Bipolar I disorder

Bipolar I disorder is the classic manic-depressive psychosis in which episodes of mania and depression occur, usually at well-spaced intervals.

Bipolar II disorder

Bipolar II disorder was introduced as a sub-type of bipolar disorder to include the group of patients who experience recurrent depressive and hypomanic, but not manic, episodes (Reference Dunner, Gershon and GoodwinDunner et al, 1970; Reference AngstAngst, 1978). As a diagnostic category, bipolar II disorder appears robust, with a typically stable symptom profile, differences in out-come from bipolar I disorder and a tendency to ‘breed true’ (Reference Gershon, Hamovit and GuroffGershon et al, 1982; Coryell et al, Reference Coryell, Endicott and Reich1984, Reference Coryell, Andreasen and Endicott1987, Reference Coryell, Keller and Endicott1989, Reference Coryell, Endicott and Maser1995; Reference Endicott, Nee and AndreasenEndicott et al, 1985; Reference DunnerDunner, 1993). Differences have been found between bipolar I and II disorders on magnetic resonance imaging (MRI) scanning and on the presence of vascular abnormalities, including Raynaud's phenomenon, migraine and ‘migraine equivalents’ (Reference Endicott and ChaninEndicott, 1984; Reference Altshuler, Curran and HauserAltshuler et al, 1995). Lithium discontinuation studies have also demonstrated differences between the two conditions (Reference Faedda, Tondo and BaldessariniFaedda et al, 1993). The defining factor for bipolar II disorder is the presence of hypomania but not mania, and difficulties in definition of hypomanic symptoms may have led to heterogeneity in assessed samples (Reference Winokur, Coryell and KellerWinokur et al, 1993; Reference CoryellCoryell, 1996). These problems have been partially resolved with the introduction of DSM-IV (American Psychiatric Association, 1994) criteria for bipolar II disorder, although the exclusion of anti-depressant-induced hypomania and the duration of hypomanic symptoms needed to reach diagnostic criteria for an episode have been questioned (Reference AkiskalAkiskal, 1996).

Bipolar III disorder

Bipolar III disorder (pseudo-unipolar bipolar disorder) refers to a more heterogeneous grouping of people who experience recurrent episodes of unipolar depression and also show clinical features suggesting that they may go on to develop a hypomanic or manic episode. Such people may have a family history of bipolar disorder, exhibit antidepressant-induced hypomanic switching, or have hyperthymic, dysthymic or cyclothymic premorbid temperaments (Reference Cassano, Musetti and PerugiCassano et al, 1988; Reference AkiskalAkiskal, 1996).

False unipolar disorder

The term ‘false unipolar’ is applied to recurrent depressions originally classified as unipolar, but with the subsequent development of mania or hypomania requiring reclassification as bipolar. The proportion of ‘false unipolars’ in the diagnosis of unipolar depressive disorder has been estimated at between 10.7% and 28.4% (Reference Goodwin and JamisonGoodwin & Jamison, 1990).

Sub-syndromal bipolar disorders

Hyperthymia, dysthymia and cyclothymia have been described as long-term components of personality — persistent temperamental dysregulations — which may later give rise to episodes of mood disorder (Reference Kukopulos, Caliari and TundoKukopulos et al, 1983; Reference AkiskalAkiskal, 1996; Reference Akiskal and CassanoAkiskal & Cassono, 1997). Cyclothymia is characterised by switches between two poles of mood and behaviour: one phenomenologically similar to bipolar depression, atypical depression and dysthymia, with hypersomnia, hyperphagia, lethargy and tearfulness; and the other characterised by decreased sleep, increased energy and jocularity. Hyperthymia resembles the ‘upper’ of these poles, perhaps with occasional spells of dysthymia, while dysthymia resembles the ‘lower’ pole and may be accompanied by a major depressive episode (double depression), or hypomania following a major depressive episode (Reference Keller, Lavori and EndicottKeller et al, 1983; Reference Klein, Taylor and HardingKlein et al, 1988).

Epidemiology

The life-time prevalence rates of both bipolar I and bipolar II disorders have been estimated at 0.6%, giving a combined figure of 1.2% (Reference Weissman and MyersWeissman & Myers, 1978). The combined prevalence of bipolar II, bipolar III and dysthymic disorders has been estimated at 7.8-12% (Reference Depue, Slater and Wolfstetter-KauschDepue et al, 1981).

