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1.
Front Psychiatry ; 15: 1333711, 2024.
Article En | MEDLINE | ID: mdl-38356912

Introduction: In this study we assessed the contribution of psychopathology, including the two domains of negative symptoms (motivational deficit and expressive deficit), processing speed as an index of neurocognition, and emotion recognition, as an index of social cognition, to poor functional outcomes in people with schizophrenia. Methods: The Positive and Negative Syndrome Scale was used to evaluate positive symptoms and disorganization and the Brief Negative Symptom Scale to assess negative symptoms. The Symbol Coding and the Trail Making Test A and B were used to rate processing speed and the Facial Emotion Identification Test to assess emotion recognition. Functional outcome was assessed with the Personal and Social Performance Scale (PSP). Regression analyses were performed to identify predictors of functional outcome. Mediation analyses was used to investigate whether social cognition and negative symptom domains fully or partially mediated the impact of processing speed on functional outcome. Results: One hundred and fifty subjects from 8 different European centers were recruited. Our data showed that the expressive deficit predicted global functioning and together with motivational deficit fully mediated the effects of neurocognition on it. Motivational deficit was a predictor of personal and social functioning and fully mediated neurocognitive impairment effects on the same outcome. Both motivational deficit and neurocognitive impairment predicted socially useful activities, and the emotion recognition domain of social cognition partially mediated the impact of neurocognitive deficits on this outcome. Conclusions: Our results indicate that pathways to functional outcomes are specific for different domains of real-life functioning and that negative symptoms and social cognition mediate the impact of neurocognitive deficits on different domains of functioning. Our results suggest that both negative symptoms and social cognition should be targeted by psychosocial interventions to enhance the functional impact of neurocognitive remediation.

2.
Front Psychiatry ; 13: 826465, 2022.
Article En | MEDLINE | ID: mdl-35173641

BACKGROUND: Negative symptoms are usually evaluated with scales based on observer ratings and up to now self-assessments have been overlooked. The aim of this paper was to validate the Self-evaluation of Negative Symptoms (SNS) in a large European sample coming from 12 countries. We wanted to demonstrate: (1) good convergent and divergent validities; (2) relationships between SNS scores and patients' functional outcome; (3) the capacity of the SNS compared to the Brief Negative Symptom Scale (BNSS) to detect negative symptoms; and (4) a five-domain construct in relation to the 5 consensus domains (social withdrawal, anhedonia, alogia, avolition, blunted affect) as the best latent structure of SNS. METHODS: Two hundred forty-five subjects with a DSM-IV diagnosis of schizophrenia completed the SNS, the Positive and Negative Syndrome Scale (PANSS), the BNSS, the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Spearman's Rho correlations, confirmatory factor analysis investigating 4 models of the latent structure of SNS and stepwise multiple regression were performed. RESULTS: Significant positive correlations were observed between the total score of the SNS and the total scores of the PANSS negative subscale (r = 0.37; P < 0.0001) and the BNSS (r = 0.43; p < 0.0001). SNS scores did not correlate with the level of insight, parkinsonism, or the total score of the PANSS positive subscale. A positive correlation was found between SNS and CDSS (r = 0.35; p < 0.0001). Among the 5 SNS subscores, only avolition subscores entered the regression equation explaining a lower functional outcome. The 1-factor and 2-factor models provided poor fit, while the 5-factor model and the hierarchical model provided the best fit, with a small advantage of the 5-factor model. The frequency of each negative dimension was systematically higher using the BNSS and the SNS vs. the PANSS and was higher for alogia and avolition using SNS vs. BNSS. CONCLUSION: In a large European multicentric sample, this study demonstrated that the SNS has: (1) good psychometric properties with good convergent and divergent validities; (2) a five-factor latent structure; (3) an association with patients' functional outcome; and (4) the capacity to identify subjects with negative symptoms that is close to the BNSS and superior to the PANSS negative subscale.

