What happens with schizophrenia patients after their discharge from hospital? Results on outcome and treatment from a "real-world" 2-year follow-up trial.

Aim of the study was to examine the course of schizophrenia patients within 2 years after discharge. Within a multicenter study of the German Competence Network on Schizophrenia, patients suffering from a schizophrenia spectrum disorder were examined regarding their psychopathological improvement, tolerability, and the treatment regime applied during hospitalization and a 2-year follow-up period. Response, remission, the level of everyday functioning, and relapse were furthermore evaluated during the follow-up period using established definitions for these outcome domains. The psychopharmacological treatment was specifically evaluated in terms of a potential association with relapse. 149 patients were available for analysis, with 65% of the patients being in response, 52% in symptomatic remission, and 64% having a satisfiable everyday functioning 2 years after their discharge from hospital. Despite these favorable outcome rates, 63% of the patients suffered from a relapse within the 2-year follow-up period with 86% of these patients being rehospitalized. Discharge non-responder and non-remitter were twice as likely to relapse during follow-up. A significant decrease of side-effects was observed with negligible rates of extrapyramidal side-effects, sedation, and weight gain during follow-up. Patients receiving treatment with atypical antipsychotics were found to have the lowest risk to relapse (p < 0.0001). The results highlight the natural and unsteady course of schizophrenia in most patients underlining the need to develop more specific treatment strategies ensuring ongoing stability and preventing relapse.

Remission in schizophrenia - What are we measuring? Comparing the consensus remission criteria to a CGI-based definition of remission and to remission in major depression.

BACKGROUND: Despite being recommended for use in clinical trials, the consensus remission criteria were found to leave patients with persisting symptoms, relevant areas of functional impairment and a decreased sense of wellbeing. Therefore, to evaluate the appropriateness of the schizophrenia consensus criteria, a definition of remission based on the Clinical Global Impression Scale (CGI) was developed and remitter subgroups were compared. METHODS: 239 patients with a schizophrenia spectrum disorder were evaluated regarding their remission status after inpatient treatment. Remission in schizophrenia was defined according to the symptom-severity component of the consensus criteria by Andreasen et al. and a CGI based definition was calculated using sensitivity and specificity using receiver operating curves (asymptomatic remitter). Both remitter groups (schizophrenia consensus versus asymptomatic remitters) were compared regarding different clinical variables at discharge as well as the likelihood to relapse within a 1-year follow-up period. Both schizophrenia remitter subgroups were compared to remitters in major depression as a reference value. RESULTS: Following the consensus criteria, 63% of the schizophrenia patients were in remission compared to only 18% following the asymptomatic criterion. The schizophrenia consensus remitters were less likely to be concurrent treatment responders (p < 0.0001), had a significantly greater illness severity (p < 0.0001) and less functioning (p = 0.0358) as well as a significantly greater risk to relapse (p = 0.0174) compared to the schizophrenia asymptomatic remitters as well as the depressed remitters. CONCLUSION: It should be critically re-evaluated if the currently proposed consensus criteria are adequate to measure what is traditionally understood to be remission.

Add-on Antidepressants in the Naturalistic Treatment of Schizophrenia Spectrum Disorder - When, Who, and How?

The aim of this study was to evaluate antidepressant add-on treatment within the acute treatment of schizophrenia spectrum disorder patients. Antidepressant add-on was evaluated in 365 patients within a naturalistic multicenter study. Patients with/without antidepressant add-on were compared regarding clinical and treatment-related variables, response and remission, and remission of depressive and negative symptoms. The efficacy of antidepressant add-on treatment was furthermore analyzed applying marginal structure models. Twenty-three percent of the patients received antidepressant add-on for a mean duration of 50.28 (33.42) days. Patients with the diagnosis of a schizoaffective disorder, multiple illness episodes, and a longer duration of their illness as well as those with significantly fewer baseline positive symptoms, more negative and depressive symptoms, more side effects, and less subjective well-being were augmented with antidepressants. At discharge no significant effect of antidepressant add-on treatment was observed in terms of a 25% improvement (p=0.2623), a 50% improvement (p=0.3946), remission (p=0.0552), or remission of depressive (p=0.6336) and negative symptoms (p=0.8756). Also, when analyzing marginal structure models considering the diagnostic subgroups, no significant effect was found. Add-on with antidepressants is common. A final recommendation in terms of this strategy's efficacy cannot be given.

