The Strauss and Carpenter Prognostic Scale in subjects clinically at high risk of psychosis.

OBJECTIVE: To investigate the predictive value of the Strauss and Carpenter Prognostic Scale (SCPS) for transition to a first psychotic episode in subjects clinically at high risk (CHR) of psychosis. METHOD: Two hundred and forty-four CHR subjects participating in the European Prediction of Psychosis Study were assessed with the SCPS, an instrument that has been shown to predict outcome in patients with schizophrenia reliably. RESULTS: At 18-month follow-up, 37 participants had made the transition to psychosis. The SCPS total score was predictive of a first psychotic episode (P < 0.0001). SCPS items that remained as independent predictors in the Cox proportional hazard model were as follows: most usual quality of useful work in the past year (P = 0.006), quality of social relations (P = 0.006), presence of thought disorder, delusions or hallucinations in the past year (P = 0.001) and reported severity of subjective distress in past month (P = 0.003). CONCLUSION: The SCPS could make a valuable contribution to a more accurate prediction of psychosis in CHR subjects as a second-step tool. SCPS items assessing quality of useful work and social relations, positive symptoms and subjective distress have predictive value for transition. Further research should focus on investigating whether targeted early interventions directed at the predictive domains may improve outcomes.

Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis.

OBJECTIVE: Numerous studies have found a robust association between cannabis use and the onset of psychosis. Nevertheless, the relationship between cannabis use and the onset of early (or, in retrospect, prodromal) symptoms of psychosis remains unclear. The study focused on investigating the relationship between cannabis use and early and high-risk symptoms in subjects at clinical high risk for psychosis. METHOD: Prospective multicenter, naturalistic field study with an 18-month follow-up period in 245 help-seeking individuals clinically at high risk. The Composite International Diagnostic Interview was used to assess their cannabis use. Age at onset of high risk or certain early symptoms was assessed retrospectively with the Interview for the Retrospective Assessment of the Onset of Schizophrenia. RESULTS: Younger age at onset of cannabis use or a cannabis use disorder was significantly related to younger age at onset of six symptoms (0.33 < r(s) < 0.83, 0.004 < P < 0.001). Onset of cannabis use preceded symptoms in most participants. CONCLUSION: Our results provide support that cannabis use plays an important role in the development of psychosis in vulnerable individuals. Cannabis use in early adolescence should be discouraged.

Three-year course of clinical symptomatology in young people at ultra high risk for transition to psychosis.

OBJECTIVE: The investigation into the course of ultra high risk (UHR) symptomatology of those patients who eventually do not meet the psychosis-threshold criteria within the 3-year timeframe of the study. METHOD: The course of UHR symptoms, GAF score and employment status was investigated in 57 patients who did not make a transition to psychosis and who were examined within the Dutch Prediction of Psychosis Study in Amsterdam, the Netherlands. RESULTS: At the 3-year follow-up, 75% of the patients who did not make a transition to psychosis had remitted from UHR status. With a Generalized Estimation Equation Model it was shown that this group recovered from positive (F = 52.7, P < 0.0001), negative (F = 24.3, P < 0.0001), disorganization (F = 14.4, P < 0.0001) and general symptoms (F = 25.0, P < 0.0001) within the timeframe of the study. In addition, the level of global functioning and likelihood of having a job and/or education significantly improved. The largest improvements occurred within the first year. UHR symptoms did not re-occur after improvement. CONCLUSION: With the current UHR criteria, a large percentage of the included subjects appear to have transitory complaints and dysfunctioning. A refinement of the UHR criteria may diminish the chance of including 'false positives' in future UHR studies.

Neurocognitive functioning before and after the first psychotic episode: does psychosis result in cognitive deterioration?

