher for those with bipolar disorder. However, not everybody with a
family history develops the illness. In addition, major depression can
occur in people who have had no family members with the illness. This
suggests that additional factors, possibly biochemistry, environmental
stressors, and other psychosocial factors, are involved in the onset of
depression.
Biochemical Factors
Evidence indicates that brain
biochemistry is a significant factor in depressive disorders. It is
known, for example, that individuals with major depressive illness
typically have dysregulation of certain brain chemicals, called
neurotransmitters. Additionally, sleep patterns, which are biochemically
influenced, are typically different in people with depressive disorders.
Depression can be induced or alleviated with certain medications, and
some hormones have mood-altering properties. What is not yet known is
whether the "biochemical disturbances" of depression are of
genetic origin, or are secondary to stress, trauma, physical illness, or
some other environmental condition.
Environmental and Other
Stressors
Significant loss, a difficult
relationship, financial problems, or a major change in life pattern have
all been cited as contributors to depressive illness. Sometimes the
onset of depression is associated with acute or chronic physical
illness. In addition, some form of substance abuse disorder occurs in
about one-third of people with any type of depressive disorder.7
Other Psychological and Social
Factors
Persons with certain
characteristics-pessimistic thinking, low self-esteem, a sense of having
little control over life events, and a tendency to worry excessively-are
more likely to develop depression. These attributes may heighten the
effect of stressful events or interfere with taking action to cope with
them or with getting well. Upbringing or sex role expectations may
contribute to the development of these traits. It appears that negative
thinking patterns typically develop in childhood or adolescence. Some
experts have suggested that the traditional upbringing of girls might
foster these traits and may be a factor in women's higher rate of
depression. WOMEN
ARE AT GREATER RISK FOR DEPRESSION THAN MEN
Major depression
and dysthymia affect twice as many women as men. This
two-to-one ratio exists regardless of racial and ethnic background or
economic status. The same ratio has been reported in ten other countries
all over the world. Men and women have about the same rate of bipolar
disorder (manic-depression), though its course in women
typically has more depressive and fewer manic episodes. Also, a greater
number of women have the rapid cycling form of bipolar disorder, which
may be more resistant to standard treatments.5
A variety of factors unique to
women's lives are suspected to play a role in developing depression.
Research is focused on understanding these, including: reproductive,
hormonal, genetic or other biological factors; abuse and oppression;
interpersonal factors; and certain psychological and personality
characteristics. And yet, the specific causes of depression in women
remain unclear; many women exposed to these factors do not develop
depression. What is clear is that regardless of the contributing
factors, depression is a highly treatable illness.
THE
MANY DIMENSIONS OF DEPRESSION IN WOMEN
Investigators are focusing on
the following areas in their study of depression in women:
The Issues of Adolescence
Before adolescence, there is
little difference in the rate of depression in boys and girls. But
between the ages of 11 and 13 there is a precipitous rise in depression
rates for girls. By the age of 15, females are twice as likely to have
experienced a major depressive episode as males.2 This comes
at a time in adolescence when roles and expectations change
dramatically. The stresses of adolescence include forming an identity,
emerging sexuality, separating from parents, and making decisions for
the first time, along with other physical, intellectual, and hormonal
changes. These stresses are generally different for boys and girls, and
may be associated more often with depression in females. Studies show
that female high school students have significantly higher rates of
depression, anxiety disorders, eating disorders, and adjustment
disorders than male students, who have higher rates of disruptive
behavior disorders.6
Adulthood: Relationships and
Work Roles
Stress in general can
contribute to depression in persons biologically vulnerable to the
illness. Some have theorized that higher incidence of depression in
women is not due to greater vulnerability, but to the particular
stresses that many women face. These stresses include major
responsibilities at home and work, single parenthood, and caring for
children and aging parents. How these factors may uniquely affect women
is not yet fully understood. For both women and men, rates
of major depression are highest among the separated and divorced, and
lowest among the married, while remaining always higher for women than
for men. The quality of a marriage, however, may contribute
significantly to depression. Lack of an intimate, confiding
relationship, as well as overt marital disputes, have been shown to be
related to depression in women. In fact, rates of depression were shown
to be highest among unhappily married women.
Reproductive Events
Women's reproductive events
include the menstrual cycle, pregnancy, the postpregnancy period,
infertility, menopause, and sometimes, the decision not to have
children. These events bring fluctuations in mood that for some women
include depression. Researchers have confirmed that hormones have an
effect on the brain chemistry that controls emotions and mood; a
specific biological mechanism explaining hormonal involvement is not
known, however.
