Predictors of treatment response from a first episode of schizophrenia or schizoaffective disorder

OBJECTIVE: This study examined the treatment response of patients with first-episode schizophrenia and schizoaffective disorder and potential predictors of response. METHOD: First-episode patients were assessed on measures of psychopathology, cognition, social functioning, and biological parameters and treated according to a standardized algorithm. RESULTS: One hundred eighteen patients (52% male, mean age 25.2 years) entered the study. The cumulative percentage of patients responding by 1 year was 87%; the median time to response was 9 weeks. The following variables were significantly associated with less likelihood of response to treatment: male sex, obstetric complications, more severe hallucinations and delusions, poorer attention at baseline, and the development of parkinsonism during antipsychotic treatment. Variables not significantly related to treatment response were diagnosis (schizophrenia versus schizoaffective disorder), premorbid functioning, duration of psychotic symptoms prior to study entry, baseline disorganization, negative and depressive symptoms, baseline motor function, akathisia and dystonia during treatment, growth hormone and homovanillic acid measures, psychotic symptom activation to methylphenidate, and magnetic resonance measures. CONCLUSIONS: Patients with first-episode schizophrenia and schizoaffective disorder have high rates of response to antipsychotic treatment; there are specific clinical and pathobiologic predictors of response.     

Symptomatic and functional recovery from a first episode of schizophrenia or schizoaffective disorder

OBJECTIVE: Follow-up studies have found that a substantial number of patients with schizophrenia achieve full recovery (i.e., sustained improvement in both symptoms and social/vocational functioning) when examined decades after an index admission. This study addressed recovery during the crucial early course of the illness. METHOD: Subjects in their first episode of schizophrenia or schizoaffective disorder (N=118) were assessed at baseline and then treated according to a medication algorithm. Full recovery required concurrent remission of positive and negative symptoms and adequate social/vocational functioning (fulfillment of age-appropriate role expectations, performance of daily living tasks without supervision, and engagement in social interactions). RESULTS: After 5 years, 47.2% (95% CI=36.0%-58.4%) of the subjects achieved symptom remission, and 25.5% (95% CI=16.1%-34.7%) had adequate social functioning for 2 years or more. Only 13.7% (95% CI=6.4%-20.9%) of subjects met full recovery criteria for 2 years or longer. Better cognitive functioning at stabilization was associated with full recovery, adequate social/vocational functioning, and symptom remission. Shorter duration of psychosis before study entry predicted both full recovery and symptom remission. More cerebral asymmetry was associated with full recovery and adequate social/vocational functioning; a schizoaffective diagnosis predicted symptom remission. CONCLUSIONS: Although some patients with first-episode schizophrenia can achieve sustained symptomatic and functional recovery, the overall rate of recovery during the early years of the illness is low.     

Predictors of risk for relapse in patients with schizophrenia or schizoaffective disorder during olanzapine drug therapy

PURPOSE: To evaluate the relationship of dose decrease, symptom worsening, and baseline covariates on subsequent relapse during olanzapine treatment in patients with schizophrenia or schizoaffective disorder. METHODS: In two 28-week, randomized, double-blind clinical trials, a Cox proportional hazards model was used to determine potential correlates of relapse (defined as > or =20% worsening on PANSS total and CGI-Severity 3) among patients (N=271) who responded to 8 weeks of olanzapine treatment (10-20mg/day). Variables examined included: demographics, illness characteristics, baseline symptoms, symptom change, dose, adverse events, and functioning. RESULTS: Patients with a lower last dose relative to the preceding visit interval were 4 times more likely to relapse during that visit interval than other patients (p<.001). A similar finding was observed for a decrease in interval modal dose, although this variable was more predictive of relapse in the visit interval immediately following dose decrease (p=.027). In a subgroup analysis by gender, there was a significantly greater incidence of relapse in men with a dose decrease, whereas a dose decrease in women did not correlate with relapse. Relapse was also correlated with the emergence or worsening of a psychiatric adverse event during the same (p<.001) and preceding (p=.007) visit intervals, and with increased rating scale measures of psychopathology. The occurrence of a non-psychiatric adverse event was not associated with relapse. CONCLUSION: Dose decrease is a significant predictor of relapse in male but not female patients. Psychiatric adverse events also predicted relapse. Patients should be periodically reassessed to determine the need for maintenance treatment with appropriate dose.     

EEG coherence in a mental arithmetic task performance in first episode schizophrenia and schizoaffective disorder

Objectives

To evaluate the coherence values of the cortical bands in patients with first episode schizophrenia and schizoaffective disorder during the performance of a mental arithmetic task.

