Cognitive impairment and cortisol levels in first-episode schizophrenia patients.

Many modalities of cognition are affected in schizophrenia. The most common findings include dysfunctions of episodic and working memory and of executive functions. Although an inverse correlation between cortisol level and memory function has been proven, few studies have focused on the relationship between cortisol level and cognitive impairment in patients with schizophrenia. In an open, naturalistic, prospective study, consecutively hospitalized males diagnosed with first-episode schizophrenia, hypothalamic-pituitary-adrenal axis activity (afternoon cortisol levels, post-dexamethasone cortisol levels) was evaluated before and at the end of acute treatment. Psychopathology was assessed using the positive and negative syndrome scale (PANSS). Cognitive functions (memory, attention, psychomotor, verbal fluency, and executive functions) were tested after symptom alleviation using a neurocognitive test battery. In the total sample (n = 23), significant decreases in total PANSS score (including all subscales), afternoon cortisol levels, and post-dexamethasone cortisol levels occurred during the course of treatment. It was found that higher afternoon cortisol levels at the beginning of treatment were significantly related to impaired performance in memory functions. Afternoon cortisol levels were not significantly associated with other measured cognitive functions. No correlation was discovered between cognitive functions and post-dexamethasone cortisol levels. The determination of afternoon cortisol levels may serve to detect potential candidates for specific cognitive intervention immediately after the first psychotic breakthrough.

Gender differences in the treatment of first-episode schizophrenia: Results from the European First Episode Schizophrenia Trial.

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.

Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients.

INTRODUCTION: High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) seemed to decrease tobacco consumption and craving in nicotine-dependent people without psychiatric disorder or otherwise healthy people. Even if the prevalence of cigarette smoking in schizophrenia patients is high and estimated to be between 45% and 88%, this technique has not been systematically studied in this indication in schizophrenia yet. THE AIM OF THE STUDY: The aim of this study was to test the ability of high-frequency (10Hz) rTMS over the left DLPFC to decrease cigarette consumption in schizophrenia patients. METHODS: The study included 35 male schizophrenia patients on stable antipsychotic medication. The patients were divided into two groups: the first (18 patients) were actively stimulated and the second (17 patients) underwent sham (placebo) stimulation. The sham rTMS was administered using a purpose-built sham coil that was identical in appearance to the real coil and made the same noise but did not deliver a substantial stimulus. The rTMS was administered at the stimulation parameters: location (left dorsolateral prefrontal cortex: DLPFC), intensity of magnetic stimulation in % of motor threshold (110%), stimulation frequency (10Hz), number of trains (20), single train duration (10s), inter-train interval (30s), and total number of stimulation sessions (21). In each stimulation session, 2000TMSpulses were given, with a total of 42,000pulses per treatment course. Patients noted the number of cigarettes smoked in the 7days before treatment, during the whole stimulation treatment (21days), and again for a 7-day period after treatment. RESULTS: Cigarette consumption was statistically significantly lower in the actively stimulated patients than in the sham rTMS group as early as the first week of stimulation. No statistically relevant correlations were found in the changes of ongoing negative or depressive schizophrenia symptoms and the number of cigarettes smoked. CONCLUSION: High-frequency rTMS over the left DLPFC has the ability to decrease the number of cigarettes smoked in schizophrenia patients.

Prevalence of remission and recovery in schizophrenia in the Czech Republic.

OBJECTIVE: The aim of the study was to map the point prevalence of remission and recovery in patients with schizophrenia in the Czech Republic. METHOD: The point-symptomatic remission criteria were based on the definition of remission in schizophrenia according to Andreasen, without the time criterion. The definition of complete remission contained, in addition to the point-symptomatic remission criteria, a time aspect which was determined by the absence of psychiatric hospitalisation or a change in antipsychotic medications due to inefficiency in the preceding six months. Functional remission was defined by a total score on the PSP scale in the range between 71 and 100 points. Recovery was defined by the simultaneous fulfilment of the criteria for complete and functional remission. RESULTS: A total of 481 patients with schizophrenia were included in the study. The point-symptomatic remission criteria were fulfilled in a total of 258 patients (54%); complete remission occurred in a total of 214 patients (44%). Functional remission was reached by 124 patients (26%) in total. Recovery was proven in a total of 91 patients (19%). CONCLUSION: The ascertained data are in accordance with the results of methodologically similar studies and confirm the known trajectories of the course of schizophrenia.

