LINE1 insertions as a genomic risk factor for schizophrenia: Preliminary evidence from an affected family.

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 non-reference 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. © 2016 Wiley Periodicals, Inc.

Speech production and disorganization in schizotypy: Investigating the role of cognitive and affective systems.

Diminished productivity and elevated disorganization have been detected in the speech of individuals with schizotypy. However, the underlying mechanisms for these disruptions are not well understood. Separate lines of research suggest potential contributions from cognitive and affective systems. In this study, disorganized speech and speech production were examined in speech samples generated by schizotypy (n = 47) and non-schizotypy (n = 51) groups by assessing "reactivity" (i.e., a change in experimental compared with baseline conditions) across baseline, affective, and dual-task (i.e., cognitive) conditions. Relationships with social functioning were also examined within each group. Three key findings emerged: 1) compared to the non-schizotypy group, those with schizotypy exhibited diminished speech production in the affective condition and affective reactivity was observed; 2) the schizotypy group displayed greater levels of disorganized speech in dual-task conditions and cognitive reactivity was observed; and 3) affective reactivity for disorganized speech was linked to worse social functioning within the schizotypy group. This study provides evidence that cognitive and affective systems are uniquely involved in separate characteristics of speech in schizotypy. At this stage, cognitive systems appear to have a specific role in the organization of speech, whereas affective systems are more heavily involved in speech production. Regarding the association between affective reactivity and social functioning, previous research has demonstrated individuals highly reactive to emotional stimuli carry additional risk for conversion to psychosis. Future research identifying a subset with schizotypy who demonstrate affective reactivity could lead to a better understanding of links between schizotypy and future psychosis symptoms.

Semantic coherence in psychometric schizotypy: An investigation using Latent Semantic Analysis.

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.

Various neurocognitive deficits and conversion risk in individuals at clinical high risk for psychosis.

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 per cent 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.