In this study, the effect of 19 possible predictor variables on 4 outcome variables was analyzed in young patients with recent-onset schizophrenia and related disorders (n = 64). Patients who participated in a 15-month intervention program were stratified into low and high parental expressed emotion and randomized over two intervention conditions: standard intervention and standard plus family intervention. Baseline variables were measured during the intervention. Outcome variables were measured over 5 years after discharge and comprised duration of psychotic episodes, living institutions for psychiatric patients, structural activities, and help from the family. From the 19 baseline variables, 6 had possible predictive value and were entered in a multivariate analysis. The resulting path model indicated that the score on the Strauss and Carpenter prognostic scale was predictive for duration of psychotic episodes. Diagnosis (schizophrenia vs. schizophrenia-related disorder) predicted help from the family. Age at first psychotic episode predicted living in institutions for psychiatric patients. Duration of psychotic episodes was associated with living in institutions for psychiatric patients and with help from the family but not with structural activities.

Duration of untreated psychosis (DUP), defined as delay in treatment with antipsychotic medication, was found to be associated with an unfavorable course of schizophrenia. Delay in intensive psychosocial treatment (DIPT) may also be related to outcome. We examined the relationship of DUP and DIPT with several outcome domains 6 years after onset in a cohort of 88 consecutively admitted patients with early-onset schizophrenia and related disorders. Patients and their parents completed an inventory concerning DUP, DIPT, and various aspects of outcome. Psychotic relapse during the first year after hospitalization was assessed with a chart review. Both DUP and DIPT were found to be associated with negative symptoms at outcome; mode of onset was not. DUP was associated with mild psychotic relapse. DIPT was associated with months of rehospitalization. There was no relation between DUP or DIPT and other aspects of outcome. When we controlled for age at onset, gender, and duration of treated first psychotic episode, only DIPT was associated with negative symptoms at outcome. DIPT may be a more important predictor of negative symptoms at outcome than is delay in starting antipsychotic medication alone.

Schizophrenia remains a major burden on patients and society. The dopamine hypothesis attempts to explain the pathogenic mechanisms of the disorder, and the neurodevelopmental hypothesis the origins. In the past 10 years an alternative, the cognitive model, has gained popularity. However, the first two theories have not been satisfactorily integrated, and the most influential iteration of the cognitive model makes no mention of dopamine, neurodevelopment, or indeed the brain. In this Review we show that developmental alterations secondary to variant genes, early hazards to the brain, and childhood adversity sensitise the dopamine system, and result in excessive presynaptic dopamine synthesis and release. Social adversity biases the cognitive schema that the individual uses to interpret experiences towards paranoid interpretations. Subsequent stress results in dysregulated dopamine release, causing the misattribution of salience to stimuli, which are then misinterpreted by the biased cognitive processes. The resulting paranoia and hallucinations in turn cause further stress, and eventually repeated dopamine dysregulation hardwires the psychotic beliefs. Finally, we consider the implications of this model for understanding and treatment of schizophrenia.

The stability of parental expressed emotion (EE) is analysed over about 9 years, and related to course of illness in patients with recent-onset schizophrenia. Families, who participated in a 15-month intervention, were randomised over two intervention conditions. Psychotic episodes were measured over 5 years after discharge. The Five Minute Speech Sample (FMSS) EE was elicited two times during the 12-month outpatient intervention and two times over 8 years after discharge on average. EE is expressed as criticism/dissatisfaction (CRIT), emotional overinvolvement (EOI), and as the classical dichotomous index. EE is not stable over the years. Intervention condition had no differential effect on EE as measured with CRIT and the dichotomous index. For EOI, an interaction between intervention condition and time was found. EE as assessed during intervention does not predict psychotic episodes during follow-up. An association was found between psychotic episodes and CRIT as assessed at 34 months after discharge. Family intervention may inhibit the development of high EOI for a limited period. Our results may be in support of the hypothesis that psychotic episodes in patients can affect the critical attitude in parents.

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.

The predictive value of personality traits and disorders for the short-term course of schizophrenia was assessed in a cohort of 93 adolescent patients. Personality disorders, particularly antisocial personality disorder, were found to be predictive of the course of schizophrenia. Axis II comorbidity as defined in the Diagnostic and statistical manual of mental disorders influences the course of schizophrenia and therefore more attention should be paid to this pathology in the prevention of relapse in schizophrenia.

In an earlier study, a quantitative measure for expressed emotion (EE) was constructed. This comprised six items of the Five-Minute Speech Sample, which formed a criticisms/dissatisfaction scale and a second scale, concerning emotional overinvolvement, which consisted of two items. In the present study, the association between psychotic relapse and the quantitative scales for EE and the original dichotomous index was investigated. A strong association with psychotic relapse was found among mothers using the criticisms/dissatisfaction scale. No interaction between the EE scores of fathers and mothers was found. Therefore, the mean score of two interviewed parents was taken as the family profile score. With this family measure, a stronger effect was found than when the parents were analysed separately. The quantitative measure for emotional overinvolvement was not associated with psychotic relapse. With the original dichotomous index, no significant effects were found, except for a trend in the subgroup of mothers. The results support the hypothesis that a quantitative measure for EE is a better predictor of psychotic relapse than a dichotomous index. (C) 1998 Rapid Science Ltd.

