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.

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.

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.

The Brain in Oral Clefting: A Systematic Review With Meta-Analyses.

Background: Neuroimaging of individuals with non-syndromic oral clefts have revealed subtle brain structural differences compared to matched controls. Previous studies strongly suggest a unified primary dysfunction of normal brain and face development which could explain these neuroanatomical differences and the neuropsychiatric issues frequently observed in these individuals. Currently there are no studies that have assessed the overall empirical evidence of the association between oral clefts and brain structure. Our aim was to summarize the available evidence on potential brain structural differences in individuals with non-syndromic oral clefts and their matched controls. Methods: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Web of Science and Embase were systematically searched in September 2020 for case-control studies that reported structural brain MRI in individuals with non-syndromic oral clefts and healthy controls. Studies of syndromic oral clefts were excluded. Two review authors independently screened studies for eligibility, extracted data and assessed risk of bias with the Newcastle-Ottawa Scale. Random effects meta-analyses of mean differences (MDs) and their 95% confidence intervals (95% CI) were performed in order to compare global and regional brain MRI volumes. Results: Ten studies from 18 records were included in the review. A total of 741 participants were analyzed. A moderate to high risk of bias was determined for the included studies. The cerebellum (MD: -12.46 cm3, 95% CI: -18.26, -6.67, n = 3 studies, 354 participants), occipital lobes (MD: -7.39, 95% CI: -12.80, -1.99, n = 2 studies, 120 participants), temporal lobes (MD: -10.53 cm3, 95% CI: -18.23, -2.82, n = 2 studies, 120 participants) and total gray matter (MD: -41.14 cm3; 95% CI: -57.36 to -24.92, n = 2 studies, 172 participants) were significantly smaller in the cleft group compared to controls. Discussion: There may be structural brain differences between individuals with non-syndromic oral clefts and controls based on the available evidence. Improvement in study design, size, methodology and participant selection could allow a more thorough analysis and decrease study heterogeneity.

Interspecies Comparisons of the Effects of Potential Antiviral 3-Amidinophenylalanine Derivatives on Cytochrome P450 1A2 Isoenzyme.

In vitro models of animals vulnerable to SARS-CoV-2 infection can support the characterization of effective antiviral drugs, such as synthetic inhibitors of the transmembrane protease serine 2 (TMPRSS2). Changes in cytochrome P450 (CYP) 1A2 activities in the presence of the potential TMPRSS2/matriptase inhibitors (MI) were measured using fluorometric and luminescent assays. Furthermore, the cytotoxicity of these inhibitors was evaluated using the MTS method. In addition, 60 min-long microsomal stability assays were performed using an UPLC-MS/MS procedure to elucidate depletion rates of the inhibitors. CYP1A2 was influenced significantly by MI-463 and MI-1900 in rat microsomes, by MI-432 and MI-482 in beagle microsomes, and by MI-432, MI-463, MI-482, and MI-1900 in cynomolgus monkey microsomes. The IC50 values in monkey microsomes were 1.30 ± 0.14 µM, 2.4 ± 1.4 µM, 0.21 ± 0.09 µM, and 1.1 ± 0.8 µM for inhibitors MI-432, MI-463, MI-482, and MI-1900, respectively. The depletion rates of the parent compounds were lower than 50%, independently of the investigated animal species. The host cell factor TMPRSS2 is of key importance for the cross-species spread of SARS-CoV-2. Studies of the in vitro biotransformation of TMPRSS2 inhibitors provide additional information for the development of new antiviral drugs.

Implicit Mentalizing in Patients With Schizophrenia: A Systematic Review and Meta-Analysis.

INTRODUCTION: Mentalizing is a key aspect of social cognition. Several researchers assume that mentalization has two systems, an explicit one (conscious, relatively slow, flexible, verbal, inferential) and an implicit one (unconscious, automatic, fast, non-verbal, intuitive). In schizophrenia, several studies have confirmed the deficit of explicit mentalizing, but little data are available on non-explicit mentalizing. However, increasing research activity can be detected recently in implicit mentalizing. The aim of this systematic review and meta-analysis is to summarize the existing results of implicit mentalizing in schizophrenia. METHODS: A systematic search was performed in four major databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science. Eleven publications were selected. Five studies were found to be eligible for quantitative synthesis, and 9 studies were included in qualitative synthesis. RESULTS: The meta-analysis revealed significantly lower accuracy, slower reaction time during implicit mentalizing in patients with schizophrenia. The systematic review found different brain activation pattern, further alterations in visual scanning, cue fixation, face looking time, and difficulties in perspective taking. DISCUSSION: Overall, in addition to the deficit of explicit mentalization, implicit mentalization performance is also affected in schizophrenia, if not to the same extent. It seems likely that some elements of implicit mentalization might be relatively unaffected (e.g., detection of intentionality), but the effectiveness is limited by certain neurocognitive deficits. These alterations in implicit mentalizing can also have potential therapeutic consequences.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021231312.

