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What clinical feature has been associated with cycloid psychosis?

A. Frequently occurring sleep disturbances.
B. Acute stress.
C. Disorganized thought.
D. Prodromal symptoms.
“Ms. A,” a 27-year-old Army captain with 5 years of service, was on her third overseas combat deployment in less than 4 years when she developed psychosis characterized by sudden onset of paranoia, sense of failure, delusional guilt, withdrawal from those around her, difficulty articulating, and an initial inability to sleep. Her commander stated that her previous level of functioning was very high and that she had been a top-performing soldier. The onset of this psychosis was sudden and was not associated with energy disturbance or mood disturbance, and it was independent of any change in stressors (the severe stress of the combat setting was relatively constant). She was initially treated for heat exhaustion, but when the symptoms did not resolve, she was started on olanzapine (5 mg/day) and then switched to risperidone (2 mg/day). She was evacuated to Europe, where she recovered within 1 week on a psychiatric ward and was diagnosed as having brief psychotic disorder. She was subsequently evacuated to a psychiatric ward in the United States, and, 3 weeks later, to her home base for further observation and outpatient care. After a 4-month observation period during which her risperidone dosage was gradually tapered and discontinued, she was returned to duty and able to resume her deployment on no medications. However, within 3 months of returning to the combat zone, the same symptoms recurred. Again, there were minimal mood symptoms and no hallucinations. She was again evacuated to Europe, recovered within a week, and was subsequently evacuated to the United States, where she was hospitalized for observation. She was treated with aripiprazole (30 mg/day), and tapered off within 3 months. She was honorably retired and released from the military and joined the civilian workforce 7 months after her return from overseas.
Ms. A experienced a recurrence 1 year later (9 months after being tapered off her medication) with similar symptoms and rapid response to treatment. Over the next 8 years, she experienced six additional episodes, although she was hospitalized for only one of them. During these episodes, she continued to sleep in her normal pattern, 7–8 hours per night, and she lacked pressured speech, motor changes, or any other indications of a mood disorder. In these post–military service episodes, the memory of her military duty was always there and was associated with a sense of dread. However, it did not feel like a flashback, and it was not delusional in content. During her periods of wellness, Ms. A never experienced her combat service as a traumatic event. She also lacked symptoms in three of the “four A’s” once described as central to the experience of schizophrenia: she did not have looseness of associations, did not have affective changes, and did not exhibit autism (i.e., focus on internal fantasy). She did have profound indecision (ambivalence), which was related to her anxiety. While the episodes were less severe, they tended to last longer and longer over the course of these 8 years. Nearly all episodes occurred in the fall. Episodes frequently occurred independently of stressors, and despite ongoing treatment with antipsychotic medications or lamotrigine (although treatment with the latter was associated with very mild recurrences). Recovery was always complete, and Ms. A was able to complete a doctoral degree, marry, have children, and work full-time in between these episodes.
The working diagnosis had always ranged between unspecified psychosis, brief reactive psychosis, bipolar, schizoaffective disorder, schizophrenia, delusional disorder, atypical psychosis, and posttraumatic stress disorder. However, the rapid onset and offset, the periodicity (recurrence in the fall), and the total recovery to baseline suggested cycloid psychosis, a condition that is listed neither in DSM-5 nor in ICD-10.

The Classification of Cycloid Psychosis

Episodic or cyclical nonaffective psychosis with rapid, full recovery between episodes does not fit into any clear diagnostic category. Patients exhibiting this pattern would clinically be assigned to DSM-5’s unspecified psychosis category or brief psychotic disorders. In the psychiatric literature, this type of illness is frequently referred to as “cycloid psychosis” (1). Most researchers see this category of psychotic illness as a distinct diagnosis from the schizophrenic or affective disorders.
The case presented here is fairly typical of cycloid psychosis. The patient experiences a clear psychotic episode with auditory hallucinations or paranoid delusions and a mild thought disorder. There are frequently significant sleep disturbances but no clear mood symptoms, although distress secondary to psychotic content is present and usually presents as anxiety. The illness is quite cyclical, in this case occurring every 1–2 years in the late fall or early winter, even at different latitudes (south and north of the Tropic of Cancer). While superficially these individual symptoms appear in both bipolar illness and schizophrenia, studies examining biological markers (25) or diagnostic specificity (6, 7) consistently demonstrate that cycloid psychosis is distinct from both schizophrenia and affective disorders, but perhaps with more similarities to the mood disorders (8). However, family members of patients with cycloid psychosis are not at an increased risk for severe psychiatric illness, with their risk being similar to that of non-ill comparison subjects (9, 10). Nonetheless, at least one study suggested that patients diagnosed with cycloid psychosis can be classified in one of two subgroups: one in which mood symptoms and family history of mood disorders predominate, and the other with a relative paucity of such features (11).
Many psychiatric disorders have waxing and waning courses of illness, but only the mood disorders have discrete episodes with apparent full interepisode recovery (at least early in the course of illness). Similarly, mood disorders are among the few conditions that have clear periodicity (for example, seasonal affective disorder (12) and premenstrual dysphoric disorder) (13). However, cycloid psychosis is characterized by the presence of psychosis in the absence of significant mood symptoms. The psychotic episode tends to be brief and is nearly always associated with full recovery.
The condition was first described in 1928 (14). Diagnostic criteria were conceptualized in 1981 (15) (Figure 1), but the disorder was never adopted into either the ICD or the DSM classifications. When classification algorithms are used, cycloid psychosis appears to be closest to brief psychotic disorder in DSM-5 or acute polymorphic psychotic disorder in ICD-10 (16).
FIGURE 1. Proposed Diagnostic Criteria for Cycloid Psychosisa
a From reference 15.