Many women experience certain
behavioral and physical changes associated with phases of their
menstrual cycles. In some women, these changes are severe, occur
regularly, and include depressed feelings, irritability, and other
emotional and physical changes. Called premenstrual syndrome
(PMS) or premenstrual dysphoric disorder (PMDD), the
changes typically begin after ovulation and become gradually worse until
menstruation starts. Scientists are exploring how the cyclical rise and
fall of estrogen and other hormones may affect the brain chemistry that
is associated with depressive illness.10
Postpartum mood changes
can range from transient "blues" immediately following
childbirth to an episode of major depression to severe, incapacitating,
psychotic depression. Studies suggest that women who experience major
depression after childbirth very often have had prior depressive
episodes even though they may not have been diagnosed and treated.
Pregnancy
(if it is desired) seldom contributes to depression, and having an
abortion does not appear to lead to a higher incidence of depression.
Women with infertility problems may be subject to extreme anxiety or
sadness, though it is unclear if this contributes to a higher rate of
depressive illness. In addition, motherhood may be a time of heightened
risk for depression because of the stress and demands it imposes.
Menopause,
in general, is not asssociated with an increased risk of depression. In
fact, while once considered a unique disorder, research has shown that
depressive illness at menopause is no different than at other ages. The
women more vulnerable to change-of-life depression are those with a
history of past depressive episodes.
Specific Cultural
Considerations
As for depression in general,
the prevalence rate of depression in African American and Hispanic women
remains about twice that of men. There is some indication, however, that
major depression and dysthymia may be diagnosed less frequently in
African American and slightly more frequently in Hispanic than in
Caucasian women. Prevalence information for other racial and ethnic
groups is not definitive.
Possible differences in
symptom presentation may affect the way depression is recognized and
diagnosed among minorities. For example, African Americans are more
likely to report somatic symptoms, such as appetite change and body
aches and pains. In addition, people from various cultural backgrounds
may view depressive symptoms in different ways. Such factors should be
considered when working with women from special populations.
Victimization
Studies show that women
molested as children are more likely to have clinical depression at some
time in their lives than those with no such history. In addition,
several studies show a higher incidence of depression among women who
have been raped as adolescents or adults. Since far more women than men
were sexually abused as children, these findings are relevant. Women who
experience other commonly occurring forms of abuse, such as physical
abuse and sexual harassment on the job, also may experience higher rates
of depression. Abuse may lead to depression by fostering low
self-esteem, a sense of helplessness, self-blame, and social isolation.
There may be biological and environmental risk factors for depression
resulting from growing up in a dysfunctional family. At present, more
research is needed to understand whether victimization is connected
specifically to depression.
Poverty
Women and children represent
seventy-five percent of the U.S. population considered poor. Low
economic status brings with it many stresses, including isolation,
uncertainty, frequent negative events, and poor access to helpful
resources. Sadness and low morale are more common among persons with low
incomes and those lacking social supports. But research has not yet
established whether depressive illnesses are more prevalent among those
facing environmental stressors such as these.
Depression in Later Adulthood
At one time, it was commonly
thought that women were particularly vulnerable to depression when their
children left home and they were confronted with "empty nest
syndrome" and experienced a profound loss of purpose and identity.
However, studies show no increase in depressive illness among women at
this stage of life.
As with younger age groups,
more elderly women than men suffer from depressive illness. Similarly,
for all age groups, being unmarried (which includes widowhood) is also a
risk factor for depression. Most important, depression should not be
dismissed as a normal consequence of the physical, social, and economic
problems of later life. In fact, studies show that most older people
feel satisfied with their lives.
About 800,000 persons are
widowed each year. Most of them are older, female, and experience
varying degrees of depressive symptomatology. Most do not need formal
treatment, but those who are moderately or severely sad appear to
benefit from self-help groups or various psychosocial treatments.
However, a third of widows/widowers do meet criteria for major
depressive episode in the first month after the death, and half of these
remain clinically depressed 1 year later. These depressions respond to
standard antidepressant treatments, although research on when to start
treatment or how medications should be combined with psychosocial
treatments is still in its early stages. 4,8
DEPRESSION
IS A TREATABLE ILLNESS
Even severe depression can be
highly responsive to treatment. Indeed, believing one's condition is
"incurable" is often part of the hopelessness that accompanies
serious depression. Such individuals should be provided with the
information about the effectiveness of modern treatments for depression
in a way that acknowledges their likely skepticism about whether
treatment will work for them. As with many illnesses, the earlier
treatment begins, the more effective and the greater the likelihood of
preventing serious recurrences. Of course, treatment will not eliminate
life's inevitable stresses and ups and downs. But it can greatly enhance
the ability to manage such challenges and lead to greater enjoyment of
life. The first step in treatment
for depression should be a thorough examination to rule out any physical
illnesses that may cause depressive symptoms. Since certain medications
can cause the same symptoms as depression, the examining physician
should be made aware of any medications being used. If a physical cause
for the depression is not found, a psychological evaluation should be
conducted by the physician or a referral made to a mental health
professional.
