Treatment Of Schizophrenic Patients Research Articles

EPA-1415 – Pharmacogenetics of antipsychotic-induced weight gain in schizophrenic patients

Background Antipsychotic-induced weight gain (AIWG) is a major drawback in the treatment of schizophrenic patients with second-generation antipsychotics (SGAs). Pharmacogenetic studies have established several polymorphisms in genes of different pathways contributing to the development of weight gain in schizophrenic patients. However interactions of genetic polymorphisms and clinical predictors have not been studied extensively enough to reliable predict weight gain before initiating antipsychotic treatment. Methods We analyzed several single-nucleotide polymorphisms (SNPs) of candidate genes (e.g. APOA, GHRL, SNAP-25, LDLR, LPL, INSIG2, Resistin, 5HTR2C, MC4R) and clinical predictors (e.g. age gender, BMI at baseline, number of episodes, pretreatment, PANSS-scores) in a sample of 259 (n=138 for regression analyses) schizophrenic patients participating in different monotherapeutic trials of atypical antipsychotics (risperidone, olanzapine, quetiapine, amisulpride, aripiprazole) with up to six weeks of treatment. We used Univariate tests, regression analysis and Classification and Regression-Tree (CART)-analysis to determine relevant clinical and genetic predictors and their interactions. Results We found younger age, male gender and weight at baseline as strongest clinical predictors. APOA variants and the Resistin -420 C/G rs1862513 polymorphism were associated with weight gain in the overall patient sample. Heterocygotic GC-allele carriers (n=53) gained less weight (1 kg) compared to 2,2 kg in homocygotic G-allele carriers (n=76) ( p p =0.09). The Resistin -420 C/G rs1862513 polymorphism showed significant interaction in patients treated with risperidone ( p 0.0001) and amisulpride ( p =0.0006) in a model adjusted for all clinical predictors. CART-analyses support to some extend the relevance of the Resistin polymorphism. Discussion In this sample we found a polymorphism in the Resistin gene (-420 C/G rs1862513) to potentially contribute to AIWG. CART-analysis shows interactions of several clinical predictors and this polymorphism. Our approach of combining clinical and genetic predictors may help to identify subgroups of patients a priori of SGA treatment in order to reduce development of severe weight gain. Further investigations on larger samples are necessary to confirm our results.

Entacapone augmentation of antipsychotic treatment in schizophrenic patients with negative symptoms; a double-blind placebo-controlled study

Negative symptoms in schizophrenia are associated with decreased dopaminergic activity in the prefrontal cortex (PFC). It is hypothesized that increasing dopamine levels would alleviate negative symptoms. Termination of dopamine activity in the PFC is mainly via catechol-O-methyl tranferase (COMT) activity. Hence, inhibition of COMT activity with entacapone should reverse PFC dopaminergic transmission. To assess the efficacy of entacapone addition to antipsychotic treatment in patients with residual schizophrenia, we conducted a double-blind, randomised, placebo-controlled study for 12 wk of treatment with entacapone or placebo. Clinical measures (PANSS, CGI and QLS) were obtained at baseline and at weeks 4, 8 and 12 and cognitive functions were assessed by the RBANSS. Significant improvement over time in PANSS and QLS scores was observed in both groups. However, entacapone did not demonstrate a beneficial effect compared to placebo. Therefore, this study does not support a therapeutic role for entacapone in residual schizophrenia.

Indications for electroconvulsive treatment in schizophrenia: A systematic review

