BIPOLAR DISORDERS

DSM-IV Diagnostic Criteria:

Hypomanic Episode:

A. A distinct period of abnormally and persistently elevated, expansive or irritable mood lasting at least 1 week (or any duration if hospitalization is necessary).

B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:

1. Inflated self-esteem or grandiosity
2. Decreased need for sleep (eg, feels rested after only 3 hours of sleep)
3. More talkative than usual or pressure to keep talking
4. Flight of ideas or subjective experience that thoughts are racing
5.  Distractibility (ie, attention too easily drawn to unimportant or irrelevant external stimuli)
6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
7. Excessive involvement in pleasurable activities that have a high potential for painful consequences (eg, engaging in unrestrained buying sprees, sexual indiscretions or foolish business investments) - (Hedonism - Ludism)

C. The symptoms do not meet the criteria for a mixed episode.

D. The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.

E. The symptoms are not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication, or other treatment) or a general medical condition (eg, hyperthyroidism).

*Note: Manic-like episodes that are clearly caused by somatic antidepressant treatment (eg, medication, electroconvulsive treatment, light therapy) should not count toward a diagnosis of bipolar I disorder.

General Considerations: Bipolar disorders can be conceptualized into three distinct entities:

  • Bipolar I disorder, consisting of episodes of mania cycling with depressive episodes;
  • Bipolar II disorder, consisting of episodes of hypomania cycling with depressive episodes; and;
  • Cyclothymic disorder, consisting of hypomania and less severe episodes of depression (see section on Cyclothymic Disorder later in this chapter).

* Note: Very few patients have only manic episodes.

Major Etiologic Theories: Despite intensive attempts to establish its etiologic or pathophysiologic basis, the precise cause of bipolar disorder is not known. As in major depressive disorder, there is consensus that multiple etiologic factors - genetic, biochemical, psychodynamic and socio-environmental - may interact in complex ways:

1. Life events- Although psychosocial stressors can occasionally precede the onset of bipolar disorder, there is no clear association between life events and the onset of manic or hypomanic episodes.

2. Biological theories:

a.] Neurotransmitters - Neurotransmitter theories initially conceptualized that depression and mania are on the opposite ends of the same continuum. For example, the norepinephrine hypothesis of affective illness centered around the availability of norepinephrine at synaptic sites, with less norepinephrine being available in depression, and more in mania. This theory, and later modifications of it, especially as they pertain to the separation of unipolar and bipolar disorders, are discussed earlier in this chapter.

b.] Neuroendocrine factors - Abnormalities in the HPA axis and, more so, in the HPT axis are common in bipolar disorder; they are discussed later in this section.

3. Psychosocial theories - Psychosocial theories pertaining to the etiology of bipolar disorders are the same as those described for major depressive disorder (see section on Major Depressive Disorder earlier in this chapter).

a.] Kindling - Environmental conditions contribute more to the timing of a bipolar episode than to the patient's underlying vulnerability. In other words, more stressful life events appear to precede early episodes than later ones, and there is a pattern of increased frequency over time. It is possible that early precipitating events merely activate preexisting vulnerability, thereby making an individual more vulnerable for future episodes.

This clinical observation is supported conceptually by the kindling model. In laboratory animals, repeated kindling of the amygdala will lead to the development of a spontaneous seizure disorder, in which seizures occur without external stimulation. Applied to bipolar disorder, this model provides a better understanding of several phenomena inherent in the illness, including the above-mentioned effects of repeated episodes on disease severity and outcome (eg, rapid-cycling bipolar disorder usually develops late in the course of the illness) and the acute and prophylactic treatment effects of ECT and anticonvulsants such as carbamazepine and valproic acid. Because these therapies inhibit kindling in laboratory animals, their therapeutic effect in bipolar disorder may involve interruption of kindling.

The kindling model also has enormous treatment implications. Because it suggests that preventing or treating early episodes will favorably affect outcome, it stresses the need for early identification and intervention techniques. This pertains particularly to younger patients, because the risk of kindling is highest during adolescence.

