Attila Szabo

Attila Szabo
University of Oslo · Institute of Clinical Medicine

PhD

About

89
Publications
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977
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Publications

Publications (89)
Article
Full-text available
Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and cell survival via activating NF-κB and mitogen-activated protein kinases. Recen...
Article
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Lithium (Li), valproate (VPA) and lamotrigine (LTG) are commonly used to treat bipolar disorder (BD). While their clinical efficacy is well established, the mechanisms of action at the molecular level are still incompletely understood. Here we investigated the molecular effects of Li, LTG and VPA treatment in induced pluripotent stem cell (iPSC)-de...
Article
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Background Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) that are part of a psychosis continuum, and dysregulated innate immune responses have been suggested to be involved in their pathophysiology. However, disease-specific immune mechanisms in SMI are not known yet. Recently, dyslipidemia has been linked to syste...
Article
Background Cell adhesion molecules (CAM) orchestrate leukocyte trafficking and could link peripheral and neuro-inflammation in patients with severe mental illness (SMI), by promoting inflammatory and immune mediated responses and mediating signals across blood-brain-barrier (BBB). We hypothesized that CAMs would be dysregulated in SMI and evaluated...
Article
Full-text available
Schizophrenia (SCZ) is a severe mental disorder with a high heritability. Although its pathophysiology is mainly unknown, dysregulated immune activation and inflammation have recently emerged as possible candidates in the underlying mechanisms of SCZ. Previous studies suggest that aberrant inflammasome activation, glia dysregulation, and brain infl...
Article
Full-text available
Objective Agitation is a challenging clinical feature in severe mental disorders, but its biological correlates are largely unknown. Inflammasome-related abnormalities have been linked to severe mental disorders and implicated in animal models of agitation. We investigated if levels of circulating inflammasome-related immune markers were associated...
Article
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5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT) is a naturally occurring tryptamine that primarily acts as an agonist at the 5‐HT1A and 5‐HT2A receptors, whereby affinity for the 5‐HT1A subtype is highest. Subjective effects following 5‐MeO‐DMT administration include distortions in auditory and time perception, amplification of emotional states and fe...
Article
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Importance White matter (WM) abnormalities are commonly reported in psychiatric disorders. Whether peripartum insufficiencies in brain oxygenation, known as birth asphyxia, are associated with WM of patients with severe mental disorders is unclear. Objective To examine the association between birth asphyxia and WM in adult patients with schizophre...
Article
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While neurodevelopmental abnormalities have been associated with schizophrenia (SCZ), the role of astroglia in disease pathophysiology remains poorly understood. In the present study, we used a human induced pluripotent stem cell (iPSC)-derived astrocyte model to investigate the temporal patterns of astroglia differentiation during developmental st...
Article
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Astrocytes are the most abundant cell type in the human brain and are important regulators of several critical cellular functions, including synaptic transmission. Although astrocytes are known to play a central role in the etiology and pathophysiology of schizophrenia, little is known about their potential involvement in clinical response to the a...
Preprint
Full-text available
Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) that are part of a psychosis continuum, and dysregulated innate immune responses have been suggested to be involved in their pathophysiology. However, disease-specific immune mechanisms in SMI are not known yet. Recently, dyslipidemia has been linked to syst...
Article
Full-text available
Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) associated with elevated cardiovascular disease (CVD) risk, including obesity. Leptin and adiponectin are secreted by adipose tissue, with pro- and anti-inflammatory properties, respectively. The second generation antipsychotics (AP) olanzapine, clozapine, a...
Article
Full-text available
Despite the high heritability of schizophrenia (SCZ), details of its pathophysiology and etiology are still unknown. Recent findings suggest that aberrant inflammatory regulation and microRNAs (miRNAs) are involved. Here we performed a comparative analysis of the global miRNome of human induced pluripotent stem cell (iPSC)-astrocytes, derived from...
Article
Full-text available
Schizophrenia (SCZ) and bipolar disorder (BIP) are severe mental disorders with a considerable disease burden worldwide due to early age of onset, chronicity, and lack of efficient treatments or prevention strategies. Whilst our current knowledge is that SCZ and BIP are highly heritable and share common pathophysiological mechanisms associated with...
