Peter Dingemans

Prediction of Psychosis in Adolescents and Young Adults at High Risk: Results From the Prospective European Prediction of Psychosis Study

CONTEXT Indicated prevention is currently regarded as the most promising strategy to attenuate, delay, or even avert psychosis. Existing criteria need improvement in terms of specificity and individual risk assessment to allow for better targeted and earlier interventions. OBJECTIVE To develop a differential predictive clinical model of transition to first-episode psychosis. DESIGN Prospective multicenter, naturalistic field study with a total follow-up time of 18 months. SETTING Six early-detection outpatient centers in Germany, Finland, the Netherlands, and England. PARTICIPANTS Two hundred forty-five help-seeking patients in a putatively prodromal state of psychosis according to either ultra-high-risk (UHR) criteria or the basic symptom-based criterion cognitive disturbances (COGDIS). MAIN OUTCOME MEASURE Incidence of transition to psychosis. RESULTS At 18-month follow-up, the incidence rate for transition to psychosis was 19%. Combining UHR and COGDIS yielded the best sensitivity. A prediction model was developed and included positive symptoms, bizarre thinking, sleep disturbances, a schizotypal disorder, level of functioning in the past year, and years of education. With a positive likelihood ratio of 19.9, an area under the curve of 80.8%, and a positive predictive value of 83.3%, diagnostic accuracy was excellent. A 4-level prognostic index further classifying the general risk of the whole sample predicted instantaneous incidence rates of up to 85% and allowed for an estimation of time to transition. CONCLUSIONS The prediction model identified an increased risk of psychosis with appropriate prognostic accuracy in our sample. A 2-step risk assessment is proposed, with UHR and cognitive disturbance criteria serving as first-step criteria for general risk and the prognostic index as a second-step tool for further risk classification of each patient. This strategy will allow clinicians to target preventive measures and will support efforts to unveil the biological and environmental mechanisms underlying progression to psychosis.

Treatment, expressed emotion and relapse in recent onset schizophrenic disorders

The effect of in-patient and individual orientated psychosocial intervention (IPI) and in-patient and individual and family orientated intervention (IPFI) across levels of expressed emotion (EE) on relapse was compared in a group of patients with recent onset schizophrenic disorders. Patients were randomly assigned to an individual orientated psychosocial intervention programme or to an identical psychosocial programme plus a behavioural family intervention. Seventy-six patients were studied during a 12 month out-patient treatment period after an in-patient treatment programme in which parents followed a psychoeducational programme. Overall relapse rates during the out-patient interventions were low (16%). Adding family intervention to the psychosocial intervention did not affect the relapse rate. Patients in low EE families relapsed slightly more often during the psychosocial plus family intervention. In-patient treatment with psychoeducation for parents, followed by an out-patient psychosocial intervention programme, has a favourable impact on relapse. Additional family intervention may increase stress in low EE families, thus affecting relapse in their children.

Baseline differences in clinical symptomatology between ultra high risk subjects with and without a transition to psychosis.

BACKGROUND The chance of transition to psychosis in patients at Ultra High Risk for developing psychosis (UHR) is 10-15%. The aim of present study was to investigate differences in baseline clinical symptomatology, general level of functioning (GAF-score) and genetic risk between UHR patients who did (UHR+T) or did not (UHR+NT) make a transition to psychosis. Sharpening UHR inclusion criteria may aid in improving prediction of transition to psychosis. METHOD The study sample was taken from 285 patients who were examined within the Dutch Prediction of Psychosis Study (DUPS) at the Academic Medical Center of the University of Amsterdam, the Netherlands. Out of 73 included UHR subjects, 18 made a transition to psychosis. Psychopathology was investigated with the Structured Interview for Prodromal Syndromes, Bonn Scale for the Assessment of Basic Symptoms and GAF-score. The follow-up period of the study was three years. RESULTS The UHR+T group showed more social anhedonia and withdrawal, more bizarre thinking and a lower GAF score at baseline than the UHR+NT group. CONCLUSIONS In agreement with the results of Cannon et al. [Cannon, T.D., Cadenhead, K., Cornblatt, B., Woods, S.W., Addington, J., Walker, E., Seidman, L.J., Perkins, D., Tsuang, M., McGlashan, T., Heinssen, R., 2008. Prediction of Psychosis in Youth at High Clinical Risk: A Multisite Longitudinal Study in North America. Arch. Gen. Psychiat. 65 (1) 28-37.], our study indicates that severity of specific symptoms at baseline is related to transition to psychosis in UHR subjects. These findings may contribute to a more accurate prediction of a first psychotic episode. Furthermore, symptoms that are increased at baseline in the UHR+T group could be a focus of cognitive behavioural therapy in the UHR period.