3.
Eur Neuropsychopharmacol ; 29(8): 947-959, 2019 08.
Article En | MEDLINE | ID: mdl-31255394

Negative symptoms represent an unmet need of treatment in schizophrenia. Although a consensus exists on negative symptom construct, and second generation assessment instruments reflecting the consensus are available, studies still rely upon old assessment instruments, that do not reflect recent conceptualizations and might limit progress in the search for effective treatments. This is often the case in the European context, where one of the challenges encountered in designing large studies is the availability of validated instruments in the many languages of the continent. To address this challenge and promote sound research on negative symptoms in Europe, the ECNP Schizophrenia Network coordinated a large multicenter, multinational validation study of the Brief Negative Symptom Scale (BNSS). Clinically-stable subjects with schizophrenia (SCZ, N = 249) were recruited from 10 European Countries. Apart from BNSS, subjects were administered the Positive and Negative Syndrome Scale (PANSS) and standardized instruments for depression, extrapyramidal symptoms and psychosocial functioning. Results showed an excellent internal consistency, convergent and discriminant validity of BNSS and replicated a 5 factor-model. A larger number of subjects with predominant negative symptoms, i.e. the target population for clinical trials, was identified by using the BNSS compared to the PANSS. Regression analysis showed that BNSS-avolition, a key negative symptom poorly assessed by PANSS, explained 23.9% of psychosocial functioning, while no combination of the PANSS core negative symptoms showed the same impact on functioning. The study demonstrated that BNSS has substantial advantages with respect to PANSS for the identification of the avolition domain and subjects with predominant negative symptoms.


Psychiatric Status Rating Scales , Schizophrenia/diagnosis , Adult , Europe , Female , Humans , Male , Schizophrenic Psychology
4.
Schizophr Res ; 172(1-3): 145-51, 2016 Apr.
Article En | MEDLINE | ID: mdl-26922655

BACKGROUND: This study had two aims: to describe patients suffering from first-episode schizophrenia who had stopped taking any antipsychotic medication, and to gain information on the predictors of successful discontinuation. METHODS: We investigated data from the European First Episode Schizophrenia Trial (EUFEST). From the 325 patients included, 15.7% discontinued all antipsychotic medication. In a first analysis, clinical and sociodemographical predictors of discontinuing any antipsychotic medication were identified, using Cox regression. In the second analysis, logistic regression was used to determine variables associated with those patients who had stopped taking antipsychotic medication and had a favourable outcome, i.e., successful discontinuation. A good outcome was defined as a) having had no relapse within the whole observation period (80.6%), and b) having had no relapse and symptomatic remission at 12-month-follow-up (37.2%). RESULTS: Cox regression revealed that a higher proportion of patients from Western European countries and Israel stopped antipsychotic medication than from Central and Eastern European countries, that relapse was associated with discontinuation, and that discontinuers had lower compliance and higher quality of life. Predictors of successful discontinuation differed with the outcome definition used. Using definition b), successful discontinuers had a better baseline prognosis and better baseline social integration. Using definition a), successful discontinuers more often were from Western European countries. CONCLUSIONS: Region and clinical factors were associated with discontinuation. Prognosis and social integration played an important role in predicting successful discontinuation. As this study had several limitations, for example the observational design regarding discontinuation, further studies are needed to identify predictors of successful discontinuation.


Antipsychotic Agents/therapeutic use , Patient Dropouts , Schizophrenia/diagnosis , Schizophrenia/drug therapy , Acute Disease , Adolescent , Adult , Europe , Female , Follow-Up Studies , Humans , Interview, Psychological , Israel , Logistic Models , Male , Prognosis , Proportional Hazards Models , Prospective Studies , Young Adult
5.
Schizophr Res ; 169(1-3): 303-307, 2015 Dec.
Article En | MEDLINE | ID: mdl-26545298

