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.     

Testing the Ultra High Risk (prodromal) criteria for the prediction of psychosis in a clinical sample of young people

Criteria for identifying individuals at imminent risk for onset of a psychotic disorder, that is "prodromal" for psychosis, have recently been described. The current study set out to test the predictive validity of these criteria in a sample of help-seeking young people aged 15-24 years who were referred to, but not necessarily treated at, a psychiatric service. Ultra High Risk (UHR) status was determined at baseline and psychosis status was assessed at 6 month follow up. Baseline psychosocial functioning was also assessed as a possible predictor of psychosis. In the sample of 292 individuals, 119 (40.7%) met UHR criteria. Of these UHR+ people, 12 became psychotic within 6 months and 107 did not. Only one person not meeting UHR criteria developed psychosis in the follow up period. Sensitivity, specificity, positive predictive value and negative predictive value of UHR+ status for prediction of psychosis were, respectively, 0.923 (95% CI 0.621, 1), 0.616 (95% CI 0.556, 0.673), 0.101 (95% CI 0.056, 0.173) and 0.994 (95% CI 0.963, 1). UHR+ individuals were significantly more likely to become psychotic than UHR- individuals (Odds Ratio 19.3, 95% CI 2.5, 150.5). Low functioning at baseline was associated with psychosis onset in the whole sample and in the UHR group. The transition to psychosis rate was much lower than in previous samples. This may be a due to the sample being a more general one, not identified as possibly "prodromal". Other potential causes of this reduction in transition are also explored.     

Outreach and support in south London (OASIS): implementation of a clinical service for prodromal psychosis and the at risk mental state.

BACKGROUND: While recent research points to the potential benefits of clinical intervention before the first episode of psychosis, the logistical feasibility of this is unclear. AIMS: To assess the feasibility of providing a clinical service for people with prodromal symptoms in an inner city area where engagement with mental health services is generally poor. METHOD: Following a period of liaison with local agencies to promote the service, referrals were assessed and managed in a primary care setting. Activity of the service was audited over 30 months. RESULTS: People with prodromal symptoms were referred by a range of community agencies and seen at their local primary care physician practice. Over 30 months, 180 clients were referred; 58 (32.2%) met criteria for an at risk mental state, most of whom (67.2%) had attenuated psychotic symptoms. Almost 30% were excluded due to current or previous psychotic illness, of which two-thirds were in the first episode of psychosis. The socio-demographic composition of the 'at risk' group reflected that of the local population, with an over-representation of clients from an ethnic minority. Over 90% of suitable clients remained engaged with the service after 1 year. CONCLUSION: It is feasible to provide a clinical service for people with prodromal symptoms in a deprived inner city area with a large ethnic minority population.     

Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability

As the number of studies related to the early identification of and intervention in the schizophrenia prodrome continues to grow, it becomes increasingly critical to develop methods to diagnose this new clinical entity with validity. Furthermore, given the low incidence of patients and the need for multisite collaboration, diagnostic and symptom severity reliability is also crucial. This article provides further data on these psychometric parameters for the prodromal assessment instruments developed by the Prevention through Risk Identification, Management, and Education (PRIME) prodromal research team at Yale University: the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms. It also presents data suggesting that excellent interrater reliability can be established for diagnosis in a day-and-a-half-long training workshop.     

Specific adolescent prodromal symptoms associated with onset of psychosis in the Northern Finland Birth Cohort 1986

Background

Several psychological symptoms in adolescence associate with later development of psychosis. However, it is unclear which symptoms specifically predict psychotic disorders rather than psychiatric disorders in general. We conducted a prospective study comparing how specific adolescent psychotic-like symptoms, predicted psychotic and non-psychotic hospital-treated psychiatric disorders in the population-based Northern Finland Birth Cohort 1986 (NFBC1986).

Methods

At age 15–16 years, 6632 members of the NFBC1986 completed the PROD-screen questionnaire. New hospital-treated mental disorders of the NFBC1986 participants were detected between age 17 and 30 years from the Finnish Care Register for Health Care. Multiple covariates were used in the analysis.

Results

During the follow-up, 1.1% of the participants developed a psychotic and 3.2% a non-psychotic psychiatric disorder. Three symptoms were specifically associated with onset of psychosis compared to non-psychotic psychiatric disorders: ‘Difficulty in controlling one's speech, behaviour or facial expression while communicating’ (adjusted OR 4.00; 95% CI 1.66–9.92), ‘Difficulties in understanding written text or heard speech’ (OR 2.25; 1.12–4.51), and ‘Difficulty or uncertainty in making contact with other people’ (OR 2.20; 1.03–4.67). Of these, the first one remained statistically significant after Bonferroni correction for multiple comparisons.

