Clinical Psychology Review 32 (2012) 229–243

Contents lists available at SciVerse ScienceDirect

Clinical Psychology Review

Cyclothymic disorder: A critical review☆,☆☆

Anna R. Van Meter a,⁎, Eric A. Youngstrom a, Robert L. Findling b
a
University of North Carolina at Chapel Hill, USA
b
Case Western Reserve University and University Hospitals Case Medical Center, USA

a r t i c l e i n f o a b s t r a c t

Article history: Cyclothymic disorder is a subtype of bipolar disorder included in the Diagnostic and Statistical Manual of
Received 23 September 2011 Mental Disorders since 1980, but largely neglected in research. Additionally, it is rarely diagnosed clinically,
Received in revised form 1 January 2012 in spite of evidence that it may be the most prevalent form of bipolar disorder. Neglect has contributed to
Accepted 3 February 2012
confusion about the diagnosis and clinical presentation of cyclothymic disorder. Its status as a mood disorder
Available online 10 February 2012
is also ambiguous due to overlap in terminology and symptoms with temperament and personality disorders.
Keywords:
Subthreshold bipolar disorder appears more prevalent among young people than previously thought, and fol-
Cyclothymic disorder lows a range of trajectories from remission to escalation—raising questions about risk factors and traits asso-
Cyclothymia ciated with the varied course. Cyclothymic disorder may be an important diathesis for major mood disorders.
Bipolar disorder Constructs such as cyclothymic disorder link major mood disorder and peri-clinical fluctuations of mood,
Subthreshold thus warranting a prominent role in dimensional models of mood and psychopathology. Current evidence in-
Review dicates that cyclothymic disorder is a prevalent and highly impairing disorder on the bipolar spectrum, with
Validation the potential to make unique contributions to our understanding of the risk factors and outcomes associated
with bipolar disorder. The inclusion of cyclothymic disorder in future research studies is essential to accurate
diagnosis and effective treatment for the full spectrum of bipolar disorder, as well as understanding the de-
velopmental trajectory of bipolar spectrum disorders.
© 2012 Elsevier Ltd. All rights reserved.

Contents

1. History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
2. Phenomenology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
2.1. Diagnostic challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
2.2. Mood presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
2.2.1. Mood instability and fluctuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
2.2.2. Elevated mood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
2.2.3. Depressed mood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
2.2.4. Irritability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
2.3. Comorbidity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
2.4. Suicidality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
2.5. Quality of life and social functioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
2.6. Pediatric cyclothymic disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
2.6.1. Pediatric cyclothymic validation studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
2.7. Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
2.7.1. Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
2.7.2. Demographics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235

☆ Dr. Findling receives or has received research support, acted as a consultant, received royalties from, and/or served on a speaker's bureau for Abbott, Addrenex, Alexza, American
Psychiatric Press, AstraZeneca, Biovail, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press, Johnson & Johnson, KemPharm Lilly, Lundbeck,
Merck, National Institutes of Health, Neuropharm, Novartis, Noven, Organon, Otsuka, Pfizer, Physicians' Post-Graduate Press, Rhodes Pharmaceuticals, Roche, Sage, Sanofi-Aventis,
Schering-Plough, Seaside Therapeutics, Sepracore, Shionogi, Shire, Solvay, Stanley Medical Research Institute, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Validus,
WebMD and Wyeth.
☆☆ Dr. E. Youngstrom has received travel support from Bristol-Myers Squibb and consulted with Lundbeck.
⁎ Corresponding author at: CB 3270, University of North Carolina, Chapel Hill, NC 27514, USA. Tel.: + 1 401 378 0209.
E-mail address: [email protected] (A.R. Van Meter).

0272-7358/$ – see front matter © 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.cpr.2012.02.001
230 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243

2.8.Longitudinal course . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235

2.8.1. Episodicity or circularity? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
2.8.2. Prodromal disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
2.8.3. Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
2.9. Psychosocial treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
3. Family studies and genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
4. Biological characteristics and laboratory studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
4.1. Temperament . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
4.2. Personality and personality disorder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
4.3. Circadian rhythms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
4.4. Hypothalamic–pituitary–adrenal axis dysregulation and cortisol level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
4.5. Psychopharmacological response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
5. The current state of cyclothymic disorder in clinical practice and research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
5.1. Clinical practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
5.1.1. Unmet need. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
5.1.2. Assessment issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
5.1.3. Early intervention versus the underdeveloped research base for treatment . . . . . . . . . . . . . . . . . . . . . . . . . 239
5.2. Research implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
6. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239

“It is still not absolutely clear, what and where the boundaries are be- bipolar disorder, along with terms related to each of the areas of focus
tween the other bipolar disorders, cyclothymia and a cyclothymic listed above. Reference lists from each article were assessed for addi-
personality or cyclothymic temperament” (Marneros, 2001a). tional citations of interest, and the historical review was further aug-
mented based on suggestions from reviewers. Unless otherwise noted,
“Cyclothymia” has been conceptualized in a number of ways within the studies referred to focus on adults. Table 1 describes the studies of
several theoretical models. The forthcoming publication of new versions cyclothymic disorder included.
of both DSM and ICD provides an opportunity to examine the data on Though the unique symptom presentation of cyclothymic disorder—
cyclothymic disorder and to decide how it best fits in contemporary chronic hypomanic and depressive symptoms—has long been recog-
clinical nomenclature. Currently, some conceive of cyclothymic disorder nized clinically, within the current categorical diagnostic system, sub-
as a subtype of bipolar disorder (American Psychiatric Association, threshold presentations of bipolar disorder are often excluded from
2001), characterized by a chronic presentation of low-grade depressive research studies, in favor of focusing on more “classic” presentations
and hypomanic symptoms. As the idea of a dimensional model of diag- of manic depressive illness (Youngstrom, 2009). As one research
nosis, rather than a categorical system, gains traction, cyclothymic dis- group put it, “Adding broader notions of the BP spectrum would compli-
order may take on an increasingly important role as the step between cate our mission at this stage” (Hasler, Drevets, Gould, Gottesman, &
nonclinical levels of mood fluctuation and acute bipolar disorder. Manji, 2006). Though subthreshold presentations add complexity,
Cyclothymia may also be thought of as a temperament style the field stands to gain much from investigation of cyclothymic disor-
(Akiskal, Khani, & Scott-Strauss, 1979), associated with moodiness der: epidemiological research suggests that the prevalence of sub-
and irritability. Under this theory, cyclothymic temperament is a risk threshold bipolar disorder (2.4%) is higher than that of bipolar I (1.0%)
factor for psychopathology, particularly the bipolar spectrum disor- (Merikangas et al., 2007), and, in some cases, cyclothymic disorder
ders. Cyclothymic temperament may significantly increase risk of de- may represent the prodrome to more severe presentations of bipolar
veloping bipolar I or II. Among the affective temperament styles, disorder (Klein, Depue, & Slater, 1986; Shankman et al., 2009). Cyclo-
cyclothymic temperament is found most often among people who thymic disorder deserves attention both in terms of the number of peo-
are diagnosed with a bipolar spectrum disorder (Akiskal & Akiskal, ple affected, and because it may be a target for intervention that
1992). The idea of temperament as diathesis is similar to the concep- prevents progression to more debilitating disorders.
tualization of cyclothymic disorder as a prodrome or intermediate
stage in the development of bipolar I or II. Cyclothymia can also be 1. History
considered a character trait, a personality descriptor without any di-
rect relation to psychopathology (Brieger & Marneros, 1997). Any of Cyclothymia has been part of the mental health nomenclature
these characterizations of cyclothymia may prove empirically correct, since the 1880s. Karl Kahlbaum coined the term “Cyclothymia”
but this range of definitions, applied to a single term, has led to con- (from the Greek kyklos, cycle and thymos, mood) to encompass the
fusion and misinterpretation. full spectrum of bipolar disorders from subclinical to the most severe
In order to develop a more precise conceptualization of cyclothymia (Kahlbaum, 1882, as cited in Goodwin & Jamison, 2007). Though the
and to promote clarity within research and clinical fields, we set out to term cyclothymia was first used by Ewald Hecker in 1877 to describe
examine the following themes as they relate to cyclothymic disorder: symptoms we would likely label bipolar I, the presentation associated
History, Phenomenology, Epidemiology, Longitudinal Course, Biological with DSM-IV-defined cyclothymia—chronic, but mild, elevated and
Characteristics and Laboratory Studies, Family Studies and Genetics, depressed moods—were first introduced in Karl Kahlbaum's 1882
and Implications. These categories follow the validating criteria origi- paper, “On Circular Insanity” and later accepted by Hecker (1898)
nally proposed by Robins and Guze (1970) and extended by Cantwell and Kraepelin (1899) (Angst & Marneros, 2001; Baethge, Salvatore,
(1996). These validating criteria have also been applied to bipolar disor- & Baldessarini, 2003; Brieger & Marneros, 1997; Marneros, 2001a;
der, including the bipolar spectrum in youths (Biederman et al., 2003; Trede et al., 2005). The disorder was described more fully in Hecker's
Findling et al., 2001; Geller & Tillman, 2005; Youngstrom, Birmaher, & 1898 paper, “Cyclothymia, a Circular Mood Disorder,” and in Jelliffe's
Findling, 2008). A comprehensive review of the extant literature was 1911 paper, “Cyclothymia—The Mild Forms of Manic-Depressive
conducted through PubMed and PsycInfo using combinations of the fol- Psychoses and the Manic-Depressive Constitution” (Angst &
lowing search terms: cyclothymia, cyclothymic disorder, subthreshold Marneros, 2001; Hecker, 2003). Later, Emil Kraepelin would write
Table 1
Studies including cyclothymic disorder as a diagnostic category.

Author Date Location Cyclothymic Total Operationalization of Ages Design Result

disorder N N cyclothymia

Akiskal, et al. 1977 Tennessee 46 500 Feighner criteria for cyclothymic Adult Prospective community Cyclothymic disorder was associated with high rates of
disorder family history, early age of onset, often progressed to BP I
Akiskal, et al. 1985 Tennessee 10 68 Alternating mixture of dysthymic Adolescent Sibling and offspring study Cyclothymic disorder is common among family member
and hyperthymic featuresa of people with bipolar I
Alloy, et al. 2008 Philadelphia and 36 293 Subthreshold, cyclothymic Young adult Prospective community BP spectrum disorders associated with increased BAS sensitivity
Madison disorder + NOSa
Alnaes, R. and 1989 Oslo, Norway 40 298 DSM III Adult Outpatient clinical Chronic affective disorders associated with neurotic and
Torgensen, S. oral personality traits
Angst, et al. 2003 Switzerland 59 591 Mild depression plus hypomaniaa Adult Epidemiological subsample Hypomania criteria are poorly defined and unreliable; a
redefinition would result in an increase in the prevalence
of bipolar disorder
Angst, et al. 2005 Switzerland 114 4547 DSM IV Adult Epidemiological Prevalence rates for subthreshold BP were high, 6.5% overall
Depue, R. 1981 Buffalo 52 126 DSM III Adult Subsample from large community Cyclothymia characterized by frequent fluctuations between
and clinical sample depressive and hypomanic symptoms; cyclothymia may

A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243

be reliably identified using the behavioral paradigm described
Depue, R. 1989 Minneapolis 43 201 DSM III Adult Subsample from large university sample The GBI was able to discriminate participants with even
very mild bipolar symptoms from controls
Faravelli, C. 1990 Florence, Italy 4 1000 DSM III Adult Epidemiological Mood disorders were prevalent in the sample; those with
MDD, BP I or BP II were most likely to pursue treatment
with a psychiatrist
Fava et al. 2011 Bologna 62 62 DSM IV 18–65 Outpatient clinical; academic A combination of cognitive behavioral therapy and
research well-being therapy that addresses high and low moods,
as well as comorbid anxiety, benefits people with
cyclothymic disorder
Findling, et al. 2005 Cleveland 31 400 DSM IV 5–17 Outpatient clinical Parental bipolar disorder increases risk for mood
symptomatology in offspring; elevated mood with
irritability and rapid mood fluctuations are key
characteristics of subsyndromal bipolar disorder
Jacobsen, F. 1993 Washington, DC 17 33 DSM III-R 19–64 Outpatient clinical Valproate may be useful for the treatment of cyclothymia;
milder forms of bipolar disorder may require lower doses
of valproate for stabilization
Kessler, et al. 2009 USA 14 347 DSM III 13–17 Epidemiological subsample Subthreshold BP is more prevalent than BP I or BP II; diagnoses
of BP I and II cannot be reliably differentiated using the CIDI
Klein, D., Depue, R., 1985 Illinois 9 58 DSM III 15–21 Offspring from parents with BP I There is a strong familial relationship of bipoalr spectrum disorders
and Slater, J. and healthy parents
Lewinsohn, P., Klein, D., 2000 Oregon 48 893 Period of elevated/expansive/ 14–24 Prospective community Subsyndromal bipolar is associated with significant
and Seeley, J. irritable mood that does not impairment
meet full criteria for BPa
Totterdell, P., and 2008 United Kingdom 1 1 DSM IV 49 Treatment case study Treatment of cyclothymia and other bipolar disorders may
Kellett, S. be enhanced by integrating circadian mood regulation
Van Meter, et al. 2011 Clevelend 52 827 DSM IV 5–17 Outpatient clinical Cyclothymic disorder can be reliably diagnosed in young people;
cyclothymic disorder shares many characteristics with other
bipolar disorders and clearly belongs on the spectrum
Van Meter, et al. 2011 Cleveland 53 894 DSM IV 5–17 Outpatient clinical; academic Results supported previous findings that cyclothymic
research disorder shares many characteristics with other bipolar
subtypes and belongs on the bipolar spectrum
Verhoeven, W. and 2001 The Netherlands 28 248 Rapid or episodic fluctuations in 18–66 Residential treatment Low dose valprioc acid led to marked and sustained
Tuinier, S. behavior, plus presence of improvement in 68% of subjects; better behavior stability,
prominent mood deviationsa and a reduction of symptoms in the mood, anxiety and
motor domains
a
Denotes study-specific criteria for cyclothymic disorder, versus DSM; does not include studies assessing cyclothymic temperament exclusively.