BackgroundElectroconvulsive therapy (ECT) is a medical treatment that is most effective for mood disorders (Bipolar Disorder and Major Depression). It has also been shown to be an effective treatment for schizophrenia accompanied by catatonia, extreme depression, mania and other affective components. ECT is currently under-used in many psychiatric settings due to its stigmatized perception by patients and mental health professionals. However, many unanswered questions remain regarding its role in the management of patients with schizophrenia. AimEvaluate the main indications of ECT in subjects suffering from schizophrenia. ObjectivesInvestigate the efficacy and the main indications of ECT in the treatment of schizophrenic patients, evaluate its effects in the short-term and the long-term, compare ECT treatment with pharmacotherapy, and assess the effects of treatment with ECT. MethodsA systematic review of the literature was conducted on the use of ECT for schizophrenia. Thirty one articles from peer-reviewed journals were identified, and the most relevant articles were selected for this review. ResultsThe most common indication for using ECT for schizophrenia patients was to augment pharmacotherapy, while the most common accompanying symptoms were, in order, catatonia, aggression and suicide. Catatonic patients responded significantly better to ECT than patients with any other subtype of schizophrenia. The combination of ECT with pharmacotherapy can be useful for drug-resistant patients. The use of an ECT-risperidone combination or ECT-clozapine combination in patients non-responsive to prior pharmacotherapy was found to be most effective. ConclusionsThis review indicates that ECT, combined with pharmacotherapy, may be a viable option for a selected group of patients with schizophrenia. In particular, the use of ECT is recommended for drug-resistant patients, for schizophrenic patients with catatonia, aggression or suicidal behavior, and when rapid global improvement and reduction of acute symptomatology are required.

Attenuated PLD1 association and signalling at the H452Y polymorphic form of the 5-HT2A receptor

The 5-HT2A receptor (5-HT2AR) is implicated in psychotropic changes within the central nervous system (CNS). A number of polymorphisms have been reported in the 5-HT2AR gene; one of these results in a non-synonymous change, H452Y, in the carboxy-terminal tail of the receptor protein. The minor allele (9% occurrence) has been statistically associated with CNS dysfunction such as impaired memory processing and resistance to neuroleptic treatment in schizophrenic patients. We investigated the impact of H452Y mutation of the 5-HT2AR expressed in COS7 cells on distinctly coupled intracellular signalling pathways from the receptor, focusing on the heterotrimeric G protein-independent phospholipase D (PLD) pathway, compared to the conventional Gq/11-linked phospholipase C (PLC) pathway. The H452Y mutation selectively attenuated PLD signalling, which as in the wild-type receptor, was mediated by a molecular complex involving PLD1 docked to the receptor's carboxy-terminal tail domain. Co-immunoprecipitation and GST-fusion protein experiments revealed that the H452Y mutation selectively reduced PLD1 binding to the receptor. Experiments with blocking peptides to mimic short sections of the 5-HT2AR tail sequence revealed that the peptide spanning residue 452 strongly reduced PLD but not PLC responses of the receptor. Similar observations were made when assessing both PLD responses and PLD-dependent cellular proliferation elicited by activation of 5-HT2ARs natively expressed in MCF-7 cells. Overall these findings indicate that the H452Y polymorphic variant of the 5-HT2AR displays selective disruption of its PLD signalling pathway. This may potentially play a role in the CNS dysfunction associated with the H452Y allele of the 5-HT2AR.

1748 – Electroconvulsive treatment in schizophrenia: A systematic review

Electroconvulsive therapy (ECT) is a medical treatment that is most effective for mood disorders.It has also been shown to be an effective form of treatment for schizophrenia. However, many unanswered questions remain regarding its role in the management of people with schizophrenia. Evaluate the main indications of ECT in schizophrenia patients. To investigate the efficacy of ECT in the treatment of schizophrenic patients, evaluating its effects in the short-term and the long-term, comparing ECT with pharmacotherapy, and assessing the effects of treatment and the main indications for use in patients with schizophrenia. A systematic review of the literature was conducted for ECT and schizophrenia. Forty-nine articles from peerreviewed journals were identified. The most common indication for using ECT for schizophrenia patients was to augment pharmacotherapy, while the most common accompanying symptoms were, in order, catatonia, aggression and suicide. Catatonic patients responded significantly better to ECT than patients with any other subtype of schizophrenia. The combination of ECT with pharmacotherapy can be useful for drug-resistant patients. The use of an ECT-risperidone combination or ECT-clozapine combination in patients non-responsive to prior pharmacotherapy was found to be most effective. ECT, combined with pharmacotherapy, may be a viable option for a selected group of people with schizophrenia. In particular, the use of ECT is recommended for drug-resistant patients, for schizophrenic patients with catatonia, aggression or suicidal behavior, and when rapid global improvement and reduction of acute symptomatology is desired.