Predictors of schizophrenia in patients with a first episode of psychosis

Early identification of schizophrenia in patients with a first episode of psychosis (FEP) may help to avoid inappropriate treatment and may enhance long-term outcome by addressing issues such as family network, treatment adherence and functional and symptomatic outcome. It was the aim of the study to determine baseline variables that significantly predicted a diagnosis of schizophrenia in patients with FEP. The sample consisted of 133 FEP patients hospitalized for at least 6 weeks, in whom a DSM-IV diagnosis was confirmed after 1 year follow-up. Patients were divided into two groups, those with a diagnosis of schizophrenia (Schizophrenia group, n = 63; 47.8%), and those with other psychosis, who were grouped under Non-Schizophrenic Psychosis (NSP, n = 70; 52.2%). Sociodemographic (marital status, educational level) and clinical variables were recorded for each patient. Substance use (alcohol, cannabis and cocaine) did not statistically differ between the two groups. Absence of characteristics defined as criteria for good prognosis, lack of ≥ 20% improvement in the total Positive and Negative Syndrome Scale score at 6 weeks, and a poor premorbid adjustment as determined by the Premorbid Adjustment Scale score significantly predicted the presence of schizophrenia. The regression model including these three variables achieved a predictive value of 76.3%, with a sensitivity of 74.6% and a specificity of 77.9%.     

Early warning signs of relapse following a first episode of psychosis

Research in schizophrenia has provided empirical support for the use of self-report inventories for early warning signs of relapse, but to date no published studies have reported on the predictive validity of self-reported early warning signs of relapse in a first-episode cohort. Sixty patients, who had remitted following their first episode of psychosis, participated in a 9-12 month prospective follow-up study. Outcome data on putative prodromal symptoms was available on 46 participants. The Early Signs Scale (ESS) achieved adequate sensitivity but poor specificity and positive predictive validity (PPV) in predicting relapse or symptom exacerbations, although a post hoc increase in the established cut-off significantly improved the outcome. The findings provide qualified support for the use of the ESS in relapse prevention with first-episode patients who are in remission. Further prospective studies with larger numbers of first-episode patients will enable sample sizes enable the comparison of the effectiveness of several prodromal scales using ROC analysis, or a combination of risk factors using regression models.     

Depressive symptoms in first episode schizophrenia spectrum disorder

Background

Depressive symptoms in ‘non-affective’ first episode schizophrenia spectrum disorders (FES) are common, but poorly understood, resulting in a range of conceptual and clinical management issues. This study had three aims: (i) to determine the prevalence of moderate to severe depressive symptoms (defined as a Clinical Global Impressions Scale-Bipolar Disorder (CGI-BP depression) score > 3) in a large representative sample of FES patients; (ii) to compare the clinical and functional characteristics of FES patients with and without these depressive symptoms at service entry; and (iii) to compare the characteristics of FES patients with and without persistent depressive symptoms.

Methods

Medical file audit methodology was employed to collect information on 405 patients with FES treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia.

Results

26.2% (n = 106) of the patients had moderate to severe depression at service entry. At service entry and at discharge, those with depressive symptoms had greater insight into their illness but did not differ from those without depressive symptoms in terms of severity of overall psychopathology. Substance use was significantly less common in those with depressive symptoms at service entry and at discharge. Of those who were depressed at baseline, 14.2% (n = 15) continued to have moderate to severe depressive symptoms at discharge.

Discussion

Depressive symptoms are common in patients with FES. Understanding the nature and characteristics of depression in FES has important clinical implications for both early intervention and treatment.     

Predictors of medication discontinuation by patients with first-episode schizophrenia and schizoaffective disorder

BACKGROUND: Enhancing medication adherence early in the course of schizophrenia and schizoaffective disorder may substantially improve long-term course. Although extensively studied in multi-episode patients, little data exist on medication adherence by first-episode patients. METHOD: Medication adherence was assessed during the first year of treatment and following recovery from the first relapse in patients treated by a standardized medication algorithm. RESULTS: During the first year of treatment, patients with poorer premorbid cognitive functioning were more likely to stop antipsychotics (t=-2.54, df=75, p=0.01). Parkinsonian side effects increased the likelihood (hazard ratio=41.22; 95% CI=2.30, 737.89; p=0.01), and better executive function decreased the likelihood (hazard ratio=0.40; 95% CI=0.18, 0.88; p=0.02) that patients discontinued maintenance medication after a first relapse. CONCLUSION: Interventions to ameliorate cognitive deficits and Parkinsonian side effects may enhance treatment adherence.     