Prevention of relapse is the main purpose of intervention in schizophrenia. Early studies found that antipsychotic medication protected patients against relapse. Subsequent research showed that family intervention therapy in combination with pharmacotherapy was superior to pharmacotherapy alone and to individual therapy in combination with pharmacotherapy. More recent research has focused on expressed-emotion (EE) status and has tried to determine what type of family intervention best suits patients from particular family types. The Amsterdam relapse prevention study investigated the effectiveness of a family behavioral management approach combined with standard individual therapy in comparison with standard individual therapy alone in young, recent-onset, first-or second-episode schizophrenic patients whose families had been taken through a supportive psychoeducational program while the patient was in hospital. The standard individual therapy was highly effective, and further benefit of family intervention could not be demonstrated. Patients in high-EE families were most at risk of relapse; cannabis abuse was the second most important risk factor. Among low-EE families, the relapse rate in the combination intervention group was higher (13%) than in patients given standard individual therapy alone (0%); this suggests that psychosocial intervention approaches need to be tailored to suit family type. Since intensive intervention has a short duration in relation to the length of the disorder in most patients, strategies must be developed for continuity of care. Involving family members in the continuity of care programs may be a crucial step in the delay or remission of psychotic relapse, combined with maintenance of atypical antipsychotic medication. (C) 1998 Rapid Science Ltd.

The possible adverse clinical effects of untreated psychosis in schizophrenic patients, particularly early in the course of illness, have been a topic of considerable interest in recent years. We examined the timing of first administration of antipsychotic medication after the first onset of psychotic symptoms in 103 patients with DSM-III-R diagnoses of schizophrenia, schizophreniform or schizo-affective disorder. Patients with a delay of one or more years between the onset of the first psychotic symptom and the initiation of antipsychotic treatment demonstrated more severe negative symptomatology on admission to hospital and more severe positive symptoms and negative symptoms at discharge. These effects were present in both first-admission patients, in whom the delay to treatment immediately preceded hospitalization and chronic patients with a history of multiple hospitalizations. Patients with one or more years of untreated psychosis prior to their first antipsychotic treatment displayed a more severe poverty syndrome at the time of admission and discharge and a more severe reality distortion syndrome at discharge from the index hospitalization. These findings were not related to age, premorbid functioning, duration of illness, first- vs multiple-episode status, or dosage of antipsychotic medication at time of admission or discharge assessment. Findings from the present study suggest that failure to initiate antipsychotic treatment early in the course of the illness may be associated with a recurrent pattern of poorer treatment response and more severe and persistent positive and negative symptomatology. These findings indicate the importance of early detection of illness and early initiation of antipsychotic treatment for the first psychotic symptoms of schizophrenia.

The items of the Five Minute Speech Sample, an instrument to elicit relatives' expressed emotion, were investigated in a follow-up study of 120 parents of adolescents with recent-onset schizophrenia. A composite scale was constructed using Mokken scale analysis. From the 9 available items, 6 formed a unidimensional and cumulative scale. This scale was applicable for the total parent group, as well as for fathers and mothers separately. A second scale of 2 items did not meet the criteria for the Mokken model completely and was applicable for the parent group as a whole, but not for fathers and mothers as separate groups. The configuration of the subscales as found with the Mokken scale analysis was comparable with the results of principal component analysis. A quantitative measure may detect smaller differences in expressed emotion than the dichotomous index and expands the possibilities for statistical tests.

d-cycloserine and l-cycloserine interactions with dl-alanine 1-C14 incorporation into the proteins of an E. coli strain were investigated.The actions of the d- and l-isomers of cycloserine on protein synthesis are closely related to alanine metabolism. The incorporation of algal protein hydrolysate C14 into bacterial proteins does not seem to be influenced by d- and l-cycloserine.A comparison of the effects promoted by d-cycloserine and by d-alanine on the incorporation of dl-alanine-1-C14 into bacterial proteins shows that d-cycloserine behaves like a d-alanine analogue.

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.

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.

Relapse and exacerbation of psychotic symptoms were investigated in a prospective study of 88 patients with recent-onset schizophrenia and related disorders. Relapse definitions were derived from expressed emotion and family intervention studies and based on the Brief Psychiatric Rating Scale (BPRS), the Present State Examination, and clinical judgment. Results indicate that research and clinical criteria represent different perspectives on relapse. Clinical criteria provide a validity check that can verify BPRS-rated changes in partially remitted patients.