Provided by the National Institute of Mental Health
Bipolar disorder, also called manic-depressive
illness, is a serious disorder of the brain. More than 2.3 million American
adults, or about 1 percent of the population in a given year, have bipolar
disorder. Abnormalities in brain biochemistry and in the structure and/or
activity of certain brain circuits are responsible for the extreme shifts in
mood, energy, and functioning that characterize bipolar disorder. Fortunately,
the intense and disabling symptoms of bipolar disorder often can be relieved
through treatment involving combinations of medications and psychotherapy.
"Manic-depression distorts moods and thoughts, incites dreadful behaviors,
destroys the basis of rational thought, and too often erodes the desire and will
to live. It is an illness that is biological in its origins, yet one that feels
psychological in the experience of it; an illness that is unique in conferring
advantage and pleasure, yet one that brings in its wake almost unendurable
suffering and, not infrequently, suicide.
"I am fortunate that I have not died from my illness, fortunate in having
received the best medical care available, and fortunate in having the friends,
colleagues, and family that I do."
Kay Redfield Jamison, Ph.D., An Unquiet Mind, 1995, p. 6. Reprinted with
permission from Alfred A. Knopf, a division of Random House, Inc.
Bipolar disorder typically emerges in late adolescence or early adulthood but in
some cases begins earlier. Episodes of depression and mania flare up across the
life course, often disrupting work, school, family, and social life. Despite the
fact that an episode may remit on its own due to the cyclic nature of the
illness, treatment to achieve and maintain a balanced state is extremely
important. Without effective treatment, the illness can lead to suicide in
nearly 20 percent of cases.1
Research is the key to understanding bipolar disorder. The National Institute of
Mental Health (NIMH), the world's leading mental health biomedical research
organization, conducts and supports studies on the causes, diagnosis, and
treatment of bipolar disorder. A variety of research approaches are being used,
including neuroscience studies, basic science approaches to brain and behavior,
genetic investigations, epidemiological studies, and clinical research. Clinical
treatment research is underway to determine the best use of available treatments
and treatment combinations. Better treatments and, eventually, ways to prevent
and cure the illness will be found only through careful scientific study.
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Symptoms and Types of Bipolar Disorder
Bipolar disorder is characterized by episodes of depression, mania, or mixed
state that typically recur and become more frequent across the life span.1 In
most patients, these episodes, especially early in the course of illness, are
separated by well periods during which there are few to no symptoms. A small
percentage of people experience chronic, unremitting symptoms despite treatment.
Depression
Symptoms include a persistent sad mood; loss of interest or pleasure in
activities that were once enjoyed; significant change in appetite or body
weight; difficulty sleeping or oversleeping; physical slowing or agitation; loss
of energy; feelings of worthlessness or inappropriate guilt; difficulty thinking
or concentrating; and recurrent thoughts of death or suicide. The depressive
episodes of people with bipolar disorder are often indistinguishable from those
of patients with unipolar major depressive disorder.
Mania
Symptoms include abnormally and persistently elevated (high) mood or
irritability occurring with at least three of the following: overly-inflated
self-esteem; decreased need for sleep; increased talkativeness; racing thoughts;
distractibility; increased goal-directed activity or physical agitation; and
excessive involvement in risky behaviors or activities (e.g., unwise spending
sprees, reckless driving, sexual affairs).
"Mixed" State
Symptoms of mania and depression are present at the same time. The symptom
picture frequently includes agitation, trouble sleeping, significant change in
appetite, psychosis, and suicidal thinking. Depressed mood accompanies manic
activation.
Sometimes severe mania or depression is accompanied by periods of psychosis.
Psychotic symptoms include hallucinations (hearing, seeing, or otherwise sensing
the presence of stimuli that are not actually there) and delusions (false fixed
beliefs that are not subject to reason or contradictory evidence and are not
explained by a person's usual cultural concepts). Psychotic symptoms associated
with bipolar disorder typically reflect the extreme mood state at the time
(e.g., grandiosity during mania, worthlessness during depression).
Bipolar disorder with rapid cycling is defined as four or more episodes of
illness within a 12-month period. This form of the illness tends to be more
resistant to treatment than non-rapid-cycling bipolar disorder.
The particular combinations and severity of symptoms vary among people with
bipolar disorder. Some people experience very severe manic episodes, during
which they may feel "out of control," have major impairment in functioning, and
suffer psychotic symptoms. Other people have milder hypomanic episodes,
characterized by low-level, non-psychotic symptoms of mania such as increased
energy, euphoria, irritability, and intrusiveness, that may cause little
impairment in functioning but are noticeable to others. Some people suffer
severe, incapacitating depressions, with or without psychosis, that prevent them
from working, going to school, or interacting with family or friends. Others
experience more moderate depressive episodes, which may feel just as painful but
impair functioning to a lesser degree. Inpatient hospitalization is often
necessary to treat severe episodes of mania and depression.