Types of Treatment for
Depression
The most commonly used
treatments for depression are antidepressant medication, psychotherapy,
or a combination of the two. Which of these is the right treatment for
any one individual depends on the nature and severity of the depression
and, to some extent, on individual preference. In mild or moderate
depression, one or both of these treatments may be useful, while in
severe or incapacitating depression, medication is generally recommended
as a first step in the treatment.3 In combined treatment,
medication can relieve physical symptoms quickly, while psychotherapy
allows the opportunity to learn more effective ways of handling
problems. Medications
There are several types of
antidepressant medications used to treat depressive disorders. These
include newer medications-chiefly the selective serotonin reuptake
inhibitors (SSRIs)-and the tricyclics and monoamine oxidase inhibitors
(MAOIs). The SSRIs-and other newer medications that affect
neurotransmitters such as dopamine or norepinephrine-generally have
fewer side effects than tricyclics. Each acts on different chemical
pathways of the human brain related to moods. Antidepressant medications
are not habit-forming. Although some individuals notice improvement in
the first couple of weeks, usually antidepressant medications must be
taken regularly for at least 4 weeks and, in some cases, as many as 8
weeks, before the full therapeutic effect occurs. To be effective and to
prevent a relapse of the depression, medications must be taken for about
6 to 12 months, carefully following the doctor's instructions.
Medications must be monitored to ensure the most effective dosage and to
minimize side effects. For those who have had several bouts of
depression, long-term treatment with medication is the most effective
means of preventing recurring episodes.
The prescribing doctor will
provide information about possible side effects and, in the case of
MAOIs, dietary and medication restrictions. In addition, other
prescribed and over-the-counter medications or dietary supplements being
used should be reviewed because some can interact negatively with
antidepressant medication. There may be restrictions during pregnancy. For bipolar disorder, the
treatment of choice for many years has been lithium, as it can be
effective in smoothing out the mood swings common to this disorder. Its
use must be carefully monitored, as the range between an effective dose
and a toxic one can be relatively small. However, lithium may not be
recommended if a person has pre-existing thyroid, kidney, or heart
disorders or epilepsy. Fortunately, other medications have been found
helpful in controlling mood swings. Among these are two mood-stabilizing
anticonvulsants, carbamazepine (Tegretol®) and valproate (Depakote®).
Both of these medications have gained wide acceptance in clinical
practice, and valproate has been approved by the Food and Drug
Administration for first-line treatment of acute mania. Since some
studies indicate that valproate can interfere with hormonal function in
adolescent girls, young girls taking valproate should be monitored
carefully by a physician. Other anticonvulsants that are being used now
include lamotrigine (Lamictal®) and gabapentin (Neurontin®);
their role in the treatment hierarchy of bipolar disorder remains under
study. Most people who have bipolar
disorder take more than one medication. Along with lithium and/or an
anticonvulsant, they often take a medication for accompanying agitation,
anxiety, insomnia, or depression. Some research indicates that an
antidepressant, when taken without a mood stabilizing medication, can
increase the risk of switching into mania or hypomania, or of developing
rapid cycling, in people with bipolar disorder. Finding the best
possible combination of these medications is of utmost importance to the
patient and requires close monitoring by the physician.
Herbal Therapy
In the past few years, much
interest has risen in the use of herbs in the treatment of both
depression and anxiety. St. John's wort (Hypericum perforatum), an herb
used extensively in the treatment of mild to moderate depression in
Europe, has recently aroused interest in the United States. St. John's
wort, an attractive bushy, low-growing plant covered with yellow flowers
in summer, has been used for centuries in many folk and herbal remedies.
Today in Germany, Hypericum is used in the treatment of depression more
than any other antidepressant. However, the scientific studies that have
been conducted on its use have been short-term and have used several
different doses.
