Despite the vagaries of epidemiology and the interpretation of various rates, it is useful to spend a moment reflecting on what constitute the "outer edges" of bipolar disorder. Kraepelin (1921) and Kretschmer (1936) both described affective states which ranged from the severest to the mildest and which existed on a continuum that included personal predisposition or temperament. Both described cyclothymic people in whom low-grade subdepressive and hypomanic presentations occurred.
Some people with cyclothymia exhibit depressive or irritable moodiness, while, in others, trait hypomanic features (hyperthymic temperament) predominate. These characteristics can be present throughout life but never progress to major episodes of affective illness. Or they can herald predisposing or prodromal of more severe episodes. Upon recovery, patients customarily return to baseline temperament.
Some large-scale studies have investigated cyclothymia. These studies differ from more typical epidemiology in that they concentrate on student or clinical populations.
Akiskal et al. (1977) at the University of Tennessee (USA) reported that just less than 10% of the mental health clinic conformed to subsyndromal mood changes over extended periods of time. Placidi et al. (1998) in Italy found subthreshold variation between hypomanic and subdepressive periods occurring in 6.3% of the population. It should be remembered, however, that these two studies employed operationalized criteria developed at the University of Tennessee by Akiskal et al., a group which favour the broadening of bipolar criteria. Nevertheless, all of these studies tend to show very similar levels of "bipolar diathesis".
One of the difficulties of this area of research is the separation on the continuum between personality disorder features and the point at which symptoms become disorder in terms of bipolar disorder rather than abnormalities of personality or temperament. An awareness of boundaries is important, as personality tests in common use have been known to misattribute subthreshold mood changes to borderline personality disorder (O'Connell et al., 1991).
There is also a very real clinical problem in separating hypomania from mania by the criteria laid down in DSM-IV (1994). One point of contention focuses on the length of time during which the symptoms must be present. Those studies validating a shorter than 4-day duration for hypomania were all conducted before the availability of DSM-IV. For example, a study by Wicki and Angst (1991) found a modal duration of 1-3 days.
Cassano et al. (1992), who used a definition of 2 days in a study of bipolar II disorder, found that these patients had rates of bipolar family history statistically indistinguishable from that of bipolar I disorder—both of which were significantly higher than that of major depressive disorders.
The most common manifestations of hypomania in a community study (Angst, 1998) were the following:
• more energy and strength
• more self-confidence
• increased activities (including working more)
• enjoying work more than usual
• more social activities
• spending too much money
• more plans and ideas
• less shy and inhibited
• more talkative than usual
• increased sex drive
• increased consumption of coffee, cigarettes, and alcohol
• overly optimistic
• increased laughter
• thinking fast/sudden ideas.
In a recent editorial commentary, Goodwin (2002) clearly described the difficulties surrounding the contemporary use of the two descriptors, mania and hypomania. The outstanding issue remains of where the boundary falls between hypomania and mania, and between hypomania and normality. DSM-IV defines both hypomania and cyclothymia as milder conditions than does ICD-10.
The boundary between hypomania and mania pivots on a definition of functional disturbance that is different between DSM-IV and ICD-10 but is dependent upon qualifications such as "severe" and "marked" whose meaning is open to interpretation. Goodwin (2002) argues that DSM-IV splits mania from hypomania in a clinically significant way. The community cohort study carried out by Angst (1998) exerts a major influence in terms of lifetime prevalence estimates. This study found DSM-IV diagnoses of mania and hypo-mania in 5.5% of the population. But extending the boundaries resulted in the inclusion of a further 14.1% of the population. The Angst study also revealed a population rate of bipolar I of 0.5% and of bipolar II of 3%.
Although the inclusion or exclusion of bipolar spectrum disorders is the subject of contemporary controversy (Baldessarini, 2000), findings from US studies support those of Angst (Carlson & Kashani, 1988; Lewisohn et al., 1995). Despite the epidemiological and nosological caveats, Goodwin emphasizes that something is being detected that requires explanation and clarification. Moreover, the diagnosis of hypomania is not merely one of abundant good health, and while it may be benign, it often is less so.
The question remains as to whether treatment paradigms specific for bipolar I disorder might be indicated in clinically significant spectrum conditions. As Goodwin concludes, accurate diagnosis has become clinically important for elated states. Moreover, the challenge remains of defining where hypomania ends and individual differences begin. Goodwin states that to make the distinction between hypomania and mania as it is drawn in DSM-IV appears to have important advantages (Goodwin, 2002).
DESCRIPTIONS OF HYPERTHYMIA
Clinically, hyperthymia is regarded as subthreshold, lifelong hypomanic symptoms. Psy-chometrically established traits in hyperthymia are as follows:
• warm, people-seeking, or extroverted
• cheerful, over-optimistic, or exuberant
• uninhibited, stimulus-seeking, or promiscuous
• over-involved and meddlesome
• vigorous, full of plans, improvident, or carried away by restless impulses
• overconfident, self-assured, boastful, bombastic, or grandiose
• articulate and eloquent.
