Historical aspects

From a historical viewpoint, the most important classificatory approach of severe psychotic diseases by Emil Kraepelin (1856–1926) strongly influenced modern concepts of psychiatry. He differentiated between “dementia praecox” with a deleterious outcome and “manic-depressive insanity” with good prognosis. According to his classification, acute psychoses with good prognosis are integrated into affective diseases. Meanwhile, the French psychiatrist Valentin Magnan (1835–1916) established the diagnosis bouffée délirante, including the sudden onset of delusions, intense symptoms with varying content, and complete remission [1]. In Germany, Carl Wernicke (1848–1905) was the first to describe “anxiety psychosis” and “motility psychosis,” which describe anxious affects and paranoid psychosis as well as motor symptoms with hyperkinetic, akinetic, and mixed states and entail a good prognosis. His scholar, Karl Kleist (1879–1960), defined the term cycloid psychoses, including motility psychosis and confusional psychosis, not leading to mental deficits [2]. He suggested this group of psychoses to be caused by temporary dysfunctions of labile brain regions [1]. In his psychiatric school, cycloid psychoses belong to an atypical disorder representing a third form of psychosis apart from manic-depressive and schizophrenia psychoses. They may occur in patients predisposed to phasic illness with often spontaneous and full recovery and no residual symptoms.

Karl Leonhard (1904–1988) further developed Kleist’s concept by adding anxiety-elation psychosis as third subform, thus extending it to a psychosis with rapid shift of mood and ecstatic feelings. Cycloid psychoses have been described as a group of acute psychoses with polymorph symptomatology and good prognosis due to complete remission. Leonhard considered three subforms entailing bipolar symptoms according to abnormalities in mood, thinking, and behavior. They consist of anxiety-elation, excited-inhibited confusion, and hyperkinetic-akinetic motility psychosis [3]. To validate his innovative concept, he longitudinally observed about 700 patients at the University hospitals in Frankfurt and Berlin and separated the distinct cycloid psychoses from “unsystematic” schizophrenia with unstable symptoms and variable course and “systematic” schizophrenia with a chronic course and stable symptoms [4–6]. Unsystematic schizophrenia included “affective paraphrenia,” “periodic catatonia,” and “cataphasia” with unfavorable long-term outcome, while systematic schizophrenia consists of “hebephrenia,” “paraphrenia,” and “catatonia” and a non-episodic, progressive course of the disease. Contrastingly, cycloid psychoses exhibit a phasic and cyclic course with full recovery or only mild residual symptoms [7, 8]. As a prominent example, based on the classification of Leonhard, the psychiatric disease of Vincent van Gogh has been considered to be an anxiety-elation psychosis with fluctuating mood that influenced his biography [9].

In 1933, Jacob Kasanin [10] described the acute schizoaffective psychoses as an episodic psychotic disease with predominant affective symptoms, that was viewed to be a good-prognosis schizophrenia. In 1950, the Japanese psychiatrist Hilrstoehi Mitsuda [11] named periodical psychoses with favorable prognosis, rapid fluctuation, emotional disturbances, and positive psychotic symptoms “atypical psychoses” and considered them to be another genetic category than schizophrenia and manic-depressive psychosis. Based on clinical and family studies in Britain and Italy in the 1970s and 1980s, Carlo Perris and Ian Brockington developed operational diagnostic criteria for cycloid psychoses with polymorphous symptoms and confusion or distressed perplexity without distinguishing between specific subforms [12–14]. Meanwhile, several investigators supported the nosological validity of the concept of cycloid psychoses [15], among them the psychiatric school of Helmut Beckmann (1940–2006) and colleagues at the University of Würzburg, Germany, prominent for differentiating the psychopathology of psychoses in the classificatory tradition of Wernicke-Kleist-Leonhard.

Incidence

The group of cycloid psychoses is not rare; among psychotic patients hospitalized for the first time they may account for 13 percent of the cases [16]. Peralta and colleagues [17] estimated a total of 10–15 percent cases with cycloid psychoses. In another clinical sample, the 1-year incidence of cycloid psychoses has been assessed in 514 patients discharged in 1983 in Lund, Sweden. Out of 83 first hospitalization patients, 29 received the diagnosis functional psychosis. In this group, 4 females and 3 males fulfilled the diagnostic criteria for cycloid psychosis based on the definition of Leonhard and Perris. Overall, the 1-year incidence for first admission in cycloid psychoses per 100,000 inhabitants of the age group 15–50 years was 5.0 in females and 3.6 in males [18]. The onset of disease occurs during the second or third decade of life with a mean age of 27.4 years [18]. While Leonhard calculated the proportion of females to be 57 percent (motility psychosis 74 percent) [19], later studies reported cycloid psychoses to be even more frequent in women, who represent 72–78 percent of the cycloid patients In contrast, no gender differences have been detected in schizophrenia [21].