231
232 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243

about cyclothymia as a subaffective disorder or disposition (Akiskal, dysthymic episode. Because mood fluctuation can also be indicative of
2001; Brieger & Marneros, 1997; Kraepelin, 1921). He favored the personality disorders, a change in behavior accompanying the mood
term “manic depressive” though, which is more consistent with a bi- shift is thought to be a more precise indicator of cyclothymic disorder
polar I presentation. Some believe Kraepelin's semantic preference is (Akiskal, Djenderedjian, Rosenthal, & Khani, 1977).
partly to blame for the longstanding focus on classic, severe presenta- The presentation of cyclothymic disorder is highly heterogeneous.
tions of bipolar disorder. Kraepelin's spectrum concept of manic de- Some people may be dysthymic nearly all the time with rare days of
pressive illness, which extended from psychotic mania through hypomania, whereas others may shift from feeling depressed to feel-
milder presentations such as hypomania and cyclothymic disposition ing hypomanic multiple times in a single day (Howland & Thase,
to include recurrent unipolar depression, was later rejected in favor of 1993). Similarly, although periods of both depressive and hypomanic
a diagnostic system composed of distinct categories. Advocates of the symptoms occur, and may do so in ways that appear episodic, more
categorical approach believed it would be more precise, complaining often the presentation is mixed, without clear demarcation between
that cyclothymia was a “wastebasket” diagnosis given too frequently moods (Akiskal et al., 1977). The quality of hypomanic symptoms
(Brieger & Marneros, 1997). In 1908, Gaston Deny conceptualized cy- also can vary between positive versus restless and irritable moods,
clothymia as an imbalance of moral sensibility, not a form of manic which have greater likelihood of negative outcomes (Akiskal,
depression (Haustgen & Akiskal, 2006). He believed it was a “consti- Hantouche, & Allilaire, 2003). Furthermore, depressed periods often
tution” that existed independent of psychopathology; this was the or- include hypomanic symptoms, resulting in a more agitated presenta-
igin of the idea of cyclothymic temperament. His student, Pierre Kahn, tion (Howland & Thase, 1993).
expanded these ideas in “Cyclothymia: the cyclothymic constitution
and its manifestations (depressions and intermittent excitements)” 2.1. Diagnostic challenges
(1909). This work established the idea of affective temperament as
persisting before and after discrete mood episodes, continuing to in- The moodiness, impulsivity, and interpersonal problems character-
fluence one's social, family and professional lives in a more chronic istic of cyclothymic disorder are phenomenologically similar to border-
way (Haustgen & Akiskal, 2006). line personality disorder (Henry et al., 2001; MacKinnon & Pies, 2006;
Though the categorical approach has been ascendant for decades, Perugi & Akiskal, 2011). Additionally, cyclothymic mood disturbance
many leading researchers in the field of bipolar disorder now believe is more moderate than found with bipolar I or II, making diagnosis
that Kraepelin's original idea of a range of symptoms and severity more challenging. In spite of community studies finding comparatively
levels is a more accurate way to define the bipolar spectrum high prevalence, the rates of clinical diagnosis are low (Youngstrom,
(Akiskal, 2001; Trede et al., 2005). A proposal for the classification of de- 2009; Youngstrom, Youngstrom, & Starr, 2005). Several factors contrib-
pression in DSM-5 advocates the use of a two-axis system—severity and ute to the low clinical rates (Hantouche & Erfurth, 2010). First, people
chronicity—rather than discrete categories (Klein, 2008). Perhaps bipo- with cyclothymic disorder often do not seek treatment for their mood
lar disorders could also be better classified using severity and chronicity disturbance (Youngstrom, Van Meter, & Perez Algorta, 2010). Similarly,
as distinct dimensions. an individual with cyclothymic disorder, may lack the insight to under-
In the decades following Kraepelin, little advancement was made in stand that his/her experience is dysfunctional, particularly during pe-
the field of bipolar illness. In the 1960s, interest in bipolar disorder grew riods of elevated mood (Ghaemi, 1995; Gupta, Basu, & Sinha, 2004;
following two important studies by Jules Angst and by Carlo Perris Smith & Ghaemi, 2006). Third, the severity of the mood symptoms
(Angst, 1966; Perris & d'Elia, 1966). Both studies delineated bipolar dis- may not be pronounced enough to trigger action by concerned third
order from unipolar depression and theorized that both genetic and en- parties, such as hospitalization or arrest.
vironmental factors influence the etiology and course of bipolar Low treatment-seeking behavior likely exacerbates the impair-
disorder, contributing to its heterogeneity (Angst & Marneros, 2001; ment associated with the disorder. People with cyclothymic disorder
Marneros, 2001a). The second version of the Diagnostic and Statistical miss potentially ameliorative care. When they seek treatment, it is
Manual of Mental Disorders (American Psychiatric Association, 1968) in- usually during a depressive phase, as the experience of hypomania
troduced manic depressive illness as a mood disorder, and “cyclothymia” can be pleasant (Akiskal, 2001; Akiskal et al., 1977; Utsumi et al.,
was listed as an affective personality disorder (Akiskal, 2001; American 2006; Youngstrom, 2009). Unfortunately, unless the clinician is vigi-
Psychiatric Association, 1968). With the publication of DSM-III (1980), lant about bipolar disorder, they will focus on the presenting com-
“manic depressive illness” changed to “bipolar disorder,” encompassing plaint and fail to detect previous hypomanic episodes (Smith &
various subtypes—bipolar disorder-manic, bipolar disorder-mixed, bi- Ghaemi, 2006), leading to misdiagnosis with dysthymia or unipolar
polar disorder-depressed, and cyclothymia (American Psychiatric depression (Klein et al., 1986).
Association, 1980; Wilson, 1993). Cyclothymic disorder has remained Less often, a person with cyclothymic disorder will seek help for ex-
one of the subtypes of bipolar disorder in subsequent versions of the ternalizing symptoms, such as impulsivity, agitation, and aggression. If
DSM. However, it is rarely diagnosed in clinical practice, indicating a the clinician and patient do not recognize the episodic nature of the dis-
disconnect between actual prevalence and clinical diagnosis (Akiskal, order, the person may be misdiagnosed with a personality disorder, op-
2001; Hantouche, 2009). positional defiant disorder, or ADHD (depending on age) (Fields &
Fristad, 2009; Youngstrom, 2009). The misdiagnosis of externalizing
2. Phenomenology symptoms is probably more common among young people because
hypomania can be harder to recognize (Youngstrom et al., 2008), and
As defined in DSM IV, cyclothymic disorder presents as alternating referrals more often focus on externalizing problems. In addition to
states with depressive and hypomanic symptoms for at least 1 year in chronic elevated and depressed mood, people with cyclothymic disor-
children and adolescents or 2 years in adults. During the initial index der often exhibit irritability, substance use, and sleep disturbance
period, the individual cannot be symptom-free for more than 2 months (Table 2) that may further cloud the diagnostic picture (Akiskal et al.,
(American Psychiatric Association, 2001). If the individual's symptoms 1977; Howland & Thase, 1993; Totterdell & Kellett, 2008).
become sufficiently severe to meet the full criteria for mania or depres- Another diagnostic issue is that many research groups lump cyclothy-
sion before the two-year duration has been met, a diagnosis of bipolar I mic disorder with other subthreshold presentations in a broad “bipolar
or II would result instead of a cyclothymic diagnosis. If symptoms NOS” category. This is common among pediatric bipolar disorders in
become more severe after the initial 2 years, concurrent diagnoses particular (Birmaher et al., 2006; Birmaher et al., 2009; Youngstrom,
of both cyclothymia and BP I or II may be assigned, similar to coding 2009), limiting our ability to learn whether or not there are unique
“double depression” when a major depression episode follows a characteristics of each of the subtypes. Furthermore, the criteria for
 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243 233

Table 2 2.2.3. Depressed mood

Differential diagnosis conceptualization. Depressive symptoms associated with cyclothymic disorder are
Neighboring diagnoses Features similar to Features differentiating more often identified clinically than hypomanic symptoms, regardless
cyclothymic disorder cyclothymic disorder of severity (Cassano et al., 1999). The depressive periods of cyclothymic
Dysthymic disorder Chronic mood disturbance Periods of elevated mood disorder often involve agitation and feelings of low self-worth and guilt,
Subthreshold depressive Mixed presentation insecurity and dependence, emotional instability and high sensitivity
symptoms (Alnaes & Torgensen, 1989), along with high levels of irritability and
Shared risk factors
anxiety (Perugi, Toni, Travierso, & Akiskal, 2003). Because of the fre-
Possible prodromal
presentation quent mood shifts common to cyclothymia, mixed presentations—in
Bipolar II disorder Lengthy mood episode No major depression which both depressive and hypomanic symptoms are present—occur
common regularly. As a result, predominantly depressive periods may also be
Intermittent hypomanic Mixed presentation more marked by extreme irritability and explosive temper (Akiskal et al.,
and depressive periods common
1977). The depression associated with cyclothymic disorder may be
Shared risk factors More frequent hypomania
Bipolar NOS disorder Lengthy mood episode Chronic presentation more resistant to treatment than unipolar depression and bipolar II
common depression (Akiskal, 1994; Peselow, Dunner, Fieve, & Lautin, 1982).
Mixed presentation Fewer well days Treatment resistance may be due to the fact that cyclothymic depres-
common
sion often includes hypomanic symptoms, or else related to the chronic
Early onset
Shared risk factors nature of cyclothymic disorder. Mixed presentations also tend to pre-
Possible prodromal dict a more refractory form of bipolar disorder, associated with higher
presentation rates of suicide (Algorta et al., 2011), fewer well days, and worse prog-
Attention-deficit/ Chronic presentation Change in mood nosis (Schneck, 2009; Strober et al., 1995). Continuous cycling and sub-
hyperactivity disorder presentation
threshold symptoms have been associated with poor treatment
(ADHD) Agitation Later onset typical
Shared risk factors More variation in symptom response (Birmaher et al., 2009; Calabrese, Fatemi, Kujawa, &
presentation Woyshville, 1996), too.
Borderline personality Chronic presentation Clear change in functioning Moreover, people with cyclothymic disorder tend to experience
disorder at onset
interpersonal difficulties during depressive periods. Lack of social
Mood instability Fewer shared risk factors
Interpersonal difficulties More variation in symptom
support or minimal positive interaction with others could contribute
presentation to the chronic nature of this disorder (Akiskal et al., 1977).
Labile affect
2.2.4. Irritability
The literature consistently describes irritability as a key character-
bipolar NOS vary across research groups, so findings are not neces- istic of cyclothymic disorder during both hypomanic and depressive
sarily generalizable (Mick, Biederman, Pandina, & Faraone, 2003; periods. In contrast to “sunny” hypomanic episodes that are described
Youngstrom et al., 2005). Just because cyclothymic disorder is rarely dif- as a pleasant, elated state, cyclothymic hypomania can be “dark,”
ferentiated from other subthreshold forms of bipolar disorder, does not characterized by irritability and impulsive risk taking (Akiskal et al.,
mean that it cannot be: cyclothymic disorder can be reliably diagnosed 2003). The presence of irritability during both depressive and elevat-
using DSM IV criteria, but it requires careful assessment (Depue, 1981; ed mood states could be a factor in the frequent misdiagnosis of cy-
Mazure & Gershon, 1979; Youngstrom, Youngstrom, & Starr, 2005). In clothymic disorder as depression (Utsumi et al., 2006), though the
order to advance research and clinical practice, a correction in diagnosis energy level and quality of irritability during elevated and depressive
must be made, to better document the real differences in phenomenolo- moods may be different.
gy and prevalence between subtypes of bipolar disorder. People with cyclothymic disorder tend to be impulsive and unpre-
dictable during hypomanic or mixed states with irritable mood di-
rected at others, whereas during depressive periods, they may be
2.2. Mood presentation
very sensitive, but also tend to have self-directed irritability consis-
tent with guilt, rumination, and low self-esteem (Akiskal et al.,
2.2.1. Mood instability and fluctuation
1977; Akiskal et al., 1985). This can be particularly important when
Cyclothymic disorder is defined by mood that fluctuates between
making a diagnosis in young people: over 90% of youth with bipolar
elevated, hypomanic-like states and depressive, low states (Akiskal
diagnoses show moderate or severe irritability, associated with ag-
et al., 1977; American Psychiatric Association, 2001). Mood lability
gression and outward hostility, during periods of elevated mood
has serious consequences for an individual's quality of life and level
(Jensen et al., 2007).
of functioning (Shen, Alloy, Abramson, & Sylvia, 2008), particularly
because these symptoms are chronic and less likely to remit than
2.3. Comorbidity
clear episodes of bipolar mood (Akiskal, 2003; Howland & Thase,
1993; Koukopoulos et al., 2003).
Adults and youth with cyclothymic disorder tend to have high rates
of comorbid psychiatric disorders, with more than 50% having at least
2.2.2. Elevated mood one comorbid Axis I disorder; a rate comparable to those found
As discussed, hypomania can be difficult to assess, has poor diagnos- among people with BP I (Lewinsohn, Klein, & Seeley, 1995; Van Meter,
tic reliability, and questionable duration criteria (Andreasen et al., 1981; Youngstrom, Youngstrom, Feeny, & Findling, 2011). Bipolar I presenta-
Howland & Thase, 1993). Because symptoms of hypomania, including tions characterized by four or more mood switches per year have
irritability, impulsivity, increased activity, are also associated with rates of psychiatric comorbidity of 1.5 to 2 times higher than those
other, non-episodic disorders, clinicians must establish a change from without frequent mood shifts (MacKinnon et al., 2003). People with cy-
baseline in order to diagnose a bipolar disorder. Proposed DSM-5 cri- clothymic disorder tend to shift moods even more often than four times
teria make the episode criteria more salient: “The episode is associated a year (Howland & Thase, 1993), also likely contributing to their high
with an unequivocal change in functioning that is uncharacteristic of levels of comorbidity. Another factor contributing to increased comor-
the person when not symptomatic” (American Psychiatric Association, bidity is the diverse history of psychiatric disorder seen among family
2010). members of people with cyclothymic disorder (Akiskal et al., 1977;
234 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243

