LSD1/KDM1A and GFI1B repress endothelial fate and induce hematopoietic fate in induced pluripotent stem cell-derived hemogenic endotheliums.

Differentiation of induced pluripotent stem cells (iPSCs) into hematopoietic lineages offers great therapeutic potential. During embryogenesis, hemogenic endothelium (HE) gives rise to hematopoietic stem and progenitor cells through the endothelial-to-hematopoietic transition (EHT). Understanding this process using iPSCs is key to generating functional hematopoietic stem cells (HSCs), a currently unmet challenge. In this study, we examined the role of the transcriptional factor GFI1B and its co-factor LSD1/KDM1A in EHT. To this end, we employed patient-derived iPSC lines with a dominant negative dysfunctional GFI1BQ287* and irreversible pharmacological LSD1/KDM1A inhibition in healthy iPSC lines. The formation of HE remained unaffected; however, hematopoietic output was severely reduced in both conditions. Single-cell RNA sequencing (scRNAseq) performed on the CD144+/CD31+ population derived from healthy iPSCs revealed similar expression dynamics of genes associated with in vivo EHT. Interestingly, LSD1/KDM1A inhibition in healthy lines before EHT resulted in a complete absence of hematopoietic output. However, uncommitted HE cells did not display GFI1B expression, suggesting a timed transcriptional program. To test this hypothesis, we ectopically expressed GFI1B in uncommitted HE cells, leading to downregulation of endothelial genes and upregulation of hematopoietic genes, including GATA2, KIT, RUNX1, and SPI1. Thus, we demonstrate that LSD1/KDM1A and GFI1B can function at distinct temporal points in different cellular subsets during EHT. Although GFI1B is not detected in uncommitted HE cells, its ectopic expression allows for partial hematopoietic specification. These data indicate that precisely timed expression of specific transcriptional regulators during EHT is crucial to the eventual outcome of EHT.

Relative performance of various biomaterials used for maxillary sinus augmentation: A Bayesian network meta-analysis.

OBJECTIVES: To assess the histomorphometric outcomes obtained in randomized clinical trials (RCTs) with different biomaterials used for maxillary sinus augmentation (MSA). MATERIALS AND METHODS: A search of the existing medical literature until October 1, 2019, was performed. Inclusion criteria were (a) RCTs assessing a two-stage MSA from the lateral approach using autologous bone or biomaterials for grafting and (b) reported histomorphometric outcomes based on crestal bone core biopsy samples. The Bayesian method was used to perform pairwise meta-analyses and network meta-analysis (NMA). The primary outcome, the new bone percentage (NB %), was calculated as mean differences with 95% credible intervals. The interventions were ranked by their posterior probability by calculating the surface under the cumulative ranking curve values. RESULTS: Thirty-four RCTs (842 MSAs) were included in the analysis with a normal healing period (5-8 months). All comparisons were presented in a league table. On the basis of the ranking probability, the most effective bone grafting material for NB% was bovine xenograft + bone marrow concentrate (BMC) (81%), followed by bovine xenograft + platelet-rich plasma (PRP) (77%), bioactive glass ceramic + autologous bone 1:1 (70%), nanocrystalline hydroxyapatite in silica gel (70%), and bioactive glass ceramic (70%). Autologous bone graft alone took the twelfth position with 57%. CONCLUSION: Within the limitations of the present NMA, the analysis did not confirm autologous bone alone as the gold standard for MSA and showed superiority of composite grafts such as bovine xenograft + BMC after 5-8 months of healing.

Assessing the risk of rapid radiographic progression in Hungarian rheumatoid arthritis patients.