Epidemiology:

Social class Found more frequently in the upper socio-economic class
Race No relationship
Life events No relationship
Personality No relationship
Childhood experience No relationship
Marital status Data not uniform
Family history Bipolar patients have both bipolar & unipolar first-degree relatives in roughly equal proportions

Risk factors for bipolar disorder (Paykel; Robins)

 

Among the key risk factors for bipolar disorder are being female, having a family history of bipolar disorder and coming from an upper socioeconomic class. Data also suggest that people under age 50 years are at higher risk of a first attack of bipolar disorder, whereas someone who already has the disorder faces an increasing risk of a recurrent manic or depressive episode as he or she grows older.

Epidemiologic Catchment Area (ECA) studies support a lifetime prevalence of bipolar disorder ranging from 0.6% to 1.1% (between 0.8% and 1.1% in men, and between 0.5% and 1.3% in women). Estimates from community samples range from 0.4% to 1.6%. The disorder affects over 3 million persons in the United States. Bipolar disorder accounts for one quarter of all mood disorders. It is likely that prevalence rates of bipolar disorders are underestimated, because of problems in identifying manic and, more so, hypomanic episodes.

Bipolar disorders are about equally distributed among males and females, but there are more females with more serious bipolar disorder, especially rapid-cycling bipolar disorder. Higher rates of hypothyroidism, greater use of antidepressant medication, and changes in reproductive status and gonadal steroids may account for the greater prevalence of rapidcycling bipolar disorder among women.

Approximately 10-15% of adolescents with recurrent major depression will go on to develop bipolar I disorder. Mixed episodes appear to be more likely in adolescents and young adults than in older adults. An age at onset for a first manic episode after age 40 years should alert the clinician to the possibility that the symptoms may be due to a general medical condition or substance use. Bipolar disorder is often misdiagnosed in adolescents (eg, as ADHD). Patients with early-onset bipolar disorder are more likely to display psychotic symptoms and to have a poorer prognosis in terms of lifetime outcome.

Mood disorders often have seasonal patterns. Acute episodes of depression are common in spring and fall, whereas mania appears to cluster in the summer months. Corresponding data on suicides also show a peak in the spring and a (smaller) peak in the late fall.

Genetics: Twin and family studies provide strong evidence for a genetic component in bipolar disorder, but the precise mechanisms of inheritance are not known. In monozygotic twins, the concordance rate is higher for bipolar disorder (80%) than for unipolar disorder (54%). In dizygotic twins, concordance rates are 24% for bipolar disorder and 19% for unipolar disorder. Adoption studies have shown that the biological children of affected parents have an increased risk for developing a mood disorder, even when reared by unaffected parents, although the data are not uniform. Finally, first-degree biological relatives of bipolar I patients have elevated rates of bipolar I disorder (4-20%), bipolar II disorder (1-5%), and major depressive disorder (4-24%).

Clinical Findings

Signs & Symptoms: Bipolar disorders can be subdivided into two diagnostic entities: Bipolar I disorder (recurrent major depressive episodes with manic episodes) and Bipolar II disorder (recurrent major depressive episodes with hypomanic episodes). The symptoms of both bipolar disorders involve changes in mood, cognition, and behavior.
1. Bipolar I disorder- Episodes typically begin suddenly, with a rapid escalation through the stages summarized in Table 21-19. In 50-60% of cases, a depressive episode immediately precedes or follows a manic episode. Pure (or monopolar) mania is very rare. The hallmark of a manic episode is abnormally and persistently elevated, expansive, or irritable mood. The elevated mood can be described as euphoric, cheerful, and with indiscriminate enthusiasm and optimism; therefore, others often perceive it as infectious. Although the patient's mood may be predominantly elevated, it may quickly become irritable, especially after demands are not satisfied.

(a.) Somatic features - Bipolar patients' sleep varies with their clinical state. When depressed, bipolar patients may sleep too much; when manic, they sleep little or not at all and typically report feeling fully rested nevertheless. As the manic episode intensifies, patients may go without sleep for nights, their insomnia further intensifying the manic syndrome. There is speculation as to whether the insomnia precedes, and perhaps triggers or fuels, the manic episode. It is difficult to control an acute manic episode clinically if one cannot control the associated insomnia. Conversely, some bipolar patients may experience a manic or hypomanic episode after a single night of sleep deprivation.

