Heterogeneity of cycloid psychoses: a latent class analysis

BACKGROUND: Three hypotheses have been proposed in regard to the origin of cycloid psychoses: (1) they are an independent nosological entity; (2) they are atypical cases of affective disorders; and (3) they are a heterogeneous group of disorders. This study examined the heterogeneity hypothesis by attempting to delineate distinct affective and non-affective subgroups. METHODS: In 60 cases drawn from a classic study of cycloid psychoses by Perris (1974), latent class analysis was used to delineate subgroups. RESULTS: Two classes were identified in the analysis: one characterized by the convergence of affective symptoms and family history of affective disorders and the other by the relative paucity of such features. CONCLUSIONS: Cycloid psychoses are composed of at least two subgroups, distinguishable on the basis of symptoms and family history.     

Cycloid Psychosis Comorbid with Prader–Willi Syndrome: A Case Series

Psychosis is a relatively common psychiatric phenomenon seen in patients with Prader–Willi Syndrome (PWS). However, the presentation is atypical and difficult to classify within currently defined affective or psychotic disorders. This distinct presentation may be better understood as a phenomenon called “cycloid psychosis,” described as an episodic psychosis with rapid full recovery between episodes. This study retrospectively analyzed the cases of 12 patients with genetically confirmed PWS who presented to an ambulatory psychiatric center for a change in behavior consistent with psychosis. Each case was then assessed for symptoms of cycloid psychosis, bipolar disorder, depression with psychotic features, schizophrenia, and schizoaffective disorder. Out of the 12 patients, 11 (91.7%) met the currently described diagnostic criteria for cycloid psychosis. Of the 12 patients, 7 (58.3%) also met the diagnostic criteria for bipolar disorder, and 1 (8.3%) also met the diagnostic criteria for schizoaffective disorder. None of the patients met the criteria for schizophrenia or depression with psychotic features. The findings in this study suggest that cycloid psychosis and bipolar disorder may both be comorbid with PWS. Psychiatric comorbidities in patients with PWS are atypical and clinicians should be aware of conditions such as cycloid psychosis when managing this vulnerable population.     

The concordance of ICD-10 acute and transient psychosis and DSM-IV brief psychotic disorder

BACKGROUND: ICD-10 acute and transient psychotic disorder (ATPD; F23) and DSM-IV brief psychotic disorder (BPD; 298.8) are related diagnostic concepts, but little is known regarding the concordance of the two definitions. METHOD: During a 5-year period all in-patients with ATPD were identified; DSM-IV diagnoses were also determined. We systematically evaluated demographic and clinical features and carried out follow-up investigations at an average of 22 years after the index episode using standardized instruments. RESULTS: Forty-two (4.1%) of 1036 patients treated for psychotic disorders or major affective episode fulfilled the ICD-10 criteria of ATPD. Of these, 61.9% also fulfilled the DSM-IV criteria of brief psychotic disorder; 31.0%, of schizophreniform disorder; 2.4%, of delusional disorder; and 4.8%. of psychotic disorder not otherwise specified. BPD showed significant concordance with the polymorphic subtype of ATPD, and DSM-IV schizophreniform disorder showed significant concordance with the schizophreniform subtype of ATPD. BPD patients had a significantly shorter duration of episode and more acute onset compared with those ATPD patients who did not meet the criteria of BPD (non-BPD). However, the BPD group and the non-BPD group of ATPD were remarkably similar in terms of sociodemography (especially female preponderance), course and outcome, which was rather favourable for both groups. CONCLUSIONS: DSM-IV BPD is a psychotic disorder with broad concordance with ATPD as defined by ICD-10. However, the DSM-IV time criteria for BPD may be too narrow. The group of acute psychotic disorders with good prognosis extends beyond the borders of BPD and includes a subgroup of DSM-IV schizophreniform disorder.     

Cycloid psychoses predominate in severe postpartum psychiatric disorders

Background: The nosological status of postpartum psychoses has remained controversial because of their often ‘atypical' symptomatology. A polydiagnostic approach may further clarify this issue. Methods: In a retrospective study, we applied the ICD-10 and Leonhard's classification to 39 patients with severe postpartum psychiatric disorders. The patients were personally reexamined on average 12.5 years (6–26 years) after the onset of the illness. Results: An acute onset and a polymorphous psychotic symptomatology with rapid changes characterized the majority of our cases. Unipolar depressive disorders (28%) and acute polymorphous psychotic disorders (21%) represented the largest proportions within the ICD-10-classification. Applying Leonhard's classification, over half the patients (54%) suffered from a cycloid psychosis. Among cycloid psychoses, motility psychoses clearly predominated. Schizophrenias occurred rarely (10%) according to both classifications. Limitations: Due to the unknown prevalence of the various diagnoses among women of child-bearing age, it is impossible to statistically infer a specific association between childbirth and a distinct diagnosis from our data. Conclusions: Our findings suggest that cycloid psychoses, in particular motility psychoses, account for the majority of postpartum psychoses, and do not support the hypothesis of a nosological independence of postpartum psychoses.     

