Radovan Prikryl

Caudate and putamen volumes in good and poor outcome patients with schizophrenia

Magnetic resonance images of 37 patients with schizophrenia and 37 age- and sex-matched volunteers were acquired. The caudate nucleus and putamen were traced on axial slices from the most superior extent of the caudate to the most inferior point where the caudate and putamen merge. Two subtypes of schizophrenia were compared, the Kraepelinian subtype (n=13), characterized by an unremitting and severe course, and the non-Kraepelinian subtype (n=24), characterized by a remitting course and some periods of self-care. Patients with good outcome schizophrenia had larger relative mean putamen size (0.0129) than poor outcome patients (0.0123) or normal controls (0.0121), but not caudate size. This enlargement was most marked for the dorsal putamen and right hemisphere. Striatal size was not related to whether patients were currently being treated with atypical or typical neuroleptics or whether they had been predominantly treated with typical or atypical neuroleptics over the past 3 years. This suggests the possibility that the expansion of putamen size may be a physiological correlate of neuroleptic responsiveness or that small putamen size at disease onset may be a predictor of outcome.

Source-based morphometry of gray matter volume in men with first-episode schizophrenia.

Objectives: There is a lot of variability between the results of studies reporting the pattern of gray matter volume changes in schizophrenia. Methodological issues may play an important role in this heterogeneity. The aim of the present study was to replicate the better performance of multivariate “source‐based morphometry” (SBM) over the mass‐univariate approach. Experimental design: Voxel‐based morphometry of Jacobian‐modulated gray matter volume images, using voxel and cluster level inference, and SBM were performed in a group of first‐episode schizophrenia patients (N = 49) and healthy controls (N = 127). Results: Using SBM we were able to find a significant reduction of gray matter volume in fronto‐temporo‐cerebellar areas whereas no significant results were obtained using voxel‐based morphometry. Conclusion: Multivariate analysis of gray matter volume seems to be a suitable method for characterization of the pattern of changes at the beginning of the illness in schizophrenia subjects. Hum Brain Mapp, 2010.

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.

Gray matter morphology and the level of functioning in one-year follow-up of first-episode schizophrenia patients.

UNLABELLED Schizophrenia is a condition with a highly variable course that is hard to predict. The aim of the present study was to investigate if local gray matter volume (GMV) can differentiate poor (PF) and good (GF) functioning patients using voxel-wise analysis in a group of first-episode schizophrenia subjects (FES). METHOD 32 FES male patients were assessed twice: at the time of the first episode of schizophrenia and one year later. 18 healthy controls matched for age, gender, and handedness were also included. Local gray matter volume was analyzed using voxel-wise full-factorial design with factors group (GF, PF) and time. RESULTS FES subjects had bilateral gray matter reduction in the lateral prefrontal cortex as compared with healthy controls. PF subjects had smaller GMV in the left orbitofrontal and frontopolar cortex. CONCLUSION GMV in the left prefrontal cortex differentiates later poor and good functioning schizophrenia patients. Morphological analysis might be considered a candidate for a biological marker in outcome prediction. However, the small sample size, and the lack of female subjects limit generalization of results. Moreover, studies analyzing the predictive value of brain morphology on a single-subject level should be performed to assess its real usefulness in outcome prediction.

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.

Occurrence of epileptic paroxysm during repetitive transcranial magnetic stimulation treatment.

The paper is about an induction of epileptic paroxysm during high frequency repetitive trancranial magnetic stimulation treatment.

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 schizophrenia—the 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. Hum Brain Mapp, 2013.

Screening for Neuroligin 4 (NLGN4) truncating and transmembrane domain mutations in schizophrenia

The present findings suggest that neither of two previously described NLGNX4 truncating mutations plays a major role in schizophrenia. Systematic screening of the transmembrane domain sequence of NLGN4X and NLGN4Y confirmed that this key functional region is also highly conserved in schizophrenic subjects. Our data currently do not rule out mutations in the remaining NLGN4 sequences, spanning 140kb on the X-chromosome, and 340kb on the Y-chromosome. More detailed investigations, however, including autosomal neuroligin genes, have now equally tempered expectations of a strong neuroligin genotype-phenotype association in other neurodevelopmental disorders (Vincent et al., 2004; Ylisaukko-Oja et al., 2005). Thus the phenotypic risk ascribable to truncating NLGN4 variants is most likely limited to rare monogenetic syndromes distinct from the majority of autistic and schizophrenic typologies.

Outcome in males with first-episode schizophrenia: 7-year follow-up.

Abstract Objectives. The early course of schizophrenia is highly variable. We assessed outcomes of patients with first-episode schizophrenia at 7-year follow-up. Methods. Consecutively hospitalized male patients were included if they were experiencing their first admission for first-episode schizophrenia and were reassessed at 1-, 4- and 7-year follow-ups. The psychopathology was evaluated using the PANSS, relative decrease of PANSS and remission status based on severity of core symptoms. Results. Forty-four of 76 patients were reassessed three times. At the end of index hospitalization 73% of patients achieved remission; however, after 1, 4 and 7 years, the percentage had dropped to 50, 50 and 52%, respectively. When compared post-hoc there was no significant difference in PANSS and response to treatment between remitters and non-remitters during the index hospitalization; however, a significant difference in psychopathology emerged first after 1, 4 and 7 years. All patients who had not achieve remission after 1 year also failed to achieve remission after 4 and 7 years. Conclusions. Response to treatment during the first psychotic break-through may not be a decisive indicator for the outlook of the disease. Our data suggest that when deterioration occurs, it does so early after the first episode.

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.