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Nanopore sequencing as a novel approach to transcend into the deep universe of schizophrenia
- I. B. Nita, O. D. Ilie, A. S. Ciobica, L. D. Hritcu, R. Popescu, R. P. Dobrin
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S439
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Introduction
Schizophrenia (SCZ) is a chronic neuropsychiatric disorder possessing a multifactorial nature and dual facets of symptoms with a core underlying genetic mechanism that is still obscure. Lately, genomic studies revealed numerous single nucleotide polymorphisms (SNPs) that are non-coding and influence ribonucleic acid (RNA) expression, particularly its splicing.
ObjectivesConsidering that next-generation sequencing (NGS) protocols focus upon long-read sequencing as opposed to conventional RNA sequencing methodologies once with the advent of Oxford Nanopore Technologies’ (ONT) MinION, we primarily aimed to gather and review all evidence into how this approach may deepen and further offer insight into SCZ still undiscovered domain.
MethodsThe relevant literature searches were performed using distinct combinations of keywords including “schizophrenia” alongside „Nanopore”, “MinION”, and “Oxford Nanopore Technologies” on four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect). We implied the entries to strictly “research articles” written in English as inclusion criteria.
ResultsBy restricting the returned results starting with the year when the platform was officially launched, a total of n = 69 studies were displayed between the pre-established interval (2014 – 2022). If taken per database, n = 2 were identified in PubMed/Medline, n = 7 in ISI Web of Knowledge, n = 4 in Scopus, and n = 56 in ScienceDirect. In chronological order, n = 0 were published in 2014, n = 3 in 2015, n = 7 in 2016, n = 7 in 2017, n = 9 in 2018, n = 3 in 2019, n = 7 in 2020, n = 19 in 2021 and n = 14 in 2022. Finally, per the strategy applied, n = 49 were returned for “schizophrenia” + “Nanopore” from which n = 2 in PubMed/Medline, n = 5 in ISI Web of Knowledge, n = 4 in Scopus, and n = 38 in ScienceDirect. For “schizophrenia” + “MinION, there was a cumulative number of n = 5, from which we had n = 0 in PubMed/Medline, n = 0 in ISI Web of Knowledge, n = 0 in Scopus, and n = 5 in ScienceDirect. Finally, for “schizophrenia” + “Oxford Nanopore Technologies” were displayed n = 15, and the situation was n = 0 in PubMed/Medline, n = 2 in ISI Web of Knowledge, n = 0 in Scopus, and n = 13 in ScienceDirect.
ConclusionsWe presently assist to a fulminant ascension in the literature, with applicability in other fields. Perhaps as cornerstone stands a recent publication in which the authors reveal the risk of the Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C) gene involved, being identified thirty-eight novel exons and two hundred and forty-one novel transcripts following RNA purification from six regions (cerebellum, striatum, and dorsolateral prefrontal cortex) among which targeted were cingulate, occipital and parietal cortexes.
Disclosure of InterestNone Declared
Chronic stress exposure paradigm in zebrafish models – focusing on neurobehavioral and biochemical changes
- I. M. Balmus, R. O. Cojocariu, R. Lefter, L. Gorgan, A. Ciobica
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S919
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Introduction
Our previous reports on rodent models suggested that chronic stress exposure could lead to cognitive impairments, gastrointestinal transit changes, and oxidative stress. Zebrafish (Danio rerio) models are nowadays gaining more attention due to their advantages, as well as their complete neurobehavioral, biochemical, and genetic description and great similarity to human.
ObjectivesThe aim of this study was to describe and to identify possible interdisciplinary applications of the neurobehavioral and biochemical changes induced by chronic stress exposure in zebrafish.
MethodsThe main scientific databases were screened for English-written studies describing chronic stress exposure effects in animal models. Inclusion criteria: (1) studies performed on zebrafish models; (2) reporting stress exposure effects on the animal behaviour, cognition, oxidative, and/or inflammatory status. Exclusion criteria: (1) studies not focussing on chronic stress exposure paradigm or (2) not using zebrafish models.
