Kazimiera
08-14-2012, 12:59 PM
Background
Bipolar disorder, or manic-depressive illness (MDI), is one of the most common, severe, and persistent mental illnesses. Bipolar disorder is a serious lifelong struggle and challenge.[1]
It is also useful to note that other mental health disorders and general medical conditions are more prevalent in patients with bipolar disorders.[2] Among the general medical conditions, cardiometabolic conditions such as cardiovascular disease, diabetes, and obesity are a common source of morbidity and mortality for persons with bipolar disorder.
Bipolar disorder is characterized by periods of deep, prolonged, and profound depression that alternate with periods of an excessively elevated or irritable mood known as mania. The symptoms of mania include a decreased need for sleep, pressured speech, increased libido, reckless behavior without regard for consequences, grandiosity, and severe thought disturbances, which may or may not include psychosis. Between these highs and lows, patients usually experience periods of higher functionality and can lead a productive life.
Unipolar major depressive disorder and bipolar disorder share depressive symptoms, but bipolar disorder is defined by episodes of mania or hypomania. A community lifetime prevalence (in its broadest measure) of 4% has been suggested. The costs of bipolar disorder include the direct costs of treatment along with the even more significant indirect costs of excess unemployment, decreased productivity, and excess mortality; it is a severely impairing illness that affects many aspects of patients' lives.[3]
Bipolar disorder constitutes 1 pole of a spectrum of mood disorders that includes including bipolar I (BPI), bipolar II (BPII), cyclothymia (oscillating high and low moods), and major depression.
BPI, also referred to as classic manic-depression, is characterized by distinct episodes of major depression contrasting vividly with episodes of mania, which lead to severe impairment of function. In comparison, BPII is a milder disorder that consists of depression alternating with periods of hypomania. Hypomania may be thought of as a less severe form of mania that does not include psychotic symptoms or lead to major impairment of social or occupational function.
Etiology
Genetic Factors
A number of factors contribute to bipolar disorder, including genetic, biochemical, psychodynamic, and environmental factors.
Genetic factors
Bipolar disorder, especially BPI, has a major genetic component, with the involvement of the ANK3,CACNA1C, and CLOCK genes.[4, 5, 6, 7, 9, 12, 25] The evidence indicating a genetic role in bipolar disorder takes several forms.
First-degree relatives of people with BPI are approximately 7 times more likely to develop BPI than the general population. Remarkably, offspring of a parent with bipolar disorder have a 50% chance of having another major psychiatric disorder. Twin studies demonstrate a concordance of 33-90% for BPI in identical twins. As identical twins share 100% of their DNA, these studies also show that environmental factors are involved and there is no guarantee that a person will develop bipolar disorder, even if they carry susceptibility genes.
Adoption studies prove that a common environment is not the only factor that makes bipolar disorder occur in families. Children whose biologic parents have either BPI or a major depressive disorder remain at increased risk of developing an affective disorder, even if they are reared in a home with adopted parents who are not affected. For more information on bipolar disorder in children, see New Findings in Childhood Bipolar Disorder.
Using probands from the Maudsley Twin Register in London, Cardno and colleagues showed that schizophrenic, schizoaffective, and manic syndromes share genetic risk factors and that the genetic liability was the same for schizoaffective disorder as for the other 2 syndromes.[26] This finding suggests an independent genetic liability for psychosis shared by both mood and schizophrenia spectrum disorders, as Berrettini[27] previously speculated and as has been confirmed in the recent large-scale GWAS studies mentioned above.[9]
Gene expression studies also demonstrate that persons with bipolar disorder, major depression, and schizophrenia share similar decreases in the expression of oligodendrocyte-myelin-related genes and abnormalities of white matter in various brain regions.
Biochemical factors
Multiple biochemical pathways likely contribute to bipolar disorder, which is why detecting one particular abnormality is difficult.
A number of neurotransmitters have been linked to this disorder, largely based on patients’ responses to psychoactive agents as in the following examples.
Drugs used to treat depression and drugs of abuse (eg, cocaine) that increase levels of monoamines, including serotonin, norepinephrine or dopamine, can all potentially trigger mania, implicating all these neurotransmitters in its etiology.
Evidence is mounting on the contribution of glutamate to both bipolar disorder and major depression. A postmortem study of the frontal lobes from persons with both these disorders revealed that the glutamate levels were increased.[28]
Calcium channel blockers have been used to treat mania, which also may result from a disruption of calcium regulation in neurons as suggested by experimental and genetic data. The proposed disruption of calcium regulation may be caused by various neurologic insults, such as excessive glutaminergic transmission or ischemia. Interestingly, valproate specifically up-regulates expression of a calcium chaperone protein, GRP 78, which may be one of its chief mechanisms of cellular protection.
Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis and the stress response may also contribute to the clinical picture of bipolar disorder.
Neurophysiological factors
In addition to structural neuroimaging studies that look for volumetric changes in brain regions regardless of brain activity, functional neuroimaging studies are performed to find regions of the brain, or specific cortical networks, that are either hypoactive or hyperactive in a particular illness. For example, a meta-analysis by Houenou et al found decreased activation and diminution of gray matter in a cortical-cognitive brain network, which has been associated with the regulation of emotions in patients with bipolar disorder.[21] An increased activation in ventral limbic brain regions that mediate the experience of emotions and generation of emotional responses was also discovered. This provides evidence for functional and anatomical alterations in bipolar disorder in brain networks associated with the experience and regulation of emotions.