DelBello & Geller, 2001). High rates of a variety of disorders among close Quality of life may be measured on a number of dimensions includ-
family members contribute risk for a number of comorbid disorders. ing one's physical and emotional status, self-esteem, school perfor-
The fact that cyclothymic disorder is a chronic disorder with an early mance, family situation, and friends (Freeman et al., 2009; Wee, Lee,
onset may also increase comorbidity. Prolonged delay in appropriate Ravens-Sieberer, Erhart, & Li, 2005). Subthreshold affective disorder
treatment may result in accumulated comorbid disorders (McElroy, symptoms are linked with significant deficits in multiple facets of qual-
Strakowski, West, Keck, & McConville, 1997; Schraufnagel, Brumback, ity of life, including physical health, emotional wellbeing, personal care
Harper, & Weinberg, 2001). The disorders most often seen coupled and independent functioning, occupational functioning, personal fulfill-
with cyclothymic disorder are ADHD, anxiety disorders, and substance ment, and global perception of quality of life (Vázquez et al., 2008).
use (Freeman, Freeman, & McElroy, 2002; Grant et al., 2005; Global impairment can be self-perpetuating, as individuals lack the in-
Lewinsohn et al., 1995; Merikangas & Pato, 2009b; Sachs, Baldassano, ternal resources and external support to improve their situation.
Truman, & Guille, 2000; Simon et al., 2004), consistent with other bipo- Cyclothymic disorder disrupts people's ability to build and maintain
lar disorders. positive relationships (Shen et al., 2008). Irritability and emotional reac-
Substance use is a large problem among both youth and adults tivity often have a detrimental effect on the ability to be socially suc-
with bipolar I (McElroy et al., 1997). Those with subthreshold cases cessful with peers and family (Angst et al., 2003). A longitudinal study
are hypothesized to be at elevated risk due to a tendency to use sub- found that people with hypomanic symptoms had consistent distress
stances to alleviate the discomfort of their symptoms, which often go and greater interpersonal conflict in their relationships across family,
untreated (Akiskal et al., 1985). Though it is plausible that cyclothy- friends, work, and romantic partners (Wicki & Angst, 1991). Few mar-
mic disorder may have rates of substance use as high or higher than riages survive more than three manic episodes (Hauser et al., 2007).
others with bipolar spectrum disorders, little research is available. A People with cyclothymic disorder do not become manic, but they do ex-
better understanding of substance use by people with cyclothymic perience troubled relationships. An investigation of the effect of cyclo-
disorder is important to prognostic and treatment considerations. thymic disorder symptoms on romantic relationships would be a
helpful addition to the literature, particularly if it could tease apart the
2.4. Suicidality effects of more chronic, moderate disturbance versus the more acute
but briefer disruptions characteristic of mania.
All bipolar disorder subtypes represent a significant risk factor for People with cyclothymic disorder may also be prone to deviant so-
suicidality and particularly for completed suicide (Baldessarini & cial behavior—sexual affairs, anti-social or malicious behavior—and an
Tondo, 2003), including adolescent populations (Lewinsohn, Seeley, inability to relate to others. Some believe this may be a helpful feature
& Klein, 2003). No direct comparison of suicide in people with cyclo- diagnostically, as it may set people with cyclothymic disorder apart
thymic disorder, relative to other BP subtypes, has been made previ- from others with mood disorders (Akiskal et al., 1977). Additionally,
ously (Goldstein et al., 2005). This is a significant gap in the literature. people with cyclothymic disorder may actively avoid social interac-
Adults with cyclothymic disorder tend to be impulsive and to have a tion, alienating them from peers and family members (Perugi,
tendency toward mixed and/or depressive episodes (Goldstein et al., 2002). Engaging in fewer activities than healthy controls limits their
2005), which make them more likely to act on suicidal impulses social exposure and opportunities to build positive relationships
(Algorta et al., 2011). In addition, multiple research studies on (Shen et al., 2008).
major depression and suicide have found that cyclothymic tempera- Though chronic mood dysregulation lowers overall quality of life,
ment is linked to significantly higher numbers of past suicide at- it may also allow habituation. On the plus side, those with cyclothy-
tempts (Akiskal, Lancrenon, & Hantouche, 2006; Mechri, Kerkeni, mic disorder may have fewer large mood-triggered disturbances—
Touati, Bacha, & Gassab, 2011). Rapid mood cycling further increases hospitalization, extended periods away from work, and they may be
risk of suicide (Azorin et al., 2010). able to function consistently, albeit at a suboptimal level. However,
tolerance of chronic mood instability also reduces motivation to
2.5. Quality of life and social functioning seek treatment. Research on bipolar spectrum disorders in general
has shown that people with other bipolar spectrum disorders suffer
Bipolar spectrum disorders markedly reduce quality of life from more physical health problems and achieve a lower level of pro-
(Freeman et al., 2009; Michalak, Yatham, Maxwell, Hale, & Lam, fessional success than people who do not have BP. More research on
2007; Michalak, Yatham, Wan, & Lam, 2005). Bipolarity can “disturb cyclothymic disorder specifically needs to ascertain its unique impact
all life aspects, even daily routines, with important consequences on the quality of multiple realms of life, ideally disentangling the con-
such as failures, isolation, job loss and severe interpersonal con- tributions of chronic versus acute mood disruption.
flicts…[and] can put subject life in danger” (Hantouche, Trybou, &
Majdalani, 2008). Although “subthreshold” variations of the disorder, 2.6. Pediatric cyclothymic disorder
including cyclothymic disorder, might be assumed to be less impair-
ing, studies have shown that their average impact is equivalent to Bipolar disorder, including cyclothymic disorder, has historically
that of BP I or II (Lewinsohn, Klein, & Seeley, 2000; Lewinsohn et al., been considered an adult disorder. But, as evidence mounts in favor
1995). Sometimes impairment is even worse, because those with sub- of the existence of bipolar disorder in young people, and, the bound-
threshold bipolar tend to be more chronically ill and less responsive ary between child and adult-specific disorders is blurred, with greater
to treatment (Birmaher et al., 2006; Birmaher et al., 2009). Cyclothy- consideration of psychiatric disorders across the lifespan (Pine et al.,
mic disorder is difficult to treat effectively (Hantouche, 2011), and the 2002), rather than within distinct developmental periods, the explo-
challenge is exacerbated when people with cyclothymic disorder ration of cyclothymic disorder among young people gains urgency.
often go many years between symptom onset and the administration Early onset mood disorder is associated with familial bipolar dis-
of appropriate treatment (Cassano et al., 1999; Hauser et al., 2007). order. In a study of offspring of parents with bipolar disorder, nearly
When people with cyclothymic disorder are treated for another disor- a quarter of the youth offspring were diagnosed with cyclothymic dis-
der with antidepressants or stimulants, poor response is likely order (Klein, Depue, & Slater, 1985). Similarly, in an outpatient youth
(Akiskal, 2001). Furthermore, the use of these medications may pro- study of subsyndromal mania, youth with a parent with bipolar disor-
long the period before appropriate treatment is administered, there- der were more likely to exhibit bipolar symptoms, including irritabil-
by diminishing an individuals' potential quality of life. High rates of ity and mood lability, than those youth with unaffected parents.
comorbidity in cyclothymic disorder predict more rapid relapse and Importantly, youth meeting criteria for subsyndromal mood symp-
a lower quality of life (Otto et al., 2006). toms (regardless of parental risk) were just as impaired as those
 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243 235

meeting criteria for BP I or II, and they were much more impaired general population (Angst et al., 2003; Chang, Blasey, Ketter, &
than youth meeting criteria for non-bipolar disorders (Findling Steiner, 2003; Kessler et al., 2009). Discrepant rates occur in part be-
et al., 2005). These results echo findings from the adult literature— cause studies use varying diagnostic criteria for cyclothymia, with
subthreshold forms of bipolar disorder are a serious public health some assessing cyclothymic temperament or personality, rather
concern and cause significant suffering. than mood disorder, muddying the distinction between the two
There is some evidence that there may be developmentally- (Howland & Thase, 1993).
limited forms of bipolar disorder, meaning that some cases diagnosed Another problem is that the time period assessed in epidemiolog-
in childhood will go on to remit permanently in young adulthood ical studies varies from point prevalence to lifetime prevalence. Be-
(Cicero, Epler, & Sher, 2009). The “developmentally limited” hypoth- cause bipolar disorders are episodic, rates reported for short time
esis may be one of the strongest arguments in favor of the pursuit of a periods (anything less than a year) may be misleadingly low and ef-
more precise understanding of pediatric bipolar subtypes. Though it fectively eliminate the option of diagnosing cyclothymic disorder,
has been shown that upwards of a third of people with cyclothymic which requires symptom duration of 2 years in adults (1 year in chil-
disorder may go on to develop bipolar I or II (Akiskal et al., 1977; dren under 18). Most studies have subsumed cyclothymia under the
Akiskal et al., 1979; Alloy et al., 2011), the idea that subthreshold “subthreshold” umbrella, along with bipolar not otherwise specified
forms of the disorder may resolve has not been explored systemati- (NOS). There has been little progress in the precise measurement of
cally. Alternately, some portion of the cases that appeared to remit bipolar subtypes in epidemiological work (Angst et al., 2003; Judd &
may have been misdiagnosed and were not actually cyclothymic dis- Akiskal, 2003; Kessler et al., 1994; Schotte & Cooper, 1999).
order to start with. Comprehensive investigation of the longitudinal
course of cyclothymic cases is vital to clarify factors that influence 2.7.2. Demographics
prognosis. Identification of factors leading to remission versus a Cyclothymic disorder may be more prevalent among women than
more protracted course would facilitate improved treatments and men (Akiskal et al., 1977; Dunner, Russek, Russek, & Fieve, 1982).
preventative interventions. Though bipolar I disorder is thought to affect both sexes equally,
epidemiological studies consistently show higher rates of other affec-
2.6.1. Pediatric cyclothymic validation studies tive disorders (including depression and bipolar II) among women
A recent validation study examined rates and correlates of cyclothy- (Goodwin & Jamison, 1990, 2007; Merikangas & Pato, 2009a). Studies
mic disorder, rather than BP NOS (the more commonly diagnosed sub- finding a higher preponderance of cyclothymic disorder among
threshold subtype), because cyclothymic disorder has distinct criteria women have drawn participants from clinical samples (Akiskal et
and should take precedence over the NOS label when appropriate al., 1977; Dunner et al., 1982), confounding incidence and treatment
(Van Meter, Youngstrom, Youngstrom, et al., 2011). This study of 829 seeking (Blanco, Laje, Olfson, Marcus, & Pincus, 2002; Merikangas &
youth from an outpatient clinic, 52 of whom were diagnosed with cy- Pato, 2009a).
clothymic disorder, found that cyclothymic disorder could be reliably Most studies of bipolar disorder among different racial groups
distinguished from other, non-affective disorders, and that it shared sig- have focused on comparisons of rates between people of African de-
nificant similarities with the other bipolar subtypes. Specifically, youth scent and Caucasians (Goodwin & Jamison, 1990, 2007). Among
with cyclothymic disorder showed significant elevations of both posi- these groups, people of African descent are more likely to be diag-
tive and negatively valenced mood symptoms compared to all nonbipo- nosed with, and treated for, psychotic symptoms, but it is not clear
lar diagnoses, and were equivalent to the other bipolar youth on whether this difference is an actual variation, or whether it is due to
measures of irritability, age of onset, sleep disturbance, and family his- cultural differences in the experience and description of mania versus
tory of psychopathology. A replication and extension of this study ethnocentric bias on the part of the clinician (Carpenter-Song, 2009;
(Van Meter, Youngstrom, Demeter, & Findling, 2011), using an another Patel et al., 2006; Strakowski et al., 2003). In multiple recent US epi-
outpatient youth sample (N = 894), yielded similar results; indicating demiological studies, bipolar rates are consistently equivalent be-
that cyclothymic disorder shares many characteristics with other bipo- tween diverse ethnic groups (Merikangas & Pato, 2009b). Similarly,
lar subtypes and belongs on the bipolar spectrum. no difference was found in the rate of cyclothymia temperament be-
The results of these studies indicate that cyclothymic disorder in tween participants of African descent and Caucasian participants in a
children is on the bipolar spectrum (and would not be better cast as US epidemiological study (Weissman & Myers, 1978).
a temperament or personality disorder), but retains characteristics
that distinguish it from the other subtypes. Future studies ought to 2.8. Longitudinal course
focus on comorbid disorders (especially ADHD), family history, and
age of onset to further elucidate differences between the bipolar sub- 2.8.1. Episodicity or circularity?
types. Additionally, both of these studies were unable to assess longi- Lingering questions about the natural course of bipolar disorder,
tudinal course or biological abnormalities, both of which may yield include age of onset, duration of episodes, frequency of remission,
important information (Van Meter, Youngstrom, Demeter, et al., and persistence of impairment with subthreshold symptoms
2011; Van Meter, Youngstrom, Youngstrom, et al., 2011). (Wittchen, Muhlig, & Pezawas, 2003). These questions are particular-
ly relevant to cyclothymic disorder due to its more chronic nature.
2.7. Epidemiology Prospective methods—such as life charting (Denicoff et al., 2000) or
daily diaries (Akiskal et al., 2000; Schrarer et al., 2002)—provide the
2.7.1. Prevalence most accurate measure of the temporal features of mood episodes.
In recent reviews of over 100 epidemiological studies of bipolar Though burdensome and costly to implement, they powerfully eluci-
disorder in both adults and children, only eight reported prevalence date the longitudinal path of bipolar spectrum disorders.
rates for cyclothymic disorder (Moreira, Van Meter, & Youngstrom, Cyclothymia may be better defined by the term “circularity” than
2010; Van Meter, Moreira, & Youngstrom, 2011). This reflects the in- by “episodicity,” given the continuous ups and downs experienced
frequent usage and relatively poor understanding of the cyclothymic within episode (Brieger & Marneros, 1997; Hantouche, 2010;
diagnosis, rather than the prevalence of the condition. Of those stud- Hantouche & Erfurth, 2010). However, each mood state may be
ies that did report rates of cyclothymia, rates ranged from 0.4% to 2.5% quite short: in a diagnostic validation study, most mood periods
(Angst et al., 2005; Faravelli, Degl'Innocenti, Aiazzi, Incerpi, & Pallanti, lasted less than a week and there were frequent mixed episodes
1990; Lewinsohn et al., 2000). Rates of undifferentiated subsyndro- with rapid polarity shifts (Akiskal et al., 1977). Cyclothymic mixed
mal bipolar disorder have been reported as high as 6% to 13% of the states often consist of the lethargy and low self-esteem of depression,
236 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243