ResultsWe found that chronic stress exposure was applied to larvae, juveniles, and adult zebrafish. The neurobehavioral effects were mainly suggesting memory deficits and socio-affective impairments (such as anxiety and depressive-like behaviours). Several studies found oxidative stress and inflammatory-related response in brain and gut. While our previous research experience in rodents thought us that chronic stress exposure could model functional gastrointestinal disorders of which mechanisms mainly address an impaired brain – gut interaction (irritable bowel syndrome), the data regarding the gastrointestinal status of zebrafish in similar experimental conditions are rather scarce. Some recent studies suggested that stress-exposed zebrafish showed impaired digestion and intestinal glucocorticoid receptors functions. Furthermore, it was reported that the zebrafish response to stress could be improved by probiotic administration and gut microbiota modulation.
ConclusionsChronic stress exposure paradigm is often associated with cognitive and affective-like impairments. Several oxidative stress and inflammation-related changes were also reported. Further studies are needed to describe the brain – gut interaction-associated functional gastrointestinal impairments in zebrafish.
Acknowledgements: *B. I.-M. is supported by the Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational Program.
Disclosure of InterestI. M. Balmus Grant / Research support from: Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational Program., R. O. Cojocariu: None Declared, R. Lefter: None Declared, L. Gorgan: None Declared, A. Ciobica: None Declared
The environmental and social stress perception in autism spectrum disorder – focusing on stress coping mechanisms and gastrointestinal manifestations
- I. M. Balmus, M. A. Robea, R. Lefter, A. Ciobica, L. Gorgan, C. Stanciu, A. Trifan
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S918-S919
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Introduction
Autism spectrum disorder (ASD) is currently defined as persistent deficits in social communication and social interaction additional to repetitive behavioural patterns, and restrictive interests or activities. Several studies suggested that ASD is accompanied by defective perception and altered response to the environmental factors, including environmental and social stress. In this context, frequent reports addressed the manifestation of different stress-related behavioural and physiological patterns, such as restless leg syndrome, migraine, and functional gastrointestinal disorders (FGIDs). Thus, a major problem in ASD patients’ management could be related to the exacerbated effects of stress.
ObjectivesIn this study, we aimed to find a correlation between the stress perception and response and the manifestation of some neurological and FGIDs in ASD.
MethodsThe main scientific databases were screened for studies describing the effects of stress in autism patients and animal models. Exclusion criteria: (1) studies not written in English language; (2) not available as full text; (3) not describing stress response; and/or (2) functional gastrointestinal manifestations in autism.
ResultsThe repetitive behaviours have a heterogenous pattern in both severity and manifestations, varying from repetitive motor movements and inflexible adherence to routines to hypo- or hyper-reactivity to exterior stimuli. Moreover, some studies describe repetitive behaviours as altered stress coping mechanisms meant to relieve anxious states – one of the main stress axis activation effects. We recently described some significantly reported FGID-like manifestations in ASD that could be the result of various abnormalities in the brain – gut interaction, such as impaired parasympathetic activity and increased endocrine stress response. In this context, there could be a correlation between the altered perception and response to stress and the FGID-like manifestations, as we previously described the stress axis implication in one of the most common FGID, irritable bowel syndrome – which is also frequently reported in ASD cases.
ConclusionsIn ASD, the perception and response to environmental and social stress could be impaired. Thus, impaired stress coping mechanisms, defective stress axis, and altered behavior could lead to stress-specific manifestations, such as restless leg syndrome, migraine, and irritable bowel syndrome.
Funding: *B. I.-M. and *R. M.-A. are supported by the Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational Program
Disclosure of InterestI. M. Balmus Grant / Research support from: B. I.-M. is supported by the Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational Program., M. A. Robea Grant / Research support from: R. M.- A. is supported by the Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational Program., R. Lefter: None Declared, A. Ciobica: None Declared, L. Gorgan: None Declared, C. Stanciu: None Declared, A. Trifan: None Declared
Neurological and neuropsychiatric comorbidities occurring in fatty liver diseases
- I. M. Balmus, M. -.-A. Robea, R. Lefter, A. Ciobica, L. Huiban, C. Stanciu, A. Trifan
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S920
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Introduction
The most common liver diseases associated with the fat accumulation in the hepatic tissue are metabolic associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH). Many studies previously reported several key mechanisms tying hepatic injury to extrahepatic manifestations. In this way, the co-occurrence of cognitive decline, mood, and affective changes could suggest the existence of a strong neurological component predisposing to neuropsychiatric comorbidities.
