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A Systematic Review of Neuroimaging and Acute Cannabis Exposure in Age-of-Risk for Psychosis

Lani Cupo, Eric Plitman, Elisa Guma, M Mallar Chakravarty

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: systematic review; cannabis; neuroimaging; age-of-onset psychosis; psychosis; schizophrenia

Online: 14 May 2021 (09:58:14 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202310.0311.v1

Cannabis induced psychosis: A comparative study between cannabis use disorder and cocaine use disorder

Maurizio Coppola, Raffaella Mondola

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: cannabis; Δ⁹-THC; induced psychosis; schizophrenia

Online: 6 October 2023 (11:10:47 CEST)

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Preprint REVIEW | doi:10.20944/preprints202309.2018.v1

Neuropsychiatric Systemic Lupus Erythematosus: Antibodies Involved, Clinical Characteristics and Treatment

Darren Avinash Gopaul, Angel Vaillant

Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Systemic Lupus Erythematosus; steroids; psychosis; DSM-V

Online: 28 September 2023 (13:37:20 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201809.0314.v1

Activation of the Immune-Inflammatory Response System and the Compensatory Immune-Regulatory Reflex System in Antipsychotic Naive First Episode Psychosis

Mariane Nunes Noto, Michael Maes, Sandra Odebrecht Vargas Nunes, Vanessa Kiyomi Ota, Ana C. Rossaneis, Waldiceu A. Verri Jr., Quirino Cordeiro, Sintia Iole Belangero, Ary Gadelha, Rodrigo Affonseca Bressan, Cristiano Noto

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: schizophrenia; first episode psychosis; antipsychotic; immune; inflammation; cytokines

Online: 17 September 2018 (14:13:38 CEST)

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Background: First episode psychosis (FEP), schizophrenia and affective disorders are accompanied by activation of the immune inflammatory response system (IRS). The compensatory immune-regulatory reflex system (CIRS) is a regulatory immune response that is induced by the IRS but exerts negative feedback through, for example, increased levels of anti-inflammatory cytokines such as IL-4, IL-13 and IL-10. Different phenotypes of schizophrenia may exhibit distinct IRS and CIRS immune profiles.Aims: This study aims to examine the IRS and CIRS components, including macrophagic M1, T-helper (Th)-1, Th-2, Th-17 and T-regulatory (Treg) phenotypes, in antipsychotic-naïve FEP patients before and after risperidone treatment.Methods: We included 31 antipsychotic-naïve FEP patients who had measurements of IRS and CIRS biomarkers before and after treatment with risperidone for 10 weeks, and 22 healthy controls.Results: Antipsychotic-naive FEP patients showed interrelated increments in M1, Th-1, Th-2, Th-17 and Treg phenotypes and a relatively greater IRS response (especially granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-12) as compared with the CIRS response (IL-4, IL-13, IL-5 and IL-10). Inflammatory markers, especially IL-6 and IL-8, were significantly correlated with negative, psychotic, affective and excitation symptom dimensions. Treatment with risperidone significantly suppressed the IRS and CIRS. Baseline levels of CIRS biomarkers, especially higher soluble tumor necrosis factor receptor-1 and IL-10 predicted clinical improvement during treatment.Discussion: Our findings indicate that FEP is characterized by robust IRS (M1 + Th-1 + Th-17) and CIRS responses, suggesting that monocytes, macrophages, Th-1, Th-2, Th-17 and Treg cells are activated. The findings indicate that a) FEP patients are prone to the detrimental effects of M1, Th-1, Th-17 and Th-2 cells, which may contribute to long-lasting abnormalities in brain circuitry; and b) in FEP, the CIRS may contribute to recovery from the acute phase of illness. Enhancing the CIRS is a new drug target to treat FEP.

