Diagnosing schizophrenia in the initial prodromal phase

BACKGROUND: In schizophrenia research, early detection in the initial prodrome before first psychotic episodes is a major topic. Therefore, the prognostic accuracy of initial prodromal symptoms was examined prospectively. METHODS: The study sample was composed of patients referred to outpatient departments of German psychiatric university departments, because of diagnostic problems, between 1987 and 1991. They were examined with the Bonn Scale for the Assessment of Basic Symptoms and the Ninth Version of the Present State Examination to detect an incipient schizophrenic disorder. Of 385 patients showing no schizophrenia-characteristic symptoms, between 1995 and 1998, 110 with and 50 without initial prodromal symptoms were followed up and reexamined with the same instruments for a transition to schizophrenia. RESULTS: During a mean follow-up period of 9.6 years, 79 (49.4%) of the 160 patients had transited to schizophrenia. The absence of prodromal symptoms excluded a subsequent schizophrenia with a probability of 96% (sensitivity: 0.98; false-negative predictions: 1.3%), whereas their presence predicted schizophrenia with a probability of 70% (specificity: 0.59; false-positive predictions: 20%). Certain disturbances, such as thought interference, disturbances of receptive language, or visual distortions, predicted schizophrenia, even with a probability up to 91% (specificity: 0.85-0.91; false-positive predictions: 1.9%-7.5%). CONCLUSIONS: The Bonn Scale for the Assessment of Basic Symptoms operationalization of prodromal symptoms performed well in the early detection of schizophrenia. It therefore might be useful for the prediction of the disorder, especially if it is further refined to select those items with particularly high prognostic accuracy.     

Symptomatology of the initial prodromal phase in schizophrenia

The initial prodromal symptoms in schizophrenia were studied in 100 DSM-diagnosed patients and 100 controls. The median number of symptoms in the patients and the controls was 8 (range 2-13) and 0 (range 0-5), respectively. Patients developed symptoms indicating social, occupational, and affective dysfunction, whereas the controls' symptoms included magical content and disturbance in mood. There were significant differences in the frequency of several symptoms appearing in the subtypes. Initial prodromal symptoms were classified into negative, positive-prepsychotic, and positive-disorganization categories. Patients with the disorganized subtype were more likely to have had negative symptoms in the prodromal state, and patients with the paranoid subtype were more likely to have had positive symptoms in the prodromal state. Observation of the course of symptoms from the prodromal to the psychotic state revealed that 58 percent of the symptoms showed increased intensity, 21 percent remained unchanged, 5 percent decreased, 3 percent evolved into other affective difficulties, 9 percent progressed into delusions, 1 percent progressed into hallucinations, and 3 percent disappeared. The Global Assessment of Functioning Scale showed that functioning is differentially affected among the subtypes even in the prodromal phase. These findings provide a better understanding of the initial prodromal state of schizophrenia, the signs and symptoms that best define it, and their prognostic significance.     

Antipsychotic drug treatment in the prodromal phase of schizophrenia

OBJECTIVE: The safety and tolerability of short-term treatment with a low dose of risperidone was evaluated in adolescents with prodromal symptoms and a family history of schizophrenia. METHOD: Four prodromal high-risk adolescents and six first-episode patients with schizophrenia were treated with average doses of 1.0 and 1.8 mg/day of risperidone, respectively, in an 8- to 12-week open-label trial. RESULTS: No significant treatment-related adverse events were noted. Severity of thought and behavior disturbance ratings declined by about 30%; performance on a test of verbal learning improved by about 100% during treatment in both prodromal and first-episode patients, changes that achieved statistical significance despite the small group sizes. CONCLUSIONS: These findings are preliminary and should not be used to guide health care decisions at this time. Randomized controlled trials are needed to determine whether antipsychotic drug treatment of prodromal patients can delay or prevent onset or attenuate the clinical course of schizophrenia.     

Plasma homovanillic acid in the prodromal phase of schizophrenia.