along with the racing thoughts and impulsivity of mania (Marneros, be shorter than those seen in BP I or II, the frequent fluctuation between
2001b). Though there is definition for “mixed mood episode” in mood states results in fewer well (euthymic) days for cyclothymic dis-
DSM-IV, this requires an individual to meet criteria for both mania order (Koukopoulos et al., 2003). In addition, individuals with BP I or II
and major depression for at least 1 week or require hospitalization. tend to achieve remission faster and enjoy extended periods relatively
People with cyclothymic disorder, by definition, cannot meet these symptom-free (Birmaher et al., 2006; Birmaher et al., 2009; Judd &
criteria, but research shows that the type of mixed mood state expe- Akiskal, 2003), whereas those with cyclothymic disorder are generally
rienced in the course of cyclothymic disorder is associated with self- symptomatic indefinitely (Howland & Thase, 1993). In a longitudinal
harm, suicidal ideation, and suicide attempt (Findling et al., 2001; study of people with cyclothymic disorder, less than 10% of participants
Goodwin & Jamison, 2007; Perlis et al., 2004). In fact, more rapid experienced periods of “even” mood during the two-to-three year
shifts between mood states may result in a more lethal mix of hope- follow-up period (Akiskal et al., 1977). Additionally, the protracted
lessness and impulsivity (Swann et al., 2005). Additionally, frequent course of cyclothymic disorder may be an important outcome determi-
and rapid shifts between moods may represent a risk factor for later nant. A more chronic symptom presentation often indicates a
progression to a more severe mood disorder (Angst et al., 2003). treatment-refractory form of the disorder (Birmaher et al., 2006;
Birmaher et al., 2009) associated with greater comorbidity (McElroy
2.8.2. Prodromal disorder et al., 1997; Schraufnagel et al., 2001).
In a retrospective study of bipolar disorder, 33% of participants Mixed symptoms tend to last longer than purely depressive or hy-
reported symptoms consistent with cyclothymic disorder prior to pomanic episodes (Cassidy & Carroll, 2001). In addition, the experi-
onset of a manic or major depressive episode (Waters, 1979). Similar- ence of a mood episode increases the likelihood that another
ly, in a prospective study of people diagnosed with cyclothymic disor- episode will occur and, the longer the episode, the shorter the time
der, 36% went on to develop bipolar disorder I or II within 2 years to recurrence (Perlis et al., 2006). This is consistent with the concept
(Akiskal et al., 1979). Additionally, in a large survey of patients with of “kindling,” which posits that, with each mood episode, the likeli-
recurrent depression and their doctors, cyclothymic mood lability hood of another episode occurring grows (Dienes, Hammen, Henry,
was the strongest predictor of the presence of hypomania in treat- Cohen, & Daley, 2006; Goldberg & Harrow, 1994; Hlastala et al.,
ment resistant and recurrent major depression, suggesting that it is 2000; Post, 1992). Cyclothymic disorder may perpetuate via a feed-
a key factor in the progression from depressed mood to bipolar II dis- back loop wherein the “trigger” for the next mood is constantly
order (Hantouche & Angst, 2008; Hantouche, Azorin, Lancrenon, being pulled. Also, cyclothymic temperament may be a diathesis,
Garay, & Angst, 2009). However, not all people with cyclothymic dis- making people more sensitive to environmental factors eliciting
order will go on to meet criteria for BP I or II (Wetzel, Cloninger, mood disruption. Early intervention, preventing the cycle of mood
Hong, & Reich, 1980). Unfortunately, little data currently exist on bi- fluctuation, may offer the best chance at a positive outcome for peo-
polar prodromes in young children (Nadkarni & Fristad, 2010), for ple predisposed to rapid cycling (Koukopoulos et al., 2003).
whom the most meaningful interventions might be possible. Identify-
ing factors that help to determine which cases of cyclothymic disor- 2.9. Psychosocial treatment
der will develop into BP I or II would have important clinical
implications (Hauser et al., 2007; Howland & Thase, 1993). Research on psychosocial treatments for cyclothymic disorder is
In a longitudinal study of adolescents to the age of 24, about half of limited (Baldessarini, Vazquez, & Tondo, 2011). There is growing ev-
the participants with cyclothymia had progressed to BP II disorder idence for the efficacy of psychosocial treatment, in conjunction
(had a major depressive episode) at follow-up, while the others with pharmacotherapy, for the treatment of bipolar disorder; but
maintained a diagnosis of cyclothymia. This is in contrast to partici- most extant studies do not include subthreshold cases (Miklowitz,
pants who were diagnosed with subthreshold bipolar disorder at en- 1996; Miklowitz et al., 2007). Two published studies focus on the
rollment—none of these participants continued to meet criteria for use of psychotherapy to improve symptoms of cyclothymia.
subthreshold bipolar at follow-up (Lewinsohn et al., 2000). This high- Totterdell and Kellett (2008) found that modified cognitive behavior-
lights the need to differentiate between subthreshold cases: differ- al therapy (CBT) was effective in reducing mood variability and im-
ences in prognosis directly inform clinical decision making about proving sleep hygiene in a case study. They postulate that, by
the risks and benefits of intervention. altering the patient's circadian rhythm, they were able to decrease
A similar pattern of conversion was found in another study of her cyclothymic symptomatology and improve her quality of life. In
youth with affective disorders. Of those with cyclothymic disorder a recent randomized controlled trial, CBT plus well-being therapy
(n = 11), more than half (n = 7) experienced an episode of mania or (WBT) was compared to clinical management (CM) in people diag-
depression during the 3 year follow-up (Akiskal et al., 1985). Addi- nosed with cyclothymic disorder (Fava, Rafanelli, Tomba, Guidi, &
tionally, Kochman et al. (2005) found that among youth with major Grandi, 2011). The results indicated that the use of CBT/WBT could
depression, cyclothymic temperament predicted transition to bipolar significantly reduce both depressive and hypomanic symptoms, com-
I or II, with 64% converting, versus 15% of those without cyclothymic pared to CM, and that over half of the people treated with CBT/WBT
temperament. Additionally, 81% of those with cyclothymic traits ex- no longer met criteria for cyclothymic disorder. These results are
perienced suicide ideation or attempt, versus 31% of the depressed promising and suggest that the prognosis and quality of life for people
youth without cyclothymic traits. These findings are provisional with cyclothymic disorder could be enhanced through augmented
based on the small sample sizes or reliance on temperament instead CBT. However, it is difficult to draw conclusions based on two studies;
of formal diagnostic criteria for cyclothymic disorder, as well as a future research should build upon these results and progress toward
lack of information about bipolar NOS. clear treatment guidelines for cyclothymic disorder.

2.8.3. Prognosis 3. Family studies and genetics

People afflicted with cyclothymic disorder can expect a variety of
negative outcomes extending beyond their mood to impact relation- Cyclothymic disorder is prevalent among the family members of
ships, finances, employment, and physical health (Wittchen et al., those with bipolar disorder (Akiskal et al., 2006; Akiskal, Lancrenon,
2003). Subthreshold symptoms tend to persist longer than symptoms & Hantouche, 2006; Edvardsen et al., 2008; Howland & Thase, 1993;
meeting full criteria, and also create significant impairment (Paykel, Klein et al., 1986; Schraufnagel et al., 2001), with concordance of bi-
Abbott, Morriss, Hayhurst, & Scott, 2006; Welner, Welner, & Leonard, polar spectrum disorders as high as 97% between identical twins
1977). Though the discrete periods of hypomania and depression may (Hasler et al., 2006). Conversely, rates of bipolar disorder among
 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243 237

relatives of probands with unipolar depression are not higher than that influence whether cyclothymic temperament develops into
rates found in controls (Klein, Taylor, Dickstein, & Harding, 1988). Ad- mood disorder (Cicchetti & Rogosch, 2002; Hauser et al., 2007).
ditionally, people with cyclothymic disorder versus bipolar I have
similar family history rates of bipolar I, suggesting shared genetics 4.2. Personality and personality disorder
(Akiskal et al., 1977; Dunner et al., 1982).
It seems nearly certain that “bipolar spectrum disorders” do not Bipolar spectrum disorder and personality disorders may act as
result from a homogenous etiology (Hasler et al., 2006). The current risk factors for one another (Wittchen et al., 2003; Akiskal et al.,
theory is that multiple genes interact with environmental factors to 1995; Savino et al., 1993). Borderline personality disorder (BPD), in
produce bipolar disorder, rather than a causal mechanism involving particular, shares many symptoms and features with bipolar disor-
a single gene or environmental factor (Faraone, Glatt, & Tsuang, ders (Henry et al., 2001); and some propose including BPD on the bi-
2003; Mick & Faraone, 2009; Serretti & Mandelli, 2008; Smoller & polar spectrum (Akiskal, 2004; MacKinnon & Pies, 2006) (c.f. Paris,
Finn, 2003). This theory incorporates both the “multifactorial thresh- Gunderson, & Weinberg, 2007). Cyclothymic disorder, more than
old model” of genetic disease, whereby multiple genes contribute to a other subtypes, shares many characteristics with borderline, includ-
disease, but must pass a critical threshold before the disease becomes ing mood lability (Reich, Zanarini, & Fitzmaurice, 2011), irritability,
manifest (Hasler et al., 2006), and the “transactional theory of devel- interpersonal difficulties, and chronicity of symptoms (Akiskal,
opment,” whereby an individual's genetics, family environment, and 2004; Lawrence, Allen, & Chanen, 2011), making differential diagno-
life experiences combine to create a unique set of risk and protective sis between borderline personality disorder and cyclothymic disorder
factors for psychopathology (Sameroff & Mackenzie, 2003). difficult (Youngstrom, 2009). Others have hypothesized that the
Cyclothymic temperament may be a main mechanism by which rapid cycling forms of bipolar disorder, including cyclothymia, and
bipolar risk is passed between generations. If so, it would be a partic- borderline personality disorder are all manifestations of affective in-
ularly strong endophenotype for additional investigation (Evans et al., stability and should be classified together; although research is not
2005), perhaps as a quantitative trait instead of a diagnosis (Evans et yet sufficient to prove this connection (MacKinnon & Pies, 2006).
al., 2008). People with bipolar disorder and their healthy relatives can From a dimensional diagnostic perspective, cyclothymic tempera-
both be reliably differentiated from healthy controls by degree of cy- ment may be a link between bipolar disorder and borderline person-
clothymic temperament (Vázquez et al., 2008). Temperament may ality (Goldberg & Garno, 2009; Perugi & Akiskal, 2011). Cyclothymic
contribute to instability of affect, emotion, activity, and sleep, which temperament is common in both bipolar and BDP (as high as 40% of
heightens risk for fully syndromal bipolar disorder (Akiskal, Akiskal, cases) (Deltito et al., 2001), but in one study cyclothymic tempera-
et al., 2006; Vázquez et al., 2008). ment was significantly more prevalent in the borderline group
(Nilsson, Jorgensen, Straarup, & Licht, 2010). Additionally, the two
diagnoses can be differentiated by borderline having higher maladap-
4. Biological characteristics and laboratory studies
tive self-schema scores (Hantouche, 2010; Lawrence et al., 2011).
More than 30% of people with bipolar may also meet criteria for bor-
Although there is research investigating genetic and biological
derline personality (Brieger, Ehrt, & Marneros, 2003; Carpiniello, Lai,
markers for bipolar disorder, results thus far may be considered largely
Pirarba, Sardu, & Pinna, 2011), and such comorbidity can lead to a
preliminary. Most studies, including those looking at brain structure
more severe presentation, with greater impulsivity and suicide risk
and function, do not include cyclothymic disorder as a diagnostic cate-
(Carpiniello et al., 2011). Although suicidality and self-mutilation are
gory. Tentative biological evidence supports inclusion of cyclothymic
commonly associated with borderline, a recent study found that bipolar
disorder on the bipolar spectrum. Biological data at this time add mod-
disorder, rather than borderline, predicted self harm behavior. Perhaps
estly to the diagnostic validity of cyclothymic disorder.
some cases of self mutilation might more accurately be diagnosed
with cyclothymic disorder instead of borderline (Joyce, Light, Rowe,
4.1. Temperament Cloninger, & Kennedy, 2010).

Extensive research has studied cyclothymic temperament, and 4.3. Circadian rhythms
some see it as the biological foundation for many cases of bipolar dis-
order (Akiskal, 1996; Akiskal et al., 2005; Hauser et al., 2007; Although people with cyclothymic disorder do not experience
Kochman et al., 2005). Inasmuch as cyclothymic temperament is a full-blown mania, and may not demonstrate decreased need for
persistent trait, whereas cyclothymic disorder is conceptualized as sleep, they often experience significant sleep disturbance, due to the
an episodic syndrome, the two should be distinguishable, in spite of restlessness and agitation associated with their disorder (Findling et
shared characteristics. al., 2005; Kowatch, Youngstrom, Danielyan, & Findling, 2005). Sleep
The disorder and the temperament tend to co-occur, which might disturbance may occur during both hypomanic and depressive pe-
help to explain the chronic course of the disorder, relative to other bi- riods. Sleep disturbance may be a chronic diathesis among people
polar subtypes that fluctuate between more severe highs and lows with bipolar disorder: many experience circadian rhythm instability,
with periods of remission in between. Temperament may enhance and are sensitive to environmental and other influences on their
the tendency for people with cyclothymic disorder to be very irrita- sleep patterns (Harvey, Mullin, & Hinshaw, 2006; Hasler et al.,
ble. People with cyclothymic temperament tend to be extremely sen- 2006). This disruption may involve a mutation of the CLOCK gene,
sitive and easily “set-off.” Within the context of bipolar disorder, which is linked to both circadian rhythm instability and bipolar
people with cyclothymic temperament maybe categorized as having mood recurrence (Benedetti et al., 2003).
“dark”—as opposed to “sunny”—hypomanic phases (Akiskal et al., It may be that the tendency toward dysregulated sleep contributes
2003). People with cyclothymic disorder are often especially sensitive to the chronic nature of cyclothymic disorder. One hypothesis,
and impulsive in their reactions (Hantouche, Angst, & Akiskal, 2003; adapted from the social zeitgeber theory, is that upsetting an indivi-
Perugi, 2002). dual's circadian rhythms may act as an “internal trigger,” disrupting
Cyclothymic temperament is likely more prevalent than cyclothy- his/her schedule and creating instability that may lead to a mood ep-
mic disorder or other forms of bipolar disorder (Akiskal, 2008; isode (Shen et al., 2008). Though most people can weather sleep
Karam, Mneimneh, Salamoun, Akiskal, & Akiskal, 2005). Although a changes without serious consequences, individuals predisposed to
major risk factor for bipolar disorder, the lack of a one-to-one conver- mood instability are susceptible to increased emotional lability and
sion rate compels exploration of additional risk and protective factors dysregulation as a result of sleep disruption. The onset of a mood
238 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243