A diagnosis of bipolar I disorder is made when a person has experienced at least
one episode of severe mania; a diagnosis of bipolar II disorder is made when a
person has experienced at least one hypomanic episode but has not met the
criteria for a full manic episode. Cyclothymic disorder, a milder illness, is
diagnosed when a person experiences, over the course of at least 2 years (1 year
for adolescents and children), numerous periods with hypomanic symptoms and
numerous periods with depressive symptoms that are not severe enough to meet
criteria for major manic or depressive episodes. People who meet criteria for
bipolar disorder or unipolar depression and who experience chronic psychotic
symptoms, which persist even with clearing of the mood symptoms, suffer from
schizoaffective disorder. The diagnostic criteria for all mental disorders are
described in the Diagnostic and Statistical Manual of Mental Disorders, 4th
Edition (DSM-IV).2
Many patients with bipolar disorder are initially misdiagnosed.3 This occurs
most often either when a person with bipolar II disorder, whose hypomania is not
recognized, is diagnosed with unipolar depression, or when a patient with severe
psychotic mania is misjudged to have schizophrenia. However, since bipolar
disorder, like other mental illnesses, cannot yet be identified physiologically
(for example, by a blood test or a brain scan), diagnosis must be made on the
basis of symptoms, course of illness, and, when available, family history.
Genetics Research
Data from family, twin, and adoption studies unequivocally demonstrate the
involvement of genetic factors in the transmission of bipolar disorder.4
Research to date leads to the conclusion that in most families the etiology of
bipolar disorder is complex, with vulnerability being produced by the
interaction of multiple genes and nongenetic factors. Scientists expect that
identification of genes conferring vulnerability to bipolar disorder, and the
brain proteins they code for, will make it possible to develop better diagnostic
procedures, treatments, and preventive interventions targeted at the underlying
illness process.
The NIMH Bipolar Disorder Genetics Initiative, launched in 1989, continues to
gather genetic material and state-of-the-art diagnostic and clinical data from
families with two or more members affected by bipolar disorder. The primary goal
of this initiative is to establish a national resource that makes DNA and
clinical information widely available to qualified investigators in the
scientific community. The genetic and clinical information is distributed in a
way that keeps the research volunteers anonymous. Ten major research groups
worldwide are currently studying DNA and clinical data from over 650 individuals
with bipolar disorder and related conditions in an effort to find genes that
confer vulnerability to bipolar disorder.
Successful genetic studies of complex disorders like bipolar disorder will
require very large samples drawn from diverse populations, and/or samples drawn
from genetically isolated populations. In order to facilitate such research,
NIMH recently funded three major collaborative projects to collect data that
will significantly augment the information already available in the NIMH Bipolar
Genetics Initiative. In one study, scientists at nine research institutions
across the United States will gather clinical and genetic data from at least 500
families in which two or more siblings suffer from bipolar disorder.5 In
another, American and Israeli researchers will use shared methods of data
collection, diagnosis, and clinical assessment to study 300 additional
families.6 A third project will study over 300 families collected from the
population of the Azores, a nine-island archipelago off the coast of Portugal.7
NIMH also recently issued a Program Announcement (http://grants.nih.gov/grants/guide/pa-files/PA-99-120.html)
to encourage collaborations among genetic research groups worldwide, by which
multiple samples of bipolar disorder pedigrees can be assembled into one large
data set for combined analysis. New genetic analytic methods and technologies
like gene chips offer great potential for identifying specific gene sites
responsible for vulnerability to bipolar disorder in such large samples of
families.
Brain Imaging
Brain imaging technologies are helping scientists learn what goes wrong in the
brain to produce mental illness. NIMH researchers are using advanced imaging
techniques to examine brain function and structure in people with bipolar
disorder.
An important area of imaging research focuses on identifying and characterizing
neural circuits—networks of interconnected nerve cells in the brain,
interactions among which form the basis for normal and abnormal behaviors.
Researchers hypothesize that abnormalities in the structure and/or function of
certain brain circuits could underlie bipolar and other mood disorders. Better
understanding of the neural circuits involved in regulating mood states will
influence the development of new and better treatments, and will ultimately aid
in diagnosis.
Structural Imaging
NIMH has supported considerable research with the new technology of magnetic
resonance imaging (MRI) to examine the structure of brain tissue in various
mental disorders, including bipolar disorder. The first such studies have
appeared only within the past 10 years, with the pace of progress accelerating
steadily since that time. The goal of this research is to discover the ways in
which specific areas of the brain in people with bipolar disorder may differ
from healthy individuals.