BACKGROUND: The outcome of rheumatoid arthritis (RA) should be determined early. Rapid radiological progression (RRP) is > or = 5 units increase according to the van der Heijde-Sharp score within a year. The risk of RRP can be estimated by a matrix model using non-radiographic indicators, such as C-reactive protein (CRP), rheumatoid factor (RF) and swollen joint count (SJC). PATIENTS AND METHODS: A non-interventional, cross-sectional, retrospective study was conducted in eleven Hungarian arthritis centres. We assessed RRP risk in biologic-naïve RA patients with the prevalence of high RRP risk as primary endpoint. RRP was calculated according to this matrix model. As a secondary endpoint, we compared RRP in methotrexate (MTX) responders vs non-responders. RESULTS: We analyzed data from 1356 patients. Mean CRP was 17.7 mg/l, RF was 139.3 IU/ml, mean 28-joint disease activity score (DAS28) was 5.00 and mean SJC was 6.56. Altogether 18.2% of patients had high risk (≥40%) of RRP. RA patients with high RRP risk of RRP (n = 247) had significantly lower age compared to those with RRP < 40% (n = 1109). MTX non-response (OR: 16.84), male gender (OR: 1.67), erosions at baseline (OR: 1.50) and ACPA seropositivity (OR: 2.18) were independent predictors of high-risk RRP. Male gender (OR: 5.20), ACPA seropositivity (OR: 4.67) and erosions (OR: 7.98) were independent predictors of high RRP risk in MTX responders. CONCLUSIONS: In this Hungarian study, high RRP risk occurred in 18% of RA patients. These patients differ from others in various parameters. RRP was associated with non-response to MTX.

Modelling the neuropathology of lysosomal storage disorders through disease-specific human induced pluripotent stem cells.

Mucopolysaccharidosis II (MPS II) is a lysosomal storage disorder (LSD), caused by iduronate 2-sulphatase (IDS) enzyme dysfunction. The neuropathology of the disease is not well understood, although the neural symptoms are currently incurable. MPS II-patient derived iPSC lines were established and differentiated to neuronal lineage. The disease phenotype was confirmed by IDS enzyme and glycosaminoglycan assay. MPS II neuronal precursor cells (NPCs) showed significantly decreased self-renewal capacity, while their cortical neuronal differentiation potential was not affected. Major structural alterations in the ER and Golgi complex, accumulation of storage vacuoles, and increased apoptosis were observed both at protein expression and ultrastructural level in the MPS II neuronal cells, which was more pronounced in GFAP + astrocytes, with increased LAMP2 expression but unchanged in their RAB7 compartment. Based on these finding we hypothesize that lysosomal membrane protein (LMP) carrier vesicles have an initiating role in the formation of storage vacuoles leading to impaired lysosomal function. In conclusion, a novel human MPS II disease model was established for the first time which recapitulates the in vitro neuropathology of the disorder, providing novel information on the disease mechanism which allows better understanding of further lysosomal storage disorders and facilitates drug testing and gene therapy approaches.

[Irony comprehension in first degree relatives of patients with bipolar disorder - a pilot fMRI study].

No abstract avalilable.

The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF.

Neural rosettes derived from human induced pluripotent stem cells (iPSCs) have been claimed to be a highly robust in vitro cellular model for biomedical application. They are able to propagate in vitro in the presence of mitogens, including basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). However, these two mitogens are also involved in anterior-posterior patterning in a gradient dependent manner along the neural tube axis. Here, we compared the regional identity of neural rosette cells and specific neural subtypes of their progeny propagated with low and high concentrations of bFGF and EGF. We observed that low concentrations of bFGF and EGF in the culturing system were able to induce forebrain identity of the neural rosettes and promote subsequent cortical neuronal differentiation. On the contrary, high concentrations of these mitogens stimulate a mid-hindbrain fate of the neural rosettes, resulting in subsequent cholinergic neuron differentiation. Thus, our results indicate that different concentrations of bFGF and EGF supplemented during propagation of neural rosettes are involved in altering the identity of the resultant neural cells.

[A new method for the measurement of social cognition in schizophrenia].

Impairments in social cognitive functions and their long-term effects are well known in schizophrenia. However, so far no computer application has been available to assess these functions of patients. Our study is about introducing a new computer application measuring social cognitive abilities. The program (SCAN) is available on the following link and can be downloaded for anyone: psychiatry.pote.hu > Research > Workgroups > Schizophrenia. The hypothesis of our present study was that SCAN is able to assess the social cognitive ability of patients with schizophrenia in a rapid, complex and objective way. METHOD: 86 schizophrenia patients and 101 healthy controls were examined. SCAN was used to present verbal and nonverbal tasks to measure four different domains of social cognition. SCAN registered the responses and the reaction times as well. Furthermore, an additional application was developed (called Scanalizer) to evaluate the results of a person being tested. RESULTS: The results were evaluated by a two-dimensional analysis. This means that both task performance and the reaction time were taken into consideration while evaluating the results. As for the results, we found that the patients showed significantly worse functioning than the healthy subjects in the four domains of social cognition. CONCLUSION: Based on our results, SCAN is effective enough to detect the atypical social processing of schizophrenia patients. Moreover, Scanalizer is capable of evaluating the social cognitive abilities of schizophrenia patients in a complex, relatively fast and objective way.

