Differential patterns of contextual organization of memory in first-episode psychosis

Abstract

Contextual information is used to support and organize episodic memory. Prior research has reliably shown memory deficits in psychosis; however, little research has characterized how this population uses contextual information during memory recall. We employed an approach founded in a computational framework of free recall to quantify how individuals with first episode of psychosis (FEP, N = 97) and controls (CON, N = 55) use temporal and semantic context to organize memory recall. Free recall was characterized using the Hopkins Verbal Learning Test-Revised (HVLT-R). We compared FEP and CON on three measures of free recall: proportion recalled, temporal clustering, and semantic clustering. Measures of temporal/semantic clustering quantified how individuals use contextual information to organize memory recall. We also assessed to what extent these measures relate to antipsychotic use and differentiated between different types of psychosis. We also explored the relationship between these measures and intelligence. In comparison to CON, FEP had reduced recall and less temporal clustering during free recall (p < 0.05, Bonferroni-corrected), and showed a trend towards greater semantic clustering (p = 0.10, Bonferroni-corrected). Within FEP, antipsychotic use and diagnoses did not differentiate between free recall accuracy or contextual organization of memory. IQ was related to free recall accuracy, but not the use of contextual information during recall in either group (p < 0.05, Bonferroni-corrected). These results show that in addition to deficits in memory recall, FEP differed in how they organize memories compared to CON.

Episodic memory impairment in children and adolescents at risk for schizophrenia: A role for context processing

“…These results suggest that young people at high risk for schizophrenia experience context processing deficits in episodic memory. This finding is consistent with the broader literature showing comparable memory deficits associated with vulnerability to schizophrenia ( Sahakyan and Kwapil, 2016 , Sahakyan and Kwapil, 2018 ), first-episode psychosis ( Murty et al, 2018 ), and clinically diagnosed schizophrenia ( Polyn et al, 2015 ).…”

“…The extent that items are recalled in the studied order, referred to as temporal contiguity (for a review, see Healey et al, 2019 ), is assumed to indicate effective context processing. Schizophrenia patients ( Polyn et al, 2015 ) and people with first episode psychosis ( Murty et al, 2018 ) who recall fewer words show less temporal contiguity than healthy controls. Similarly, young adults with high negative schizotypy symptoms, which predict schizophrenia-spectrum disorders ( Kwapil et al, 2013 ), show poorer free recall accuracy and temporal contiguity than people in the normal range of negative symptoms ( Sahakyan and Kwapil, 2016 , Sahakyan and Kwapil, 2018 ).…”

Contiguity in episodic memory

“…Sahakyan and Kwapil (2018) found a reduction in contiguity relative to control among patients with negative schizotypy but not among those with positive schizotypy. Murty et al (2018) found a similar reduction in contiguity among a group of patients suffering their first episode of psychosis. Pajkossy et al (2017) found that a bias for short lag transitions was positively correlated with trait worry but negatively correlated with trait anxiety.…”

Schizophrenia-associated SAP97 mutations increase glutamatergic synapse strength in the dentate gyrus and impair contextual episodic memory in rats

“…Given that reduced βSAP97 expression results in dramatic augmentation of glutamatergic synapse strength in the DG granule neurons, we were interested in whether reduced βSAP97 expression within the dentate gyrus produces behavioral phenotypes associated with schizophrenia. A favored cognitive model of the abnormal behaviors and experiences characteristic of schizophrenia suggests that they may be linked to a disturbance in the effects of context 41,[46][47][48][49][50][51][52] . More specifically, it has been suggested that individuals with schizophrenia exhibit a diminished ability to assess the relative importance of contextual cues in their environment, and that such a deficit may ultimately lead to the development of delusions, disorganization, hallucinations, and the loss of a sense of personal identity [40][41][42][43][44][45] .…”

“…Furthermore, we find that reducing βSAP97 expression specifically within the dentate gyrus is sufficient to disrupt contextual episodic memory processing in rats. Similar memory deficits are present in individuals with schizophrenia and have been proposed to contribute to the development of delusions, disorganization, hallucinations, and the loss of a sense of personal identity observed with this disorder [40][41][42][43][44][45][46][47][48][49][50][51][52] . Finally, we show that schizophrenia-related missense mutations clustered in SAP97's PDZ2 domain also produce large increases in synaptic AMPAR function in DG granule neurons that can be attributed to the release of perisynaptic GluA1-containing AMPARs into the PSDs of perforant pathway synapses.…”