episode may further disturb sleep, making it more difficult for the ep- 5. The current state of cyclothymic disorder in clinical practice
isode to resolve. Sleep hygiene has become a target of many psycho- and research
social treatments for bipolar disorder (Fristad, Verducci, Walters, &
Young, 2009; D. Miklowitz et al., 2004; Schwartz & Feeny, 2007; 5.1. Clinical practice
Young & Fristad, 2007), with promising results in a treatment study
of cyclothymic disorder (Totterdell & Kellett, 2008). 5.1.1. Unmet need
Very few people with cyclothymic disorder obtain sufficient treat-
ment. According to epidemiological studies, most do not seek treatment.
4.4. Hypothalamic–pituitary–adrenal axis dysregulation and cortisol
When they do, the chances of misdiagnosis are high. Cyclothymic
level
disorder is rarely diagnosed clinically—most clinicians “stay blind to cy-
clothymia” (Hantouche et al., 2008). Differentiation within the bipolar
People with both unipolar depression and bipolar disorder have
spectrum might be less important, if the treatment prescription is likely
dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis, in-
to be similar. However, the nonbipolar diagnoses considered when
cluding elevated cortisol levels (Gallagher, Watson, Smith, Young, &
someone presents with cyclothymic disorder—depression, ADHD, and
Ferrier, 2007; Holsboer, 2001; Porter & Gallagher, 2006; Salaria et
disruptive behavior disorders, or borderline personality—indicate a
al., 2006). Elevated cortisol levels covary with poor emotion regula-
much different treatment course. There are potential negative effects as-
tion in cyclothymic disorder, consistent with other affective disorders
sociated with treatment using antidepressants or stimulants, and little
(Depue, Kleiman, Davis, Hutchinson, & Krauss, 1985). Subjects with
data supporting their efficacy for cyclothymia. The risk of misdiagnosis
cyclothymic disorder showed patterns of cortisol stress response
leading to mismatched treatment choices is substantial, given the simi-
that were twice as high and more prolonged compared to healthy
larity between depression and comorbid ADHD versus cyclothymic
controls, which may help to explain the chronic mood dysregulation
disorder (Van Meter, Youngstrom, Demeter, et al., 2011; Van Meter,
associated with cyclothymic disorder (Depue et al., 1985; Goplerud
Youngstrom, Youngstrom, et al., 2011).
& Depue, 1985). Cortisol response also suggested an altered circadian
rhythm. These findings support the inclusion of cyclothymic disorder
5.1.2. Assessment issues
within the bipolar spectrum.
Clinicians should be better trained to assess for subthreshold bipolar
symptoms among their patients with symptoms of affective dysregula-
4.5. Psychopharmacological response tion, anxiety, or impulsivity (Katzow, Hsu, & Ghaemi, 2003). The limited
available data are not being fully utilized clinically (Youngstrom et al.,
There are no blinded randomized clinical trials for pharmacologi- 2010). Clinical training needs more emphasis on recognition of early
cal acute treatment of cyclothymic disorder, and few published stages of bipolar disorder and its subtypes (Hauser et al., 2007). The ac-
open trials or case studies. Current adult and pediatric treatment curate assessment of hypomanic symptoms should be a priority, along
guidelines do not differentiate between cyclothymic disorder and with the recognition of the episodic nature of bipolar disorders
other bipolar disorders (Goodwin, 2009). People with cyclothymic (Youngstrom et al., 2010). These are key features to distinguishing bipo-
disorder and other bipolar subtypes appear to respond to pharmaceu- lar II from unipolar depression, as well as identification of cyclothymic
tical treatment similarly (Findling et al., 2007; Goto, Terao, Hoaki, & disorder.
Wang, 2010; Klein et al., 1986). The limited data on the treatment Another complicating factor is that symptoms of cyclothymic dis-
of cyclothymic disorder with mood stabilizing agents that are avail- order may present in childhood or adolescence. Diagnosis of bipolar
able suggest potential positive response to agents such as lithium, disorder in youth has been controversial, although extensive data
valproate, and possibly other anti-convulsants or antipsychotics about validity have become available. There is often a lingering per-
(Baldessarini et al., 2011; Deltito, 1993). For example, in a study of ception, in spite of data to the contrary (Geller, Tillman, Bolhofner,
28 adults exhibiting unstable mood, similar to cyclothymia, 68% expe- & Zimerman, 2008; Ghaemi et al., 2008), that pediatric bipolar disor-
rienced a reduction of symptoms and a stabilization of mood when der is different than in adults, and that the current DSM-IV criteria are
treated with valproic acid (Verhoeven & Tuinier, 2001). Offspring not appropriate for young people. This contributes to a lack of confi-
(N = 24, aged 6 to 18) of people with bipolar disorder, diagnosed dence in making a diagnosis, amplified by media coverage on the
with cyclothymic disorder or exhibiting mild mood symptoms, “over-diagnosis of bipolar disorder” (Carmichael, 2008). However,
showed a 78% response rate during open treatment with divalproex no change to the criteria for cyclothymic disorder—in adults or chil-
(Chang, Dienes, et al., 2003). A blinded targeted prevention study dren—has been proposed for DSM 5 (nor has any change been pro-
found that those youths with a combination of cyclothymic disorder posed for bipolar I, bipolar II, or bipolar NOS, with the exception of
and greater familial loading of bipolar disorder tended to remain sta- the most recent episode mixed qualifier) (American Psychiatric
ble longer on divalroex than placebo (Findling et al., 2007), but this Association, 2010). Emerging data, reviewed above, indicate that the
was a post hoc finding. Additionally, in an open trial of 33 adult pa- use of consistent definitions across the age span can be done with
tients, diagnosed with cyclothymic disorder or bipolar II, 79% im- high reliability and growing evidence of validity (Van Meter,
proved on low dose valproate (Jacobsen, 1993). In a case series, Youngstrom, Youngstrom, et al., 2011). Pediatric bipolar disorder, in
Bisol and Lara (2010) found that four adults with cyclothymic disor- general, is likely both under- and over-diagnosed (Geller et al.,
der, BP NOS, or cluster B personality disorder traits responded favor- 2002), but cyclothymic disorder is, almost always, undiagnosed. Fail-
ably to a low dose of quetiapine with more stable mood, improved ing to consider the cyclothymic diagnosis creates a problem of “the
sleep, and less emotion reactivity. Similarly, a naturalistic study of excluded middle” and forces clinicians to either mislabel the patholo-
24 women, most of whom had failed previous medication trials, gy as not on the bipolar spectrum, with the attendant risks for treat-
lamotrigine reduced symptoms of depression and cyclothymic tem- ment mismatch, or else to “upgrade” the diagnosis to bipolar I,
perament (Manning et al., 2005). There is a major gap between the contributing to concerns about overdiagnosis.
evidence base for treatment of cyclothymic disorder versus the clini- Furthermore, temperament has proven to be a significant risk fac-
cal need based on its prevalence and impairment. In the absence of tor for both cyclothymic disorder and other forms of bipolar disorder,
stronger evidence, data suggest that a cyclothymic behaves as if on yet it is almost never assessed in clinical practice. In addition to sys-
the bipolar spectrum, and cautious approaches to treatment should tematically assessing DSM criteria, temperament seems as valuable
use similar algorithms but perhaps starting with lower doses and ti- as family psychiatric risk or developmental history in a diagnostic as-
trating slowly. sessment (Akiskal, 2008; Akiskal, Lancrenon, & Hantouche, 2006). Of
 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243 239

note, in alternate dimensional models of psychopathology (Kraemer, bipolar disorders is not yet well understood. There are hints that the
2007) cyclothymic disorder would occupy an important position be- construct of cyclothymic disorder plays a central role in the develop-
tween more severe mood disorders and subclinical presentations of ment and course of affective psychopathology, but the lack of diag-
moodiness and affective temperament. The temperament measures nostic precision in current studies precludes definitive conclusions
also offer a framework for assessment relevant constructs within a di- and slows progress in the field. The examination of diagnostic criteria
mensional approach. currently taking place for the revision of DSM-IV-TR and ICD-10 pro-
vides an opportunity to consider how to best conceptualize cyclothy-
5.1.3. Early intervention versus the underdeveloped research base for mic disorder, and whether it should continue each of its historical
treatment roles: as a subtype of bipolar disorder, an affective temperament, a di-
Failing to diagnose cyclothymic disorder limits the opportunity to athesis, prodrome, and personality style. Bipolar is a heterogeneous
ameliorate current symptoms and to forestall or prevent progression disorder; the paths to onset and ultimate results vary widely, and
to bipolar I or II. Early intervention is important to a positive progno- the task of investigating them is large. But, we have a significant foun-
sis (Hauser et al., 2007); however, treatment and outcomes data on dation of knowledge from which to build—once the field acknowl-
cyclothymic disorder, especially in youth samples, does not yet offer edges that its focus on bipolar I has come at the expense of the
guidance about preventative interventions. Though pharmaceutical much larger population of people with subthreshold subtypes.
treatment is the first line for bipolar spectrum disorders, psychosocial
treatments are gaining credibility as a valuable tool to improve func- References
tioning and to increase duration between mood episodes (Miklowitz,
1996; Miklowitz, 2006; Totterdell & Kellett, 2008; Youngstrom et al., Akiskal, H. S. (1994). Dysthymic and cyclothymic depressions: Therapeutic consider-
ations. Journal of Clinical Psychiatry, 55(Supplement), 46–52.
2010). Psychosocial treatments may be the most appropriate way to Akiskal, H. (1996). The temperamental foundations of affective disorders. In C. Mundt,
approach early presentations of mood symptoms, but without sys- & H. L. Freeman (Eds.), Interpersonal factors in the origin and course of affective
tematically investigating these, and other treatment options, we do disorders (pp. 3–30). London: RCPsych Publications.
Akiskal, H. (2001). Dysthymia and cyclothymia in psychiatric practice a century after
not know how to best treat the range of presentations seen in clinics. Kraepelin. Journal of Affective Disorders, 62(1–2), 17–31. doi:10.1016/S0165-0327
(00)00347-5.
5.2. Research implications Akiskal, H. S. (2003). Validating ‘hard’ and ‘soft’ phenotypes within the bipolar spec-
trum: Continuity or discontinuity? Journal of Affective Disorders, 73(1–2), 1–5.
Akiskal, H. (2004). Demystifying borderline personality: Critique of the concept and
A recurring theme in this review has been the need for the inclu- unorthodox reflections on its natural kinship with the bipolar spectrum. Acta
sion of cyclothymic disorder in studies of mood disorders. Opportuni- Psychiatrica Scandinavica, 110(6), 401–407. doi:10.1111/j.1600-0447.2004.00461.x.
Akiskal, H. (2008). The emergence of the bipolar spectrum: Validation along clinical–
ties for impact appear to be greater through the study of the
epidemiological and familial–genetic lines. Psychopharmacology Bulletin, 40(4),
subthreshold presentations as targets to prevent or forestall progres- 99–115.
sion to more acute or treatment resistant stages of illness (DelBello & Akiskal, H., & Akiskal, K. (1992). Cyclothymic, hyperthymic, and depressive tempera-
Geller, 2001; Miklowitz & Chang, 2008; Shankman et al., 2009). Cy- ments as subaffective variants of mood disorders. American Psychiatric Press Review
of Psychiatry, 11, 43–62.
clothymic disorder is a topic well-suited to a developmental psycho- Akiskal, H., Akiskal, K., Allilaire, J., Azorin, J., Bourgeois, M., Sechter, D., et al. (2005). Val-
pathology approach: it tends to have a young age of onset and it is idating affective temperaments in their subaffective and socially positive attri-
important that diagnosis and treatment are initiated early (Goto et butes: Psychometric, clinical and familial data from a French national study.
Journal of Affective Disorders, 85(1–2), 29–36.
al., 2010). Developmentally, cyclothymic disorder may shed light on Akiskal, H., Akiskal, K., Lancrenon, S., Hantouche, E., Fraud, J. P., Gury, C., et al. (2006).
risk factors, including family history, environment, comorbidity, and Validating the bipolar spectrum in the French National EPIDEP Study: Overview
biological traits that contribute to psychopathology. Taking a more in- of the phenomenology and relative prevalence of its clinical prototypes. Journal
of Affective Disorders, 96(3), 197–205.
terdisciplinary approach, incorporating objective measurement of Akiskal, H., Bourgeois, M., Angst, J., Post, R., Möller, H. J., & Hirschfeld, R. (2000). Re-
potentially-related biological traits, could be the best way to expand evaluating the prevalence of and diagnostic composition within the broad clinical
our understanding and fully define the boundaries of bipolar disorder, spectrum of bipolar disorders. Journal of Affective Disorders, 59(Supplement 1),
S5–S30. doi:10.1016/S0165-0327(00)00203-2.
eventually leading to more precise assessment and treatment of the
Akiskal, H., Djenderedjian, A., Rosenthal, R., & Khani, M. (1977). Cyclothymic disorder:
myriad bipolar presentations. The prospective study of young people Validating criteria for inclusion in the bipolar affective group. The American Journal
with cyclothymic disorder is essential to our understanding of the of Psychiatry, 134(11), 1227–1233.
Akiskal, H., Downs, J., Jordan, P., Watson, S., Daugherty, D., & Pruitt, D. (1985). Affective
risk, treatment effectiveness, course, and outcome of this disorder.
disorders in referred children and younger siblings of manic-depressives: Mode of
Another key issue is the examination of burden of illness: some evi- onset and prospective course. Archives of General Psychiatry, 42(10), 996–1003.
dence suggests that the greater chronicity associated with cyclothy- doi:10.1001/archpsyc.1985.01790330076009.
mic disorder may lead to equal or greater impairment than occurs Akiskal, H., Hantouche, E., & Allilaire, J. F. (2003). Bipolar II with and without cyclothy-
mic temperament: “Dark” and “sunny” expressions of soft bipolarity. Journal of
with more acute but brief mood disorders. Prospective longitudinal Affective Disorders, 73(1–2), 49–57. doi:10.1016/S0165-0327(02)00320-8.
investigations will help clarify this possibility. It is crucial that inves- Akiskal, H., Khani, M., & Scott-Strauss, A. (1979). Cyclothymic temperamental disor-
tigations separate cyclothymic disorder from bipolar NOS, rather than ders. The Psychiatric Clinics of North America, 2, 527–554.
Akiskal, H., Lancrenon, S., & Hantouche, E. (2006). Validating the soft bipolar spectrum
lumping them together. in the French National EPIDEP Study: The prominence of BP-II 1/2. Journal of Affective
Disorders, 96(3), 207–213. doi:10.1016/j.jad.2006.03.011.
6. Conclusion Akiskal, H., Maser, J., Zeller, P., Endicott, J., Coryell, W., Keller, M., et al. (1995). Switch-
ing from 'Unipolar' to Bipolar II: An 11-year prospective study of clinical and tem-
peramental predictors in 559 patients. Archives of General Psychiatry, 52(2),
The goal of this review was to describe the current state of the 114–123. doi:10.1001/archpsyc.52.2.114.
literature on cyclothymic disorder, and to make note of areas in Algorta, G. P., Youngstrom, E. A., Frazier, T. W., Freeman, A. J., Youngstrom, J. K., &
Findling, R. L. (2011). Suicidality in pediatric bipolar disorder: Predictor or out-
need of further investigation. Data indicate that cyclothymic disorder come of family processes and mixed mood presentation? Bipolar Disorders, 13(1),
is prevalent in both community and clinical samples, affecting mil- 76–86. doi:10.1111/j.1399-5618.2010.00886.x.
lions of people worldwide, and often leading to considerable impair- Alloy, L., Urošević, S., Abramson, L., Jager-Hyman, S., Nusslock, R., Whitehouse, W., et al.
(2011). Progression along the bipolar spectrum: A longitudinal study of predictors
ment. Its position on the bipolar spectrum seems relatively secure
of conversion from bipolar spectrum conditions to bipolar I and II disorders. Journal
based on validity data, consistent with the current proposal to retain of Abnormal Psychology. doi:10.1037/a0023973.supp (Supplemental).
it in the mood disorder section of DSM-5. Less clear are the ways in Alnaes, R., & Torgensen, S. (1989). Personality and personality disorders among pa-
which cyclothymic disorder intersects with other psychological phe- tients with major depression in combination with dysthymic or cyclothymic disor-
ders. Acta Psychiatrica Scandinavica, 79, 363–369.
nomena. The relation between cyclothymic disorder and tempera- American Psychiatric Association (2001). Diagnostic and statistical manual of mental
ment, personality, depressive disorders, and other subthreshold disorders (4th-Text Revision ed.). Washington, DC: Author.
240 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243