One of the most consistent findings to date has been the appearance of specific
abnormalities, or lesions, in the white matter of the brain in patients with
bipolar disorder.8 White matter consists of groups of nerve cell fibers
surrounded by fatty sheaths that appear white in color. These sheaths help the
transmission of electrical signals within the brain. While the white matter
abnormalities appear in many parts of the brain in individuals with bipolar
disorder, they tend to be concentrated in areas that are responsible for
emotional processing. These brain changes increase in frequency with age both in
people with bipolar disorder and individuals with no mental illness, but they
appear more often than expected in young patients with bipolar disorder. This
finding suggests that the white matter abnormalities seen with MRI are related
to the presence of the disorder. However, some patients with bipolar disorder do
not show the white matter changes, and conversely, some entirely healthy
individuals have the lesions. Also, it is not yet clear whether these changes
contribute to the onset of the disorder, or are in some way a result of becoming
ill. While these MRI abnormalities likely indicate one type of malfunction in
the brain circuits involved in bipolar disorder, more research is clearly needed
to understand their significance and their utility for early diagnosis and
treatment.
Functional Imaging
Functional neuroimaging is an important tool for NIMH-supported researchers
studying bipolar and other mood disorders. Studies using positron emission
tomography (PET), a technique that measures brain function in terms of blood
flow or glucose metabolism, have found abnormal activity in specific brain
regions including the prefrontal cortex, basal ganglia, and temporal lobes
during manic and depressive episodes.9 It is not yet known whether these
functional abnormalities are a cause or consequence of mood disorders.
When neurons become more active, their demand for oxygen, delivered via the
blood supply, increases. Using a special measurement technique called functional
magnetic resonance imaging (fMRI), scientists can measure these changes in blood
oxygen levels in different brain areas in healthy people and those with specific
brain disorders, including unipolar and bipolar disorder and schizophrenia. This
technique provides a powerful tool for understanding how the brains of
individuals with mental disorders process information differently from healthy
individuals, and for understanding and even predicting how people with these
diseases might respond to different types of drug therapy. For example, NIMH
supported researchers have studied how brain regions of healthy people and of
people with depression respond differently when emotionally evocative pictures
are viewed, and how drug treatment changes the response to these pictures in
individuals with depression.10 Modified versions of both the fMRI and PET
techniques, which allow scientists to directly study changes in brain chemistry
and the activity of specific signaling molecules (neurotransmitters) in both
healthy individuals and people with mood disorders, are enabling researchers to
better understand the fundamental characteristics of bipolar disorder.
Treatment Research
NIMH is dedicated to improving treatments for bipolar disorder and is investing
considerable research effort in pursuit of this goal. Although many people with
bipolar disorder can be helped by currently available treatments, significant
challenges remain. Rapid cycling is a form of the illness that is difficult to
manage. Medication side effects are often troublesome and can lead to reduced
treatment adherence. Some regimens work well for years and then gradually lose
their effectiveness. NIMH researchers are working at multiple levels—from
molecular genetics, to neuroimaging, to behavioral science, to clinical
trials—to learn what underlies these and other treatment-related problems and to
apply this knowledge toward the development of better treatments and enhanced
treatment strategies.
Medication
For years, lithium has been the "gold standard" pharmacological treatment for
bipolar disorder. When taken regularly, lithium can effectively control mania
and depression in many patients and can reduce the likelihood of episode
recurrence.1 However, scientists still do not know exactly how it works, nor do
they understand why it works well for some people but not others. In an attempt
to answer these questions, NIMH researchers are investigating the biochemical
mechanisms of action of lithium.11,12 This and future work will inform the
development of new and better treatments.
For patients who either do not respond to lithium or cannot tolerate its side
effects, which can include weight gain, tremor, and excessive urination, there
are several anticonvulsant medications that may serve as alternative mood
stabilizers. Valproate and carbamazepine have been used for the past two decades
for treatment of acute mania and prevention of cycling. However, valproate is
the only anticonvulsant approved by the U.S. Food and Drug Administration (FDA)
for use with bipolar disorder—specifically, for the acute treatment of mania.
NIMH researchers are currently investigating the efficacy of newer
anticonvulsant drugs, including lamotrigine and gabapentin, as mood stabilizers
for treatment refractory bipolar disorder.13 Topiramate is also receiving
attention in clinical studies.
Treatment of Bipolar Depression
Antidepressant medications have long been used to treat the depressive phase of
bipolar disorder. However, research has shown that antidepressants, 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. Therefore, mood-stabilizing medications are generally required, alone
or in combination with antidepressants, to protect patients with bipolar
disorder from this switch. Lithium and valproate are the most commonly used mood
stabilizing drugs today. Research studies are evaluating the potential mood
stabilizing properties of newer medications.