Conclusion

To our knowledge, this is the first general-population-based prospective study exploring psychiatric symptoms predicting the onset of hospital-treated first-episode psychosis in comparison to non-psychotic disorders. We found three symptoms related with difficulties in social interaction which predicted onset of psychosis. This is a novel finding and should be replicated.     

Sex differences in symptoms of psychosis in a non-selected,general population sample

BACKGROUND: Little is known about sex differences in psychosis beyond the borders of clinical disorder. METHODS: A general population sample of 7,076 subjects was assessed using the Composite International Diagnostic Interview, in order to explore sex differences in the prevalence of any positive and negative symptoms of psychosis, and to examine to what degree any differences could be explained by differences in level of affective symptoms. RESULTS: Male sex was associated with higher prevalence of negative symptoms (OR = 1.6, 95% CI = 1.0, 2.5), independent of differences in affective symptoms and presence of DSM-III-R psychotic disorder. Women had higher rates of positive psychotic experiences (OR = 0.8, 95% CI = 0.7, 0.9), but this difference disappeared after adjustment for depressive symptoms (adjusted OR = 1.2, 95% CI = 0.9, 1.5). CONCLUSION: The sex differences in psychopathology that are seen in schizophrenia are expressed beyond the clinical phenotype, suggesting sex-dependent continuous and normal variation of several psychosis dimensions. The higher rates of positive psychotic experiences seen in women may be secondary to differences in the rate of affective symptoms.     

Violence in psychosis: estimating the predictive validity of readily accessible clinical information in a community sample

OBJECTIVE: This study sought to assess the validity of different combinations of readily available clinical information in predicting assaults by patients with psychosis, predominantly in the community. The combinations of information were: a) age and sex, b) age, sex and history of criminality/violence c) age, sex, history of violence and drug use and d) age, sex, history of violence, drug use and personality disorder. METHOD: 708 subjects were followed for 2 years. Assaults were measured using multiple sources of information. Prediction validity was measured using the area under the receiver operating curves (AUC) and the number needed to detain (NND). A simple prediction tool was developed. RESULTS: The AUC values using the four combinations of information were a) 0.65, b) 0.70, c) 0.71, and d) 0.73. Prediction based on combination b), c), and d) implied a NND of 3. A rule based on c), the most accessible information, is suggested as a simple screening tool. CONCLUSIONS: Readily available clinical information allowed the prediction of assault over 2 years, in a sample of general psychiatric patients with psychosis, with a level of predictive accuracy comparable to that described using more detailed risk assessment tools. The information used in the predictive model was: age, sex, having committed an assault in the last 2 years (self-report) and having used any drug in the last year (self-report).     

The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. II. Baseline characteristics of the "prodromal" sample

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology.The purpose of this report is to describe the study's "prodromally symptomatic" sample at baseline, i.e., at intake immediately prior to randomization and prior to receiving study medication. Sixty treatment-seeking patients meeting prodromal inclusion criteria were recruited across four sites: New Haven, CT (n=39), Toronto, Ontario (n=9), Calgary, Alberta (n=6), and Chapel Hill, NC (n=6). The sample was young (median age 16), largely male (65%), and came from families with high titers of serious mental illness (44%). Most patients (93%) met criteria for the Attenuated Positive Symptom (APS) prodromal syndrome and presented with significant but nonpsychotic suspiciousness, perceptual aberrations, unusual thought content, and conceptual disorganization. They presented with minimal to mild affective symptoms and substance use/abuse, but they were quite functionally compromised (mean Global Assessment of Functioning (GAF) score=42). The prodromal sample was compared with other clinical-trial samples of adolescent depression, adolescent mania, and first episode schizophrenia. Prodromal patients proved not to be depressed or manic. They were less severely ill than untreated first episode schizophrenia but more severely ill than treated first episode schizophrenia. While not psychotically disabled, these patients nevertheless present with a clinical syndrome. Subsequent reports will detail the effects of drug versus placebo on prodromal symptoms, neuropsychological profile, and the rate of conversion to psychosis.     

Clarifying the diversity of first-episode psychosis: Neuropsychological correlates of clinical symptoms

The aetiology of relatives' criticism (CC), hostility (H), and emotional overinvolvement (EOI) towards patients with schizophrenia is not clear. We analysed data from a study about expressed emotion (EE) in relatives of patients with schizophrenia according to DSM-III-R, to explore evidence of a relationship between EE pattern and a stress response syndrome in the relatives. CC, H, and EOI in 58 relatives of 40 patients with schizophrenia were assessed with the Camberwell Family Interview (CFI) shortly after admission and 4.5 months after discharge. Each relative's stress response was assessed with the General Health Questionnaire (GHQ-30). Relatives with a consistently high or a shifting EOI level reported prolonged higher stress scores than relatives with consistently low EOI level. We found no association between CC, H, and prolonged higher stress scores. Our study suggests that EOI could be linked to a stress response syndrome, whereas this does not seem to be the case for CC and H. If confirmed in future studies, this finding indicates that different treatment approaches should be offered to families of psychotic patients depending on the pattern of CC and EOI.     