BACKGROUND: Cognitive impairment is considered to be a core characteristic of schizophrenia. The relationship between psychosis and cognitive deterioration, however, remains unclear. This longitudinal study investigated the neuropsychological functioning of patients before and after their first psychotic episode. Cognitive functioning of participants who later developed a psychosis was compared to that of people at ultra-high risk (UHR) for psychosis who did not develop psychosis at follow-up and healthy controls.MethodParticipants were 41 persons at UHR for psychosis (the UHR group), of whom 17 developed psychosis between the first and second assessment. Seventeen healthy controls were included in the study. Cognitive performance was assessed at intake (T0) and again after 18 months (T1). The areas of cognitive functioning assessed include verbal memory and learning, visuospatial working memory, executive function, sustained attention and motor speed. RESULTS: The transition group did not perform significantly worse at the second assessment than at the first on any of the outcome measures. The UHR group performed better on a verbal learning and memory test at T1 compared to T0. At T0, the control group scored significantly better than the UHR group and the transition group on the verbal learning and memory test and the verbal fluency test. CONCLUSIONS: The results indicate that no cognitive deterioration occurs during the first psychotic episode. Problems in verbal memory may be present before the first episode of psychosis.

White-matter markers for psychosis in a prospective ultra-high-risk cohort.

BACKGROUND: Subjects at 'ultra high risk' (UHR) for developing psychosis have differences in white matter (WM) compared with healthy controls. WM integrity has not yet been investigated in UHR subjects in relation to the development of subsequent psychosis. Hence, we investigated a prospective cohort of UHR subjects comparing whole brain fractional anisotropy (FA) of those later developing psychosis (UHR-P) to those who did not (UHR-NP). METHOD: We recruited 37 subjects fulfilling UHR criteria and 10 healthy controls. Baseline 3 Tesla magnetic resonance imaging (MRI) scans and Positive and Negative Syndrome Scale (PANSS) ratings were obtained. UHR subjects were assessed at 9, 18 and 24 months for development of frank psychosis. We compared baseline FA of UHR-P to controls and UHR-NP subjects. Furthermore, we related clinical data to MRI outcome in the patient population. RESULTS: Of the 37 UHR subjects, 10 had transition to psychosis. UHR-P subjects showed significantly lower FA values than control subjects in medial frontal lobes bilaterally. UHR-P subjects had lower FA values than UHR-NP subjects, lateral to the right putamen and in the left superior temporal lobe. UHR-P subjects showed higher FA values, compared with UHR-NP, in the left medial temporal lobe. In UHR-P, positive PANSS negatively correlated to FA in the left middle temporal lobe. In the total UHR group positive PANSS negatively correlated to FA in the right superior temporal lobe. CONCLUSIONS: UHR subjects who later develop psychosis have differences in WM integrity, compared with UHR subjects who do not develop psychosis and to healthy controls, in brain areas associated with schizophrenia.

Pathways to psychosis: a comparison of the pervasive developmental disorder subtype Multiple Complex Developmental Disorder and the "At Risk Mental State".

BACKGROUND: The comparison of high-risk populations with different developmental pathways to psychosis may lend more insight into the heterogeneity of the manifestation of the psychotic syndrome, and possible differing etiological pathways. AIM: To compare high-risk traits and symptoms in two populations at risk for psychosis, i.e. (1) help-seeking adolescents presenting with prodromal symptoms meeting the criteria for At Risk Mental State (ARMS), and (2) adolescents with Multiple Complex Developmental Disorder (MCDD), a PDD-NOS subtype characterized by severe, early childhood-onset deficits in affect regulation, anxieties, disturbed social relationships, and thought disorder. METHOD: 80 ARMS- and 32 MCDD-adolescents (12-18 years) were compared on prodromal symptoms (Structured Interview of Prodromal Symptoms, and Bonn Scale for the Assessment of Basic Symptoms-Prediction list), and autism traits (Social Communication Questionnaire). In addition, both high-risk groups were compared with 82 healthy controls on schizotypal traits (Schizotypal Personality Questionnaire-Revised). RESULTS: Although the high-risk groups clearly differed in early developmental and treatment histories as well as autism traits, they did not differ with regard to schizotypal traits and basic symptoms, as well as disorganized and general prodromal symptoms. There were, however, group differences in positive and negative prodromal symptoms. Interestingly, 78% of the adolescents with MCDD met criteria for ARMS. CONCLUSION: These findings suggest that children diagnosed with MCDD are at high risk for developing psychosis later in life, and support the notion that there are different developmental pathways to psychosis. Follow-up research is needed to compare the rates of transition to psychosis in both high-risk groups.

