Cyclothymic Disorder

Etiology

The suspected etiologies of bipolar disorders include genetic susceptibility, neurotransmitter dysregulation, and environmental triggers. Cyclothymia is thought to belong to this family of affective disorders and its etiology is regarded in kind.[2]

Genetic factors have been robustly implicated in the etiology of cyclothymia. This influence is demonstrable by the concordance rate--57%--seen in monozygotic twins. Current genotypic studies are investigating several loci, including 18p11, 13q32, CLOCK genes, and ANK3.[2][3]

Environmental factors play a large role in the development of bipolar disorders. Negative life events and negative cognitive styles are associated with an increased incidence of affective dysregulation and emotional instability.[3]

Epidemiology

Cyclothymia is associated with a lifetime prevalence of approximately 0.4%-1% and a male to female ratio of 1:1. Prevalence may increase in clinics with some surveys reporting rates as high as 5%.[2][3][4]

Pathophysiology

As mentioned in the introduction, the phenomenology of cyclothymia overlaps with a multitude of separate disorders. One striking similarity is the emotional dysregulation observed in both cyclothymic patients and those with neurodevelopmental disorders.[5] These subsets of individuals have difficulty modulating their affect, suggesting a putative common neurophysiological aberration. Recent studies have determined that this commonality precipitates secondary to some deviance of the amygdala and fronto-limbic neural circuitry. This finding correlates with the observation that hyper-reactivity and regulatory deficits are associated with functional abnormalities of the amygdala and orbitofrontal cortex, respectively.[6][7]

History and Physical

The essential characteristic of cyclothymia is a chronic, pervasive, fluctuating mood disturbance. These fluctuations are described as periods of distinguishable depressive and elevated episodes. Unlike conventional bipolar spectrum disorders, cyclothymia can induce spontaneous fleeting oscillations between euphoric and depressive dispositions. Depressive symptomatology may include depressed mood, irritability, hopelessness, helplessness, insomnia, fatigue, anhedonia, avolition, negativity of affect, headaches, neurasthenia, and suicidal ideation. Hypomanic symptoms consist of impulsivity, grandiosity, racing thoughts, increased sociability, excessive physical activity, and increased speech production.

A developmental history will most likely reveal a chronic and pervasive pattern of emotional lability, hypersensitivity, recurrent interpersonal altercations, incidents of self-harming, episodes of excessive gambling, reckless sexual activity, multiple divorces, legal or financial problems, and recurrent job loss.[8][9]

Less frequently, some will experience displacement of their distress and anxiety in the form of somatic pain. Such complaints include chest pain, asthenia, weight loss, hair loss, and headaches. 

Evaluation

In accordance with the propriety of the psychiatric evaluation, organicity should first be ruled out. [10]Thus, the clinician should order standard laboratory panels and indicated imaging studies to rule out any underlying etiology. Standard work-ups include a complete blood count, comprehensive metabolic profile, thyroid panel, vitamin B-12, folate, ammonia, urinalysis, and brain imaging. Toxic effects from iatrogenic sources, as well as illicit substances, can induce behavior resembling mania and/or depression, and thus drug screens and medication profiles are recommended. 

Once organic perturbations have been ruled out, a full psychiatric exam should be performed. This includes a history of present illness, psychiatric history, social history, substance use history, family psychiatric history, psychiatric review of symptoms, and mental status exam.

