Recovery from an at-risk state: clinical and functional outcomes of putatively prodromal youth who do not develop psychosis

Background: The "clinical high risk" (CHR) construct was developed to identify individuals at imminent risk of developing psychosis. However, most individuals identified as CHR do not convert to psychosis, and it is unknown whether these nonconverting individuals actually recover from an at-risk state. Methods: Eighty-four prospectively identified patients meeting CHR criteria, and 58 healthy comparison subjects were followed in a 2-year longitudinal study. Analyses examined rates of conversion, clinical, and functional recovery. Proportional cause-specific hazard models were used to examine the effects of baseline and time-varying predictors on conversion and remission. Trajectories of symptoms and psychosocial functioning measures were compared across outcome groups. Results: Competing risk survival analyses estimated that 30% of CHR subjects convert to psychosis by 2 years, while 36% symptomatically remit and 30% functionally recover by 2 years. Lower levels of negative and mood/anxiety symptoms were related to increased likelihood of both symptomatic and functional recovery. CHR subjects who remitted symptomatically were more similar to healthy controls in terms of both their baseline and longitudinal symptoms and functioning than the other outcome groups. Conclusions: Nonconverting CHR cases represented a heterogeneous group. Given that nonconverted subjects who remitted symptomatically also presented initially with less severe prodromal symptomatology and showed a distinct normative trajectory of both symptoms and psychosocial functioning over time, it may be possible to refine the CHR criteria to reduce the number of "false positive" cases by eliminating those who present with less severe attenuated positive symptoms or show early improvements in terms of symptoms or functioning.     

The reliability of DSM-III prodromal symptoms in first-episode psychotic patients

Thirty-one first-episode psychotic patients were assessed via a semistructured interview to determine the presence or absence of the 8 DSM-III prodromal symptoms. Interrater reliability data were calculated for the same symptoms according to the patient, an informant and the raters blending the previous 2 sources of information. Levels of reliability, reported as kappa and percentage agreements, were generally acceptable.     

A putative animal model of the "prodromal" state of schizophrenia.

BACKGROUND: There is growing interest in detecting and treating schizophrenia during the "prodrome," before the symptoms are fully manifested. The objective of this study was to develop a putative model of the prodrome and study the effects of medications on it. METHODS: Rats were treated with different regimens of amphetamine to produce full sensitization (full syndrome) and partial sensitization (to model the prodromal state) and were then treated with typical and atypical antipsychotics and a D1 antagonist to mimic early intervention. After several weeks of withdrawal, locomotor activity in response to amphetamine and behavioral deficits (prepulse inhibition [PPI] and latent inhibition [LI]) were examined. RESULTS: Animals that received the full sensitization showed significant increase in locomotor activity and a disruption in both PPI and LI. Animals treated with a partial regimen showed only a muted phenotype. The animals that received "early intervention" did not show progression from the prodromal to the full-blown phenotype. CONCLUSIONS: The partial regimen of amphetamine injections provided a modified phenotype that could be regarded as a representative of the "prodromal" state. Early intervention, instituted once the prodromal state was already developed, prevented further progression into the full phenotype analogous to schizophrenia.     

Identification and treatment of the prodromal phase of psychotic disorders: perspectives from the PACE Clinic

Aim: To describe the development of the field of prodromal intervention in psychotic disorders and to summarize the findings from the PACE Clinic, the inaugural service devoted to this area. Method: A review of the PACE Clinic studies, with reference to the work of other groups. Results: The aims of intervention before the onset of psychosis are to alleviate current distress and impairment and to either prevent, delay or ameliorate the onset of more severe psychotic disorder. To do this, it is necessary to be able to first accurately identify those in the earliest stages of a potentially serious psychotic disorder, and second to effectively slow or prevent progression to more advanced illness. Criteria have been developed which have predicted onset of psychotic disorder inover 30% of so‐called ‘ultra high risk’ individuals. Treatment trials have been promising, and to date have examined the effects of antipsychotic medication, cognitive therapy and a combination of the two. Recently, omega‐3 fatty acids have also been shown to be effective. However, there are also pitfalls of working in the prodromal area, including ethical concerns and more recently the possibility that there is a decline in the rate of transition from ultra‐high‐risk state to first‐episode psychosis. Conclusions: The field of prodromal intervention in psychotic disorders is an exciting one as it offers the possibility of prevention of full‐blown disorder and its related negative sequelae. However, there are many issues that need to be dealt with in order to achieve this goal, and ongoing evaluation of methods to identify and treat such individuals is needed.     