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.

PSYCHO-EDUCATION IN BIPOLAR DISORDER: EFFECT ON EXPRESSED EMOTION

In a waiting-list controlled study on a multi-family psycho-educational intervention in bipolar disorder, key relatives in the treatment group showed a significant change from high to low levels of expressed emotion (EE) compared with the control group. In addition, patients with low-EE key relatives had a significantly lower number of hospital admissions compared with those living with high-EE key relatives. The multi-family groups were well received by the participants, and there were only a few drop-outs.

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.

Disability in people clinically at high risk of psychosis

BACKGROUND Decline in social functioning occurs in individuals who later develop psychosis. AIMS To investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition. METHOD Prospective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS-II). RESULTS At baseline, the transition group displayed significantly greater difficulties in making new friends (z = -3.40, P = 0.001), maintaining a friendship (z =-3.00, P = 0.003), dealing with people they do not know (z =-2.28, P = 0.023) and joining community activities (z =-2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (β = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238-2.550). CONCLUSIONS Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.

White matter fibertracking in first-episode schizophrenia, schizoaffective patients and subjects at ultra-high risk of psychosis

There is increasing evidence of white matter pathology in schizophrenia. The aim of this study was to examine whether white matter abnormalities found with diffusion tensor imaging (DTI) in previous schizophrenia studies are present in the early phase of the illness. DTI was performed at 3 T on 10 male patients with a first (n = 8) or second (n = 2) psychotic episode of schizophrenia or schizoaffective disorder, 10 male patients at ultra-high risk of psychosis with (pre)psychotic symptoms and 10 healthy controls. Fibertracts found to be abnormal in other DTI studies (uncinate and arcuate fasciculus, anterior and dorsal cingulum, subdivisions of the corpus callosum) were calculated and visualized; tract-specific measurements (fractional anisotropy and trace) were performed. No differences were found between the healthy subjects and the 2 patient groups. These preliminary findings suggest that there is no white matter pathology of these association tracts detectable with DTI in the early stages of schizophrenic illness in males. Our findings are in contrast with DTI abnormalities found in some other first-episode studies. This discrepancy in findings may be related to differences in subject characteristics and DTI methodology. Possible effects of age, gender, level of education and illicit substance use on DTI findings in schizophrenia are discussed.

Predictive value of cognition for different domains of outcome in recent-onset schizophrenia

The aim of this study was to see whether and how cognition predicts outcome in recent-onset schizophrenia in a large range of domains such as course of illness, self-care, interpersonal functioning, vocational functioning and need for care. At inclusion, 115 recent-onset patients were tested on a cognitive battery and 103 patients participated in the follow-up 2 years after inclusion. Differences in outcome between cognitively normal and cognitively impaired patients were also analysed. Cognitive measures at inclusion did not predict number of relapses, activities of daily living and interpersonal functioning. Time in psychosis or in full remission, as well as need for care, were partly predicted by specific cognitive measures. Although statistically significant, the predictive value of cognition with regard to clinical outcome was limited. There was a significant difference between patients with and without cognitive deficits in competitive employment status and vocational functioning. The predictive value of cognition for different social outcome domains varies. It seems that cognition most strongly predicts work performance, where having a cognitive deficit, regardless of the nature of the deficit, acts as a rate-limiting factor.

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.