CURRENT OPTIONS OF BIOLOGICAL PSYCHIATRY IN THE TREATMENT OF SCHIZOPHRENIA
Libor Ustohal, Brno
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Background: Identifying patients with intractable epilepsy who would benefit from therapeutic chronic vagal nerve stimulation (VNS) preoperatively remains a major clinical challenge. We have developed a statistical model for predicting VNS efficacy using only routine preimplantation electroencephalogram (EEG) recorded with the TruScan EEG device (Brazdil et al., 2019). It remains to be seen, however, if this model can be applied in different clinical settings.
Objective: To validate our model using EEG data acquired with a different recording system.
Methods: We identified a validation cohort of eight patients implanted with VNS, whose preimplantation EEG was recorded on the BrainScope device and who underwent the EEG recording according to the protocol. The classifier developed in our earlier work, named Pre-X-Stim, was then employed to classify these patients as predicted responders or non-responders based on the dynamics in EEG power spectra.
Temporal lobe epilepsy (TLE) is the most common epilepsy type. TLE onset in infancy aggravates features like severity, drug responsiveness, or development of comorbidities. These aggravations may arise from altered micro RNA (miRNA) expression specific to the early onset of the disease. Although the miRNA involvement in TLE is widely studied, the relationship between the onset-age and miRNA expression has not been addressed. Here, we investigated the miRNA profile of infantile and adult-onset TLE in rats combining sequencing and PCR. Since miRNA expression changes with the disease progression, we scrutinized miRNA dynamics across three stages: acute, latent, and chronic. We report that infantile-onset TLE leads to changes in the expression of fewer miRNAs across these stages. Interestingly, the miRNA profile in the acute stage of infantile-onset TLE overlaps in dysregulation of miR-132-5p, -205, and -211-3p with the chronic stage of the disease starting in adulthood. The analysis of putative targets linked the majority of dysregulated miRNAs with pathways involved in epilepsy.
Background: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications.
Objectives: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity).
Methods: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses.
Results: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81.
Remyelination is a naturally occurring response to demyelination and has a central role in the pathophysiology of multiple sclerosis and traumatic brain injury. Recently we demonstrated that a novel MRI technique entitled Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn) achieved exceptional sensitivity in detecting the demyelination processes induced by lysophosphatidylcholine (LPC) in rat brain. In the present work, our aim was to test whether RAFF4, along with magnetization transfer (MT) and diffusion tensor imaging (DTI), would be capable of detecting the changes in the myelin content and microstructure caused by modifications of myelin sheets around axons or by gliosis during the remyelination phase after LPC-induced demyelination in the corpus callosum of rats. We collected MRI data with RAFF4, MT and DTI at 3 days after injection (demyelination stage) and at 38 days after injection (remyelination stage) of LPC (n = 12) or vehicle (n = 9). Cell density and myelin content were assessed by histology.
Since its inception as a science, psychology has been explicitly preoccupied with the mind-body relationship, specifically with the role that the nervous system plays in shaping how we perceive the world around us and how we react in our interaction with it. The evidence in this regard are the second and third chapters of William James's 1890 “The Principle of Psychology” (Volume 1) (1), which explain the functions of the brain and the general conditions underlying its activity, as well as the entire work of Wilhelm Wundt's 1904 “Principles of Physiological Psychology” (2), which explicitly linked the evolution of various mental functions to the organization and physiology of the nervous system. Yet, it was not until 1980s when the neuropsychology has established itself as a branch of psychology in its own right, aiming to explain how the brain and the other parts of the nervous system influence one's cognition, emotions and behaviors using a variety of methods from observation and questionnaires to computerized tasks gathering reaction time and electrophysiology. The knowledge thus obtained in healthy individuals was then employed by neuropsychologists in assessing the impact of various diseases on brain structure and function.
Objective: It is assumed that temporal lobe resection in older people is associated with worse seizure outcomes and potential postsurgical memory decline. We studied postsurgical memory development and surgical efficacy in patients over 45 years of age compared with younger patients.
Methods: We studied 88 patients (51 male and 37 female) after temporal lobe surgery, which involved hippocampal resection. The patients were evaluated before surgery and in the first (72 patients) and/or third (57 patients) postsurgical year. The Wechsler Memory Scale III test was performed to evaluate the MQ postsurgical development. Engel's classification was used to evaluate the postsurgical seizure outcome.
Results: The presurgical MQ (median 88) in ≥45 years age group was significantly lower than in both younger groups (median MQ = 100 for ≤30 years age group, p = 0.002; median MQ = 107 for 31-44 years age group, p = 0.002). Three years after the surgery, the MQ decreased significantly in ≤30 years age group (p = 0.012), while only non-significant MQ decline was observed in both older groups. We found no significant impact of age on the surgical outcome.
Background: Statistical analysis, which has become an integral part of evidence-based medicine, relies heavily on data quality that is of critical importance in modern clinical research. Input data are not only at risk of being falsified or fabricated, but also of being mishandled by investigators.
Objective: The urgent need to assure the highest data quality possible has led to the implementation of various auditing strategies designed to monitor clinical trials and detect errors of different origin that frequently occur in the field.
Methods: A particular electronic data capture (EDC) system, which is used for data management in clinical registries, is presented including its architecture and data structure. This EDC system features an algorithm based on machine learning designed to detect anomalous patterns in quantitative data. The detection algorithm combines clustering with a series of seven distance metrics that serve to determine the strength of an anomaly. For the detection process, the thresholds and combinations of the metrics were used and the detection performance was evaluated and validated in the experiments involving simulated anomalous data and real-world data.
Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients.