Testing the Psychopathology of Psychosis: Evidence for a General Psychosis Dimension

Background: Psychiatric taxonomists have sometimes argued for a unitary psychosis syndrome and sometimes for a pentagonal model, including 5 diagnostic constructs of positive symptoms, negative symptoms, cognitive disorganization, mania, and depression. This continues to be debated in preparation for impending revisions of the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases. We aimed to identify general and specific dimensions underlying psychopathological features of psychosis. Methods: The samples comprised 309 patients admitted to psychiatric services in the acute phase of their first or second episode of psychosis and 507 patients with enduring psychosis recruited from community mental health teams. Patients’ symptoms were assessed on the Positive and Negative Symptom Scale. Analyses compared unitary, pentagonal, and bifactor models of psychosis. Results: In both samples, a bifactor model including 1 general psychosis factor and, independently, 5 specific factors of positive symptoms, negative symptoms, disorganization, mania, and depression gave the best fit. Scores of general and specific symptom dimensions were differentially associated with phase of illness, diagnosis, social functioning, insight, and neurocognitive functioning. Conclusions: The findings provide strong evidence for a general psychosis dimension in both early and enduring psychosis. Findings further allowed for independent formation of specific symptom dimensions. This may inform the current debate about revised classification systems of psychosis.     

Psychosis risk syndrome is not prodromal psychosis

概述

精神分裂症研究中最令人振奋的趋势之一是从治疗学研究转向精神分裂症的早期识别和早期干预研究。后者的研究对象主要集中于处于精神病“前驱期”或“临床高危”的青少年或年轻的成年患者，他们出现的认知功能障碍和社会功能障碍与精神分裂症患者相似，因而被认为具有精神分裂症或其他精神病性障碍的高患病风险。有学者将这种认知和社会功能障碍的表现称为精神病风险综合征（psychosis risk syndrome, PRS）。在某些范围内已有试图将这一状态重新定义为一种精神障碍的举动，如：美国精神医学学会的《精神障碍诊断与统计手册》第五版（DSM-5）将“轻微精神病综合征”（attenuated psychosis syndrome, APS）列入“需要进一步研究的状态”。存在PRS的个体出现精神病性障碍的风险的确比没有PRS的人要高，但多数PRS个体以后也不会患精神病性障碍，因此，我们反对将PRS或APS作为一种亚型列入精神分裂症谱系障碍中。

中文全文

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The First‐Episode Psychosis Outcome Study: premorbid and baseline characteristics of an epidemiological cohort of 661 first‐episode psychosis patients

Aims: Studies conducted in first‐episode psychosis (FEP) samples avoid many biases. However, very few studies are based on epidemiological cohorts treated in specialized FEP services. The aim of this file audit study was to examine premorbid and baseline characteristics of a large epidemiological sample of FEP. Methods: File audit study of all patients admitted to the Early Psychosis Prevention and Intervention Centre between 1998 and 2000 using a specialized questionnaire. Results: There were 661 patient files included in the study. Premorbid evaluation revealed high rates of substance use disorder (74.1%), history of psychiatric disorder (47.5%), past traumatic events (82.7%) suicide attempts (14.3%) and family history of psychiatric illness (55.6%). Baseline characteristics revealed high intensity of illness (mean CGI 5.5), high prevalence of lack of insight (62%) and high rate of comorbidity (70%). Conclusion: High rates of traumatic events or episodes of mental illness before treatment for FEP must be considered when designing treatment approaches because a too narrow focus on positive psychotic symptoms will inevitably lead to incomplete treatment. Additionally, early intervention programmes need sufficient range of resources to address the multiple challenges presented by FEP patients such as high severity of illness, comorbidities and functional impairment. Finally, observation of an important degree of functional impairment despite short duration of untreated psychosis suggests that while early detection of FEP is a necessary step in early intervention, it may not be sufficient to improve functional recovery in psychosis and that efforts aimed at identifying people during the prodromal phase of psychotic disorders should be pursued.     

