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Dynamics of contrast-frequency characteristics of the visual system in patients with schizophrenia
- M. A. Tumova, I. I. Shoshina, V. V. Stanovaya, Z. T. Guseynova, M. V. Ivanov
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S450
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Introduction
Visual impairment in schizophrenia is of interest as a potential biomarker of the mental state. The study of visual impairment in patients with schizophrenia is difficult due to the fact that visual perception can be influenced not only by the patient’s condition, but also by age, drug treatment, concomitant eye diseases, etc. To reduce the influence of these factors, we studied visual disturbances in schizophrenic patients in dynamics at the second and eighth weeks of stable antipsychotic single treatment.
ObjectivesTo reveal changes in visual impairment in inpatients with schizophrenia on the background of changes in mental state.
MethodsEleven inpatients with schizophrenia who received antipsychotic monotherapy and thirteen healthy subjects of the same age and sex were included in the study. Examinations were performed at weeks 2 and 8 of treatment. The contrast-frequency characteristics of the visual system were examined using computer visocontrastometry. Visocontrastometry was performed in Gabor element contrast detection (gratings) with spatial frequencies of 0.4, 0.6, 0.8, 1.0, 4.0, 10.0 and 17.9 cycles/degree. Images of Gabor elements of different spatial frequency were repeated in random order 8 times each. The severity of the mental state was assessed during the interview using the PANSS (Positive and Negative Syndrome Scale).
ResultsPatients’ total PANSS score at week 2 averaged 94.09±17.58 and at week 8 averaged 52.45±6.06; at week 8 the total score was significantly lower than at week 2 (V = 66, p-value = 0.004). In the low-frequency region after treatment, patients tended to have lower thresholds (V = 2207, p-value = 0.060), but both at week 2 and week 8, thresholds were significantly higher in patients than in the healthy group (W = 7233, p-value < 2.2e-16, W = 6924.5, p-value = 1.204e-11, respectively). Mid-range frequencies increased at week 8 compared with week 2 (V = 925, p-value = 0.003), but were also lower at weeks 2 and 8 than in the healthy group (W = 1479, p-value = 7.247e-12, W = 3156.5, p-value = 0.004, respectively). In the high frequency region, thresholds also increased after the treatment (V = 908, p-value = 2.084e-05), at week 2, thresholds in patients were significantly lower than in healthy controls (W = 2574.5, p-value = 2.757e-07), and at week 8, thresholds in the patient and healthy groups were not different (W = 4759.5, p-value = 0.461).
ConclusionsThe impairments in the low spatial frequencies in schizophrenic patients appear earliest and, apparently, are the most persistent. Changes in the middle and high frequencies appeared to be more variable with changes in the mental state. Unfortunately, our design does not allow us to judge the persistence of the revealed changes. Further prospective studies are needed to investigate the relationship of visual disturbances with other symptoms.
Disclosure of InterestNone Declared
This work was supported by a grant from the Russian Science Foundation (project no. 22-18-00074).
Antipsychotic treatment and cognitive function in patients with schizophrenia
- M. A. Tumova, A. A. Stepanova, M. G. Yanushko, A. P. Kotsyubinsky, M. V. Ivanov
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S125-S126
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Introduction
It is known that cognitive impairment is one of the main symptoms of schizophrenia, which determines the functional outcome. The question of the effect of antipsychotics on the cognitive functions of these patients is still unresolved. Cognitive impairment while taking antipsychotics is thought to be mostly related to extrapyramidal abnormalities. In practice, it is difficult to distinguish what causes a patient’s complaints of cognitive decline. Is it related to taking the medication? Or a worsening mental state? Age, lifestyle, etc.?
ObjectivesWe analyzed the relationship of cognitive impairment with the severity of extrapyramidal symptoms, mental status gravity, age, and dose of antipsychotic and cholinergic medication at weeks 2 and 8 of treatment.
MethodsWe examined 37 patients with schizophrenia on stable antipsychotic treatment at weeks 2 and 8 of therapy. Thirty patients received a 2nd-generation antipsychotic, and seven patients received a 1st-generation antipsychotic. The anticholinergic drug was trihexyphenidyl. The antipsychotic dose was estimated in olanzapine equivalent. Extrapyramidal symptoms were assessed by The Scale for Extrapyramidal Symptoms (SAS), severity of mental condition was rated by The Positive and Negative Syndrome Scale (PANSS), cognitive function was measured by The Brief Assessment of Cognition in Schizophrenia (BACS).