ObjectivesIn this study, we aimed to describe the neurological and neuropsychiatric comorbidities of MALFD, NAFLD, and NASH.
MethodsThe main scientific databases were screened for English-written studies using the following key words: ”cognitive decline”, ”neuronal loss”, ”affective disorders”, ”anxiety”, ”depression”, ”MAFLD”, ”NAFLD”, ”NASH”. Exclusion criteria: (1) studies not focussing on fatty liver diseases; (2) not describing comorbid conditions; (3) not providing correlative analysis of disease co-occurrence or mechanistic associations.
ResultsHepatic encephalopathy (HE) is the main NAFLD/NASH extrahepatic manifestation commonly characterized by impaired cognition, rapid mood swings, depressive and anxious behaviours, and defective sleep. It is currently reported that more than 70% of the cirrhotic patients develop HE. Cognitive impairments and brain tissue reduction were found in NAFLD patients, while MAFLD patients’ cognitive dysfunctions (mild cognitive impairment and hippocampal-dependent memory impairment) were not associated with the presence of metabolic syndrome. Similarly Alzheimer’s disease (AD) was not described as comorbid in MAFLD. By contrast, since NAFLD and NASH are often characterized by insulin resistance and dyslipidaemia – significant triggers of dementia. By far the most prevalent neuropsychiatric comorbidity in NAFLD and NASH is the major depressive syndrome, diagnosed in almost 30% of the cases. Also, a correlation between the anxiety manifestation and the progression from NAFLD to NASH was described. In this context, as a response to the vast evidence that connect liver dysfunction to cognitive impairments, the liver-brain axis function was hypothesized.
ConclusionsMAFLD, NAFLD, and NASH are frequently associated with cognitive decline. The main NASH neurological comorbidity is hepatic encephalopathy, but it could also be seen in NAFLD. While Alzheimer’s disease occurs in NAFLD and NASH, more studies are needed to explain the severity-dependent association. Depression and anxiety were also reported in NAFLD and NASH.
Acknowledgements: B.I.-M. and R.M.-A. is currently supported through the Project entitled “Platformă multidisciplinară de cercetare-dezvoltare medicală în regiunea N-E” (CENEMED, code: 127606), cofinanced through the Operational Program of Competitivity, Prioritary Axis: Research, Technological development, and Inovation (CDI).
Disclosure of InterestI. M. Balmus Grant / Research support from: Project entitled “Platformă multidisciplinară de cercetare-dezvoltare medicală în regiunea N-E”(acronym: CENEMED, mySMIS code: 127606), cofinanced through the Operational Program of Competitivity, Prioritary Axis: Research, Technological development, and Inovation (CDI)., M. -.-A. Robea Grant / Research support from: Project entitled “Platformă multidisciplinară de cercetare-dezvoltare medicală în regiunea N-E”(acronym: CENEMED, mySMIS code: 127606), cofinanced through the Operational Program of Competitivity, Prioritary Axis: Research, Technological development, and Inovation (CDI)., R. Lefter: None Declared, A. Ciobica: None Declared, L. Huiban: None Declared, C. Stanciu: None Declared, A. Trifan: None Declared
Gluten and anxiety: a difficult balance in people with celiac disease
- M. A. Robea, A. Ciobica, C. Stanciu, A. Trifan
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S686-S687
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Introduction
Celiac disease (CD), triggered by gluten ingestion, occurs in people genetically predisposed to develop this chronic autoimmune condition. The triggering environmental factor, gluten, is known as a protein present in wheat, rye and barley. In recent decades, specialists have found more knowledge about the disease mechanisms, how it develops and other disturbances which accompany it. The CD was considered a pediatric main gastrointestinal disorder, associated with symptoms of abdominal pain, diarrhea, constipation and bloating, and characterized by damage to the villi of the small intestine. People with CD may experience anemia, fatigue, osteopenia or osteoporosis, bone fracture, neurological and psychiatric problems beside anxiety as depression, ataxia, neuropathy. However, the results of several studies conducted on the fact that people with CD have an increased level of anxiety are mixed.