Current data cast an uncertain light on the boundary between hyperthymic temperament and normality (Akiskal et al., 1998), and this temperament may be considered abnormal only in the presence of clinical depression.
A common clinical situation is a patient presenting with a major depressive episode and further examination revealing a history of hypomania. The accuracy of the diagnosis is dependent on the sharpness of the patient's memory, and recall bias can be a significant problem. It can be seen as a problem with state-dependent memory in particular. When high, all previous highs are remembered; when low, only previous depressions are remembered (Kelsoe, personal communication to Akiskal, 31 March 2000).
Bipolar II is a complex diagnosis owing to the reportedly high levels of comorbidity, such as anxiety, bulimia, substance misuse, and personality disorder (Benazi, 1999; Perugi et al., 1998). There is also some evidence that so-called atypical depressions frequently progress to bipolar spectrum disorders (Ebert et al., 1993).
An analysis of the NIMH Collaborative Depression Study on unipolar patients who switched to bipolar II examined 559 patients with unipolar depression at entry during a prospective observation period of 11 years. Of these, 48 converted to bipolar II (Akiskal et al., 1995)—that is, just over 8.5%. It has been suggested that mood lability is a key variable in the cyclothymic temperament and the hallmark of those unipolar patients who switch to bipolar II. However, more systematic evidence is required before this claim can be substantiated. According to Coryell et al. (1995), in those with at least a 5-year history of affective illness, a diagnosis of bipolar II represents a stable condition which rarely progresses to bipolar I.
This is a form of hypomania that manifests itself on treatment with antidepressants. Neither of the major classification systems (ICD-10 and DSM-IV) have accorded bipolar status to these patients. Some authors disagree and regard this as a separate bipolar state, which they call "bipolar III" (Akiskal et al., 2000).
According to standard classification systems (ICD-10 and DMS-IV), those with rapid cycling suffer a minimum of four episodes of illness per year (Maj et al., 1994). The term "alternating" has been advocated as preferable, as many patients have no remission from episodes during a rapid-cycling phase.
There are degrees of cycling severity: rapid (four per year), ultrarapid (four per month), and ultradian (within a day). Coryell et al. (1992) regard rapid cycling as a phase in the illness rather than a distinct subtype. There is no clear indication from current literature on what risk factors exist for rapid cycling. Those highlighted include female gender, cyclothymic temperament, borderline hypothyroidism, and excessive use of antidepressants (Bauer et al., 1994; Koukopoulos et al., 1980; Wehr et al., 1988). By no means are all these agreed upon. Indeed, in one meta-analysis, Tondo and Baldessarini (1998) found an inconsistent association with female gender. One important factor in this literature is the difficulty associated with what is essentially a post hoc diagnosis.
One retrospective analysis of a large sample showed that bipolar illness with depression as the primary onset illness was significantly more likely than manic/mixed onsets to develop rapid cycling, suicidal behaviour, and psychotic symptoms (Perugi et al., 2000).
Mixed states of bipolar affective disorder have been recognized since the earliest days of modern classification (Kraepelin, 1921; Weygandt, 1901). Kraepelin described depressive admixtures occurring during mania as well as hypomanic intrusions into depression. His categorization included six subtypes. Mixed states are not fully reflected in ICD-10, and the DSM-IV definition requires manic and depressive symptoms in their full manifestations.
In their review of the phenomenology of mania, Goodwin and Jamison (1990) found that symptoms of depression and irritability, rather than elation, occur in 70-80% of patients with mania. Recent research has attempted to define mixed states with greater precision (e.g., Cassidy et al., 1998; McElroy et al., 1992). Various conceptualizations have included transitional states between mania and depression, an intermediate state, and a distinct affective state. However, little consensus has emerged on how best to diagnose mixed states. DSM-IV remains the most widely accepted convention, but there is growing criticism of its rigidity (e.g., Perugi et al., 1997). This has prompted alternative definitions; for example, the criteria derived from existing depression-rating scales (Post et al., 1989, Prien et al., 1988, Secunda et al., 1985, Swann et al., 1993), the use of depression items or subscales from general rating instruments (Cohen et al., 1988; Himmelhoch & Garfinkel, 1986), and a reduction in the number of DSM-IV major depression criteria required to make the diagnosis (Tohen et al., 1990; McElroy et al., 1992). Another approach has involved revisiting the essential constituents of mania. Cassidy et al. (1998) have produced the most comprehensive factor analysis of manic symptoms on a large sample to date. Five independent factors were found. Importantly, the most significant factor, dysphoric mood, was found to have a bimodal distribution. This finding raises the possibility that mixed bipolar disorder is a distinct entity.
Although it has been little studied, estimates have been made of the clinical epidemiology of mixed states. Cassidy and Carroll (2001) concluded that an earlier age of first hospitalization and increased duration of illness were compatible with the view that mixed manic episodes occur more frequently later in the course of bipolar disorder. Differences in ethnicity, gender, and clinical history also add to the evidence supporting the separation of mixed mania as a diagnostic subtype.
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