Psychodynamic factors
Many practitioners see the dynamics of manic-depressive illness as being linked through a single common pathway. They see the depression as the manifestation of losses (ie, the loss of self-esteem and the sense of worthlessness). Therefore, the mania serves as a defense against the feelings of depression. Melanie Klein was one of the major proponents of this formulation. A study by Barnett et al found that personality disturbances in extraversion, neuroticism, and openness are often noted in patients with bipolar disorder and may be enduring characteristics.[29]
Environmental factors
In some instances, the cycle may be directly linked to external stresses or the external pressures may serve to exacerbate some underlying genetic or biochemical predisposition.
Pregnancy is a particular stress for women with a manic-depressive illness history and increases the possibility of postpartum psychosis.[30]
Because of the nature of their work, certain individuals have periods of high demands followed by periods of few requirements. For example, a landscaper and gardener would be busy in the spring, summer, and fall but relatively inactive during the winter, except for plowing snow. Thus, he or she might appear manic for a good part of the year and then would crash and hibernate for the cold months.
Prognosis
Bipolar disorder has significant morbidity and mortality rates. In the United States during the early part of the 1990s, the cost of lost productivity resulting from this bipolar disorder was estimated at approximately $15.5 billion annually. Approximately 25-50% of individuals with bipolar disorder attempt suicide, and 11% actually commit suicide.
Additionally, a recent study from the United Kingdom suggests that for patients with bipolar disorder, mortality one year after hospital discharge was also higher than that of the general population for natural causes, chiefly respiratory and circulatory disorders.[35]
Patients with BPI fare worse than patients with a major depression. Within the first 2 years after the initial episode, 40-50% of patients experience another manic attack. Only 50-60% of patients with BPI who are on lithium gain control of their symptoms. In 7% of these patients, symptoms do not recur, 45% of patients experience more episodes, and 40% go on to have a persistent disorder. Often, the cycling between depression and mania accelerates with age.
Factors suggesting a worse prognosis include the following:
Poor job history
Alcohol abuse
Psychotic features
Depressive features between periods of mania and depression
Evidence of depression
Male sex
Factors suggesting a better prognosis include the following:
Length of manic phases (short in duration)
Late age of onset
Few thoughts of suicide
Few psychotic symptoms
Few medical problems
History and Diagnostics
Correct diagnosis of a disorder leads to proper effective treatment. Nowhere is that more relevant than in diagnosing a patient with bipolar affective disorder. Wolkenstein et al have pointed out the advantages of applying all DSM-specific criteria in order to make the correct diagnosis.[39]
The diagnosis of bipolar I (BPI) disorder requires the presence of a manic episode of at least 1 week’s duration that leads to hospitalization or other significant impairment in occupational or social functioning. The episode of mania cannot be caused by another medical illness or by substance abuse. These criteria are based on the specifications of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR).[40]
Manic episodes are characterized by at least 1 week of profound mood disturbance, characterized by elation, irritability, or expansiveness (referred to as gateway criteria). At least 3 of the following symptoms must also be present:
Grandiosity
Diminished need for sleep
Excessive talking or pressured speech
Racing thoughts or flight of ideas
Clear evidence of distractibility
Increased level of goal-focused activity at home, at work, or sexually
Excessive pleasurable activities, often with painful consequences
The mood disturbance is sufficient to cause impairment at work or danger to the patient or others. The mood is not the result of substance abuse or a medical condition.
Hypomanic episodes are characterized by an elevated, expansive, or irritable mood of at least 4 days’ duration. At least 3 of the following symptoms are also present:
Grandiosity or inflated self-esteem
Diminished need for sleep
Pressured speech
Racing thoughts or flight of ideas
Clear evidence of distractibility
Psychomotor agitation at home, at work, or sexually
Engaging in activities with a high potential for painful consequences
The mood disturbance is observable to others. The mood is not the result of substance abuse or a medical condition.
Major depressive episodes are characterized by the following: For the same 2 weeks, the person experiences 5 or more of the following symptoms, with at least 1 of them being either a depressed mood or characterized by a loss of pleasure or interest:
Depressed mood
Markedly diminished pleasure or interest in nearly all activities
Significant weight loss or gain or significant loss or increase in appetite
Hypersomnia or insomnia
Psychomotor retardation or agitation
Loss of energy or fatigue
Decreased concentration ability or marked indecisiveness
Preoccupation with death or suicide; patient has a plan or has attempted suicide
The symptoms cause significant impairment and distress.
The mood is not the result of substance abuse or a medical condition.
Mixed episodes are characterized by the following:
Persons must meet both the criteria for mania and major depression; the depressive event is required to be present for 1 week only.
The mood disturbance results in marked disruption in social or vocation function.
The mood is not the result of substance abuse or a medical condition.