1194 – Traumatic experiences and dissociative symptoms in schizophrenic inpatients

Introduction There is emerging evidences that presence of dissociative symptoms could be a significant co morbid condition in a proportion of schizophrenic patients with a history of traumatic events. Aim The purpose of this study is to analyze the effects of traumatic experiences and the intensity of co morbid dissociative symptoms in the course of schizophrenia. Method 80 inpatients diagnosed with schizophrenia according to DSM IV and being treated in acute psychiatry clinics at Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery were enrolled to the study. Socio- demographic Data Form, Traumatic Experiences Check List, Dissociative Experiences Scale (DES), Dissociative Disorder Interview Schedule were performed. Findings 39 of the patients (48.8%) were found to be exposed to traumatic events at least once in their childhood or adulthood. Significant positive correlation was found between the average DES scores and total number of traumas (r= 0,683; p Results The results of this investigation claim that the high scores of DES, independent of traumatic life experiences, may cause resistance to treatment in schizophrenic patients.

Pharmacokinetic–Pharmacodynamic Modeling of Severity Levels of Extrapyramidal Side Effects With Markov Elements

A major problem in the treatment of schizophrenic patients with current antipsychotic drugs, mainly acting as dopamine-2 receptor antagonists, is the occurrence of side effects such as extrapyramidal symptoms (EPS). Meta-analyses of summary data of EPS occurrence, and receptor occupancies inferred from mean plasma concentrations, have shown the incidence of EPS to rise when receptor occupancy is above ~80%. In this analysis, individual longitudinal EPS data from 2,630 patients participating in one of seven different trials and treated with haloperidol, paliperidone, ziprasidone, olanzapine, JNJ-37822681, or placebo were analyzed using a continuous time probability model with Markov elements. The developed pharmacokinetic–pharmacodynamic model describes the longitudinal changes of spontaneously reported EPS-related adverse events and their severity levels rated by clinicians. Individual steady-state concentrations and occupancy levels were found to be predictors for EPS. The results confirm 80% occupancy as a level of increased EPS occurrence rates, also at the individual level.

Inter-relationship of plasma markers of oxidative stress and thyroid hormones in schizophrenics

BackgroundThe relationship of oxidative stress to thyroid hormones has not been studied in the schizophrenics. The present study determined the status and interrelationship of plasma markers of oxidative stress, nitric oxide and thyroid hormones in thirty (17 males and 13 females) newly diagnosed patients with acute schizophrenia before initiation of chemotherapy. Twenty five (13 males and 12 females) mentally healthy individuals served as controls. Patients and controls with history of hard drugs (including alcohol and cigarette), pre-diagnosis medications (e.g. antiparkinsonian/antipsychotic drugs), chronic infections, liver disease and diabetes mellitus were excluded from the study. Plasma levels of total antioxidant potential (TAP), total plasma peroxides (TPP), nitric oxide (NO), malondialdehyde (MDA), thyroxine (T4), tri-iodothyronine (T3) and thyroid stimulating hormone (TSH) were determined in all participants using spectrophotometric and enzyme linked immunosorbent assay (ELISA) methods respectively. Oxidative stress index (OSI) was calculated as the percent ratio of total plasma peroxides and total antioxidant potential.FindingsSignificantly higher plasma levels of MDA (p < 0.01), TPP (p < 0.01), OSI (p < 0.01), T3 (p < 0.01) and T4 (p < 0.05) were observed in schizophrenics when compared with the controls. The mean levels of TAP, NO and TSH were significantly lower in schizophrenics (p < 0.01) when compared with the controls. The result shows that T3 values correlate significantly with MDA (p < 0.05) and TPP (p < 0.01) in schizophrenics.ConclusionsHigher level of TPP may enhance thyroid hormogenesis in schizophrenics. Adjuvant antioxidant therapy may be a novel approach in the treatment of schizophrenic patients.