A meta-analysis of P50 studies in patients with schizophrenia and relatives: differences in methodology between research groups.

OBJECTIVE: To determine whether patients with schizophrenia as well as their relatives show deficits in sensory gating reflected by an abnormal P50 ratio and to quantify the differences from controls. METHODS: A systematic search on articles published between 1982 and 2006 was conducted. 28 patient studies that were suitable for analysis including 891 patients and 686 controls were retrieved. Six studies on P50 of relatives of schizophrenic patients were identified, including 317 relatives and 294 controls. RESULTS: In the patient studies we found an P50 effect size of 1.28 (SD=0.72). We confirmed high variability in outcomes across studies. Almost half of the studies included where published by one laboratory of the University of Colorado and these results differed significantly from the results found in studies performed in other laboratories. We found correlations between effect size outcome and sound intensity, filter settings and subjects' position which could be explained by differences between the Colorado laboratory and the other groups. In the relative studies we found a mean P50 effect size of 0.85 (+/-0.42). CONCLUSIONS: The differences in methodology and lack of reported demographics and methodology including raters blinding in some studies makes it hard to compare results across studies and to evaluate the validity and reliability of P50 as a candidate endophenotype for schizophrenia. There are large differences in outcomes from Colorado studies and non-Colorado studies. In contrast to the Colorado studies in the non-Colorado studies P50 suppression would not qualify as an endophenotype for schizophrenia. These differences might be explained by the differences in methodology e.g. lower levels of sound intensity, differences in filter settings and subjects' position. Finally we make some recommendations for future research based on the outcomes of this meta-analysis.

Failure to find P50 suppression deficits in young first-episode patients with schizophrenia and clinically unaffected siblings.

OBJECTIVE: To evaluate whether the P50 gating deficit is present in young first-episode patients with schizophrenia and their healthy young siblings. METHODS: An auditory paired-click paradigm was used to assess P50 gating in 53 patients, 27 unaffected siblings, and 28 healthy controls. P50 parameters were compared between patients, sibs, and unrelated controls by a mixed-effects regression model. RESULTS: P50 gating was not significantly impaired in patients with schizophrenia and healthy siblings as compared with controls. CONCLUSIONS: P50 gating was not found to be significantly impaired in young first-episode schizophrenia patients and in healthy young siblings. These results are in contrast with the existing literature. We suggest that P50 gating impairment may be developmentally or age dependent.

Cannabis abuse and the course of recent-onset schizophrenic disorders.

OBJECTIVE: We sought to examine the relation between cannabis abuse and the symptomatic course of recent-onset schizophrenia and related disorders. DESIGN: A prospective cohort study over a year using monthly Brief Psychiatric Rating Scale assessments. PARTICIPANTS: Cannabis-abusing patients (n = 24) were compared with nonabusers (n = 69). Eleven patients were mild and 13 were heavy cannabis-abusing patients. RESULTS: Significantly more and earlier psychotic relapses occurred in the cannabis-abusing group (P = .03). This association became stronger when mild and heavy cannabis abuse were distinguished (P = .002). No confounding effect of other variables, eg, other street drugs, was found. In all but one patient, cannabis abuse preceded the onset of the first psychotic symptoms for at least 1 year. CONCLUSIONS: Cannabis abuse and particularly heavy abuse can be considered a stressor eliciting relapse in patients with schizophrenia and related disorders and possibly a premorbid precipitant.

Significantly reduced docosahexaenoic and docosapentaenoic acid concentrations in erythrocyte membranes from schizophrenic patients compared with a carefully matched control group.

