Radovan Přikryl

Prefrontal but not temporal grey matter changes in males with first-episode schizophrenia.

INTRODUCTION Changes of brain morphology are now considered as a part of the pathology of schizophrenia. Voxel-based morphometry may be used to study regional changes of the grey matter in the whole brain. It is advantageous to study first-episode patients to prevent the influence of many possible biasing factors when trying to identify primary pathological processes underlying the manifestation of the illness. OBJECTIVE To investigate regional grey matter changes in the first-episode schizophrenia patients. METHODS Optimized voxel-based morphometry was used to detect changes in grey matter volume in 22 patients with first-episode schizophrenia compared with 18 healthy volunteers of comparable age, gender and handedness. RESULTS The first-episode schizophrenia group had significantly reduced grey matter volume in the prefrontal cortex (inferior and middle prefrontal gyrus, cingulate gyrus). We identified no differences in the temporal cortex. CONCLUSION Our data support the theoretical assumption that prefrontal dysfunction underlines the primary pathology and clinical manifestation of schizophrenia. We are inclined to explain the differences in the pattern of morphological changes reported in other first-episode studies--especially the lack of changes in the temporal cortex--by heterogeneity of schizophrenia, potential progression and antipsychotic medication effect.

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. Clinical RecommendationsThere is an evidence showing that rTMS can be considered the effective treatment option for negative symptoms of schizophrenia.Based on the results of current meta-analyses, the effect size of high-frequency rTMS in the treatment of negative symptoms of schizophrenia seems to be mild to moderate (Cohen d = 0.43–0.63).Despite limited evidence base, the associations between efficacy and stimulation approaches (higher stimulation intensity, higher number of sessions or 10 Hz stimulus frequency) appear. Additional CommentsNeither the European Medicines Agency nor the Food and Drug Administration has approved rTMS for the treatment of negative symptoms of schizophrenia.Furthermore, large clinical studies are necessary to verify the natural benefit of rTMS for general clinical practice.

A118G Polymorphism of OPRM1 Gene is Associated with Schizophrenia

Schizophrenia is ranked among multifactor diseases in whose pathogenesis, besides environmental factors, an interplay of functional polymorphisms of a larger number of candidate genes is involved. Neurodevelopmental abnormities are among the most accepted hypotheses in the etiology of schizophrenia. Recently, the role of oligodendrocytes in the development of the cortex has been cited repeatedly. During their various phases of differentiation oligodendrocytes present on their surfaces diverse receptors, among others the μ-opioid receptor (OPRM1). The study was focused on the relationship between the functional A118G polymorphism of the OPRM1 gene (rs1799971) and schizophrenia in groups of 130 male patients and 452 male controls. An association study revealed yet unpublished statistically significant difference of allelic and genotypic frequencies between the control and patient groups. According to our present knowledge, we assume that the OPRM1 gene polymorphism can influence the myelination of CNS neurons through regulations of expression of OPRM1 receptors on surfaces of oligodendrocytes. The neuronal myelination seems to be one of the important factors in the pathogenesis of schizophrenia.

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.

Aberrant EEG responses to gamma-frequency visual stimulation in schizophrenia

Disturbance in the integration of visual information is one of the hallmarks of schizophrenia. In the spatial domain, visual integration is compromised, resulting in impaired perceptual grouping and contour integration. In the time domain, in contrast, visual integration is enhanced, as manifested by increased backward masking and lower ability of patients to detect successively presented visual stimuli as asynchronous. There is much evidence that integrative processes in the brain are supported by dynamic synchronization, or phase-locking, of neural firing. In particular, synchrony in the gamma band (>30 Hz) has been related to local visual information binding whereas synchrony in lower frequencies has been linked to global-scale integration. We recorded EEG signals evoked by steady-state gamma-frequency (40 Hz) photic stimulation in order to directly test the phase-locking of neural responses in schizophrenia. Compared with healthy control subjects, patients showed higher phase-locking of early evoked activity in the gamma band (36-44 Hz) over the posterior cortex, but lower phase-locking in theta (4-8 Hz), alpha (8-13 Hz) and beta (13-24 Hz) frequencies over the anterior cortex. Phase-locking of evoked responses separated schizophrenia and control subjects with accuracy of 86%. This result suggests that schizophrenia is associated with an enhanced early low-level integration in the visual cortex but a deficient high-level integration of visual information within the brain global workspace.