Symptoms and course of the group of disorders

According to Leonhard’s classification, symptoms of cycloid psychoses are expressed in a dichotomic manner. The anxiety-elation psychosis with rapid changes of anxiety and ecstatic mood consists of severe anxiety, accompanied by distrust and self-references, delusions of threat and persecution and affect-congruent sensory illusions or hallucinations. The other pole has been described as ecstatic mood with happiness and delusions of reference, calling, or salvation (often religious or political ideas) as well as affect-generated illusions or hallucinations such as divine messages or inspirations. The excited-inhibited confusion psychosis is composed of excitation on the one hand such as incoherence of thought and speech, fleeting misrecognition of persons, ideas of reference and hallucinations, and on the other hand of inhibition of thought with perplexedness and language impoverishment up to mutism. The hyperkinetic-akinetic motility psychosis entails a hyperkinetic pole with excess of movements, increase in expressive and reactive motions, severe distractibility by environment, and senseless motor activity. The akinetic pole is composed of reduction of expressive and reactive motions, reduction of voluntary movements, incoherence and lack of spontaneous speech, and akinetic stupor [22]. The symptoms may be confluent between the three subtypes, but all of them exhibit a phasic course with bipolarity and complete remission except for secondary effects of repeated illness, hospitalizations, and impaired functioning [15].

The Perris and Brockington criteria for cycloid psychoses comprise age between 15 and 50 years, acute psychosis, and sudden change from health to psychosis within hours to a few days plus symptoms across the spectrum of the three subforms primarily described by Leonhard. These demand at least four of the following symptoms: confusion from perplexity to severe disorientation with derealization or depersonalization, mood-incongruent delusions or paranoid symptoms inclusive ideas of reference, influence or persecution. Furthermore, hallucinations of any kind, deep feelings of happiness or ecstasy, deep anxiety and fear that something terrifying is about to happen, motility disturbances with increased or decreased activity, and particular concern about death or dying. They describe mood swings that are not sufficient to support the diagnosis of affective disorders. Symptoms are considered to be polymorph with opposite polar phases within a single episode [15].

Overall, after an acute onset the course of the disease has been described as cyclic with recurrent psychotic episodes lasting days to months and possible spontaneous remission. A mean onset of 32.1 years and 3.2 episodes during 7 years within the course of the disease has been observed in patients fulfilling the Perris and Brockington criteria [20]. Corresponding to the initial hypothesis of full remission, Beckmann and colleagues [23] verified lacking residual morbidity in reevaluating 31 of Leonhard’s cycloid psychoses patients during a period of 4 years. The team thus could demonstrate stability and prognostic validity of the diagnosis. The investigation of another group of 108 female patients with psychotic disorders during a follow-up period of 30 years provided good evidence for stability and validity of diagnostic groups according to Leonhard’s classifications of cycloid psychoses, bipolar disorder, and systematic schizophrenias [24]. In the subsequent prospective analysis of 276 psychosis patients, including 222 female patients for a period of 21–33 years, predictive validity of the diagnostic categories have been assessed. Leonhard’s classifications of hebephrenias and schizophrenias were the most valid categories, followed by bipolar and cycloid psychoses [25]. Reevaluating 22 schizophrenia patients (ICD-10 and DSM-IIR diagnosis) by 4 independent raters using Leonhard’s classification, a high interrater reliability was achieved in separating cycloid psychoses from systematic and unsystematic schizophrenias [26]. A prospective study reexamined 39 females with postpartum psychiatric disorders on average 12.5 years after the first episode of psychosis. Using Leonhard’s classification, 54 percent of the patients suffered from cycloid psychosis with a motility psychosis predominating the clinical picture [27]. These results accord with previous reports of Wernicke [28], who considered puerperal psychoses predominantly to be motility psychosis. Schizophrenia, in contrast, is only rarely present in this group of disorders [29]. Outcome criteria such as Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), symptoms as expressed by the Positive and Negative Syndrome Scale (PANSS), and quality of life as measured by the Lancashire Quality of Life Profile (QoL) have been assessed in 33 patients with cycloid psychoses compared to 44 schizophrenia patients after 13 years since first hospitalization [19]. According to the unfavorable course of the illness, schizophrenia patients developed symptoms earlier, revealed more frequent and longer periods of hospitalization, and received higher neuroleptic doses than patients with cycloid psychoses. Corresponding with the hypothesis of remission without residual symptoms, patients with cycloid psychoses displayed better scores in CGI, GAF, Strauss-Carpenter Outcome, and PANSS scales. Other than in schizophrenia, patients did not differ from healthy controls with respect to quality of life in three out of four domains. Furthermore, they specifically exhibit a favorable outcome in employment status and familial relations such as marriage and children [19]. In the entire group of psychotic disorders, symptoms of confusion, acute and late onset of the disease, and intact premorbid personality have been considered to be an important factor in remission quality [30]. Female patients with psychosis were shown to have an increased age at onset [21]. The good outcome in female patients may be related to their preponderance with respect to the diagnosis cycloid psychoses and may be due to positive effects of estrogen on outcome. Animal studies, for example, have shown that estradiol reduces catalepsy caused by the dopamine antagonist haloperidol and behavioral changes by the dopamine agonist apomorphine [31]. This led to the application of adjuvant estrogens as a therapeutic attempt in female patients with schizophrenia [32].