(b.) Behavioral features - Patients are initially social, outgoing, self-confident, and talkative and can be difficult to interrupt. Their speech is full of puns, jokes, and irrelevancies. Patients are often hypersexual, promiscuous, disinhibited, and seductive; they may present to an emergency room setting dressed in colorful, flamboyant, and inappropriate clothing. As the manic episode intensifies, their speech becomes loud, intrusive, rapid, and difficult to follow, and they can become irritable, assaultive, and threatening.

(c.) Cognitive features - Manic patients are easily distracted. Their thought processes are difficult to follow because of racing thoughts and flight of ideas. They appear to have an unrestrained and accelerated flow of thoughts and ideas, which are often unrelated. Patients can be overly self-confident and become preoccupied with political, personal, religious, and sexual themes. They may exhibit an inappropriate increase in self-esteem and open grandiosity. Their judgment is impaired significantly, resulting in buying sprees, sexual indiscretions, and unwise business investments. Psychotic features such as paranoia, delusions, and hallucinations are often present, not unlike those seen in patients with schizophrenia.

(d.) Risk of suicide - Bipolar patients are at a substantial risk for suicide, with a mortality rate 2-3 times higher than the general population. Evidence indicates that lithium maintenance treatment can markedly attenuate the risk of suicide attempts and completions. When 16,800 bipolar patients were followed for a 2-year period, the annual risk of suicide or suicide attempts was 0.26 ±0.4 with lithium and 1.68 ±1.5 without lithium. Risk factors for suicide among bipolar patients include previous suicide attempts, comorbid substance abuse, mixed episode, current depressive episode, and a history of rapid-cycling bipolar disorder.

2. Bipolar II disorder- Characterized by recurrent episodes of major depression and hypomania, bipolar II disorder has been identified as a distinct disorder only in DSM-IV. Hypomanic symptoms are similar to manic symptoms but typically do not reach the same level of symptom severity or social impairment (ie, the patient's capacity to function vocationally is seldom compromised). Hypomania, though associated with, say, elated mood and increased self-assuredness, does not usually present with psychotic symptoms, racing thoughts, or marked psychomotor agitation. Hypomanic patients thus do not perceive themselves as being ill and are likely to minimize their symptoms and to resist treatment.

3. Rapid-cycling bipolar disorder- By definition, patients with rapid-cycling bipolar disorder experience four or more affective episodes per year. Approximately 10-15% of bipolar patients experience rapid cycling. Although similar to other bipolar patients nosologically and demographically, patients with rapid-cycling bipolar disorder tend to have a longer duration of illness, and the illness has a more refractory course. Women are represented disproportionately, making up 80-95% of rapid-cycling patients, compared to about 50% of non-rapid-cycling patients. A variety of factors may predispose bipolar illness to a rapid-cycling course, including treatment with TCAs, MAOIs, lithium, and antipsychotics. The development of clinical or subclinical hypothyroidism (spontaneously or during lithium treatment) in a manic patient predisposes to a more rapidly cycling course. The kindling hypothesis, invoked to conceptualize these changes pathophysiologically, receives further confirmation by the clinical usefulness of the anticonvulsants valproic acid and carbamazepine.

Laboratory Findings & Imaging

No laboratory findings are diagnostic of a bipolar disorder or of a manic or hypomanic episode; however, several laboratory findings have been noted to be abnormal in groups of individuals with bipolar disorder. Compared to the wealth of findings in major depressive disorder, research findings in bipolar disorder are in general scarce and inconclusive. For one thing, bipolar disorder is not as common as major depressive disorder. Beyond that, patients with acute manic states are not as likely to collaborate in research studies; they experience lack of insight, agitation, irritability, and racing thoughts, among other symptoms; and they are normally in need of rapid containment of symptoms.

1. Hypothalamic-pituitary-adrenal axis - The few available cross-sectional and longitudinal studies reveal increased plasma cortisol levels in some depressed bipolar patients. Abnormalities in the DST have also been noted. DST nonsuppression occurs more frequently in the mixed phase of the illness (78%) but also occurs in bipolar depression (38%) and mania (49%). Both hypercortisolemia and DST results normalize after the acute episode subsides, suggesting that these abnormalities are state and not trait dependent. Although these abnormalities are not specific for bipolar disorder or even major depression, their pathophysiology is suggestive of central (ie, hypothalamic) rather than peripheral dysregulation of cortisol.