ResultsAs previously described, patients with more severe extrapyramidal symptoms tended to have lower BACS composite scores (rxy = -0.318, p-value = 0.055) at week 8 of therapy. The total score on the SAS scale, as expected, only negatively correlated with scores on the Token Motor Task test (rxy = -0.412, p-value = 0.011) at the 8th week of therapy. There were also negative correlations between Token Motor Task scores and trihexyphenidyl dose (rxy = -0.496, p-value = 0.002). At both weeks 2 and 8, there was a negative relationship between age and Symbol Coding scores (rxy = -0.387, p-value = 0.018; rxy = -0.35, p-value = 0.034, respectively). Verbal Fluency scores were lower in patients with high scores on the PANSS excitement component and at week 2 (rxy = -0.42, p-value = 0.01), this trend continued at week 8 (rxy = -0.31, p-value=0.063) . Tower of London scores were negatively associated at week 8 with cognitive and positive PANSS scores (rxy = -0.46, p-value = 0.004; rxy = -0.336, p-value = 0.042, respectively).
ConclusionsThus, we have demonstrated that cognitive impairment in patients with schizophrenia is associated with various factors, and not only antipsychotic treatment.
Disclosure of InterestNone Declared
Interrelation of visual and olfactory impairments in schizophrenia
- M. Tumova, V. Karpinskaya, E. Bezgacheva, L. Muslimova, E. Bigday, M. Ivanov
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- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, pp. S162-S163
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Introduction
In schizophrenia, there are disorders in all sensory modalities, but the regularities of their occurrence, their pathogenesis and attitude towards cognitive functions are not sufficiently studied.
ObjectivesExamine the interrelation between the dysfunctions in different analysers (olfactory and visual) and their dependence on the duration of the disease and the severity of psychotic symptoms and cognitive deficit in schizophrenic patients (F20 according to ICD 10 criteria).
MethodsAll subjects were determined the threshold of olfactory sensitivity to n-butanol, the ability to discriminate against odors and the amount of error in comparing the same sections. Cognitive functions were evaluated using the BACS scale.
ResultsThe inverse correlation between the value of the visual assessment error and the reduction of the threshold of olfactory sensitivity (r=- 0.56; p < 0.05) and the inverse correlation between the value of the visual assessment error and the ability to discriminate smells (0.64; p < 0.05) were revealed. There are no significant correlations between the duration of the disease and sensory disturbances. Olfactory and visual disturbances in schizophrenic patients were connected with cognitive functions ((r=-0,62; p< 0,05 and r=-0,84, p< 0,001 accordingly).
ConclusionsThe data confirm that sensory impairments have a common pathogenesis and are closely related to cognitive deficits. Sensory and cognitive deficits in schizophrenia may be the result of top-down regulation failure.
DisclosureNo significant relationships.
Calcineurin role in porcine oocyte activation
- L. Tůmová, E. Chmelíková, T. Žalmanová, V. Kučerová-Chrpová, R. Romar, M. Dvořáková, K. Hošková, J. Petr
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Calcineurin is required for oocyte exit from meiotic block in metaphase II (MII) stage in invertebrates and also in lower vertebrates. However, the role of calcineurin in mammalian oocyte activation is still unclear. The aim of this study was to determine whether calcineurin is involved in the processes regulating porcine oocyte activation. Indirect immunofluorescence demonstrated localization of both calcineurin subunits, CnA and CnB, especially in the cortex area of MII oocytes, in vitro fertilized and also parthenogenetically activated oocytes. After activation, the fluorescence intensity of the protein in the cortex area of oocytes remains unchanged; the protein calcineurin in the cytoplasm was recorded mainly around the pronuclei. Treatment of matured oocytes with calcineurin inhibitors, cyclosporin A (CsA) and hymenistatin I (HS-I), followed by activation with calcium ionophore A23187, significantly decreased the rate of activated oocytes compared to oocytes that were treated only with calcium ionophore (Ca-Io), (CsA+Ca-Io 25.0% v. Ca-Io 83.3%; HS-I+Ca-Io 32.5% v. Ca-Io 85.0%). Compared to the control, CsA treatment of matured oocytes followed by activation with Ca-Io did not affect the activity level of metaphase-promoting factor (MPF) and mitogen-activated protein kinase (MAPK) in activated oocytes evaluated by kinase activity assay. Simultaneous staining of calcineurin and cortical granule content in matured oocytes showed that calcineurin distributed in the cortical area of the oocyte has not been colocalized with cortical granules content. On the other hand, the calcineurin inhibition before parthenogenetic activation leads to a reduction of the cortical reaction level compared to oocytes that were not treated with CsA (complete exocytosis: CsA+Ca-Io 2.6% v. Ca-Io 83.9%; sum of cortical granule brightness: CsA + Ca-Io 0.69 v. Ca-Io 0.15). Our results showed that calcineurin is involved in the process of pig oocyte activation and cortical granule exocytosis; however this regulation seems to be MPF and MAPK independent.