Validity of remission and recovery criteria for schizophrenia and major depression: comparison of the results of two one-year follow-up naturalistic studies.

The objective of the present study was the application and comparison of common remission and recovery criteria between patients with the diagnosis of schizophrenia and major depressive disorder (MDD) under inclusion of other outcome parameters. Patients with schizophrenia and MDD who were treated as inpatients at the beginning of the study were examined within two naturalistic follow-up trials from admission to discharge of an inpatient treatment period and the one-year follow-up assessment. PANSS criteria of the Remission in Schizophrenia Working Group (RSWG) for schizophrenia and HAMD criteria of the ACNP Task Force in MDD for depressive patients as well as the Clinical Global Impression-Severity Scale (CGI-S) were applied as symptomatic outcome measures additionally to functional outcome parameters. Data of 153 schizophrenia patients and 231 patients with a MDD episode have been included in the analysis. More depressive than schizophrenia patients reached a threshold score of ≤3 on the CGI-S, indicating symptomatic remission at discharge and at the one-year follow-up. In contrast similar proportions of patients reaching symptomatic remission at discharge from inpatient treatment and at the one-year follow-up in the schizophrenia and in the MDD group were found when disease-related consensus criteria (RSWG vs. ACNP Task Force) were used. Functional remission and recovery rates were significantly lower in schizophrenia than in depressive patients at the one-year follow-up visit. Common outcome criteria for remission and recovery in schizophrenia and major depression were not directly comparable. However, our results indicated a significantly poorer outcome in schizophrenia than in depressive patients according to terms of remission and recovery.

Are female daycare workers at greater risk of cytomegalovirus infection? A secondary data analysis of CMV seroprevalence between 2010 and 2013 in Hamburg, Germany.

BACKGROUND: Close contact with asymptomatic children younger than three years is a risk factor for a primary cytomegalovirus (CMV) infection. In pregnant women, such primary infection increases the risk of CMV-induced feto- or embryopathy. Daycare providers have therefore implemented working restrictions for pregnant daycare workers (DCWs) in accordance with legislation and guidelines for maternity protection. However, little is known about the infection risk for DCWs. We therefore compared the prevalence of CMV antibodies of pregnant DCWs to that of female blood donors (BDs). METHOD: In a secondary data analysis, the prevalence of anti-CMV IgG among pregnant DCWs (N=509) in daycare centers (DCCs) was compared to the prevalence of female first-time BDs (N=14,358) from the greater region of Hamburg, Germany. Data collection took place between 2010 and 2013. The influence of other risk factors such as age, pregnancies and place of residence was evaluated using logistic regression models. RESULTS: The prevalence of CMV antibodies in pregnant DCWs was higher than in female BDs (54.6 vs 41.5%; OR 1.6; 95%CI 1.3-1.9). The subgroup of BDs who had given birth to at least one child and who lived in the city of Hamburg (N=2,591) had a prevalence of CMV antibodies similar to the prevalence in pregnant DCWs (53.9 vs 54.6%; OR 0.9; 95%CI 0.8-1.2). Age, pregnancy history and living in the center of Hamburg were risk factors for CMV infections. CONCLUSION: The comparison of pregnant DCWs to the best-matching subgroup of female first-time BDs with past pregnancies and living in the city of Hamburg does not indicate an elevated risk of CMV infection among DCWs. However, as two secondary data sets from convenience samples were used, a more detailed investigation of the risk factors other than place of residence, age and maternity was not possible. Therefore, the CMV infection risk in DCWs should be further studied by taking into consideration the potential preventive effect of hygiene measures.

Challenging the understanding of significant improvement and outcome in schizophrenia - the concept of reliable and clinically significant change methods.

Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety-six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (= reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (= clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thresholds were applied to define the clinically significant change (40, 45 and 50 points). These changes were then compared to established outcome criteria such as response and remission. Seventy-nine of the 396 patients (20%) showed a reliable improvement of symptoms, whereas 70% improved without achieving a reliable change of their condition. Of the 79 patients achieving a reliable change during treatment 8-15% concurrently showed a clinically significant change depending on the respective PANSS threshold. In contrast, 56% of the patients achieved response and 60% were in remission at discharge when applying established outcome criteria. Our results showed that a rather small number of schizophrenia patients were found to reliably change during inpatient treatment, with even less patients achieving a clinically significant change. The concept of reliable and clinically significant changes revealed to be a lot more stringent than today's established outcome criteria and should be critically evaluated regarding its use in schizophrenia patients.