BACKGROUND: Plasma levels of homovanillic acid (pHVA) have been used as a peripheral measure of central dopaminergic activity. Despite a large body of studies investigating pHVA in schizophrenia, little is known about pHVA in patients in the prodromal phase of the illness. METHODS: Plasma HVA levels of 12 male outpatients meeting DSM-III-R criteria for the prodromal phase of schizophrenia at the time of blood sampling (who later developed psychotic symptoms) were compared with those of 12 normal male healthy volunteers. Task amounts in the Kraepelin arithmetic test at the time of blood sampling were compared between the prodromal patients and normal controls and were correlated with pHVA levels. RESULTS: The prodromal patients had significantly higher pHVA levels compared with normal control subjects. The mean amount of the arithmetic task for the prodromal patients was significantly less than that for controls. In the patient group, a significant negative correlation was observed between pHVA levels and the task amounts. CONCLUSIONS: Data from the present study indicate the presence of dopaminergic dysfunction in the prodromal stage of schizophrenia that is associated with neuropsychological impairment. Increased pHVA levels in the prodromal patients may have implications for early detection of schizophrenia.     

Early detection and intervention in the initial prodromal phase of schizophrenia

Attenuated and transient psychotic symptoms as well as a combination of different risk indicators and a recent significant deterioration in global functioning are currently used as a preliminary definition of the initial prodromal or at-risk mental state by the vast majority of investigators in research on early psychosis detection and intervention. Recently published results demonstrated a mean progression to frank psychosis within one year in 36.7 % of cases showing emerging symptoms, indicating that these criteria already seem to provide a satisfying assessment for risk of an imminent psychosis. However, as functional decline often sets in before this time, detection in earlier prodromal stages seems necessary. In a prospective study, certain basic cognitive and perceptive symptoms showed good to excellent predictive accuracy for schizophrenic psychosis, thus potentially offering a reasonable approach for earlier detection. Early intervention is aimed at improving prodromal symptoms, avoiding functional deterioration, and suppressing or delaying transition to psychosis. Initial study results targeting an earlier or later prodromal phase are promising, but longer follow-ups and larger samples are needed.     

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.     

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.     

The prevalence of DSM-III-R "prodromal" symptoms of schizophrenia in non-psychotic psychiatric outpatients

A cross-sectional point prevalence study of the DSM-III-R prodromal symptoms in non-psychotic (n = 501) consecutive outpatients from a catchment area with 260000 inhabitants is presented. The relationship between the three most psychosis-specific prodromal symptoms and the development of psychosis during the following 6 months was also explored. The prevalence of any prodromal symptom was 25%, the most prevalent being impairment of role functioning (14%), isolation and withdrawal (11%) and lack of initiative (8%). The most prevalent symptom in affective disorders was lack of initiative (14%); in personality disorders, it was impairment of role functioning (21%). The prevalences of the most psychosis-specific symptoms "peculiar behaviour", "magical thinking" and "unusual perceptual experiences" was 1-2%. At re-evaluation 6 months later, three of 20 patients (15%) with one or more such symptoms had become psychotic, two with schizoaffective disorder, one with affective psychosis. It was concluded that DSM-III prodromal symptoms are common among non-psychotic outpatients, but most such symptoms are non-specific for psychosis. Persistent peculiar behaviour, magical thinking and unusual perceptual experiences have a very low prevalence but may indicate an increased risk for psychosis. Such patients should be followed with that risk in mind.     

The prevalence of DSM-III-R "prodromal" symptoms of schizophrenia in non-psychotic psychiatric outpatients

A cross-sectional point prevalence study of the DSM-III-R prodromal symptoms in non-psychotic ( n = 501) consecutive outpatients from a catchment area with 260,000 inhabitants is presented. The relationship between the three most psychosis-specific prodromal symptoms and the development of psychosis during the following 6 months was also explored. The prevalence of any prodromal symptom was 25%, the most prevalent being impairment of role functioning (14%), isolation and withdrawal (11%) and lack of initiative (8%). The most prevalent symptom in affective disorders was lack of initiative (14%); in personality disorders, it was impairment of role functioning (21%). The prevalences of the most psychosis-specific symptoms "peculiar behaviour", "magical thinking" and "unusual perceptual experiences" was 1-2%. At re-evaluation 6 months later, three of 20 patients (15%) with one or more such symptoms had become psychotic, two with schizoaffective disorder, one with affective psychosis. It was concluded that DSM-III prodromal symptoms are common among non-psychotic outpatients, but most such symptoms are non-specific for psychosis. Persistent peculiar behaviour, magical thinking and unusual perceptual experiences have a very low prevalence but may indicate an increased risk for psychosis. Such patients should be followed with that risk in mind.     