Article
Full-text available
It is suggested that neurodevelopmental abnormalities are involved in the disease mechanisms of psychotic disorders. Although cellular adhesion molecules (CAMs) participate in neurodevelopment, modulate blood–brain barrier permeability, and facilitate leukocyte migration, findings concerning their systemic levels in adults with psychosis are incons...
Article
Full-text available
With a rise in the incidence of autoimmune diseases (AiD), health care providers continue to seek out more efficacious treatment approaches for the AiD patient population. Classic serotonergic psychedelics have recently been gaining public and professional interest as novel interventions to a number of mental health afflictions. Psychedelics have a...
Preprint
Full-text available
While neurodevelopmental abnormalities have been associated with schizophrenia (SCZ), the role of astroglia in disease pathophysiology remains poorly understood. In this study we used a human induced pluripotent stem cell (iPSC)-derived astrocyte model to investigate the temporal patterns of astroglia differentiation during developmental stages cri...
Article
Full-text available
Purpose. This study is aimed at investigating the phenotype, differentiation potential, immunomodulatory properties, and responsiveness of saphenous vein vessel wall-derived mesenchymal stromal cells (SV-MSCs) to various TLR ligands and proinflammatory cytokines, as well as comparing their features to those of their bone marrow-derived counterparts...
Article
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Background: Cardiovascular disease (CVD) is a major cause of premature death in patients with psychotic disorders, where dyslipidemia occurs frequently. In the pathogenesis of these serious mental disorders, a low-grade inflammation seems to be a possible contributor. Concurrently, systemic inflammation and its interplay with dyslipidemia is a cen...
Article
Full-text available
The complex effects of plant cannabinoids on human physiology is not yet fully understood, but include a wide spectrum of effects on immune modulation. The immune system and its inflammatory effector pathways are recently emerging as possible causative factors in psychotic disorders. The present study aimed to investigate whether self-administered...
Article
Full-text available
Rationale 5-methoxy-N,N-dimethyltryptamine is a psychotropic substance found in various plant and animal species and is synthetically produced. 5-methoxy-N,N-dimethyltryptamine is used in naturalistic settings for spiritual exploration, recreation, or to address negative affect and mood problems. However, scientific knowledge on the effects of 5-me...
Article
Background and purpose: N,N-dimethyltryptamine (DMT) is an endogenous ligand of the Sigma 1 receptor (Sig-1R) with documented in vitro cytoprotective properties against hypoxia. Our aim was to demonstrate the in vivo neuroprotective effect of DMT following ischemia-reperfusion injury in the rat brain. Methods: Transient middle cerebral occlusion...
Article
Full-text available
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translate...
Preprint
Full-text available
The complex effects of plant cannabinoids on human physiology is not yet fully understood, but include a wide spectrum of effects on immune modulation. The immune system and its inflammatory effector pathways are recently emerging as possible causative factors in psychotic disorders. The present study aimed to investigate whether self-administered...
Article
Background Cardiovascular disease (CVD) is a major cause of premature death in patients with psychotic disorders. The interaction between lipid accumulation, inflammation and vascular remodeling promotes atherogenesis and adverse CVD outcomes. We hypothesize that inflammatory markers reflecting different inflammatory pathways with relevance for ath...
Article
Full-text available
Recent advances reveal that metabolic reprogramming is required for adequate antiviral responses of dendritic cells (DCs) that possess the capacity to initiate innate and adaptive immune responses. Several reports indicate that Toll-like receptor (TLR) stimulation of DCs is accompanied by a rapid induction of glycolysis; however, the metabolic requ...
Article
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Unique members of the nucleotide-binding domain leucine-rich repeat (NLR) family have been found to regulate intracellular signaling pathways initiated by other families of pattern recognition receptors (PRR) such as Toll-like receptors (TLRs) and retinoic-acid inducible gene I (RIG-I)-like receptors (RLRs). Plasmacytoid dendritic cells (pDCs), the...
Article
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In this paper we discuss the definitional problems of altered states of consciousness and their potential relevance in phenomenological investigation. We suggest that visionary states or visionary phantasy working induced by psychedelics (VSs), as extraordinary types of altered states, are appropriate subjects for phenomenological analysis. Natural...