The mixed symptomatology is quite common in patients presenting with bipolar symptomatology. This often causes a diagnostic dilemma.[41]
Physical Examination
Use the Mental Status Examination (MSE) to diagnose bipolar disorder. This section highlights the major findings for a person with bipolar disorder. Because the patient’s mental status depends on whether he or she is depressed, hypomanic, manic, or mixed, the following discussions of the various areas of the MSE include consideration of each of these particular phases
Appearance
Persons experiencing a depressed episode may demonstrate poor to no eye contact. Their clothes may be unkempt, unclean, holed, unironed, and ill-fitting. If the person has lost significant weight, the garments may fit loosely.
The personal hygiene of individuals experiencing a depressed episode reflects their low mood, as evidenced by poor grooming, lack of shaving, and lack of washing. In women, fingernails may show different layers of polish or one layer partially removed. They may not have paid attention to their hair. Men may exhibit dirty fingernails and hands. When these individuals move, their depressed affect is demonstrated. They move slowly and very little. They show psychomotor retardation. They may talk in low tones or in a depressed or monotone voice.
Persons experiencing a hypomanic episode are busy, active, and involved. They have energy and are always on the go. They are always planning and doing things. Others notice their energy levels and mood changes.
In many ways, the behavior of a patient in the manic phase is the opposite of that of a person in the depressed phase. Patients experiencing the manic phase are hyperactive and might be hypervigilant. They are restless, energized, and active. They talk and act fast. Their attire reflects the mania. Their clothes might have been put on in haste and are disorganized. Alternately, their garments are often too bright, colorful, or garish. They stand out in a crowd because their dress frequently attracts attention.
Affect/mood
In persons experiencing a depressed episode, sadness dominates the affect. These individuals feel sad, depressed, lost, vacant, and isolated. The "2 Hs"— h opeless and h elpless—often accompany their mood. When in the presence of such patients, one comes away feeling sad and down.
In persons experiencing a hypomanic episode, the mood is up, expansive, and often irritable.
In persons experiencing a manic episode, the mood is inappropriately joyous, elated, and jubilant. These individuals are euphoric. They also may demonstrate annoyance and irritability, especially if the mania has been present for a significant length of time.
Persons experiencing a mixed episode exhibit both depression and mania within a brief period (1 wk or less).
Thought content
Patients experiencing a depressed episode have thoughts that reflect their sadness. They are preoccupied with negative ideas and nihilistic concerns, and they tend to "see the glass as half empty." They are likely to focus on death and morbid persons. Many think about suicide.
Patients experiencing a hypomanic episode are optimistic, forward thinking, and have a positive attitude.
Patients experiencing a manic episode have very expansive and optimistic thinking. They may be excessively self-confident or grandiose. They often have a very rapid production of ideas and thoughts. They perceive their minds as being very active and see themselves as being highly engaging and creative. They are highly distractible and quickly shift from one person to another.
Patients experiencing a mixed episode can oscillate dramatically between depression and euphoria, and they often demonstrate marked irritability.
Perceptions
Two forms of a major depression are described, one with psychotic features and the other without. With psychosis, the patient experiences delusions and hallucinations that are either consistent or inconsistent with the mood.
In the former, the patient’s delusions of having sinned are accompanied by guilt and remorse, or the patient feels he or she is utterly worthless and should live in total deprivation and degradation; hence, the delusional content remains consistent with the depressed mood. In the latter, some patients experience delusions that are inconsistent with the depression, such as paranoia or persecutory delusions.
Patients experiencing a hypomanic episode do not experience perceptual disturbances.
Approximately three fourths of patients experiencing a manic episode have delusions. As in major depression, the delusional content is either consistent or inconsistent with the mania. Manic delusions reflect perceptions of power, prestige, position, self-worth, and glory.
Patients experiencing a mixed episode might exhibit delusions and hallucinations consistent with either depression or mania or congruent to both.
Suicide/self-destruction
Patients experiencing a depressed episode have a very high rate of suicide. They are the individuals who attempt and succeed at killing themselves. Query patients to determine if they have any thoughts of hurting themselves (suicidal ideation) and any plans to do so. The more specific the plan, the higher the danger.
Dubovsky reports that the highest lifetime suicide risk (17.08%) is in men with bipolar disorder and deliberate self-harm.[44]
Bellivier and collogues found in a European study of adults with bipolar disorder that 29.9% had a history of at least 1 attempt of suicide (663 of 2219 patients who provided data on lifetime history of suicide attempts). Female sex, history of alcohol abuse, history of substance abuse, young age at first treatment for a mood episode, longer disease duration, greater depressive symptom severity (5-item Hamilton Depression Rating Scale [HAMD-5] total score), current benzodiazepine use, higher overall symptom severity (Clinical Global Impression-Bipolar Disorder [CGI-BP] scale: mania and overall score), and poor compliance were the baseline factors associated with a history of suicidal behavior.[45]
As patients emerge from a period of depression, their suicide risk may increase. This may be because, as the illness remits, executive functions are improved to the point where the person is again capable of making and carrying out a plan while the subjective feeling of depression and accompanying suicidal thoughts persist.
Patients experiencing a hypomanic or manic episode have a low incidence of suicide.
In mixed episodes, the depressed phases put the patient at risk for suicide.
Homicide/violence/aggression
In patients experiencing a depressed episode, suicide generally remains the paramount issue. However, certain persons in the depths of a depression see the world as hopeless and helpless not only for themselves but also for others. Frequently, that perspective can create and lead to a homicide followed by a suicide.
hich led to an emergency intervention and her hospitalization.