What are residual symptoms in schizophrenia spectrum disorder? Clinical description and 1-year persistence within a naturalistic trial.

The aim of this study was to evaluate residual symptoms in patients achieving remission according to the consensus criteria and to analyze their potential influence on the patient's outcome one year after discharge. In total, 399 patients suffering from a schizophrenia spectrum disorder were evaluated within a naturalistic study. Remission status was examined using the consensus criteria. Residual symptoms were defined as any symptom present at the time-point of remission following analogous analyses performed in depressed patients. Therefore, a PANSS item with a symptom severity of >1 (= at least borderline mentally ill) was defined to be a residual symptom. Remitters with and without residual symptoms were compared regarding psychopathology, functioning and side effects. In total, 236 patients (59%) were remitters at discharge with 94% of them suffering from at least one residual symptom. The most common residual symptoms were blunted affect (49%), conceptual disorganization (42%) and social withdrawal (40%). A significant association was found between the presence of residual symptoms and the severity of side effects (p < 0.0001) and functioning (p = 0.0003) at discharge as well as between residual symptoms and the risk of relapse and chance of remission one year after discharge. Residual symptoms were highly prevalent in remitted schizophrenia inpatients following the suggested definition. Most residual symptoms were persistent baseline symptoms suggesting an ongoing illness severity. Also, the necessity to re-evaluate the consensus criteria questioning the status of remission in these patients is also pointed out.

Evaluating depressive symptoms in schizophrenia: a psychometric comparison of the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale.

BACKGROUND: The aim of this study was to compare two measures of depression in patients with schizophrenia and schizophrenia spectrum disorder, including patients with delusional and schizoaffective disorder, to conclude implications for their application. SAMPLING AND METHODS: A total of 278 patients were assessed using the Calgary Depression Scale for Schizophrenia (CDSS) and the Hamilton Depression Rating Scale (HAMD-17). The Positive and Negative Syndrome Scale (PANSS) was also applied. At admission and discharge, a principal component analysis was performed with each depression scale. The two depression rating scales were furthermore compared using correlation and regression analyses. RESULTS: Three factors were revealed for the CDSS and HAMD-17 factor component analysis. A very similar item loading was found for the CDSS at admission and discharge, whereas results of the loadings of the HAMD-17 items were less stable. The first two factors of the CDSS revealed correlations with positive, negative and general psychopathology. In contrast, multiple significant correlations were found for the HAMD-17 factors and the PANSS subscores. Multiple regression analyses demonstrated that the HAMD-17 accounted more for the positive and negative symptom domains than the CDSS. CONCLUSIONS: The present results suggest that compared to the HAMD-17, the CDSS is a more specific instrument to measure depressive symptoms in schizophrenia and schizophrenia spectrum disorder, especially in acutely ill patients.

Response trajectories in "real-world" naturalistically treated schizophrenia patients.

BACKGROUND: To date, research has identified distinct antipsychotic response trajectories yet focussing on data from randomized-controlled trials (RCTs). Therefore, the heterogeneity of response in "real-world" schizophrenia patients is still unknown. METHODS: Antipsychotic response was evaluated in 399 patients suffering from a schizophrenia spectrum disorder within a naturalistic multicenter study of the Competence Network on Schizophrenia using latent class regression. Baseline and illness-related variables were compared between the different trajectory classes as well as currently proposed outcome definitions (early improvement, response, remission) using univariate tests. In order to predict the trajectory group membership classification and regression tree analysis were furthermore performed. RESULTS: Five distinct trajectories of antipsychotic response were identified: Class 1 (15%) showing an early and considerable improvement, Class 2 (14%) incorporating patients with the greatest response to treatment, Class 3 (34%) again showing an early improvement to treatment yet with a slightly lower degree of improvement, Class 4 (22%) featuring patients gradually responding to treatment, and Class 5 (15%) with the poorest antipsychotic response. Fewer depressive symptoms at admission, better functioning, a shorter duration of illness and less previous hospitalizations were found to be significant predictors of good response. No considerable differences were found comparing the present results to the previous trajectory analyses deriving from RCTs. CONCLUSION: Our results underline the heterogeneous course of response independent of the study or treatment design suggesting that the diversity in schizophrenia response and outcome is determined primarily by different pathophysiological underpinnings.