Article
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Serotonin is a monoamine neurotransmitter that signals through a wide array of receptors (5-HT1-7) many of which are also involved in immune processes. Dendritic cells (DCs) are crucial players in immune defense by bridging innate and adaptive immune responses via their vast repertoire of pattern recognition receptors and antigen-presenting capabil...
Article
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Signaling lymphocyte activation molecule family (SLAMF) receptors are essential regulators of innate and adaptive immune responses. The function of SLAMF5/CD84, a family member with almost ubiquitous expression within the hematopoietic lineage is poorly defined. In this article, we provide evidence that in human monocyte-derived dendritic cells (mo...
Data
SLAMF5 expression in IRF8 knockdown moDCs. On day 5 of moDC differentiation, cell surface expression of SLAMF5 in IRF8-silenced or control moDCs was measured by flow cytometry. Values are expressed as relative fluorescence and are the mean ± SD of five independent experiments (*p < 0.05).
Data
Accumulation of ubiquitinated proteins in the presence of the proteasome inhibitor MG132. This panel shows a representative blot of control experiments to confirm the activity of MG132 in our experimental system. MoDCs were treated as described in the legend for Figure 5B. Western blot was developed by a ubiquitin-specific antibody as described in...
Data
Additional information to SLAMF5-mediated enhancement of dendritic cell autophagy. (A) This panel shows the uncropped version of Figure 2A. (B) Analysis of basal level of autophagy in control and SLAMF5-silenced cells. Control and SLAMF5-silenced moDCs were left untreated or incubated with 20 nM bafilomycin A1 (BafA1) for 2 h. LC3 and β-actin level...
Data
EAT-2 expression levels in human monocytes and moDCs. Western blot analysis of EAT-2 expression in monocytes and moDCs on day 5 of in vitro differentiation treated or not with LPS/IFNγ. A representative blot of three independent experiments is shown, with β-actin as loading control.
Data
Phenotypic maturation of SLAMF5-silenced moDCs. (A) moDCs were exposed to 100 ng ml−1 LPS and 10 ng ml−1 IFNγ for 24 h. Cell surface expression of HLA-A, B, C, HLA-DQ, CD40, and CD86 was measured by flow cytometry; values are expressed as reléative fluorescence. Expression of the above cell surface receptors was measured on the CD1a+ (B) and CD1a−...
Data
TRIM21 expression is enhanced in response to treatment with LPS/IFNγ. SLAMF5 knockdown or control moDCs were exposed to 100 ng ml−1 LPS and 10 ng ml−1 IFNγ for 8 h. TRIM21 protein levels were determined by western blot analysis. A representative of three independent experiments is shown. Bar chart on the right displays TRIM21 protein levels of SLAM...
Article
Full-text available
Purpose: In contemporary phenomenology, Dieter Lohmar has suggested that the new task of phenomenological research is to analyze the “alternative representational systems” of fantasy. In line with this program, we propose that psychedelic experience could also be suitable subject to this project subsumed under the wider category of fantasy activity...
Article
Full-text available
Mitochondrial reactive oxygen species (mtROS) generated continuously under physiological conditions have recently emerged as critical players in the regulation of immune signaling pathways. In this study we have investigated the regulation of antiviral signaling by increased mtROS production in plasmacytoid dendritic cells (pDCs), which, as major p...
Article
Full-text available
Ayahuasca is a brew made of two admixture plants containing dimethyltryptamine (DMT) and β-carbolines (harmine and tetrahydroharmine). The indigenous groups of the Amazonas basin have been using it for centuries as an ethnomedical substance in healing and spiritual-religious rituals. During the last two decades the brew has raised increased scienti...
Article
Full-text available
N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticul...
Data
The effect of Sig-1R inhibition on the DMT-mediated cell survival of human iPSC-derived cortical neurons, moMACs and moDCs in hypoxia. Specific Sig-1R blocking was performed by using the highly selective Sig-1R antagonist BD1063 dihydrochloride at working concentrations of 1–100 μM. Cellular survival was monitored similarly to Figures 2, 4. Cells w...
Data
DMT does not influence the hypoxia-modulated expression of the ER-stress sensor ATF6 in human primary cells. (A) Prior to their placement into hypoxia chamber (0.5% O2), cells were treated with 50 μM DMT (+DMT) or left non-treated (ctrl). Protein level expression of ATF6 was evaluated by Western blotting after 6 h of hypoxia treatment (6 h) in comp...