Exploring the borders of the schizoaffective spectrum: a categorical and dimensional approach

BACKGROUND: Schizoaffective disorder has long been considered as an intermediate condition between major mood disorders and schizophrenia, however, the nature of the relationship to these diagnoses remains unclear. We aimed at examining the nature of such a relationship in a mixed sample of psychotic disorders by using a dimensional and categorical approach to psychopathology. METHODS: Six-hundred and sixty psychotic inpatients were assessed for lifetime ratings of mania, depression, psychosis and incongruence, diagnosed according to Research Diagnostic Criteria, and classified as having nonaffective psychosis without mood syndromes (n=429), nonaffective psychosis with mood syndromes (n=101), schizoaffective disorder mainly schizophrenic (n=41), schizoaffective disorder mainly affective (n=42) or mood disorder with psychotic symptoms (n=47). We tested for associations of illness-related features including risk factors, premorbid, clinical and outcome variables with classes of disorders and lifetime ratings of psychopathology, and examined the relative contribution of categorical and dimensional representations of psychopathology in explaining disease characteristics. RESULTS: While categories at the extreme end of the psychotic spectrum meaningfully differed across a number of the illness-related variables, no substantial discontinuity was apparent between adjacent categories of psychotic disorders. Risk factors, premorbid adjustment, clinical features and impairment appeared to be present in a mostly monotonic continuous fashion from nonaffective psychoses to mood disorders with psychotic features. The overall association pattern of illness-related variables with mood and psychotic syndromes was largely independent of specific diagnostic categories, and the dimensional approach was neatly superior to the traditional diagnostic approach in explaining the characteristics of the illness. LIMITATIONS: This was a cross-sectional study with retrospective assessment of illness-related-variables and lifetime psychopathology. CONCLUSION: The results are compatible with the notion of the schizoaffective spectrum and with a continuum model of the psychotic illness.     

Psychosis associated with demonstrable brain disease

Sixty-five psychotic patients with unequivocal evidence of brain pathology and a variety of neurological disorders were assessed with respect to phenomenology and outcome. No relationship was found between site of brain pathology and type of psychotic disorder. A majority of patients had a syndrome indistinguishable from schizophrenia without coarse brain involvement and shared similar variables predicting outcome of psychosis, thus raising important issues concerning their nosological status.     

Minor physical anomalies in patients with first-episode psychosis: their frequency and diagnostic specificity

BACKGROUND: An increased prevalence of minor physical anomalies (MPAs) has been extensively documented in schizophrenia but their specificity for the disorder remains unclear. We investigated the prevalence and the predictive power of MPAs in a large sample of first-episode psychotic patients across a range of diagnoses. METHOD: MPAs were examined in 242 subjects with first-episode psychosis (50% schizophrenia, 45% affective psychosis and 5% substance-induced psychosis) and 158 healthy controls. Categorical principal components analysis and analysis of variance were undertaken, and individual items with the highest loading were tested using the chi2 test. RESULTS: Overall facial asymmetry, assymetry of the orbital landmarks, and frankfurt horizontal significantly differentiated patients with schizophrenia and affective psychosis from controls, as did a 'V-shaped' palate, reduced palatal ridges, abnormality of the left ear surface and the shape of the left and right ears. Patients with affective psychosis had significantly lowered eye fissures compared with control subjects. CONCLUSIONS: MPAs are not specific to schizophrenia, suggesting a common developmental pathway for non-affective and affective psychoses. The topographical distribution of MPAs in this study is suggestive of an insult occurring during organogenesis in the first trimester of pregnancy.     