Patients who are hypomanic frequently show evidence of irritability and aggressiveness. They can be pushy and impatient with others.
Persons experiencing a manic episode can be openly combative and aggressive. They have no patience or tolerance for others. They can be highly demanding, violently assertive, and highly irritable. The homicidal element is particularly likely to emerge if these individuals have a delusional content to their mania. They are acting out of the grandiose belief that others must obey their commands, wishes, and directives. The patient may become violent toward those "disordent" subjects. If their delusions become persecutory in nature, they may defend themselves against others in a homicidal fashion.
Persons experiencing a mixed episode may exhibit aggression, especially in the manic phases.
Judgment/insight
In persons experiencing a depressed episode, the depression clouds and dims their judgment and colors their insights. They fail to make important actions, because they are so down and preoccupied with their own plight. They see no tomorrow; therefore, planning for it is difficult. Frequently, persons in the middle of a depression have done things such as forgetting to pay their income taxes. At that time, they have little insight into their behavior. Often, others have to persuade them to seek therapy because of their lack of insight.
Persons experiencing a hypomanic episode generally have good but expansive judgment. They may take on too many tasks or become overinvolved. Often, their distractibility impairs their judgment, and they have little insight into their driven qualities. They see themselves as productive and conscientious, not as hypomanic.
In patients experiencing a manic episode, judgment is seriously impaired. These persons make terrible decisions in their work and family. They may invest the family fortune in very questionable programs, become professionally overinvolved in work activities or with coworkers, or start dramatically unsound fiscal or professional ventures. They ignore feedback, suggestions, and advice from friends, family, and colleagues. They have no insight into the extreme nature of their demands, plans, and behavior. Often, commitment proves the only way to contain them.
In persons experiencing a mixed episode, major shifts in affect during short lengths of time severely impair their judgment and interfere with their insight.
Cognition
Impairments in orientation and memory are seldom observed in patients with bipolar disorder unless they are very psychotic. They know the time and their location, and they recognize people. They can remember immediate, recent, and distant events. In some cases of hypomanic and even manic episodes, their ability to recall information can be extremely vivid and expanded. In extremes of depression and mania, they may experience difficulty in concentrating and focusing.
Physical health
Although the MSE has been used here to highlight key aspects of the examination, the clinician must pay particular attention to the patient’s physical health. As Fagiolini points out, patients with bipolar disorder have a high incidence of endocrine disorders, cardiovascular disorders, and obesity, and these factors must be considered when medications are prescribed.[46, 47]
Complications
The main complications of bipolar disorder are suicide, homicide, and addictions.
Suicidal patients remain at risk for suicide. Patients emerging from a depression are thought to be at an increased risk for suicide. The risk of self-destructive behavior and death is lifelong. Hong’s 2003 study demonstrates a genetic link between bipolar disorder and suicidal behavior, especially in white individuals.[48] According to one study, men with bipolar disorder are at higher risk for suicide.[49]
The European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study, a 2-year prospective, observational study, suggests the following characteristics found in patients with bipolar disorder who are suicidal, may help identify subjects at risk for suicidal behavior[45] :
Female gender
A history of alcohol abuse
A history of substance abuse
Young age at first treatment for a mood episode
Longer disease duration
Greater depressive symptom severity (HAMD-5 total score)
Current benzodiazepine use
Higher overall symptom severity (CGI-BP: mania and overall score)
Poor compliance
Homicidal patients, often in the manic phase, can be very demanding and grandiose. In this context, they are angered if others do not immediately comply with their wishes. This can make them turn dramatically violent. In addition, they can become homicidal by acting on delusions.
Individuals with bipolar disorder are at risk for an addiction. This creates the problem of a dual diagnosis and, therefore, complicates treatment.
One area of major concern is the relationship between violent crime and bipolar disorder. This danger is particularly present and prominent with patients who have a substance abuse problem.[50] Although some persons with bipolar disorder may become violent, clinicians must be vigilant when treating patients with the dual diagnosis of substance abuse.
Quality of life (QOL) has been an important way to look at the effects of mental illness. BPI results in diminished quality of life as measured by health utility and QOL and utility-based health-related quality of life. The QOL losses in patients with BPI were less than those in persons with schizophrenia. The patients with depression sustained the greatest loss in QOL.[51]
In a study by Fiedorowicz et al, hypomania symptoms were frequently associated with progression to bipolar disorder, even when symptoms were low intensity; however, most patients did not have hypomania symptoms at baseline.[52] The study concluded that monitoring for progression to bipolar disorder is necessary in patients with long-term major depressive disorder.
Some of the most challenging situations involve children and adolescents with severe emotional lability. Often, psychiatrists have applied the bipolar diagnosis to this group. Leibenluft reviewed this situation and concluded that children have increasingly been diagnosed with bipolar disorder.[53] In some cases, the criteria were clearly met, whereas other cases were less clear.
Severe mood dysregulation is a syndrome formulated to describe the symptoms of children who do not clearly meet the criteria for bipolar disorder. Leibenluft’s findings revealed that nonepisodic irritability in youths is common and is associated with an elevated risk for anxiety and unipolar depressive disorders (not bipolar disorders) in adulthood. In fact, data suggest that children and adolescents with severe mood dysregulation have lower familiar rates of bipolar disorder than children and adolescents with bipolar disorder.