One-year functional outcomes of naturalistically treated patients with schizophrenia.

Against the background of the growing evidence that the patient's functioning significantly influences the course and outcome of schizophrenia, the aims of this analysis were to examine what proportion of patients achieve functional outcome criteria after 1 year, and to identify clinical and sociodemographic predictive factors for functional remission. Patients with the diagnosis of schizophrenia who were treated as inpatients at the beginning of the study were examined within a naturalistic follow-up trial. The present study reports on the time frame from admission to discharge of an inpatient treatment period and the 1-year follow-up assessment. The Global Assessment of Functioning (GAF) Scale and Social and Occupational Functioning Assessment Scale (SOFAS) were evaluated with respect to functional outcome, whereas Positive and Negative Syndrome Scale (PANSS) scores were rated as psychopathological outcome measures. Functional remission thresholds were defined according to a GAF score of ≥61 points and a SOFAS score ≥61 points. Symptomatic remission criteria were applied according to the remission criteria of the Schizophrenia Working Group. The Strauss-Carpenter Prognostic Scale (SCPS), the Phillips Premorbid Adjustment Scale, medical history, sociodemographic and psychopathologic parameters were evaluated in order to find valuable predictors for functional remission. One year after discharge from inpatient treatment, 211 out of 474 patients were available for analysis according to both rating scales used to assess functional remission (GAF and SOFAS). Forty-seven percent of patients fulfilled criteria for functional remission (GAF and SOFAS) at discharge and 51% of patients at the 1-year follow-up visit. With regard to symptomatic remission criteria, the corresponding remitter rates were 61% of patients at discharge and 54% at the 1-year follow-up visit. Forty-two percent of patients fulfilled both remission criteria at discharge and 37% at the 1-year follow-up visit. A significant association was found between functional and symptomatic remission at discharge and at the 1-year follow-up visit. The strongest predictors for functional remission at the 1-year follow-up visit were: a higher SCPS total score at admission, a lower number of previous hospitalizations, a status of employment, lower scores in all PANSS subscales at discharge, a better premorbid social adjustment, the occurrence of a first psychotic episode, a younger age, a lower PANSS negative subscore at admission, a status of being an early responder, a shorter duration of inpatient treatment, a later age of onset, and female gender.

Predictors of relapse in the year after hospital discharge among patients with schizophrenia.

OBJECTIVE: Relapse and its predictors were examined among patients with schizophrenia in the year after hospital discharge. METHODS: The sample included 200 patients with schizophrenia participating in a German multicenter study. Relapse was defined as a worsening of psychopathological symptoms or rehospitalization in the year after hospital discharge. Predictors examined were variables related to course of illness and to response and remission at discharge. RESULTS: Fifty-two percent of participants had a relapse. Patients whose symptoms were not in remission at discharge were more likely to have a relapse, as were those who had more severe symptoms and more side effects at discharge. Those who experienced a relapse were less likely to be taking a second-generation antipsychotic at discharge, less likely to have a positive attitude toward treatment adherence, and less likely to be employed. CONCLUSIONS: The high rate of relapse among patients with schizophrenia highlights the need to improve current treatment strategies.

Persistent antinociception through repeated self-injury in patients with borderline personality disorder.

Patients with borderline personality disorder, mostly female, exhibit severe autoaggressive behavior, namely an intentionally performed, nonsuicidal self-injury and severe blunting of pain perception, the mechanism of which is hitherto not understood. Because the nociceptive system displays a high degree of plasticity, the aim of this study was to analyze the relationship of pain perception to self-injurious behavior. Pain perception of mechanical and chemical noxious stimuli was studied by quantitative sensory testing in 22 patients (15 female, 7 male) with borderline personality disorder (BPD) according to DSM-IV and 22 age- and gender-matched controls. BPD patients exhibited a significantly higher pain threshold to pinprick stimuli (2.7 times higher than healthy control subjects), and significantly lower pain ratings to mechanical (pinprick, -28%) and chemical (capsaicin, -38%) stimulation. Capsaicin-induced pain decayed significantly faster in BPD patients (τ=49 seconds) than in controls (τ=76 seconds). These alterations of pain perception were generally present in the female, but not in the male subgroup of BPD patients. Analysis of pain intensity vs unpleasantness suggested that primarily the unpleasantness aspect of the pain experience was reduced. Blunting of pain sensation was significantly predicted by the recency of self-injurious behavior (multiple r=0.58). In line with recent data, we suggest an excess of endogenous antinociception in BPD patients resulting from self-inflicted multiple injuries. This exaggerated pain control is conceived to operate via an uncoupling of the evaluative or emotional-affective from the sensory-discriminative dimension of pain.