Epidemiology

Since cycloid psychosis is not a recognized diagnosis, it has never been studied in large population samples. All available studies that provide some insight were conducted in Europe. A study in Sweden (17) looked at 514 patients who had been admitted for psychosis in 1983. For 83 patients it was their first hospitalization, and of these, 29 were under age 50 and had psychotic illness. Seven patients (four women and three men) fulfilled the diagnostic criteria for cycloid psychosis. In other words, nearly one-quarter of the first-onset psychosis patients (24.1%) had cycloid psychosis. The calculated 1-year incidence of first admission for cycloid psychosis was 5.0 per 100,000 women and 3.6 per 100,000 men. A study of 139 consecutively admitted psychotic patients in the Netherlands (16) found that 13% of the patients had cycloid psychosis. In a study that reexamined a cohort of patients studied in 1945 (18), three women (0.016%) were found to have cycloid psychosis, for an incidence of 0.7%, or half of that for schizophrenia in the same cohort. The female preponderance has been consistent across all of the studies. While none of these studies provides an accurate rate, taken together they suggest that cycloid psychosis is not a rare condition.

Treatment

There have been no controlled studies of the acute or prophylactic treatment of cycloid psychosis. ECT is clearly effective (17), but so is treatment with medications. Treatment with antipsychotic agents appears to be beneficial in the acute setting (19, 20), but it has not been examined in preventing recurrence. It is interesting that in our case, ongoing antipsychotic treatment (although at modest dosages) did not prevent recurrences. (It should be noted that the long intervals between episodes may indeed represent a reduction in the recurrence rate of psychosis in this patient.) Lithium, a mood stabilizer, appears to have some efficacy in the prevention of recurrence, and, as with bipolar disorder, higher intraerythrocyte/plasma lithium concentrations (lithium ratio) predicts response (21, 22). Anticonvulsants have not been investigated in this condition, but the patient in this case appeared to do better with lamotrigine monotherapy. Cycloid psychosis generally responds quite well and quickly to treatment, and nearly always better than both schizophrenia and affective disorders (19, 20).

Outcome

Cycloid psychosis has a generally good outcome. Interepisode recovery is nearly always complete, and response to medications, particularly antipsychotics, is very good (19, 20). As in the case presented here, patients are frequently able to function well in their lives (23). A similar pattern is seen in the earlier literature that predates standardized diagnostic criteria (24).

Pathophysiology

The exclusion of cycloid psychosis from mainstream diagnostic compendia has hampered research in this category of patients, and few studies have explored potential pathophysiologic markers. In one study of 10 patients with cycloid psychosis and 33 with schizophrenia, plasma glycine levels were higher and tryptophan levels were lower in the patients with cycloid psychosis compared with those with schizophrenia (20). In studies with auditory evoked responses, patients with cycloid psychosis had normal latencies but higher amplitudes, suggesting a greater level of activation (2527). On an electrophysiologically monitored continuous performance test, 37 patients with cycloid psychosis showed reduced global field power and decreased latencies during no-go trials compared with 37 healthy control subjects, suggesting a frontalization of the brain electrical field in cycloid psychosis (5).

Summary and Conclusions

Cycloid psychosis is not a widely recognized psychotic illness, and in nearly all studies it appears to be clinically and biologically distinct from both severe mood disorders and schizophrenia. Interestingly, it does not appear to be familial. In the current classification schemes, cycloid psychosis is most frequently determined to be a brief psychotic disorder (DSM-5) or acute polymorphic psychotic disorder (ICD-10). However, if one does not attempt to include cycloid psychosis in a categorical framework, it can also be envisioned as an intermediate step between the psychoses (e.g., schizophrenia) and the mood disorders (e.g., bipolar illness) in a continuum of severe psychiatric disorders.
The condition is characterized by recurrent nonaffective episodes that have a rapid onset and a rapid acute response to treatment, particularly antipsychotics or ECT. Reduction of recurrence can be frequently accomplished with lithium. As with bipolar illness, higher intraerythrocyte lithium levels (i.e., a higher lithium ratio) are associated with better lithium effectiveness. Interepisode recovery is nearly complete, and prognosis tends to be better than that for either bipolar or schizophrenic disorders. While inclusion in DSM-5 or ICD-10 may not be necessary, wider recognition and more directed research may edify clinicians and patients regarding both cycloid psychosis and bipolar and schizophrenic disorders.