Preprint REVIEW | doi:10.20944/preprints202201.0098.v1

New Hope for Behavioural and Psychological Symptoms in Dementia (BPSD): A Narrative Review of Clinical Studies Conducted in the Symptomatic Treatments for Agitation and Psychosis Episodes in Alzheimer’s Disease/Dementia

Haider Saddam Qasim, Maree Donna Simpson

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: BPSD; Alzheimer’s dementia; agitation; psychosis; SSRIs; antipsychotics; brexpiprazole; dextromethorphan

Online: 10 January 2022 (11:12:38 CET)

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Background: The psychomotor agitation of the BPSD is one of the common issues in aged care facilities, leading to the poor functional and medical consequences. Psychotropic interventions are the preferable choice of treatment. But which medication should be the prescribers first preference? This review aims to compare pharmacological interventions for psychomotor agitation, judging them according to their effectuality and justifiability profiles. This is to be achieved by retrieving information from RCTs and systematic reviews. Objectives: This review evaluates evidence from RCTs, systematic reviews, and meta-analyses of BPSD patients who had taken agitation treatments. Assessing the efficacy of antidepressants and antipsychotic treatments when compared to each other for the purpose of improving agitation outcomes. Methods: This narrative review includes RCTs and retrospective studies that were comparing one or more active ingredient medications with another or with a placebo, along with sys-tematic reviews comparing antidepressants with antipsychotics such as quetiapine, olanzapine, and risperidone. Studies extracted by searching accessing databases, such as PubMed, OVID, and Cochrane with restrictions of date from 2000 to 2021 and English language. Quality of evidence: The quality of systematic reviews was judged against AMSTAR score, and RCTs were judged according to CONSORT checklist for RCT protocols. Conclusion: There are still few studies of serotonin targeting treatment of agitation in BPSD. The SSRIs such as citalopram were associated with a reduction in symptoms of agitation, and lower risk of adverse effects compared to antipsychotics. This review also illustrates brexpiprazole as a target of multimodal neurotransmitters such as dopamine, serotonin, and norepinephrine; and dextromethorphan, OR dextromethorphan associated with bupropion or quinidine as a blockade of NMDA receptors. The outcome of this review suggests that further studies involving more dementia/Alzheimer’s participants should be conducted. Future studies are required also to assess the long-term safety and efficacy of SSRI, brexpiprazole, dextromethorphan treatments for agitation in BPSD.

Preprint ARTICLE | doi:10.20944/preprints201710.0169.v1

A Longitudinal Approach to Biological Psychiatric Research: The PsyCourse Study

Monika Budde, Heike Anderson-Schmidt, Katrin Gade, Daniela Reich-Erkelenz, Kristina Adorjan, Janos L. Kalman, Fanny Senner, Sergi Papiol, Till F. M. Andlauer, Ashley L. Comes, Eva C. Schulte, Farah Klöhn-Saghatolislam , Anna Gryaznova, Maria Hake, Kim Bartholdi, Laura Flatau, Markus Reitt, Silke Quast, Sophia Stegmaier, Milena Meyers, Barbara Emons, Ida Sybille Haußleiter, Georg Juckel, Vanessa Nieratschker, Udo Dannlowski, Max Schmauß, Jörg Zimmermann, Jens Reimer, Sybille Schulz, Jens Wiltfang, Eva Reininghaus, Ion-George Anghelescu, Volker Arolt, Bernhard T. Baune, Carsten Konrad, Andreas Thiel, Andreas J. Fallgatter, Christian Figge, Martin von Hagen, Manfred Koller, Fabian U. Lang, Moritz E. Wigand, Thomas Becker, Markus Jäger, Detlef E. Dietrich, Sebastian Stierl, Harald Scherk, Carsten Spitzer, Here Folkerts, Stephanie H. Witt, Franziska Degenhardt, Andreas J. Forstner, Marcella Rietschel, Markus M. Nöthen, Peter Falkai, Thomas G. Schulze, Urs Heilbronner

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: Schizophrenia; bipolar; psychosis; depression; polygenic risk score; diagnosis; RDoC

Online: 27 October 2017 (11:58:11 CEST)

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Preprint REVIEW | doi:10.20944/preprints202402.0030.v1

Biological Peripartum Predictors of Postpartum Depression: Protocol for Systematic Review and Meta-Analysis

Marwa Alhaj Ahmad, Shamsa Al Awar, Gehan Sayed Sallma, Meera Alkaabi, Darya Smetanina, Yauhen Statsenko, Kornelia Zareba

Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: postpartum; depression postpartum; blues postpartum; psychosis review article; risk factors

Online: 1 February 2024 (12:48:14 CET)

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Preprint REVIEW | doi:10.20944/preprints202109.0449.v1

