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Aim was to evaluate influencing factors of response and symptomatic remission in first-episode schizophrenia patients treated with risperidone or haloperidol.
229 first-episode schizophrenic patients were examined within a double blind controlled trial of the German Study Group on first-episode schizophrenia with biweekly PANSS ratings. Response was defined according to the definition by Lieberman et al. (2003) and symptomatic remission as the severity component of the consensus remission criteria by the Remission in Schizophrenia Working Group. Sociodemographic, psychopathological and functional variables as well as the treatment applied were evaluated regarding their potential predictive validity for treatment outcome. Univariate tests, logistic regression and CART-analyses were consulted as statistical methods.
126 patients (55%) achieved response and 118 patients (52%) symptomatic remission at discharge with no significant differences between the risperidone (51%) and haloperidol (49%) treated patients. Better baseline functioning, early treatment response, less depressive symptoms and a shorter duration of untreated psychosis were revealed significant predictors of response. Patients with symptomatic remission also had a significantly shorter duration of untreated psychosis and significantly less depressive symptoms at baseline. Logistic regression and CART-analyses revealed low general psychopathology, early treatment response and a high score in the Strauss-Carpenter-Prognostic-Scale at admission to be significantly positive predictive for symptomatic resolution.
Early treatment response, depressive symptoms and the level of psychosocial functioning were revealed to significantly predict outcome, with no significant differences between risperidone and haloperidol. The importance of an early adequate symptom control and the implementation of early intervention programs is highlighted.
Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.
The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome.
Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission.
Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.
To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement.
Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge.
Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC = 0.659) and response (AUC = 0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%).
The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.
Winter births have been associated with a higher risk of Alzheimer’s disease (AD) and other psychiatric disorders. In the present investigation, this putative association was examined in a sample of gerontopsychiatric patients. An analysis of the quarterly birth rates of 83 patients with AD, 78 elderly depressive patients with an early onset and 74 patients with a late onset of the depressive disorder, 48 patients with both AD and depression (co-morbid patients) and 107 healthy control subjects, revealed no particular seasonal distribution for any of the diagnostic groups. In AD and co-morbid patients, controlling for the ApoE genotype did not change this finding. Logistic regression analysis revealed the expected findings that increasing age and the presence of the ApoE4 allele were associated with a higher risk of dementia. Younger age and female gender were identified as risk factors for a depressive disorder. A winter birth (birth in the first three months of the year) was not associated with any of the diagnostic subgroups.
We concluded that in our sample a seasonal distribution of births was not found to increase the risk for AD or geriatric depression.
Although a series of DNA-sequence variants in proposed disposition genes for schizophrenia have been identified, the mechanisms to translate the genetic vulnerability for schizophrenia to the manifestation of the disease remain obscure. The analysis of the relationship of disease-associated alleles and combinations of alleles (haplotypes) to the clinical features and associated neurobiological correlates offer a tool to increase our understanding of the aetiology of schizophrenia.
We will explore this relationship in a series of case-control samples by (1) extracting schizophrenia-associated alleles and haplotypes of postulated susceptibility and modifying genes, (2) testing these identified genetic markers for association with neuropsychological and neuroimaging features of schizophrenia.
Neuropsychological deficits are considered endophenotypes for schizophrenia, because they are not only found in patients but also in many of their unaffected relatives, albeit in attenuated form. It is not yet clear which of these deficits in relatives are related to genetic or to environmental causes. We tested effects of inferred genetic liability for schizophrenia on neurocognitive variables to address this problem.
Twenty-eight patients with schizophrenia, 129 non-affected biological parents and 143 matched controls were assessed with an extensive neuropsychological test battery including tests of attention, memory, executive functioning and motor soft signs. Twenty-two parents had an ancestral history of schizophrenia and therefore were hypothesized to be more likely than their spouses without such a history (n = 17) to carry a genetic risk for schizophrenia.
Unaffected parents of schizophrenic patients showed significant deficits in a wide array of neuropsychological tasks and task domains. However, comparison of more likely and less likely carriers of illness-related genes showed specifically attentional and executive functioning, but not memory, to vary with degree of inferred genetic loading.
Attentional and executive (frontal) impairments vary with genetic loading for schizophrenia and can be considered true endophenotypes for this disorder. Consequently, these functions are particularly suited to evaluate the functional impact of candidate genes for schizophrenia in future studies.
Disturbances of the oculomotor system are promising endophenotypes for schizophrenia. In two separate studies, we examined antisaccade task performance, a measure of inhibitory control, in first degree relatives of schizophrenic patients (genetic risk without manifest disorder) and in clinical high risk subjects with symptoms suggestive of a prodromal phase of schizophrenia.
In the first study, 41 parents of schizophrenia patients and 22 controls were tested with with a prosaccade task and an antisaccade task. Parents were grouped into more likely, less likely, and indeterminate risk carriers. The second study involved 160 subjects clinically at risk for schizophrenia, 32 first episode schizophrenic patients, and 76 healthy controls.
In study 1 we found an increase of antisaccade latencies and error rates in parents of schizophrenics which varied with inferred genetic load, more likely gene carriers performing worst. In study 2, antisaccade performance varied with symptom load: subjects at risk with basic symptoms only were unimpaired, while at-risk subjects who had experienced brief psychotic episodes (BLIPS) showed deficits similar to first episode patients.
Reduced inhibitory control of oculomotor performance is associated with genetic loading for schizophrenia, and also with symptoms placing subjects at imminent risk of psychosis.
The WHO Collaborative Study on Psychological Problems in General Health Care examined the frequency, form, course and outcome of psychological problems in general health care settings. A total of 25,916 general health care attenders at 15 sites in 14 countries were screened using the 12-item General Health Questionnaire (GHQ-12). Of those screened, 5,438 were assessed in detail using a Primary Health Care version of the Composite International Diagnostic Interview (CIDI-PHC) in conjunction with the Brief Disability Questionnaire, the Social Disability Schedules, a self rated overall health status form and the 28-item General Health Questionnaire. The analysis has shown that sleep problems were common at all sites with: 26.8% of all patients having some form of sleep problem and 15% of the patients examined had trouble falling or staying asleep. Of those with sleep problems, 51.5% had a well-defined International Classification of Diseases 10th Revision (ICD-10) mental disorder (such as depression, anxiety, somatoform disorders or alcohol problems) and 48.5% of those with sleep problems for at least two weeks or more did not fulfil the criteria for any well defined ICD-10 diagnosis. Persons with sleep problems reported a degree of disability in the performance of their daily activities and social roles even when they had no symptoms of psychological disorders. When such symptoms were present the disability was significantly increased.
Uncertainties in individual response to specific antipsychotics are a major limitation in improving treatment. Pharmacogenetics offers the opportunity to help the clinical decision process by allocating individuum-specific odds for response versus non-response. Pharmacogenetics in schizophrenia has up to now produced only a very limited number of valid results. A main reason might be the heterogeneity of samples under study and lack by standardization of treatment (e.g. mixture of first onset and chronic patients).
The German Competence Network of Schizophrenia has completed a long-term treatment protocol in first-episode patients with schizophrenia (double-blind randomized study with risperidone versus haloperidol). We explored the predictive power of disease-associated variants in disposition genes and modifier genes for schizophrenia. We detected predictive markers in the genes for dysbindin, neuregulin 1 and COMT. These variants were also associated with neuropsychological correlates of schizophrenia.
Thus we can be confident that time has come to improve the tools for prediction of response to antipsychotics.