Semantic association fMRI impairments represent a potential schizophrenia biomarker

Semantic association retrieval task (SORT) requires participants to indicate whether word pairs recall a third object, e.g. 'honey' and 'stings' activates 'bees'. We have previously shown that individuals with schizophrenia with more severe positive symptoms tend to report associations between unrelated word pairs than healthy controls; schizophrenia individuals with more severe negative symptoms tend to fail to report associations between related word pairs. This over-retrieval and under-retrieval on SORT correlates with functional magnetic resonance imaging (fMRI) activity in inferior parietal lobule (IPL). To examine the suitability of SORT as an endophenotype for schizophrenia, we examined SORT performance and activity across multiple stages of the illness: chronic, relapse, and first episode. We also examine SORT performance and activity in unaffected relatives. SORT performance and fMRI activity in schizophrenia-first episode, schizophrenia-chronic and schizophrenia-relapse were significantly impaired relative to healthy controls and unaffected relatives. Schizophrenia-chronic and schizophrenia-relapse participants showing more severe PANSS-positive and -general symptoms showed larger SORT impairments. For schizophrenia-first episode more severe negative symptoms were related to lower IPL activation, consistent with previous results showing that negative symptoms are among the first to emerge in the schizophrenia prodrome and that more severe symptoms in the first episode predict worse future outcomes. Unaffected relatives showed no impairments on SORT performance or fMRI activity relative to healthy controls, which is incompatible with the concept of SORT as an endophenotype for schizophrenia, but is consistent with the concept of SORT as a potential schizophrenia biomarker.