ObjectivesThe present work is highlighting the importance of observing the anxiety levels in people diagnosed with CD beside the suitable interventions in reducing it.
MethodsFor our study scientific databases were screened using certain keywords and combinations of it as: ”celiac disease”, ”gluten”, ”gastrointestinal disorder”, ”treatment”, ”neurological problems”, ”anxiety”. Inclusion criteria were studies that (1) investigated anxiety levels in CD people, (2) reported gender results, (3) were written in English, and (4) were published within the last 20 years.
ResultsIn some cases, as main intervention in CD, gluten removal from the people’s diet usually reported improvements of the present symptoms. In addition, data from literature are describing a higher level of anxiety in females compared to males diagnosed with CD. This can be a consequence of females concerns about how they can manage the CD issues and, especially, what this is bringing in their lifestyle. On the opposite, there are reports which showed that demographic parameters (gender, age, education) are not associated with CD presence.
ConclusionsThe balance between CD and anxiety needs to be more investigated in order to identify and fully understand what is the background mechanism and how this can be regulated through specific interventions.
Disclosure of InterestM. Robea Grant / Research support from: ,Platformă multidisciplinară de cercetare-dezvoltare medicală în regiunea N-E,,, acronim: CENEMED, cod mySMIS: 127606, proiect cofinanțat prin Programul Operațional Competitivitate, Axa Prioritară: Cercetare, Dezvoltare tehnologică și Inovare (CDI)., A. Ciobica: None Declared, C. Stanciu: None Declared, A. Trifan: None Declared
VITAMIN D – A KEY FACTOR IN THE TREATMENT OF ASD PEOPLE?
- M. A. Robea, M. I. Balmus, M. Nicoara, A. Ciobica
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- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S922
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Introduction
Autism spectrum disorder (ASD) is a disorder with social, communication and behavioral disturbances that start from early childhood. There are many difficulties in diagnosing people with ASD. The diagnostic criteria are in terms of behavior descriptions, and as methods of intervention the most used is the applied behavior analysis (ABA). Although, the treatment of autism is not based on drugs, there are a number of reports that sustains the vitamin supplementation. For example, the deficiency of vitamin D (VD) was often outlined in the serum of the ASD people. Nowadays, zebrafish (Danio rerio) plays an important role in the modeling era; being one of the main organisms used in animal studies.
ObjectivesIn this study, we aimed to describe the influence of VD in autistic people, and the possibility of vitamin investigation through animal models studies.
MethodsFor analyzing this subject specific scientific databases were screened using certain keywords as: ”autism spectrum disorder”, ”vitamin D”, ”treatment”, ”deficiency”,”animal models” and ”zebrafish”. Inclusion criteria were studies that (1) investigated a behavioral intervention, (2) used animal models for ASD modelling, (3) reported vitamin D results, and (4) were published within the last 20 years.
ResultsThe majority of the studies supported the importance of an adequate level of VD in the body, mainly due to its implication during pregnancy and early brain development. The few existing data bring information about the positive impact of its administration in ASD children; in which a considerable improvement in typical symptoms was observed. For further knowledge about VD activity in ASD it was suggested the animal modelling, especially zebrafish organisms due to its numerous advantages (high similarity of its genome with the human one).
ConclusionsVD deficiency during pregnancy and early brain development is a real risk factor besides genetic predisposition. Moreover, the use of animal models for investigating the effect of VD is required for a better understanding of the vitamin mechanism in ASD people.
Acknowledgement: *R. M.-A. and B. M.-I. are supported by the Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational Program.
Disclosure of InterestM. Robea Grant / Research support from: Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational Program., M. Balmus Grant / Research support from: Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational Program, M. Nicoara: None Declared, A. Ciobica: None Declared
The suitability of zebrafish (danio rerio) as an optimal organism to further investigate the associated schizophrenia-like phenotype
- I. B. Nita, O. D. Ilie, A. S. Ciobica, L. D. Hritcu, C. Solcan, R. P. Dobrin
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S439-S440
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Introduction
Zebrafish (Danio rerio) has evolved over the years as a preferred organism due to its vast repertoire in research fields that mimic a targeted phenotype, particularly behavioral typologies and specific attributes comparable to murine models and relatively high homology with humans. Considering this consideration, different pharmacological treatments have been tested and proven that under different concentrations may trigger schizophrenia (SCZ)-like symptoms.