PRACTICES OF ANTIPSYCHOTIC POLYPHARMACY IN SCHIZOPHRENIA: A REVIEW

With an increase in the new generation of antipsychotic drugs and resulting antipsychotic polypharmacy, treatment of schizophrenic patients has again come into the daily agenda. In spite of the annual increase of these new drugs in recent years no expected benefit in the treatment of patients has been observed. A lack of alternative treatments of schizophrenia and the increase of polypharmaceutical approaches to treatment have led to clinicians feeling helpless; especially as schizophrenia is known to be treatment resistant over time and is often subject to poor prognosis. According to the treatment algorhythm the application of antipsychotic polypharmacy can be the choice of treatment for treatment-resistant patients but only following a program of sufficient monotherapy. For a short period, antipsychotic polypharmacy can ease the transition from the use of one antipsychotic to that of another. However it is thought that this approach is often over used in clinical experiments and observations. The frequency of the antipsychotic polypharmacy use in schizophrenia has been discussed in this review. Key words: atypical antipsychotics, combination treatment, polypharmacy, schizophrenia

Forms of antipsychotic therapy: improved individual outcomes under personalised treatment of schizophrenia focused on depression.

Depressive symptoms are common in schizophrenia and they can occur during any phase of the disorder. Early diagnosis, adequate differential diagnosis and promptly initiated interventions have been shown to reduce further deterioration of illness and to improve patients’ quality of life. Common psychiatric rating scales for early detection of depressive symptoms in schizophrenia are Calgary Depression Scale for Schizophrenia and Hamilton Depression Rating Scale, but the most appropriate assessment instrument today regarding this topic is Calgary Depression Scale for Schizophrenia. Treatment of depression in schizophrenia consists of a combination of pharmacologic and psychosocial approach. Atypical antipsychotics have advantages over typical in reducing depressive symptoms in the context of schizophrenia. Most of the studies referred that clozapine, olanzapine, quetiapine and risperidone have an antidepressant spectrum of activity in patients with schizophrenia. Antidepressant augmentation of antipsychotic treatment in schizophrenic patients with depressive symptoms improves depressive symptomatology, particularly SSRI and SNRI augmentation.

Effects of haloperidol on cognition in schizophrenia patients depend on baseline performance: A saccadic eye movement study

Schizophrenic patients are heterogeneous with respect to voluntary eye movement performance, with some showing impairment (e.g., high antisaccade error rates) and others having intact performance. To investigate how this heterogeneity may correlate with different cognitive outcomes after treatment, we used a prosaccade and antisaccade task to investigate the effects of haloperidol in schizophrenic subjects at three time points: baseline (before medication), 3-5 days post-medication, and 12-14 days post-medication. We also investigated changes on the Stroop Task and the Positive and Negative Syndrome Scale (PANSS) in these same subjects. Results were compared to matched controls. When considered as a single patient group, haloperidol had no effects across sessions on reflexive and voluntary saccadic eye movements of schizophrenic patients. In contrast, the performance of the Control group improved slightly but significantly across sessions on the voluntary eye movement task. When each subject was considered separately, interestingly, for schizophrenic patients change in voluntary eye movement performance across sessions depended on the baseline performance in a non-monotonic manner. That is, there was maximal worsening of voluntary eye movement performance at an intermediate level of baseline performance and the worsening decreased on either side of this intermediate baseline level. When patients were divided into categorical subgroups (nonimpaired and impaired), consistent with the non-monotonic relationship, haloperidol worsened voluntary eye movement performance in the nonimpaired patients and improved performance in the impaired patients. These results were only partially reflected in the Stroop Test. Both patient subgroups showed clinically significant improvement over time as measured by the PANSS. These findings suggest that haloperidol has different effects on cognitive performance in impaired and nonimpaired schizophrenic patients that are not evident in clinical ratings based on the PANSS. Given that good cognitive function is important for long-term prognosis and that there is heterogeneity in schizophrenia, these findings are critical for optimal evaluation and treatment of schizophrenic patients.

Dopamine receptor changes after long-term haloperidol treatment in rats.