Bipolar disorder, or manic-depressive illness (MDI), is one of the most common, severe, and persistent mental illnesses. Bipolar disorder is a serious lifelong struggle and challenge.[1]
It is also useful to note that other mental health disorders and general medical conditions are more prevalent in patients with bipolar disorders.[2] Among the general medical conditions, cardiometabolic conditions such as cardiovascular disease, diabetes, and obesity are a common source of morbidity and mortality for persons with bipolar disorder.
Bipolar disorder is characterized by periods of deep, prolonged, and profound depression that alternate with periods of an excessively elevated or irritable mood known as mania. The symptoms of mania include a decreased need for sleep, pressured speech, increased libido, reckless behavior without regard for consequences, grandiosity, and severe thought disturbances, which may or may not include psychosis. Between these highs and lows, patients usually experience periods of higher functionality and can lead a productive life.
Unipolar major depressive disorder and bipolar disorder share depressive symptoms, but bipolar disorder is defined by episodes of mania or hypomania. A community lifetime prevalence (in its broadest measure) of 4% has been suggested. The costs of bipolar disorder include the direct costs of treatment along with the even more significant indirect costs of excess unemployment, decreased productivity, and excess mortality; it is a severely impairing illness that affects many aspects of patients' lives.[3]
Bipolar disorder constitutes 1 pole of a spectrum of mood disorders that includes including bipolar I (BPI), bipolar II (BPII), cyclothymia (oscillating high and low moods), and major depression.
BPI, also referred to as classic manic-depression, is characterized by distinct episodes of major depression contrasting vividly with episodes of mania, which lead to severe impairment of function. In comparison, BPII is a milder disorder that consists of depression alternating with periods of hypomania. Hypomania may be thought of as a less severe form of mania that does not include psychotic symptoms or lead to major impairment of social or occupational function.
Etiology
Genetic Factors
A number of factors contribute to bipolar disorder, including genetic, biochemical, psychodynamic, and environmental factors.
Genetic factors
Bipolar disorder, especially BPI, has a major genetic component, with the involvement of the ANK3,CACNA1C, and CLOCK genes.[4, 5, 6, 7, 9, 12, 25] The evidence indicating a genetic role in bipolar disorder takes several forms.
First-degree relatives of people with BPI are approximately 7 times more likely to develop BPI than the general population. Remarkably, offspring of a parent with bipolar disorder have a 50% chance of having another major psychiatric disorder. Twin studies demonstrate a concordance of 33-90% for BPI in identical twins. As identical twins share 100% of their DNA, these studies also show that environmental factors are involved and there is no guarantee that a person will develop bipolar disorder, even if they carry susceptibility genes.
Adoption studies prove that a common environment is not the only factor that makes bipolar disorder occur in families. Children whose biologic parents have either BPI or a major depressive disorder remain at increased risk of developing an affective disorder, even if they are reared in a home with adopted parents who are not affected. For more information on bipolar disorder in children, see New Findings in Childhood Bipolar Disorder.
Using probands from the Maudsley Twin Register in London, Cardno and colleagues showed that schizophrenic, schizoaffective, and manic syndromes share genetic risk factors and that the genetic liability was the same for schizoaffective disorder as for the other 2 syndromes.[26] This finding suggests an independent genetic liability for psychosis shared by both mood and schizophrenia spectrum disorders, as Berrettini[27] previously speculated and as has been confirmed in the recent large-scale GWAS studies mentioned above.[9]
Gene expression studies also demonstrate that persons with bipolar disorder, major depression, and schizophrenia share similar decreases in the expression of oligodendrocyte-myelin-related genes and abnormalities of white matter in various brain regions.
Biochemical factors
Multiple biochemical pathways likely contribute to bipolar disorder, which is why detecting one particular abnormality is difficult.
A number of neurotransmitters have been linked to this disorder, largely based on patients’ responses to psychoactive agents as in the following examples.
Drugs used to treat depression and drugs of abuse (eg, cocaine) that increase levels of monoamines, including serotonin, norepinephrine or dopamine, can all potentially trigger mania, implicating all these neurotransmitters in its etiology.
Evidence is mounting on the contribution of glutamate to both bipolar disorder and major depression. A postmortem study of the frontal lobes from persons with both these disorders revealed that the glutamate levels were increased.[28]
Calcium channel blockers have been used to treat mania, which also may result from a disruption of calcium regulation in neurons as suggested by experimental and genetic data. The proposed disruption of calcium regulation may be caused by various neurologic insults, such as excessive glutaminergic transmission or ischemia. Interestingly, valproate specifically up-regulates expression of a calcium chaperone protein, GRP 78, which may be one of its chief mechanisms of cellular protection.
Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis and the stress response may also contribute to the clinical picture of bipolar disorder.
Neurophysiological factors
In addition to structural neuroimaging studies that look for volumetric changes in brain regions regardless of brain activity, functional neuroimaging studies are performed to find regions of the brain, or specific cortical networks, that are either hypoactive or hyperactive in a particular illness. For example, a meta-analysis by Houenou et al found decreased activation and diminution of gray matter in a cortical-cognitive brain network, which has been associated with the regulation of emotions in patients with bipolar disorder.[21] An increased activation in ventral limbic brain regions that mediate the experience of emotions and generation of emotional responses was also discovered. This provides evidence for functional and anatomical alterations in bipolar disorder in brain networks associated with the experience and regulation of emotions.