Andreasen, N., Grove, W., Shapiro, R., Keller, M., Hirschfeld, R., & McDonald-Scott, P. Cicchetti, D., & Rogosch, F. A. (2002). A developmental psychopathology perspective on
(1981). Reliability of lifetime diagnosis. Archives of General Psychiatry, 38, 400–404. adolescence. Journal of Consulting and Clinical Psychology, 70(1), 6–20. doi:
Angst, J. (1966). On the etiology and nosology of endogenous depressive psychoses. A 10.1037/0022-006x.70.1.6.
genetic, sociologic and clinical study. Monographien aus dem Gesamtgebiete der Cicero, D., Epler, A., & Sher, K. (2009). Are there developmentally limited forms of bipolar
Neurologie und Psychiatrie, 112, 1. disorder? Journal of Abnormal Psychology, 118(3), 431–447. doi:10.1037/a0015919.
Angst, J., Gamma, A., Benazzi, F., Ajdacic, V., Eich, D., & Rössler, W. (2003). Toward a re- DelBello, M., & Geller, B. (2001). Review of studies of child and adolescent offspring
definition of subthreshold bipolarity: Epidemiology and proposed criteria for of bipolar parents. Bipolar Disorders, 3(6), 325–334. doi:10.1034/j.1399-5618.
bipolar-II, minor bipolar disorders and hypomania. Journal of Affective Disorders, 2001.30607.x.
73(1–2), 133–146. doi:10.1016/S0165-0327(02)00322-1. Deltito, J. (1993). The effect of valproate on bipolar spectrum temperamental disorders.
Angst, J., Gamma, A., Neuenschwander, M., Ajdacic-Gross, V., Eich, D., Rossler, W., et al. The Journal of Clinical Psychiatry, 54(8), 300–304.
(2005). Prevalence of mental disorders in the Zurich Cohort Study: A twenty year Deltito, J., Martin, L., Riefkohl, J., Austria, B., Kissilenko, A., Corless, C., et al. (2001). Do
prospective study. Epidemiologia e Psichiatria Sociale, 14(2), 68–76. patients with borderline personality disorder belong to the bipolar spectrum?
Angst, J., & Marneros, A. (2001). Bipolarity from ancient to modern times: Conception, Journal of Affective Disorders, 67(1–3), 221–228.
birth and rebirth. Journal of Affective Disorders, 67(1), 3–19. doi:10.1016/S0165- Denicoff, K., Leverich, G., Nolen, W., Rush, A., McElroy, S., Keck, P., et al. (2000). Validation
0327(01)00429-3. of the prospective NIMH-Life-Chart Method (NIMH-LCMTM-p) for longitudinal as-
American Psychiatric Association (1968). Diagnostic and statistical manual of mental sessment of bipolar illness. Psychological Medicine, 30(06), 1391–1397 doi:null.
disorders (Second Edition). Washington, DC: American Psychiatric Association. Depue, R. (1981). A behavioral paradigm for identifying persons at risk for bipolar de-
American Psychiatric Association (1980). Diagnostic and statistical manual of mental pressive disorder: A conceptual framework and five validation studies. Journal of
disorders (Third Edition). Washington, DC: American Psychiatric Association. Abnormal Psychology, 90(5). doi:10.1037/0021-843X.90.5.381.
American Psychiatric Association (2010, May 21). DSM-5 development. Retrieved Depue, R., Kleiman, R., Davis, P., Hutchinson, M., & Krauss, S. (1985). The behavioral
August 3, 2010, 2010, from http://www.dsm5.org/ProposedRevisions/Pages/ high-risk paradigm and bipolar affective disorder, VIII: Serum free cortisol in non-
proposedrevision.aspx?rid=426 patient cyclothymic subjects selected by the General Behavior Inventory. The
Azorin, J. M., Kaladjian, A., Besnier, N., Adida, M., Hantouche, E., Lancrenon, S., et al. American Journal of Psychiatry, 142(2), 175–181.
(2010). Suicidal behaviour in a French Cohort of major depressive patients: Char- Dienes, K., Hammen, C., Henry, R., Cohen, A., & Daley, S. (2006). The stress sensitization
acteristics of attempters and nonattempters. Journal of Affective Disorders, 123 hypothesis: Understanding the course of bipolar disorder. Journal of Affective Disor-
(1–3), 87–94. doi:10.1016/j.jad.2009.09.004. ders, 95(1–3), 43–49. doi:10.1016/j.jad.2006.04.009.
Baethge, C., Salvatore, P., & Baldessarini, R. J. (2003). “On cyclic insanity” by Karl Lud- Dunner, D. L., Russek, F. D., Russek, B., & Fieve, R. R. (1982). Classification of bipolar
wig Kahlbaum, MD: A translation and commentary. Harvard Review of Psychiatry, affective disorder subtypes. Comprehensive Psychiatry, 23(2), 186–189. doi:
11(2), 78–90. doi:10.1080/10673220303958. 10.1016/0010-440X(82)90064-5.
Baldessarini, R., & Tondo, L. (2003). Suicide risk and treatments for patients with bipo- Edvardsen, J., Torgersen, S., Røysamb, E., Lygren, S., Skre, I., Onstad, S., et al. (2008). Her-
lar disorder. Journal of the American Medical Association, 290(11), 1517–1519. doi: itability of bipolar spectrum disorders. Unity or heterogeneity. Journal of Affective Dis-
10.1001/jama.290.11.1517. orders, 106(3), 229–240.
Baldessarini, R. J., Vazquez, G., & Tondo, L. (2011). Treatment of cyclothymic disorder: Evans, L. M., Akiskal, H. S., Greenwood, T. A., Nievergelt, C. M., Keck, P. E., Jr., McElroy, S. L.,
Commentary. Psychotherapy and Psychosomatics, 80, 131–135. et al. (2008). Suggestive linkage of a chromosomal locus on 18p11 to cyclothymic
Benedetti, F., Serretti, A., Colombo, C., Barbini, B., Lorenzi, C., Campori, E., et al. (2003). temperament in bipolar disorder families. American Journal of Medical Genetics. Part
Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness B, Neuropsychiatric Genetics, 147, 326–332. doi:10.1002/ajmg.b.30601.
recurrence in bipolar depression. American Journal of Medical Genetics. Part B, Evans, L., Akiskal, H., Keck, P., McElroy, S., Sadovnick, A. D., Remick, R., et al. (2005).
Neuropsychiatric Genetics, 123B(1), 23–26. doi:10.1002/ajmg.b.20038. Familiality of temperament in bipolar disorder: Support for a genetic spectrum.
Biederman, J., Mick, E., Faraone, S., Spencer, T., Wilens, T., & Wozniak, J. (2003). Journal of Affective Disorders, 85(1–2), 153–168.
Current concepts in the validity, diagnosis and treatment of paediatric bipolar dis- Faraone, S., Glatt, S., & Tsuang, M. (2003). The genetics of pediatric-onset bipolar disor-
order. The International Journal of Neuropsychopharmacology, 6, 293–300. doi: der. Biological Psychiatry, 53(11), 970–977. doi:10.1016/S0006-3223(02)01893-0.
10.1017/S1461145703003547. Faravelli, C., Degl'Innocenti, B. G., Aiazzi, L., Incerpi, G., & Pallanti, S. (1990). Epidemiology
Birmaher, B., Axelson, D., Goldstein, B., Strober, M., Gill, M. K., Hunt, J., et al. (2009). Four- of mood disorders: A community survey in Florence. Journal of Affective Disorders, 20,
year longitudinal course of children and adolescents with bipolar spectrum disor- 135–141.
ders: The course and outcome of bipolar youth (COBY) study. The American Journal Fava, G. A., Rafanelli, C., Tomba, E., Guidi, J., & Grandi, S. (2011). The sequential combi-
of Psychiatry. doi:10.1176/appi.ajp.2009.08101569 appi.ajp.2009.08101569. nation of cognitive behavioral treatment and well-being therapy in cyclothymic
Birmaher, B., Axelson, D., Strober, M., Gill, M. K., Valeri, S., Chiappetta, L., et al. (2006). disorder. Psychotherapy and Psychosomatics, 80(3), 136–143.
Clinical course of children and adolescents with bipolar spectrum disorders. Fields, B., & Fristad, M. (2009). Assessment of childhood bipolar disorder. Clinical Psychol-
Archives of General Psychiatry, 63(2), 175–183. doi:10.1001/archpsyc.63.2.175. ogy: Science and Practice, 16(2), 166–181. doi:10.1111/j.1468-2850.2009.01156.x.
Bisol, L. W., & Lara, D. R. (2010). Low-dose quetiapine for patients with dysregulation of Findling, R., Frazier, T., Youngstrom, E., McNamara, N., Stansbrey, R., Gracious, B., et al.
hyperthymic and cyclothymic temperaments. Journal of Psychopharmacology, 24 (2007). Double-blind, placebo-controlled trial of divalproex monotherapy in the
(3), 421–424. doi:10.1177/0269881108097715. treatment of symptomatic youth at high risk for developing bipolar disorder. The
Blanco, C., Laje, G., Olfson, M., Marcus, S., & Pincus, H. (2002). Trends in the treatment of Journal of Clinical Psychiatry, 68(5), 781–788.
bipolar disorder by outpatient psychiatrists. The American Journal of Psychiatry, 159 Findling, R., Gracious, B., McNamara, N., Youngstrom, E., Demeter, C., Branicky, L., et al.
(6), 1005–1010. doi:10.1176/appi.ajp. 159.6.1005. (2001). Rapid, continuous cycling and psychiatric co-morbidity in pediatric bipolar I
Brieger, P., Ehrt, U., & Marneros, A. (2003). Frequency of comorbid personality disorders disorder. Bipolar Disorders, 3, 202–210. doi:10.1034/j.1399-5618.2001.30405.x.
in bipolar and unipolar affective disorders. Comprehensive Psychiatry, 44(1), 28–34. Findling, R., Youngstrom, E., McNamara, N., Stansbrey, R., Demeter, C., Bedoya, D., et al.
Brieger, P., & Marneros, A. (1997). Dysthymia and cyclothymia: Historical origins and (2005). Early symptoms of mania and the role of parental risk. Bipolar Disorders, 7
contemporary development. Journal of Affective Disorders, 45(3), 117–126. doi: (6), 623–634. doi:10.1111/j.1399-5618.2005.00260.x.
10.1016/S0165-0327(97)00053-0. Freeman, M. P., Freeman, S. A., & McElroy, S. L. (2002). The comorbidity of bipolar and
Calabrese, J., Fatemi, S., Kujawa, M., & Woyshville, M. (1996). Predictors of response to anxiety disorders: Prevalence, psychobiology, and treatment issues. Journal of
mood stabilizers. Journal of Clinical Psychopharmacology, 16(2), 24S. Affective Disorders, 68(1), 1–23.
Cantwell, D. (1996). Classification of child and adolescent psychopathology. Journal of Child Freeman, A., Youngstrom, E., Michalak, E., Siegel, R., Meyers, O., & Findling, R. (2009).
Psychology and Psychiatry, 37(1), 3–12. doi:10.1111/j.1469-7610.1996.tb01377.x. Quality of life in pediatric bipolar disorder. Pediatrics, 123(3), e446–e452. doi:
Carmichael, M. (2008, May 26). Bipolar disorder is a mystery and a subject of medical 10.1542/peds.2008-0841.
debate. But for the Blakes, it's just reality. Newsweek, 7. Fristad, M. A., Verducci, J. S., Walters, K., & Young, M. E. (2009). Impact of multifamily
Carpenter-Song, E. (2009). Caught in the psychiatric net: Meanings and experiences of psychoeducational psychotherapy in treating children aged 8 to 12 years with
ADHD, pediatric bipolar disorder and mental health treatment among a diverse mood disorders. Archives of General Psychiatry, 66(9), 1013–1021. doi:10.1001/
group of families in the United States. Culture, Medicine and Psychiatry, 33(1), archgenpsychiatry.2009.112.
61–85. doi:10.1007/s11013-008-9120-4. Gallagher, P., Watson, S., Smith, M., Young, A., & Ferrier, I. N. (2007). Plasma cortisol-
Carpiniello, B., Lai, L., Pirarba, S., Sardu, C., & Pinna, F. (2011). Impulsivity and aggressive- dehydroepiandrosterone (DHEA) ratios in schizophrenia and bipolar disorder.
ness in bipolar disorder with co-morbid borderline personality disorder. Psychiatry Schizophrenia Research, 90(1–3), 258–265.
Research, 188(1), 40–44. doi:10.1016/j.psychres.2010.10.026. Geller, B., & Tillman, R. (2005). Prepubertal and early adolescent bipolar I disorder: Re-
Cassano, G., Dell'Osso, L., Frank, E., Miniati, M., Fagiolini, A., Shear, K., et al. (1999). The bi- view of diagnostic validation by Robins and Guze criteria. The Journal of Clinical
polar spectrum: A clinical reality in search of diagnostic criteria and an assessment Psychiatry, 66, 21–28.
methodology. Journal of Affective Disorders, 54(3), 319–328. doi:10.1016/S0165- Geller, B., Tillman, R., Bolhofner, K., & Zimerman, B. (2008). Child bipolar I disorder:
0327(98)00158-X. prospective continuity with adult bipolar I disorder; characteristics of second
Cassidy, F., & Carroll, B. J. (2001). The clinical epidemiology of pure and mixed manic and third episodes; predictors of 8-year outcome. Archives of General Psychiatry,
episodes. Bipolar Disorders, 3(1), 35–40. doi:10.1034/j.1399-5618.2001.030105.x. 65(10), 1125–1133. doi:10.1001/archpsyc.65.10.1125.
Chang, K., Blasey, C., Ketter, T., & Steiner, H. (2003). Temperament characteristics of Geller, B., Zimmerman, B., Williams, M., DelBello, M., Frazier, J., & Beringer, L. (2002).
child and adolescent bipolar offspring. Journal of Affective Disorders, 77(1), 11–19. Phenomenology of prepubertal and early adolescent bipolar disorder: Examples
doi:10.1016/S0165-0327(02)00105-2. of elated mood, grandiose behaviors, decreased need for sleep, racing thoughts
Chang, K. D., Dienes, K., Blasey, C., Adleman, N., Ketter, T., & Steiner, H. (2003). Divalproex and hypersexuality. Journal of Child and Adolescent Psychopharmacology, 12(1),
monotherapy in the treatment of bipolar offspring with mood and behavioral disor- 3–9. doi:10.1089/10445460252943524.
ders and at least mild affective symptoms. The Journal of Clinical Psychiatry, 64(8), Ghaemi, S. (1995). Lack of insight in bipolar disorder: The acute manic episode. The
936–942. Journal of Nervous and Mental Disease, 183(7), 464–467.
 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243 241