Because of the widespread
interest in St. John's wort, the National Institutes of Health (NIH) is
conducting a 3-year study, sponsored by three NIH components-the
National Institute of Mental Health, the National Institute for
Complementary and Alternative Medicine, and the Office of Dietary
Supplements. The study is designed to include 336 patients with major
depression, randomly assigned to an 8-week trial with one-third of
patients receiving a uniform dose of St. John's wort, another third an
SSRI commonly prescribed for depression, and the final third a placebo
(a pill that looks exactly like the SSRI and the St. John's wort, but
has no active ingredients). The study participants who respond
positively will be followed for an additional 18 weeks. After the 3-year
study has been completed, results will be analyzed and published.
The Food and Drug
Administration issued a Public Health Advisory on February 10, 2000. It
stated that St. John's wort appears to affect an important metabolic
pathway that is used by many drugs prescribed to treat conditions such
as heart disease, depression, seizures, certain cancers, and rejection
of transplants. Therefore, health care providers should alert their
patients about these potential drug interactions. Any herbal supplement
should be taken only after consultation with the doctor or other health
care provider. Psychotherapy
In mild to moderate cases of
depression, psychotherapy is also a treatment option. Some short-term
(10 to 20 week) therapies have been very effective in several types of
depression. "Talking" therapies help patients gain insight
into and resolve their problems through verbal give-and-take with the
therapist. "Behavioral" therapies help patients learn new
behaviors that lead to more satisfaction in life and "unlearn"
counter-productive behaviors. Research has shown that two short-term
psychotherapies, interpersonal and cognitive-behavioral, are helpful for
some forms of depression. Interpersonal therapy works to change
interpersonal relationships that cause or exacerbate depression.
Cognitive-behavioral therapy helps change negative styles of thinking
and behaving that may contribute to the depression.
Electroconvulsive Therapy
For individuals whose
depression is severe or life threatening or for those who cannot take
antidepressant medication, electroconvulsive therapy (ECT) is useful.3
This is particularly true for those with extreme suicide risk, severe
agitation, psychotic thinking, severe weight loss or physical
debilitation due as a result of physical illness. Over the years, ECT
has been much improved. A muscle relaxant is given before treatment,
which is done under brief anesthesia. Electrodes are placed at precise
locations on the head to deliver electrical impulses. The stimulation
causes a brief (about 30 seconds) seizure within the brain. The person
receiving ECT does not consciously experience the electrical stimulus.
At least several sessions of ECT, usually given at the rate of three per
week, are required for full therapeutic benefit.
Treating Recurrent Depression
Even when treatment is
successful, depression may recur. Studies indicate that certain
treatment strategies are very useful in this instance. Continuation of
antidepressant medication at the same dose that successfully treated the
acute episode can often prevent recurrence. Monthly interpersonal
psychotherapy can lengthen the time between episodes in patients not
taking medication. THE
PATH TO HEALING
Reaping the benefits of
treatment begins by recognizing the signs of depression. The next step
is to be evaluated by a qualified professional. Although depression can
be diagnosed and treated by primary care physicians, often the physician
will refer the patient to a psychiatrist, psychologist, clinical social
worker, or other mental health professional. Treatment is a partnership
between the patient and the health care provider. An informed consumer
knows her treatment options and discusses concerns with her provider as
they arise.
If there are no positive
results after 2 to 3 months of treatment, or if symptoms worsen, discuss
another treatment approach with the provider. Getting a second opinion
from another health or mental health professional may also be in order.
Here, again, are the steps to
healing:
Depressive illnesses make you
feel exhausted, worthless, helpless, and hopeless. Such feelings make
some people want to give up. It is important to realize that these
negative feelings are part of the depression and will fade as treatment
begins to take effect.
Along with professional
treatment, there are other things you can do to help yourself get
better. Some people find participating in support groups very helpful.
It may also help to spend some time with other people and to participate
in activities that make you feel better, such as mild exercise or yoga.
Just don't expect too much from yourself right away. Feeling better
takes time. WHERE
TO GET HELP
If unsure where to go for
help, ask your family doctor, OB/GYN physician, or health clinic for
assistance. You can also check the Yellow Pages under
"mental health," "health," "social
services," "suicide prevention," "crisis
intervention services," "hotlines,"
"hospitals," or "physicians" for phone numbers and
addresses. In times of crisis, the emergency room doctor at a hospital
may be able to provide temporary help for an emotional problem and will
be able to tell you where and how to get further help.
Listed below are the types of
people and places that will make a referral to, or provide, diagnostic
and treatment services.
Research on
Treatments for Depression
Medication
Studies on the
mechanisms of action of antidepressant medication comprise an important
area of depression research. Existing antidepressant drugs are
known to influence the functioning of certain neurotransmitters in the
brain, primarily serotonin and norepinephrine, known as monoamines.