BACKGROUND: Fatty acid research in schizophrenia has demonstrated an altered cell membrane phospholipid metabolism. Erythrocyte membrane phospholipid composition closest reflects that of neuronal membranes. METHODS: (Poly)(un)saturated fatty acid concentrations were measured in the erythrocyte membranes of 19, consecutively admitted, medicated young schizophrenic patients and then compared with matched control subjects. Psychiatric symptomatology was rated with the Positive and Negative Symptom Scale and Montgomery-Asberg Depression Rating Scale. Because diet, hormones, and cannabis influence fatty acid metabolism, we included these factors in our study. RESULTS: The most distinctive findings concerned the omega-3 series: C22:5 omega-3, C22:6 omega-3 (docosahexaenoic acid), and the sum of omega-3 fatty acids were significantly decreased. Interestingly, C20:4 omega-6 (arachidonic acid) was not lowered. In the omega-9 series, higher levels of C22:1 omega-9 and lower levels its elongation product, C24:1 omega-9 (nervonic acid), were found. Interestingly, the other arm of the desaturation-elongation sequence of C18:1 omega-9, C20:3 omega-9, was lower in patients. The total omega-9 fatty acid levels were also lower in patients. CONCLUSIONS: Significant differences in erythrocyte fatty acid composition were found. The differences were not due to diet or hormonal status and could not be explained by the medication or cannabis use. No consistent pattern emerged from the different fatty acid abnormalities and the clinical symptom scores.

Subjective experience and striatal dopamine D(2) receptor occupancy in patients with schizophrenia stabilized by olanzapine or risperidone.

OBJECTIVE: The authors' goal was to study the relationship between subjective experience during treatment with olanzapine or risperidone and dopamine D(2) receptor occupancy in stabilized patients with schizophrenia. METHOD: Subjective experience, psychopathology, and extrapyramidal symptoms were assessed, and D(2) receptor occupancy was determined with [(123)I]iodobenzamide single photon emission computed tomography, in 22 patients whose schizophrenia was stabilized by olanzapine or risperidone. RESULTS: Subjective experience, depression, and negative symptoms were related to dopamine D(2) receptor occupancy, but extrapyramidal symptoms were not. CONCLUSIONS: These results provide preliminary evidence that negative subjective experience is related to high D(2) receptor occupancy. Longitudinal study is required because this relationship may have implications for dosing strategies.

Component structure of the expanded Brief Psychiatric Rating Scale (BPRS-E).

The component structure of the expanded Brief Psychiatric Rating Scale (BPRS-E) was analyzed in a sample (n = 150) of consecutively admitted general psychiatric inpatients and compared with a group (n = 97) of adolescent patients with schizophrenia spectrum diagnoses. A stable five-component solution, of which four were interpretable, was found across groups. The component scales of the 24-item version of the BPRS had good internal consistency, allowed better coverage of schizophrenia and affective symptoms than the 18-item version but did not distinguish the schizophrenia diagnostic subgroups. The implications of the findings are discussed.

A cross-cultural study of the reliability and factorial dimensions of the Brief Psychiatric Rating Scale (BPRS).

The factor-structure and the reliability of the Brief Psychiatric Rating Scale (BPRS) was investigated in a group of short stay psychiatric patients in a Dutch university clinic. It was found that the BPRS has a good inter-rater reliability. With the exception of a new Disorientation subscale all original five subscales could be replicated when compared with an American study.

Psychometric properties of the Subjective Well-Being Under Neuroleptics scale and the Subjective Deficit Syndrome Scale.