Gender differences in the response to antipsychotic treatment have been detected in the past, but not studied in great detail. The results of the European First-Episode Schizophrenia Trial (EUFEST) were analyzed with a focus on gender differences in the response to randomized treatment of first-episode schizophrenia. A total of 498 patients (298 men and 200 women) were randomly assigned by a web-based online system to open-label treatment with haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone. Treatment response was evaluated using the positive and negative syndrome scale (PANSS). Data were collected at baseline and then prospectively for one year. Baseline characteristics (age and proportion of patients assigned to individual antipsychotics) were the same between the male and female patients with the exception of ziprasidone: significantly fewer men, proportionately, were prescribed ziprasidone. There was no significant difference between genders between the initial total PANSS and subscale scores. A significant interaction between time and gender was found, with more robust PPANSS and TPANSS score improvement in women during the course of treatment. Of all of the antipsychotics used, only olanzapine led to significantly greater improvement in the total PANSS score in women during the follow-up period. Gender differences should be given more attention in research and clinical practice. Their causes require clarification, and future strategies for dealing with them may be considered in early intervention programs and guidelines.


Antipsychotic Agents/therapeutic use , Schizophrenia/drug therapy , Sex Characteristics , Treatment Outcome , Adolescent , Adult , Europe , Female , Humans , International Cooperation , Male , Outcome Assessment, Health Care , Psychiatric Status Rating Scales , Young Adult
7.
Eur Neuropsychopharmacol ; 23(3): 196-204, 2013 Mar.
Article En | MEDLINE | ID: mdl-22647933

Negative symptoms that do not improve following antipsychotic treatment represent a challenge for development of effective treatments. Few studies have been carried out so far, especially in first-episode schizophrenia patients, to clarify prevalence, correlates and impact of persistent negative symptoms (PNS) on short- and long-term outcome of the disease. All patients from EUFEST study for whom both baseline and 12-month assessments were available were included (N=345). PNS were defined as the presence of at least one negative symptom of moderate or higher severity, not confounded by depression or parkinsonism, at baseline and after 1 year of treatment. Patients with PNS were compared to those with at least one negative symptom of moderate or higher severity at the baseline, not persisting after 1 year, on demographic, clinical, neurocognitive, global functioning and quality of life measures. PNS not confounded by depression or parkinsonism were present in 6.7% of the sample. The symptom that more often persisted was blunted affect. Patients with PNS differed from those without PNS for a longer duration of untreated psychosis (DUP) and a more frequent discontinuation of study treatment; they also had a poorer psychopathological outcome and a worse global functioning after 1 year of treatment. The presence of PNS was associated to poorer improvement of all psychopathological dimensions and worse global functioning after 1 year of treatment. The longer DUP in subjects with PNS suggests that programs aimed at shortening DUP might reduce the prevalence of PNS and improve prognosis of schizophrenia.


Antipsychotic Agents/therapeutic use , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Schizophrenic Psychology , Adolescent , Adult , Amisulpride , Benzodiazepines/therapeutic use , Cognition Disorders/psychology , Dibenzothiazepines/therapeutic use , Female , Haloperidol/therapeutic use , Humans , Male , Neuropsychological Tests , Olanzapine , Piperazines/therapeutic use , Psychomotor Disorders/psychology , Psychotic Disorders/psychology , Quetiapine Fumarate , Sulpiride/analogs & derivatives , Sulpiride/therapeutic use , Thiazoles/therapeutic use , Treatment Outcome , Young Adult
8.
J Psychiatr Res ; 46(6): 811-8, 2012 Jun.
Article En | MEDLINE | ID: mdl-22502820

Dysfunction of the N-methyl-d-aspartate receptor, which is modulated by excitatory amino acids (EAA), is involved in the pathophysiology of schizophrenia. The effects of antipsychotics on EAA metabolism are uncertain. Positive clinical effects of treatment with antipsychotics were not always associated with changes in EAA serum levels in patients with schizophrenia in clinical trials. To examine EAA serum levels in relation to the intensity of psychotic symptoms and the type of medication received we compared these variables among patients with schizophrenia (n = 49) treated with first (FGA) or second (SGA) generation antipsychotics or clozapine. Glutamate, aspartate, glycine, total serine and d-serine serum levels were measured by High Performance Liquid Chromatography. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to assess symptoms of schizophrenia. Lower average levels of glycine and total serine were found in the serum of patients receiving clozapine when compared to the groups of patients treated with FGA or SGA. There were no differences in serum glutamate, aspartate or d-serine levels or in the intensity of schizophrenic symptoms assessed by PANSS or SANS among the groups of patients treated with FGA or SGA or clozapine. Lower glycine and total serine serum levels could be caused by the particular characteristics of the population of patients receiving clozapine rather than as an effect of the clozapine. The results suggest selective deficiency of l-serine synthesis in the patients with resistance to non-clozapine treatment. It might be an unique biochemical and pathophysiological characteristic of the treatment-resistance in schizophrenia.


Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Glycine/blood , Schizophrenia/blood , Schizophrenia/drug therapy , Serine/blood , Adult , Aged , Excitatory Amino Acids/blood , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Statistics, Nonparametric , Young Adult
9.
Eur Arch Psychiatry Clin Neurosci ; 262(3): 207-16, 2012 Apr.
Article En | MEDLINE | ID: mdl-22113521

The interrelation between needs for care and quality of life has been described and replicated by several studies. The present work aims to add to the understanding of longitudinal interrelations between needs for care, quality of life, and other outcome measures by analyzing a sample of patients at the onset of schizophrenia. This study relied on data from the EUFEST trial, designed to compare first- and second-generation antipsychotics during 1 year. At baseline, 498 patients have been included. The first (baseline) and the last assessment (12 months after baseline) were used for the analyses. Predictors of quality of life were determined using regression analyses. We tested the complex longitudinal interrelations between baseline and outcome measures with structural equation models. Unmet needs were not definitively confirmed as a predictor of subsequent quality of life, unless unmet needs changing to no needs were separated from unmet needs changing to met needs. Each unmet need that changed to no need enhanced the quality of life (mean score 1-7) by 0.136 scale points. This study suggests that when studying quality of life and needs for treatment, it is crucial to differentiate whether unmet needs disappeared or whether they were met, as the former has a stronger impact on quality of life.


Health Services Needs and Demand , Quality of Life/psychology , Schizophrenia/therapy , Schizophrenic Psychology , Adolescent , Adult , Europe , Female , Humans , Longitudinal Studies , Male , Psychiatric Status Rating Scales , Regression Analysis , Retrospective Studies , Schizophrenia/diagnosis , Schizophrenia/physiopathology , Young Adult
10.
J Clin Psychiatry ; 72(7): 955-61, 2011 Jul.
Article En | MEDLINE | ID: mdl-21824456

OBJECTIVE: To compare the effects of haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on hostility in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. METHOD: We used the data acquired in the European First-Episode Schizophrenia Trial, an open, randomized trial (conducted in 14 countries) comparing 5 antipsychotic drugs in 498 patients aged 18-40 years with first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. DSM-IV diagnostic criteria were used. Patients were assessed between December 23, 2002 and January 14, 2006. Most subjects joined the study as inpatients and then continued with follow-ups in outpatient clinic visits. The Positive and Negative Syndrome Scale (PANSS) was administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. We analyzed the scores on the PANSS hostility item in a subset of 302 patients showing at least minimal hostility (a score > 1) at baseline. We hypothesized (1) that the treatments would differ in their efficacy for hostility and (2) that olanzapine would be superior to haloperidol. Our primary statistical analysis tested the null hypothesis of no difference among the treatment groups in change in hostility over time. Secondary analysis addressed the question of whether the effects on hostility found in the primary analysis were specific to this item. All our analyses were post hoc. RESULTS: The primary analysis of hostility indicated an effect of differences between treatments (F(4,889) = 4.02, P = .0031). Post hoc treatment-group contrasts for hostility change showed that, at months 1 and 3, olanzapine was significantly superior (P < .05) to haloperidol, quetiapine, and amisulpride in reducing hostility. Secondary analyses demonstrated that these results were at least partly specific to hostility. CONCLUSIONS: Both hypotheses were supported. Olanzapine appears to be a superior treatment for hostility in early phases of therapy for first-episode schizophrenia, schizoaffective disorder, and schizophreniform disorder. This efficacy advantage of olanzapine must be weighed against its adverse metabolic effects and propensity to cause weight gain. TRIAL REGISTRATION: ISRCTN Register Identifier: ISRCTN68736636.