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

本文全文中文版从2015年4月8日起在http://dx.doi.org/10.11919/j.issn.1002-0829.214178可供免费阅览下载     

The Validity of the 16-Item Version of the Prodromal Questionnaire (PQ-16) to Screen for Ultra High Risk of Developing Psychosis in the General Help-Seeking Population

In order to bring about implementation of routine screening for psychosis risk, a brief version of the Prodromal Questionnaire (PQ; Loewy et al., 2005) was developed and tested in a general help-seeking population. We assessed a consecutive patient sample of 3533 young adults who were help-seeking for nonpsychotic disorders at the secondary mental health services in the Hague with the PQ. We performed logistic regression analyses and CHi-squared Automatic Interaction Detector decision tree analysis to shorten the original 92 items. Receiver operating characteristic curves were used to examine the psychometric properties of the PQ-16. In the general help-seeking population, a cutoff score of 6 or more positively answered items on the 16-item version of the PQ produced correct classification of Comprehensive Assessment of At-Risk Mental State (Yung et al., 2005) psychosis risk/clinical psychosis in 44% of the cases, distinguishing Comprehensive Assessment of At-Risk Mental States (CAARMS) diagnosis from no CAARMS diagnosis with high sensitivity (87%) and specificity (87%). These results were comparable to the PQ-92. The PQ-16 is a good self-report screen for use in secondary mental health care services to select subjects for interviewing for psychosis risk. The low number of items makes it quite appropriate for screening large help-seeking populations, thus enhancing the feasibility of detection and treatment of ultra high-risk patients in routine mental health services.     

Generalized and specific neurocognitive deficits in prodromal schizophrenia.

BACKGROUND: Neurocognitive deficits are considered to be central to the pathophysiology of schizophrenia, and the neurodevelopmental model suggests that such deficits precede full-blown psychosis. The present study examined performance on a broad neuropsychological battery of young subjects considered to be at clinical high risk for schizophrenia, who were subsequently followed to determine clinical outcome. METHODS: Subjects were 38 clinical high-risk patients (58% male patients; mean age = 16.5) and 39 sex- and age-matched healthy control subjects. At baseline, all high-risk patients had attenuated (subpsychotic) schizophrenialike positive symptoms. Clinical follow-up data of at least 6 months duration was available on 33 patients, of whom 12 developed nonaffective psychotic disorders. RESULTS: At baseline, clinical high-risk patients had significantly impaired global cognitive performance relative to control subjects and to estimates of their own prior intellectual functioning. Measures of verbal memory and executive functioning/working memory showed significantly greater impairments; visuospatial functioning was relatively spared. Prodromal patients who later developed psychosis had significantly lower verbal memory scores at baseline compared with patients who remained nonpsychotic. CONCLUSIONS: Verbal memory deficits may be an important risk marker for the development of schizophrenia-spectrum psychotic disorders, possibly indicating the presence of a prefrontal-hippocampal neurodevelopmental abnormality. Generalized neurocognitive impairment may be a nonspecific vulnerability marker.     

The prevalence of prodromal features of schizophrenia in adolescence: a preliminary survey

In most cases of schizophrenia the onset of frank psychosis is preceded by a period of prodromal features. This period has been relatively neglected by researchers and is potentially important in promoting early intervention. The prevalence of DSM-III-R schizophrenia prodrome symptoms was assessed as part (n= 657) of a large (n= 2525) questionnaire-based survey of high school students. Individual symptoms were highly prevalent and the prevalence of DSM-III-R prodromes ranged from 10–15% to 50%. Despite methodological weaknesses, the data suggest that DSM-III-R prodromal features are extremely prevalent among older adolescents and unlikely to be specific for subsequent schizophrenia. Clinically these features cannot be regarded as sufficient evidence of early schizophrenia and more accurate predictors of incipient schizophrenia need to be defined.     

The stigma of psychiatric treatment and help-seeking intentions for depression

Aims  The stigma of mental illness has often been considered a potential cause for reluctant willingness to seek help for mental problems, but there is little evidence on this issue. We examine two aspects of stigma related to seeing a psychiatrist and their association with help-seeking intentions for depression: anticipated discrimination by others when seeking help and desire for social distance from those seeking help. Methods  Representative population survey in Germany 2007 (n = 2,303), containing a depression vignette with a question on readiness to seek psychiatric care for this problem, a focus group developed scale anticipated discrimination when seeing a psychiatrist (ADSP), and a scale on desire for social distance from someone seeing a psychiatrist (SDSP). We further elicited previous contact to psychiatric treatment, depressive symptoms, and socio-demographic data. Results  Both scales had good internal consistency (Cronbach’s alpha ADSP 0.87, SDSP 0.81). Exploratory factor analysis of all items revealed a distinct factor representing the social distance scale and three factors “anticipated discrimination”, “anticipated job problems” and “anticipated shame” derived from the ADSP scale. In both the general population and in those with current depressive syndrome, personal desire for social distance significantly decreased willingness to seek psychiatric help, but anticipated discrimination by others did not. Other factors related to likely help-seeking were female gender and previous contact to psychiatric treatment or to psychotherapy. Conclusion  Contrary to expectations, anticipated discrimination from others was unrelated to help-seeking intentions, while personal discriminatory attitudes seem to hinder help-seeking. Our findings point to self-stigmatization as an important mechanism decreasing the willingness to seek psychiatric help.     