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

Lena Palaniyappan, Min Tae M. Park, Peter Jeon, Roberto Limongi, Kun Yang, Akira Sawa, Jean Théberge

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: glutathione; glutamate; psychosis; schizophrenia; redox; antioxidant; oxidative stress; myelin; spectroscopy

Online: 27 September 2021 (12:47:39 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202108.0243.v1

Cardiometabolic Health Risks, Lifestyle Behaviours and Quality of Life in People with Early Psychosis – A Cross Sectional Study

Soontareeporn Meepring, Richard Gray, Yan Li, Grace WK Ho, Wai Tong Chien, Daniel Bressington

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Early Psychosis; Cardiovascular Disease Risk; Quality of Life; Lifestyle Behaviours.

Online: 11 August 2021 (08:55:02 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201810.0083.v2

In Schizophrenia, Low Natural IgM Antibody Titers to Oxidative Specific Epitopes and Higher IgM Responses to Nitrated and Nitrosylated Proteins Strongly Predict Negative Symptoms, Neurocognitive Impairments and the Deficit Syndrome

Michael Maes, Buranee Kanchanatawan, Sunee Sirivichayakul, Andre F. Carvalho

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: immune, inflammation, natural IgM autoimmune, oxidative stress, kynurenine, schizophrenia, psychosis

Online: 8 October 2018 (13:51:40 CEST)

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Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory reflex system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in natural regulatory autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative specific epitopes (OSEs), nitroso (NO) and nitro (NO₂) adducts in schizophrenia remain unknown.This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl and NO₂-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls.Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO₂-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2 – 42.2 %) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO₂-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall.These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in lowered IgM responses to MDA and azelaic acid (part of the CIRS) attenuate the negative immune-regulatory feedback on the primary immune response and that this process may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.

Preprint REVIEW | doi:10.20944/preprints202107.0180.v1

Neural Correlates of Aberrant Salience and Source Monitoring in Schizophrenia and at-Risk Mental States - A Systematic Review of fMRI Studies

Joachim Kowalski, Adrianna Aleksandrowicz, Małgorzata Dąbkowska, Łukasz Gawęda

Subject: Social Sciences, Psychology Keywords: aberrant salience; source monitoring; psychosis; cognitive biases; self-disturbance; neuroimagining; fMRI

Online: 7 July 2021 (13:05:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202103.0632.v1

Leukocyte Telomere Length Is Not Shortened in Methamphetamine Dependence or Methamphetamine-Induced Psychosis but Is Increased Following Traumatic Events.

Teerayuth Rungnirundorn Teerayuth Rungnirundorn, Kuakarun Krusong, Rasmon Kalayasiri, Michael Maes

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: methamphetamine; psychosis; schizophrenia; withdrawal; depression; neuro-immune; oxidative stress; telomere length

Online: 25 March 2021 (15:13:56 CET)

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Preprint HYPOTHESIS | doi:10.20944/preprints202004.0215.v1

The Role of Endocannabinoid System in Sleep Deprivation-Induced Psychosis-Like Symptoms through Hampering Prepulse Inhibition; A Hypothesis

Mohammad Nami, Ali-Mohammad Kamali, Milad Kazemiha, Rao kosagisharaf, Sabri Derman

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: endocanabinoid system; sleep deprivation; animal models; psychosis-like symptoms; drug development

Online: 14 April 2020 (06:28:23 CEST)

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Preprint REVIEW | doi:10.20944/preprints201809.0289.v1

The Role of Aberrations in the Immune-inflammatory Reflex System (IRS) and the Compensatory Immune-regulatory Reflex System (CIRS) in Different Phenotypes of Schizophrenia: The IRS-CIRS Theory of Schizophrenia

Chutima Roomruangwong, Cristiano Noto, Buranee Kanchanatawan, George Anderson, Marta Kubera, Andre F. Carvalho, Michael Maes

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: schizophrenia, immune system, inflammation, cytokines, immune regulatory, CIRS, psychiatry, immunology, psychosis

Online: 17 September 2018 (08:57:53 CEST)