Article
Full-text available
Ayahuasca is a brew made of two admixture plants containing dimethyltryptamine (DMT) and b-carbolines (harmine and tetrahydroharmine). The indigenous groups of the Amazonas basin have been using it for centuries as an ethnomedical substance in healing and spiritual-religious rituals. During the last two decades the brew has raised increased scienti...
Article
A tanulmány reflexió Horgász Csaba Összeegyeztethető-e a pszichoanalitikus identitás a vallásos világnézettel istenhittel? című írására. Filozófiai-mélylélektani vizsgálódásunk során a Kohuti és jungi iskolák összemérhetőségének rövid bemutatása után megkísérlünk olyan konvergencia pontokat találni az analitikus pszichológia és a szelfpszichológia...
Article
Full-text available
A posztstrukturalizmus és a dekonstrukció mozgalmai visszhangra találtak a poszt-Jungiánus lélektanban, különösképpen James Hillman és napjainkban Stanton Marlan írásaiban. A következő tanulmányban amellett érvelünk, hogy Jung Selbst (mély-én) koncepciójának dekonstrukciójába végül mégis csak visszaszivárognak a metafizika – pontosabban egy termész...
Article
Full-text available
One of the major philosophical aspirations in contemporary consciousness research is to find a framework of explanation that could successfully address the problem of mind-body relations. Descartes is often regarded as the father of dualism in modern philosophy of mind. Phenomenology and embodiment may dissolve the problem of dualism in the waters...
Article
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In lack of professional research and appropriate concepts our scientific knowledge of psychedelic agents is limited. According to the long-held official view these drugs are entirely harmful and have no medical use. However, a recent surge of clinical and pharmacological studies in the field indicates that many psychedelic-like agents have therapeu...
Article
The major reservoir of human multipotent mesenchymal stem/stromal cells (MSC) is the bone marrow (BM) with the capability to control hematopoietic stem cell (HSC) development. The regenerative potential of MSC is associated with enhanced endogenous repair and healing mechanisms that modulate inflammatory responses. Our previous results revealed tha...
Conference Paper
Full-text available
Background: The orphan receptor sigma-1 is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation, cell survival, and mediates anti-inflammatory responses and immunosuppressive effects in murine in vivo models. The hallucinogenic N,N-dimethyltryptami...
Article
Inflammation is associated with oxidative stress and characterized by elevated levels of damage-associated molecular pattern (DAMP) molecules released from injured or even living cells into the surrounding microenvironment. One of these endogenous danger signals is the extracellular mitochondrial DNA (mtDNA) containing evolutionary conserved unmeth...
Conference Paper
Recent studies have revealed that the mammalian target of rapamycin (mTOR), a well-known regulator of several cellular processes, plays a crucial role in the regulation of both innate and adaptive immune responses. It has also been shown that the mTOR pathway is involved in TLR9-induced type I interferon (IFN) production by plasmacytoid dendritic c...
Article
Full-text available
The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not...
Conference Paper
Background: Neuropsychiatric diseases have recently been attributed to chronic inflammation in the central nervous system, and correlation between gene polymorphisms of innate immune receptors and the frequency of late onset of Alzheimer's disease (AD) has also been shown. Ligation of murine maternal Toll-like receptors (TLRs) and RIG-I-like recept...
Article
Type I and III IFNs are crucial, soluble components of potent antiviral responses. It has been explored recently that mTOR is involved in the regulation of IFN-α/β production by pDCs, albeit its role in the induction of IFN responses in cDCs remained unrevealed. In this study, we demonstrate that the PI3K/mTOR pathway is indispensable for eliciting...
Article
Full-text available
In this paper, we compare two main paradigms of the examination of altered states of consciousness, and we propose a new horizon of interpretation. On the one hand, we review the complicated matters of psychedelics in the context of psychology (and especially in that of transpersonal psychology); on the other hand we use some of the basic concepts...
Article
Full-text available
Plasmacytoid dendritic cells (pDCs) are professional type I interferon (IFN)-producing cells that play an essential role in antiviral immunity. In many cell types, detection of intracellular pathogens is mostly dependent on endosomal Toll-like receptors (TLRs) and cytosolic sensors, such as retinoic acid-inducible gene I (RIG-I). However, the possi...