Diminished social motivation in early psychosis is associated with polygenic liability for low vitamin D

Insufficiency of vitamin D levels often occur in individuals with schizophrenia and first-episode psychosis (FEP). However, it is unknown whether this represents a biological predisposition, or it is essentially driven by illness-related alterations in lifestyle habits. Lower vitamin D has also been associated with adverse neurodevelopmental outcomes and predominant negative psychotic symptoms. This study aimed to investigate the contribution of polygenic risk score for circulating 25-hydroxyvitamin D concentration (PRS-vitD) to symptom presentation among individuals with FEP enrolled in the Athens First-Episode Psychosis Research Study (AthensFEP n = 205) and the Psychosis Incident Cohort Outcome Study (PICOS n = 123). The severity of psychopathology was evaluated using the Positive and Negative Syndrome Scale at baseline and follow-up assessments (AthensFEP: 4-weeks follow-up, PICOS: 1-year follow-up). Premorbid intelligence and adjustment domains were also examined as proxy measures of neurodevelopmental deviations. An inverse association between PRS-vitD and severity of negative symptoms, in particular lack of social motivation, was detected in the AthensFEP at baseline (adjusted R2 = 0.04, p < 0.001) and follow-up (adjusted R2 = 0.03, p < 0.01). The above observation was independently validated in PICOS at follow-up (adjusted R2 = 0.06, p < 0.01). No evidence emerged for a relationship between PRS-vitD and premorbid measures of intelligence and adjustment, likely not supporting an impact of lower PRS-vitD on developmental trajectories related to psychotic illness. These findings suggest that polygenic vulnerability to reduced vitamin D impairs motivation and social interaction in individuals with FEP, thereby interventions that encourage outdoor activities and social engagement in this patient group might attenuate enduring negative symptoms

A molecular biology study of meningiomas

In the present study we examined the presence of mutations of the IDH1 and IDH2 genes in meningioma samples. Furthermore, promoter methylation status for the APC, RASSF1A, MGMT, DAPK, hMLH1 and PTEN genes was studied.78 paraffin embedded meningioma samples of all three meningioma Grades were analysed. The main methods applied were DNA bisulfite treatment of our samples, conventional PCR, PCR followed by High Resolution Melting Analysis and DNA sequencing with the use of the Sanger technique and pyrosequencing.Our results show that 5.3% of our samples carried IDH1 gene mutations and 4.8% had IDH2 gene mutations. All of these samples carrying the aforementioned mutations were Grade II and III. We also found in 38% of the samples that the APC gene promoter was methylated, 44% were methylated in the DAPK gene promoter region, 24.5% in the RASSF1A gene promoter region and 36% had a methylated MGMT gene promoter. The degree and extent of gene promoter methylation varied in terms of the number of methylated CpG islands. Our results of the hMLH1 and PTEN gene promoter methylation were not included, due to the small number of samples that were successfully analysed.Στην παρούσα διατριβή μελετήσαμε τις μεταλλαγές δύο γονιδίων, των IDH1 και IDH2 τα οποία είναι γνωστό πως συμμετέχουν στην αιτιοπαθογένεια των γλοιωμάτων, όπως επίσης είναι γνωστό πως λειτουργούν ως παράγοντες ρύθμισης των επιπέδων της μεθυλίωσης του DNA στα γλοιώματα. Επίσης, μελετήθηκε ο βαθμός μεθυλίωσης των υποκινητών έξι γονιδίων, των APC, RASSF1A, MGMT, DAPK, hMLH1 και PTEN. Το υλικό που αναλύθηκε ήταν 78 ιστολογικά δείγματα μηνιγγιωμάτων διαφόρων βαθμών κακοήθειας. Οι κύριες μέθοδοι που χρησιμοποιήθηκαν ήταν η χημική τροποποίηση του DNA, η συμβατική PCR, η PCR ακολουθούμενη από HRMA και η αλληλούχιση των υποκινητών με την μέθοδο Sanger και την μέθοδο της πυροαλληλούχισης. Όσον αφορά στα αποτελέσματά μας για τα γονίδια IDH1 και IDH2, ανιχνεύτηκαν στο IDH1 μεταλλαγές σε ποσοστό 5.3% και στο γονίδιο IDH2 ανιχνεύτηκαν μεταλλαγές σε ποσοστό 4.8%, σε δείγματα μηνιγγιωμάτων βαθμού κακοήθειας (Grade) ΙΙ και ΙΙΙ. Επίσης βρήκαμε διαφόρων βαθμών ετερογενή μεθυλίωση των υποκινητών των γονιδίων APC, DAPK, RASSF1A και MGMT. Συγκεκριμένα, για το γονίδιο ΑPC ανιχνεύτηκε μεθυλίωση του υποκινητή του στο 38% των δειγμάτων, για τον υποκινητή του γονιδίου DAPK στο 44% των δειγμάτων, για τον υποκινητή του γονιδίου RASSF1A στο 24.5% και για τον υποκινητή του γονιδίου MGMT στο 36%. Λόγω των χαμηλών αριθμών των δειγμάτων που αναλύθηκαν των υποκινητών των γονιδίων hMLH1 και PTEN, τα αποτελέσματα αυτά δεν συμπεριελήφθησαν

Association between exposome score for schizophrenia and functioning in first-episode psychosis: results from the Athens first-episode psychosis research study

BACKGROUND: Evidence suggests that environmental factors not only increase psychosis liability but also influence the prognosis and outcomes of psychotic disorders. We investigated temporal and cross-sectional associations of a weighted score of cumulative environmental liability for schizophrenia - the exposome score for schizophrenia (ES-SCZ) - with functioning in first-episode psychosis (FEP). METHODS: Data were derived from the baseline and 1-month assessments of the Athens FEP Research Study that enrolled 225 individuals with FEP. The Global Assessment of Functioning (GAF) and the Personal and Social Performance Scale (PSP) were used to measure social, occupational, and psychological functioning. The ES-SCZ was calculated based on the previously validated method. RESULTS: ES-SCZ was associated with the total scores of GAF and PSP at baseline and 1-month assessments. These findings remained significant when accounting for several associated alternative explanatory variables, including other environmental factors (obstetric complications, migration, ethnic minority), clinical characteristics (duration of untreated psychosis, symptom severity, previous antipsychotic use), and family history of psychosis, demonstrating that the association between ES-SCZ and functioning is over and above other risk factors and cannot be explained by symptom severity alone. Functioning improved from baseline to 1-month assessment, but no significant ES-SCZ-by-time interaction was found on functioning, indicating that functioning changes were not contingent on ES-SCZ. CONCLUSIONS: Our findings suggest that rather than a predictor of functional improvement, ES-SCZ represents a stable severity indicator that captures poor functioning in early psychosis. Environmental risk loading for schizophrenia (ES-SCZ) can be beneficial for clinical characterization and incorporated into transdiagnostic staging models