自编住院精神病人《社会功能评定量表》:信度、效度的初步检验

目的 编制一套适合于研究精神科住院病人的《社会功能评定量表(SSFPI)》。方法 根据住院精神病人的实际生活状况及康复活动特点，拟定出含12个条目的量表，并将条目性质类同者归纳为三个因子。同时在住院病人中进行初测及信度、效度检验。结果 总分及各条目重测相关在0．72～0．89之间；分半信度相关为0．943；总分及各因子间内部一致性相关在0．46～0．89之间；与SDSS进行效度检验相关r值为-0．863，社会功能缺陷阳性区分率达98．3％。结论 SSFPI信度和效度符合要求，与中、基层医院的住院精神病人的生活特点吻合，具有一定的研究及应用价值。     

Assessing self-reported clinical high risk symptoms in community-derived adolescents: A psychometric evaluation of the Prodromal Questionnaire-Brief

BackgroundThe reliable early identification of individuals at risk for psychosis requires well-validated screening measures. To date, there is little information about the psychometric properties of the screening measures for psychosis risk in nonclinical adolescents. The main purpose of the present study was to validate the Prodromal Questionnaire-Brief (PQ-B) in a community sample of non-clinical Spanish adolescents. We also analyzed the prevalence, factorial validity, and reliability of the PQ-B scores as well as the relationship between self-reported clinical high risk symptoms and schizotypal traits.MethodFour hundred and forty-nine high-school students participated in a cross-sectional survey. The PQ-B and the Oviedo Schizotypy Assessment Questionnaire (ESQUIZO-Q) were used.ResultsAlthough 85.1% of the total sample reported at least one clinical high risk symptom, only 16% of the adolescents scored above the standardized cut-off. The PQ-B revealed an essentially unidimensional structure. The internal consistency of the PQ-B total score was 0.93. Pearson correlation coefficients indicated a high degree of overlap between self-reported clinical high risk symptoms and Positive and Disorganized schizotypal traits. A Canonical correlation between the PQ-B total score and ESQUIZO-Q dimensions showed that the associated variance between both sets of variables was 45.4% (adjusted R² = 0.45).ConclusionsThe PQ-B is a brief, easy, and reliable tool for screening self-reported clinical high risk symptoms in adolescents from the general population. These results also indicated that self-reported clinical high risk symptoms and schizotypal traits are closely associated at the subclinical level. The assessment of psychosis risk symptoms and their relationship with other distal risk factors, in a close-in strategy, may enhance the early identification of individuals at heightened risk for psychosis spectrum disorders.     

Reliability and validity of a Japanese version of the Cambridge depersonalization scale as a screening instrument for depersonalization disorder

Aims:  The Cambridge Depersonalization Scale (CDS) is an instrument that has obtained reliability and validity in some countries for use in detecting depersonalization disorder under clinical conditions, but not yet in Japan under non-psychiatric conditions. The purposes of this study were to develop a Japanese version of the CDS (J-CDS) and to examine its reliability and validity as an instrument for screening depersonalization disorder under non-clinical conditions.
Methods:  The CDS was translated from English into Japanese and then back-translated into English by a native English-speaking American. After making the J-CDS, we examined its reliability and validity. Questionnaires that were composed of J-CDS, the Dissociative Experience Scale (DES), the Zung self-rating scale and the Maudsley Obsessional–Compulsive Inventory were administrated to 59 participants (12 patients with depersonalization disorder, 11 individuals who had recovered from depersonalization and 36 healthy controls).
Results:  Cronbach's alpha and split-half reliability were 0.94 and 0.93, respectively. The J-CDS score in the depersonalization group was significantly higher than in the healthy control group. The J-CDS score was significantly correlated with scores of total DES, and DES-depersonalization. The best compromise between the true positive and false negative rate was at a cut-off point of 60, yielding a sensitivity of 1.00 and a specificity of 0.96.
Conclusions:  In this study, J-CDS showed good reliability and validity. The best cut-off point, when we use this for distinguishing individuals with depersonalization disorder from individuals without psychiatric disorders, is 60 points.     