A. Frequently occurring sleep disturbances.

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References

1.
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2.
Beckman G, Beckman L, Cedergren B, et al: Genetic markers in cycloid psychosis. Neuropsychobiology 1978; 4:276–282
3.
Warkentin S, Nilsson A, Karlson S, et al: Cycloid psychosis: regional cerebral blood flow correlates of a psychotic episode. Acta Psychiatr Scand 1992; 85:23–29
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Pfuhlmann B, Jabs B, Althaus G, et al: Cycloid psychoses are not part of a bipolar affective spectrum: results of a controlled family study. J Affect Disord 2004; 83:11–19
10.
Jabs B, Althaus G, Bartsch A, et al: [Cycloid psychoses as atypical manic-depressive disorders: results of a family study]. Nervenarzt 2006; 77:1096–1100, 1102–1104 (German)
11.
Mojtabai R: Heterogeneity of cycloid psychoses: a latent class analysis. Psychol Med 2000; 30:721–726
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Kurlansik SL, Ibay AD: Seasonal affective disorder. Am Fam Physician 2012; 86:1037–1041
13.
Parry BL, LeVeau B, Mostofi N, et al: Temperature circadian rhythms during the menstrual cycle and sleep deprivation in premenstrual dysphoric disorder and normal comparison subjects. J Biol Rhythms 1997; 12:34–46
14.
Kleist K: Über zycloide, paranoide, und epileptoid psychosen und über die frage der degenerationspsychosen. Schweiz Arch Neurol Psychiatr 1928; 23:1–35 (German with English abstract)
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Perris C, Brockington IF: Cycloid psychoses and their relation to the major psychoses, in Biological Psychiatry. Edited by Perris C, Struwe D, Janson B. Amsterdam, Elsevier, 1981, pp 447–450
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van der Heijden FM, Tuinier S, Kahn RS, et al: Nonschizophrenic psychotic disorders: the case of cycloid psychoses. Psychopathology 2004; 37:161–167
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Montgomery JH, Vasu D: The use of electroconvulsive therapy in atypical psychotic presentations: a case review. Psychiatry (Edgmont) 2007; 4:30–39
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Lindvall M, Axelsson R, Ohman R: Incidence of cycloid psychosis: a clinical study of first-admission psychotic patients. Eur Arch Psychiatry Clin Neurosci 1993; 242:197–202
19.
García-Andrade RF, López-Ibor JJ: Acute treatment of cycloid psychosis: study on a sample of naive hospitalized patients with first-episode psychosis (FEP). Actas Esp Psiquiatr 2015; 43:51–57
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van de Kerkhof NW, Fekkes D, van der Heijden FM, et al: Cycloid psychoses in the psychosis spectrum: evidence for biochemical differences with schizophrenia. Neuropsychiatr Dis Treat 2016;12:1927–1933
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Perris C: Morbidity suppressive effect of lithium carbonate in cycloid psychosis. Arch Gen Psychiatry 1978; 35:328–331
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Perris C, Strandman E, Wählby L: HL-A antigens and the response to prophylactic lithium. Neuropsychobiology 1979; 5:114–118
23.
Jabs B, Krause U, Althaus G, et al: [Comparative study of life quality in patients with cycloid and schizophrenic psychoses]. Nervenarzt 2004; 75:460–466 (German)
24.
Trostorff SV: [Pattern of familial psychoses: systematic and unsystematic schizophrenia and cycloid psychoses]. Psychiatr Neurol Med Psychol (Leipz) 1975; 27:80–100 (German)
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26.
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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 502 - 505
PubMed: 29869551

History

Received: 8 March 2017
Revision received: 4 September 2017
Accepted: 23 October 2017
Published online: 1 June 2018
Published in print: June 01, 2018

Keywords

  1. Psychosis
  2. Bipolar Disorder
  3. Lithium
  4. Antipsychotics

Authors

Details

Rif S. El-Mallakh, M.D. [email protected]
From the Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville; and Rehabilitation Services, University of Louisville Hospital, Louisville.
Carolyn Furdek, D.P.T.
From the Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville; and Rehabilitation Services, University of Louisville Hospital, Louisville.

Notes

Address correspondence to Dr. El-Mallakh ([email protected]).

Funding Information

Dr. El-Mallakh has received research funding from Alexza, Janssen, and the State of Kentucky, and he has served as a speaker for Allergan, Lundbeck, Merck, Neurocrine, Otsuka, Takeda, and Teva. Dr. Furdek reports no financial relationships with commercial interests.

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