ObjectivesStarting from the actual stage of knowledge according to which agents used as N-methyl-D-aspartate (NMDA) inhibitors (MK-801, ketamine, and phencyclidine) alongside psychedelic (mescaline, lysergic acid diethylamide), psychoactive substances (amphetamine), and non- and essential amino acids (proline and methionine), we aimed to reunite and review all existing evidence. This approach may offer an updated and critical overview regarding the possible future directions surrounding these compounds regarding the pharmaco-dynamics/kinetics.
MethodsTo ensure the coverage of all relevant literature, we performed searches in four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect) per combinations of keywords: “schizophrenia” with “MK-801”, “ketamine”, “phencyclidine”, “mescaline”, “lysergic acid diethylamide”, “amphetamine”, “proline”, “methionine”, and “zebrafish”. Eligible studies had to be “research article(s)” written in English.
ResultsA total of n = 246 studies were returned during the established interval (2010 – 2022). Precisely, n = 16 were identified in PubMed/Medline, n = 16 in ISI Web of Knowledge, n = 17 in Scopus, and n = 197 in ScienceDirect per database. If taken per year, n = 13 were published in 2010, n = 12 in 2011, n = 15 in 2012, n = 24 in 2013, n = 21 in 2014, n = 21 in 2015, n = 32 in 2016, n = 8 in 2017, n = 12 in 2018, n = 9 in 2019, n = 17 in 2020, n = 34 in 2021, and n = 28 in 2022. Depending on the combination of keywords, we had the following situation: n = 65 for “schizophrenia+MK-801+zebrafish”, n = 42 for “schizophrenia+ketamine+zebrafish”, n = 21 for “schizophrenia+phencyclidine+zebrafish”, n = 4 for “schizophrenia+mescaline+zebrafish”, n = 5 for “schizophrenia+lysergic acid diethylamide+zebrafish”, n = 36 for “schizophrenia+amphetamine+zebrafish”, n = 37 for “schizophrenia+proline+zebrafish”, n = 36 for “schizophrenia+ methionine+zebrafish”.
ConclusionsThere can be seen an uprising trend in the current literature of studies focused on the administration of MK-801, ketamine, amphetamine, proline, methionine, and phencyclidine aiming to trigger SCZ-like symptoms as opposed to mescaline and lysergic acid diethylamide. Most of the data is contradicting, with either a decrease/increase in behavior (locomotion, aggression, sociability, circling behavior, and memory deficits), which is why additional studies are mandatory.
Disclosure of InterestNone Declared
A populational review of the amyloid precursor protein gene mutations relevant to alzheimer’s disease
- I.M. Balmus, A. Ciobica, L.D. Gorgan
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- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S718
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Introduction
The genetic component of Alzheimer’s disease was previously studied and more than sixty amyloid precursor protein (APP) gene mutations were identified. However, the populational aspects of this component were scarcely discussed despite that many of the reports mentioned the demographic ancestry of the carriers or probands.
ObjectivesIn this short study, we aimed to review the APP gene mutations relevant to Alzheimer’s disease from a Populational Genetics point of view by evaluating the current literature for the demographic description of the carriers or families in which the mutations were identified.
MethodsIn this regard, multiple genetic studies on the APP gene mutations relevant to Alzheimer’s disease were reviewed and the incidence of the mutations was analyzed considering the ancestry of the patients.
ResultsWe found many possible scenarios regarding the incidence of the APP gene mutations in Alzheimer’s disease patients and general population. On the one hand, we could identify several mutations which were present in more than one population (eg. V615M, V717I, V717L) and on the other hand, some mutations could be observed in certain populations (eg. E693delta, the Osaka mutation, which was until now observed in Japanese patients, while E693G was found in a Swedish family). One particular case is that of the isolated populations (eg. the Icelandic population in which an APP mutation protecting against Alzheimer’s disease is more frequent in the general population as compared to the patients).
ConclusionsWe were able to identify several mutations which were characteristic to many populations, but also some population-specific features regarding the APP genotypes.
DisclosureNo significant relationships.