RATIONALE: Subjective experience of antipsychotic drugs is relevant for medication compliance and quality of life. There is, however, sparse knowledge about the assessment of subjective experience. OBJECTIVES: To examine the internal consistency, test-retest reliability, sensitivity to medication change and concurrent validity of two test instruments: the Subjective Well-Being Under Neuroleptics (SWN) and the Subjective Deficit Syndrome Scale (SDSS). METHODS: Both instruments were used at admission and after 6 weeks of medication stabilization in 105 consecutively admitted patients diagnosed with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edn) diagnoses of recent-onset schizophrenia, schizophreniform disorder or schizoaffective disorder. RESULTS: Almost all patients were capable of reproducing their subjective experience in a consistent way both before and after medication stabilization. The internal consistency of both instruments was high. The test-retest reliability was high if medication was not changed, especially for the SWN. The SWN was sensitive for changes in medication and dosage. The short form of the SWN (SWN-20 items) had comparable psychometric qualities to the original instrument (SWN-38 items). The concurrent validity of the SWN and the SDSS was good, indicating that both tests measure the same concept. CONCLUSIONS: The assessment of subjective experience with the SWN (both versions) may be used in evaluating differential effects of anti-psychotics and dose on subjective well-being.

Component structure of the positive and negative syndrome scale (PANSS) in patients with recent-onset schizophrenia and spectrum disorders.

RATIONALE: Earlier studies have examined the symptom dimensions of the PANSS (Positive And Negative Syndrome Scale) in patients with chronic schizophrenia. Results have suggested that three to eight component solutions best explain underlying symptom dimensions. OBJECTIVES: To examine the component structure of the PANSS and the MADRS (Montgomery Asberg Depression Rating Scale) in young patients with recent-onset schizophrenia and related disorders and the correlations between the components of both instruments. METHODS: Symptomatology was measured in 138 patients with recent-onset schizophrenia, by administering the PANSS and the MADRS. RESULTS: Principal component analysis of the PANSS revealed five components: a positive, negative, depression, agitation-excitement and disorganisation component. The MADRS only showed one component. A high correlation was found between the depression component of the PANSS and the overall score of the MADRS (p=0.87, P<0.001). A moderate correlation was found between the PANSS negative component and the overall score of the MADRS (p=0.51, P<0.001). CONCLUSIONS: The data suggest a five component structure of the PANSS. The depression component of the PANSS seems to be a valid way of assessing depression in patients with recent-onset schizophrenia.

Early intervention and a five year follow up in young adults with a short duration of untreated psychosis: ethical implications.

In a Dutch treatment intervention study of patients (n=76) with first psychotic episodes of schizophrenia the hypothesis tested was whether early differential treatment after an acute psychotic break improved outcome as compared with other studies. Patients had a relatively short duration of untreated psychosis. No significant effect between two treatment conditions on relapse rate was found. The 15-month intervention program kept the psychotic relapse rate as low as 15%; lower than comparable studies. Thus, the initial results were in support of the hypothesis. After completion of the 15 months study, patients were referred to other agencies and followed for five years. Results of the follow up study showed that the low relapse rate could not be maintained. Of the remaining 71 patients of the initial sample, 52% had one or more psychotic relapses, 25% developed chronic positive symptoms and 23% did not have another psychotic episode. In addition, the level of social functioning turned out to be low: the majority of patients were dependent upon their parents, few held down a skilled or paid job and also their quality of life seemed low, results indicate that early intervention may improve short term but not long term outcome in schizophrenia. Our results also suggest that referral to other mental health agencies after intervention is not sufficient. Continuity of outpatient care, including continuity of a professional relationship, continuity of support for the family, and the continuity in management of illness, medication and stress may be a key issue in the first five years after the onset of psychosis in schizophrenia. Early recognition and intervention may not nearly be as important for outcome as continuity in care and caregivers. At present, however, it remains questionable whether early intervention programs in first-episode patients with a short duration of untreated psychosis can offer the prospect of altering the course of schizophrenia without a sustained comprehensive treatment program.

Clinical and neuropsychological correlates of the P300 in schizophrenia.

