Abstract

BackgroundPresumed obligate carriers (POCs) are the first-degree relatives of people with schizophrenia who, although do not exhibit the disorder, are in direct lineage of it. Thus, this subpopulation of first-degree relatives could provide very important information with regard to the investigation of endophenotypes for schizophrenia that could clarify the often contradictory findings in schizophrenia high-risk populations. To date, despite the extant literature on schizophrenia endophenotypes, we are only aware of one other study that examined the neural mechanisms that underlie cognitive abnormalities in this group. The aim of this study was to investigate whether a more homogeneous group of relatives, such as POCs, have neural abnormalities that may be related to schizophrenia.MethodsWe used functional magnetic resonance imaging (fMRI) to collect blood oxygenated level dependent (BOLD) response data in six POCs and eight unrelated healthy controls while performing under conditions of sustained, selective and divided attention.ResultsThe POCs indicated alterations in a widely distributed network of regions involved in attention processes, such as the prefrontal and temporal (including the parahippocampal gyrus) cortices, in addition to the anterior cingulate gyrus. More specifically, a general reduction in BOLD response was found in these areas compared to the healthy participants during attention processes.ConclusionThese preliminary findings of decreased activity in POCs indicate that this more homogeneous population of unaffected relatives share similar neural abnormalities with people with schizophrenia, suggesting that reduced BOLD activity in the attention network may be an intermediate marker for schizophrenia.

Highlights

  • Presumed obligate carriers (POCs) are the first-degree relatives of people with schizophrenia who, do not exhibit the disorder, are in direct lineage of it

  • This study reports preliminary findings from a cohort of individuals who are the presumed obligate carriers of genes linked to schizophrenia

  • Our findings showed that presumed obligate carriers (POCs) have altered neural function in the attention network that is similar to the abnormalities previously reported in patients with schizophrenia

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Summary

Introduction

Presumed obligate carriers (POCs) are the first-degree relatives of people with schizophrenia who, do not exhibit the disorder, are in direct lineage of it. A study of 20 subjects with 1 relative with schizophrenia will effectively deal with a risk increase from 1% to 2–4%, which does not necessarily reflecting strong genetic load Another possibility for these inconsistencies may be due to the subtlety of the deficits that make them undetectable behaviourally. Electrophysiological abnormalities (i.e., late P300) during target detection despite normal task performance has been reported in first-degree relatives of people with schizophrenia [12,13]. This is evidence to suggest that these enduring traits related to attentional processing are present in those who are genetically related to people with schizophrenia

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