Psychosis and adults with intellectual disabilities

Objective To determine the point prevalence, incidence, and remission over a 2-year period of psychosis in adults with intellectual disabilities, and to investigate demographic and clinical factors hypothesised to be associated with psychosis. Method A population-based cohort of adults with intellectual disabilities (n = 1,023) was longitudinally studied. Comprehensive face-to-face mental health assessments to detect psychosis, plus review of family physician, psychiatric, and psychology case notes were undertaken at two time points, 2 years apart. Results Point prevalence is 2.6% (95% CI = 1.8–3.8%) to 4.4% (95% CI = 3.2–5.8%), dependant upon the diagnostic criteria employed. Two-year incidence is 1.4% (95% CI = 0.6–2.6), and for first episode is 0.5% (95% CI = 0.1–1.3). Compared with the general population, the standardised incidence ratio for first episode psychosis is 10.0 (95% CI = 2.1–29.3). Full remission after 2 years is 14.3%. Visual impairment, previous long-stay hospital residence, smoking, and not having epilepsy were independently associated with psychosis, whereas other factors relevant to the general population were not. Conclusions The study of psychosis in persons with intellectual disabilities benefits the population with intellectual disabilities, and advances the understanding of psychosis for the general population. Mental health professionals need adequate knowledge in order to address the high rates of psychosis in this population.     

Autoimmune diseases,bipolar disorder,and non‐affective psychosis

Eaton WW, Pedersen MG, Nielsen PR, Mortensen PB. Autoimmune diseases, bipolar disorder, and non‐affective psychosis. Bipolar Disord 2010: 12: 638–646. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objective: Clinic‐based studies of immune function, as well as comorbidity of autoimmune diseases, bipolar disorder, and schizophrenia, suggest a possible autoimmune etiology. Studies of non‐affective psychosis and schizophrenia suggest common etiologies. The objective was to determine the degree to which 30 different autoimmune diseases are antecedent risk factors for bipolar disorder, schizophrenia, and non‐affective psychosis. Methods: A cohort of 3.57 million births in Denmark was linked to the Psychiatric Case Register and the National Hospital Register. There were 20,317 cases of schizophrenia, 39,076 cases of non‐affective psychosis, and 9,920 cases of bipolar disorder. Results: As in prior studies, there was a range of autoimmune diseases which predicted raised risk of schizophrenia in individuals who had a history of autoimmune diseases, and also raised risk in persons whose first‐degree relatives had an onset of autoimmune disease prior to onset of schizophrenia in the case. These relationships also existed for the broader category of non‐affective psychosis. Only pernicious anemia in the family was associated with raised risk for bipolar disorder (relative risk: 1.7), suggesting a small role for genetic linkage. A history of Guillain‐Barré syndrome, Crohn’s disease, and autoimmune hepatitis in the individual was associated with raised risk of bipolar disorder. Conclusions: The familial relationship of schizophrenia to a range of autoimmune diseases extends to non‐affective psychosis, but not to bipolar disorder. The data suggest that autoimmune processes precede onset of schizophrenia, but also non‐affective psychosis and bipolar disorder.     

Schizophrenia and the Environment: Within-Person Analyses May be Required to Yield Evidence of Unconfounded and Causal Association—The Example of Cannabis and Psychosis

Hypotheses about the link between cannabis use and psychosis apply to the within-person level but have been tested mostly at the between-person level. We used a within-person design, in which a person serves as his own control, thus removing the need to consider confounding by any fixed (genetic and nongenetic) characteristic to study the prospective association between cannabis use and the incidence of attenuated psychotic experiences, and vice versa, adjusted for time-varying confounders. We combined 2 general population cohorts (at baseline: Early Developmental Stages of Psychopathology Study, n = 1395; Netherlands Mental Health Survey and Incidence Study-2, n = 6603), which applied a similar methodology to study cannabis use and attenuated psychotic experiences with repeated interviews (T0, T1, T2, and T3) over a period of approximately 10 years. The Hausman test was significant for the adjusted models, indicating the validity of the fixed-effects model. In the adjusted fixed-effects model, prior cannabis use was associated with psychotic experiences (aOR = 7.03, 95% CI: 2.39, 20.69), whereas prior psychotic experiences were not associated with cannabis use (aOR = 0.59, 95% CI: 0.21, 1.71). Longitudinal studies applying random-effects models to study associations between risk factors and mental health outcomes, as well as reverse causality, may not yield precise estimates. Cannabis likely impacts causally on psychosis but not the other way round.     