Abstract Tardive dyskinesia is a neurological syndrome associated with prolonged neuroleptic treatment of schizophrenic patients (Crane 1968; Faurbye 1970; Faurbye et al 1964). It has been suggested that tardive dyskinesia results from chemical denervation of central dopamine neurons and subsequent development of supersensitivity of the postsynaptic receptor (Rubovits &amp; Klawans 1972). Experiments based on animal models of tardive dyskinesia support this hypothesis. Chronic neuroleptic treatment increases postsynaptic dopamine receptor sensitivity when measured either behaviourally or biochemically (Christensen et al 1976; Klawans &amp; Rubovits 1972; Moore &amp; Thornburg 1975; Sayers et al 1975; Tarsy &amp; Baldessarini 1974; Von Voigtlander et al 1975). The molecular basis for this behavioural change has been reported to be an increase in the number of receptor sites with no change in their affinity as measured by 3H-neuroleptic binding to striatal membrane homogenates (Burt et al 1977; Klawans et al 1977; Muller &amp; Seeman 1977). Previous biochemical reports of the development of model tardive dyskinesia after neuroleptic treatment of animals have generally used treatment periods of 3 weeks or less (Burt et al 1977; Klawans et al 1977; Muller &amp; Seeman 1977). Only one report treated animals for longer periods (Clow et al 1978). In the present experiments we studied the kinetics of [3H]spiroperidol binding to rat caudate nucleus homogenates after 3 and 10 weeks of haloperidol treatment.

Relapse according to antipsychotic treatment in schizophrenic patients: a propensity-adjusted analysis

ObjectiveTo compare the rate of relapse as a function of antipsychotic treatment (monotherapy vs. polypharmacy) in schizophrenic patients over a 2-year period.MethodsUsing data from a multicenter cohort study conducted in France, we performed a propensity-adjusted analysis to examine the association between the rate of relapse over a 2-year period and antipsychotic treatment (monotherapy vs. polypharmacy).ResultsOur sample consisted in 183 patients; 50 patients (27.3%) had at least one period of relapse and 133 had no relapse (72.7%). Thirty-eight (37.7) percent of the patients received polypharmacy. The most severely ill patients were given polypharmacy: the age at onset of illness was lower in the polypharmacy group (p = 0.03). Patients that received polypharmacy also presented a higher general psychopathology PANSS subscore (p = 0.04) but no statistically significant difference was found in the PANSS total score or the PANSS positive or negative subscales. These patients were more likely to be given prescriptions for sedative drugs (p < 0.01) and antidepressant medications (p = 0.03). Relapse was found in 23.7% of patients given monotherapy and 33.3% given polypharmacy (p = 0.16). After stratification according to quintiles of the propensity score, which eliminated all significant differences for baseline characteristics, antipsychotic polypharmacy was not statistically associated with an increase of relapse: HR = 1.686 (0.812; 2.505).ConclusionAfter propensity score adjustment, antipsychotic polypharmacy is not statistically associated to an increase of relapse. Future randomised studies are needed to assess the impact of antipsychotic polypharmacy in schizophrenia.

4-Aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators

Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent activity and desired drug-like properties. Compound 2b was further characterized as a PAM using several in vitro experiments, and produced robust activity in several preclinical animal models.

Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients

The HOMER 1 protein plays a crucial role in mediating glutamatergic neurotransmission. It has previously shown to be a candidate gene for etiology and pathophysiology of different psychiatric diseases such as schizophrenia. To identify genes involved in response to antipsychotics, subgroups of animals were treated with haloperidol (1 mg/kg, n = 11) or saline ( n = 12) for one week. By analyzing microarray data, we replicated the observed increase of Homer 1 gene expression. Furthermore, we genotyped 267 schizophrenic patients, who were treated monotherapeutically with different antipsychotics within randomized-controlled trials. Psychopathology was measured weekly using the PANSS for a minimum of four and a maximum of twelve weeks. Correlations between PANSS subscale scores at baseline and PANSS improvement scores after four weeks of treatment and genotypes were calculated by using a linear model for all investigated SNP’s. We found an association between two HOMER 1 polymorphisms (rs2290639 and rs4704560) and different PANSS subscales at baseline. Furthermore all seven investigated polymorphisms were found to be associated with therapy response in terms of a significant correlation with different PANSS improvement subscores after four weeks of antipsychotic treatment. Most significant associations have been shown between the rs2290639 HOMER 1 polymorphism and PANSS subscales both at baseline conditions and after four weeks of antipsychotic treatment. This is the first study which shows an association between HOMER 1 polymorphisms and psychopathology data at baseline and therapy response in a clinical sample of schizophrenic patients. Thus, these data might further help in detecting differential therapy response in individuals with schizophrenia.

