DSM-5 Category: Bipolar and Related Disorders
Introduction
Extremes of mood have been recognized since Greek antiquity. “Melancholy” was named for the “black (melas) bile (chole)” that Hippocrates thought was responsible for low mood. “Mania” may derive from mainesthai (to rage). “Depression” was coined later by Roman physicians, from the Latin depremire (to press down). The alternation of mania and melancholy was described in the 1st Century AD by Aretaeus of Cappadocia, who also described migraine. Jules Baillarger identified folie á double forme (dual-form insanity) in the 19th Century, and Jean-Pierre Falret observed the clustering in affected families of alternating mania and depression (folie circulaire). At the turn of the 20th Century, Emil Kraepelin distinguished this illness from schizophrenia (dementia praecox) and termed it “manic-depressive psychosis” (Burton, 2012).
What by the 1950s was called Manic-Depressive Illness has now been elaborated into a spectrum of Bipolar Disorder. The new nomenclature derives from the fundamental characteristic of these illnesses, that patients have periods of mania (elevated or agitated mood) in alternation with major depression, as well as the great variability in clinical features and course that has been recognized. Patients may also have hypomania (less severe mood elevation or agitation) and depression that is less severe than the “major” variety. Bipolar affective disorders are classified as Type I (one or more manic episodes, with or without depression or hypomania), Type II (one or more depressive episodes with at least one episode of hypomania), and Cyclothymic (hypomania alternating with non-major depression) disorders. Previous editions of the Diagnostic and Statistical Manual of Mental Disorders additionally recognized the catchall category of “Bipolar Disorder NOS (not otherwise specified)” for manic-depressive illness that did not fit into the other categories (American Psychiatric Association, 2000).
The new edition of the manual (DSM-5) has eliminated the “NOS” categories for incompletely-characterized psychiatric disorders, and allows clinicians in such cases to either identify the reason(s) that criteria for a particular disorder are not met (“other specified disorder”) or forgo specification if information is not available (“unspecified disorder”) (American Psychiatric Association, 2013). DSM-5 changes for the bipolar disorders simplify the characterization of mood episodes in which manic and depressive features alternate (“mixed features”) and recognize the importance of anxiety as an aggravating factor in mania and depression (“anxious distress”), even though anxiety is not part of bipolar disorder diagnostic criteria.
Symptoms of Bipolar I Disorder
The defining feature of bipolar disorder generally, and of Type I particularly, is mania. It represents a distinct period of elevated or irritable mood, lasting for at least a week. Patients may be euphoric, grandiose, anxious, or irritable and even enraged. Increased energy, decreased need for sleep, increased sexual drive and decreased attention span are frequent, along with racing thoughts and pressured speech, impaired judgement and risky or inappropriate behavior, substance abuse and impulsive behavior such as spending sprees. Severe mania may result in psychosis, with delusions and thought disorder as well as mood disorder, but not hallucinations. Manic episodes are preceded by changes in activity, appetite and sleep, and sometimes by anxiety, for up to 3 weeks (Mansell & Pedley, 2008).
Depressive symptoms are similar to those of major depression, except that major depression persists for more than 2 weeks and the depressive episodes of bipolar disorder may not. Severe depression may progress to psychosis, and this may be accompanied by hallucinations as well as delusions. The initial mood episodes of bipolar disorders tend to be depressive in younger patients, and the onset of bipolar depression may be mistaken for major depression (Muzina et al., 2007). Hypomania involves mild-to-moderate mood elevation, often with optimism rather than grandiosity, slight pressure of speech, increased activity level and decreased need for sleep. Hypersexuality may be present, but not delusions or hallucinations. Many hypomanic patients feel good, have increased energy and are more productive, while patients with mania are often irritable and less productive due to inattention (Angst & Sellaro, 2000). Mixed episodes are increasingly recognized, and can be problematic and even dangerous, These episodes combine manic and depressive features, and suicide attempts, substance abuse and unpredictable behavior are increased in likelihood in these periods (Goldman, 1999).
Diagnostic Criteria
Bipolar I disorder is characterized by at least one episode of mania or mixed depressive and manic symptoms. The symptoms must cause social or occupational distress or impairment, and cannot be better accounted for by schizoaffective disorder. The manic or mixed episodes must not be superimposed on schizoaffective disorder, schizophrenia, delusional disorder or other psychotic condition. Manic episodes are characterized by elevated, expansive or irritable mood and increased energy and activity, which last for a week or more, accompanied by 3 of the following (4 if the mood is irritable): grandiosity or inflated self-esteem, decreased need for sleep, increased talkativeness, racing thoughts or flight of ideas, distractibility, psychom*otor agitation or increased goal-directed behavior, or increased risky behavior. These symptoms must be severe enough to cause occupational or social impairment, hospitalization or psychosis, and may not be due to substance use or a medical condition. Mixed episodes involve mania or hypomania with at least 3 depressive symptoms occurring concurrently nearly every day: subjective depression, guilt or self-reproach, worry, negative self-evaluation, hopelessness, anhedonia, fatigue, psychom*otor retardation or suicidal thought or behavior (American Psychiatric Association, 2013).