A detailed analysis of the effect of repetitive transcranial magnetic stimulation on negative symptoms of schizophrenia: a double-blind trial.

OBJECTIVE: The aim of the study was to assess the effect of rTMS not only on the general severity of negative schizophrenia symptoms, but also particularly on their individual domains, such as affective flattening or blunting, alogia, avolition or apathy, anhedonia, and impaired attention. METHODS: Forty schizophrenic male patients on stable antipsychotic medication with prominent negative symptoms were included in the study. They were divided into two groups: 23 were treated with active and 17 with placebo rTMS. Both treatments were similar, but placebo rTMS was administered using a purpose-built sham coil. Stimulation was applied to the left dorsolateral prefrontal cortex (DLPFC). The stimulation frequency was 10 Hz; stimulation intensity was 110% of the individual motor threshold intensity. Each patient received 15 rTMS sessions on 15 consecutive working days (five working days "on" and two weekend days "off" design). Each daily session consisted of 20 applications of 10-second duration with 30-second intervals between sequences. The patients and raters were blind to condition of stimulation treatment. RESULTS: The active rTMS led to a statistically significantly higher reduction of the Scale for the Assessment of Negative Symptoms (SANS) total score and of all domains of negative symptoms of schizophrenia. After Bonferroni adjustments for multiple testing, the statistical significance disappeared in alogia only. CONCLUSION: High-frequency rTMS stimulation over the left DLPFC at a high stimulation intensity with a sufficient number of applied stimulating pulses may represent an efficient augmentation of antipsychotics in alleviating the negative symptoms of schizophrenia.

Brain functional connectivity of male patients in remission after the first episode of schizophrenia.

OBJECTIVES: Abnormal task-related activation and connectivity is present in schizophrenia. The aim of this study was the analysis of functional networks in schizophrenia patients in remission after the first episode. EXPERIMENTAL DESIGN: Twenty-nine male patients in remission after the first episode of schizophrenia and 22 healthy controls underwent examination by functional magnetic resonance during verbal fluency tasks (VFT). The functional connectivity of brain networks was analyzed using independent component analysis. RESULTS: The patients showed lower activation of the salience network during VFT. They also showed lower deactivation of the default mode network (DMN) during VFT processing. Spectral analysis of the component time courses showed decreased power in slow frequencies of signal fluctuations in the salience and DMNs and increased power in higher frequencies in the left frontoparietal cortex reflecting higher fluctuations of the network activity. Moreover, there was decreased similarity of component time courses in schizophrenia­the patients had smaller negative correlation between VFT activated and deactivated networks, and smaller positive correlations between DMN subcomponents. CONCLUSIONS: There is still an abnormal functional connectivity of several brain networks in remission after the first episode of schizophrenia. The effect of different treatment modalities on brain connectivity, together with temporal dynamics of this functional abnormality should be the objective of further studies to assess its potential as a marker of disease stabilization.

Can repetitive transcranial magnetic stimulation be considered effective treatment option for negative symptoms of schizophrenia?

OBJECTIVE: Despite the development of second-generation antipsychotic drugs, treatment-resistant symptoms still represent a serious problem in schizophrenia. The aim of the present article was to review studies with repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia and draw conclusions for clinical decision making. METHOD: Literature for this review was identified by searching MEDLINE and ISI Web of Science up to the year 2011. RESULTS: Five open studies, 13 sham-controlled studies, and 2 meta-analysis and 2 review articles were included in the present paper. The effect size of the high frequency repetitive transcranial magnetic stimulation (rTMS) over the left prefrontal cortex in the treatment of negative symptoms of schizophrenia is thought to be mild to moderate (Cohen d = 0.43-0.68). CONCLUSION: Despite the promising results of some rTMS studies, the potential of rTMS for the treatment of negative symptoms is currently relatively unclear. Large clinical studies are therefore needed, especially large multicentric studies such as depression rTMS studies.

Role of long-acting injectable second-generation antipsychotics in the treatment of first-episode schizophrenia: a clinical perspective.