Remission and recovery and their predictors in schizophrenia spectrum disorder: results from a 1-year follow-up naturalistic trial.

Remission and recovery are major outcome goals in schizophrenia yet their predictors have not been studied in detail. Therefore, 186 patients were examined regarding remission and recovery including their potential sociodemographic and clinical predictors 1 year after discharge. Remission was defined according to the consensus remission criteria and recovery following the definition by Liberman et al. (2002). Of the 186 patients 54% achieved remission and 26% recovery at the 1-year follow-up. The remission status at discharge was found to significantly influence remission and recovery at follow-up. A higher SOFAS score (P = 0.0002) as well as a positive attitude towards treatment at discharge (P = 0.0038) were identified to be significant predictors of remission at 1-year follow-up. Having a job (P = <0.0001) and being without pharmacological treatment at follow-up (P = 0.0113) were found to be significantly predictive of recovery. Our results underline the need to implement more specific treatment strategies to improve long-term outcome.

Influencing factors and predictors of early improvement in the acute treatment of schizophrenia and schizophrenia spectrum disorder.

BACKGROUND: To examine the influencing factors and predictors of early improvement in schizophrenia patients. METHODS: 370 patients suffering from a schizophrenia spectrum disorder were examined within a naturalistic multicenter study. Early improvement was defined as a ≥30% PANSS total score reduction within the first two treatment weeks, response as a ≥50% improvement of the PANSS total score from admission to discharge and remission according to the consensus remission criteria. Baseline and course-related variables such as positive, negative and depressive symptoms, side effects, functioning and subjective well-being were examined regarding their explanatory value for early improvement. RESULTS: 46% of the patients were identified to be early improvers. Of these, 77% became treatment responder at discharge and 74% achieved the consensus remission criteria. Amongst others, early improvers were significantly more often first-episode patients (p = 0.009), with a significantly shorter duration of current episode (p = 0.024) and a shorter duration of the illness (p = 0.0094). A higher PANSS positive subscore (p = 0.0089), a higher score in the Strauss-Carpenter-Prognostic Scale (SCPS) (p < 0.0001), less extrapyramidal side effects (p = 0.0004) at admission and the development of less extrapyramidal side effects within the first two treatment weeks (p = 0.0013) as well as a duration of current episode of ≤6 months (p = 0.0373) were identified to be significant predictors of early improvement. CONCLUSION: Early improvement is associated with less illness chronicity and seems to be independent of the type of antipsychotic and the antipsychotic dosage applied. The SCPS was found to be a valuable tool to detect early improvers already at the initiation of antipsychotic treatment.

Does clinical judgment of baseline severity and changes in psychopathology depend on the patient population? Results of a CGI and PANSS linking analysis in a naturalistic study.

BACKGROUND: Linking of the Clinical Global Impression (CGI) Scale and the Positive and Negative Syndrome Scale (PANSS) was performed within a naturalistic sample. Furthermore, these linking results were compared with those derived from randomized controlled trials to examine if the baseline severity might influence the linking results. METHODS: Biweekly PANSS and CGI ratings were performed from admission to discharge in 398 schizophrenia patients treated within a naturalistic study. Equipercentile linking was performed using the statistical program, R 2.8.1. To evaluate how the naturalistic study design would influence linkage results, a so-called study sample was computed with patients of the naturalistic study fulfilling common inclusion criteria of randomized controlled trials (n = 199). Patients not fulfilling these criteria (less ill sample) and those fulfilling the criteria (study sample) were compared using confidence intervals. RESULTS: We found a considerable difference between the linking of the CGI severity score and the PANSS total score comparing the less ill sample and the study sample. Being considered "mildly ill" at admission in the less ill sample corresponded to a PANSS total score of 47 points and to a PANSS total score of 67 points in the study sample. Considering the linking of the CGI improvement score and PANSS changes, similar results were found for CGI improvement ratings ranging from "very much improved" to "minimally improved". CONCLUSIONS: Despite considerable differences, a 50% PANSS reduction was found to correspond to a clinical rating of much improved, which seems to be a suitable definition for response in clinical drug trials.