DSM5 changes with respect to bipolar I disorder involve recognition that manic and hypomanic episodes involve increased energy and activity, not just elevated mood. The diagnosis of mixed episodes previously required that the patient meet criteria for both mania and major depressive episode; the new specifier “with mixed episodes” includes both manic and hypomanic episodes when features of major depression are present and episodes of depression when features of mania and hypomania are present. Since anxiety frequently aggravates the severity of the bipolar disorders, a new specifier for “anxious distress” allows the identification of patients whose manic episodes or periods of mixed mania and depression are complicated by severe anxiety.
Epidemiology
The lifetime prevalence of bipolar I disorder is approximately 2 per cent (Soldani et al., 2005). Men and women are about equally affected and prevalence and incidence of the bipolar disorders are about the same throughout the world, but disability may be greater in developing countries (Ayuso-Mateos, 2006). In the United States, blacks and whites are equally affected, while Asians have lower rates of bipolar disorder (Kurasaki, 2002). The peak incidence is in late adolescence, but mania begins after age 50 in approximately 10 per cent of cases (Goodwin, 2007). Approximately 50 per cent of those hospitalized for first-episode mania or hypomania achieve syndromic recovery in 6 weeks, and 98 per cent no longer meet diagnostic criteria after 2 years. Forty per cent had a recurrent episode within 2 years after recovery, and 19 per cent switched from mania to depression or vice versa without recovery (Tohen et al., 2003). Suicide is a source of mortality: 1/3 of bipolar patients reported past suicide attempts or were successful, and the suicide rate is 0.4 per cent annually, which is 10 to 20 times that of the general population (Novick et al., 2010).
Pathophysiology
A familial tendency toward all bipolar disorders has been noted since the 19th Century. Twin studies suggest that the concordance rate for bipolar I in monozygotic twins with the same genes is about 40 per cent, versus 10 to 20 per cent in genetically-distinct dizygotic twins (Kieseppa et al., 2004). If type II and cyclothymic disorders are included, the overall heritability is about 0.71 (Edvardsen et al., 2008). There have been suggestions of responsible genetic loci on chromosomes 6q and 8q21, but a specific gene or genes has not been identified, suggesting that different genes are involved in different families (Kato, 2007).
MRI studies have suggested increased volume of thee lateral ventricles and globus pallidus, along with hyperintensities in deep white matter (Kempton et al., 2008). Functional MRI findings suggest that the limbic system, especially the amygdale, and ventral prefrontal cortex may be deficient in modulating mood and emotions (Strakowski, 2012). Mostly nonspecific and rarely epileptiform EEG abnormalities are reported in bipolar disorder, especially with rapid cycling between mania and depression or negative family history of affective disorder (Shelley et al., 2008). Computer-assisted quantitative EEG has shown increased slow activity and left temporal asymmetry in nonresponders to therapy (Small et al., 1999). . Neuropsychological assessments have shown widespread cognitive abnormalities in symptomatic patients, and deficits in verbal memory and sustained attention in between episodes. (Quraishi & Frangou, 2002).
Dopamine is generally believed to play a prominent role in manic and depressive symptoms, with an increase during manic periods causing homeostatic down-regulation of dopamine receptors. This results in decreased dopaminergic transmission during a depressive episode, and homeostatic up-regulation eventually restarts the cycle (Berk et al., 2007). It has been suggested (the “kindling” hypothesis) that environmental stresses in susceptible individuals initiate this cycle but the threshold for its activation becomes lower and lower, until at length spontaneous cycling occurs (Post, 1992). Glutamate also causes elevated mood, and is increased in dorsolateral prefrontal cortex during mania but returns to normal when the manic phase is over (Michael et al., 2003).. Gamma-amino-butyric acid (GABA) causes mood elevation, and is higher in concentration in bipolar disorder (Brady et al., 2013). The hypothalamic-pituitary-adrenal axis may also be involved in an abnormal cyclical response to stressors, with cortisol increased in both manic and depressive episodes (Watson et al., 2004).