Premorbid adjustment in first episode schizophrenia and schizoaffective disorders: a comparison of social and academic domains

OBJECTIVE: Recent evidence suggests that premorbid adjustment in schizophrenia and related disorders can be separated into social and academic domains. In this paper, we examine the correlates of and prognostic significance of social and academic premorbid adjustment in a sample of 113 patients. METHOD: Premorbid adjustment, symptoms and cognitive functioning were assessed at presentation for treatment and symptoms were re-assessed after a year of treatment. RESULTS: Females and those with a diagnosis of schizoaffective disorder were found to have better premorbid adjustment in the academic domain, but not in the social domain. Neurocognitive functioning was more consistently related to academic than social adjustment. Better social and academic premorbid adjustment was correlated with lower negative symptoms after 1 year of treatment, but neither was a significant predictor of positive symptoms. CONCLUSION: Social and academic premorbid adjustments show different relations to gender, specific diagnosis and neurocognitive functioning in schizophrenia and related disorders.     

Clinical features of illness in siblings with schizophrenia or schizoaffective disorder

Evidence implicating genetic or prenatal-perinatal environmental causes in the familial aggregation of schizophrenia led us to study 53 sets of siblings, two or more of whom had chronic psychosis, either schizophrenia or schizoaffective disorder. We looked for similarities in clinical features and concordance of diagnosis within sibships to test for shared familial causes. Clinical variables, including diagnosis, specific symptoms, age at onset, and nongenetic perinatal factors, were studied. Auditory hallucinations, paranoid delusions, thought disorder, negative symptoms, and poor premorbid social adjustment did not significantly correlate in siblings. Concordance was found for schizoaffective disorder and history of major depressive episodes, suggesting that schizophrenia with a depressive component and Research Diagnostic Criteria schizoaffective illness may represent a specific etiologic subtype(s) of the illness, whereas the other noted symptoms may represent the variable expression of the disorder. Age at onset and at first hospitalization were significantly correlated, consistent with genetic or other familial factors on time of onset. Birth complications were significantly more frequent among the schizophrenic compared with non-psychotic siblings, had a familial component, and tended to be associated with an earlier age at onset. Thus, nongenetic perinatal factors may increase the risk for schizophrenia in a familial form of the illness and contribute to the correlation of ages at onset in siblings.     

Twelve-month outcome of adolescents with bipolar disorder following first hospitalization for a manic or mixed episode

OBJECTIVE: Although adolescent-onset bipolar disorder is associated with significant morbidity, there have been few prospective outcome studies of this population. The aim of this study was to examine the 12-month outcome of bipolar adolescents following an initial hospitalization for a manic or mixed episode. METHOD: Bipolar adolescents (N=71) were recruited during their first hospitalization for a manic or mixed episode and were evaluated using diagnostic, symptomatic, and functional assessments. Patients were also evaluated at 1, 4, 8, and 12 months after hospitalization to assess syndromic, symptomatic, and functional outcomes. Predictors of each type of outcome were identified. RESULTS: Kaplan-Meier estimates of the cumulative probabilities of syndromal, symptomatic, and functional recovery and syndromic recurrence during the first 12 months following initial hospitalization were 0.86, 0.43, 0.41, and 0.54, respectively. Only 35% of bipolar adolescents reported full medication adherence. Individual predictors of poor syndromic recovery included co-occurring attention deficit hyperactivity disorder (ADHD), anxiety disorders, and disruptive behavior disorders as well as nonadherence to psychotropic medication and lower socioeconomic levels. Co-occurring alcohol use disorders, treatment with antidepressants, and the absence of psychotherapeutic intervention predicted syndromic recurrence. Boys were more than twice as likely as girls to experience symptomatic recovery. CONCLUSIONS: Most bipolar adolescents experienced syndromic recovery following their first hospitalization. However, rates of symptomatic and functional recoveries were much lower. Future studies examining effective pharmacological and nonpharmacological treatment strategies for bipolar youth with co-occurring disorders and investigating factors that contribute to the development of substance use disorders and treatment adherence in bipolar youth are necessary to improve outcome.     

Predictors of noncompliance in males with first-episode schizophrenia, schizophreniform and schizoaffective disorder.

PURPOSE: Many factors influencing compliance in schizophrenia have been reported in the literature. Our aim was to assess predictors of noncompliance in male patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder in a naturalistic setting. SUBJECTS AND METHODS: Fifty-six male patients, discharged from hospital, were included in a 1-year follow-up study. Psychopathological symptoms were assessed with positive and negative syndrome scale at admission and discharge, while extrapyramidal side effects were recorded weekly during hospitalisation using the Simpson-Angus and Barnes akathisia scales. Socio-demographic and some other variables were also recorded. RESULTS: Thirty patients (53.6%) dropped out of treatment in the first year and 21 of them relapsed. With the Cox survival analysis three predictors of noncompliance were found: diagnosis of schizophrenia versus the other two diagnoses, positive symptoms at admission, and lack of insight at discharge. Discussion. In spite of a specific methodology and selection of only first-episode male patients, the results are in accordance with the findings of other authors. This confirms the universality of noncompliance in psychotic patients. CONCLUSIONS: First-episode patients have a high dropout rate. However, in compliant patients, the relapse rate was low, and therefore special attention and compliance-promoting interventions in first-episode patients are needed.     