Cycle frequency

Cycle frequency of mood variation in bipolar disorder varies in a range from illness-free spells of many years' duration, with apparent peaks at multiples of 1 year, to mood variations of an extreme form occurring over the course of hours or minutes (Reference Goodwin and JamisonGoodwin & Jamison, 1990). A sub-classification has been developed, determined by the cycle frequency of mood variation within the course of the condition: rapid cycling, ultrarapid cycling, ultra-ultrarapid (ultradian) cycling, mixed states and continuous cycling. ‘Normal cycling’ has not been defined. Rapid cycling has been defined as the occurrence of four or more episodes of significant mood disturbance in a year. Ultrarapid cycling involves cycle frequencies in the range of weeks to days, and ultradian cycling involves significant mood variation within a day (Reference Bauer, Calabrese and DunnerBauer et al, 1994). Mixed states may be seen either as coexisting depressive and (hypo)manic symptoms or as an extreme of rapid cycling. Continuous cycling refers to the absence of illness-free spells between episodes (Reference Goodwin and JamisonGoodwin & Jamison, 1990).

Antidepressants and psychoactive substance misuse have been implicated in the development of rapid cycling, which appears to be a complication predominantly of bipolar II disorder (Reference Wehr and GoodwinWehr & Goodwin, 1979; Reference Kukopulos, Reginaldi and LaddomadaKukopulos et al, 1980; Reference Bauer, Calabrese and DunnerBauer et al, 1994). Other organic factors, including seizure threshold abnormalities and thyroid dysfunction, may relate to the development of accelerated mood cycles. Rapid cycling is associated with a high risk of suicide (Reference Fawcett, Scheeftner and ClarkFawcett et al, 1987). The origins and treatment of rapid cycling have recently been reviewed (Reference Ahmed and MorrissAhmed & Morriss, 1997). Mixed affective states, in which depressive and (hypo)manic symptoms either alternate so rapidly that they may become indistinguishable, or coexist, are increasingly recognised. The DSM-IV classification includes non-induced mixed states with bipolar I disorder. Rapid cycling, commonly induced by pharmacological agents in bipolar II disorder, may be confused with mixed states and lead to misclassification. Mixed states have implications for treatment, with even a modest degree of depressive symptomatology present during a manic episode indicating a greater chance of response to an anticonvulsant agent than to lithium (Reference Calabrese and DelucchiCalabrese & Delucchi, 1990; Reference Swann, Bowden and MorrisSwann et al, 1997).

Relationship between subtypes

Although bipolar I and II disorders appeared to be diagnostically stable over a 10-year follow-up period (Reference Coryell, Endicott and MaserCoryell et al, 1995), with only 5% of bipolar II ‘converting’ to bipolar I, there is more interaction between the ‘soft bipolar’ conditions, which include bipolar II and III, and the temperamental variants, cyclothymia, hyperthymia and dysthymia. Few (6%) people with cyclothymia switch to bipolar I disorder, but 25% switch to bipolar II (Reference Akiskal, Djenderedjian and RosenthalAkiskal et al, 1977).

Prospective follow-up of patients with apparently unipolar depression demonstrated a 20% switching rate into bipolarity, although some of this high figure may be the result of ascertainment bias. The clearest markers for this switching are the presence of antidepressant-induced hypomanic episodes, onset in young adulthood, hypersomnia, retardation, family history and post-partum episodes (Reference Strober and CarlsonStrober & Carlson, 1982; Reference Akiskal, Walker and PuzantianAkiskal et al, 1983).

Another study of the rate of conversion from apparent unipolarity to bipolarity revealed rates of 8.6% conversion to bipolar II and 3.9% to bipolar I. Patients converting to bipolar II disorder had a more protracted course of illness and demonstrated temperamental instability, with mood lability the most specific (86%) although least sensitive (42%) predictor of switching (Reference Akiskal, Maser and ZellerAkiskal et al, 1995).

Sub-syndromal bipolarity appears to become apparent at a mean age of 14 years, while the initial episode of bipolar I disorder occurs at a median age of 18 years and bipolar II disorder at a median age of 21 years (Reference Depue, Slater and Wolfstetter-KauschDepue et al, 1981; Reference Goodwin and JamisonGoodwin & Jamison, 1990).