Antipsychotic Agents/therapeutic use , Hostility , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Schizophrenic Psychology , Adult , Aggression/drug effects , Aggression/psychology , Amisulpride , Antipsychotic Agents/adverse effects , Benzodiazepines/adverse effects , Benzodiazepines/therapeutic use , Dibenzothiazepines/adverse effects , Dibenzothiazepines/therapeutic use , Haloperidol/adverse effects , Haloperidol/therapeutic use , Humans , Olanzapine , Piperazines/adverse effects , Piperazines/therapeutic use , Psychiatric Status Rating Scales , Psychotic Disorders/diagnosis , Psychotic Disorders/psychology , Quetiapine Fumarate , Sulpiride/adverse effects , Sulpiride/analogs & derivatives , Sulpiride/therapeutic use , Thiazoles/adverse effects , Thiazoles/therapeutic use , Treatment Outcome
11.
Soc Psychiatry Psychiatr Epidemiol ; 46(2): 159-65, 2011 Feb.
Article En | MEDLINE | ID: mdl-20119828

BACKGROUND: Relatively few studies have examined how patients with schizophrenia and depression view psychiatric research and what influences their readiness to participate. METHODS: A total of 763 patients (48% schizophrenia, 52% depression) from 7 European countries were examined using a specifically designed self-report questionnaire ["Hamburg Attitudes to Psychiatric Research Questionnaire" (HAPRQ)]. RESULTS: Most patients (98%) approved of psychiatric research, in general, at least "a little". There was a tendency to approve psychosocial rather than biological research topics (e.g. research on the role of the family by 91% of patients compared to 79% in genetics). Reasons to participate were mainly altruistic. Only a minority (28%) considered monetary incentives important. Patients wanted extensive background information and a feedback of the results; both were significantly more expressed by schizophrenia as compared to depressive patients, although these findings need to be interpreted with care because of age and gender differences between the diagnostic groups. CONCLUSION: While patients expressed discerning views of psychiatric research, only few differences were apparent between the two diagnostic groups. Patients' research priorities are not the same as those of many professionals and funding bodies. Their demonstrated critical appraisal should inform future research ensuring an increased patient role in the research process.


Attitude to Health , Depressive Disorder/psychology , Patient Participation , Research Subjects/psychology , Schizophrenia/diagnosis , Schizophrenic Psychology , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Cultural Comparison , Depressive Disorder/diagnosis , Europe , Female , Humans , Male , Middle Aged , Motivation , Psychiatric Status Rating Scales/statistics & numerical data , Surveys and Questionnaires
12.
Psychiatry Res ; 176(2-3): 103-8, 2010 Apr 30.
Article En | MEDLINE | ID: mdl-20096465

Glycine acts as an endogenous selective co-agonist at the glycine modulatory site of the NMDA (N-methyl-d-aspartate) receptor. Significantly decreased glycine serum levels were reported in patients with schizophrenia in comparison to healthy controls. Administration of glycine improved negative symptoms in patients with schizophrenia treated with antipsychotics in some clinical trials. We hypothesized that glycine serum levels might be associated with intensity of negative symptoms in schizophrenia. Fifty outpatients with the diagnosis of schizophrenia as defined by ICD-10 and fifty age- and gender-matched healthy controls were recruited into the study. Glycine serum levels were measured by high performance liquid chromatography (HPLC). We used the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) to assess the symptoms of schizophrenia in the patients. We found mean glycine serum levels to be significantly lower in patients than in controls. This difference was only caused by findings in the male study population. Glycine serum levels were negatively associated with intensity of negative symptoms assessed by the PANSS negative subscale and the SANS total scores in the patients. These data suggest a possible implication of NMDA receptor dysfunction in the pathogenesis of negative symptoms in schizophrenia.