A Modular Synthetic Approach to Isosteric Sulfonic Acid Analogues of the Anticoagulant Pentasaccharide Idraparinux.

Heparin-based anticoagulants are drugs of choice in the therapy and prophylaxis of thromboembolic diseases. Idraparinux is a synthetic anticoagulant pentasaccharide based on the heparin antithrombin-binding domain. In the frame of our ongoing research aimed at the synthesis of sulfonic acid-containing heparinoid anticoagulants, we elaborated a modular pathway to obtain a series of idraparinux-analogue pentasaccharides bearing one or two primary sulfonic acid moieties. Five protected pentasaccharides with different C-sulfonation patterns were prepared by two subsequent glycosylation reactions, respectively, using two monosaccharide and four disaccharide building blocks. Transformation of the protected derivatives into the fully O-sulfated, O-methylated sulfonic acid end-products was also studied.

Strategies for rapidly mapping proviral integration sites and assessing cardiogenic potential of nascent human induced pluripotent stem cell clones.

Recent methodological advances have improved the ease and efficiency of generating human induced pluripotent stem cells (hiPSCs), but this now typically results in a greater number of hiPSC clones being derived than can be wholly characterized. It is therefore imperative that methods are developed which facilitate rapid selection of hiPSC clones most suited for the downstream research aims. Here we describe a combination of procedures enabling the simultaneous screening of multiple clones to determine their genomic integrity as well as their cardiac differentiation potential within two weeks of the putative reprogrammed colonies initially appearing. By coupling splinkerette-PCR with Ion Torrent sequencing, we could ascertain the number and map the proviral integration sites in lentiviral-reprogrammed hiPSCs. In parallel, we developed an effective cardiac differentiation protocol that generated functional cardiomyocytes within 10 days without requiring line-specific optimization for any of the six independent human pluripotent stem cell lines tested. Finally, to demonstrate the scalable potential of these procedures, we picked 20 nascent iPSC clones and performed these independent assays concurrently. Before the clones required passaging, we were able to identify clones with a single integrated copy of the reprogramming vector and robust cardiac differentiation potential for further analysis.

[MENTALIZING DEFICIT IN NEUROLOGICAL DISORDERS: A REVIEW ARTICLE]. / MENTALIZÁCIÓS DEFICIT NEUROLÓGIAI BETEGSÉGEKBEN: ÖSSZEFOGLALÓ KÖZLEMÉNY.

INTRODUCTION: Mentalization is the ability to attribute mental states (intentions, desires, thoughts, emotions) to others, and hence to predict their behaviour. This ability fundamentally determines our participation in social relationships and adaptation to society. A significant proportion of the disorders of the central nervous system (CNS) affects those brain structures and neurotransmitter systems that play a role in the mentalizing processes. Accordingly, a number of CNS disorders may be associated with mentalizing deficits, which may affect the outcome of these diseases. Here, we review recent research on mentalizing abilities in neurological diseases. METHODS: An internet database search was performed to identify publications on the subject. RESULTS: Sixty-two publications in English corresponded to the search criteria. These publications reported impaired mentalization in several neurological disorders (e.g. epilepsy, Parkinson's disease, multiple sclerosis, dementias, traumatic brain injury). DISCUSSION: The results indicate that a number of neurological disorders associate with mentalizing deficit. This deficit is often present in the early stages of the diseases and has a prognostic value, which in turn emphasizes the importance of the early detection and adequate rehabilitation.

[Good general cognitive skills on irony understanding in schizophrenia - an fMRi study]. / Jó általános kognitív készségek hatása az irónia megértesére szkizofréniában. Funkcionális MRI vizsgálat.

In this study we have examined a group of schizophrenia patients during the understanding of irony tasks, who had normal IQ. 14 patients and 14 healthy control subjects were included, 15 irony and 15 control tasks were invertigated during an fMRI investigation. During the contextual phase patients had shown a higher activitation in different brain regions. The healthy controls had shown deactivitation during this phase, while this couldn't be seen in the patiens group. During the irony phase healthy subjects activated brain regions known as mentalisation areas, while patients didn't. Our results can support the view, that behind schizophrenia patients mentalisation deficit the contextual phase can play the central role.

