Mathilde Kazes

Methylomic changes during conversion to psychosis

The onset of psychosis is the consequence of complex interactions between genetic vulnerability to psychosis and response to environmental and/or maturational changes. Epigenetics is hypothesized to mediate the interplay between genes and environment leading to the onset of psychosis. We believe we performed the first longitudinal prospective study of genomic DNA methylation during psychotic transition in help-seeking young individuals referred to a specialized outpatient unit for early detection of psychosis and enrolled in a 1-year follow-up. We used Infinium HumanMethylation450 BeadChip array after bisulfite conversion and analyzed longitudinal variations in methylation at 411 947 cytosine–phosphate–guanine (CpG) sites. Conversion to psychosis was associated with specific methylation changes. Changes in DNA methylation were significantly different between converters and non-converters in two regions: one located in 1q21.1 and a cluster of six CpG located in GSTM5 gene promoter. Methylation data were confirmed by pyrosequencing in the same population. The 100 top CpGs associated with conversion to psychosis were subjected to exploratory analyses regarding the related gene networks and their capacity to distinguish between converters and non-converters. Cluster analysis showed that the top CpG sites correctly distinguished between converters and non-converters. In this first study of methylation during conversion to psychosis, we found that alterations preferentially occurred in gene promoters and pathways relevant for psychosis, including oxidative stress regulation, axon guidance and inflammatory pathways. Although independent replications are warranted to reach definitive conclusions, these results already support that longitudinal variations in DNA methylation may reflect the biological mechanisms that precipitate some prodromal individuals into full-blown psychosis, under the influence of environmental factors and maturational processes at adolescence.

[Validation of the French version of the expanded Brief Psychiatric Rating Scale with anchor BPRS-E(A)].

INTRODUCTION The Brief Psychiatric Rating Scale was initially developed as a rapid method to assess symptom change in psychiatric inpatients of various diagnoses. The original version was expanded to an 18-item version and thereafter to a 24-item version to increase sensitivity to a broader range of psychotic and affective symptoms. The latest version of the expanded 24- item BPRS provides probe questions and detailed anchor points for the ratings for each item. LITERATURE FINDINGS Studies have shown the expanded and anchored 24-item BPRS to be a sensitive and effective measure of psychiatric symptoms with good interrater reliability that can be maintained over time. To our knowledge, there are eight published papers including factor analyses of the BPRS-E(A). While many similarities are evident between these studies, inconsistencies are apparent that may have been due to sample size, characteristics and / or methodological differences in the factor analysis computation. Among these studies, six provided a four-factor solution. There was no French version of this scale available. METHODS After its translation into French and back translation, we investigated the validity of the French BPRS-E(A) version. We carried out a component analysis on the data of 111 participants of various diagnoses, mostly hospitalised for a first psychotic episode, yielding to a three-factor solution (positive symptoms--disorganisation; depression-anxiety and negative symptoms). RESULTS A good internal consistency and interrater reliability were found. These results confirm the psychometric value of the BPRS-E(A) in its French version. We compared those findings to earlier reports; similarities and differences are discussed.

2816 – Obsessive compulsive symptoms and premorbid adjustment as predictors of transition to psychosis in ultra-high risk subjects

Introduction Identifying at-risk mental states of psychosis can reduce the duration of untreated psychosis and the rate of transition. Meanwhile, it may improve prevention strategies of suicide, substance abuse and anxiety disorders comorbidities. Objectives We aim to investigate the clinical symptomatology differences at baseline, especially in non-specific symptoms, between UHR (Ultra High Risk) patients who did or did not make a transition to psychosis. Sharpening UHR inclusion criteria may improve prediction of transition to psychosis. Method The study included 85 young help-seekers (mean age= 20 y.o.) meeting UHR CAARMS’ criteria. 46 were followed up over a period of 30 months and 27 of them were assessed in a comprehensive clinical interview. Out of 46 finally included UHR subjects, 11 (40%) made a transition to psychosis. Psychopathology was investigated with the Comprehensive Assessment of At-Risk Mental State (CAARMS), BPRS and GAF-score. To identify the most predictive variables of transition, we applied a stepwise logistic regression on CAARMS’ criteria plus other variables (premorbid adjustment scale, cannabis use, subjective experienced life events, treatment and suicide). Results At baseline, premorbid adjustment and severity of CAARMS’ Obesssive-Compulsive Symptoms (OCS) were found to significantly influence the transition: poor premorbid adjustment, associated with moderate level of OCS increased the sensitivity (72.7%) and the specificity (92.8%) of the prediction. Conclusions Premorbid adjustment and level of OCS were predictive of transition in subjects at UHR. These characteristics could increase the level of prediction of psychosis.

Validation de la version française de l’échelle abrégée d’appréciation psychiatrique étendue avec ancrage, BPRS-E(A) [Validation of the French version of the expanded Brief Psychiatric Rating Scale with anchor BPRS-E(A)].

INTRODUCTION The Brief Psychiatric Rating Scale was initially developed as a rapid method to assess symptom change in psychiatric inpatients of various diagnoses. The original version was expanded to an 18-item version and thereafter to a 24-item version to increase sensitivity to a broader range of psychotic and affective symptoms. The latest version of the expanded 24- item BPRS provides probe questions and detailed anchor points for the ratings for each item. LITERATURE FINDINGS Studies have shown the expanded and anchored 24-item BPRS to be a sensitive and effective measure of psychiatric symptoms with good interrater reliability that can be maintained over time. To our knowledge, there are eight published papers including factor analyses of the BPRS-E(A). While many similarities are evident between these studies, inconsistencies are apparent that may have been due to sample size, characteristics and / or methodological differences in the factor analysis computation. Among these studies, six provided a four-factor solution. There was no French version of this scale available. METHODS After its translation into French and back translation, we investigated the validity of the French BPRS-E(A) version. We carried out a component analysis on the data of 111 participants of various diagnoses, mostly hospitalised for a first psychotic episode, yielding to a three-factor solution (positive symptoms--disorganisation; depression-anxiety and negative symptoms). RESULTS A good internal consistency and interrater reliability were found. These results confirm the psychometric value of the BPRS-E(A) in its French version. We compared those findings to earlier reports; similarities and differences are discussed.