Older medications – tricyclic antidepressants (TCAs) and monoamine
oxidase inhibitors (MAOIs) – affect the activity of both of these
neurotransmitters simultaneously. Their disadvantage is that they can be
difficult to tolerate due to side effects or, in the case of MAOIs,
dietary restrictions. Newer medications, such as the selective serotonin
reuptake inhibitors (SSRIs), have fewer side effects than the older
drugs, making it easier for patients to adhere to treatment. Both
generations of medications are effective in relieving depression,
although some people will respond to one type of drug, but not another. Antidepressant
medications take several weeks to be clinically effective even though
they begin to alter brain chemistry with the very first dose. Research
now indicates that antidepressant effects result from slow-onset
adaptive changes within the brain cells, or neurons. Further, it appears
that activation of chemical messenger pathways within neurons, and
changes in the way that genes in brain cells are expressed, are the
critical events underlying long-term adaptations in neuronal function
relevant to antidepressant drug action. A current challenge is to
understand the mechanisms that mediate, within cells, the long-term
changes in neuronal function produced by antidepressants and other
psychotropic drugs and to understand how these mechanisms are altered in
the presence of illness. Knowing how and
where in the brain antidepressants work can aid the development of more
targeted and potent medications that may help reduce the time between
first dose and clinical response. Further, clarifying the mechanisms of
action can reveal how different drugs produce side effects and can guide
the design of new, more tolerable, treatments. As one route
toward learning about the distinct biological processes that go awry in
different forms of depression, researchers are investigating the
differential effectiveness of various antidepressant medications in
people with particular subtypes of depression. For example, this
research has revealed that people with atypical depression, a
subtype characterized by reactivity of mood (mood brightens in response
to positive events) and at least two other symptoms (weight gain or
increased appetite, oversleeping, intense fatigue, or rejection
sensitivity), respond better to treatment with MAOIs, and perhaps with
SSRIs than with TCAs. Many patients
and clinicians find that combinations of different drugs work most
effectively for treating depression, either by enhancing the therapeutic
action or reducing side effects. Although combination strategies are
used often in clinical practice, there is little research evidence
available to guide psychiatrists in prescribing appropriate combination
treatment. Untreated
depression often has an accelerating course, in which episodes become
more frequent and severe over time. Researchers are now considering
whether early intervention with medications and maintenance treatment
during well periods will prevent recurrence of episodes. To date, there
is no evidence of any adverse effects of long-term antidepressant use. Psychotherapy
Like the
process of learning, which involves the formation of new connections
between nerve cells in the brain, psychotherapy works by changing the
way the brain functions. Research has shown that certain types of
psychotherapy, particularly cognitive-behavioral therapy (CBT) and
interpersonal therapy (IPT), can help relieve depression. CBT helps
patients change the negative styles of thinking and behaving often
associated with depression. IPT focuses on working through disturbed
personal relationships that may contribute to depression. Research on
children and adolescents with depression supports CBT as a useful
initial treatment, but antidepressant medication is indicated for those
with severe, recurrent, or psychotic depression. Studies of adults have
shown that while psychotherapy alone is rarely sufficient to treat
moderate to severe depression, it may provide additional relief in
combination with antidepressant medication. In one recent study,
older adults with recurrent major depression who received IPT in
combination with an antidepressant medication during a three-year period
were much less likely to experience a recurrence of illness than those
who received medication only or therapy only. For mild depression,
however, a recent analysis of multiple studies indicated that
combination treatment is not significantly more effective than CBT or
IPT alone. Preliminary
evidence from an ongoing study indicates that IPT may hold promise in
the treatment of dysthymia. Electroconvulsive
Therapy (ECT)
Electroconvulsive
therapy (ECT) remains one of the most effective yet most stigmatized
treatments for depression. Eighty to ninety percent of people with
severe depression improve dramatically with ECT. ECT involves producing
a seizure in the brain of a patient under general anesthesia by applying
electrical stimulation to the brain through electrodes placed on the
scalp. Repeated treatments are necessary to achieve the most complete
antidepressant response. Memory loss and other cognitive problems are
common, yet typically short-lived side effects of ECT. Although some
people report lasting difficulties, modern advances in ECT technique
have greatly reduced the side effects of this treatment compared to
earlier decades. Research on ECT has found that the dose of electricity
applied and the placement of electrodes (unilateral or bilateral) can
influence the degree of depression relief and the severity of side
effects. A current
research question is how best to maintain the benefits of ECT over time.
Although ECT can be very effective for relieving acute depression, there
is a high rate of relapse when the treatments are discontinued. NIMH is
currently sponsoring two multicenter studies on ECT follow-up treatment
strategies. One study is comparing different medication treatments, and
the other study is comparing maintenance medication to maintenance ECT.