2. Hypothalamic-pituitary-thyroid axis - HPT axis abnormalities are rather common in bipolar disorder, especially in rapid-cycling bipolar disorder, but the precise relationship of these abnormalities with the illness and its various clinical presentations is not known. Among these abnormalities are an attenuated nocturnal TSH peak, a blunted TSH response to TRH administration, and a high prevalence of various degrees of hypothyroidism.

There are intriguing associations among thyroid function, bipolar disorder, and gender. Hypothyroidism is very common in patients with bipolar disorder; it is especially common in female patients who present with a rapid-cycling course. Treatment with hypermetabolic doses of T4 has shown some promise in that it may reduce acute symptoms, number of relapses, and duration of hospitalizations.

Two main conclusions can be drawn from these observations. Clinically, comorbid hypothyroidism seems to negatively affect disease outcome by predisposing the individual patient to a rapid-cycling course. Substitution with T4 has proven useful in some patients, but often high doses are necessary to induce clinical response. Conceptually these findings support the hypothesis that a relative central thyroid hormone deficit may predispose to the marked and frequent mood swings that characterize rapid-cycling bipolar disorder. We may ask whether the central thyroid hormone deficit serves only as a risk factor for the development of rapid cycling in a known bipolar patient, or whether it can predispose most affectively ill patients to any major behavioral change (ie, the switch from depression into recovery, from recovery into depression, or from depression into mania).

3. Sleep electroencephalogram- Sleep EEG recordings have revealed normal results in acutely ill bipolar patients, including normal REM latencies, but not all studies agree. These data, of course, are in stark contrast to those reported in major depressive disorder, in which shortened REM latencies are common. However, bipolar patients in full clinical remission can exhibit an increased density and percentage of REM and a sleep architecture more sensitive to arecoline (an acetylcholine agonist known to produce a shortened REM latency). The discrepancies between unipolar and bipolar patients are thought to be the result of different levels of clinical severity, variable proportions of bipolar I and bipolar II patients, and age differences.

4. Brain imaging- Patients with right (ie, nondominant) frontotemporal or left (ie, dominant) parieto-occipital lesions are especially vulnerable to mania or hypomania. These observations are consistent with the literature on laterality, which indicates right-sided dysfunction in mania. It is not known whether manic symptoms occurring after such lesions represent a new emergence of mania, or whether the lesions triggered a manic episode in vulnerable individuals.

Differential Diagnosis

Medical Disorders: Numerous medical disorders and medications can induce or mimic the clinical picture of bipolar disorder, exacerbate its course and severity, or complicate its treatment. It has been widely noted that psychopharmacologic interventions are less successful if the bipolar disorder is due to a primary medical condition; whenever possible, it is advisable to attempt to correct the underlying medical disorder before beginning psychopharmacologic treatment.

DSM-IV criteria specify that to make a diagnosis of bipolar disorder, the symptoms cannot be the direct result of a substance or a general medical condition. A late onset of the first manic episode (over age 50) should prompt the clinician to carefully exclude a possible medical cause.

Psychiatric Disorders: The Axis I and Axis II disorders associated with hypomanic or manic symptoms need to be included in the differential diagnosis of bipolar disorders (Table 21-21). First, the psychotic features associated with schizophrenia or schizoaffective disorder are often indistinguishable from those associated with acute mania. Second, major depressive episodes may be associated prominently with irritable mood and may thus be difficult to distinguish from a mixed bipolar episode. Third, in children and adolescents, ADHD and mania are both characterized by overactivity, impulsive behavior, poor judgment and academic performance, and psychological denial. Fourth, patients with certain personality disorders (eg, borderline or histrionic personality disorders) can exhibit impulsivity, affective instability, and paranoid ideations, as do manic patients.

Finally, substance abuse is exceedingly common in patients with bipolar disorder. As many as 41% of bipolar patients abuse or are dependent on drugs, 46% abuse or are dependent on alcohol, and as many as 61% abuse or are dependent on any substance. Careful etiologic evaluation, and a drug-free washout period after intoxication, are often necessary to distinguish whether the mood disturbance is the consequence of substance abuse or whether the substance abuse is the consequence of a mood disturbance. Such differentiation is important because psychiatric comorbidity complicates the acute manic state and negatively affects disease outcome. The mood disorders complicated by substance abuse are therefore treated in units especially designed to treat aspects of dual diagnosis.

(Source: Ebert, Loosen, Nurcombe)