Generation of induced pluripotent stem cells from human foetal fibroblasts using the Sleeping Beauty transposon gene delivery system.

Transposon gene delivery systems offer an alternative, non-viral-based approach to generate induced pluripotent stem cells (iPSCs). Here we used the Sleeping Beauty (SB) transposon to generate four human iPSC lines from foetal fibroblasts. In contrast to other gene delivery systems, the SB transposon does not exhibit an integration bias towards particular genetic elements, thereby reducing the risk of insertional mutagenesis. Furthermore, unlike the alternative transposon piggyBac, SB has no SB-like elements within the human genome, minimising the possibility of mobilising endogenous transposon elements. All iPSC lines exhibited the expected characteristics of pluripotent human cells, including the ability to differentiate to derivatives of all three germ layers in vitro. Re-expression of the SB transposase in the iPSCs after reprogramming resulted in the mobilisation of some of the transposons. These results indicate that the SB transposon system is a useful addition to methods for generating human iPSCs, both for basic and applied biomedical research, and in the context of future therapeutic application.

[Social cognitive differences in first-degree relatives of patients with schizophrenia. A systematic review]. / Szociális kognitiv eltérések szkizofrén paciensek elso foku hozzátartozói között.

The impairment of social functioning and difficulties in social integration are frequently found in patients with schizophrenia, and may affect the quality of life, thus revealing the underlying mechanisms of these differences appear to be of high importance. The impairment of social functioning has been reported in first-degree relatives of schizophrenia patients and individuals at ultra-high risk for psychosis. Two meta-analyses and 15 studies were reviewed, in which various ToM tests were performed involving first-degree relatives of patients with schizophrenia,with diverse findings, both positive and negative results have been found, and in addition other cognitive deficits were reported in some cases. In the background of different findings methodological differences can be presumed. Overall the social cognitive functions of first-degree relatives were found affected, which suggests the role of social cognition as endophenotypic marker of schizophrenia.

[Minor physical anomalies in the relatives of schizophrenia patients. A systematic review of the literature]. / Minor fizikális anomáliák szkizofrén betegek hozzátartozói között. Szisztematikus áttekinto közlemény.

Minor physical anomalies are mild, clinically and cosmetically insignificant errors of morphogenesis which have a prenatal origin and may bear major informational value for diagnostic, prognostic and epidemiological purposes. Since both the central nervous system and the skin are derived from the same ectodermal tissue in utero, minor physical anomalies can be external markers of abnormal brain development and they appear more commonly in neurodevelopmental disorders. Recently studies were published on the prevalence of minor physical anomalies in the relatives of patients with schizophrenia. In a systematic review of literature 11 studies were identified with mixed results. We suppose that the differentiation of minor malformations and phenogenetic variants can help to clarify the minor anomaly profile as a potential endophenotype in schizophrenia.

Investigation of peripheral inflammatory biomarkers in association with suicide risk in major depressive disorder.

Suicide is the most severe complication of major depressive disorder (MDD). Novel research assumes the role of immunological dysregulation in the background - several studies have reported alterations in the number of inflammatory cells related to both MDD and suicidality. There are currently no objective, routinely measured parameters to indicate suicidal vulnerability. However, altered inflammatory cell numbers and ratios have been proposed as potential biomarkers of suicide risk (SR). The present research aims to examine changes of these values related to increased SR in MDD as an assumed inflammatory state. We investigated laboratory parameters of psychiatric in-patients diagnosed with MDD (n = 101) retrospectively. Individuals with recent suicide attempt (SA) (n = 22) and with past SA (n = 19) represented the high SR group. MDD patients with no history of SA (n = 60) composed the intermediate SR group. We compared the number of neutrophil granulocytes, monocytes, lymphocytes, platelets, white blood cell count (WBC), neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red blood cell distribution width (RDW) and erythrocyte sedimentation rate (ESR). Furthermore, we evaluated alterations of these parameters related to antidepressant (AD) and antipsychotic (AP) treatment, which have been proved to have anti-inflammatory effects. We found a significant increase in neutrophil granulocyte count, NLR, monocyte count, MLR, WBC and ESR in patients with recent SA compared to patients with no history of SA. Moreover, there was a significant elevation in monocyte count, MLR, ESR and RDW in patients with high SR compared to patients with intermediate SR. AD treatment resulted in a significant decrease in neutrophil granulocyte count and NLR, however, it did not affect monocyte count and MLR. Assuming immunological mechanisms in the background of MDD and suicidality, our findings support the role of NLR as a biomarker of acute SR, though its alterations may be masked by possible anti-inflammatory effects of AD treatment in the long term. However, MLR, a marker exhibiting changes which are not attenuated by pharmacotherapy, may be a possible indicator of both acute and long-term suicidal vulnerability.