Early work in defining this disorder was done by Hagop Akiskal.  His validated questionnaires, the TEMPS-A and Cyclothymic-Hypersensitivity, have been translated into nearly 20 languages with research on several continents.[11][12]

As mentioned in the introduction, cyclothymic symptomatology overlaps with manic, hypomanic, and depressive episodes, without meeting their full diagnostic threshold. Per DSM-5, cyclothymia is classified as the existence of symptomatology for the last two years, present for more days than not. Stability of mood cannot have exceeded any length of time longer than 2 consecutive months. The symptoms identified must have caused significant impairment in the patient's life. And lastly, the symptoms cannot be secondary to another psychiatric or medical illness. [13]

Treatment / Management

The treatment of cyclothymia rests upon managing risk factors, recognizing early symptoms, and implementing appropriate interventions, including psychoeducation, pharmacotherapy, and counseling. The primary target of the aforementioned therapies should be focused on the pervasive underlying affective dysregulation. Psychoeducation is paramount and emphasizes the necessity of medication compliance, confidence in the doctor, acknowledging the interpersonal consequences of the maladaptive behavior patterns, and acceptance of the illness. To date, there are no approved FDA-recommended psychotropic medications for the treatment of cyclothymic disorder. In spite of this, there still remain viable alternatives in the management of this disorder. First-line psychotropic treatment of cyclothymia is the administration of a mood stabilizer--valproate if anxiety is dominant, lamotrigine if the anxious-depressive polarity is more prominent, and lithium for significant affective intensity. Some patients may benefit from the dual therapy of both lithium and lamotrigine.[6] Furthermore, atypical antipsychotics can be applied as a monotherapy or an adjunct in conjunction with a mood stabilizer. Current research recommends withholding the use of antidepressants in the setting of cyclothymia as it can exacerbate symptomatology. [1][9][14] In addition to pharmacotherapy and psychoeducation, cognitive-behavioral therapy (CBT) has shown the most robust evidence of psychotherapies in the setting of cyclothymia.[6] Moreover, treatment plans should be modified ad hoc, and not on some predetermined algorithm. 

Differential Diagnosis

As previously mentioned, deviant physiological states precipitating from organic etiologies can mimic symptoms of cyclothymia. Common abnormalities that can incite such symptomatology include endocrine diseases, autoimmune disorders, vitamin deficiencies, electrolyte abnormalities, infections, and traumatic brain injuries. Furthermore, iatrogenic causes can also induce manic and depressive-like symptoms, most notably steroids, levodopa, and antibiotics.[1][9] Lastly, intoxication and/or withdrawal of illicit substances almost always precipitate overlapping affective symptoms with cyclothymia. Thus, a thorough medical evaluation and work-up will help differentiate between organic and substance-related etiologies from primary psychiatric disorders.

Once the primacy has been established, the clinician must then distinguish between psychiatric differentials. Cyclothymia shares many overlapping features with several psychiatric diagnoses. These include major depressive disorder, bipolar disorder type II, generalized anxiety disorder, neurodevelopmental disorders, and personality disorders. 

A detailed psychiatric evaluation will help the clinician to decipher between ambiguous presentations. Additionally, providers can administer psychiatric batteries for adjunctive and more objective assessments. Examples of assessment batteries include the Beck Depression Inventory, Beck Anxiety Inventory, Bipolar Spectrum Diagnostic Scale, and the My Mood Monitor (M-3) checklist.[14]

Prognosis

The prognosis of cyclothymia is variable. Features of this disorder inherently make normative functioning almost untenable in the absence of appropriate psychiatric aid. The constellation of hypersensitivity, emotional dysregulation, impulsivity, emotional-reactivity, and limited self-efficacy leads to chronic interpersonal, professional, and intrapsychic difficulties. Prognosis varies by internal coping styles, personality factors, family support, and early initiation of medications and psychotherapy. Fortunately, the literature suggests that with sufficient support and resources those afflicted with cyclothymia can lead fulfilling lives with minimal perturbations.[1][15]

Complications

Complications of this disorder are just as heterogeneous as its protean presentation. The severity of complications ranges from subtle iatrogenic side effects to suicide. The most common manifestations of complications include iatrogenic worsening of mood cyclicity and sequelae of emotional dysregulation, such as impulse control and substance use disorders. Less commonly, cyclothymia in youth can prove to be heterotypic, developing into bipolar disorder in adulthood.[1][2]