The aim of the study was to identify electrophysiological biomarkers of major depressive disorder (MDD) through high-density EEG technique.

IntroductionDeficits in behavioral inhibition leading to impulsivity occur frequently in many otherwise different psychiatric diseases, mainly ADHD and borderline personality disorder (BPD). However, the research is complicated by using of different tests and their parameters. Further, the role of frontoparietal network in behavioral inhibition has been questioned recently.ObjectivesThe aims of our studies were:– to present the influence of differences in inhibition tasks parameters;– to describe neural correlates of behavioral inhibition in healthy people;– to compare them with BPD and ADHD patients.MethodsWe implemented two different variants of Go/NoGo Task, one designed for behavioral research and the second for neuroimaging. Thirty healthy participants (37% of women, age range 15 to 33 years) underwent behavioral and fMRI measurement. Further, groups of patients with BPD, ADHD and their healthy controls underwent the Go/NoGo Task under both fMRI and EEG.ResultsThe results show differences in behavioral performance based on different task parameters. The fMRI results in healthy people show specific activation patterns within the frontoparietal network associated with inhibition trials (mainly inferior frontal gyrus, insula, cingulate gyrus, SMA, inferior parietal lobule). Further, we present differences between patients with BPD, ADHD and controls in BOLD signal and ERPs.ConclusionsGo/NoGo Task design substantially influences the subjects’ behavioral performance. Our results with methodologically upgraded Go/NoGo Task design provide support for the inhibition frontoparietal brain network and its different activations in BPD and ADHD patients. The research was supported by Ministry of Health of the Czech Republic, grant nr. 15-30062A.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Introduction Cognitive impairment in patients with depressive disorder is a subject of intensive research. Objectives This study deals with the cognitive impairment in patients with severe depressive episode with psychotic symptoms and patients with major depressive disorder during the acute state of illness. Aims The aim was to define domains and the level of cognitive impairment in both groups of patients. The next aim was to compare profiles of cognitive impairment in both groups of patients. The last aim was to find out a relationship between cognitive performance and severity of depressive episode during the acute state of illness. Methods We have used neuropsychological test battery (Auditory–Verbal Learning Test, Rey-Osterrieth Complex Figure Test, Logical Memory, Digit span test, Trail making test, Verbal Fluency Test, Block Design and Benton Visual Retention Test) for the evaluation of the cognitive functions in patients with severe depressive episode with psychotic symptoms (n = 5) and patients with major depressive disorder (n = 8). Results We found cognitive impairment in all examined domains in both groups of patients. More profound cognitive impairment was found in patients with severe depressive episode with psychotic symptoms, particularly in visual memory, visuo-constructive abilities, speed of cognitive processing and executive functions. We found no correlation between cognitive performance and severity of depressive episodes. Conclusions Our findings suggest a strong correlation between psychotic symptoms in depression and cognitive performance.

Alcohol dependence leads to adaptations of the nervous system that leads to withdrawal syndrome manifestation when regular alcohol consumption is abruptly discontinued. Withdrawal syndrome is characterized mainly by excessive excitatory and diminished inhibitory mechanisms, mediated by glutamatergic and gaba-ergic systems. This imbalance leads to anxiety, restlessness, tremor and decreased seizure threshold. Furthermore, changes to dopaminergic, serotoninergic, noradrenergic, opioid system, or corticotropin releasing hormone-related activation of stress reaction contribute to the clinical picture that includes vegetative hyperactivity, affective changes, dysphoria, hypohedonia, etc. Delirium - a complication of severe withdrawal - is a significant clinical syndrome that complicates health care management and may lead to fatal outcomes. Treatment of alcohol withdrawal and delirium is based on gradual establishment of a new balance of excitatory and inhibitory systems without the presence of external inhibitory substance - alcohol. In clinical practice the pathophysiology is reflected in the administration of gaba-ergic compounds (benzodiazepines, clomethiazole) with gradual dose tapering. Complex effect of alcohol with a number of related somatic complications requires additional systematic somatic care.