男性精神分裂症患者抗精神病药治疗前后血浆MicroRNA-181b表达水平

目的:研究血浆中microRNA-181b(miR-181b)在男性精神分裂症患者抗精神病药治疗过程的不同阶段表达水平的变化。方法:40例精神分裂症患者和40例正常对照,均为成年男性。以实时荧光定量PCR(RT-PCR)技术检测患者组(用药前、治疗2周和治疗4周)和对照组血浆miR-181b的表达水平。结果:和正常对照组相比,精神分裂症组在治疗前、治疗2周和治疗4周血浆miR-181b的表达水平均显著上调(P<0.001)。随着抗精神病药的治疗,病情逐渐好转,男性精神分裂症患者血浆miR-181b表达水平逐渐下降(治疗2周、治疗4周与治疗前比较,P均<0.001)。结论:血浆miR-181b可能参与精神分裂症的发病机制,其表达水平受抗精神病药影响。     

Clinical features of childhood-onset schizophrenia with obsessive-compulsive symptoms during the prodromal phase

Abstract Thirty-nine patients with schizophrenia, diagnosed according to DSM-III-R, who were under 15 years of age, were studied in two groups; 16 subjects with obsessive-compulsive symptoms during the prodromal phase, and 23 with no obsessive-compulsive disorders. The group with obsessive-compulsive symptoms during the prodromal phase was characterized by a higher ratio of males, higher incidences of perinatal and brain computed tomography (CT) abnormalities, fewer hereditary factors, longer duration of the prodromal phase, and a higher incidence of insidious onset and negative symptoms compared with the group without such prodromal symptoms. Schizophrenic patients with obsessive-compulsive symptoms during the prodromal phase were clinically distinct from those without, which suggests the possibility of subtype categorization.     

Evaluation of home care treatment for schizophrenic patients

Twenty-seven patients diagnosed as schizophrenics suffering their first episode of illness and who had not received any prior medical treatment for the present illness, have been treated in their own homes. The treatment was carried out by a visiting nurse, trained in follow-up assessment and counselling. The outcome of this group was compared with a similar group of 27 patients who underwent initial mental hospital admission and subsequent outpatient follow-up. Both groups were followed up for 6 months. The results reveal that the home treatment through a visiting nurse gives a better clinical outcome, better social functioning of the patient and greatly reduces the burden on the patients' families. This treatment modality is also more economical.     

Randomized controlled multicentre trial of cognitive behaviour therapy in the early initial prodromal state: effects on social adjustment post treatment

Aim: Improvement of social adjustment is a major aim of indicated prevention in young people at risk of developing psychosis. The present study explores the effect of specific cognitive behaviour therapy (CBT) as compared with supportive counselling (SC) on social adjustment in people in a potential early initial prodromal state of psychosis (EIPS) primarily defined by self‐experienced cognitive thought and perception deficits (basic symptoms). Methods: A total of 128 help‐seeking outpatients in the EIPS were randomized to receive either specific CBT or SC for 12 months. Social adjustment was assessed with the Social Adjustment Scale II (SAS II) at baseline, time of transition or post treatment Results: From 113 patients, who completed the SAS II at intake, 67 (59.3%) completed the SAS assessments at time of transition or post treatment. Both specific CBT and SC resulted in improvements in scales of SAS II, with no significant between‐group differences post treatment. Conclusions: Although treatment in specially designed early detection and intervention centres improves functioning of people in the EIPS, specific CBT was not superior to SC. One could hypothesize that additional vocational rehabilitation, case management and involvement of multidisciplinary teams are needed to further improve short‐term outcome of specific interventions on this dimension.     