Schneiderian first rank symptoms predict poor outcome within first episode manic psychosis

BACKGROUND: The validity of a sub-classification of affective psychosis according to the mood congruence of psychotic features has been questioned in the literature. While some authors have found a correlation between such symptoms and outcome, their predictive value was rather limited in these studies. METHOD: Prospective study of 108 subjects presenting with a first DSM-III-R manic episode with psychotic features to determine the frequency of different types of psychotic symptoms and to measure the predictive utility of mood incongruent psychotic symptoms (MIPS) and first-rank Schneiderian symptoms (FRSS) during the first episode for a 12-month outcome. Outcome was measured by the level of positive, negative, depressive symptoms, and psychosocial functioning. Duration of affective and psychotic symptoms was also assessed. RESULTS: Patients presented with a wide variety of psychotic symptoms. The presence of MIPS at baseline was significantly correlated with a longer persistence of psychotic symptoms, but not with poorer outcome at 12 months. By contrast, the presence of FRSS at baseline was significantly associated with earlier onset of psychosis as well as increased severity of negative symptoms and poorer psychosocial functioning after 12 months. CONCLUSION: The presence of FRSS during a first manic episode with psychotic features identifies a sub-group of patients with more severe presentation and poorer short-term outcome. These results question the prognostic utility of MIPS. Limitations: Despite the relatively large number of subjects compared with other studies, the statistical power to detect all but large effect sizes is limited by the sample size.     

Dimensions and classes of psychosis in a population cohort: a four-class, four-dimension model of schizophrenia and affective psychoses

BACKGROUND: Classification of psychosis lacks a biological basis and current diagnostic categories may obscure underlying continuities. Data reduction methods of symptom profiles within a population-based cohort of people with a wide range of affective and non-affective psychoses may permit an empirical classification of psychosis. METHOD: OPCRIT (operational criteria) analysis was performed on 387 adults aged 18-65 years in an attempted ascertainment of all patients with psychosis from a geographical area with a stable population. The data were analysed firstly using principal components analysis with varimax rotation to identify factors, and secondly to establish latent classes. Information relating to key variables known to be of relevance in schizophrenia was coded blind to the establishment of the classes and dimensions. RESULTS: Striking correspondence was obtained between the two methods. The four dimensions emerging were labelled 'depression', 'reality distortion', 'mania' and 'disorganization'. Latent classes identified were 'depression', 'bipolar', 'reality distortion/depression' and 'disorganization'. The latent classes corresponded well with DSM-III-R diagnoses, but also revealed groupings usually obscured by diagnostic boundaries. The latent classes differed on gender ratio, fertility, age of onset and self-harming behaviour, but not on substance misuse or season of birth. CONCLUSIONS: Both dimensional and categorical approaches are useful in tapping the latent constructs underlying psychosis. Broad agreement with other similar studies suggests such findings could represent discrete pathological conditions. The four classes described appear meaningful, and suggest that the term non-affective psychosis should be reserved for the disorganization class, which represents only a subgroup of those with schizophrenia.     

Diagnostic stability in subjects with multiple admissions for psychotic illness

BACKGROUND: Although studies investigating changes in diagnosis between psychotic episodes have differed in design, some consistent findings have emerged. This study seeks to clarify and extend these findings by describing and comparing clinical and operationally defined diagnostic stability in a group of subjects with multiple episodes of functional psychotic illness. METHODS: The OPCRIT programme was applied to case notes of 204 subjects with multiple admissions for psychotic illness. Clinical and operationally defined diagnoses were compared and the spread and stability of diagnoses determined. RESULTS: An increase in the frequency of diagnosis of schizophrenia from initial to subsequent episodes was demonstrated. High levels of stability were found for schizophrenia (58 to 98%), moderate levels for affective disorders (24 to 83%), low levels for other non-organic psychotic conditions (27 to 54%) and atypical psychosis (27 to 53%), and very low levels for schizoaffective disorder (5 to 39%) and other conditions (0 to 4%). CONCLUSIONS: The stability levels for schizophrenia and affective disorders are adequate, but the low levels for a range of other psychotic conditions raise questions regarding their predictive validity.     

Signs and symptoms in the pre-psychotic phase: description and implications for diagnostic trajectories

BACKGROUND: Few studies have examined the underlying factor structure of signs and symptoms occurring before the first psychotic episode. Our objective was to determine whether factors derived from early signs and symptoms are differentially associated with non-affective versus affective psychosis. METHOD: A principal components factor analysis was performed on early signs and symptoms reported by 128 individuals with first-episode psychosis. Factor scores were examined for their associations with duration of untreated illness, drug abuse prior to onset of psychosis, and diagnosis (schizophrenia versus affective psychosis). RESULTS: Of the 27 early signs and symptoms reported by patients, depression and anxiety were the most frequent. Five factors were identified based on these early signs and symptoms: depression, disorganization/mania, positive symptoms, negative symptoms and social withdrawal. Longer duration of untreated illness was associated with higher levels of depression and social withdrawal. Individuals with a history of drug abuse prior to the onset of psychosis scored higher on pre-psychotic depression and negative symptoms. The two mood-related factors, depression and disorganization/mania, distinguished the eventual first-episode diagnosis of affective psychosis from schizophrenia. Individuals with affective psychosis were also more likely to have a 'mood-related' sign and symptom as their first psychiatric change than individuals later diagnosed with schizophrenia. CONCLUSIONS: Factors derived from early signs and symptoms reported by a full diagnostic spectrum sample of psychosis can have implications for future diagnostic trajectories. The findings are a step forward in the process of understanding and characterizing clinically important phenomena to be observed prior to the onset of psychosis.     

