Recurrent schizophrenia-like psychosis as first manifestation of epilepsy: a diagnostic challenge in neuropsychiatry

Since the 1950s, several studies have been carried out to investigate the occurrence of schizophrenia-like psychoses in epilepsy. The psychopathological profile comprises symptoms from the affective, schizophrenic, and cognitive domains and the prevalence varies between 2% to 20%. Classification of such conditions is performed according to their temporal relationship with the seizure itself. Although it is well known that epilepsy may be associated with psychotic disorders, it is less widely recognized that relapsing psychotic phenomena may be the first and only symptom of epilepsy. In this research, two patients are described who were initially referred for recurrent episodes of bipolar affective disorder and schizophrenic psychosis, respectively. In both patients, a diagnosis of relapsing postictal psychotic states due to previously undiagnosed epilepsy was made and consequently, treatment with antiepileptics was started. During follow up over several months, they remained free of both epileptic and psychotic symptoms. Given the kaleidoscopic nature of the postictal psychosis and full recovery from this, such psychoses best meet the criteria for a cycloid psychosis. These observations illustrate diagnostic and therapeutic pitfalls due to the conceptual disintegration emerging from the inadequate separation between psychiatry and neurology. Therefore, the importance of a neuropsychiatric viewpoint should be promoted

Age-related gene and miRNA expression changes in airways of healthy individuals

© 2019, The Author(s). Knowledge on age-related miRNA changes in healthy individuals and their interaction with mRNAs is lacking. We studied age-related mRNA and miRNA expression changes and their interactions in normal airways. RNA and small RNA sequencing was performed on bronchial biopsies of 86 healthy individuals (age: 18–73) to determine age-related expression changes. Per age-related miRNA we determined the enrichment of age-related predicted targets and their correlation. We identified 285 age-related genes and 27 age-related miRNAs. Pathway enrichment showed that genes higher expressed with age were involved in synapse-related processes. Genes lower expressed with age were involved in cell cycle regulation, the immune system and DNA damage/repair. MiR-146a-5p, miR-146b-5p and miR-142-5p were lower expressed with increasing age and we found a significant enrichment for predicted targets of these miRNAs among genes that were higher expressed with age. The expression levels of the enriched predicted targets RIMS2 and IGSF1 were negatively correlated with both miR-146a-5p and miR-146b-5p. RIMS2 was present in the enriched process, i.e. positive regulation of synaptic transmission. In conclusion, genes decreased with ageing are involved in several of the ageing hallmarks. Genes higher expressed with ageing were involved in synapse-related processes, of which RIMS2 is potentially regulated by two age-related miRNAs

Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression

© 2017 The Author(s). Background: Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium. Methods: Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls. Results: In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate < 0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA < 0.001). Conclusion: We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD. Trial registration:ClinicalTrials.govregistration number NCT01351792(registration date May 10, 2011), ClinicalTrials.govregistration number NCT00848406(registration date February 19, 2009), ClinicalTrials.govregistration number NCT00807469(registration date December 11, 2008)

Recurrent schizophrenia-like psychosis as first manifestation of epilepsy: a diagnostic challenge in neuropsychiatry