NIMH-funded research has evaluated the efficacy of atypical antipsychotic
medications in the treatment of bipolar disorder. One recent NIMH study
demonstrated mood stabilizing and antimanic effects of clozapine in patients
with treatment-resistant bipolar disorder.14 Another NIMH study found olanzapine
to help relieve psychotic depression in patients with a diagnosis of major
depression or bipolar I disorder.15Other research has supported the efficacy of
olanzapine for acute mania,16 an indication that has recently received FDA
approval. The efficacy of risperidone is also under study.
A nutritional approach under investigation for maintenance treatment of bipolar
disorder involves omega-3 fatty acids found in fish oil. Preliminary research
has found a combination of the two main omega-3 fatty acids to be better than
placebo, when added to ongoing conventional medications, in avoiding an acute
illness episode and in improving a variety of symptoms over 4 months.17 However,
due to several limitations in this preliminary study, more definitive research
is required to validate the appeal of a naturally occurring, apparently safe
substance in the treatment of bipolar disorder.
Psychotherapy
Interest in using psychotherapy in combination with medication for bipolar
disorder has grown in recent years with the recognition of the continuing high
rate of relapse, some of which appears preventable, during pharmacological
maintenance treatment.18 NIMH researchers are conducting studies to evaluate the
benefits of specific types of adjunctive psychotherapy in the long-term
management of bipolar disorder. These psychotherapies include Psychoeducation
(PE), Cognitive-Behavioral Therapy (CBT), Family Focused Therapy (FFT), and
Interpersonal and Social Rhythm Therapy (IPSRT). PE involves teaching patients
with bipolar disorder about their illness and its treatment. Emphasis is placed
on recognizing early signs of relapse so that patients can seek medical care
before a full-blown illness episode develops. CBT helps patients modify
detrimental or inappropriate thought patterns and behaviors associated with
bipolar disorder. FFT employs strategies to reduce the level of distress within
the family that may either contribute to or result from the ill person's
symptoms. IPSRT uses techniques aimed at regularizing daily routines and
improving interpersonal relationships. Research indicates that regular daily
routines and sleep schedules may protect against manic episodes.19 A large-scale
NIMH study (called STEP-BD, described below) will compare the effectiveness of
intensive CBT, FFT, and IPSRT, each in combination with medication, for
treatment of acute depressive episodes and for prevention of recurrent episodes
in people with bipolar disorder.
Efficacy vs. Effectiveness Research
In recent years there has been an increasing emphasis on extending clinical
trials research—research that examines how well treatments work in patients—from
tightly controlled, inpatient hospital settings to settings in the "real world."
Many past studies have established the safety and efficacy of various treatments
for bipolar disorder—that is, how well they work in very specific groups of
patients under ideal conditions. However, few studies have adequately tested the
effectiveness of particular treatments or treatment strategies—how well they
work, for example, in patients who live in the community, come from diverse
backgrounds, have co-occurring illnesses, or experience atypical patterns of
manic and depressive episodes. In addition, quality of life, ability to work,
social functioning, treatment adherence, and treatment cost-effectiveness are
among the important, real world issues that only effectiveness research can
adequately assess. In contrast to efficacy research, effectiveness studies have
very few exclusionary criteria and enroll very large numbers of
participants—several hundred to thousands—so that the findings will be
representative of and broadly applicable to an entire population group.
To improve the standards of treatment for bipolar disorder, NIMH has taken the
lead in treatment effectiveness research on this illness. Major goals are:
to establish treatment effectiveness both in the short and long term;
to develop guidelines for treating patients who do not respond to standard
single therapies;
to evaluate combinations of pharmacological and psychosocial treatments;
to define a core set of outcome measures to make findings across studies
comparable; and
to translate research findings more quickly into routine clinical practice.
NIMH recently awarded a multi-million dollar contract for a bipolar disorder
research study designed to achieve these goals. The study is called the
Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).
The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)
STEP-BD is a large-scale, 5-8 year clinical study being conducted at 20 sites
across the U.S. to determine the most effective treatment strategies for people
with bipolar disorder. The study will evaluate both individual and combined
pharmacological and psychosocial treatments.
Because STEP-BD is an effectiveness study, there are very few exclusionary
criteria. Anyone who is age 15 or older and formally diagnosed with bipolar
disorder is eligible. (Individuals younger than 18 need parental consent to
participate.) In addition, individuals may join the study during any phase of
their illness, whether or not they are currently in treatment, and whether or
not their symptoms are controlled.