Haplotypes of dopamine and serotonin transporter genes are associated with antisocial personality disorder in alcoholics.

INTRODUCTION: A different genetic background is postulated for alcoholics with early onset and with antisocial personality disorder (type 2 alcoholics) compared with those with late onset and without antisocial personality disorder (type 1 alcoholics). The dopamine transporter (DAT) and the serotonin transporter (SERT) are involved in endophenotypes that are associated with these subtypes. Our study was aimed at investigating whether distinct haplotypes, defined by polymorphisms associated with the expressions of DAT and SERT, were associated with subgroups of alcohol dependence. METHODS: Intron 8 variable number of tandem repeats (VNTR), exon 15 rs27072 and VNTR (DAT), promoter VNTR and rs25531, and intron 2 VNTR (SERT) were genotyped in a case-control sample comprising 360 alcoholics and 368 controls, and in a family-based sample of 65 trios, all of German origin. RESULTS: DAT: The haplogenotypes 6-A-10/6-G-10 and 5-G-9/5-G-9 were more often present in type 2 alcoholics as compared with type 1 alcoholics [odds ratio (OR): 2.8], and controls (OR: 5.8), respectively. The daily ethanol consumption was associated with haplogenotypes. SERT: haplotypes SA-10 (OR: 2.3) and LG-12 (OR: 2.5) were more often present in type 2 alcoholics compared with controls. Haplotype LA-10 was less often present in type 2 alcoholics (OR: 0.5), and was more often transmitted, in families, to the affected offspring (transmission disequilibrium test: OR: 5.2; family-based association test: Z: 1.9). The haplotype LA-12 was significantly undertransmitted to affected offspring in the whole group (transmission disequilibrium test: OR: 0.216; family-based association test: Z: -2.2). A gene by environment interaction was observed with respect to the time course of the depression score after alcohol withdrawal and with respect to the positive family history of alcohol dependence. CONCLUSION: Haplotype analysis, sub-grouping with respect to more homogeneous endophenotypes, and inclusion of quantifiable characteristics are sensible strategies to untangle the genetic background of such a complex disorder like alcohol dependence.

Quality of life and subjective well-being in schizophrenia and schizophrenia spectrum disorders: valid predictors of symptomatic response and remission?

OBJECTIVES: To examine quality of life and subjective well-being as predictors of symptomatic treatment outcome. METHODS: Biweekly PANSS ratings were performed in 285 inpatients with schizophrenia spectrum disorders within a multicenter trial by the German Research Network on Schizophrenia. Quality of life and subjective well-being were assessed using the Medical Outcomes Study-Short Form 36-Item Health Survey (SF-36), the Subjective Well-being Under Neuroleptic Treatment Scale (SWN-K) and the Adjective Mood Scale (AMS). Response was defined as an initial 20% PANSS total score reduction and remission according to the consensus criteria. Correlation analysis, logistic regression and CART-analysis were performed. RESULTS: In total, 81% of the sample achieved symptom response and 48% symptom remission. The statistical analyses revealed early improvement within the first two treatment weeks in the SWN-K scale to be a significant predictor for symptomatic response. Concerning symptomatic remission the SF-36 and SWN-K baseline scores as well as SWN-K early improvement showed significant predictive value. CONCLUSIONS: These results highlight the importance of the patient's self-perception and especially of early improvement of quality of life and subjective well-being for symptomatic treatment outcome.

Serotonin transporter promoter polymorphism and dopaminergic sensitivity in alcoholics.

The central serotonin (5-HT) system plays an important role in the rewarding and addictive properties of alcohol by a direct activation of the mesolimbic dopamine (DA) system. An insertion/deletion (L/S) promoter polymorphism (5-HTTLPR) of the 5-HT transporter (5-HHT) gene (SLC6A4) has been shown to influence transcriptional activity. It is predicted that reduced transynaptic 5-HT neurotransmission in alcoholics with the L/L genotype of 5-HTTLPR would result in a change in DA function compared to the S/S genotype. Thus the present study has tested whether dopaminergic sensitivity is influenced by the 5-HTTLPR genotype. Dopaminergic sensitivity, 5-HTTLPR genotype and smoking status were assessed in 121 alcoholics. Dopaminergic sensitivity as an indicator of the functional state of the dopaminergic system was measured by the amount of growth hormone (GH) secretion after subcutaneous administration of apomorphine (APO, 0.01 mg/kg). 5-HTTLPR genotype was significantly associated with dopaminergic sensitivity (P = 0.004) explaining 9.2% of the variance of GH response. Subjects homozygous for the L allele (with high 5-HTT expression) showed the lowest GH response, whereas those homozygous for the S allele (with low 5-HTT expression) showed the highest GH response (this was intermediate in heterozygous participants). Furthermore smoking was associated with a significantly reduced GH response (P = 0.006). Our findings indicate that the postsynaptic dopaminergic sensitivity is influenced by the 5-HTTLPR genotype. It is hypothesized that the reduction of sensitivity of the central DA receptors in alcoholics with the L/L genotype might be due to their higher vulnerability to the neurotoxic effects of chronic alcohol consumption than the S carriers.