Psychodynamic factors
Many practitioners see the dynamics of manic-depressive illness as being linked through a single common pathway. They see the depression as the manifestation of losses (ie, the loss of self-esteem and the sense of worthlessness). Therefore, the mania serves as a defense against the feelings of depression. Melanie Klein was one of the major proponents of this formulation. A study by Barnett et al found that personality disturbances in extraversion, neuroticism, and openness are often noted in patients with bipolar disorder and may be enduring characteristics.[29]
Environmental factors
In some instances, the cycle may be directly linked to external stresses or the external pressures may serve to exacerbate some underlying genetic or biochemical predisposition.
Pregnancy is a particular stress for women with a manic-depressive illness history and increases the possibility of postpartum psychosis.[30]
Because of the nature of their work, certain individuals have periods of high demands followed by periods of few requirements. For example, a landscaper and gardener would be busy in the spring, summer, and fall but relatively inactive during the winter, except for plowing snow. Thus, he or she might appear manic for a good part of the year and then would crash and hibernate for the cold months.
Prognosis
Bipolar disorder has significant morbidity and mortality rates. In the United States during the early part of the 1990s, the cost of lost productivity resulting from this bipolar disorder was estimated at approximately $15.5 billion annually. Approximately 25-50% of individuals with bipolar disorder attempt suicide, and 11% actually commit suicide.
Additionally, a recent study from the United Kingdom suggests that for patients with bipolar disorder, mortality one year after hospital discharge was also higher than that of the general population for natural causes, chiefly respiratory and circulatory disorders.[35]
Patients with BPI fare worse than patients with a major depression. Within the first 2 years after the initial episode, 40-50% of patients experience another manic attack. Only 50-60% of patients with BPI who are on lithium gain control of their symptoms. In 7% of these patients, symptoms do not recur, 45% of patients experience more episodes, and 40% go on to have a persistent disorder. Often, the cycling between depression and mania accelerates with age.
Factors suggesting a worse prognosis include the following:
Poor job history
Alcohol abuse
Psychotic features
Depressive features between periods of mania and depression
Evidence of depression
Male sex
Factors suggesting a better prognosis include the following:
Length of manic phases (short in duration)
Late age of onset
Few thoughts of suicide
Few psychotic symptoms
Few medical problems
History and Diagnostics
Correct diagnosis of a disorder leads to proper effective treatment. Nowhere is that more relevant than in diagnosing a patient with bipolar affective disorder. Wolkenstein et al have pointed out the advantages of applying all DSM-specific criteria in order to make the correct diagnosis.[39]
The diagnosis of bipolar I (BPI) disorder requires the presence of a manic episode of at least 1 week’s duration that leads to hospitalization or other significant impairment in occupational or social functioning. The episode of mania cannot be caused by another medical illness or by substance abuse. These criteria are based on the specifications of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR).[40]
Manic episodes are characterized by at least 1 week of profound mood disturbance, characterized by elation, irritability, or expansiveness (referred to as gateway criteria). At least 3 of the following symptoms must also be present:
Grandiosity
Diminished need for sleep
Excessive talking or pressured speech
Racing thoughts or flight of ideas
Clear evidence of distractibility
Increased level of goal-focused activity at home, at work, or sexually
Excessive pleasurable activities, often with painful consequences
The mood disturbance is sufficient to cause impairment at work or danger to the patient or others. The mood is not the result of substance abuse or a medical condition.
Hypomanic episodes are characterized by an elevated, expansive, or irritable mood of at least 4 days’ duration. At least 3 of the following symptoms are also present:
Grandiosity or inflated self-esteem
Diminished need for sleep
Pressured speech
Racing thoughts or flight of ideas
Clear evidence of distractibility
Psychomotor agitation at home, at work, or sexually
Engaging in activities with a high potential for painful consequences
The mood disturbance is observable to others. The mood is not the result of substance abuse or a medical condition.
Major depressive episodes are characterized by the following: For the same 2 weeks, the person experiences 5 or more of the following symptoms, with at least 1 of them being either a depressed mood or characterized by a loss of pleasure or interest:
Depressed mood
Markedly diminished pleasure or interest in nearly all activities
Significant weight loss or gain or significant loss or increase in appetite
Hypersomnia or insomnia
Psychomotor retardation or agitation
Loss of energy or fatigue
Decreased concentration ability or marked indecisiveness
Preoccupation with death or suicide; patient has a plan or has attempted suicide
The symptoms cause significant impairment and distress.
The mood is not the result of substance abuse or a medical condition.
Mixed episodes are characterized by the following:
Persons must meet both the criteria for mania and major depression; the depressive event is required to be present for 1 week only.
The mood disturbance results in marked disruption in social or vocation function.
The mood is not the result of substance abuse or a medical condition.
The mixed symptomatology is quite common in patients presenting with bipolar symptomatology. This often causes a diagnostic dilemma.[41]
Physical Examination
Use the Mental Status Examination (MSE) to diagnose bipolar disorder. This section highlights the major findings for a person with bipolar disorder. Because the patient’s mental status depends on whether he or she is depressed, hypomanic, manic, or mixed, the following discussions of the various areas of the MSE include consideration of each of these particular phases
Appearance
Persons experiencing a depressed episode may demonstrate poor to no eye contact. Their clothes may be unkempt, unclean, holed, unironed, and ill-fitting. If the person has lost significant weight, the garments may fit loosely.