Results from these studies will help guide and improve follow-up
treatment plans for patients who respond well to ECT. Genetics
Research
Research on the
genetics of depression and other mental illnesses is a critical
component of current research efforts. Researchers are increasingly
certain that genes play an important role in vulnerability to depression
and other severe mental disorders. In recent
years, the search for a single, defective gene responsible for each
mental illness has given way to the understanding that multiple gene
variants, acting together with yet unknown environmental risk factors or
developmental events, account for the expression of psychiatric
disorders. Identification of these genes, each of which contributes only
a small effect, has proven extremely difficult. However, new
technologies, which continue to be developed and refined, are beginning
to allow researchers to associate genetic variations with disease. In
the next decade, two large-scale projects that involve identifying and
sequencing all human genes and gene variants will be completed and are
expected to yield valuable insights into the causes of mental disorders
and the development of better treatments. Stress and
Depression
Psychosocial
and environmental stressors are known risk factors for depression.
Research has shown that stress in the form of loss, especially death of
close family members or friends, can trigger depression in vulnerable
individuals. Genetics research indicates that environmental stressors
interact with depression vulnerability genes to increase the risk of
developing depressive illness. Stressful life events may contribute to
recurrent episodes of depression in some individuals, while in others
depression recurrences may develop without identifiable triggers. Other research
indicates that stressors in the form of social isolation or early-life
deprivation may lead to permanent changes in brain function that
increase susceptibility to depressive symptoms. Brain
Imaging
Recent advances
in brain imaging technologies are allowing scientists to examine the
brain in living people with more clarity than ever before. Functional
magnetic resonance imaging (fMRI), a safe, noninvasive method for
viewing brain structure and function simultaneously, is one new
technique that researchers are using to study the brains of
individuals with and without mental disorders. This technique will
enable scientists to evaluate the effects of a variety of treatments on
the brain and to associate these effects with clinical outcome. Brain imaging
findings may help direct the search for microscopic abnormalities in
brain structure and function responsible for mental disorders.
Ultimately, imaging technologies may serve as tools for early diagnosis
and subtyping of depression and other mental disorders, thus advancing
the development of new treatments and evaluation of their effects. Hormonal
Abnormalities
The hormonal
system that regulates the body’s response to stress, the
hypothalamic-pituitary-adrenal (HPA) axis, is overactive in many
patients with depression, and researchers are investigating
whether this phenomenon contributes to the development of the illness. The
hypothalamus, the brain region responsible for managing hormone release
from glands throughout the body, increases production of a substance
called corticotropin releasing factor (CRF) when a threat to physical or
psychological well-being is detected. Elevated levels and effects of CRF
lead to increased hormone secretion by the pituitary and adrenal glands
which prepares the body for defensive action. The body’s responses
include reduced appetite, decreased sex drive, and heightened alertness.
Research suggests that persistent overactivation of this hormonal system
may lay the groundwork for depression. The elevated CRF levels
detectable in depressed patients are reduced by treatment with
antidepressant drugs or ECT, and this reduction corresponds to
improvement in depressive symptoms. Scientists are
investigating how and whether the hormonal research findings fit
together with the discoveries from genetics research and monoamine
studies. Co-occurrence
of Depression and Anxiety Disorders
NIMH research
has revealed that depression often co-exists with anxiety disorders
(panic disorder, obsessive-compulsive disorder, post-traumatic stress
disorder, social phobia, or generalized anxiety disorder). In such
cases, it is important that depression and each co-occurring illness be
diagnosed and treated. Several studies
have shown an increased risk of suicide attempts in people with
co-occurring depression and panic disorder – the anxiety disorder
characterized by unexpected and repeated episodes of intense fear and
physical symptoms, including chest pain, dizziness, and shortness of
breath. Rates of
depression are especially high in people with post-traumatic stress
disorder (PTSD), a debilitating condition that can occur after exposure
to a terrifying event or ordeal in which grave physical harm occurred or
was threatened. In one study supported, more than 40 percent of patients
with PTSD had depression when evaluated both at one month and four
months following the traumatic event. Co-occurrence
of Depression and Other Illnesses
Depression
frequently co-occurs with a variety of other physical illnesses,
including heart disease, stroke, cancer, and diabetes, and also can
increase the risk for subsequent physical illness, disability, and
premature death. Depression in the context of physical illness, however,
is often unrecognized and untreated. Furthermore, depression can impair
the ability to seek and stay on treatment for other medical illnesses.