Patients with chronic bipolar disorder show impairments in interpreting literary fiction - A preliminary explorative study with the short story task.

INTRODUCTION: Theory of mind (ToM) is a crucial skill in navigating and functioning in the social world. Significant ToM impairment was consistently found in bipolar disorder; it can be both a state and trait marker of the disorder. However, most of the ToM tests are not sensitive enough to detect subtle individual differences, which would be necessary for an individualized treatment plan. The Short Story Task (SST) is a new way to sensitively assess individual differences in ToM performance. The aim of the study was to test the feasibility of SST in patients with bipolar disorder. METHOD: 31 persons (11 male, 20 female) with bipolar I disorder and 31 healthy individuals (15 males and 16 females) as a control group were recruited. SST was used to evaluate ToM performance. The SST uses a Hemingway novel, in which the patient is presented with a realistic social situation, where the motivations of the characters and the underlying relationships of events are not explicitly described. RESULTS: In the explicit mental state reasoning questions the CG (M = 8.06) had significantly higher (p < 0.001) scores than the persons with bipolar I disorder (M = 5.03). There was no ceiling effect for explicit ToM scores in either group. Participants in CG (M = 8.03) also significantly outperformed (p = 0.006) the BG participants (M = 6.55) in the comprehension questions. The spontaneous mental state inference question was performed equally (M = 0.23) in both groups. Group assignment (t = -3.503, p < 0.001), comprehension score (t = 2.864, p = 0.006), and spontaneous mentalization (t = 2.846, p = 0.006) significantly predicted the explicit ToM performance. CONCLUSIONS: Overall, we found that the Short Story Task is a promising tool for measuring ToM in patients with bipolar disorder without ceiling effect. Primarily explicit ToM was found to be deficient, which corresponds well with the ToM literature in bipolar disorder. Contrary to our hypothesis we could not detect impairment in spontaneous ToM and found that patients living with bipolar disorder also showed deficits in comprehension. The lack of assessment of neurocognitive skills is a significant limitation of the current study.

White-matter microstructure and language lateralization in left-handers: a whole-brain MRI analysis.

Most people are left-hemisphere dominant for language. However the neuroanatomy of language lateralization is not fully understood. By combining functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), we studied whether language lateralization is associated with cerebral white-matter (WM) microstructure. Sixteen healthy, left-handed women aged 20-25 were included in the study. Left-handers were targeted in order to increase the chances of involving subjects with atypical language lateralization. Language lateralization was determined by fMRI using a verbal fluency paradigm. Tract-based spatial statistics analysis of DTI data was applied to test for WM microstructural correlates of language lateralization across the whole brain. Fractional anisotropy and mean diffusivity were used as indicators of WM microstructural organization. Right-hemispheric language dominance was associated with reduced microstructural integrity of the left superior longitudinal fasciculus and left-sided parietal lobe WM. In left-handed women, reduced integrity of the left-sided language related tracts may be closely linked to the development of right hemispheric language dominance. Our results may offer new insights into language lateralization and structure-function relationships in human language system.

Generation of mouse induced pluripotent stem cells from different genetic backgrounds using Sleeping beauty transposon mediated gene transfer.