Approximately 80% of patients with the first-episode schizophrenia reach symptomatic remission after antipsychotic therapy. However, within two years most of them relapse, mainly due to low levels of insight into the illness and nonadherence to their oral medication. Therefore, although the formal data available is limited, many experts recommend prescribing long-acting injectable second-generation antipsychotics (mostly risperidone or alternatively paliperidone) in the early stages of schizophrenia, particularly in patients who have benefited from the original oral molecule in the past and agree to receive long-term injectable treatment. Early application of long-acting injectable second-generation antipsychotics can significantly reduce the risk of relapse in the future and thus improve not only the social and working potential of patients with schizophrenia but also their quality of life.

Does repetitive transcranial magnetic stimulation have a positive effect on working memory and neuronal activation in treatment of negative symptoms of schizophrenia?

OBJECTIVE: The objective of the study was to find out whether, under the conditions of a double-blind, placebo coil controlled study, high-frequency repetitive transcranial magnetic stimulation (TMS) over the left prefrontal cortex will show positive effects on working memory with simultaneous assessment of respective changes in neuronal activation. RESULTS: Stimulation treatment led to a reduction of seriousness of negative schizophrenia symptoms in both comparative groups. However, mutual comparison of real (n=19) and sham (n=11) rTMS, respectively, has shown that the effect of real rTMS was statistically significantly higher compared with placebo stimulation. During stimulation treatment an improvement in working memory performance was also found. No statistically significant difference between the real and placebo sham rTMS, respectively, was established. The rate of neuronal activation did not change at all during rTMS treatment. CONCLUSIONS: From clinical point of view rTMS seems to be a well-tolerated neurostimulation method for treatment of negative schizophrenia symptoms with favourable of impact on cognitive functions.

Dynamics of neurological soft signs and its relationship to clinical course in patients with first-episode schizophrenia.

The aim of the study was to assess the dynamics of neurological soft signs (NSS) over four years from the clinical onset of schizophrenia, depending on the clinical course of the disease, and to evaluate the relationship of NSS to symptomatic dimensions in patients with first-episode schizophrenia. Sixty-eight patients with first-episode schizophrenia were included in the trial. The clinical status was assessed using Positive and Negative Syndrome Scale (PANSS) at the same time as the neurological examination, at admission to the hospital for first-episode schizophrenia and at a check-up examination four years later. The assessment of NSS using the Neurological Evaluation Scale (NES) coincided with the assessment of the clinical condition of the patients. According to the Andreasen remission criterion of schizophrenia, after four years we found that 57% of patients' were remitters and 43% were non-remitters. During the monitoring period, in remitters total NES score and sensory integration/sequencing of motor acts items of the NES decreased. In non-remitters, increase in the total NES score and the 'others' item of the NES was observed. A connection between the dynamics of NSS and the clinical course of schizophrenia, over the period of four years, and a relationship between NSS and negative schizophrenia symptoms was found.

Importance of gender in the treatment of schizophrenia.

OBJECTIVE: To compare male and female patients participating in e-STAR (electronic Schizophrenia Treatment Adherence Registry), an international, prospective, observational study assessing use of risperidone long-acting injection in patients with schizophrenia or schizoaffective disorder in both the Czech and Slovak Republics. METHOD: The demographic, clinical, and treatment-related data were collected at baseline and then prospectively for 24 months. We focused on gender differences in demographic and clinical data (hospitalizations, concomitant medication, and clinical improvement using Clinical Global Impressions-severity of illness [CGI-S], Global Assessment of Functioning [GAF], and Personal and Social Performance [PSP] scales). All psychiatric diagnoses were made according to International Classification of Diseases, Tenth Revision criteria. Data were collected from September 2006 through September 2009. RESULTS: A total of 868 patients (488 men and 380 women) were included in the assessment. At baseline, the women were significantly older than the men (42.1 ± 12.8 vs 34.8 ± 11.1 years, respectively; P < .0001). The women were also significantly more frequently diagnosed with schizoaffective disorder (P = .0048). There was no difference between men and women in the proportion of patients hospitalized in the retrospective and prospective period (including length of stay). At 24 months, the men were taking fewer antidepressants and benzodiazepines than the women (controlled for baseline values). In men and women, a significant decrease in the CGI-S score (P < .001) and a significant increase in the GAF and PSP scores (P < .001) from baseline were observed. The improvements in CGI-S and PSP scores were similar in both groups (no significant difference between male and female patients). The improvement (increase) in the mean GAF score was significantly higher in women than in men (P = .0317). CONCLUSIONS: The treatment with risperidone long-acting injection was associated with clinically significant improvement in both male and female patients with schizophrenia with comparable severity of illness. There were no significant differences in most outcome measures. Gender differences, especially concerning treatment response to individual antipsychotics and their different forms, should be more intensively studied.