Induction of subcutaneous adipose proliferation by olanzapine in rodents

Weight gain induced by atypical antipsychotics causes a serious health concern in the treatment of schizophrenic patients. In the present study chronic treatment of female Wistar rats with olanzapine caused weight gain, but limited effect on food intake. A dramatic drug-induced morphological change of the subcutaneous adipose tissue was observed, i.e. development of a pinkish coloration with the appearance of a “fish egg”-like texture. Histological examination revealed a massive increase in the proliferation of undifferentiated adipocytes. Such proliferation was detected as early as the third day after olanzapine treatment. The changes progressed in a time- and dose-dependent manner. The proliferation of adipose tissue was detected in rats treated with olanzapine independent of increases in weight gain. Protein profiles of the adipose tissue were also altered by olanzapine. These results suggest that olanzapine-induced weight gain may be not solely due to an effect on behavioural satiety. The potential involvement of adipose neuronal input and proliferation are discussed.

The need for efficient long-term neuroleptic treatment in schizophrenic patients and the place of long acting injectable antipsychotics

Schizophrenia is a chronic disorder with a high risk of poor outcome in terms of symptoms and social functioning and possibly also progressive brain alterations. The relapse rate is high and each relapse can induce further aggravations. Thus, long-term treatment with the highest degree of effectiveness should be provided to the patients. Amongst others, the suitable drug for the individual patient has to be selected as well as the high risk of non-compliance to be carefully considered. All the available evidence from randomised controlled studies indicates that antipsychotic medications substantially reduce the risk of relapse. The lowest dose should be chosen at which preferably no side effects occur, the risk of relapse seems to be optimally reduced and, if symptoms are still present, suppression of these is optimised. Side effects have to be assessed and, if necessary, pharmacotherapy has to be adjusted. Despite several methodological design issues, second-generation antipsychotics have proven superior efficacy in preventing relapse to FGAs. Available studies of the specific agents supply evidence for periods of up to 2 years. Due to the decreased risk of EPS, especially tardive dyskinesia and the superior efficacy in improving negative, cognitive and depressive symptoms, second-generation antipsychotics should be preferred in long-term treatment. Given all the known problems in compliance and discontinuation, which were underlined in recent years by the CATIE and the EUFEST study, depot preparations should be considered for optimum effectiveness in preventing relapse. Altogether, randomised, control-group studies to determine the long-term advantages of depot preparations of atypical neuroleptics compared to depots of typical neuroleptics are still lacking. However, the huge database for long acting injectable risperidone is so convincing in terms of efficacy, tolerability and effectiveness that its special place in the long-term treatment of schizophrenia becomes obvious. The target strategy in long-term treatment of schizophrenia should be a combination of long-term antipsychotic treatment and psycho- and sociotherapeutic procedures, so that the relapse rate is further reduced and the course of disease can be further improved.

