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.

The relation between dimensions of normal and pathological personality and childhood maltreatment in incarcerated boys.

The relation between subtypes of maltreatment and dimensions of personality and personality pathology was investigated in a representative sample of 142 incarcerated Dutch male juveniles. Normal personality dimensions were assessed with the Big Five Inventory, the Dimensional Assessment of Personality Pathology-Basic Questionnaire for Adolescents was used to measure pathological personality dimensions, and the Childhood Trauma Questionnaire was used to assess childhood maltreatment. The five maltreatment subtypes were found to be differentially and uniquely related to the normal and pathological personality dimensions in juvenile delinquents. The association between the abusive subtypes and Emotional Dysregulation depended on the co-occurrence of neglect. It was concluded that subtypes of maltreatment are distinctively related to dimensions of personality and personality pathology, possibly due to specific gene-environment interactions. Further research on this interplay is needed to be able to recognize genetic vulnerability. Early identification of children at risk could aid to limit the long-term consequences of maltreatment.

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.

Verbal fluency as a possible predictor for psychosis.

BACKGROUND: Neurocognitive abnormalities are prevalent in both first episode schizophrenia patients and in ultra high risk (UHR) patients. AIM: To compare verbal fluency performance at baseline in UHR in patients that did and did not make the transition to psychosis. METHOD: Baseline verbal fluency performance in UHR-patients (n=47) was compared to match first episode patients (n=69) and normal controls (n=42). RESULTS: Verbal fluency (semantic category) scores in UHR-patients did not differ significantly from the score in first episode schizophrenia patients. Both the UHR group (p<0.003) and the patient group (p<0.0001) performed significantly worse than controls. Compared to the non-transition group, the transition group performed worse on verbal fluency, semantic category (p<0.006) at baseline. CONCLUSIONS: Verbal fluency (semantic category) is disturbed in UHR-patients that make the transition to psychosis and could contribute to an improved prediction of transition to psychosis in UHR-patients.

P300 deficits are present in young first-episode patients with schizophrenia and not in their healthy young siblings.

OBJECTIVE: To evaluated P300 (P3b) abnormalities in young first episode patients with schizophrenia and their healthy young siblings. METHODS: An auditory oddball paradigm was used to assess P300 in 53 patients, 27 unaffected siblings and 28 healthy controls. Amplitude and latency of the three midline sites (Fz, Cz, and Pz) were compared between patients, siblings, and controls by a mixed-effects regression model. RESULTS: P300 amplitude was significantly reduced in patients with schizophrenia but not in healthy siblings, when compared to healthy controls. P300 latency did not significantly differ between the three groups. CONCLUSIONS: P300 amplitude but not latency was found to be affected in young patients with recent onset schizophrenia. However, P300 amplitude and latency were found not to be affected in healthy unaffected young siblings and, therefore, did not qualify as an endophenotype for schizophrenia. SIGNIFICANCE: The failure to find the P300 (P3b) abnormality in healthy siblings of patients with schizophrenia is an important finding and should be added to P300 literature.

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.

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.

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.

Social functioning and the course of early-onset schizophrenia: five-year follow-up of a psychosocial intervention.

BACKGROUND: Schizophrenia implies severe social impairments. Since the treatment of patients with schizophrenia shifted from long-term hospital admissions to community services, research on social functioning has become increasingly important. AIMS: Follow-up assessment of social functioning in young patients with schizophrenia during a 5-year period after intervention. METHOD: During intervention, families were randomised into two conditions: standard intervention and standard plus family intervention. RESULTS: Although no differential treatment effect with regard to the course of the illness was found, patients from the standard plus family intervention condition stayed for fewer months in institutions for psychiatric patients than patients from the standard intervention condition. CONCLUSIONS: Family intervention has helped parents to support their children, thereby diminishing institutional care.

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.

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.

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.

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.

Early detection and intervention in schizophrenia.

During the course of schizophrenia, symptoms tend to increase at the highest rate during the first 5 years of the disease. Moreover, 10% of suicides by schizophrenic patients occur within the first 10 years of schizophrenia being diagnosed. These facts emphasize the importance of early intervention to improve the course of the disease before further deterioration. The use of psychosocial interventions and drug management programmes, in addition to maintenance antipsychotic medication, reduces the risk of psychotic relapse. Continuity of care from inpatient to outpatient treatment also significantly improves outcome, largely as a result of better drug compliance. It appears, however, that the addition of a behavioural family intervention alone to a standard programme offers little additional benefit. The benefits of intervention programmes last only as long as the programme, and patients should continue with such intensive treatment strategies for at least the duration of the critical phase. Under these circumstances, very mild psychotic complaints may be recognized at an early stage so that treatment can begin even earlier, further increasing the chance of an optimal long-term outcome. Further studies of early intervention and relapse prevention are required to support these findings.

Parental communication deviance: its stability and the effect of family treatment in recent-onset schizophrenia.

The influence of a behavioural family treatment on parental communication deviance (CD) was investigated in a longitudinal treatment study. Subjects were the parents of young patients with recent-onset schizophrenia or related disorders. Parents and patients were randomly assigned to one of two treatment conditions: individual out-patient treatment or a combination of individual out-patient and family treatment. Parental CD was assessed with the Thematic Apperception Test (TAT) both at the start of the out-patient treatment and after completion of treatment 1 year later. Most families had high levels of CD, a finding which is in agreement with previous CD studies. These high CD levels remained stable over the 12-month period. Family treatment was not effective in influencing the level of CD. The findings suggest that high CD is a stable trait-marker of parents, and they support the notion that high levels of CD may precede the onset of serious psychotic disorders. Studies with more chronic patients are needed to replicate the findings.