Family Work in Early Psychosis

Abstract

Many individuals with schizophrenia have family members who are actively involved in their care. Often, these family members feel burdened and experience significant distress as a consequence of this increased responsibility. Family interventions have been shown to reduce relapse in individuals with psychosis, highlighting the importance of the family component in psychosis treatment programs. This paper describes how an optimal family intervention can be devised using a recovery framework, and used within an early psychosis treatment program. Three-year outcome data is presented demonstrating improvement in family well-being, and clinical implications are discussed.     

The Psychopathology and Neuroanatomical Markers of Depression in Early Psychosis

Depression frequently occurs in first-episode psychosis (FEP) and predicts longer-term negative outcomes. It is possible that this depression is seen primarily in a distinct subgroup, which if identified could allow targeted treatments. We hypothesize that patients with recent-onset psychosis (ROP) and comorbid depression would be identifiable by symptoms and neuroanatomical features similar to those seen in recent-onset depression (ROD). Data were extracted from the multisite PRONIA study: 154 ROP patients (FEP within 3 months of treatment onset), of whom 83 were depressed (ROP+D) and 71 who were not depressed (ROP−D), 146 ROD patients, and 265 healthy controls (HC). Analyses included a (1) principal component analysis that established the similar symptom structure of depression in ROD and ROP+D, (2) supervised machine learning (ML) classification with repeated nested cross-validation based on depressive symptoms separating ROD vs ROP+D, which achieved a balanced accuracy (BAC) of 51%, and (3) neuroanatomical ML-based classification, using regions of interest generated from ROD subjects, which identified BAC of 50% (no better than chance) for separation of ROP+D vs ROP−D. We conclude that depression at a symptom level is broadly similar with or without psychosis status in recent-onset disorders; however, this is not driven by a separable depressed subgroup in FEP. Depression may be intrinsic to early stages of psychotic disorder, and thus treating depression could produce widespread benefit.     

From Real-World Events to Psychosis: The Emerging Neuropharmacology of Delusions

The earliest stages of delusion are characterized by an overabundance of meaningful coincidences impinging on the sufferer''s existing worldview. Successive events are seen by him as pointing to, and then confirming, a fundamentally new reality that takes him over and engulfs his everyday life. Research over the last 4 decades has revealed the importance of dopamine (DA), D2 receptors, and the basal ganglia in psychotic thinking. Recent work has implicated the aberrant reward learning initiated by the excess release of striatal DA in the attribution of excessive importance or “salience” to insignificant stimuli and events. But our knowledge of what is happening beyond D2 receptors has remained scant. The gap is especially apparent at the cellular and microcircuit levels, encompassing the plastic changes, which are believed to be essential for new learning, and whose processes may go awry in major mental illness. Now new pharmacological findings are advancing our understanding of information processing and learning within the striatum. DA has an important role in setting the strength of individual striatal connections, but it does not act in isolation. Two other modulator systems are critical, the endocannabinoids and adenosine. Thus, at medium spiny neurons belonging to the indirect pathway, D2 stimulation evokes endocannabinoid-mediated depression of cortical inputs. Adenosine acting at A2A receptors elicits the opposite effect. Remarkably, drugs that target the endocannabinoid and purinergic systems also have pro- or antipsychotic properties. Here, we discuss how the 3 modulators regulate learning within the striatum and how their dysfunction may lead to delusional thinking.     

Epidemiological factors associated with treated incidence of first-episode non-affective psychosis in Cantabria: insights from the Clinical Programme on Early Phases of Psychosis

Aim: The aim of the study was to analyse the treated incidence of schizophrenia in Cantabria (Northern Spain) and the sociodemographic risk factors associated with the illness onset. Methods: Data were obtained from patients included in the Cantabria's Clinical Programme on First‐Episode Psychosis (schizophrenia spectrum DSM‐IV diagnosis) from 2001 to 2005, from the Cantabria first‐episode schizophrenia study (carried out between 1988 and 1989) and from the 2001 Spanish census. Results: Annual incidence was 1.38 per 10 000 inhabitants in the risk‐ageperiod. Identified risk factors were male gender (relative risk (RR): 1.61), age 15–25 years (RR: 3.48), unemployment (RR: 2.82), single status (RR: 5.88), low educational level (RR: 4.38), urban environment (RR: 1.62) and cannabis consumption (odds ratio: 12.83). The incidence in females was significantly lower than the one obtained 15 years ago. Conclusions: The reported factors suggest that underlying biological and social factors modulate the risk of psychosis. This balance operates differently in males and females.     