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In this paper we propose a novel theoretical framework, which was previously developed for major depression and bipolar disorder, namely the compensatory immune-regulatory reflex system (CIRS), as applied to the neuro-immune pathophysiology of schizophrenia and its phenotypes, including first episode psychosis (FEP), acute relapses, chronic and treatment resistant schizophrenia (TRS), comorbid depression, and deficit schizophrenia. These schizophrenia phenotypes and manifestations are accompanied by increased production of positive acute phase proteins, including haptoglobin and α2-macroglobulin, complement factors, and macrophagic M1 (IL-1β, IL-6 and TNF-α), T helper (Th)-1 (interferon-γ and IL-2R), Th-2 (IL-4, IL-5), Th-17 (IL-17) and T regulatory (Treg; IL-10 and transforming growth factor (TGF)-β1) cytokines, cytokine-induced activation of the tryptophan catabolite (TRYCAT) pathway as well as chemokines, including CCL-11 (eotaxin), CCL-2, CCL-3 and CXCL-8. While the immune profiles in the different schizophrenia phenotypes indicate activation of the immune-inflammatory response system (IRS), there are simultaneous signs of CIRS activation, including increased levels of the IL-1 receptor antagonist (sIL-1RA), sIL-2R and tumor necrosis factor-a receptors, Th-2 and Treg phenotypes with increased IL-4 and IL-10 production, and increased levels of TRYCATs and haptoglobin, α2-macroglobulin and other acute phase reactants, which have immune-regulatory and anti-inflammatory effects. Signs of activated IRS and CIRS pathways are also detected in TRS, chronic and deficit schizophrenia indicating that these conditions are accompanied by a new homeostatic setpoint between upregulated IRS and CIRS components. In FEP, increased baseline CIRS activity is a protective factor which may predict favorable clinical outcomes. Moreover, impairments in the CIRS are associated with deficit schizophrenia and greater impairments in semantic and episodic memory. It is concluded that CIRS plays a key role in the pathophysiology of schizophrenia by negatively regulating the primary IRS and contributing to recovery from the acute phase of illness. Components of the CIRS may offer promising therapeutic targets for schizophrenia.

Preprint COMMUNICATION | doi:10.20944/preprints201712.0059.v2

Extreme Overvalued Beliefs: How Violent Extremist Beliefs Become “Normalized”

Tahir Rahman

Subject: Social Sciences, Behavior Sciences Keywords: psychosis; delusion; over valued idea; terrorism; mass shootings; violence; forensic psychiatry

Online: 23 January 2018 (02:41:33 CET)

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Preprint ARTICLE | doi:10.20944/preprints202012.0754.v1

Impact of Service User Video Presentations on Explicit and Implicit Stigma toward Mental Illness among Medical Students in Nepal: A Randomized Controlled Trial

Cori L. Tergesen, Dristy Gurung, Saraswati Dhungana, Ajay Risal, Prem Basel, Dipesh Tamrakar, Archana Amatya, Lawrence P. Park, Brandon A. Kohrt

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: attitudes; depression; developing countries; medical education; mental health; psychosis; service users; stigma

Online: 30 December 2020 (14:12:49 CET)

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Preprint ARTICLE | doi:10.20944/preprints201810.0414.v1

In Schizophrenia, Increased Plasma Igm/Iga Responses to Gut Commensal Bacteria are Associated with Negative Symptoms, Neurocognitive Impairments and the Deficit Phenotype

Michael Maes, Buranee Kanchanatawan, Sunee Sirivichayakul, Andre F. Carvalho

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: immune, inflammation, natural IgM, B1 cells, oxidative stress, TRYCATs, schizophrenia, psychosis, psychiatry

Online: 18 October 2018 (10:55:52 CEST)