STEP-BD offers all the standard treatment options used for bipolar disorder. The
aim is to examine existing, efficacious treatments to come up with the best set
of strategies for tackling this very complex illness. Participants may choose
their own preferred treatment plan with their study doctor or may decide to have
treatments chosen for them through a randomization process. Randomized treatment
"pathways" were built into the study to compare competing treatment strategies
where existing guidelines and expert recommendations offer no clear treatment of
choice. Either way, all participants will always receive active treatment with
one or more mood stabilizing medications. Placebos (inactive pills) will never
be used alone in any part of the study but may be used in combination with a
mood stabilizer for limited periods during the randomized treatment pathways.
The investigators will track participants for up to 8 years to document and
evaluate long-term treatment outcome. More information about NIMH clinical
trials can be obtained by accessing the NIMH home page at www.nimh.nih.gov/studies/index.cfm
or the National Library of Medicine clinical trials database at
www.clinicaltrials.gov.
Sleep Loss and Social Rhythms
Findings from NIMH-supported research indicate that sleep deprivation can
trigger a manic episode in some people with rapid-cycling bipolar disorder.19
For reasons that are still unknown, people with bipolar disorder appear to have
very delicate "internal clock" mechanisms, and disruption of these mechanisms by
losing even a single night's sleep often results in mania. Developing and
adhering to a structured daily routine and sleep schedule may help protect
against mood disturbances. NIMH researchers are investigating the independent
effects of the internal clock and the sleep-wake cycle on mood in patients with
rapid-cycling bipolar disorder.20
Based on the clinical observation that episodes are often precipitated by
disruptions of sleep or other daily routines, a group of NIMH-funded researchers
developed interpersonal and social rhythm therapy (IPSRT) to help stabilize the
course of bipolar disorder. IPSRT teaches patients techniques to regularize
their daily routines and improve their interpersonal relationships. In
preliminary studies, IPSRT, in combination with ongoing medication maintenance,
reduced depressive symptoms and improved the quality of remission from active
bipolar disorder.21 Patients who received IPSRT as a preventive intervention
spent more time in a balanced state and less time in a subclinical depressive
condition.
Stress, Life Events, and Social Support
NIMH researchers are currently investigating the influence of stress, life
events, and social support on the course of bipolar disorder. These
relationships can be determined most accurately by studies that follow patients
forward through time—that is, by prospective research. One prospective, NIMH-funded
study is examining the impact of life events and social support on the time to
recovery and relapse in people with bipolar disorder.22
Another prospective study supported by NIMH is investigating the influence of
psychosocial factors—life events, stress, cognitive processes, and personality
factors—on the onset and course of cyclothymia (periods of mild hypomanic
symptoms alternating with periods of mild depressive symptoms), and on the onset
and course of bipolar disorder among people with cyclothymia.23 Cyclothymia is a
known risk factor for developing bipolar disorder. However, little is known
about what factors determine which people with cyclothymia will develop bipolar
disorder, or about the mechanisms involved in the change from cyclothymia to the
more severe illness. Findings from this study will help clarify the role of
various psychosocial factors in the course of cyclothymia and in the initial
onset and subsequent course of full-blown bipolar disorder; help explain the
relationship between unipolar major depression and the depressive phases of
bipolar disorder; and suggest new methods for treating and preventing bipolar
disorder.
Co-occurring Illnesses
The most common co-occurring illnesses among people with bipolar disorder are
substance abuse disorders. Approximately 60 percent of people with bipolar
disorder have drug and/or alcohol abuse or dependence problems—the highest rate
across all patients with major psychiatric illnesses.24 Research suggests that
many factors likely contribute to these substance abuse problems, including
self-medication of symptoms, mood symptoms either initiated or perpetuated by
substance abuse, and risk factors that may influence the occurrence of both
disorders.25
A review of multiple research studies revealed several factors that increase the
risk for co-occurring substance use among individuals with bipolar disorder,
including early age of illness onset, family history of substance use disorders,
and presence of mixed symptoms.26 A current NIMH-funded study is investigating
how substance abuse affects the frequency, duration, and severity of episodes in
people with bipolar disorder.27 Better understanding of the relationship between
substance use and bipolar disorder will help improve both treatment and
preventive interventions for co-occurring substance use, leading to better
mental health outcome.
Other research has indicated that certain anxiety disorders may co-occur with
bipolar disorder. In one recent NIMH-supported study of post-traumatic stress
disorder (PTSD) in people with bipolar disorder or schizophrenia, almost all
patients reported having experienced at least one traumatic event in their
lifetime.28 While 43 percent of study participants met criteria for PTSD, only 2
percent had the diagnosis listed in their medical charts. The results suggest
that PTSD commonly co-occurs with severe mental disorders. Routine screening for
PTSD during medical visits would lead to improved diagnosis and treatment of
this anxiety disorder, thus allowing the other co-occurring illness—bipolar
disorder, schizophrenia, etc.—to be more effectively treated.