Association of the dopamine D2 receptor gene with alcohol dependence: haplotypes and subgroups of alcoholics as key factors for understanding receptor function.

OBJECTIVES: The dopamine D2 receptor (DRD2) plays an important role in the reinforcing and motivating effects of ethanol. Several polymorphisms have been reported to affect receptor expression. The amount of DRD2, expressed in a given individual, is the result of the expression of both alleles, each representing a distinct haplotype. We examined the hypothesis that haplotypes composed of polymorphisms, associated with reduced receptor expression, are more frequent in alcoholics compared with healthy individuals. METHODS: The polymorphisms -141ins/del, C957T, A1385G, and TaqlA were genotyped in a case-control sample comprising 360 alcoholics and 368 controls, and in a family-based sample of 65 trios. To investigate more homogenous groups, we constructed two subgroups with respect to age at onset and antisocial personality disorder. In addition, a subgroup with positive family history of alcoholism was investigated. RESULTS: The haplotypes I-C-G-A2 and I-C-A-A1 occurred with a higher frequency in alcoholics [P=0.026, odds ratio (OR): 1.340; P=0.010, OR: 1.521, respectively]. The rare haplotype I-C-A-A2 occurred less often in alcoholics (P=0.010, OR: 0.507), and was also less often transmitted from parents to their affected offspring (1 vs.7). Among the subgroups, I-C-G-A2 and I-C-A-A1 had a higher frequency in Cloninger 1 alcoholics (P=0.083 and 0.001, OR: 1.917, respectively) and in alcoholics with a positive family history (P=0.031, OR: 1.478; P=0.073, respectively). Cloninger 2 alcoholics had a higher frequency of the rare haplotype D-T-A-A2 (P<0.001, OR: 4.614) always compared with controls. In patients with positive family history haplotype I-C-A-A2 (P=0.004, OR: 0.209), and in Cloninger 1 alcoholics haplotype I-T-A-A1 (P=0.045 OR: 0.460) were less often present. CONCLUSION: We confirmed the hypothesis that haplotypes, which are supposed to induce a low DRD2 expression, are associated with alcohol dependence. Furthermore, supposedly high-expressing haplotypes weakened or neutralized the action of low-expressing haplotypes.

Attitude towards adherence in patients with schizophrenia at discharge.

BACKGROUND: Purpose of the present study was to assess the attitude towards adherence at discharge and to verify its predictability using anamnestic and sociodemographic variables, factors influencing clinical treatment as well as the medical treatment applied. METHODS: Attitude towards adherence was evaluated in 369 inpatients with schizophrenic spectrum disorders within a naturalistic multicenter trial using the Compliance Rating Scale (CRS) by Kemp. Biweekly ratings of the PANSS, UKU and the Subjective Well-being under Neuroleptic Treatment Scale (SWN-K) were applied. Logistic regression and CART analyses were used to determine significant predictor variables for the attitude towards adherence at discharge. RESULTS: Sixty-seven percent of the patients were rated to have an attitude of active participation and moderate participation (=positive attitude towards adherence) and 33% of the patients to have an attitude of passive acceptance, occasional or permanent reluctance towards treatment as well as refusing treatment (=negative attitude towards adherence). A significant correlation was found between patients with a positive attitude towards adherence and course of all PANSS subscales. Statistical analyses revealed a reduction in PANSS general psychopathology subscore, employment status, greater illness insight and treatment with atypical antipsychotics to be significantly predictive for a positive attitude towards adherence at discharge. CONCLUSIONS: The importance of an adequate antipsychotic treatment as a precondition for a favourable adherence attitude and the need to incorporate adherence-focused psychotherapy and psychoeducation into daily clinical practice are highlighted.