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Increased gut permeability (leaky gut) with increased translocation of Gram-negative bacteria plays a role in the gut-brain axis through effects on systemic immune-inflammatory processes. Deficit schizophrenia is characterized by an immune-inflammatory response combined with a deficit in natural IgM antibodies to oxidative specific epitopes (OSEs), which are a first line defense against bacterial infections. This study measured plasma IgA/IgM responses to 5 Gram-negative bacteria in association with IgM responses to malondialdehyde (MDA) and azelaic acid in 80 schizophrenia patients (40 with the deficit syndrome and 40 without) and in 38 healthy controls.Deficit schizophrenia was characterized by significantly increased IgA responses to Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii and Klebsiella pneumoniae as compared with non-deficit schizophrenia. The presence of deficit schizophrenia was highly predicted by increased IgA responses to Pseudomonas putida and IgM responses to all 5 Gram-negative bacteria and lowered natural IgM to MDA and azelaic acid with a bootstrap area under the ROC curve of 0.960 (2000 random curves). A large proportion of the variance (41.5%) in the PANSS negative score was explained by the regression on IgA responses to K. pneumoniae and IgM responses to the 5 enterobacteria coupled with lowered IgM antibodies to azelaic acid. There were significant associations between IgA levels to Gram-negative bacteria and Mini Mental State Examination, Boston naming test, Verbal Fluency and Word List Memory test scores.These findings provide further evidence that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by an increased impact of Gram-negative commensal bacteria coupled with a deficit in natural IgM, pointing to aberrations in B1 cells. It is concluded that increased bacterial translocation and deficits in the compensatory immune-regulatory system (CIRS) may drive negative symptoms and neurocognitive impairments, which are hallmarks of deficit schizophrenia.

Preprint ARTICLE | doi:10.20944/preprints202401.1404.v1

Investigating the Effectiveness of Brexpiprazole in Schizophrenic Patients with Concurrent Alcohol and Substance Use Disorder: A Prospective, Multicentric, Real-World Study

Stefania Chiappini, Clara Cavallotto, Alessio Mosca, Francesco Di carlo, Tommaso Piro, Chiara Lorenzini, Maria pia Di paolo, Maria Pepe, Marco Di nicola, Valerio Ricci, Mauro Pettorruso, Giovanni Martinotti

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: dual disorders; substance use disorder; brexpiprazole; real-world study; addiction; substance-induce-psychosis.

Online: 18 January 2024 (14:03:17 CET)

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Preprint ARTICLE | doi:10.20944/preprints202303.0392.v1

Mediation Effects of Social Cognition on the Relationship between Neurocognition and Social Functioning in Major Depressive Disorder and Schizophrenia

Takashi Uchino, Ryo Okubo, Youji Takubo, Akiko Aoki, Izumi Wada, Naoki Hashimoto, Satoru Ikezawa, Takahiro Nemoto

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: ACSo; cognitive function; depression; PDQ; psychosis; real-world functioning; schizophrenia; SFS; social functioning

Online: 22 March 2023 (06:36:20 CET)

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Preprint REVIEW | doi:10.20944/preprints201802.0146.v1

Acupuncture as Add-On Treatment of the Positive, Negative, and Cognitive Symptoms of Patients with Schizophrenia: A Systematic Review

Maurits Van den Noort, Sujung Yeo, Sabina Lim, Sook-Hyun Lee, Heike Staudte, Peggy Bosch

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: schizophrenia; psychosis; sleep; sleep disturbances; sleep disorders; integrative medicine; acupuncture; add-on therapy

Online: 23 February 2018 (04:59:52 CET)

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Preprint REVIEW | doi:10.20944/preprints202403.0259.v1

From Lab to Life: Exploring Cutting-Edge Models for Neurological and Psychiatric Disorders

Masaru Tanaka, László Vécsei

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: psychosis; Parkinson's disease; antioxidants; genetic therapy; stroke; anxiety; migraine; epilepsy; aphasia; cardiovascular diseases; cognition

Online: 5 March 2024 (12:31:24 CET)

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Preprint REVIEW | doi:10.20944/preprints202010.0163.v1

SSRIs as Risk Reduction for Cardiovascular Disease in Patients with Schizophrenia

Alfredo Bellon, Kieuhanh Nguyen

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: cholesterol; BMI; blood sugar; psychosis; LDL; HDL; antidepressants; antipsychotics; metabolism; metabolic abnormalities, platelet aggregation

Online: 8 October 2020 (09:03:41 CEST)

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Preprint REVIEW | doi:10.20944/preprints202107.0289.v1

Pharmaco-Magnetic Resonance as Tool for Monitoring the Medication-Related Effects in the Brain May Provide Potential Biomarkers for Psychotic Disorders

Katrin Aryutova, Drozdstoy Stoyanov

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: schizophrenia; psychosis; cognitive symptoms; neurotransmission; dopamine; glutamate; brain connectivity; pharmacological magnetic-resonance imaging; translational neuroscience.

Online: 13 July 2021 (10:13:56 CEST)

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