Another NIMH-funded study found a high co-occurrence of both PTSD and
obsessive-compulsive disorder (OCD) among patients with bipolar disorder across
a 12-month period.29 While the course of PTSD was independent of the mood
disorder, the course of OCD frequently waxed and waned along with mood episodes.
More research is needed to determine the nature of this apparent connection
between OCD and bipolar disorder in some patients.
Children and Adolescents
Both children and adolescents can develop bipolar disorder. NIMH research
efforts are attempting to clarify the diagnosis, course, and treatment of
bipolar disorder in youth. Evidence suggests that bipolar disorder beginning in
childhood or early adolescence may be a different, possibly more severe form of
the illness than older adolescent- and adult-onset bipolar disorder.30 When the
illness begins before or soon after puberty, it is often characterized by a
continuous, rapid-cycling, irritable, and mixed symptom state that may co-occur
with disruptive behavior disorders, particularly attention deficit hyperactivity
disorder (ADHD) or conduct disorder (CD), or may have features of these
disorders as initial symptoms. In contrast, later adolescent- or adult-onset
bipolar disorder tends to begin suddenly, often with a classic manic episode,
and to have a more episodic pattern with relatively stable periods between
episodes. There is also less co-occurring ADHD or CD among those with later
onset illness.
Findings from one NIMH-supported study suggest that the illness may be at least
as common among youth as among adults. In this study, 1 percent of adolescents
ages 14 to 18 were found to have met criteria for bipolar disorder or
cyclothymia in their lifetime.31 In addition, close to 6 percent of adolescents
in the study had experienced a distinct period of abnormally and persistently
elevated, expansive, or irritable mood even though they never met full criteria
for bipolar disorder or cyclothymia. Compared to adolescents with a history of
major depressive disorder and to a never-mentally-ill group, both the teens with
bipolar disorder and those with subclinical symptoms had greater functional
impairment and higher rates of co-occurring illnesses (especially anxiety and
disruptive behavior disorders), suicide attempts, and mental health services
utilization. The study highlights the need for improved recognition, treatment,
and prevention of even the milder and subclinical cases of bipolar disorder in
adolescence.
Bipolar disorder in children and adolescents has been difficult to recognize and
diagnose because it does not fit precisely the symptom criteria established for
adults, and because its symptoms can resemble or co-occur with those of ADHD and
CD. In addition, symptoms of bipolar disorder may be initially mistaken for
normal emotions and behaviors of children and adolescents. But unlike normal
mood changes, bipolar disorder significantly impairs functioning in school, with
peers, and at home with family.
Although research in adults indicates that the essential treatment for bipolar
disorder is the use of appropriate doses of mood stabilizing medications, few
studies of the safety and efficacy of these drugs have been conducted in
children and adolescents. NIMH is attempting to fill the current gaps in
treatment knowledge with carefully designed studies. Data from adults does not
necessarily apply to younger patients, because the differences in development
may have implications for treatment efficacy and safety. Thus, research in
children and adolescents is needed to properly guide clinicians, patients, and
families.
Current multi-site studies funded by NIMH are investigating the value of
long-term treatment with lithium and other mood stabilizers in preventing
recurrence of bipolar disorder in adolescents.32,33,34 Specifically, these
studies aim to determine how well lithium and other mood stabilizers prevent
recurrences of mania or depression and control subclinical symptoms in
adolescents; to identify factors that predict outcome; and to assess side
effects and overall adherence to treatment. Another NIMH-funded study is
evaluating the safety and efficacy of valproate for treatment of acute mania in
children and adolescents, and also is investigating the biological correlates of
treatment response.35 Other NIMH-supported investigators are studying the
effects of antidepressant medications in the treatment of the depressive phase
of bipolar disorder in youth.36
Women
Although bipolar disorder is equally common in women and men, research indicates
that approximately three times as many women as men experience rapid cycling.37
NIMH researchers and others are investigating possible causes for this gender
difference, including greater use of antidepressant medication among women
(antidepressants may induce mania or hypomania if not used in combination with a
mood stabilizing drug, such as lithium or valproate), differences in thyroid
activity (see below), and effects of sex hormones. Other research findings have
indicated that women with bipolar disorder may have more depressive episodes and
more mixed episodes than men with the illness.37
A number of studies have found that among people with bipolar disorder, women
are more likely than men to have a thyroid disorder.1 In addition, lithium
treatment may cause low thyroid levels in some patients, particularly women,
which may account for some depressive episodes that occur during treatment. Low
thyroid levels also have been associated with rapid-cycling bipolar disorder.
Thyroid hormone supplementation may be needed to restore normal thyroid levels.
However, since too much or too little thyroid hormone alone can lead to mood and
energy fluctuations, it is important that thyroid levels are carefully monitored
in all patients with bipolar disorder.