The effect of vitamin C on sociability in a juvenile zebrafish pesticide-induced model of autism spectrum disorder
- M.A. Robea, A. Ciobica, S.-A. Strungaru, G. Plavan, M. Nicoara, C. Solcan
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- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S206
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Introduction
Autism spectrum disorder (ASD) is a multi-factorial disease characterized by impairments in social interaction, communication and repetitive behaviors. The necessity of developing an adequate treatment for ASD is essential. There is an increase in clinical studies assessing the positive effects of vitamins in ASD children. Vitamin C (vit. C) is implicated in biosynthesis of neurotransmitters and in protein metabolism.
ObjectivesThis study evaluated the possible effect of vit. C on zebrafish sociability after a single insecticide mixture administration as inductor for ASD.
MethodsA single dose of insecticide mixture (600 μg L-1 fipronil and 600 μg L-1 pyriproxyfen) was administrated to zebrafish juvenile. Vit. C (25 μg L−1) was daily administrated during 14 days. A control group simulated the administration of insecticide mixture and vitamin. Each animal was tested in the experimental tank designed for the social interaction test. The trials were recorded and analysed using EthoVision XT 11 (NOLDUS, Netherlands). The locomotor activity parameters and the time spent next to the group were measured. Each trial had 4 minutes duration.
ResultsWe have found no significant differences in the average levels between pre-treatment and treatment days (P< 0.05 ANOVA) regarding the locomotor activity parameters. Significant changes in sociability were observed for the group exposed to insecticide mixture and for vit. C group (P > 0.05 ANOVA). It was also found that 14 days vitamin administration can lead to sociability improvements after a single administration of mixture insecticide.
ConclusionsThe results of the current study bring some positive insights for the future of ASD therapy.
Conflict of interestThis work was co-funded by the European Social Fund, through Operational Programme Human Capital 2014-2020, project number POCU/380/6/13/123623, project title
Gastrointestinal functional impairments and epilepsy: Searching the possible connection mechanisms
- R. Lefter, A. Ciobica, I.M. Balmus
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- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S411
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Introduction
Epilepsy is one of the most common neurological disorders worldwide characterized by unpredictable and recurrent seizures, resulting from abnormal brain activity, accompanied by loss of consciousness and control of bowel or bladder function.
ObjectivesA higher risk of comorbid disorders in epilepsy has been reported for psychiatric affective conditions (i.e., depression and schizophrenia), sleep alterations, as well as some gastrointestinal disorders (inflammatory bowel disease and constipation), and lately there is an interest to determine and explain a putative association between functional gastrointestinal disorders (FGID) such as Irritable bowel syndrome (IBS) and epilepsy.
MethodsIn this way, we decided to review the current aspects of the gastrointestinal functional impairments and epilepsy by searching in the literature possible connection mechanisms.
ResultsA handful of studies have only recently reported an increased prevalence of IBS in epilepsy in children, in adults, and conversely a higher incidence of epilepsy in IBS patients at the populational level. Paroxysmal abdominal complaints resulting from seizure activity are present in the abdominal epilepsy syndrome and the link between constipation and seizures has been demonstrated in animal models. Currently, there is no data to directly address the cellular and molecular connections between epilepsy and FGID, but these would probably involve the bidirectional dysregulation of the brain-gut axis with increased afferent processing of visceral nociceptive signals and subsequent hyperalgesia.
ConclusionsThus, intestinal dysbiosis may play a role in triggering inflammatory and immune-related mechanisms reported in IBS manifestations and epilepsy, while vagal neuroimunomodulation issues are likely to be involved in both pathologies as well.
Conflict of interestThe authors are currently supported by a Young Research Teams supporting research grant PN-III-P1-1.1-TE2016-1210, named ”Complex study on oxidative stress status, inflammatory processes and neurological manifestations correlations in irritable bowel synd
P02-290 - Oxidative Stress in Patients with Mild Cognitive Impairment and Depression Could be an Important Risk Factor for Dementia
- M. Padurariu, A. Ciobica, R. Branzei, L. Hritcu, C. Stefanescu
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- European Psychiatry / Volume 25 / Issue S1 / 2010
- Published online by Cambridge University Press:
- 17 April 2020, 25-E916
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Introduction
Mild Cognitive Impairment (MCI) seems to represent an early stage of Alzheimer's disease (AD) and there is a great interest in the relationship between MCI and the progression to AD.