Research suggests that early diagnosis and treatment of depression in
patients with other physical illnesses may help improve overall health
outcome. The results of
a recent study provide the strongest evidence to date that depression
increases the risk of having a future heart attack. Analysis of data
from a large-scale survey revealed that individuals with a history of
major depression were more than four times as likely to suffer a heart
attack over a 12-13 year follow-up period, compared to people without
such a history. Even people with a history of two or more weeks of mild
depression were more than twice as likely to have a heart attack,
compared to those who had had no such episodes. Although associations
were found between certain psychotropic medications and heart attack
risk, the researchers determined that the associations were simply a
reflection of the primary relationship between depression and heart
trouble. The question of whether treatment for depression reduces the
excess risk of heart attack in depressed patients must be addressed with
further research. Women and
Depression
At some point
during their lives, as many as 20 percent of women have at least one
episode of depression that should be treated. Although conventional
wisdom holds that depression is most closely associated with menopause,
in fact, the childbearing years are marked by the highest rates of
depression, followed by the years prior to menopause. NIMH
researchers are investigating the causes and treatment of depressive
disorders in women. One area of research focuses on life stress and
depression. Data from a recent study suggests that stressful life
experiences may play a larger role in provoking recurrent episodes of
depression in women than in men. The influence
of hormones on depression in women has been an active area of
research. One recent study was the first to demonstrate that the
troublesome depressive mood swings and physical symptoms of premenstrual
syndrome (PMS), a disorder affecting three to seven percent of
menstruating women, result from an abnormal response to normal hormone
changes during the menstrual cycle. Among women with normal menstrual
cycles, those with a history of PMS experienced relief from mood and
physical symptoms when their sex hormones, estrogen and progesterone,
were temporarily "turned off" by administering a drug that
suppresses the function of the ovaries. PMS symptoms developed within a
week or two after the hormones were re-introduced. In contrast, women
without a history of PMS reported no effects of the hormonal
manipulation. The study showed that female sex hormones do not cause
PMS – rather, they trigger PMS symptoms in women with a preexisting
vulnerability to the disorder. The researchers currently are attempting
to determine what makes some women but not others susceptible to PMS.
Possibilities include genetic differences in hormone sensitivity at the
cellular level, differences in history of other mood disorders, and
individual differences in serotonin function. Researchers
also are currently investigating the mechanisms that contribute to
depression after childbirth (postpartum depression), another serious
disorder where abrupt hormonal shifts in the context of intense
psychosocial stress disable some women with an apparent underlying
vulnerability. In addition, an ongoing NIMH clinical trial is evaluating
the use of antidepressant medication following delivery to prevent
postpartum depression in women with a history of this disorder after a
previous childbirth. Child and
Adolescent Depression
Large-scale
research studies have reported that up to 2.5 percent of children and up
to 8.3 percent of adolescents in the United States suffer from
depression. In addition, research has discovered that depression onset
is occurring earlier in individuals born in more recent decades. There
is evidence that depression emerging early in life often persists,
recurs, and continues into adulthood, and that early onset depression
may predict more severe illness in adult life. Diagnosing and treating
children and adolescents with depression is critical to prevent
impairment in academic, social, emotional, and behavioral functioning
and to allow children to live up to their full potential. Research on the
diagnosis and treatment of mental disorders in children and adolescents,
however, has lagged behind that in adults. Diagnosing depression in
these age groups is often difficult because early symptoms can be hard
to detect or may be attributed to other causes. In addition, treating
depression in children and adolescents remains a challenge, because few
studies have established the safety and efficacy of treatments for
depression in youth. Children and adolescents are going through rapid,
age-related changes in their physiological states, and there remains
much to be learned about brain development during the early years of
life before treatments for depression in young people will be as
successful as they are in older people. NIMH is pursuing brain-imaging
research in children and adolescents to gather information about normal
brain development and what goes wrong in mental illness. Depression in
children and adolescents is associated with an increased risk of
suicidal behaviors. Over the last several decades, the suicide rate in
young people has increased dramatically. In 1996, the most recent year
for which statistics are available, suicide was the third leading cause
of death in 15-24 year olds and the fourth leading cause among 10-14
year olds. Researchers are developing and testing various interventions
to prevent suicide in children and adolescents. However, early diagnosis
and treatment of depression and other mental disorders, and accurate
evaluation of suicidal thinking, possibly hold the greatest suicide
prevention value. Until recently,
there were limited data on the safety and efficacy of antidepressant
medications in children and adolescents. The use of antidepressants in
this age group was based on adult standards of treatment. A recent study
supported fluoxetine, an SSRI, as a safe and efficacious medication for
child and adolescent depression. The response rate was not as high as in
adults, however, emphasizing the need for continued research on existing
treatments and for development of more effective treatments, including
psychotherapies designed specifically for children. Other complementary
studies in the field are beginning to report similar positive findings
in depressed young people treated with any of several newer
antidepressants. In a number of studies, TCAs were found to be
ineffective for treating depression in children and adolescents, but
limitations of the study designs preclude strong conclusions. Older Adults
and Depression
In a given
year, between one and two percent of people over age 65 living in the
community, i.e., not living in nursing homes or other institutions,
suffer from major depression and about two percent have dysthymia.