There is also a suggestion that manic episodes may have evolutionary value, accounting for the preservation of genes for bipolar disorder that might be expected to be selected against on account of the functional impairment and mortality of mixed depression and mania. Hypomanic or mild manic episodes can increase productivity and creativity, while depressive episodes may facilitate withdrawal, sleep and conservation of resources at times of adversity. This has been suggested to have operated in the extremely cold climate of the northern temperate zone during the Pleistocene age: manic hyperactivity facilitated the completion during a short summer of the tasks necessary for survival through a long winter, during which depressive hypersomnia and decreased appetite would be adaptive (Sherman, 2012).
Treatment of Bipolar I Disorder
Pharmacological treatment of the bipolar disorders, and particularly type I, focuses on mood stabilizers, which prevent the emergence of manic and depressive episodes. Maintenance therapy is generally required after acute episodes have resolved. It is important to distinguish bipolar disorders from major depression, as antidepressants can cause the emergence of mania in the former; this is a particular problem in bipolar I disorder, and the use of antidepressants is not recommended in type I disorder, although they have some place in the treatment of refractory type II disorder as an adjunct to lithium.
Mood stabilizers include lithium salts, anticonvulsants, and antipsychotics, usually the atypical or second-generation ones. Lithium was inadvertently used in antiquity, as mentally ill patients were often sent to drink from alkaline springs, the water of which was high in lithium salts. It has been used in modern treatment since 1949, and is effective for the prevention of manic episodes and reduction of suicide risk, less clearly so for prevention of depression. It may work by inhibiting inositol monophosphatase, a key enzyme in a neuronal signaling pathway that is hyperactive in bipolar disorder. There is a narrow therapeutic range, and adverse effects include gastrointestinal upset, sedation, tremor, incoordination, hair loss, excessive thirst and the development of hypothyroidism (Stahl, 2008).
The rationale for anticonvulsants, which in various ways stabilize neuronal membranes, is the “kindling” theory, in which manic episodes lower the threshold for subsequent manic episodes as may be seen with seizures. Carbamazepine was the first to be studied, and prevents the appearance of mania, less clearly depression. Blurred vision, diplopia, ataxia, sedation, weight gain and nausea, as well as rare blood dyscrasias and liver damage, have made it a second-line drug (Ceron-Litvoc, 2009). Valproic acid was also studied early, and is effective for acute mania but less so as an antimanic or antidepressant agent. Gastric upset and sedation are lessened by the use of enteric-coated divalproex (Depakote), but weight gain, tremor and virilization in girls and polycystic ovarian syndrome in women need to be watched for (Kessing et al., 2011). Lamotrigine is effective for preventing depressive episodes without triggering mania and will prevent manic or mixed episodes, but may not be effective for treating current mood symptoms. The dose must be slowly increased to avoid rashes or exfoliative dermatitis (Goldberg et al., 2009). Topiramate is also approved for bipolar treatment and may cause weight loss rather than weight gain; sedation, slowed speech and cognition, loss of sweating, acute myopia and glaucoma, kidney stones and interference with oral contraceptives plus teratogenic potential are the main adverse effects (Amone, 2005).
Atypical antipsychotics affect dopamine and serotonin pathways, but may stabilize bipolar disorders through an effect on glutamate. Aripiperazole is FDA- approved for treatment of manic and mixed episodes and for maintenance therapy. Olanzapine is also approved for these uses, and for depressive episodes in combination with fluoxetine. Quetiapine is approved for manic and depressive episodes but not for maintenance treatment, and risperidone for prevention of manic and mixed episodes only. Ziprasidone is approved for mania. The typical (first-generation) antipsychotics, particularly haloperidol and chlorpromazine, are useful for mania, but have the concern of dyskinesias with long-term use. Extrapyramidal effects are much less with the atypical agents, but sedation, weight gain and metabolic syndrome are long-term concerns (Derry, 2007).
Psychotherapy of several types has been shown to be helpful. Family therapy improves communication, compliance with therapy and social function, apparently more in women than in men. Cognitive behavioral therapy finds modest support in several studies. Psychoeducation was shown to diminish lapses in compliance with lithium therapy. Interpersonal psychotherapy and social rhythm therapy were not effective for bipolar disorder in controlled studies (Goodnick, 2002).
The manic and depressive episodes of bipolar disorder have been likened to the Jungian archetypes of “puer” and “senex”. “Puer”, characterized by enthusiasm, spontaneity and impulsiveness, has been analogized to mania or hypomania, while “senex” manifests orderly and cautious thought and behavior with sober mood and is analogized to depression. A series of archetypal subcategories have been proposed, invoking Hermes (hypomania), Icarus (mania), Saturn (melancholy) and Kronos (major depression). Jungian psychotherapy aims to establish a transcendant function that reintegrates the two archetypal polarities (Thompson, 2014).
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