We investigated the relationship between the P300, neuropsychological test performance and symptomatology in recent-onset schizophrenic patients (n = 45) to gain insight into underlying mechanisms of abnormal P300 in schizophrenia. The P300 was recorded in two sessions with an intermission of five minutes, at the midline frontal, central and parietal electrode site. P300 amplitude and latency were compared with those obtained in 25 controls. Twenty patients were treated with olanzapine and 19 patients with risperidone. P300 amplitude was smaller and latency longer in patients than in controls. In the patient group, parietal P300 amplitude reduction was related to poorer performance on neuropsychological tests of memory. Frontal P300 amplitude reduction was related to impaired selective attention. In patients with negative symptomatology, P300 amplitude was reduced in the second P300 session compared with the first. Patients on risperidone demonstrated a smaller parietal P300 amplitude than patients using olanzapine. Reduced parietal P300 amplitude could signify a dysfunction in the continuous memory updating of current events. Negative symptomatology may be associated with a time dependent decrease in neuronal firing, as indicated by reduced P300 amplitude in the second P300 session.

Dopamine transporter density in young patients with schizophrenia assessed with [123]FP-CIT SPECT.

Disturbances in the dopamine (DA) system are thought to play a major role in schizophrenia. Amphetamine-induced release of endogenous DA is shown to be enhanced in schizophrenia, as is striatal [18F]FDOPA uptake in the striatum. It is not clear if the density of DA neurons is altered in schizophrenia. By studying the DA transporter with [123I]FP-CIT single photon emission computed tomography (SPECT), the density of nigrostriatal dopaminergic cells can be studied. Using [123I]FP-CIT SPECT, DA transporter density in the striatum was studied in 36 young patients with schizophrenia. Ten patients were antipsychotic (AP)-naive, 15 were treated with olanzapine, eight with risperidone and three were AP-free. A control group of 10 age-matched volunteers was included. Striatal [123I]FP-CIT binding was not significantly different between AP-naive patients (2.87), patients treated with olanzapine (2.76), patients treated with risperidone (2.76), AP-free patients (2.68) and controls (2.82) (F=0.07,p=0.98). Unexpectedly, striatal [123I]FP-CIT binding in females was significantly higher than in males (3.29 and 2.70, respectively; t=-2.56, p=0.014).Concluding, functional changes in the dopaminergic system in schizophrenia are not likely to be reflected in a change in DA transporter density. Moreover, DA transporter density does not seem to be altered by AP medication.

Symptoms, cognitive and social functioning in recent-onset schizophrenia: a longitudinal study.

The relationships among symptoms, cognitive functioning and social functioning were investigated in patients with schizophrenia over a period of 15 months. Patients with a mood disorder, a normal control group and a sample of parents of the schizophrenic patients also completed the cognitive tests. In the schizophrenia sample, only disorganisation was correlated with cognitive performance, which was interpreted as further evidence that disorganisation is a separate symptom dimension of schizophrenia. Against expectations, with two of three measurements no significant correlations were found between negative symptoms and cognitive performance. With these two measurements, however, a curvilinear association between negative symptoms and cognitive performance was observed, suggesting that negative symptoms are not a unitary concept. Finally, tentative evidence could be obtained for speed of information processing and selective attention as markers for vulnerability, although the latter is not specific for schizophrenia.

Patient attributes and expressed emotion as risk factors for psychotic relapse.

In the context of a prospective, controlled treatment study, contrasting family interventions with individual treatment, the role of expressed emotion (EE) as a predictor of relapse was examined in patients with recent-onset schizophrenia and related disorders (n = 97). EE was compared with 13 predictor variables. The variables, taken from EE and family intervention studies, related to demography, premorbid functioning, present and past illness history, and comorbid substance abuse. Psychotic relapse was operationalized with a conservatively measured relapse criterion, composed of monthly ratings based on the Brief Psychiatric Rating Scale and on clinical judgment during the 12 months of outpatient treatment. Of the 14 predictor variables entered in stepwise survival analyses, 6 variables had probable predictive power on the conservative relapse criterion. These variables were entered in a Cox regression model. EE turned out to be the major predictor of relapse in the overall sample (hazard ratio [HR] 4.90; confidence interval [CI] 1.05-22.92). This finding remained when only patients with a first psychotic episode (p = 0.02) and patients in the individual treatment condition (p = 0.001) were examined. Cannabis abuse was the major predictor of relapse in patients with high-EE families (HR 4.27; CI 1.12-16.29).