Older Adults
Although bipolar disorder typically appears between early and mid-life, some
people develop the disorder for the first time late in life. Research indicates
that the factors contributing to late-onset bipolar disorder may differ from
those influencing early-onset illness.
A recent NIMH-supported study found that older adults with late-onset bipolar
disorder reported less family history of psychiatric problems, more co-occurring
vascular disease, and more social support than older adults with early-onset
illness.38 In addition, the study revealed that stressful life events were more
frequent among individuals with earlier age of depressive symptom onset compared
to individuals with later onset. The study findings suggest that while
psychosocial factors may play an important role in early-onset illness, physical
medical factors may be particularly important in late-onset bipolar disorder.
Ongoing NIMH-funded research continues to investigate neuroanatomical and
clinical features of bipolar disorder in older adults.39 This research is likely
to help scientists better understand the psychobiology of bipolar disorder in
older adults and may lead to better diagnosis and management of the illness in
this population.
The Broad NIMH Research Program
In addition to bipolar disorder, 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 illnesses
include schizophrenia, clinical depression, panic disorder, and
obsessive-compulsive disorder.
Increasingly, the public as well as health care professionals are recognizing
these disorders as real and treatable medical illnesses of the brain. Still,
there is a need for more research that examines 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.
NIMH Human Genetics Initiative
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.
Human Brain Project
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 Research Initiative
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.
More Than 2,000 Grants and Contracts
In total, NIMH supports more than 2,000 research grants and contracts at
universities and other institutions across the nation and overseas. It also
conducts basic research and clinical studies involving 9,000 patient visits per
year at its own facilities on the National Institutes of Health campus in
Bethesda, MD, and elsewhere. NIMH research projects focus on:
basic research on behavior, emotion, and cognition to provide a knowledge base
for a better understanding of mental illnesses
basic sciences, including cellular and molecular biology, developmental
neurobiology, neurochemistry, neurogenetics, and neuropharmacology, to provide
essential information about the anatomical and chemical basis of brain function
and brain disorders
neuroscience and behavioral aspects of acquired immune deficiency syndrome
(AIDS) and behavioral strategies to reduce the spread of HIV (human
immunodeficiency virus)
interventions to treat, prevent, and reduce the frequency of mental disorders
and their disabling consequences
mental health services research, including mental health economics and improved
methods of services delivery
co-morbidity among mental disorders and with substance abuse and other medical
conditions, such as depression and heart disease
the prevalence of mental disorders
risk factors for mental disorders
differences in mental health and mental illness among special populations
children and adolescents who suffer from or who are at risk for serious mental
disorders and learning disabilities
psychotherapies and pharmacotherapies for specific disorders
At the beginning of the 21st century, NIMH stands poised to surmount the burden,
loss, and tragedy of mental illnesses that afflict millions of Americans.
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References
1Goodwin FK & Jamison KR, 1990. Manic-depressive illness. New York: Oxford
University Press.
2American Psychiatric Association (APA), 1994. The Diagnostic and Statistical
Manual of Mental Disorders, 4th Edition. Washington, DC: American Psychiatric
Press.
3Goodwin FK & Ghaemi SN, 1998. Understanding manic-depressive illness. Archives
of General Psychiatry, 55(1): 23-25.
4Tsuang MT & Faraone SV, 1990. The genetics of mood disorders. Baltimore, MD:
Johns Hopkins University Press.
5Nurnberger J, in progress. Collaborative genomic study of bipolar disorder.
NIMH Grant Number: 1R01MH59545-01 (project coordination site).
6Baron M, in progress. Molecular genetics of bipolar disorder. NIMH Grant
Number: 1R01MH59602-02.
7Pato C, in progress. Genetic analysis of bipolar disorder. NIMH Grant Number:
1R01MH58693-01A1.
8Soares JC & Mann JJ, 1997. The anatomy of mood disorders-review of structural
neuroimaging studies. Biological Psychiatry, 41: 86-106.
9Soares JC & Mann JJ, 1997. The functional neuroanatomy of mood disorders.
Journal of Psychiatric Research, 31(4): 393-432.
10Kalin NH, et al., 1997. Functional magnetic resonance imaging studies of
emotional processing in normal and depressed patients: Effects of venlafaxine.
Journal of Clinical Psychiatry, 58 (Suppl 16): 32-39.
11Klein P, in progress. Molecular mechanism for lithium action. NIMH Grant
Number: 1R01MH58324-03.
12Nonaka S, et al., 1998. Chronic lithium treatment robustly protects neurons in
the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate
receptor-mediated calcium influx. Proceedings of the National Academy of
Sciences USA, 95(5): 2642-2647.