Ghaemi, S., Bauer, M., Cassidy, F., Malhi, G., Mitchell, P., Phelps, J., et al. (2008). Diagnostic personality disorder, temperament and character. The Australian and New Zealand
guidelines for bipolar disorder: A summary of the International Society for Bipolar Journal of Psychiatry, 44(3), 250–257. doi:10.3109/00048670903487159.
Disorders Diagnostic Guidelines Task Force Report. Bipolar Disorders, 10, 117–128. Judd, L., & Akiskal, H. (2003). The prevalence and disability of bipolar spectrum disor-
doi:10.1111/j.1399-5618.2007.00556.x. ders in the US population: Re-analysis of the ECA database taking into account
Goldberg, J., & Garno, J. (2009). Age at onset of bipolar disorder and risk for comorbid subthreshold cases. Journal of Affective Disorders, 73(1–2), 123–131. doi:
borderline personality disorder. Bipolar Disorders, 11(2), 205–208. 10.1016/S0165-0327(02)00332-4.
Goldberg, J., & Harrow, M. (1994). Kindling in bipolar disorders: A longitudinal follow- Karam, E., Mneimneh, Z., Salamoun, M., Akiskal, K., & Akiskal, H. (2005). Psychometric
up study. Biological Psychiatry, 35(1), 70–72. properties of the Lebanese-Arabic TEMPS-A: A national epidemiologic study. Journal
Goldstein, T., Birmaher, B., Axelson, D., Ryan, N., Strober, M., Gill, M. K., et al. (2005). His- of Affective Disorders, 87(2–3), 169–183.
tory of suicide attempts in pediatric bipolar disorder: Factors associated with in- Katzow, J., Hsu, D., & Ghaemi, S. (2003). The bipolar spectrum: A clinical perspective.
creased risk. Bipolar Disorders, 7(6), 525–535. doi:10.1111/j.1399-5618.2005.00263.x. Bipolar Disorders, 5(6), 436–442. doi:10.1046/j.1399-5618.2003.00068.x.
Goodwin, G. (2009). Evidence-based guidelines for treating bipolar disorder: Revised sec- Kessler, R., Avenevoli, S., Green, J., Gruber, M., Guyer, M., He, Y., et al. (2009). National
ond edition recommendations from the British Association for Psychopharmacology. Comorbidity Survey replication adolescent supplement (NCS-a): III. Concordance
Journal of Psychopharmacology, 23(4), 346–388. doi:10.1177/0269881109102919. of DSM-IV/CIDI diagnoses with clinical reassessments. Journal of the
Goodwin, F., & Jamison, K. (1990). Manic-depressive illness (1 ed.). New York: Oxford American Academy of Child and Adolescent Psychiatry, 48(4), 386–399. doi:
University Press. 10.1097/CHI.0b013e31819a1cbc.
Goodwin, F., & Jamison, K. (2007). Manic-depressive illness (2nd ed.). New York: Oxford Kessler, R., McGonagle, K., Zhao, S., Nelson, C., Hughes, M., Eshleman, S., et al. (1994).
University Press. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United
Goplerud, E., & Depue, R. A. (1985). Behavioral response to naturally occurring stress in States. Results from the National Comorbidity Survey. Archives of General Psychiatry,
cyclothymia and dysthymia. Journal of Abnormal Psychology, 94(2), 128–139. doi: 51(1), 8–19.
10.1037/0021-843x.94.2.128. Klein, D. (2008). Classification of depressive disorders in the DSM-V: Proposal for a
Goto, S., Terao, T., Hoaki, N., & Wang, Y. (2010). Cyclothymic and hyperthymic temper- two-dimension system. Journal of Abnormal Psychology, 117(3), 552–560. doi:
aments may predict bipolarity in major depressive disorder: A supportive evidence 10.1037/0021-843X.117.3.552.
for bipolar II1/2 and IV. Journal of Affective Disorders. doi:10.1016/j.jad.2010.07.016. Klein, D. N., Depue, R. A., & Slater, J. F. (1985). Cyclothymia in the adolescent offspring
Grant, B., Stinson, F., Hasin, D., Dawson, D., Chou, S. P., Ruan, W. J., et al. (2005). Preva- of parents with bipolar affective disorder. Journal of Abnormal Psychology, 94(2),
lence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: 115–127. doi:10.1037/0021-843x.94.2.115.
Results from the national epidemiologic survey on alcohol and related conditions. Klein, D., Depue, R., & Slater, J. (1986). Inventory identification of cyclothymia: IX.
The Journal of Clinical Psychiatry, 66(10), 1205–1215. Validation in offspring of bipolar I patients. Archives of General Psychiatry, 43(5),
Gupta, S., Basu, S., & Sinha, V. (2004). Prodrome in childhood and adolescent mania. 441–445.
Hong Kong Journal of Psychiatry, 14(3), 26. Klein, D., Taylor, E., Dickstein, S., & Harding, K. (1988). Primary early-onset dysthymia:
Hantouche, E. (2009). Validating cyclothymia as a distinct variant of bipolarity. Paper Comparison with primary nonbipolar nonchronic major depression on demo-
presented at the International Review of Bipolar Disorders, Lisbon. graphic, clinical, familial, personality, and socioenvironmental characteristics and
Hantouche, E. (2010). Cyclothymia, affective basic temperaments, and schema focused short-term outcome. Journal of Abnormal Psychology, 97(4), 387–398. doi:
diagnosis: Exploring soft bipolarity. Paper presented at the International Review of 10.1037/0021-843X.97.4.387.
Bipolar Disorders, Budapest. Kochman, F., Hantouche, E., Ferrari, P., Lancrenon, S., Bayart, D., & Akiskal, H. (2005).
Hantouche, E. (2011). Dealing with BP-II complexity: Toward simplexity. Paper pre- Cyclothymic temperament as a prospective predictor of bipolarity and suicidality
sented at the International Review of Bipolar Disorders, Rome. in children and adolescents with major depressive disorder. Journal of Affective
Hantouche, E., & Angst, J. (2008). Rate and risk factors of hypomania in recurrent and Disorders, 85(1–2), 181–189.
resistant depression. Paper presented at the International Society on Brain and Be- Koukopoulos, A., Sani, G., Koukopoulos, A. E., Minnai, G. P., Girardi, P., Pani, L., et al.
haviour: 3rd International Congress on Brain and Behaviour. (2003). Duration and stability of the rapid-cycling course: A long-term personal
Hantouche, E., Angst, J., & Akiskal, H. (2003). Factor structure of hypomania: Interrelation- follow-up of 109 patients. Journal of Affective Disorders, 73(1–2), 75–85. doi:
ships with cyclothymia and the soft bipolar spectrum. Journal of Affective Disorders, 73 10.1016/S0165-0327(02)00321-X.
(1–2), 39–47. Kowatch, R., Youngstrom, E., Danielyan, A., & Findling, R. (2005). Review and meta-
Hantouche, E. G., Azorin, J. M., Lancrenon, S., Garay, R. P., & Angst, J. (2009). Prevalence of analysis of the phenomenology and clinical characteristics of mania in children and
hypomania in recurrent or resistant depression: Bipolact surveys. Annales Medico- adolescents. Bipolar Disorders, 7(6), 483–496. doi:10.1111/j.1399-5618.2005.00261.x.
Psychologiques, Revue Psychiatrique, 167(1), 30–37. doi:10.1016/j.amp. 2008.11.016. Kraemer, H. (2007). DSM categories and dimensions in clinical and research contexts.
Hantouche, E., & Erfurth, A. (2010). Rethinking subthreshold bipolarity: The rebirth of International Journal of Methods in Psychiatric Research, 16, S8–S15. doi:
Kahlbaum–Hecker syndrome. European Psychiatry, 25(Supplement 1). doi: 10.1002/mpr.211.
10.1016/s0924-9338(10)70170-x 170–170. Kraepelin, E. (1921). Manic-depressive insanity and paranoia. Edinburgh: Livingstone.
Hantouche, E., Trybou, V., & Majdalani, C. (2008). Cyclothymia: From nosological vali- Lawrence, K., Allen, J., & Chanen, A. (2011). A study of maladaptive schemas and bor-
dation to patient caring. Annals of General Psychiatry, 7(Suppl. 1), S3. derline personality disorder in young people. Cognitive Therapy and Research, 35
Harvey, A., Mullin, B., & Hinshaw, S. (2006). Sleep and circadian rhythms in children (1), 30–39. doi:10.1007/s10608-009-9292-4.
and adolescents with bipolar disorder. Development and Psychopathology, 18(04), Lewinsohn, P., Klein, D., & Seeley, J. (1995). Bipolar disorders in a community sample of
1147–1168. doi:10.1017/S095457940606055X. older adolescents: Prevalence, phenomenology, comorbidity, and course. Journal of
Hasler, G., Drevets, W. C., Gould, T. D., Gottesman, I. I., & Manji, H. K. (2006). Toward the American Academy of Child and Adolescent Psychiatry, 34(4), 454–463.
constructing an endophenotype strategy for bipolar disorders. Biological Psychiatry, Lewinsohn, P., Klein, D., & Seeley, J. (2000). Bipolar disorder during adolescence and
60(2), 93–105. doi:10.1016/j.biopsych.2005.11.006. young adulthood in a community sample. Bipolar Disorders, 2, 281–293. doi:
Hauser, M., Pfennig, A., Özgürdal, S., Heinz, A., Bauer, M., & Juckel, G. (2007). Early 10.1034/j.1399-5618.2000.20309.x.
recognition of bipolar disorder. European Psychiatry, 22(2), 92–98. doi:10.1016/ Lewinsohn, P., Seeley, J., & Klein, D. (2003). Bipolar disorder in adolescents. Epidemiology
j.eurpsy.2006.08.003. and suicidal behavior. In B. Geller, & M. DelBello (Eds.), Child and early adolescent bi-
Haustgen, T., & Akiskal, H. (2006). French antecedents of “contemporary” concepts in polar disorder (pp. 7–24). New York: Guilford Press.
the American Psychiatric Association's classification of bipolar (mood) disorders. MacKinnon, D., & Pies, R. (2006). Affective instability as rapid cycling: Theoretical and
Journal of Affective Disorders, 96(3), 149–163. doi:10.1016/j.jad.2006.09.014. clinical implications for borderline personality and bipolar spectrum disorders.
Hecker, E. (2003). Cyclothymia, a circular mood disorder. History of Psychiatry, 14(3), Bipolar Disorders, 8(1), 1–14. doi:10.1111/j.1399-5618.2006.00283.x.
377–390. doi:10.1177/0957154x030143007. MacKinnon, D., Zandi, P., Gershon, E., Nurnberger, J., Reich, T., & DePaulo, J. (2003).
Henry, C., Mitropoulou, V., New, A., Koenigsberg, H., Silverman, J., & Siever, L. (2001). Rapid switching of mood in families with multiple cases of bipolar disorder.
Affective instability and impulsivity in borderline personality and bipolar II Archives of General Psychiatry, 60(9), 921–928. doi:10.1001/archpsyc.60.9.921.
disorders: Similarities and differences. Journal of Psychiatric Research, 35(6), Manning, J. S., Haykal, R. F., Connor, P. D., Cunningham, P. D., Jackson, W. C., &
307–312. Long, S. (2005). Sustained remission with lamotrigine augmentation or
Hlastala, S., Frank, E., Kowalski, J., Sherrill, J., Tu, X., Anderson, B., et al. (2000). Stressful monotherapy in female resistant depressives with mixed cyclothymic‚
life events, bipolar disorder, and the “kindling model”. Journal of Abnormal Psychology, Äìdysthymic temperament. Journal of Affective Disorders, 84(2–3), 259–266.
109(4), 777–786. doi:10.1016/j.jad.2004.01.016.
Holsboer, F. (2001). Stress, hypercortisolism and corticosteroid receptors in depres- Marneros, A. (2001). Expanding the group of bipolar disorders. Journal of Affective Disorders,
sion: Implications for therapy. Journal of Affective Disorders, 62(1–2), 77–91. 62(1–2), 39–44.
Howland, R., & Thase, M. (1993). A comprehensive review of cyclothymic disorder. The Marneros, A. (2001). Origin and development of concepts of bipolar mixed states. Journal
Journal of Nervous and Mental Disease, 181(8), 485–493. of Affective Disorders, 67(1–3), 229–240.
Jacobsen, F. M. (1993). Low-dose valproate: A new treatment for cyclothymia, mild Mazure, C., & Gershon, E. (1979). Blindness and reliability in lifetime psychiatric diagnosis.
rapid cycling disorders, and premenstrual syndrome. Journal of Clinical Psychiatry, Archives of General Psychiatry, 36(5), 521–525. doi:10.1001/archpsyc.1979.
54(6), 229–234. 01780050031002.
Jensen, P., Youngstrom, E., Steiner, H., Findling, R., Meyer, R., Malone, R., et al. (2007). McElroy, S., Strakowski, S., West, S., Keck, P., Jr., & McConville, B. (1997). Phenomenol-
Consensus report on impulsive aggression as a symptom across diagnostic cate- ogy of adolescent and adult mania in hospitalized patients with bipolar disorder.
gories in child psychiatry: Implications for medication studies. Journal of the The American Journal of Psychiatry, 154(1), 44–49.
American Academy of Child and Adolescent Psychiatry, 46(3), 309–322. doi: Mechri, A., Kerkeni, N., Touati, I., Bacha, M., & Gassab, L. (2011). Association between
10.1097/chi.0b013e31802f1454. cyclothymic temperament and clinical predictors of bipolarity in recurrent
Joyce, P. R., Light, K. J., Rowe, S. L., Cloninger, C. R., & Kennedy, M. A. (2010). Self-muti- depressive patients. Journal of Affective Disorders, 132(1–2), 285–288. doi:
lation and suicide attempts: Relationships to bipolar disorder, borderline 10.1016/j.jad.2011.02.006.
242 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243

