Search

Schizophrenia is a serious mental disorder without a fully understood pathomechanism, but which involves dysregulation of neurotransmitters and their receptors. The best option for the management of schizophrenia comprises so-called multi-target ligands, similar to the third generation of neuroleptics. Dopamine type 2 receptors (D

According to recent findings schizophrenia and bipolar disorder as separate disease entities manifest similarities in neuropsychological functioning. Typical disturbances in both disorders are related to sensory gating deficits characterized by decreased inhibitory functions in responses to various insignificant perceptual signals which are experimentally tested by event related potentials (ERP) and measured P50 wave. In this context, recent findings implicate that disrupted binding and disintegration of consciousness in schizophrenia and bipolar disorder that are related to inhibitory deficits reflected in P50 response may explain similarities in psychotic disturbances in both disorders. With this aim, this review summarizes literature about P50 in both schizophrenia and bipolar disorder.

Serotonin (5-hydroxytryptophan [5-HT]) is a biologically active amine expressed in platelets, in gastrointestinal (GI) cells and, to a lesser extent, in the central nervous system (CNS). This biogenic compound acts through the activation of seven 5-HT receptors (5-HT1-7 Rs). The 5-HT3 R is a ligand-gated ion channel belonging to the Cys-loop receptor family. There is a wide variety of 5-HT3 R modulators, but only receptor antagonists (known as setrons) have been used clinically for chemotherapy-induced nausea and vomiting and irritable bowel syndrome treatment. However, since the discovery of the setrons in the mid-1980s, a large number of studies have been published exploring new potential applications due their potency in the CNS and mild side effects. The results of these studies have revealed new potential applications, including the treatment of neuropsychiatric disorders such as schizophrenia, depression, anxiety, and drug abuse. In this review, we provide information related to therapeutic potential of 5-HT3 R antagonists on GI and neuropsychiatric disorders. The major attention is paid to the structure, function, and pharmacology of novel 5-HT3 R modulators developed over the past 10 years.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depressive disorder, with outcomes approaching 45–55% response and 30–40% remission. Eligible predictors of treatment outcome, however, are still lacking. Few studies have investigated quantitative electroencephalography (QEEG) parameters as predictors of rTMS treatment outcome and none of them have addressed the source localization techniques to predict the response to low-frequency rTMS (LF rTMS). We investigated electrophysiological differences based on scalp EEG data and inverse solution method, exact low-resolution brain electromagnetic tomography (eLORETA), between responders and non-responders to LF rTMS in resting brain activity recorded prior to the treatment. Twenty-five unmedicated depressive patients (mean age of 45.7 years, 20 females) received a 4-week treatment of LF rTMS (1 Hz; 20 sessions per 600 pulses; 100% of the motor threshold) over the right dorsolateral prefrontal cortex. Comparisons between responders (≥50% reduction in Montgomery-Åsberg Depression Rating Scale score) and non-responders were made at baseline for measures of eLORETA current density, spectral absolute power, and inter-hemispheric and intra-hemispheric EEG asymmetry. Responders were found to have lower current source densities in the alpha-2 and beta-1 frequency bands bilaterally (with predominance on the left side) in the inferior, medial, and middle frontal gyrus, precentral gyrus, cingulate gyrus, anterior cingulate, and insula. The most pronounced difference was found in the left middle frontal gyrus for alpha-2 and beta-1 bands (p < 0.05). Using a spectral absolute power analysis, we found a negative correlation between the absolute power in beta and theta frequency bands on the left frontal electrode F7 and the change in depressive symptomatology. None of the selected asymmetries significantly differentiated responders from non-responders in any frequency band. Pre-treatment reduction of alpha-2 and beta-1 sources, but not QEEG asymmetry, was found in patients with major depressive disorder who responded to LF rTMS treatment. Prospective trials with larger groups of subjects are needed to further validate these findings.

Background The study evaluated the effectiveness of EEG alpha 1, alpha 2 and theta power, along with prefrontal theta cordance (PFC), frontal and occipital alpha 1, alpha 2 asymmetry (FAA1/2, OAA1/2) at baseline and their changes at week 1 in predicting response to antidepressants. Method: Resting-state EEG data were recorded from 103 depressive patients that were treated in average for 5.1 ± 0.9 weeks with SSRIs (n = 57) and SNRIs (n = 46). Results Fifty-five percent of patients (n = 56) responded to treatment (i.e.reduction of Montgomery-Asberg Depression Rating Scale score ≥ 50%) and 45% (n = 47) of treated subjects did not reach positive treatment outcome. No differences in EEG baseline alpha and theta power or changes at week 1 for prefrontal, frontal, central, temporal and occipital regions were found between responders and non-responders. Both groups showed no differences at baseline PFC, FAA1/2 and OAA1/2 as well as change of FAA1/2 at week 1. The only parameters associated with treatment outcome were decrease of PFC in responders and increase of OAA1/2 at week 1 in non-responders. There was no influence of the used antidepressant classes on the results. The PFC change at week 1 (PFCC) (area under curve-AUC = 0.75) showed only a numerically higher predictive ability than OAA change in alpha 1 (OAA1C, AUC = 0.64)/alpha 2 (OAA2C, AUC = 0.63). A combined model, where OAA1C was added to PFCC (AUC = 0.79), did not significantly improve response prediction. Conclusion Besides PFCC, we found that OAA1C/OAA2C might be another candidate for EEG predictors of antidepressant response.

Sensory gating disturbances in schizophrenia are often described as an inability to filter redundant sensory stimuli that typically manifest as inability to gate neuronal responses related to the P50 wave, characterizing a decreased ability of the brain to inhibit various responses to insignificant stimuli. It implicates various deficits of perceptual and attentional functions, and this inability to inhibit, or “gate”, irrelevant sensory inputs leads to sensory and information overload that also may result in neuronal hyperexcitability related to disturbances of habituation mechanisms. These findings seem to be particularly important in the context of modern electrophysiological and neuroimaging data suggesting that the filtering deficits in schizophrenia are likely related to deficits in the integrity of connections between various brain areas. As a consequence, this brain disintegration produces disconnection of information, disrupted binding, and disintegration of consciousness that in terms of modern neuroscience could connect original Bleuler’s concept of “split mind” with research of neural information integration.