Generation and characterization of a human iPSC line SANi008-A from a Chédiak-Higashi Syndrome patient.

Induced pluripotent stem cells (iPSCs) were generated from erythroblasts (EBLs) obtained from a patient diagnosed with Chédiak-Higashi Syndrome (CHS), caused by mutations in LYST (c.4322_4325delAGAG and c.10127A>G). EBLs were reprogrammed with CytoTune-iPS 2.0 Sendai Reprogramming Kit, where the generated iPSCs showed normal karyotype, expression of pluripotency associated markers and in vitro spontaneous differentiation towards the three germ layers. The generated iPSCs can be used to study CHS pathophysiology and the role of LYST in different cell types.

Generation and characterization of a human iPSC line SANi007-A from a patient with a heterozygous dominant mutation in ELANE.

Induced pluripotent stem cell (iPSC) line was generated from erythroblasts (EBLs) derived from a patient diagnosed with severe congenital neutropenia, caused by mutations in ELANE (c.614delG). Transgene-free iPSC line was generated using Sendai virus reprogramming. The iPSC line showed normal karyotype, expressed pluripotency associated genes and was capable of in vitro spontaneous differentiation towards the three germ layers. The generated iPSC line can be used to study severe congenital neutropenia and the role of neutrophil elastase protein.

Generation and characterization of a human iPSC line SANi006-A from a Gray Platelet Syndrome patient.

Induced pluripotent stem cells (iPSCs) were generated from erythroblasts (EBLs) obtained from a patient diagnosed with Gray Platelet Syndrome (GPS), caused by compound heterozygous NBEAL2 mutations (c.6568delT and c.7937T>C). GPS is an autosomal recessive bleeding disorder characterized by a lack of α-granules in platelets and progressive myelofibrosis. EBLs were reprogrammed with CytoTune-iPS 2.0 Sendai Reprogramming Kit, where the generated iPSCs showed normal karyotype, expression of pluripotency associated markers and in vitro spontaneous differentiation towards the three germ layers. The generated iPSCs can be used to study GPS pathophysiology and the basic functions of NBEAL2 protein in different cell types.

Minor Physical Anomalies in Bipolar Disorder-A Meta-Analysis.

Introduction: Minor physical anomalies (MPAs) may reflect basic neurobiological features underlying bipolar disorders (BPD), as they are sensitive physical indicators of morphogenetic failure of the brain. Despite several researches about the presence of MPAs in BPD, the results are still controversial. Objectives: The aim of the present meta-analysis was to assess the standardized weighted mean effect sizes of MPAs in BPD and to examine if MPAs may be found predominantly in the head and/or facial regions in BPD patients compared to controls (HC). Methods: Four studies, involving 155 patients with BPD, and 187 HC, were involved in the analysis after searching the literature. For the investigation of MPAs in the peripheral (MPA-P) and in the head and facial regions (MPA-CF), two studies involving 121 BPD patients, and 133 HC passed the inclusion criteria. Results: The number of the MPAs in the BPD group was significantly higher compared to HC. Another important finding of the present study is that BPD patients' MPA-P scores do not significantly differ from those of the HC. In contrast, BPD patients' MPA-CF scores were found to be significantly higher compared to HC subjects. It is important to note that there was a low number of eligible publications included, which caused higher heterogeneity. Conclusions: Low quality of evidence suggests that MPAs are more common in patients with BPD than in HC and the higher rate of MPAs is found predominantly in the head and facial regions.

Generation and characterization of a control and patient-derived human iPSC line containing the Hermansky Pudlak type 2 (HPS2) associated heterozygous compound mutation in AP3B1.

Induced pluripotent stem cells (iPSCs) were generated from blood outgrowth endothelial cells (BOECs) obtained from a healthy donor and from a patient diagnosed with Hermansky Pudlak Syndrome type 2 (HPS2), caused by compound heterozygous AP3B1 mutations (c.177delA and c.1839-1842delTAGA). BOECs were reprogrammed with a hOKSM self-silencing polycistronic lentiviral vector, where the generated iPSCs showed normal karyotype, expression of pluripotency associated markers and in vitro spontaneous differentiation towards the three germ layers. The generated iPSCs can be used to study HPS2 pathophysiology and the basic functions of AP3B1 protein in different cell types.

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.

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.

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

No abstract avalilable.

Assessment of two prophylactic fluid strategies in aneurysmal subarachnoid hemorrhage: A randomized trial.