D-amino acid oxidase (DAO) genotype and mood symptomatology in schizophrenia

A series of genetic studies have identified the D-amino acid oxidase (DAO) gene as potentially contributing to schizophrenia susceptibility. An interacting gene, D-amino acid oxidase activator (DAOA) has also been implicated and it has been suggested that variation at these genes may influence the efficiency of glutamate gating at N-methyl-D-aspartate-type (NMDA) receptors. However, recent data suggests that DAOA may influence susceptibility to mood episodes across the spectrum of psychotic disorders rather than contributing to a specific psychosis phenotype. The aim of this study was to determine whether risk variation at DAO is similarly associated with affective or other clinical symptoms in psychosis. We have previously reported association between risk variation at DAO and schizophrenia in an Irish case-control sample. In this study we investigated the relationship between a defined genetic risk variant at DAO and PANSS-derived clinical symptom factors in a sample of 249 patients using principal component and Kruskal-Wallis analyses. Carriers of the DAO risk variant scored significantly higher on the 'depression/anxiety' factor than non-carriers (H=9.02, d.f.=2, p=0.01). These data suggest a potential role for DAO in susceptibility to depressive symptoms in schizophrenia, but a more general role for DAO in affective disorders cannot be excluded.     

Association between psychotic disorder and urban place of birth is not mediated by obstetric complications or childhood socio-economic position: a cohort study

BACKGROUND: Although urban place of birth has been identified as a risk factor for schizophrenia, the extent to which this association is mediated by socially patterned risk factors such as obstetric complications and childhood socio-economic position is unclear. The diagnostic specificity of the association within the clinical psychotic syndromes is also unclear. METHOD: A population cohort of 696025 males and females, born in Sweden between 1973 and 1980 and with linked birth and socio-economic data was followed up from age 16 for up to 9.8 years. Hospitalized cases of schizophrenia and other non-affective psychosis were identified from the Swedish Inpatient Discharge Register. We examined associations of these disorders with a three-level measure of urbanicity of birthplace before and after controlling for measures of foetal nutrition, obstetric complications and level of maternal education. RESULTS: Urban compared to rural birthplace was associated both with increased risk of adult onset schizophrenia (hazard ratio 1.34, CI 0.91-1.96) and other non-affective psychoses (hazard ratio 1.63, CI 1.18-2.26). None of these associations was greatly affected by adjustment for obstetric complications or maternal educational level. In the group of other non-affective psychoses urban-rural differences in disease risk were strongest among those born in the winter months. CONCLUSION: Urbanization of birthplace is associated with increased risk of non-affective psychosis but this is not confined to narrowly defined cases. The magnitude of the association in Sweden is lower than that reported in other studies. Causal factors underlying this association appear to operate independently of risks associated with obstetric complications and parental educational status.     

The prevalence and correlates of self-harm in pregnant women with psychotic disorder and bipolar disorder

Women with severe mental illness are at increased risk of suicide in the perinatal period, and these suicides are often preceded by self-harm, but little is known about self-harm and its correlates in this population. This study aimed to investigate the prevalence of suicidal ideation and self-harm, and its correlates, in women with psychotic disorders and bipolar disorder during pregnancy. Historical cohort study using de-identified secondary mental healthcare records linked with national maternity data. Women pregnant from 2007 to 2011, with ICD-10 diagnoses of schizophrenia and related disorders, bipolar disorder or other affective psychoses were identified. Data were extracted from structured fields, natural language processing applications and free text. Logistic regression was used to examine the correlates of self-harm in pregnancy. Of 420 women, 103 (24.5 %) had a record of suicidal ideation during the first index pregnancy, with self-harm recorded in 33 (7.9 %). Self-harm was independently associated with younger age (adjusted odds ratio (aOR) 0.91, 95 % CI 0.85–0.98), self-harm in the previous 2 years (aOR 2.55; 1.05–6.50) and smoking (aOR 3.64; 1.30–10.19). A higher prevalence of self-harm was observed in women with non-affective psychosis, those who discontinued or switched medication and in women on no medication at the start of pregnancy, but these findings were not statistically significant in multivariable analyses. Suicidal thoughts and self-harm occur in a significant proportion of pregnant women with severe mental illness, particularly younger women and those with a history of self-harm; these women need particularly close monitoring for suicidality.     