Glycine/blood , Schizophrenia/blood , Schizophrenia/physiopathology , Adult , Case-Control Studies , Chromatography, High Pressure Liquid/methods , Female , Humans , International Classification of Diseases , Male , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Sex Factors , Statistics, Nonparametric , Young Adult
13.
Schizophr Res ; 115(2-3): 97-103, 2009 Dec.
Article En | MEDLINE | ID: mdl-19819114

BACKGROUND: Predefined response and remission criteria may hold more clinical relevance than mean scores on rating scales. We compared the effectiveness of low doses of haloperidol and regular doses of second generation antipsychotics (SGAs) on >or=50% response and remission. METHODS: In an open randomized clinical trial in 14 countries, 498 unselected first-episode patients with schizophrenia were assigned to haloperidol (1-4 mg/d; n=103), amisulpride (200-800 mg/d; n=104), olanzapine (5-20mg/d; n=105), quetiapine (200-750 mg/d; n=104), or ziprasidone (40-160 mg/d; n=82). Primary outcomes were >or=50% response and remission within 12 months, as measured with the Positive and Negative Syndrome Scale. Analysis was by intention-to-treat. RESULTS: Within 12 months, the proportions of patients with >or=50% response were 37% for haloperidol, 67% for amisulpride, 67% for olanzapine, 46% for quetiapine, and 56% for ziprasidone. Comparisons with haloperidol showed a higher likelihood for >or=50% response with amisulpride (hazard ratio [HR] 2.27, [95% CI 1.51-3.42]), olanzapine (HR 2.07 [1.38-3.10]), and ziprasidone (HR 1.62 [1.02-2.56]). Within 12 months, the proportions of patients in remission were 17% for haloperidol, 40% for amisulpride, 41% for olanzapine, 24% for quetiapine, and 28% for ziprasidone. Comparisons with haloperidol showed a better chance for remission on amisulpride (HR 2.49, [95% CI 1.43-4.35]), olanzapine (HR 2.58 [1.48-4.48]), quetiapine (HR 1.96 [1.06-3.64]), and ziprasidone (HR 2.03 [1.07-3.87]). CONCLUSIONS: Substantial proportions of first-episode patients with schizophrenia showed clinically meaningful response and remission rates within 12 months. The proportions of response and remission were higher for most SGAs as compared to haloperidol.


Antipsychotic Agents/therapeutic use , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Adolescent , Adult , Cross-Cultural Comparison , Dose-Response Relationship, Drug , Europe , Female , Humans , International Cooperation , Israel , Male , Outcome Assessment, Health Care , Predictive Value of Tests , Proportional Hazards Models , Psychiatric Status Rating Scales , Retrospective Studies , Secondary Prevention , Time Factors , Young Adult
14.
Schizophr Res ; 115(2-3): 104-14, 2009 Dec.
Article En | MEDLINE | ID: mdl-19822407

BACKGROUND: Profile and correlates of cognitive deficits in first episode (FE) schizophrenia patients are still debated. The present study is aimed to clarify in a large sample of FE patients the extent of impairment in key cognitive domains and its relationships with demographic and clinical variables. METHOD: The European First Episode Schizophrenia Trial collected demographic, clinical and neurocognitive baseline data in 498 FE patients with minimal or no prior exposure to antipsychotics. Two-hundred-twenty healthy subjects (HS) were also evaluated. Neurocognitive assessment included the Rey Auditory Verbal Learning Test; Trail Making A and B, Purdue Pegboard and Digit-Symbol Coding. RESULTS: Patients performed worse than HS on all tests (effect sizes from -0.88 to -1.73). Correlations with psychopathological dimensions were weak and involved reality distortion and disorganization. The duration of untreated psychosis (DUP) was not associated with cognitive impairment. Subjects living alone had a better neurocognitive performance, while the occupation status did not reveal any association with cognition. CONCLUSIONS: A moderate/severe impairment of processing speed, motor dexterity, verbal memory and cognitive flexibility was found in the largest sample of FE patients analyzed so far. The impairment was largely independent from psychopathology and not associated with DUP.