P03-45 - Psychosocial functioning of schizophrenic patients in post-acute treatment with long-acting injectable risperidone in ambulatory care

IntroductionImprovement of social and occupational functioning is a major goal in the treatment of schizophrenic patients and therefore may improve reintegration of patients and their ability to lead an independent life.MethodsNon-interventional, 52-week study (RIS-SCH-4091) in schizophrenic patients after treatment of exacerbation or first manifestation of schizophrenia (ICD-10 F20.x; duration of disease ≤10 years) with long-acting injectable risperidone (RLAI) in monotherapy. Presented here is the assessment of the treatment based on the Clinical Global Impression (CGI), the Global Assessment of Functioning (GAF), and skills assessing the ability of patients for reintegration as quantified by the short version of the International Classification of Functioning, Disability and Health for Mental Disorders (Mini ICF-APP).ResultsInterim-analysis after 12 months of 75 patients (ITT, m 64%; 32.7±9.1 years; N=88 safety set). Duration of observation was 278.8±119.3 days. GAF total scores improved significantly (24.4±23.7); 76.0% of the patients improved in CGI-C. Mini-ICF-APP total scores improved significantly from 1.96±0.68 to 1.18±0.94 at final observation. All Mini-ICF-APP sub-items improved significantly, particularly within: participation in public roles, non-occupational activities, self maintenance, competency, flexibility, family relations. 119 adverse events (AEs; 28 serious AEs) were reported in 47 patients. Most common AEs at least possibly related to RLAI were lack of effectiveness 8.0%, weight increase 8.0%, psychotic disorder 5.7%, anxiety 3.4%, EPS 3.4%.ConclusionsResults indicate that treatment with RLAI may improve global functioning of patients by reducing typical disorder of functioning, capacity and participation. Treatment with RLAI may help patients to reintegrate into social and occupational environments.

S28-04 - Pharmacogenetics of extrapyramidal motor side effects in the treatment of schizophrenia

IntroductionSince the introduction of second generation antipsychotics (SGA) extrapyramidal-motor symptoms (EPS) have become a lesser problem in the treatment of schizophrenic patients. Yet, some SGAs display these adverse events and first generation antipsychotics are still widely used. Several genetic polymorphisms have been found to be associated with the occurance of EPS.ObjectivesIn this study we tried to identify genes related to EPS from an animal model and then replicated the findings in schizophrenic patients.AimsTo identify new genes and show their relevance in the treatment of schizophrenic patients.MethodsRats were treated with haloperidol or saline and differential gene expression was assessed by using microarrays. We genotyped 285 schizophrenic patients for candidate genes and differentially expressed genes derived from the animal model. All patients were treated monotherapeutically with different antipsychotics within randomized controlled trials. EPS were assessed weekly using the ESRS and BAS. We used a linear model (ANCOVA) with PANSS total at baseline, type of medication and premedication as covariates for all investigated SNP's.ResultsWe found several SNPs to be associated with the occurance of EPS. The best results were obtained for SNPs within the genes of Phospholipase C epsilon 1 (PLCe1), Methionine Sulfoxide Reductase B3 (MSRB3), Chloride Intracellular Channel 6 (CLIC6), Prolactin Receptor (PRLR) and Dopamine Receptor D4 (DRD4). Effect sizes were between 1.7 and 4.9.ConclusionsWe could replicate some findings of the literature and identified four new genes possibly related to EPS. Some of these genes were recently related to schizophrenia.

No influence of FAT polymorphisms in response to aripiprazole

The aim of this study was to investigate possible influences of a set of markers in the FAT gene (rs2306987, rs2306990, rs2637777 and rs2304865) on efficacy and tolerability of aripiprazole in the treatment of schizophrenic patients. Efficacy was assessed at baseline and weeks 1, 2, 4, 6, 8 and 12 using the Clinical Global Impression Severity and Improvement scale (CGI-S; CGI-I), the Brief Psychiatric Rating Scale and the Schedule for the Assessment of Negative Symptoms scale. Side effects were evaluated by means of the Simpson-Angus Scale for Extrapyramidal Symptoms, the Barnes Akathisia Scale and the Abnormal Involuntary Movement Scale. Multivariate analyses were employed to test possible influences of single nucleotide polymorphisms on clinical and safety variables. Analysis of haplotypes was also performed. No relevant association between FAT variants and clinical or safety scores was observed. Haplotype analysis did not reveal any significant association with clinical and safety scores at any time as well. Our data suggest no association between investigated alleles and genotypes in FAT and response to aripiprazole. However, because several limitations characterize the present study, further investigations on larger studies are required.