The personal hygiene of individuals experiencing a depressed episode reflects their low mood, as evidenced by poor grooming, lack of shaving, and lack of washing. In women, fingernails may show different layers of polish or one layer partially removed. They may not have paid attention to their hair. Men may exhibit dirty fingernails and hands. When these individuals move, their depressed affect is demonstrated. They move slowly and very little. They show psychomotor retardation. They may talk in low tones or in a depressed or monotone voice.
Persons experiencing a hypomanic episode are busy, active, and involved. They have energy and are always on the go. They are always planning and doing things. Others notice their energy levels and mood changes.
In many ways, the behavior of a patient in the manic phase is the opposite of that of a person in the depressed phase. Patients experiencing the manic phase are hyperactive and might be hypervigilant. They are restless, energized, and active. They talk and act fast. Their attire reflects the mania. Their clothes might have been put on in haste and are disorganized. Alternately, their garments are often too bright, colorful, or garish. They stand out in a crowd because their dress frequently attracts attention.
Affect/mood
In persons experiencing a depressed episode, sadness dominates the affect. These individuals feel sad, depressed, lost, vacant, and isolated. The "2 Hs"— h opeless and h elpless—often accompany their mood. When in the presence of such patients, one comes away feeling sad and down.
In persons experiencing a hypomanic episode, the mood is up, expansive, and often irritable.
In persons experiencing a manic episode, the mood is inappropriately joyous, elated, and jubilant. These individuals are euphoric. They also may demonstrate annoyance and irritability, especially if the mania has been present for a significant length of time.
Persons experiencing a mixed episode exhibit both depression and mania within a brief period (1 wk or less).
Thought content
Patients experiencing a depressed episode have thoughts that reflect their sadness. They are preoccupied with negative ideas and nihilistic concerns, and they tend to "see the glass as half empty." They are likely to focus on death and morbid persons. Many think about suicide.
Patients experiencing a hypomanic episode are optimistic, forward thinking, and have a positive attitude.
Patients experiencing a manic episode have very expansive and optimistic thinking. They may be excessively self-confident or grandiose. They often have a very rapid production of ideas and thoughts. They perceive their minds as being very active and see themselves as being highly engaging and creative. They are highly distractible and quickly shift from one person to another.
Patients experiencing a mixed episode can oscillate dramatically between depression and euphoria, and they often demonstrate marked irritability.
Perceptions
Two forms of a major depression are described, one with psychotic features and the other without. With psychosis, the patient experiences delusions and hallucinations that are either consistent or inconsistent with the mood.
In the former, the patient’s delusions of having sinned are accompanied by guilt and remorse, or the patient feels he or she is utterly worthless and should live in total deprivation and degradation; hence, the delusional content remains consistent with the depressed mood. In the latter, some patients experience delusions that are inconsistent with the depression, such as paranoia or persecutory delusions.
Patients experiencing a hypomanic episode do not experience perceptual disturbances.
Approximately three fourths of patients experiencing a manic episode have delusions. As in major depression, the delusional content is either consistent or inconsistent with the mania. Manic delusions reflect perceptions of power, prestige, position, self-worth, and glory.
Patients experiencing a mixed episode might exhibit delusions and hallucinations consistent with either depression or mania or congruent to both.
Suicide/self-destruction
Patients experiencing a depressed episode have a very high rate of suicide. They are the individuals who attempt and succeed at killing themselves. Query patients to determine if they have any thoughts of hurting themselves (suicidal ideation) and any plans to do so. The more specific the plan, the higher the danger.
Dubovsky reports that the highest lifetime suicide risk (17.08%) is in men with bipolar disorder and deliberate self-harm.[44]
Bellivier and collogues found in a European study of adults with bipolar disorder that 29.9% had a history of at least 1 attempt of suicide (663 of 2219 patients who provided data on lifetime history of suicide attempts). Female sex, history of alcohol abuse, history of substance abuse, young age at first treatment for a mood episode, longer disease duration, greater depressive symptom severity (5-item Hamilton Depression Rating Scale [HAMD-5] total score), current benzodiazepine use, higher overall symptom severity (Clinical Global Impression-Bipolar Disorder [CGI-BP] scale: mania and overall score), and poor compliance were the baseline factors associated with a history of suicidal behavior.[45]
As patients emerge from a period of depression, their suicide risk may increase. This may be because, as the illness remits, executive functions are improved to the point where the person is again capable of making and carrying out a plan while the subjective feeling of depression and accompanying suicidal thoughts persist.
Patients experiencing a hypomanic or manic episode have a low incidence of suicide.
In mixed episodes, the depressed phases put the patient at risk for suicide.
Homicide/violence/aggression
In patients experiencing a depressed episode, suicide generally remains the paramount issue. However, certain persons in the depths of a depression see the world as hopeless and helpless not only for themselves but also for others. Frequently, that perspective can create and lead to a homicide followed by a suicide.
hich led to an emergency intervention and her hospitalization.