Merikangas, K., Akiskal, H., Angst, J., Greenberg, P., Hirschfeld, R., Petukhova, M., et al. in anxiety. In D. Kupfer, M. First, & D. Regier (Eds.), A research agenda for DSM-V
(2007). Lifetime and 12-month prevalence of bipolar spectrum disorder in the (pp. 85–122). Washington, DC: American Psychiatric Association.
National Comorbidity Survey Replication. Archives of General Psychiatry, 64(5), Porter, R., & Gallagher, P. (2006). Abnormalities of the HPA axis in affective disorders:
543–552. doi:10.1001/archpsyc.64.5.543. Clinical subtypes and potential treatments. Acta Neuropsychiatrica, 18(5), 193–209.
Merikangas, K., & Pato, M. (2009). Recent developments in the epidemiology of bipolar Post, R. (1992). Transduction of psychosocial stress into the neurobiology of recurrent
disorder in adults and children: Magnitude, correlates and future directions. Clinical affective disorder. The American Journal of Psychiatry, 149(8), 999–1010.
Psychology: Science and Practice, 16(2), 121–133. Reich, D. B., Zanarini, M. C., & Fitzmaurice, G. (2011). Affective lability in bipolar disor-
Merikangas, K., & Pato, M. (2009). Recent developments in the epidemiology of bipolar der and borderline personality disorder. Comprehensive Psychiatry, Corrected Proof..
disorder in adults and children: Magnitude, correlates, and future directions. doi:10.1016/j.comppsych.2011.04.003.
Clinical Psychology: Science and Practice, 16(2), 121–133. doi:10.1111/j.1468- Robins, E., & Guze, S. (1970). Establishment of diagnostic validity in psychiatric illness:
2850.2009.01152.x. Its application to schizophrenia. The American Journal of Psychiatry, 126(7),
Michalak, E., Yatham, L., Maxwell, V., Hale, S., & Lam, R. (2007). The impact of bipolar 983–987. doi:10.1176/appi.ajp. 126.7.983.
disorder upon work functioning: A qualitative analysis. Bipolar Disorders, 9(1–2), Sachs, G. S., Baldassano, C. F., Truman, C. J., & Guille, C. (2000). Comorbidity of attention
126–143. deficit hyperactivity disorder with early- and late-onset bipolar disorder. The
Michalak, E., Yatham, L., Wan, D., & Lam, R. (2005). Perceived quality of life in patients American Journal of Psychiatry, 157(3), 466–468. doi:10.1176/appi.ajp. 157.3.466.
with bipolar disorder: Does group psychoeducation have an impact? Canadian Salaria, S., Chana, G., Caldara, F., Feltrin, E., Altieri, M., Faggioni, F., et al. (2006). Micro-
Journal of Psychiatry, 50, 95–100. array analysis of cultured human brain aggregates following cortisol exposure: Im-
Mick, E., Biederman, J., Pandina, G., & Faraone, S. (2003). A preliminary meta-analysis of plications for cellular functions relevant to mood disorders. Neurobiology of
the child behavior checklist in pediatric bipolar disorder. Biological Psychiatry, 53 Disease, 23(3), 630–636.
(11), 1021–1027. doi:10.1016/S0006-3223(03)00234-8. Sameroff, A., & Mackenzie, M. (2003). Research strategies for capturing transactional
Mick, E., & Faraone, S. (2009). Family and genetic association studies of bipolar disorder in models of development: The limits of the possible. Development and Psychopathol-
children. Child and Adolescent Psychiatric Clinics of North America, 18(2), 441–453. ogy, 15, 613–640. doi:10.1017/S0954579403000312.
Miklowitz, D. (1996). Psychotherapy in combination with drug treatment for bipolar Savino, M., Perugi, G., Simonini, E., Soriani, A., Cassano, G. B., & Akiskal, H. S. (1993). Af-
disorder. Journal of Clinical Psychopharmacology, 16(2), 56S. fective comorbidity in panic disorder: Is there a bipolar connection? Journal of Af-
Miklowitz, D. J. (2006). A review of evidence-based psychosocial interventions for bi- fective Disorders, 28(3), 155–163. doi:10.1016/0165-0327(93)90101-o.
polar disorder. The Journal of Clinical Psychiatry, 67(Suppl. 11), 28–33. Schneck, C. (2009). Mixed depression: The importance of rediscovering subtypes of
Miklowitz, D., & Chang, K. (2008). Prevention of bipolar disorder in at-risk children: mixed mood states. The American Journal of Psychiatry, 166(2), 127–130. doi:
Theoretical assumptions and empirical foundations. Development and Psychopa- 10.1176/appi.ajp. 2008.08111669.
thology, 20(03), 881–897. doi:10.1017/S0954579408000424. Schotte, K., & Cooper, B. (1999). Subthreshold affective disorders: A useful concept in
Miklowitz, D., George, E., Axelson, D., Kim, E., Birmaher, B., Schneck, C., et al. (2004). psychiatric epidemiology? Epidemiologia e Psichiatria Sociale, 8(4), 255–261.
Family-focused treatment for adolescents with bipolar disorder. Journal of Affective Schrarer, L. O., Hartweg, V., Hoern, M., Graesslin, Y., Strobl, N., Frey, S., et al. (2002).
Disorders, 82(1001), S113–S128. doi:10.1016/j.jad.2004.05.020. Electronic diary for bipolar patients. Neuropsychobiology, 46(Suppl. 1), 10–12.
Miklowitz, D. J., Otto, M. W., Frank, E., Reilly-Harrington, N. A., Wisniewski, S. R., Kogan, Schraufnagel, C., Brumback, R., Harper, C., & Weinberg, W. (2001). Affective illness in
J. N., et al. (2007). Psychosocial treatments for bipolar depression: A 1-year ran- children and adolescents: Patterns of presentation in relation to pubertal matura-
domized trial from the systematic treatment enhancement program. Archives of tion and family history. Journal of Child Neurology, 16(8), 553–561.
General Psychiatry, 64(4), 419–426. doi:10.1001/archpsyc.64.4.419. Schwartz, L., & Feeny, N. (2007). The nature of and behavioral treatment of sleep prob-
Moreira, A. L., Van Meter, A., & Youngstrom, E. (2010). Meta-analysis of published lems in youth with bipolar disorder. International Journal of Behavioral Consultation
epidemiological studies adult bipolar disorder. Paper presented at the International and Therapy, 3(1), 8.
Review of Bipolar Disorders, Budapest, Hungary. Serretti, A., & Mandelli, L. (2008). The genetics of bipolar disorder: genome ‘hot re-
Nadkarni, R., & Fristad, M. (2010). Clinical course of children with a depressive spec- gions’, genes, new potential candidates and future directions. Molecular Psychiatry,
trum disorder and transient manic symptoms. Bipolar Disorders, 12, 494–503. 13(8), 742–771.
doi:10.1111/j.1399-5618.2010.00847.x. Shankman, S., Lewinsohn, P., Klein, D., Small, J., Seeley, J., & Altman, S. (2009). Sub-
Nilsson, A. K. K., Jorgensen, C., Straarup, K. N., & Licht, R. W. (2010). Severity of affective threshold conditions as precursors for full syndrome disorders: A 15-year longitu-
temperament and maladaptive self-schemas differentiate borderline patients, bipo- dinal study of multiple diagnostic classes. Journal of Child Psychology and
lar patients, and controls. Comprehensive Psychiatry, 51(5), 486–491. doi: Psychiatry, 50(12), 1485–1494. doi:10.1111/j.1469-7610.2009.02117.x.
10.1016/j.comppsych.2010.02.006. Shen, G., Alloy, L., Abramson, L., & Sylvia, L. (2008). Social rhythm regularity and the onset
Otto, M., Simon, N., Wisniewski, S., Miklowitz, D., Kogan, J., Reilly-Harrington, N., et al. of affective episodes in bipolar spectrum individuals. Bipolar Disorders, 10, 520–529.
(2006). Prospective 12-month course of bipolar disorder in out-patients with and Simon, N. M., Otto, M. W., Wisniewski, S. R., Fossey, M., Sagduyu, K., Frank, E., et al.
without comorbid anxiety disorders. The British Journal of Psychiatry, 189(1), (2004). Anxiety disorder comorbidity in bipolar disorder patients: Data from the
20–25. doi:10.1192/bjp.bp. 104.007773. first 500 participants in the Systematic Treatment Enhancement Program for Bipo-
Paris, J., Gunderson, J., & Weinberg, I. (2007). The interface between borderline person- lar Disorder (STEP-BD). The American Journal of Psychiatry, 161(12), 2222–2229.
ality disorder and bipolar spectrum disorders. Comprehensive Psychiatry, 48(2), doi:10.1176/appi.ajp. 161.12.2222.
145–154. doi:10.1016/j.comppsych.2006.10.001. Smith, D., & Ghaemi, S. (2006). Hypomania in clinical practice. Advances in Psychiatric
Patel, N., DelBello, M., & Strakowski, S. (Writers). (2006). Ethnic differences in symp- Treatment, 12(2), 110–120. doi:10.1192/apt.12.2.110.
tom presentation of youths with bipolar disorder [Article], Bipolar disorders: Smoller, J., & Finn, C. (2003). Family, twin, and adoption studies of bipolar disorder.
Blackwell Publishing Limited. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 123C
Paykel, E., Abbott, R., Morriss, R., Hayhurst, H., & Scott, J. (2006). Sub-syndromal and (1), 48–58. doi:10.1002/ajmg.c.20013.
syndromal symptoms in the longitudinal course of bipolar disorder. The British Strakowski, S., Keck, P., Arnold, L., Collins, J., Wilson, R., Fleck, D., et al. (2003). Ethnicity
Journal of Psychiatry, 189(2), 118–123. doi:10.1192/bjp.bp. 105.013870. and diagnosis in patients with affective disorders. The Journal of Clinical Psychiatry,
Perlis, R., Miyahara, S., Marangell, L., Wisniewski, S., Ostacher, M., DelBello, M., et al. 64(7), 747–754.
(2004). Long-term implications of early onset in bipolar disorder: Data from Strober, M., Schmidt-Lackner, S., Freeman, R., Bower, S., Lampert, C., & Deantonio, M.
the first 1000 participants in the systematic treatment enhancement program (1995). Recovery and relapse in adolescents with bipolar affective illness: A five-
for bipolar disorder (STEP-BD). Biological Psychiatry, 55(9), 875–881. doi: year naturalistic, prospective follow-up. Journal of the American Academy of Child
10.1016/j.biopsych.2004.01.022. and Adolescent Psychiatry, 34(6), 724–731.
Perlis, R., Ostacher, M., Patel, J., Marangell, L., Zhang, H., Wisniewski, S., et al. (2006). Swann, A. C., Dougherty, D. M., Pazzaglia, P. J., Pham, M., Steinberg, J. L., & Moeller, F. G.
Predictors of recurrence in bipolar disorder: Primary outcomes from the systemat- (2005). Increased impulsivity associated with severity of suicide attempt history in
ic treatment enhancement program for bipolar disorder (STEP-BD). Focus, 4(4), patients with bipolar disorder. The American Journal of Psychiatry, 162(9),
553–561. 1680–1687. doi:10.1176/appi.ajp. 162.9.1680.
Perris, C., & d'Elia, G. (1966). A study of bipolar (manic-depressive) and unipolar recur- Totterdell, P., & Kellett, S. (2008). Restructuring mood in cyclothymia using cognitive
rent depressive psychoses. X. Mortality, suicide and life-cycles. Acta Psychiatrica behavior therapy: An intensive time-sampling study. Journal of Clinical Psychology,
Scandinavica. Supplementum, 194, 172. 64(4), 501–518. doi:10.1002/jclp. 20444.
Perugi, G. (2002). The soft bipolar spectrum redefined: focus on the cyclothymic, Trede, K., Salvatore, P., Baethge, C., Gerhard, A., Maggini, C., & Baldessarini, R. J. (2005).
anxious-sensitive, impulse-dyscontrol, and binge-eating connection in bipolar II Manic-depressive illness: Evolution in Kraepelin's textbook, 1883–1926. Harvard
and related conditions. Psychiatric Clinics of North America, 25(4), 713–737. doi: Review of Psychiatry, 13(3), 155–178. doi:10.1080/10673220500174833.
10.1016/S0193-953X(02)00023-0. Utsumi, T., Sasaki, T., Shimada, I., Mabuchi, M., Motonaga, T., Ohtani, T., et al. (2006).
Perugi, G., & Akiskal, H. (2011). Are bipolar II, atypical depression, and borderline per- Clinical features of soft bipolarity in major depressive inpatients. Psychiatry and
sonality overlapping manifestations of a common cyclothymic-sensitive diathesis? Clinical Neurosciences, 60(5), 611–615. doi:10.1111/j.1440-1819.2006.01566.x.
World Psychiatry, 10, 45–51. Van Meter, A., Moreira, A., & Youngstrom, E. (2011). Meta-analysis of epidemiologic
Perugi, G., Toni, C., Travierso, M., & Akiskal, H. (2003). The role of cyclothymia in atyp- studies of pediatric bipolar disorder. The Journal of Clinical Psychiatry, 72(9),
ical depression: Toward a data-based reconceptualization of the borderline-bipolar 1250–1256. doi:10.4088/JCP.10m06290.
II connection. Journal of Affective Disorders, 73, 87–98. Van Meter, A., Youngstrom, E., Demeter, C., & Findling, R. (2011). Examining the valid-
Peselow, E., Dunner, D., Fieve, R., & Lautin, A. (1982). Lithium prophylaxis of depression ity of cyclothymic disorder in a youth sample: Replication and extension. Paper
in unipolar, bipolar II, and cyclothymic patients. The American Journal of Psychiatry, presented at the 2011 Pediatric Bipolar Disorder Conference, Boston, MA.
139(6), 747–752. Van Meter, A., Youngstrom, E., Youngstrom, J., Feeny, N., & Findling, R. (2011). Examin-
Pine, D., Costello, E., Dahl, R., James, R., Leckman, J., Leibenluft, E., et al. (2002). Increasing ing the validity of cyclothymic disorder in a youth sample. Journal of Affective Dis-
the developmental focus in DSM-V: Broad issues and specific potential applications orders, 132(1–2), 55–63. doi:10.1016/j.jad.2011.02.004.
 A.R. Van Meter et al. / Clinical Psychology Review 32 (2012) 229–243 243

Vázquez, G. H., Kahn, C., Schiavo, C. E., Goldchluk, A., Herbst, L., Piccione, M., et al. (2008). Wilson, M. (1993). DSM-III and the transformation of American psychiatry: A history.
Bipolar disorders and affective temperaments: A national family study testing the The American Journal of Psychiatry, 150(3), 399–410.
“endophenotype” and “subaffective” theses using the TEMPS-A Buenos Aires. Journal Wittchen, H., Muhlig, S., & Pezawas, L. (2003). Natural course and burden of bipolar
of Affective Disorders, 108(1–2), 25–32. doi:10.1016/j.jad.2007.09.011. disorders. The International Journal of Neuropsychopharmacology, 6(02), 145–154.
Verhoeven, W. M. A., & Tuinier, S. (2001). Cyclothymia or unstable mood disorder? A doi:10.1017/S146114570300333X.
systematic treatment evaluation with valproic acid. Journal of Applied Research in Young, M., & Fristad, M. (2007). Evidence based treatments for bipolar disorder in chil-
Intellectual Disabilities, 14(2), 147–154. doi:10.1046/j.1468-3148.2001.00063.x. dren and adolescents. Journal of Contemporary Psychotherapy, 37(3), 157–164. doi:
Waters, B. (1979). Early symptoms of bipolar affective psychosis: Research and clinical 10.1007/s10879-007-9050-4.
implications. Canadian Journal of Psychiatry, 2, 55–60. Youngstrom, E. (2009). Definitional issues in bipolar disorder across the life cycle.
Wee, H., Lee, W., Ravens-Sieberer, U., Erhart, M., & Li, S. (2005). Validation of the English ver- Clinical Psychology: Science and Practice, 16(2), 140–160. doi:10.1111/j.1468-
sion of the KINDL® generic children's health-related quality of life instrument for an 2850.2009.01154.x.
Asian population — Results from a pilot test. Quality of Life Research, 14(4), 1193–1200. Youngstrom, E., Birmaher, B., & Findling, R. (2008). Pediatric bipolar disorder: Validity,
Weissman, M. M., & Myers, J. K. (1978). Affective disorders in a US urban community: The phenomenology, and recommendations for diagnosis. Bipolar Disorders, 10,
use of research diagnostic criteria in an epidemiological survey. Archives of General 194–214. doi:10.1111/j.1399-5618.2007.00563.x.
Psychiatry, 35(11), 1304–1311. doi:10.1001/archpsyc.1978.01770350030002. Youngstrom, E., Meyers, O., Demeter, C., Youngstrom, J., Morello, L., Piiparinen, R., et al.
Welner, A., Welner, Z., & Leonard, M. A. (1977). Bipolar manic-depressive disorder: A (2005). Comparing diagnostic checklists for pediatric bipolar disorder in academic
reassessment of course and outcome. Comprehensive Psychiatry, 18(4), 327–332. and community mental health settings. [Article]. Bipolar Disorders, 7, 507–517.
doi:10.1016/0010-440X(77)90003-7. doi:10.1111/j.1399-5618.2005.00269.x.
Wetzel, R. D., Cloninger, C. R., Hong, B., & Reich, T. (1980). Personality as a subclinical Youngstrom, E., Van Meter, A., & Perez Algorta, G. (2010). The bipolar spectrum: Myth or
expression of the affective disorders. Comprehensive Psychiatry, 21(3), 197–205. reality. Current Psychiatry Reports, 12(6), 479–489. doi:10.1007/s11920-010-0153-3.
doi:10.1016/0010-440X(80)90003-6. Youngstrom, E., Youngstrom, J., & Starr, M. (2005). Bipolar diagnoses in community
Wicki, W., & Angst, J. (1991). The Zurich study. European Archives of Psychiatry and Clin- mental health: Achenbach Child Behavior Checklist profiles and patterns of comor-
ical Neuroscience, 240(6), 339–348. doi:10.1007/BF02279764. bidity. Biological Psychiatry, 58(7), 569–575. doi:10.1016/j.biopsych.2005.04.004.