What is known and Objective: Accurate prediction of actual CYP2D6 metabolic activity may prevent some adverse drug reactions and improve therapeutic response in patients receiving CYP2D6 substrates. Dextromethorphan-to-dextrorphan metabolic ratio (MRDEM/DOR) is well established as a marker of CYP2D6 metabolizer status. The relationship between urine and plasma or serum MRDEM/DOR is not well established nor is there evidence of antimode for separation of intermediate and especially poor metabolizers (PM) from extensive metabolizers (EM). This study addressed whether CYP2D6 phenotyping using molar metabolic ratio of dextromethorphan to dextrorphan (MRDEM/DOR) in serum is usable and reliable in clinical practice as urinary MRDEM/DOR. Methods: We measured MRDEM/DOR in serum and CYP2D6 genotype in 51 drug-naive patients and 30 volunteers. Receiver-operator characteristic (ROC) analysis was used for the evaluation of optimum cut-off value for discriminating between extensive, intermediate and PM. In addition, we studied the correlation of serum MRDEM/DOR with urine MRDEM/DOR in the 30 healthy volunteers. Results and Discussion: A trimodal distribution of log MRDEM/DOR in serum was observed, with substantial overlap between extensive and intermediate metabolizer groups. We obtained an acceptable cut-off serum MRDEM/DOR value to discriminate between PM and either extensive or extensive + intermediate metabolizers. Using serum MRDEM/DOR, it seems to be unreliable to discriminate EM from intermediate metabolizers (IM). A strong correlation between serum MRDEM/DOR and urine MRDEM/DOR was found. What is new and Conclusion: Serum MRDEM/DOR (3 h) correlated with MRDEM/DOR in urine (08 h). Serum MRDEM/DOR discriminated between extensive and PM and between extensive + intermediate and PM. Our CYP2D6 phenotyping using serum dextromethorphan/dextrorphan molar ratio appears reliable but requires independent validation.

Acknowledgement The study was supported by the grant of Czech Ministry of Health No. NS 9676-4/2008.

IntroductionRisperidone is an antipsychotic used as the first-line treatment of schizophrenia. Risperidone is metabolised by enzyme CYP2D6. Activity of this enzyme can be predicted by genotypization.ObjectivesTo explore the possibility of different response rate to risperidone in first-episode schizophrenia patients with different CYP2D6 genotype.AimTo asses the utility of CYP2D6 pharmacogenetic testing in patients with schizophrenia treated with risperidone.MethodsCYP2D6 genotype was assessed in 22 first-episode schizophrenic patients by use of automatic sequencing of DNA isolated from peripheral leukocytes. PANSS score was assessed every week of treatment until the change in medication or patient release.Response was defined as at least 30% reduction in total PANSS. Differences in response rate between groups were tested by Fisher's exact test.Results10 CYP2D6 extensive metabolisers (EM), 8 intermediate metabolisers (IM) and 4 poor metabolisers (PM) were identified. Criteria for response met 4 EM, 4 IM and 1 PM. Differences in response rate between groups were not statistically significant.ConclusionsAlthough group of IM had higher response rate than EM and PM, differences in response rate did not reach statistical significance. Further differences may be found by extending the sample size. An useful approach would be also to examine differences in occurrence of adverse effects and subjective tolerance of the treatment.AcknowledgementThe study was supported by the grant of Czech Ministry of Health No. NS 9676-4/2008.

IntroductionPsychiatric Patients show abnormalities in volumes of several subcortical structures. Recently wider usage of automated segmentation methods in research of these abnormalities based on MR images has become possible. However manual segmentation is still considered to be the gold standard.ObjectivesTo compare differences in hippocampus volumes between manual segmentation and 2 packages for automatic segmentation (FSL and FreeSurfer).AimTo explore the overlap and differences between different segmentation methods used for segmentation of subcortical structures.MethodsStructural MR brain scans were aquired from 98 subjects (53 schizophrenia patients, 45 controls). Volumes of left and right hippocampus were measured after manual, FreeSurfer and FSL segmentations. Differences between volumes from different methods were tested by the t-test (using R). In addition percent volume differences, Pearson correlations, Bland-Altman plots and Cronbach’s alpha were computed.ResultsBoth automatic methods yielded significantly larger hippocampal volumes than the manual segmentation. FreeSurfer volumes showed a higher correlation and lower percent volume difference with manual segmentation than FSL. Bland-Altman plots and Cronbach’s alpha showed only limited agreement between manual and both automatic methods.ConclusionsAlthough volumes acquired by FreeSurfer appeared to be more related to manual segmentation, clear superiority of either of automatic methods could not be demonstrated. Therefore, all three methods seem to measure other aspects of hippocampus volume. An useful approach would be to compare effect-size of the difference between patients and healthy controls using different segmentation methods. We are currently pursuing this in a larger sample.

Several approaches utilizing selective probe substrates were used for CYP2D6 metabolic activity assessment. The aim of this work was to find out the correlation between conventional urine dextromethorphan to dextrorphan metabolic ratio (MRDEM/DOR), and MRDEM/DOR measured in serum and to verify the ability of serum MRDEM/DOR to discriminate poor and intermediate metabolizers from extensive metabolizers. We measured MRDEM/DOR in 4h serum and CYP2D6 genotype in 51 drug-naive patients and MRDEM/DOR in 4h serum and 0-8h urine in 30 healthy volunteers. Strong correlation between the serum MRDEM/DOR and urine MRDEM/DOR was found. There was proved ability of 4h serum MRDEM/DOR to discriminate poor from extensive and intermediate metabolizers, but not intermediate from extensive metabolizers.

The study sumarizes the knowledge of the correlation of metabolic phenotype and genotype of CYP2D6 with the therapeutical response in first episode- schizphrenic patients treated with risperidone.

Article about Comparison of serum and urine analyses in CYP2D6phenotyping for psychiatric purposes