Induced pluripotent stem (iPS) cell technology involves reprogramming somatic cells to a pluripotent state. The original technology used to produce these cells requires viral gene transduction and results in the permanent integration of exogenous genes into the genome. This can lead to the development of abnormalities in the derived iPS cells. Here, we report that non-viral transfection of a Sleeping Beauty (SB) transposon containing the coding sequences Oct3/4 (Pouf1), Sox-2, Klf-4 and c-Myc (OSKM) linked with 2A peptides, can reprogram mouse fibroblasts. We have established reprogrammed mouse cell lines from three different genetic backgrounds: (1) ICR-outbred, (2) C57BL/6-inbred and (3) F1-hybrid (C57BL/6 x DBA/2J), with parallel robust expression of all exogenous (Oct3/4, Sox-2, Klf-4, and c-Myc) and endogenous (e.g. Oct3/4 and Nanog) pluripotency genes. The iPS cell lines exhibited characteristics typical for undifferentiated embryonic stem (ES) cell lines: ES cell-like morphology, alkaline phosphatase (ALP) positivity and gene expression pattern (shown by reverse transcription PCR, and immunofluorescence of ES cell markers-e.g. Oct3/4, SSEA1, Nanog). Furthermore, cells were able to form embryoid bodies (EBs), to beat rhythmically, and express cardiac (assayed by immunofluorescence, e.g. cardiac Troponin T, desmin) and neuronal (assayed by immunofluorescence e.g. nestin, Tuj1) markers. The in vitro differentiation potential was found to be the highest in the ICR-derived iPS lines (ICR-iPS). Interestingly, the ICR-iPS lines had even higher differentiation potential than the ICR-ES cell lines: the rate of EBs forming rhythmically beating cardiomyocytes was 4% in ICR-ES and 79% in ICR-iPS cells, respectively. In vivo, the ICR and F1 hybrid iPS cells formed chimeras and one of the iPS cells from the F1 hybrid background transmitted to the germline. Our results suggest that iPS technology may be useful for generating pluripotent stem cells from genetic backgrounds of which good quality ES cell generation is difficult. These studies provide insights into viral-free iPS technology and may contribute towards defining future cell-based therapies, drug-screening methods and production of transgenic animals using genetically modified iPS cells.

Seasonal patterns in the epidemiology of Bell's palsy in Hungary.

Introduction: Epidemiological data on Bell's palsy are vital for elucidating disease prevalence and enhancing therapeutic options. Our objective was to explore the prevalence and possible risk factors associated with Bell's palsy recurrence in the Clinical Center of the University of Debrecen service area. Secondary data analysis was performed using hospital discharge data, including patient information and comorbidities. Methods: Data was obtained from the Clinical Center of the University of Debrecen, on Bell's palsy patients who were treated at the hospital between January 1, 2015 and December 31, 2021. Multiple logistic regression analysis was used to examine the factors associated with Bell's palsy recurrence. Results: Of the 613 patients analyzed, 5.87% had recurrent paralysis, and the median time interval between episodes was 315 days. Hypertension was significantly associated with Bell's palsy recurrence. Moreover, seasonal distribution analysis revealed that the number of Bell's palsy episodes was higher in colder seasons, with spring and winter having a significantly higher number of episodes than summer and autumn. Discussion: This study provides insights into the prevalence and associated risk factors of Bell's palsy recurrence, which could aid in its management and help reduce the long-term consequences of the disease. Further research is necessary to determine the precise mechanisms underlying these findings.

The effect of reading literary fiction on the theory of mind skills among persons with schizophrenia and normal controls.

Introduction: Recent research data suggest that theory of mind (ToM) skills may improve after reading literary fiction. However, beside this short term favorable effect, regular long-term reading of literary fiction may also support ToM development or may improve ToM performance. The presence of impaired ToM abilities is well-documented in schizophrenia; however, the role of reading in these deficits is unknown. In the present study our aim was to assess the effect of prior reading experiences on theory of mind performance in patients with schizophrenia, and in healthy controls. Materials and methods: ToM assessment was done with the Short Story Task, which is based on the interpretation of a Hemingway short story. After reading the short story, questions were asked in an interview format regarding comprehension, explicit and implicit ToM skills, then comparative analysis of schizophrenia patients was performed (n = 47) and matched to a normal control (n = 48) group concerning deficits of ToM abilities. Participants were also stratified according to their prior reading experiences. Results: Previous reading experience was associated with better comprehension and explicit ToM performance both in patients with schizophrenia, and in healthy controls. However, the explicit ToM performance of patients with prior reading was still weaker compared to healthy controls with reading experiences. Path model analysis revealed that reading had a direct positive effect on ToM, and an indirect effect through improving comprehension. Conclusions: Prior reading experience is associated with better ToM performance not just in healthy controls but also in patients living with schizophrenia. Previous reading experience also improves comprehension, which in turn has a favorable impact on ToM. Our results support the idea that literary fiction reading may have a therapeutic potential in the rehabilitation of schizophrenia.