Movement sequencing abilities and basal ganglia morphology in first-episode schizophrenia

Introduction. Studies of brain morphology suggest a link between movement sequencing ability and basal ganglia dysfunction. Unfortunately, relevant studies have provided inconsistent data, which may be the result of differences in the methods of brain morphology assessment, statistical analysis or heterogeneity of the populations studied. Aim. to test the hypothesis of a link between the dysfunction of movement sequencing and basal ganglia morphology in a homogenous sample of first-episode schizophrenia patients. Method. Thirty-seven first-episode schizophrenia patients underwent an assessment of movement sequencing abilities using the NES scale and basal ganglia morphology from MR images. The data were compared with a group of 19 age- and sex-matched healthy controls. Results. The group of first-episode patients had a higher concentration of gray matter than healthy controls in the putamen and pallidum in both hemispheres. Patients with abnormal sequencing of movements had lower gray matter concentration than patients without such abnormalities in the left putamen, and no differences were found between the symptomatic group and healthy controls. Summary and conclusion. Our study suggests the involvement of the left putamen in the movement sequencing abnormalities in schizophrenia. Because of the potential confounding effect of medication, the lack of support from external evidence and the low power to perform the whole-brain analysis the results should be considered as preliminary. Further studies, especially with antipsychotic-naive first-episode schizophrenia patients are needed to solve these issues.

Cognitive impairment and cortisol levels in first-episode schizophrenia patients

Abstract 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.

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, &ggr;-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.

Insight in first-episode schizophrenia

Objective. To compare insight impairment, including its temporal changes, between remitters and nonremitters in patients with first-episode schizophrenia. Method. Males, consecutively hospitalized with diagnosed first-episode schizophrenia (according to ICD 10), who provided written informed consent, and were reassessed at the 1-year follow-up were included. The psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS) prior to acute treatment – on admission; at the end of the acute treatment – at discharge; at the 1-year follow-up. Insight was measured using item G12 from the PANSS. Results. Ninety-three patients (mean age 23 years, mean duration of illness 0.77 years) were reassessed after 1 year. A total of 73/93 patients (78%) fulfilled the criteria for remission. When compared, remitters and nonremitters showed no significant difference in impaired judgement and insight on admission. The mean value of this item was significantly lower at discharge even in nonremitters; however, a significantly higher value was found after 1 year in nonremitters. In remitters the impaired insight decreased significantly at discharge and there was a significant additional decrease after 1 year. In nonremitters there was a significant decrease at discharge; however, a significant increase was observed after 1 year. In the 73 remitters the rate of insight impairment was 79.4% on admission, 46.6% at discharge and 10.9% after 1 year; the same values were 90, 20 and 70% in the 20 nonremitters. In both remitters and nonremitters the lack of judgement and insight was the first or second most frequently observed item at all three time points. The impaired insight on admission was strongly associated with the overall symptomatology, including positive, negative and general psychopathology on admission in both remitters and nonremitters. Only in remitters was the impaired insight at discharge associated with symptoms at discharge, on admission and also after 1 year. The impaired insight at the 1-year follow-up was associated with some symptoms after 1 year in both remitters and nonremitters. Conclusion. Insight may be state dependent, especially in patients with a good outcome. Attitudes towards treatment and insight into the illness may vary during the course of the illness. However, more longitudinal prospective studies are needed to verify such state-related change, and the factors that may underlie the acquisition of insight.

Prolaction levels in risperidone treatment of first - episodeschizophrenia

OBJECTS: To evaluate the risperidone effect on prolactin (PRL) levels and to analyse the relation between PRL change and treatment response in first-episode schizophrenia patients. METHOD: Patients with a first-episode of schizophrenia who were consecutively admitted for hospitalisation participated in a longitudinal follow-up study that included clinical evaluation (PANSS) and PRL assessment. All patients were treated under open conditions with risperidone. RESULTS: Risperidone in an average dose lower than 4 mg significantly improved both positive and negative symptoms. Co-operating responders undergoing maintenance therapy showed a mild trend towards further long-term improvement. At the end of acute treatment the average elevation of PRL levels almost doubled the baseline value. There was a trend among responders to return to their initial values during long-term therapy. Three-quarters of the subjects had hyperprolactinaemia at the end of acute treatment (44 days), and after 1 year about one-quarter had hyperprolactinaemia. No significant correlation between PRL change and PANSS score change was found. CONCLUSION: There is a considerable variation of PRL elevation among subjects. In some patients the development of tolerance of the PRL-elevating effect was observed. Risperidone-induced changes of PRL levels may not be associated with treatment response.