Willem MA Verhoeven1,2, Jos IM Egger1,3, W Boudewijn Gunning4, Martijn Bevers1, Boudewijn JHB de Pont11Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands; 2Erasmus University Medical Centre, Department of Psychiatry, Rotterdam, The Netherlands; 3Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands; 4Epilepsy Centre Kempenhaeghe, Heeze, The NetherlandsAbstract: Since the 1950s, several studies have been carried out to investigate the occurrence of schizophrenia-like psychoses in epilepsy. The psychopathological profile comprises symptoms from the affective, schizophrenic, and cognitive domains and the prevalence varies between 2% to 20%. Classification of such conditions is performed according to their temporal relationship with the seizure itself. Although it is well known that epilepsy may be associated with psychotic disorders, it is less widely recognized that relapsing psychotic phenomena may be the first and only symptom of epilepsy. In this research, two patients are described who were initially referred for recurrent episodes of bipolar affective disorder and schizophrenic psychosis, respectively. In both patients, a diagnosis of relapsing postictal psychotic states due to previously undiagnosed epilepsy was made and consequently, treatment with antiepileptics was started. During follow up over several months, they remained free of both epileptic and psychotic symptoms. Given the kaleidoscopic nature of the postictal psychosis and full recovery from this, such psychoses best meet the criteria for a cycloid psychosis. These observations illustrate diagnostic and therapeutic pitfalls due to the conceptual disintegration emerging from the inadequate separation between psychiatry and neurology. Therefore, the importance of a neuropsychiatric viewpoint should be promoted.Keywords: postictal psychosis, epilepsy, classification, cycloid psychosis, neuropsychiatr

Current smoking is associated with decreased expression of mir-335-5p in parenchymal lung fibroblasts

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Cigarette smoking causes lung inflammation and tissue damage. Lung fibroblasts play a major role in tissue repair. Previous studies have reported smoking-associated changes in fibroblast responses and methylation patterns. Our aim was to identify the effect of current smoking on miRNA expression in primary lung fibroblasts. Small RNA sequencing was performed on lung fibroblasts from nine current and six ex-smokers with normal lung function. MiR-335-5p and miR-335-3p were significantly downregulated in lung fibroblasts from current compared to ex-smokers (false discovery rate (FDR) <0.05). Differential miR-335-5p expression was validated with RT-qPCR (p-value = 0.01). The results were validated in lung tissue from current and ex-smokers and in bronchial biopsies from non-diseased smokers and never-smokers (p-value <0.05). The methylation pattern of the miR-335 host gene, determined by methylation-specific qPCR, did not differ between current and ex-smokers. To obtain insights into the genes regulated by miR-335-5p in fibroblasts, we overlapped all proven miR-335-5p targets with our previously published miRNA targetome data in lung fibroblasts. This revealed Rb1, CARF, and SGK3 as likely targets of miR-335-5p in lung fibroblasts. Our study indicates that miR-335-5p downregulation due to current smoking may affect its function in lung fibroblasts by targeting Rb1, CARF and SGK3

Current Smoking Alters Gene Expression and DNA Methylation in the Nasal Epithelium of Patients with Asthma.

Current smoking contributes to worsened asthma prognosis and more severe symptoms and limits the beneficial effects of corticosteroids. As the nasal epithelium can reflect smoking-induced changes in the lower airways, it is a relevant source to investigate changes in gene expression and DNA methylation. This study explores gene expression and DNA methylation changes in current and ex-smokers with asthma. Matched gene expression and epigenome-wide DNA methylation samples collected from nasal brushings of 55 patients enrolled in a clinical trial investigation of current and ex-smoker patients with asthma were analyzed. Differential gene expression and DNA methylation analyses were conducted comparing current smokers with ex-smokers. Expression quantitative trait methylation (eQTM) analysis was completed to explore smoking-relevant genes by CpG sites that differ between current and ex-smokers. To investigate the relevance of the smoking-associated DNA methylation changes for the lower airways, significant CpG sites were explored in bronchial biopsies from patients who had stopped smoking. A total of 809 genes and 18,814 CpG sites were differentially associated with current smoking in the nose. The cis-eQTM analysis uncovered 171 CpG sites with a methylation status associated with smoking-related gene expression, including AHRR, ALDH3A1, CYP1A1, and CYP1B1. The methylation status of CpG sites altered by current smoking reversed with 1 year of smoking cessation. We confirm that current smoking alters epigenetic patterns and affects gene expression in the nasal epithelium of patients with asthma, which is partially reversible in bronchial biopsies after smoking cessation. We demonstrate the ability to discern molecular changes in the nasal epithelium, presenting this as a tool in future investigations into disease-relevant effects of tobacco smoke