The evolution of insight, paranoia and depression during early schizophrenia

BACKGROUND: How insight, paranoia and depression evolve in relation to each other during and after the first episode of schizophrenia is poorly understood but of clinical importance. METHOD: Serial assessments over 18 months were made using multiple instruments in a consecutive sample of 257 patients with first episode DSM-IV non-affective psychosis. Repeated measures of paranoia, insight, depression and self-esteem were analysed using structural equation modelling, to examine the direction of relationships over time after controlling for confounds. RESULTS: Depression was predicted directly by greater insight, particularly at baseline, and by greater paranoia at every stage of follow-up. Neither relationship was mediated by self-esteem, although there was a weak association of lower self-esteem with greater depression and better insight. Paranoia was not strongly associated with insight. Duration of untreated psychosis and substance use at baseline predicted depression at 18 months. CONCLUSIONS: In first-episode psychosis, good insight predicts depression. Subsequently, paranoia is the strongest predictor. Neither effect is mediated by low self-esteem. Effective treatment of positive symptoms is important in preventing and treating low mood in early schizophrenia.     

Urinary dimethyltryptamine and psychiatric symptomatology and classification.

The excretion of dimethyltryptamine (DMT) was studied amongst 122 recently admitted psychiatric patients and 20 normal subjects. DMT was detected in the urine of 47% of those diagnosed by their psychiatrists as schizophrenic, 38% of those with other non-affective psychoses, 13% of those with affective psychoses, 19% of those with neurotic and personality disorders and 5% of normal subjects. Ninety-nine patients were interviewed in a semi-standardized fashion, and also categorized according to a variety of operational definitions of the psychoses. The operational definitions failed to reveal any group significantly more correlated with urinary DMT than a hospital diagnosis of schizophrenia, but a discriminant function analysis of symptomatology could be used to define a group of 21 patients of whom 15 (71%) excreted detectable DMT. There was a general relationship between psychotic symptoms and urinary DMT, but specifically schizophrenic symptoms did not appear to be major determinants of DMT excretion.     

Tumour necrosis factor alpha and bipolar affective puerperal psychosis

The macrophage theory of depression proposes that an excessive secretion of monocyte/macrophage cytokines causes symptoms of depression. It has been suggested that changes in immune function that accompany pregnancy and childbirth could contribute to the affective symptoms suffered by many puerperal women. Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine that has been implicated in inflammatory infections and immune diseases. Production of TNFalpha has been shown to be regulated by oestrogen, which suggests it as a potential candidate for susceptibility to post-partum mood disorders. Several polymorphisms have been identified in the TNFalpha gene. The -308 promoter polymorphism has been associated with elevated production of TNFalpha and has been found to influence the neurological outcome of various infections. In a case-control association study, we have examined the frequency of this polymorphism in groups of parous DSM-IV Bipolar females with (N = 116) and without (N = 56) puerperal psychosis, and a female non-psychiatric comparison group (N = 72). We provided no support for the hypothesis that this polymorphism influences susceptibility to bipolar disorder, or acts as a trigger for puerperal psychosis. However, variation at other polymorphisms within TNFalpha or in other oestrogen-regulated genes involved in immune function remain interesting candidates for study in post-partum mood disorders.     

Symptomatology and social inference: A theory of mind study of schizophrenia and psychotic affective disorder

Introduction. There is evidence that certain patients with schizophrenia have deficits in theory of mind (ToM) capabilities. It is, however, unclear whether these are symptom or diagnosis-specific. Methods. A ToM hinting task was given to 15 patients with a DSM-IV diagnosis of schizophrenia, 15 patients with affective disorder and 15 healthy controls. Severity of the current psychopathology was measured using the Krawiecka standardised scale of psychotic symptoms (Krawiecka, Goldberg, & Vaughan, 1977); IQ was estimated via the Ammons and Ammons Quick Test (Ammons & Ammons, 1962). Results. The group with schizophrenia performed significantly worse than the affective and control groups. Poor performance on the hinting task was found to be significantly related to the presence of positive symptoms (instead of negative ones) and specifically related to delusions and hallucinations. These findings remained when covariance for potentially confounding variables was applied. Conclusions. Individuals with high levels of delusions and hallucinations performed significantly worse on this ToM task, regardless of diagnosis, implying ToM impairment is not exclusive to schizophrenia but is evident in other forms of psychosis. Between-group analyses showed the schizophrenia group had a significicantly poorer performance on this task than the others.