Schizotypal personality disorder in individuals with the Attenuated Psychosis Syndrome: Frequent co-occurrence without an increased risk for conversion to threshold psychosis.

The Attenuated Psychosis Syndrome (APS), proposed as a condition warranting further study in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), is a controversial diagnostic construct originally developed to identify individuals at clinical high-risk for psychosis. The relationship of APS and Schizotypal Personality Disorder (SPD) remains unclear with respect to their potential co-occurrence and the effect of SPD on risk for conversion to threshold psychosis. We examined the prevalence and effect on conversion of SPD in a cohort of 218 individuals whose symptoms met APS criteria. Results indicated that SPD was highly prevalent (68%), and that SPD did not influence risk for conversion. Rather, total positive symptom burden measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS; OR 1.12, p = 0.02) emerged as the strongest predictor of conversion. These data suggest that when encountering a patient whose presentation meets SPD criteria, the clinician should assess whether APS criteria are also met and, for 1-2 years, carefully monitor positive symptoms for possible conversion to threshold psychosis.

A computational approach for deciphering the organization of glycosaminoglycans.

BACKGROUND: Increasing evidence has revealed important roles for complex glycans as mediators of normal and pathological processes. Glycosaminoglycans are a class of glycans that bind and regulate the function of a wide array of proteins at the cell-extracellular matrix interface. The specific sequence and chemical organization of these polymers likely define function; however, identification of the structure-function relationships of glycosaminoglycans has been met with challenges associated with the unique level of complexity and the nontemplate-driven biosynthesis of these biopolymers. METHODOLOGY/PRINCIPAL FINDINGS: To address these challenges, we have devised a computational approach to predict fine structure and patterns of domain organization of the specific glycosaminoglycan, heparan sulfate (HS). Using chemical composition data obtained after complete and partial digestion of mixtures of HS chains with specific degradative enzymes, the computational analysis produces populations of theoretical HS chains with structures that meet both biosynthesis and enzyme degradation rules. The model performs these operations through a modular format consisting of input/output sections and three routines called chainmaker, chainbreaker, and chainsorter. We applied this methodology to analyze HS preparations isolated from pulmonary fibroblasts and epithelial cells. Significant differences in the general organization of these two HS preparations were observed, with HS from epithelial cells having a greater frequency of highly sulfated domains. Epithelial HS also showed a higher density of specific HS domains that have been associated with inhibition of neutrophil elastase. Experimental analysis of elastase inhibition was consistent with the model predictions and demonstrated that HS from epithelial cells had greater inhibitory activity than HS from fibroblasts. CONCLUSIONS/SIGNIFICANCE: This model establishes the conceptual framework for a new class of computational tools to use to assess patterns of domain organization within glycosaminoglycans. These tools will provide a means to consider high-level chain organization in deciphering the structure-function relationships of polysaccharides in biology.