The assessment of "prodromal schizophrenia": unresolved issues and future directions

Because of the novelty of research with clinical high risk ("prodromal") patients, many unresolved issues exist concerning how the prodromal state is defined and measured. Data are presented from the Recognition and Prevention (RAP) program at the Zucker Hillside Hospital to address several outstanding questions. Baseline attenuated positive symptoms were rated in 42 putatively prodromal patients in the RAP program using the Scale of Prodromal Symptoms (SOPS). Followup data of 6 months or more were available on 34 of these subjects; 9 of these (26.5%) developed psychotic disorders. Patients who developed psychosis had significantly higher SOPS positive symptom scores at baseline than those who did not. Various thresholds, using both total SOPS positive symptom scores and highest single item score, significantly predicted transition to psychosis, which calls into question appropriate cutoffs for the distinction between health, prodromal status, and psychosis. The SOPS positive symptom "conceptual disorganization" was found to be significantly related to disorganized behavior but not to other positive symptoms or to psychotic outcome, suggesting the importance of examining dimensions of psychopathology. The dimensional quantification of prodromal symptom severity may be an important direction for future studies of the assessment of at-risk states.     

精神分裂症患者前驱症状的调查与分析

目的 调查与分析精神分裂症患者的前驱症状。方法 在有明显社会心理诱发因素的首发精神分裂症住院患者中，随机抽取100例作为精神分裂症组。在向危机干预中心求助的正常人群中，随机抽取100例作为危机干预组。并对两组的社会心理诱因和前驱症状进行比较分析。结果 正常人(危机干预组)在精神压力下产生的症状与有明显社会心理诱发的精神分裂症(精神分裂症组)的前驱症状元显著差异。结论 在危机干预过程中，警惕一些人群的症状表现可能就是精神分裂症的前驱症状。     

Evaluating and treating the prodromal stage of schizophrenia

Identification of a person in the prodromal stage of schizophrenia, before the onset of the first episode of psychosis, provides an opportunity for early, potentially preventative, interventions. Recent attempts to develop at risk or prodromal syndrome diagnostic criteria have proved to be successful at identifying individuals at high risk for psychosis. Preliminary investigations find that pharmacologic and psychotherapeutic interventions may reduce the risk of psychosis in at risk individuals, but until more is known, current treatment guidelines recommend close monitoring, therapeutic interventions that address identified problems, including supportive or cognitive therapies to reduce the functional consequences of the presenting symptoms, family interventions to reduce family distress and improve coping, and intervention with schools to decrease likelihood of school failure. Pharmacologic intervention targeting the prodromal symptoms is not recommended, given the uncertain risk to benefit ratio.     

Preliminary findings for two new measures of social and role functioning in the prodromal phase of schizophrenia

INTRODUCTION: Research on prediction and prevention of schizophrenia has increasingly focused on prodromal (prepsychosis) social and role dysfunction as developmentally early, stable, and treatment-resistant illness components. In this report, 2 new measures, Global Functioning: Social and Global Functioning: Role, are presented, along with preliminary findings about psychometric properties and course of social and role (academic/work) functioning in the prodromal phase of psychosis. METHODS: Subjects included 69 participants from the Recognition and Prevention program and 52 from the Center for the Assessment and Prevention of Prodromal States. Ages ranged from 12 to 29 years, and all met criteria for Attenuated Positive Symptom syndrome. Retrospective (past year) and baseline data are reported for all 121 prodromal subjects and for 44 normal controls (NCs). Prospective follow-up data are reported for a subsample of patients reevaluated at both 6 and 12 months (N = 44). RESULTS: For both scales, interrater reliability was high, and preliminary data supported construct validity. Relative to NCs, prodromal individuals displayed impaired social and role functioning at baseline. Analyses of change over time indicated that role functioning declined over the year before ascertainment and improved over 12-month follow-up, presumably with treatment. Social impairment, by contrast, was constant across time and predicted later psychosis (P = .002). DISCUSSION: Using 2 new global measures, social functioning was found to be a stable trait, unchanged by treatment, with considerable potential to be a marker of schizophrenia. Role functioning, by contrast, may be a more direct barometer of clinical change and may be responsive to treatment and environmental change.     

Evaluating and treating the prodromal stage of schizophrenia

Identification of a person in the prodromal stage of schizophrenia, before the onset of the first episode of psychosis, provides an opportunity for early, potentially preventative, interventions. Recent attempts to develop “at risk#x201D; or #x201C;prodromal syndrome#x201D; diagnostic criteria have proved to be successful at identifying individuals at high risk for psychosis. Preliminary investigations find that pharmacologic and psychotherapeutic interventions may reduce the risk of psychosis in #x201C;at risk#x201D; individuals, but until more is known, current treatment guidelines recommend close monitoring, therapeutic interventions that address identified problems, including supportive or cognitive therapies to reduce the functional consequences of the presenting symptoms, family interventions to reduce family distress and improve coping, and intervention with schools to decrease likelihood of school failure. Pharmacologic intervention targeting the prodromal symptoms is not recommended, given the uncertain riskbenefit ratio.     

