Recent studies show that human-specific LINE1s (L1HS) play a key role in the development of the central nervous system (CNS) and its disorders, and that their transpositions within the human genome are more common than previously thought. Many polymorphic L1HS, that is, present or absent across individuals, are not annotated in the current release of the genome and are customarily termed "non-reference L1s." We developed an analytical workflow to identify L1 polymorphic insertions with next-generation sequencing (NGS) using data from a family in which SZ segregates. Our workflow exploits two independent algorithms to detect nonreference L1 insertions, performs local de novo alignment of the regions harboring predicted L1 insertions and resolves the L1 subfamily designation from the de novo assembled sequence. We found 110 non-reference L1 polymorphic loci exhibiting Mendelian inheritance, the vast majority of which are already reported in dbRIP and/or euL1db, thus, confirming their status as non-reference L1 polymorphic insertions. Four previously undetected L1 polymorphic loci were confirmed by PCR amplification and direct sequencing of the insert. A large fraction of our non-reference L1s is located within the open reading frame of protein-coding genes that belong to pathways already implicated in the pathogenesis of schizophrenia. The finding of these polymorphic variants among SZ offsprings is intriguing and suggestive of putative pathogenic role. Our data show the utility of NGS to uncover L1 polymorphic insertions, a neglected type of genetic variants with the potential to influence the risk to develop schizophrenia like SNVs and CNVs. Ó2016WileyPeriodicals, Inc.

Technological advancements have led to the development of automated methods for assessing semantic coherence in psychiatric populations. Latent Semantic Analysis (LSA) is an automated method that has been used to quantify semantic coherence in schizophrenia-spectrum disorders. The current study examined whether: 1) Semantic coherence reductions extended to psychometrically-defined schizotypy and 2) Greater cognitive load further reduces semantic coherence. LSA was applied to responses generated during category fluency tasks in baseline and cognitive load conditions. Significant differences between schizotypy and non-schizotypy groups were not observed. Findings suggest that semantic coherence may be relatively preserved at this point on the schizophrenia-spectrum.

Aim Individuals at clinical high risk for psychosis (CHR) exhibit neurocognitive deficits in multiple domains. The aim of this study is to investigate whether several components of neurocognition are predictive of conversion to psychosis. Methods Fifty-two CHR individuals were assessed with the Structured Interview for Psychosis Risk Syndromes and completed a battery of neurocognitive tests at baseline including measures of executive functioning, attention, working memory, processing speed, and reaction time. Neurocognitive functioning at baseline was scored based on an external normative control group. Most subjects were followed for 2.5 years to determine conversion status. Results Significant differences in neurocognitive functioning between CHR individuals and the control group were present in all domains. Twenty-six percent of the participants converted to psychosis within 9.8 (standard deviation=8.0) months on average (median 9 months), but there were no significant differences in neurocognition converters and non-converters. Conclusions Individuals at CHR have deficits in neurocognitive functioning, but such deficits do not appear to be related to conversion risk.

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