Evidence of complex involvement of serotonergic genes with restrictive and binge purge subtypes of anorexia nervosa

Peer reviewedPreprin

Further evidence of association of OPRD1 & HTR1D polymorphisms with susceptibility to anorexia nervosa

Background: A recent study reported strong evidence for the involvement of a region on human chromosome 1 and genetic susceptibility to anorexia nervosa (AN). A more detailed analysis of this region has suggested 2 genes that may account for this\ud susceptibility. These data suggest that polymorphisms in both the serotonin 1D (HTR1D) and opioid delta 1 (OPRD1) receptor genes show a significant association with restricting AN (RAN). Methods: In the current study, we have conducted an independent association study on 226 females meeting DSM-IV criteria for AN and 678 matched volunteers.\ud Results: We genotyped 4 SNPs in HTR1D and 6 SNPs in OPRD1. 3 SNPs were found to be associated with both RAN and binge-purge\ud AN (BPAN) within the gene for OPRD1. We also found evidence of association between 2 polymorphisms within HTR1D and RAN.\ud Conclusions: These data support the hypothesis that polymorphisms within this region form a component of the genetic basis to susceptibility to RAN. However, further work is required to understand the processes that may be mediated by these genes

Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson's disease diagnosis.

Cerebrospinal fluid (CSF) has often been used as the source of choice for biomarker discovery with the goal to support the diagnosis of neurodegenerative diseases. For this study, we selected 15 CSF protein markers which were identified in previously published clinical investigations and proposed as potential biomarkers for PD diagnosis. We aimed at investigating and confirming their suitability for early stage diagnosis of the disease. The current study was performed in a two-fold confirmatory approach. Firstly, the CSF protein markers were analysed in confirmatory cohort I comprising 80 controls and 80 early clinical PD patients. Through univariate analysis we found significant changes of six potential biomarkers (α-syn, DJ-1, Aβ42, S100β, p-Tau and t-Tau). In order to increase robustness of the observations for potential patient differentiation, we developed-based on a machine learning approach-an algorithm which enabled identifying a panel of markers which would improve clinical diagnosis. Based on that model, a panel comprised of α-syn, S100β and UCHL1 were suggested as promising candidates. Secondly, we aimed at replicating our observations in an independent cohort (confirmatory cohort II) comprising 30 controls and 30 PD patients. The univariate analysis demonstrated Aβ42 as the only reproducible potential biomarker. Taking into account both technical and clinical aspects, these observations suggest that the large majority of the investigated CSF proteins currently proposed as potential biomarkers lack robustness and reproducibility in supporting diagnosis in the early clinical stages of PD