Depression, however, is not a normal part of aging. Research has clearly
demonstrated the importance of diagnosing and treating depression in
older persons. Because major depression is typically a recurrent
disorder, relapse prevention is a high priority for treatment research.
As noted previously, a recent study established the efficacy of combined
antidepressant medication and interpersonal psychotherapy in reducing
depressive relapses in older adults who had recovered from an episode of
depression. Additionally,
recent studies show that 13 to 27 percent of older adults have
subclinical depressions that do not meet the diagnostic criteria for
major depression or dysthymia but are associated with increased risk
of major depression, physical disability, medical illness, and high use
of health services. Subclinical depressions cause considerable
suffering, and some clinicians are now beginning to recognize and treat
them. Suicide is more
common among the elderly than in any other age group. Research has shown
that nearly all people who commit suicide have a diagnosable mental or
substance abuse disorder. In studies of older adults who committed
suicide, nearly all had major depression, typically a first episode,
though very few had a substance abuse disorder. Suicide among white
males aged 85 and older was nearly six times the national U.S. rate (65
per 100,000 compared with 11 per 100,000) in 1996, the most recent year
for which statistics are available. Alternative
Treatments
Recently there
has been an enormous growth in public interest in herbal remedies for
various medical conditions including depression. One herbal supplement, hypericum
or St. John’s Wort, has been promoted as having antidepressant
properties. However, no carefully designed studies of adequate duration
have been done to determine the antidepressant efficacy of the
supplement. National
Institute of Mental Health Depression Research Research on the
causes, treatment, and prevention of all forms of depression will remain
a high NIMH priority for the foreseeable future. Areas of interest and
opportunity include the following:
The
Broad NIMH Research Program
In
addition to studying depression, NIMH supports and conducts a broad
based, multidisciplinary program of scientific inquiry aimed at
improving the diagnosis, prevention, and treatment of other mental
disorders. These conditions include manic-depressive illness, clinical
depression, and schizophrenia. Increasingly,
the public as well as health care professionals are recognizing these
disorders as real and treatable medical illnesses of the brain. Still,
more research is needed to examine in greater depth the relationships
among genetic, behavioral, developmental, social and other factors to
find the causes of these illnesses. NIMH is meeting this need through a
series of research initiatives.
This
project has compiled the world's largest registry of families affected
by schizophrenia, manic-depressive illness, and Alzheimer's disease.
Scientists are able to examine the genetic material of these family
members with the aim of pinpointing genes involved in the diseases.
This
multi-agency effort is using state-of-the-art computer science
technologies to organize the immense amount of data being generated
through neuroscience and related disciplines, and to make this
information readily accessible for simultaneous study by interested
researchers.
Prevention
efforts seek to understand the development and expression of mental
illness throughout life so that appropriate interventions can be found
and applied at multiple points during the course of illness. Recent
advances in biomedical, behavioral, and cognitive sciences have led NIMH
to formulate a new plan that marries these sciences to prevention
efforts. While
the definition of prevention will broaden, the aims of research will
become more precise and targeted. FURTHER
INFORMATION
National Institute of Mental
Health
National Alliance for the
Mentally Ill National Depressive and Manic
Depressive Association National Foundation for
Depressive Illness, Inc. National Mental Health
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differences in depression. Medscape Women's Health, 1997;2:3.
Revised from: Women's increased vulnerability to mood disorders:
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E, Shear MK. Adolescent onset of the gender difference in lifetime rates
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Andreasen, Nancy. The
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Carter, Rosalyn. Helping
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1996. The following three booklets
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Road, Suite 300, Madison, WI 53717, telephone 1-608-827-2470:
Tunali D, Jefferson JW, and
Greist JH, Depression & Antidepressants: A Guide, rev. ed.
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and Manic Depression: A Guide, 1996 (formerly Valproate guide).
Bohn J and Jefferson JW. Lithium
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