Work-related subjective experiences among community residents with schizophrenia or schizoaffective disorder

OBJECTIVE: To develop a self-report scale of subjective experiences of illness perceived to impact on employment functioning, as an alternative to a diagnostic perspective, for anticipating the vocational assistance needs of people with schizophrenia or schizoaffective disorders. METHOD: A repeated measures pilot study (n(1) = 26, n(2) = 21) of community residents with schizophrenia identified a set of work-related subjective experiences perceived to impact on employment functioning. Items with the best psychometric properties were applied in a 12 month longitudinal survey of urban residents with schizophrenia or schizoaffective disorder (n(1) = 104; n(2) = 94; n(3) = 94). RESULTS: Construct validity, factor structure, responsiveness, internal consistency, stability, and criterion validity investigations produced favourable results. Work-related subjective experiences provide information about the intersection of the person, the disorder, and expectations of employment functioning, which suggest new opportunities for vocational professionals to explore and discuss individual assistance needs. CONCLUSION: Further psychometric investigations of test-retest reliability, discriminant and predictive validity, and research applications in supported employment and vocational rehabilitation, are recommended. Subject to adequate psychometric properties, the new measure promises to facilitate exploring: individuals' specific subjective experiences; how each is perceived to contribute to employment restrictions; and the corresponding implications for specialized treatment, vocational interventions and workplace accommodations.     

A trial of compliance therapy in outpatients with schizophrenia or schizoaffective disorder

OBJECTIVE: To evaluate the efficacy of compliance therapy when delivered to outpatients with schizophrenia or schizoaffective disorder. METHOD: Thirty patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) were recruited from urban psychiatric outpatient clinics in an open trial of compliance therapy. Compliance therapy is a cognitive/psychoeducational approach consisting of 4 to 6 sessions lasting 30 to 60 minutes each. The primary outcome was electronically measured antipsychotic medication adherence. Adherence data were analyzed for effects during an initial treatment period (month -1 to month +1) and a subsequent 5-month follow-up period. Secondary outcome measures included clinician and patient ratings of adherence, symptoms, insight, and attitudes to medication treatment. Data were collected from August 2001 to January 2004. RESULTS: Compliance therapy was not associated with improvements in antipsychotic medication adherence. Patient ratings of adherence improved during the month -1 to month +1 period, but not in the subsequent 5-month follow-up. A diagnosis of schizoaffective disorder was associated with poorer adherence than was a diagnosis of schizophrenia during the month -1 to month +1 period. A higher degree of insight at baseline (end of month -1) was associated with greater adherence in the 5-month follow-up period. Symptoms, insight, and attitudes to medication treatment did not change significantly during the study. CONCLUSION: In this uncontrolled trial, outpatients with schizophrenia or schizoaffective disorder did not benefit from compliance therapy.     

Psychopathy and violent behavior among patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: Although a strong association between violence and psychopathy has been demonstrated in nonpsychotic forensic populations, the relationship between psychopathy and violence among patients with schizophrenia has not been thoroughly explored. Patients with and without a history of persistent violent behavior were compared for comorbidity of psychopathy and schizophrenia or schizoaffective disorder. METHODS: Violent and nonviolent patients were identified through reviews of hospital charts and records of arrests and convictions. The Psychopathy Checklist: Screening Version was administered to 51 patients, 26 violent patients and 25 matched nonviolent patients. Analysis of variance was used as the principal statistical method for comparing violent and nonviolent groups. RESULTS: Mean psychopathy scores were higher for violent patients than nonviolent patients. Five of the violent patients (19 percent) had scores exceeding the cutoff for psychopathy, and 13 (50 percent) scored in the possible psychopathic range. All of the nonviolent patients scored below the cutoff for possible psychopathy. Higher psychopathy scores were associated with earlier age of onset of illness and more arrests for both violent and nonviolent offenses. CONCLUSIONS: The comorbidity of schizophrenia and psychopathy was found to be higher among violent patients than among nonviolent patients. Violent patients with schizophrenia who score high on measures of psychopathy may have a personality disorder that precedes the emergence of psychotic symptoms, or they may constitute a previously unclassified subtype of schizophrenia, characterized by early symptoms of conduct disorder symptoms and persistent violent behavior.