Patients who are hypomanic frequently show evidence of irritability and aggressiveness. They can be pushy and impatient with others.
Persons experiencing a manic episode can be openly combative and aggressive. They have no patience or tolerance for others. They can be highly demanding, violently assertive, and highly irritable. The homicidal element is particularly likely to emerge if these individuals have a delusional content to their mania. They are acting out of the grandiose belief that others must obey their commands, wishes, and directives. The patient may become violent toward those "disordent" subjects. If their delusions become persecutory in nature, they may defend themselves against others in a homicidal fashion.
Persons experiencing a mixed episode may exhibit aggression, especially in the manic phases.
Judgment/insight
In persons experiencing a depressed episode, the depression clouds and dims their judgment and colors their insights. They fail to make important actions, because they are so down and preoccupied with their own plight. They see no tomorrow; therefore, planning for it is difficult. Frequently, persons in the middle of a depression have done things such as forgetting to pay their income taxes. At that time, they have little insight into their behavior. Often, others have to persuade them to seek therapy because of their lack of insight.
Persons experiencing a hypomanic episode generally have good but expansive judgment. They may take on too many tasks or become overinvolved. Often, their distractibility impairs their judgment, and they have little insight into their driven qualities. They see themselves as productive and conscientious, not as hypomanic.
In patients experiencing a manic episode, judgment is seriously impaired. These persons make terrible decisions in their work and family. They may invest the family fortune in very questionable programs, become professionally overinvolved in work activities or with coworkers, or start dramatically unsound fiscal or professional ventures. They ignore feedback, suggestions, and advice from friends, family, and colleagues. They have no insight into the extreme nature of their demands, plans, and behavior. Often, commitment proves the only way to contain them.
In persons experiencing a mixed episode, major shifts in affect during short lengths of time severely impair their judgment and interfere with their insight.
Cognition
Impairments in orientation and memory are seldom observed in patients with bipolar disorder unless they are very psychotic. They know the time and their location, and they recognize people. They can remember immediate, recent, and distant events. In some cases of hypomanic and even manic episodes, their ability to recall information can be extremely vivid and expanded. In extremes of depression and mania, they may experience difficulty in concentrating and focusing.
Physical health
Although the MSE has been used here to highlight key aspects of the examination, the clinician must pay particular attention to the patient’s physical health. As Fagiolini points out, patients with bipolar disorder have a high incidence of endocrine disorders, cardiovascular disorders, and obesity, and these factors must be considered when medications are prescribed.[46, 47]
Complications
The main complications of bipolar disorder are suicide, homicide, and addictions.
Suicidal patients remain at risk for suicide. Patients emerging from a depression are thought to be at an increased risk for suicide. The risk of self-destructive behavior and death is lifelong. Hong’s 2003 study demonstrates a genetic link between bipolar disorder and suicidal behavior, especially in white individuals.[48] According to one study, men with bipolar disorder are at higher risk for suicide.[49]
The European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study, a 2-year prospective, observational study, suggests the following characteristics found in patients with bipolar disorder who are suicidal, may help identify subjects at risk for suicidal behavior[45] :
Female gender
A history of alcohol abuse
A history of substance abuse
Young age at first treatment for a mood episode
Longer disease duration
Greater depressive symptom severity (HAMD-5 total score)
Current benzodiazepine use
Higher overall symptom severity (CGI-BP: mania and overall score)
Poor compliance
Homicidal patients, often in the manic phase, can be very demanding and grandiose. In this context, they are angered if others do not immediately comply with their wishes. This can make them turn dramatically violent. In addition, they can become homicidal by acting on delusions.
Individuals with bipolar disorder are at risk for an addiction. This creates the problem of a dual diagnosis and, therefore, complicates treatment.
One area of major concern is the relationship between violent crime and bipolar disorder. This danger is particularly present and prominent with patients who have a substance abuse problem.[50] Although some persons with bipolar disorder may become violent, clinicians must be vigilant when treating patients with the dual diagnosis of substance abuse.
Quality of life (QOL) has been an important way to look at the effects of mental illness. BPI results in diminished quality of life as measured by health utility and QOL and utility-based health-related quality of life. The QOL losses in patients with BPI were less than those in persons with schizophrenia. The patients with depression sustained the greatest loss in QOL.[51]
In a study by Fiedorowicz et al, hypomania symptoms were frequently associated with progression to bipolar disorder, even when symptoms were low intensity; however, most patients did not have hypomania symptoms at baseline.[52] The study concluded that monitoring for progression to bipolar disorder is necessary in patients with long-term major depressive disorder.
Some of the most challenging situations involve children and adolescents with severe emotional lability. Often, psychiatrists have applied the bipolar diagnosis to this group. Leibenluft reviewed this situation and concluded that children have increasingly been diagnosed with bipolar disorder.[53] In some cases, the criteria were clearly met, whereas other cases were less clear.
Severe mood dysregulation is a syndrome formulated to describe the symptoms of children who do not clearly meet the criteria for bipolar disorder. Leibenluft’s findings revealed that nonepisodic irritability in youths is common and is associated with an elevated risk for anxiety and unipolar depressive disorders (not bipolar disorders) in adulthood. In fact, data suggest that children and adolescents with severe mood dysregulation have lower familiar rates of bipolar disorder than children and adolescents with bipolar disorder.