Integrated genetic and genomic approach in the SingaporeTranslational and Clinical Research in Psychosis Study: an overview

Aims: Schizophrenia is a severe mental disorder with onset frequently in adolescence and followed by a chronic and disabling course. Although the exact pathophysiology of this devastating disorder has not been clearly elucidated, a large part of it has been attributed to genetic influences. This article seeks to provide an overview on what our group has embarked on – to elucidate genetic risk factors for schizophrenia within the Chinese ethnic group. Methods: We plan to conduct an integrated approach to interrogate comprehensively the genome from different angles and in stages. The first stage involves a genome‐wide association study of 1000 cases of schizophrenia‐control pairs, with a follow‐up replication study in another 1000 cases of schizophrenia and in 1000 controls, and combination analyses with groups from other places including China and Hong Kong. Other than the genome‐wide association study, gene sequencing for purported candidate genes and copy number variation analysis will be performed. Neurocognitive intermediate phenotypes will be employed to deconstruct the complex schizophrenia phenotype in a bid to improve association findings. Promising leads from longitudinal gene and protein expression in ultra‐high‐risk subjects who develop psychosis and schizophrenia (in a parallel study) will be followed up as candidate genes and sequenced in the genetic analysis. Functional analysis forms the last stage of this integrated approach. Conclusion: This integrated genetic and genomic approach will hopefully help in further characterizing and deepening our understanding of molecular pathophysiological mechanisms underlying schizophrenia.     

Associations Between Non-neurological Autoimmune Disorders and Psychosis: A Meta-analysis

Background

A relationship between non-neurological autoimmune (NNAI) disorders and psychosis has been widely reported but not yet subjected to meta-analysis. We conducted the first meta-analysis examining the association between NNAI disorders and psychosis and investigated the effect of 1) temporality (as determined by study design), 2) psychiatric diagnosis, and 3) specific autoimmune disorders.

Schizophrenia-like Psychosis in a 46, XX Male

Abstract: XX male is a rather rare condition among general population. A case of schizophrenia-like psychosis in a 46, XX male found among 4,129 male inpatients in Japanese mental hospitals was presented. The main clinical feature was a formal thought disorder that included delusions, auditory hallucinations and poor reality testing. This is the first report of the 46, XX male with schizophrenia-like psychosis.     

Chronic Schizophrenia-Like States in Methamphetamine Psychosis

Abstract: In order to clarify the characteristic psychopathology of chronic methamphetamine (MAP) psychosis, the clinical symptoms of 11 chronic MAP psychotics were compared with those of the same number of chronic schizophrenics matched for sex and age. The positive symptoms were almost similar in both groups. However, the negative symptoms evaluated by the Scale for the Assessment of Negative Symptoms (SANS) differed considerably. According to the SANS, the scores of avolition-apathy, anhedonia-asociality and attentional impairment were moderately high in both groups. The scores of affective flattening or blunting and alogia were lower in the MAP group than those in the schizophrenia group. The SANS scores of negative symptoms increased in accordance with the age of onset in the MAP group, while such a correlation was not observed in the schizophrenia group. Furthermore, detailed clinical observations of the patients revealed the following differences between the two groups: 1) spontaneous affective expression during the interviews was more vivid in the MAP group compared to the schizophrenia group, and 2) affective expressions or interpersonal behaviors changed immediately depending on the situation in the MAP group. From the viewpoint of clinical psychopathology, a group of MAP psychotics whose hallucinatory-delusional state persisted for a long period of one month or more after cessation of MAP use seemed to differ from either chronic schizophrenics or patients with acute MAP psychosis. The author proposed that this group of patients should be a clinical entity and be called as "residual methamphetamine psychosis."     