It has been demonstrated that patients with depression and mild cognitive impairment present a doubled risk of developing dementia of Alzheimer type as those with MCI only. Considering the importance of oxidative stress in MCI and Alzheimer disease, our current objective was to determine the level of oxidative stress in MCI patients with depression, compared with non-depressed MCI patients.
MethodsThe patients were selected using Petersen criteria for mild cognitive impairment. The cognitive performance was assessed using MMSE (Mini Mental State Examination) and ADAS-cog (Alzheimer's disease Assessment Scale- cognitive subscale) and Geriatric Depression Scale for depression.
We assessed the levels of some enzymatic antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX), as well as lipid oxidation makers like MDA (malondialdehyde), from the patients peripheral blood.
The results were compared to an aged-matched non-depressed MCI group.
ResultsA significant decrease in the specific activity of both superoxide dismutase and glutathione peroxidase was found in MCI patients with depression compared with non-depressed MCI patients. Also, the concentration of serum malondialdehyde was increase in MCI patients with depression.
ConclusionsWe conclude that patients with MCI and depression have an increased level of oxidative stress, compared with non depressed MCI patients. This could explain the increased risk of patients with depression and mild cognitive impairment in developing dementia of Alzheimer type.
PW01-81 - Deficits of Spatial Memory and Oxidative Stress Damage Following Exposure to Lipopolysaccharide in a Rat Model of Parkinson's Disease
- L. Hritcu, A. Ciobica, M. Stefan, T. Nabeshima
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- European Psychiatry / Volume 25 / Issue S1 / 2010
- Published online by Cambridge University Press:
- 17 April 2020, 25-E1480
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Objectives
The present work was undertaken in order to investigate the effects of systemic lipopolysaccharide endotoxin administration (250 μg/kg) on spatial memory formation and oxidative stress in rats subjected to right-unilateral lesion of the dopaminergic neurons of the substantia nigra by means of 6- hydroxydopamine (6-OHDA) compared to normal and lipopolysaccharide alone treated rats.
MethodsThirty male Wistar rats weighing 200 ± 50 at the start of the experiment were used. The substantia nigra was right-unilateral lesioned by stereotaxic microinjections of 8 micrograms (free base) 6-OHDA. The rats were pretreated 30 min before the 6-OHDA infusion with 25 mg/kg desipramine to protect noradrenergic projections. Sham-operated rats received only an injection of desipramine, followed by vehicle in the substantia nigra. Lipopolysaccharide (LPS from Escherichia coli serotype 0111:B4, Sigma) was dissolved in pyrogen-free 0.9% NaCl at the concentration of 250 μg/kg and intraperitonealy injected in normal and 6-OHDA-lesioned rats for a period of 7 continuous days. 7 days after continuous LPS administration we assessed memory formation by means of Y-maze and radial arm-maze task, and the endogenous antioxidants activity in rat temporal cortical area.
ResultsSystemic lipopolysaccharide administration significantly decreased spontaneous alternation in Y-maze task, working memory and reference memory in radial arm-maze task, suggesting impairment of both short-term memory and long term-memory, respectively. Furthermore, lipopolysaccharide administration significantly decreased activity of the biochemical markers of endogenous antioxidants in rat temporal cortical area.
ConclusionsOur results further validate that lipopolysaccharide may exacerbate the development of neurological dysfunctions associated with Parkinson's disease.
Oxidative stress markers in patients treated with typical and atypical antipsychotics
- M. Padurariu, A. Ciobica, I. Dobrin, C. Joacabine, C. Stefanescu
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- Journal:
- European Psychiatry / Volume 26 / Issue S2 / March 2011
- Published online by Cambridge University Press:
- 16 April 2020, p. 1465
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Introduction
Studies performed in schizophrenia patients have generally suggested the presence of a compromised antioxidant system, but this is not always consistent with specific observed parameters, which on the whole, show evidences of dysregulation. There are also controversies regarding the oxidative stress status in patients treated with typical vs. atypical antipsychotics.