Comorbidity

An important, potentially confounding variable is the high rate of comorbid substance misuse in bipolar disorder, as high as 50% in cyclothymia and 46% in bipolar I disorder in the Epidemiologic Catchment Area study (Reference Goodwin and JamisonGoodwin & Jamison, 1990). Women with bipolar II disorder are more likely to drink alcohol to excess (12%) than those with bipolar I disorder (0%). Men with bipolar I and II disorders have equal likelihoods of problems with alcohol, at rates of 19% and 20% respectively (Reference Dunner, Hensel and FieveDunner et al, 1979; Reference Hensel, Dunner and FieveHensel et al, 1979). People with bipolar disorder may have a particular sensitivity to mood-altering agents. It has been suggested that the high rate of substance misuse represents either attempted self-medication or a character trait that may predispose people to developing bipolar disorder (Reference Goodwin and JamisonGoodwin & Jamison, 1990; Reference Winokur, Coryell and AkiskalWinokur et al, 1994; Reference AkiskalAkiskal, 1996).

Birth season effects

People with bipolar disorder appear to show an excess of spring and winter births. This finding appears consistent and may suggest a causal mechanism (Reference Moore, Shepherd and AshtonMoore et al, 1996; Reference Torrey, Rawlings and EnnisTorrey et al, 1996), or may be the result of parental bipolarity leading to increased activity the preceding summer.

Organic and neuropsychological issues

The view that patients with bipolar disorder make a full recovery between episodes of illness has been widely accepted despite a lack of systematic investigation. Neuropsychological impairment has been identified in depression and mania (Reference Wolfe, Granholm and ButtersWolfe et al, 1987; Reference Sackheim, Steif, Georgatos and CancroSackheim & Steif, 1988) but has always been thought to be entirely a state effect. Imaging studies have shown the presence of patchy white matter lesions (PWMLs) in the brains of patients with bipolar disorder, particularly those with poor outcome (Reference VidebechVidebech, 1997). Such lesions may be associated with neuropsychological impairment (particularly of executive function) in healthy elderly subjects and in patients with unipolar depression or bipolar disorder (Reference DeCarli, Murphy and TranhDeCarli et al, 1995; Reference Dupont, Jernigan and HeindelDupont et al, 1995; Reference Lesser, Boone and MehringerLesser et al, 1996). It has been suggested that cognitive deficits in bipolar disorder may persist after clinical recovery (Reference Trichard, Martinot and AlagilleTrichard et al, 1995) or in states of remission (Reference Coffman, Bornstein and OlsonCoffman et al, 1990; Reference MoriceMorice, 1990). Direct evidence of impairment, particularly in frontal executive function, has been found in euthymic bipolar I disorder (Reference van Gorp, Altshuler and Thebergevan Gorp et al, 1998; Reference Ferrier, Stanton and KellyFerrier et al, 1999). Furthermore, there is evidence that such impairment may precede the onset of illness (Reference Gourovitch, Torrey and GoldGourovitch et al, 1999; Reference Sigurdsson, Fombonne and SayalSigurdsson et al, 1999) and may be worsened by illness progression (Reference KessingKessing, 1998; Reference van Gorp, Altshuler and Thebergevan Gorp et al, 1998).

Evidence has accumulated that some patients with bipolar disorder have structural changes in the brain such as smaller temporal lobes or caudate nuclei on MRI (Reference Elkis, Friedman and WiseElkis et al, 1995; Reference VidebechVidebech, 1997). Not all patients show these abnormalities, which tend to be more frequent with increasing age, although they may be found in younger patients. The pathological basis of these abnormalities and of the PWMLs found in excess in bipolar disorder (Reference Altshuler, Curran and HauserAltshuler et al, 1995; Reference VidebechVidebech, 1997) is unknown. Measurements of brain metabolism by positron emission tomography (PET) show a hypofrontal pattern of metabolic activity in bipolar disorder which persists despite improvements in the patient's clinical state (Reference Martinot, Hardy and FelineMartinot et al, 1990). A study by Drevets et al (Reference Drevets, Price and Simpson1997) showed reduced blood flow in the subgenual area deep in the prefrontal cortex in both bipolar and unipolar depression. The decrease in blood flow appeared to be partly accounted for by a reduction in cortical volume, which was observed in both symptomatic patients and those in remission.