Multivariate Analyses of CT Findings in Typical Schizophrenia and Atypical Psychosis

Abstract: In order to investigate the brain morphological differences between typical schizophrenia and atypical psychosis, the brain CTs of 41 : patients with typical schizophrenia, 27 : patients with atypical psychosis (ATP), and 20 : controls were examined. The schizophrenics had larger values for 9 : CT indices, i.e., interhemispheric fissure UHF) index, VBR, 2 : lateral ventricles (GV) and 3rd ventricle (III-V) indices, and 4 : sylvian fissure (SF) indices, while the values of ATP patients for 3 : SF indices were greater than for the controls. Moreover, the schizophrenics had greater III-V and L-V indices than the ATP patients. The correlation matrix of CT indices indicates that the III-V Index correlated well with the other Cl' indices, whereas the VBR, IHF and right SF indices did not. Therefore, it was speculated that there might be 3 : subgroups, each of which has a main focus of alteration in the above-mentioned regions. Therefore, all the cases were divided by means of a cluster analysis into 5 : groups. Group I, which contained mainly normal controls, and Group II, which consisted mainly of atypical psychosis patients, had no abnormal CT findings. Group III, which comprised mainly ATP patients and paranoid type schizophrenics, had right SF enlargement. Group IV, which showed signillcant IHF enlargement, and the residue group, which had larger VBR and significant left SF enlargement, consisted mostly of schizophrenics. Thus, our results suggest that the classiflcation by CT data corresponds on the whole to our clinical diagnosis, according to which schizophrenic psychosis is divided into typical schizophrenia and atypical psychosis, and that each of the two psychosis groups may be further classified into distinct subgroups.     

自身免疫性脑炎与睡眠障碍

自身免疫性脑炎与睡眠障碍关系密切。抗Ma2抗体介导的神经系统副肿瘤综合征可以导致发作性睡病和快速眼动睡眠期行为障碍。边缘性脑炎和Morvan综合征可以导致严重失眠及其他睡眠障碍,常伴抗电压门控性钾离子通道抗体(包括抗富亮氨酸胶质瘤失活基因1抗体和抗接触蛋白相关蛋白-2抗体)阳性。中枢性低通气常见于抗N-甲基-D-天冬氨酸受体脑炎患者。阻塞性睡眠呼吸暂停、喘鸣和异态睡眠是抗IgLON家族蛋白5抗体相关脑病的常见表现。由此可见,睡眠障碍是自身免疫性脑炎的重要表现,免疫治疗有可能改善临床症状和预后。     

One-year prevalence of long-term functional psychosis in three different areas of Uppsala

The 1-year prevalence of long term functional psychoses (LFP) in Uppsala was found to be 0.73%, with a clear gradient from the central city area (0.87%) to the rural area (0.60%). The highest prevalence was found in the 35–54 years age group (1.01%), and the lowest prevalence in the 18–34 years age group (0.45%). There were no pronounced sex differences. The majority of the LFP patients were diagnosed as having schizophrenia. The 1-year prevalence of schizophrenia was 0.42%, with a clear gradient from the central city area to the rural area (0.53%, 0.44% and 0.30%, respectively). The same gradient was not observed with regard to the other diagnostic subgroups relating to LFP.     

A Population Based Analysis of Subclinical Psychosis and Help-Seeking Behavior

Clinically defined psychosis is recognizable and distinguishable from nonclinical or subclinical psychosis by virtue of its clinical relevance (ie, its associated distress and its need for care and/or treatment). According to the continuum hypothesis, subclinical psychosis is merely quantitatively different from more extreme phenotypic expressions and as such should also be indicative of distress and help-seeking behavior but to a lesser extent. Using data from the Adult Psychiatric Morbidity Survey, the current study focused on self-reported psychosis and help-seeking experiences in a general population sample free from clinically defined psychosis (N = 7266). After statistically controlling for the effects of a series of potential help-seeking correlates the findings showed that subclinical psychosis symptom experience was significantly associated with various forms of help-seeking behavior. Individuals who reported subclinical experiences of thought control, paranoia, and strange experiences were on average 2 times more likely to attend their general practitioner for emotional problems compared with those individuals who reported no psychosis. Individuals who reported subclinical experiences of paranoia were 3 times more likely to be in receipt of counseling/therapy compared with those with no experience of paranoia. Multiple subclinical psychotic experiences also predicted elevated help-seeking behavior. These findings may have a positive impact on the detection of individuals who are at increased risk of psychological distress and aid in the design and implementation of more effective treatments at both clinical and subclinical levels.