AimIn this context, the aim of the present work was to evaluate the specific activity of some peripheral antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX) and the level of a lipid peroxidation maker (malondialdehyde-MDA), in schizophrenic patients treated with typical (haloperidol) or atypical (olanzapine, quetiapine and risperidone) antipsychotics, compared with age-matched healthy subjects.
MethodsThe subjects of this study (n = 45), consisted of 35 patients who met DSM-IV criteria for schizophrenia and 10 healthy control age and gender-matched subjects. Patients were of paranoid subtype, with duration of illness for at least 5 years. Nine patients were under haloperidol (1–2 mg daily dose) treatment and 26 (8/10/8) patients were under atypical treatment: quetiapine (300 mg daily dose), olanzapine (20 mg daily dose) or risperidone (2–4 mg daily dose), respectively.
ResultsWe found a significant decrease in GPX specific activity and also a significant increase of MDA levels in schizophrenic patients, compared to age-matched control group, regardless of their type of treatment. Additionally, an increase in SOD specific activity was observed, mainly in the patients treated with haloperidol and quetiapine.
ConclusionsFurther research is necessary in order to elucidate the effects of different antipsychotic agents on antioxidant enzymes.
Behavioral Changes Induced by Angiotensin AT1 Receptors Blockade in the Rat Brain
- L. Hritcu, W. Bild, A. Ciobica, V. Artenie, I. Haulica
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- Journal:
- European Psychiatry / Volume 24 / Issue S1 / January 2009
- Published online by Cambridge University Press:
- 16 April 2020, 24-E859
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Aims:
The brain renin-angiotensin system is involved in learning and memory, but the actual role of angiotensin II and its metabolites in this process has been difficult to comprehend. In the present study we assessed the role of the angiotensin AT1 receptors in certain behavioral effects of angiotensin II using their selective antagonist losartan and PD123319, intracerebroventricularly (icv) administrated.
Methods:Male Wistar rats were divided into three groups: 1. sham-operated; 2. Losartan; 3. PD123319. All drugs were stereotaxically icv injected. Learning and memory tests began 2 weeks after the operation, and the ability of the rats to acquire the operant task was studied by means of Y-maze task and passive avoidance task, respectively. The anxiety state was measured in elevated plus maze.
Results:Losartan and PD123319 significantly impaired spatial memory in Y-maze task, suggesting significant effects on short-term memory. In passive avoidance task, both angiotensin II antagonist, significantly decreased step-through-latency, suggesting significant effects on long-term memory. In elevated plus maze measuring anxiety, both drugs diminished anxiety state.
Conclusions:Our results suggest the considerable involvement of the brain ATi angiotensin receptors in the cognition improving effects of angiotensin.
Comparative Effects of Captopril, Losartan and PD123319 on the Memory Processes in Rats
- W. Bild, L. Hritcu, A. Ciobica, V. Artenie, I. Haulica
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- Journal:
- European Psychiatry / Volume 24 / Issue S1 / January 2009
- Published online by Cambridge University Press:
- 16 April 2020, 24-E860
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Aims:
Renin-angiotensin system in the central nervous system participates in the processing of sensory information, learning and memory processes. Inhibitors of renin-angiotensin system, particularly angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists are reported to have potential effects in various learning and memory processes. In the present study we assessed the effects of angiotensin converting enzyme inhibitor captopril and the angiotensin AT1 receptors antagonists, lostartan and PD123319, in learning and memory processes by means of Y-maze and passive avoidance tasks. The anxiety state was measured in elevated plus maze.
Methods:Male Wistar rats were divided into three groups: 1. sham-operated; 2. Captopril; 3. Losartan; 4. PD123319. All drugs were stereotaxically icv injected, rather than captopril (i.p.). Learning and memory tests began 2 weeks after the operation, and the ability of the rats to acquire the operant task was studied by means of Y-maze task and passive avoidance task, respectively. The anxiety state was measured in elevated plus maze.
Results:Captopril, losartan and PD123319 significantly impaired spatial memory in Y-maze task, suggesting significant effects on short-term memory. In passive avoidance task, all drugs, significantly decreased step-through-latency, suggesting significant effects on long-term memory. In elevated plus maze measuring anxiety, all drugs diminished anxiety state.
Conclusions:These results suggest the involvement of the brain renin-angiotensin system in learning and memory formation.