OBJECTIVE: To compare the effect of two prophylactic euvolemic fluid strategy regimens on the incidence of cerebral vasospasm and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: Ninety-six patients with a basal intravenous intake of 15 mL/kg/day of Ringer's lactate solution were included, and an additional 15 to 50 mL/kg/day Ringer's lactate (RL-group) or hydroxyethyl starch 130/0.4 solution (HES-group) was administered to maintain the targeted mean arterial pressure. The primary end point was the occurrence of cerebral vasospasm during the first 14 days. The secondary end points were case fatality, Barthel's index, and Glasgow Outcome Scores (GOS) at 30 days after SAH. RESULTS: Cerebral vasospasm developed in 42 patients (43.7%), and nine of these events were severe. The vasospasm rate among the RL- and HES-based groups was 25/48 and 17/48, respectively. For the secondary endpoint, four patients (4%) died by the end of follow-up (two in each group). Unfavorable outcome cases were not different in the RL and HES groups (9 vs. 14, respectively). There was no difference between the Barthel's scores at 30 days between the two groups. CONCLUSIONS: Using starches in a prophylactic treatment strategy in aneurysmal SAH in not supported by the study.The trial was registered at Clinicaltrials.gov under the number NCT02064075.

Persons With Schizophrenia Misread Hemingway: A New Approach to Study Theory of Mind in Schizophrenia.

INTRODUCTION: Theory of Mind (ToM) is a key component of social cognition. Recently the Short Story Task (SST) was developed as a new measurement of ToM. SST uses a short story of Ernest Hemingway to assess ToM skills. SST proved to be a suitable tool, and sensitive to individual differences among healthy subjects. Our aim was to test SST to evaluate the ToM skills of persons with schizophrenia. MATERIALS AND METHODS: SST was used to assess ToM skills. After reading the short story "The End of Something" a structured interview was done with 14 questions. Spontaneous mental state reasoning, explicit mental state inference and comprehension of nonmental aspects of the story were evaluated. 47 persons with schizophrenia in remission and 48 healthy controls were assessed and compared. RESULTS: Persons with schizophrenia performed significantly more poorly in the explicit mental state inference questions. Ceiling effect was not detectable in explicit ToM scores. Patients made less spontaneous mental state references as well, although the occurrence of spontaneous mental state terms was infrequent in both groups. Patients were also less accurate in answering comprehension questions, but the difference was not significant after Bonferroni correction. DISCUSSION: Our results lined up with the original findings and we found SST to be a sensitive tool to explore the individual differences in ToM performance, not only among healthy subjects, but also among persons with schizophrenia especially in explicit mental state inferences without observing the ceiling effect. We found, however, SST to be less sensitive to measure spontaneous mental state reasoning and also the lack of the use of another ToM test to assess convergent validity of SST for indicating ToM deficits in schizophrenia stands as a limitation of current study.

Large-scale in vitro production of red blood cells from human peripheral blood mononuclear cells.

Transfusion of donor-derived red blood cells (RBC) is the most common form of cellular therapy. Donor availability and the potential risk of alloimmunization and other transfusion-related complications may, however, limit the availability of transfusion units, especially for chronically transfused patients. In vitro cultured, customizable RBC would negate these concerns and further increase precision medicine. Large-scale, cost-effective production depends on optimization of culture conditions. We developed a defined medium and adapted our protocols to good manufacturing practice (GMP) culture requirements, which reproducibly provided pure erythroid cultures from peripheral blood mononuclear cells without prior CD34+ isolation, and a 3 × 107-fold increase in erythroblasts in 25 days (or from 100 million peripheral blood mononuclear cells, 2 to 4 mL packed red cells can be produced). Expanded erythroblast cultures could be differentiated to CD71dimCD235a+CD44+CD117-DRAQ5- RBC in 12 days. More than 90% of the cells enucleated and expressed adult hemoglobin as well as the correct blood group antigens. Deformability and oxygen-binding capacity of cultured RBC was comparable to in vivo reticulocytes. Daily RNA sampling during differentiation followed by RNA-sequencing provided a high-resolution map/resource of changes occurring during terminal erythropoiesis. The culture process was compatible with upscaling using a G-Rex bioreactor with a capacity of 1 L per reactor, allowing transition toward clinical studies and small-scale applications.

Human-induced pluripotent stem cell-derived blood products: state of the art and future directions.

In vitro cultured blood cells for transfusion purposes provide a safe alternative to donor blood, particularly for patients who require recurrent transfusions, and can be used as carriers of therapeutic molecules. In vitro derivation of hematopoietic cell types from human-induced pluripotent stem cells (iPSCs) allows for a constant, well-defined production pipeline for such advanced therapeutic and medicinal products. Application of selected iPSC-derived hematopoietic stem cells and hematopoietic effector cells in transplantation/transfusions would avoid the risk of alloimmunization and blood-borne diseases, as well as enable the production of enhanced blood cells expressing molecules that enforce blood cell function or endow novel therapeutic properties. Here, we discuss the state of the art approaches to produce erythroid, megakaryoid and myeloid cells from iPSCs and the biological and technical hurdles that we need to overcome prior to therapeutic application.

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.