Cognition Disorders/etiology , Schizophrenia/complications , Schizophrenic Psychology , Statistics as Topic , Adult , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Cognition Disorders/drug therapy , Cross-Cultural Comparison , Europe , Female , Humans , International Cooperation , Male , Multivariate Analysis , Neuropsychological Tests , Psychiatric Status Rating Scales , Regression Analysis , Schizophrenia/drug therapy , Substance-Related Disorders/complications , Substance-Related Disorders/diagnosis , Young Adult
15.
Am J Psychiatry ; 166(6): 675-82, 2009 Jun.
Article En | MEDLINE | ID: mdl-19369319

OBJECTIVE: Cognitive impairment, manifested as mild to moderate deviations from psychometric norms, is present in many but not all schizophrenia patients. The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia. METHODS: Subjects were 498 patients with schizophreniform disorder or first-episode schizophrenia who were randomly assigned to open-label haloperidol (1 to 4 mg/day [N=103]), amisulpride (200 to 800 mg/day [N=104]), olanzapine (5 to 20 mg/day [N=105]), quetiapine (200 to 750 mg/day [N=104]), or ziprasidone (40 to 160 mg/day [N=82]). The Rey Auditory Verbal Learning Test, Trail Making Test Part A and Part B, WAIS Digit Symbol Test, and Purdue Pegboard Test were administered at baseline and the 6-month follow-up evaluation. RESULTS: Compared with scores at baseline, composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation. However, there were no overall differences among the treatment groups. In addition, there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores. CONCLUSION: Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change.


Antipsychotic Agents/adverse effects , Cognition Disorders/chemically induced , Psychotic Disorders/drug therapy , Adolescent , Adult , Antipsychotic Agents/therapeutic use , Cognition Disorders/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Male , Neuropsychological Tests , Psychotic Disorders/diagnosis , Schizophrenia/diagnosis , Schizophrenia/drug therapy , Severity of Illness Index , Young Adult
16.
17.
Neuro Endocrinol Lett ; 29(4): 485-92, 2008 Aug.
Article En | MEDLINE | ID: mdl-18766161

OBJECTIVES: The main objective was to test the hypothesis of the association between D-serine serum levels and negative symptoms in patients with schizophrenia. Secondary objective was to examine the assumption of D-serine serum levels difference between a population of mostly chronic patients with schizophrenia and healthy controls. METHODS: We recruited outpatients with schizophrenia and age and gender matched healthy controls for the study. D-serine and total serine serum levels were measured by high-performance liquid chromatography (HPLC). The Positive and Negative Syndrome Scale (PANSS) and The Scale for the Assessment of Negative Symptoms (SANS) were used to assess schizophrenic symptoms. Non-parametric statistics was used to test the differences in D-serine and total serine serum levels and rank correlation was used to detect the associations with psychopathology. RESULTS: We did not find any differences between patients (n=50) and controls (n=50) in D-serine serum levels. Patients had significantly lower total serine serum levels and higher D-serine/total serine ratio. D-serine serum levels were not associated with the PANSS or the SANS total and subscales scores. Total se-rine serum levels inversely correlated with the SANS total and the PANSS negative symptom subscale scores. CONCLUSION: Decreased, not increased, serum levels of total serine negatively associated with intensity of negative symptoms were detected in patients with schizophrenia. We did not find any relationship between D-serine serum levels and negative symptoms among the patients. These findings do not agree with the previous reports of decreased D-serine and increased total serine serum levels in schizophrenia.


Schizophrenia/blood , Schizophrenia/physiopathology , Serine/blood , Antipsychotic Agents/therapeutic use , Female , Humans , Male , Schizophrenia/drug therapy , Statistics as Topic
18.
Neuro Endocrinol Lett ; 29(4): 435-7, 2008 Aug.
Article En | MEDLINE | ID: mdl-18766167

Clozapine is an atypical antipsychotic indicated for the treatment of refractory schizophrenia. Clozapine treatment is associated with the metabolic side effects. Weight gain, hyperlipidemia and hyperglycemia are the risk factors for onset of diabetes and cardiovascular disorders. We report a case vignette of a patient in whom the decrease in negative and general psychopathology after adjunctive aripiprazole appeared simultaneously with a reduction of clozapine-induced increase in weight and metabolic measures. Combined application of clozapine and aripiprazole is in accordance with a neurobiological rationale and appears to be a safe and well tolerated.