Factors disturbing treatment for cancer in patients with schizophrenia

Patients with schizophrenia who develop cancer often have a variety of complicated medical and psychiatric problems. Problems associated with receiving a diagnosis of cancer and with understanding or cooperating with medical treatment may develop. Research in managing and treating schizophrenia patients with cancer is scarce. Presented herein is the experience of the authors' consultation-liaison psychiatry service in treating patients with schizophrenia who have cancer, and discussion of the medical management of such cases. Fourteen patients were treated between April 1999 and March 2003 and included patients receiving consultation psychiatric services at Shimane University Hospital as well as patients referred from other psychiatric hospitals. These patients were divided into two groups based on whether they were amenable to cancer treatment or not. The treated group consisted of patients who accepted cancer treatment, and the untreated group consisted of patients who refused or interrupted the cancer treatment. The clinical course, clinical psychiatric symptoms, problems in understanding cancer, cancer treatment course and convalescence were retrospectively assessed. Psychiatric symptoms and state were measured using the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS). The mean of the duration of schizophrenia in these two groups was not significantly different. The mean scores on measures of psychiatric symptoms in each group (treated and untreated) were as follows: BPRS, 45.3+/-15.4 and 64.9+/-9.2 (P<0.05); positive symptoms scores on PANSS, 14.4+/-8.8 and 20.6+/-6.0 (NS); negative symptoms scores on PANSS, 20.6+/-4.7 and 33.6+/-4.4 (P<0.01); and total scores on PANSS, 31.7+/-7.0 and 48.6+/-7.4 (P<0.01). Patients with severe negative symptoms had greater difficulty understanding and cooperating with the cancer treatment. Regarding cancer stage, when cancer was discovered, the disease had already advanced and was no longer amenable to first-line treatment. Regarding notification of the diagnosis, it was rarely possible to give sufficiently early notice to patients in the untreated group. The important role of consultation-liaison psychiatrist in treating cancer patients is suggested. Some steps are proposed for managing schizophrenia patients with cancer who are not able to give informed consent.     

Experience of trauma and conversion to psychosis in an ultra‐high‐risk (prodromal) group

Bechdolf A, Thompson A, Nelson B, Cotton S, Simmons MB, Amminger GP, Leicester S, Francey SM, McNab C, Krstev H, Sidis A, McGorry PD, Yung AR. Experience of trauma and conversion to psychosis in an ultra‐high‐risk (prodromal) group. Objective: We aimed to replicate a recent finding of high prevalence of trauma history in patients at ‘ultra‐high risk’ (UHR) of psychotic disorder and to investigate whether trauma predicts conversion to psychosis in this population. Method: A consecutive sample of UHR patients was assessed. History of trauma was accessed with the General Trauma Questionnaire. Cox regression models were used to explore relationship between conversion to psychosis and trauma. Results: Of 92 UHR patients nearly 70% had experienced a traumatic event and 21.7% developed psychosis during follow‐up (mean 615 days). Patients who had experienced a sexual trauma (36%) were significantly more likely to convert to first‐episode psychosis (OR 2.96) after controlling for meeting multiple UHR intake groups. Conclusion: UHR patients have a high prevalence of history of trauma. Previous sexual trauma may be a predictor of onset of psychotic disorder in this population.     

Prospective investigations of the prodromal state of schizophrenia: assessment instruments

OBJECTIVE: To review assessment instruments used for detection of prodromal or at-risk mental states, and discuss their role in current research. METHOD: A systematic electronic literature search was conducted and supplemented by a manual search. All relevant scales were selected for the purpose of the review. RESULTS: Six interviews and four screening instruments were found. Two main traditions are prevailing: the Attenuated Positive Symptoms approach and the Basic Symptoms approach. Reports of psychometric properties of the interviews are preliminary. CONCLUSION: The instruments detect individuals with an increased risk of psychosis in clinical populations, but predictive validity and measures of reliability is insufficiently evaluated. Studies including instruments from both traditions should be conducted, in order to obtain an empirical basis of hypothesized relations between instruments. Instruments elucidating phenomenological aspects of anomalies in self-experience may contribute with valuable data on the pre-onset phase of psychosis.     

Prospective investigations of the prodromal state of schizophrenia: review of studies

OBJECTIVE: The paper presents a comprehensive overview of prospective studies monitoring or intervening in the pre-onset phase of first episode psychosis. METHOD: A systematic literature search was conducted and supplemented by a manual search. All relevant studies were ordered and intensively reviewed according to specified criteria. Methodological and conceptual issues are discussed. RESULTS: Reports of 23 prospective studies were found, some describing subsamples of larger samples. Major methodological and conceptual divergences exist. CONCLUSION: Applied criteria detect individuals with a significantly increased risk of psychosis within the schizophrenia spectrum, but these criteria are only validated on clinical populations. The significance of differences in sample-characteristics is unclear. Most study samples are small. Results are preliminary and in need of further research before they constitute a realistic knowledge base. Methodological and conceptual issues should not be underestimated.