Repetitive transcranial magnetic stimulation and treatment of negative symptoms of schizophrenia.

One of the fundamental prerequisites of the successful schizophrenia treatment is represented by an adequately significant impact on the negative symptoms of schizophrenia. Since the present pharmacotherapy has probably reached its limit in this area, there is a logical effort to utilize other, non-pharmacological methods. One of the most promising supplements that has been for a long time verified in the clinical practice is rTMS. Most of the studies have arrived at the conclusion that rTMS is an efficient method in the treatment of negative symptoms of schizophrenia. A valuable contribution to the assessment of the rTMS application in the treatment of negative symptoms is represented by meta-analyses. The meta-analyses indicate that the effect is mild to moderate (d=0.43 to 0.68). To sum it up, there will be higher probability of the rTMS effect on negative symptoms if 10 Hz stimulating frequency and a longer stimulation period in the extent at least three, ideally four to six weeks is used.

Maximum-uncertainty linear discrimination analysis of first-episode schizophrenia subjects.

Recent techniques of image analysis brought the possibility to recognize subjects based on discriminative image features. We performed a magnetic resonance imaging (MRI)-based classification study to assess its usefulness for outcome prediction of first-episode schizophrenia patients (FES). We included 39 FES patients and 39 healthy controls (HC) and performed the maximum-uncertainty linear discrimination analysis (MLDA) of MRI brain intensity images. The classification accuracy index (CA) was correlated with the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning scale (GAF) at 1-year follow-up. The rate of correct classifications of patients with poor and good outcomes was analyzed using chi-square tests. MLDA classification was significantly better than classification by chance. Leave-one-out accuracy was 72%. CA correlated significantly with PANSS and GAF scores at the 1-year follow-up. Moreover, significantly more patients with poor outcome than those with good outcome were classified correctly. MLDA of brain MR intensity features is, therefore, able to correctly classify a significant number of FES patients, and the discriminative features are clinically relevant for clinical presentation 1 year after the first episode of schizophrenia. The accuracy of the current approach is, however, insufficient to be used in clinical practice immediately. Several methodological issues need to be addressed to increase the usefulness of this classification approach.

Suicides in males after the first episode of schizophrenia.

The aim of this study was a retrospective analysis of available data on patients who committed suicide after the first episode of schizophrenia with focus on risk factors for suicide. Seven of 162 patients consecutively hospitalized at the Department of Psychiatry in Brno with first-episode schizophrenia and followed up for 10 years committed suicide by hanging (n = 4), shooting (n = 1), jumping from height (n = 1), and drowning (n = 1). All patients had more known risk factors and had visited a psychiatrist shortly before their suicide. However, according to the documentation, the patients were not asked about their intention to commit suicide and the potentially modifiable risk factors. Under the conditions of routine clinical practice, the prevention of suicide after the first psychotic episode should include early aggressive treatment and careful monitoring for suicidal behaviors in patients with known risk factors.

Effect of electroconvulsive therapy on cortical excitability in a patient with long-term remission of schizophrenia: a transcranial magnetic stimulation study.

The exact effects of electroconvulsive therapy (ECT) on the brain are still not accurately known. Hypotheses considered include the effect of ECT on cortical excitability of the brain. The aim of this trial was to assess the changes in cortical excitability in the brain of a patient with remitted schizophrenia, undergoing maintenance ECT. Three successive ECT applications resulted in significant prolongation of the cortical silent period, which implies augmentation of inhibitory cortical mechanisms in the brain, most likely mediated by the GABAergic (GABA, γ-aminobutyric acid) system with direct involvement of GABAB receptors. The actual therapeutic effect of ECT is therefore probably due to facilitation of cortical inhibitory mechanisms induced by GABAergic neurotransmission.