首发精神分裂症前驱期症状学分析

目的：探讨首发精神分裂症患者前驱期的症状学特征。方法：对71例符合中国精神疾病分类方案与诊断标准第2版修订本精神分裂症诊断标准的首次发作患者，按照自编精神分裂症前驱症状调查表的32条症状进行检查，并与62名正常成年人进行对比分析。结果：首发精神分裂症患者所有的前驱症状正常人在某些情况下也可能出现，但发生率以患者明显较高。其中灵敏度≥0．25、阳性预测值≥0．70的症状是：个人卫生形象变差；行为怪异；情感不适切；赘述或话不切题；孤僻等。结论：这些前驱期表现有助于理解精神分裂症早期的发病过程，并为早期识别和干预提供参考。     

Revisiting the relapse predictive validity of prodromal symptoms in schizophrenia

After recovering from a first episode in schizophrenia, relapse prevention is a major objective and long-term treatment is indicated. Due to empirical findings regarding relapse preventive efficacy of antipsychotics, guidelines recommend maintenance neuroleptic treatment, which however is not feasible for all patients. Both under maintenance treatment and drug withdrawal, doctors and patients try to anticipate a reexacerbation by means of early signs of relapse in order to intervene as early as possible. Prodromal symptoms are supposed to be such early indicators, although empirical evidence is not uniform. In order to prepare a new research program, data from an earlier study were reanalyzed to examine the relapse predictive validity of prodromal symptoms. 339 outpatients observed prospectively for 2 years under different long-term treatment strategies were included in this analysis resulting in a total amount of 5861 observations/visits. Several prognostic parameters were computed regarding relationship between clinical state (relapse yes/no) and the occurrence of prodromal symptoms the immediate visit before. As to the results, none of the 22 single prodromal symptoms exceeded a sensitivity of 40%, with specificities ranging from 69% to 95%. An overall prodrome score led to a sensitivity of 72%, however specificity declined to 38%. The performed logistic regression analyses including other potential predictors (psychopathology, clinical change etc.) yielded other relevant 'early signs'. It is concluded that the relapse predictive validity of prodromal symptoms has to be enhanced e.g. by supplement of other clinical parameters with predictive potential or by closer monitoring.     

Translational and clinical research in Singapore: ethical issues in a longitudinal study of the prodromal phase of schizophrenia

Aims: This paper aims to provide an overview of the ethical issues that have been raised by The Longitudinal Youth at Risk Study, which is being led by the Institute of Mental Health in Singapore as part of a multi‐centre and multinational study in translational and clinical research in psychosis. This project is designed to identify the biomarkers of the trajectory to psychosis. As well as providing insights into the psychopathology and psychophysiology of the disease, the study will prospectively identify those in the Singaporean population with an ultra‐high risk of developing psychosis. The project will collect both observational and clinically relevant data from an at‐risk group: adolescents and young adults. Methods: A normative analysis was used to consider the ethical issues that arise as a result of this study, its methods, sample population and clinical management policy. Results: The project was found to raise particular and sensitive ethical and legal issues relating to the conduct of research with vulnerable populations who may be entering the prodromal phase of psychosis. Issues raised included notions of consent, privacy, confidentiality, stigmatization, duty of care and therapeutic misconception. Conclusion: Whereas some of the issues raised by this study present with manageable solutions, others may be justifiable within the cultural context of Singapore and warrant further discussion.     

Motor signs in the prodromal phase of Parkinson's disease

Relatively subtle deterioration of the motor system likely occurs well before the patient meets established motor criteria for a clinical diagnosis of Parkinson's disease; ie, the occurrence of at least 2 of the cardinal motor deficits: bradykinesia, rigidity, tremor, and/or postural instability. Powerful compensatory mechanisms may mask these clinical symptoms and make them difficult to identify and evaluate in the earliest stages of the illness. This review summarizes our current knowledge of motor signs that are thought to occur in the prodromal phase of Parkinson's disease and suggests how motor assessment batteries could be designed to detect these subclinical motor deficits with a high degree of accuracy and sensitivity.