13Post RM, in progress. New treatments for refractory affective illness. NIMH
Grant Number: 1Z01MH02755-02.
14Suppes T, et al., 1999. Clinical outcome in a randomized 1-year trial of
clozapine versus treatment as usual for patients with treatment-resistant
illness and a history of mania. American Journal of Psychiatry, 156(8):
1164-1169.
15Rothschild AJ, et al., 1999. Olanzapine response in psychotic depression.
Journal of Clinical Psychiatry, 60(2): 116-118.
16Tohen M, et al., 1999. Olanzapine versus placebo in the treatment of acute
mania. Olanzapine HGEH Study Group. American Journal of Psychiatry, 156(5):
702-709.
17Stoll AL, et al., 1999. Omega-3 fatty acids in bipolar disorder: A preliminary
double-blind, placebo-controlled trial. Archives of General Psychiatry, 56:
407-412.
18Jamison KR, 1999. Suicide and manic-depressive illness: An overview and
personal account. In Jacobs DG, Ed., The Harvard Medical School Guide to Suicide
Assessment and Intervention. San Francisco, CA: Jossey-Bass, p. 251.
19Leibenluft E, et al., 1996. Relationship between sleep and mood in patients
with rapid-cycling bipolar disorder. Psychiatry Research, 63(2-3): 161-168.
20Leibenluft E, in progress. Chronobiological evaluation of rapid-cycling
bipolar disorder. NIMH Grant Number: 1Z01MH02614-07.
21Frank E, et al., 1997. Inducing lifestyle regularity in recovering bipolar
disorder patients: Results from the maintenance therapies in bipolar disorder
protocol. Biological Psychiatry, 41(12): 1165-1173.
22Johnson S, in progress. Life events, social support, and bipolar disorder.
NIMH Grant Number: 5R29MH55950-05.
23Abramson L, in progress. Course of cyclothymia-role of cognition and stress.
NIMH Grant Number: 5R10MH52662-03.
24Regier DA, et al., 1990. Comorbidity of mental disorders with alcohol and
other drug abuse: Results from the Epidemiologic Catchment Area (ECA) study.
Journal of the American Medical Association, 264: 2511-2518.
25Winokur G, et al., 1995. Alcoholism in manic-depressive (bipolar) illness:
Familial illness, course of illness, and the primary-secondary distinction.
American Journal of Psychiatry, 152: 365-372.
26Tohen M, et al., 1998. The effect of comorbid substance use disorders on the
course of bipolar disorder: A review. Harvard Review of Psychiatry, 6(3):
133-141.
27Strakowski SM, in progress. Substance abuse comorbidity in first episode
mania. NIMH Grant Number: 1R01MH58170-01A1.
28Mueser KT, et al., 1998. Trauma and posttraumatic stress disorder in severe
mental illness. Journal of Consulting and Clinical Psychology 66(3): 493-499.
29Strakowski SM, et al., 1998. Course of psychiatric and substance abuse
syndromes co-occurring with bipolar disorder after a first psychiatric
hospitalization. Journal of Clinical Psychiatry, 59(9): 465-471.
30Geller B & Luby J, 1997. Child and adolescent bipolar disorder: A review of
the past 10 years. Journal of the American Academy of Child and Adolescent
Psychiatry, 36(9): 1168-1176.
31Lewinsohn PM, et al., 1995. Bipolar disorders in a community sample of older
adolescents: Prevalence, phenomenology, comorbidity, and course. Journal of the
American Academy of Child and Adolescent Psychiatry, 34(4): 454-463.
32Kafantaris V, in progress. Lithium in hospitalized bipolar manic adolescents.
NIMH Grant Number: 5K07MH00970-05.
33Ryan N, in progress. Psychobiology of childhood anxiety and depression. NIMH
Grant Number: 5P01MH41712-14.
34Keller M, Strober M, & Ryan N. Lithium prophylaxis in adolescents with bipolar
illness. NIMH Grant Numbers: 5R10MH48877-05, 5R10MH48878-05, 5R10MH48879-05.
Collaborative study.
35Davanzo P, in progress. Research training in juvenile bipolar disorder. NIMH
Grant Number: 5K01MH01601-02.
36Birmaher B, in progress. Research Units on Pediatric Psychopharmacology. NIMH
Grant Number: 5N01MH70008-003 (project coordination site).
37Leibenluft E, 1997. Issues in the treatment of women with bipolar illness.
Journal of Clinical Psychiatry, 58(Suppl. 15): 5-11.
38Hays JC, et al., 1998. Age of first onset of bipolar disorder: Demographic,
family history, and psychosocial correlates. Depression and Anxiety, 7(2):
76-82.
39Krishnan K, in progress. Bipolar disorder in late life. NIMH Grant Number:
5R01MH57027-03.
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