Prevalence of self-reported symptoms attributed to hypoglycaemia within a general female population of the UK

OBJECTIVE: To investigate the prevalence of symptoms attributed to hypoglycaemia that are reported by a general female population of the UK. METHOD: A health and well-being questionnaire, including questions relating to symptoms of low blood 'sugar', medical history and anthropometry, was administered by post to 2000 randomly selected women (17-50 years) in Nottinghamshire. To avoid biasing responses, participants were not made aware of the specific focus of the study. RESULTS: One thousand one hundred and thirty-six women returned the questionnaire (56.8% response rate). After exclusions, 37.9% of respondents reported symptoms that they attributed to hypoglycaemia, with a median of four episodes reported per month. A significant variation in the reporting of symptoms was found across body mass index (BMI) categories, with the highest prevalence of symptomatic subjects being found at the lowest BMI range (P<.05). CONCLUSION: More than a third of women in the UK report experiencing symptoms that they attribute to hypoglycaemia. Body mass index appears to be related to the experiencing of symptoms.     

A semi-structured clinical interview for psychosis sub-groups (SCIPS): development and psychometric properties

Background

Clinical sub-groups of schizophrenia, namely drug related, traumatic, anxiety and stress sensitivity sub-types, have been proposed for use in research, training and practice. They were developed on the basis of clinical observation but have not yet been used in research or clinical practice to any great extent.

Aims

To develop a semi-structured clinical interview for psychosis sub-groups (SCIPS) and determine the best diagnostic criteria with the highest inter-rater reliability, test–retest reliability and concurrent validity for sub-grouping patients with schizophrenia according to a newly developed classification scheme.

Methods

The SCIPS was developed based upon discussion with the clinician researchers who had developed and were using the sub-groups. Kappa coefficients were calculated between two independent diagnostic assessments with the SCIPS (for inter-rater reliability and test–retest reliability, n?=?20) and between the SCIPS diagnosis and the sub-groupings as determined independently with highest achievable validity (for concurrent validity, n?=?21) for patients with schizophrenia. These inter-rater reliability and concurrent validity were compared among five different sets of diagnostic criteria to determine which was most reliable and valid.

Results

A set of diagnostic criteria with the highest inter-rater reliability and concurrent validity was determined. Kappa coefficients (95% confidence interval) for the inter-rater reliability and concurrent validity were 0.93 (0.66–1.20) and 0.73 (0.47–1.00), respectively, with these diagnostic criteria.

Conclusions

The SCIPS is a promising tool with which to sub-group patients with schizophrenia according to this recently developed classification scheme. The semi-structured interview achieves acceptable inter-rater and test–retest reliability and concurrent validity.     

The prodromal questionnaire (PQ): preliminary validation of a self-report screening measure for prodromal and psychotic syndromes

This study aims to establish preliminary validity of the Prodromal Questionnaire (PQ), a 92-item self-report screening measure for prodromal and psychotic symptoms. Adolescents and young adults (N = 113) referred to a prodromal psychosis research clinic completed the PQ and the Structured Interview for Prodromal Syndromes (SIPS [Miller, T.J., McGlashan, T.H., Woods, S.W., Stein, K., Driesen, N., Corcoran, C.M., Hoffman, R., Davidson, L., 1999. Symptom assessment in schizophrenic prodromal states. Psychiatric Quarterly 70(4), 273-287]), an interview with established validity for predicting future psychosis. When maximizing selection of true positive cases, scores on a subset of PQ items that assess positive symptoms predicted a concurrent prodromal or psychotic SIPS diagnosis with 90% sensitivity and 49% specificity. The PQ shows good preliminary validity in detecting individuals with an interview-diagnosed prodromal or psychotic syndrome, but it is less sensitive to the threshold between prodromal and full-blown psychosis.     

The prodromal questionnaire (PQ): preliminary validation of a self-report screening measure for prodromal and psychotic syndromes

This study aims to establish preliminary validity of the Prodromal Questionnaire (PQ), a 92-item self-report screening measure for prodromal and psychotic symptoms. Adolescents and young adults (N = 113) referred to a prodromal psychosis research clinic completed the PQ and the Structured Interview for Prodromal Syndromes (SIPS [Miller, T.J., McGlashan, T.H., Woods, S.W., Stein, K., Driesen, N., Corcoran, C.M., Hoffman, R., Davidson, L., 1999. Symptom assessment in schizophrenic prodromal states. Psychiatric Quarterly 70(4), 273-287]), an interview with established validity for predicting future psychosis. When maximizing selection of true positive cases, scores on a subset of PQ items that assess positive symptoms predicted a concurrent prodromal or psychotic SIPS diagnosis with 90% sensitivity and 49% specificity. The PQ shows good preliminary validity in detecting individuals with an interview-diagnosed prodromal or psychotic syndrome, but it is less sensitive to the threshold between prodromal and full-blown psychosis.