Antipsychotic Agents/therapeutic use , Clozapine , Piperazines/therapeutic use , Quinolones/therapeutic use , Schizophrenia, Paranoid/drug therapy , Adult , Aripiprazole , Clozapine/adverse effects , Clozapine/therapeutic use , Drug Therapy, Combination , Humans , Male , Weight Gain
19.
Doc Ophthalmol ; 117(3): 245-55, 2008 Nov.
Article En | MEDLINE | ID: mdl-18563464

OBJECTIVE: Methamphetamine (MAP) is an indirect dopamine agonist that can temporarily increase cognitive performance. However, its long-term abuse may cause dopamine depletion and consequent cognitive and attentional impairment. The worsening of visual functions in Parkinson's disease and their improvement after levodopa administration implicates the role of dopamine in the physiology of vision. This provides the rationale for the investigation of visual functions in abstaining MAP abusers. METHODS: We investigated changes in visually evoked potentials (VEPs) to pattern-reversal and motion-onset stimuli. Such changes serve as indices of visual information processing in the primary and associative areas in a group of recently abstaining MAP abusers (5 females, 18 males, MAP abuse 5.3 +/- 2.8 years) and in 23 age- and gender-paired controls. RESULTS: We did not find differences between the groups in visual acuity. In the group of MAP abusers we observed an attenuation of the early responses around 80 ms and a prolongation of the P1 peak latency after the reversal of high spatial frequency checkerboards (10 and 20 arcmin checks). Furthermore, an attenuation of the latter positive response (170-250 ms) was observed among all the stimuli in parieto-frontal derivations for the MAP abusers. CONCLUSIONS: This is the first report suggesting a slowing and attenuation of VEP responses during visual processing in abstaining methamphetamine abusers.


Amphetamine-Related Disorders/physiopathology , Evoked Potentials, Visual/physiology , Motion Perception/physiology , Visual Pathways/physiopathology , Adult , Female , Humans , Male , Methamphetamine/adverse effects , Young Adult
20.
Schizophr Res ; 102(1-3): 320-8, 2008 Jul.
Article En | MEDLINE | ID: mdl-18472402

Event related potentials (ERPs) provide an insight into sensory and cognitive processes in health and disease. Studies of an ERP negative amplitude deflection elicited by a change in a series of auditory stimuli is known as mismatch negativity (MMN). The generation of MMN is impaired in schizophrenia. Its deficit is associated with lower everyday functioning and may be also interpreted as the marker of progression in schizophrenia. MMN elicited by visual stimuli (vMMN) was described by several research teams, but it has not been investigated in schizophrenia as yet. Using a motion-direction paradigm, we elicited visual MMN in 24 patients with schizophrenia and schizoaffective disorder. The vMMN was computed as differences in areas under curve of visual ERPs to standard and deviant motion-direction stimuli recorded from midline derivations at the interval of 100-200 ms. They were compared between groups of patients with schizophrenia and healthy controls. The significantly smaller vMMN indicated an impaired generation of mismatch negativity in patients with schizophrenia. In secondary analyses there was an association of vMMN impairment among patients with higher dose of medication, lower level of functioning and the presence of deficit syndrome. This impairment appears analogous to the impairment of MMN in the auditory domain and is probably related to early visual information processing. Its relationship to cognitive functioning of patients with schizophrenia deserves further attention.


Brain/physiology , Cognition Disorders/diagnosis , Electroencephalography/statistics & numerical data , Evoked Potentials, Visual/physiology , Schizophrenia/diagnosis , Visual Perception/physiology , Adult , Area Under Curve , Attention/physiology , Cognition Disorders/physiopathology , Control Groups , Cross-Sectional Studies , Female , Functional Laterality/physiology , Humans , Male , Memory/physiology , Middle Aged , Motion Perception/physiology , Neuropsychological Tests , Photic Stimulation/methods , Psychotic Disorders/diagnosis , Psychotic Disorders/physiopathology , Reaction Time/physiology , Schizophrenia/physiopathology , Schizophrenic Psychology , Visual Pathways/physiology
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