The effect of protein kinase C activator and nitric oxide donor on oocyte activation and cortical granule exocytosis in porcine eggs
- L. Tůmová, R. Romar, J. Petr, M. Sedmíková
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Nitric oxide (NO) and protein kinase C (PKC) are involved in the activation of mammalian oocytes, although their role in the exit from the metaphase II stage and cortical granule (CG) exocytosis is still not fully understood. The aim of this study was to verify whether the NO-donor together with specific PKC-activators induce the complete activation of porcine oocytes assessed as meiosis resumption and a cortical reaction. Pig maturated oocytes were treated with the NO-donor S-nitroso-N-acetylpenicillamine (SNAP, 2 mM) or PKC-activators such as phorbol-12-myristate-13-acetate (PMA, 100 nM), 1-oleoyl-2-acetyl-sn-glycerol (OAG, 400 μM) and l-α-phosphatidylinositol-3,4,5-trisphosphate dipalmitoyl heptaammonium salt (DPAM, 2 μM). To study the combined effect of NO-donor and PKC-activators, aliquots of oocytes were also incubated with SNAP (0.5 mM) together with PKC-activators at the same concentration as above (SNAP–DPAM, SNAP–OAG and SNAP–PMA groups). After invitro maturation, an aliquot of oocytes was placed in a fresh medium without NO-donor or PKC-activators (Control group). Another aliquot of oocytes was activated by calcium ionophore A23187 (25 μM, 5 min). The results showed that 0% of the control oocytes reassumed meiosis. However, both the PKC-activators (DPAM 44.0 ± 10.0%, OAG 63.3 ± 1.0% and PMA 45.0 ± 16.5%) as well as the NO-donor alone (48.7 ± 21.0%) significantly induced exit from MII. Interestingly, the combination of PKC-activators and SNAP mainly restrained to the meiosis resumption (SNAP–OAG 0, SNAP–DPAM 17.4 ± 2.5% and SNAP–PMA 38.4 ± 8.5%). Control oocytes did not show a cortical reaction and the area occupied by CG reached 25.9 ± 1.7%, whereas CGs were partially released after Ca2+ ionophore treatment (13.0 ± 3.2%). Treatment with PKC-activators induced a cortical reaction compared with the control group (8.6 ± 2.5, 6.7 ± 1.9 and 0.7 ± 0.4%, respectively, for DPAM, OAG and PMA groups). However, treatment with the NO-donor alone (SNAP group 17.2 ± 2.2%) or combined with any PKC-activator prevented cortical reaction (SNAP–DPAM 20.7 ± 2.6%, SNAP–OAG 16.7 ± 2.9% or SNAP–PMA 20.0 ± 2.4%). Besides, meiosis resumption was not always accompanied by a cortical reaction, indicating that these two activation events are independent. In conclusion, PKC-activators alone induce CG exocytosis to the same degree as calcium ionophore. However, an NO-donor alone or combined with PKC-activators is not able to induce a cortical reaction in pig oocytes.
Nitric oxide and meiotic competence of porcine oocytes
- H. Tichovská, J. Petr, E. Chmelíková, M. Sedmíková, L. Tůmová, M. Krejčová, A. Dörflerová, R. Rajmon
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Reproductive biotechnology such as in vitro fertilization, the creation of transgenic animals or cloning by nuclear transfer depends on the use of fully grown, meiotically competent oocytes capable of completing meiotic maturation by reaching the stage of metaphase II. However, there exists only a limited quantity of these oocytes in the ovaries of females. In view of their limited number, growing oocytes without meiotic competence represent a possible source. The mechanisms controlling the acquisition of meiotic competence, however, are still not completely clear. A gas with a short half-life, nitric oxide (NO), produced by NO-synthase (NOS) enzyme can fulfill a regulatory role in this period. The objective of this study was to ascertain the role of NO in the growth phase of pig oocytes and its influence on the acquisition of meiotic competence with the help of NOS inhibitors, NO donors and their combinations. We demonstrated that the selective competitive iNOS inhibitor aminoguanidine and also the non-selective NOS inhibitor l-NAME block meiotic maturation of oocytes with partial or even full meiotic competence at the very beginning. NOS inhibitors influence even competent oocytes in the first stage of meiotic metaphase. However, blockage is less effective than at the beginning of meiotic maturation. The number of parthenogenetically activated competent oocytes greatly increased in a pure medium after inhibitor reversion. A large quantity of NO externally added to the in vitro cultivation environment disrupts the viability of oocytes. The effectiveness of the inhibitor can be reversed in oocytes by an NO donor in a very low concentration. However, the donor is not capable of pushing the oocytes farther than beyond the first stage of meiotic metaphase. The experiments confirmed the connection of NO with the growth period and the acquisition of meiotic competence. However, it is evident from the experiments that NO is not the only stimulus controlling the growth period.