Cyclothymia

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Bipolar Disorder background
Bipolar Disorder (BD) is a mood disorder in which individuals experience varying episodes of mania, hypomania, hyperthymia and depression [1]. The four classified subtypes of BD are bipolar I and II, Cyclothymia and bipolar NOS (Not Otherwise Specified). BD has been studied extensively, especially bipolar I and II, however the other subtypes have been left in the grey area. Although bipolar I and II dominate in the literature, it has recently been shown that the four BD subtypes have comparable prevalence rates [2]. In total, BD affects 1-2% of the population, however more recent findings suggest prevalence rates as high as 5-10% [3][4].

Cyclothymia background
Cyclothymia, also known as Cyclothymic disorder or Cyclothymic temperament, is considered to be a ‘sub-threshold’ type of BD characterized by oscillating episodes of hypomanic and depressive episodes, usually transitioning abruptly [5]. Many do not recognize Cyclothymia as a distinct disorder, but rather as a temperament trait or a co-morbid characteristic, despite its classification in the DSM-IV since 1980 [6][7][8]. This disagreement in the literature is impeding our understanding of Cyclothymia and this neglect needs to be revised. Currently, a circadian component to Cyclothymia is being investigated.

Bipolar Disorder Subtypes
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Differentiating between the different subtypes of BD:
Bipolar I involves episodes of mania and depression.
Bipolar II involves episodes of hypomania and depression.
Cyclothymia involves oscillating episodes of hypomania and a state nearing depression

Symptoms

Differentiating Cyclothymia
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Van Meter, A.R., Youngstrom, E.A., Findling, R.L. (2012). Cyclothymic disorder: a critical review.
Clin Psychol Rev. 32(4):229-43.[34]

DSM-IV-TR criteria for Cyclothymia

In the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), Cyclothymia is described as “a chronic, fluctuating mood disturbance” that involves episodes of hypomania and depression [5]. Neither the hypomanic symptoms nor the depressive symptoms are severe or frequent enough to qualify for a manic episode or a major depression episode respectively, however they do cause noticeable change in functioning in daily life [5]. These symptoms must have been present for a minimum of two years for adults but only one year for children and adolescents [5]. During this one or two year time interval, any period that is free of symptoms cannot exceed two months in duration [5].

Characteristic Cyclothymic episodes

The depressive episodes in Cyclothymia resemble depression in several aspects including decreased confidence and motivation, listlessness, affected sleep, feelings of worthlessness and guilt, emotional instability and irritability [10]. The hypomanic episodes include impulsivity, decreased need for sleep, increased energy, motivation and confidence however unlike mania, does not include hallucinations or delusions [11]. In the literature, the depressive episodes of Cyclothymia are better characterized than the hypomanic episodes. The main feature that distinguishes Cyclothymia from the other bipolar subtypes is the absence of major depressive episodes. In addition, the elevated hypomanic mood states of Cyclothymia tend to be more negatively irritable and impulsive than the manic state of bipolar I, and encompass some feelings of guilt and low self-esteem [12].

Co-morbidity

There is a high level of comorbidity between Cyclothymia and other psychiatric conditions. Youngstrom and colleagues found that approximately 50% of Cyclothymic individuals have at least one comorbid Axis I disorder [13]. It has also been shown that Cyclothymia is significantly more prevalent in adults with Attention Deficit Hyperactive Disorder (ADHD) [14].

Assessment tools for diagnosis

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Structured interviews

Typically, the Structured Clinical Interview for DSM-IV-TR Axis I disorders (SCID-I) is used as a diagnostic tool, though it is used for the diagnosis for BD in general and may underdiagnose Cyclothymia [15]. The Mood Disorder Questionnaire (MDQ), which contains questions on mania and hypomania, may also be used as a screening tool along with an unstructured review of the symptoms [16]. Most of the diagnostic tools being used for Cyclothymia are for the diagnosis of bipolar disorder in general. However, there are a few self-report questionnaires for cyclothymic temperament that have been developed and a few being developed and currently being tested.

Self-report instruments

TEMPS-A

Akiskal and collegues developed a self-report questionnaire known as the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire (TEMPS-A), which has been useful for identifying Cyclothymia [17]. This questionnaire measures temperament on four subscales: dysthymic, cyclothymic, hyperthymic and irritable temperament [18]. TEMPS-A is currently being assessed in several countries and its validation is underway [19]. The cyclothymic subscale of TEMPS-A has shown to be quite promising in identifying Cyclothymia [20].

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TCI, CEATS and AFECTS

While TEMPS-A assesses affective temperaments, Temperament and Character Inventory (TCI) assesses the emotional nature of temperaments. This validated self-report instrument developed by Cloginger et al. is based on a psychobiological model of temperament and character [21][22]. Combined Emotional and Affective Temperaments Scale (CEATS), as the name suggests, is a tool that has been developed to assess temperaments from the emotional and affective aspect simultaneously [23]. This tool recognizes 10 affective temperaments: depressive, anxious, apathetic, cyclothymic, dysphoric, volatile, euthymic, hyperthymic, irritable and disinhibited, on 5 emotional dimensions [23]. Following approximately the same rationale, the same authors developed The Affective Emotional Composite Temperament Affect Scale (AFECTS), which recognizes 2 more temperaments, euphoric and obsessive, in addition to the 10 mentioned [24].

Circadian Component of Cyclothymia

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Circadian rhythm of Cyclothymics

A circadian component of Cyclothymia has long been alluded to abstractly, but never formally investigated. This is due in part to the lack of diagnostic tools for Cyclothymia, however there are more useful tools on the rise. Lara, Ottoni and colleagues provide some insight in this aspect and provide some evidence that cyclothymics have an altered circadian rhythm and possibly a cycling pattern that is synchronized to that circadian cycle [25]. The authors study the circadian topology of temperaments by examining the associations between circadian preference and the different temperaments. The authors recognize a temperament on an emotional and affective scale (AFECTS) that was based on the AFECT model they developed recently [24]. They show that cyclothymics (and euphorics) have a later circadian preference and tend to have more mood swings [25]. As well as this later circadian rhythm, they exhibit an increasing energy pattern throughout the day that peaks in the evening [25]. They were able to show that cyclothymics have later circadian preferences in the energy-based chronotype, as well as the sleep-based chronotype [25].

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Sleep patterns of Cyclothymics

In another paper, Lara, Ottoni and colleagues show that Cyclothymic temperaments are associated with sleep disturbances [26]. Their analysis was based on the CEATS and they assessed sleep using a specialized sleep questionnaire (the Basic Nordic Sleep Questionnaire). They identified that cyclothymics tend to sleep later and also wake up later than average, overall experiencing a lower quality of sleep [26] (see Sleep irregularities). They also spend a significantly longer time to fall asleep and have more awakenings during the night [26]. Papers providing this type of information are helpful in providing better diagnostic instruments for Cyclothymia as well as better treatments, or rather, better timing of treatment administration.

fMRI
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Whalley, H.C., et al. (2011). The neural basis of
familial risk and temperamental variation in individuals at high
risk of bipolar disorder. Biol Psychiatry. 70(4):343-9.

Functional Magnetic Resonance Imaging

Very few functional Magnetic Resonance Imaging (fMRI) studies differentiate between Cyclothymia and other BD subtypes, and there are no fMRI studies on Cyclothymia alone. To date, there is only one study that showed that there might be an association between Cyclothymia and a hypoactive ventral prefrontal cortex, specifically the inferior frontal gyrus [9].

Treatment of Cyclothymia

Pharmacological treatments

There have been a few studies that showed that Lithium, the conventional treatment for bipolar disorder, might have positive effects on cyclothymics. One study showed that cyclothymics that were treated with Lithium had higher remission rates than the control group of untreated cyclothymics [27]. In two other studies, it was shown that 60% of cyclothymics improved with Lithium treatment compared to only 20% in the control group [8][28]. Lamotrigine is an anticonvulsant drug useful for treating bipolar individuals that exhibit some features resembling Cyclothymia, but not as effective in treating ‘pure’ Cyclothymics [29]. In a study with individuals experiencing mood instability similar to cyclothymics, Valproic acid, an anticonvulsant drug more commonly known as Valproate, proved to be an effective mood-stabilizer, reducing the unstable symptoms in 68% of the subjects [30]. Treatment of Quetiapine, an atypical antipsychotic popularly known as Seroquel, at very low doses can ameliorate symptoms in individuals experiencing mild to moderate mood cycling symptoms [31].

Psychosocial treatments

Although BD is generally treated with pharmaceuticals, physchosocial treatments have been shown to be more appropriate and effective for cyclothymics. In contrast to pharmacological treatments that are aimed at mood states, psychosocial interventions concentrate on regulating the mood variability associated with Cyclothymia. Totterdell and Kellet show that Cognitive Behavioural Therapy (CBT) effectively helped cyclothymics in recognizing their variable mood states and progress further to managing this mood variability [32]. They successfully showed that after CBT, cyclothymics had reduced mood variability and the intervals between episodes had increased in duration [32]. Furthermore, these individuals exhibited earlier sleep onsets and extended sleep [32]. In a randomized clinical trial, Fava and collegues showed that sequentially combining CBT with Well-Being Therapy (WBT) was significantly more effective than CBT alone or clinical management alone [33].

Poor diagnosis of Cyclothymia has undoubtedly hindered the development of effective treatments [34]. Integrating circadian mood regulation in the treatment of Cyclothymia can significantly improve the effectiveness of the treatment [32].

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34. Van Meter, A.R., Youngstrom, E.A., Findling, R.L. (2012). Cyclothymic disorder: a critical review. Clin Psychol Rev. 32(4):229-43.

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