RETRACTED: Mnemonic Discrimination Deficits in First-Episode Psychosis and a Ketamine Model Suggests Dentate Gyrus Pathology Linked to N-Methyl-D-Aspartate Receptor Hypofunction

Kraguljac, Nina; Carle, Matthew S.; Frölich, Michael A.; Tran, Steve; Yassa, Michael A.; White, David M.; Reddy, Abhishek; Lahti, Adrienne C.

doi:10.1016/j.bpsc.2017.02.005

Cited by 27 publications

(24 citation statements)

References 73 publications

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“…Investigating differential drug effects on brain metabolite levels in an animal model, McLoughlin and colleagues report antipsychotic induced reductions of glutamate in the frontal cortex only with clozapine and olanzapine, but not risperidone, haloperidol, or aripiprazole 47 . This is further supported by experiments with the NMDA receptor blocker ketamine, a popular pharmacological model of psychosis 11,12,[48][49][50][51][52][53] , showing that pretreatment with high dose olanzapine, but not risperidone attenuates ketamine induced alterations in brain metabolism 54 .…”

Section: Discussionmentioning

confidence: 80%

Neurometabolic correlates of 6 and 16 weeks of treatment with risperidone in medication-naive first-episode psychosis patients

et al. 2020

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Antipsychotic medications are the cornerstone of treatment in schizophrenia spectrum disorders. In first-episode psychosis, the recommended time for an antipsychotic medication trial is up to 16 weeks, but the biological correlates of shorter and longer antipsychotic treatment trials in these cohorts remain largely unknown. We enrolled 29 medication-naive first-episode patients (FEP) and 22 matched healthy controls (HC) in this magnetic resonance spectroscopy (MRS) study, examining the levels of combined glutamate and glutamine (commonly referred to as Glx) in the bilateral medial prefrontal cortex (MPFC) with a PRESS sequence (TR/TE = 2000/80 ms) before initiation of antipsychotic treatment, after 6 and 16 weeks of treatment with risperidone. Data were quantified in 18 HC and 20 FEP at baseline, for 19 HC and 15 FEP at week 6, and for 14 HC and 16 FEP at week 16. At baseline, none of the metabolites differed between groups. Metabolite levels did not change after 6 or 16 weeks of treatment in patients. Our data suggest that metabolite levels do not change after 6 or 16 weeks of treatment with risperidone in FEP. It is possible that our choice of sequence parameters and the limited sample size contributed to negative findings reported here. On the other hand, longer follow-up may be needed to detect treatment-related metabolic changes with MRS. In summary, our study adds to the efforts in better understanding glutamatergic neurometabolism in schizophrenia, especially as it relates to antipsychotic exposure.

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Section: Discussionmentioning

confidence: 80%

Neurometabolic correlates of 6 and 16 weeks of treatment with risperidone in medication-naive first-episode psychosis patients

et al. 2020

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“…Individuals with schizophrenia have impaired object discrimination but not impaired general recognition memory compared with healthy controls 121,122 . Similar deficits have been shown in a ketamine-administration model of schizophrenia, which suggests that NMDA-receptor-mediated mechanisms might underlie the deficit 122 . Overall, these studies suggest that pattern separation may be impaired in schizophrenia, although neural recording studies (for example, using fMRI) would be needed to draw this conclusion.…”

Section: Neuropsychiatric Diseasementioning

confidence: 86%

Integrating new findings and examining clinical applications of pattern separation

2018

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Pattern separation, the ability to independently represent and store similar experiences, is a crucial facet of episodic memory. Growing evidence suggests that the hippocampus possesses unique circuitry that is computationally capable of resolving mnemonic interference by using pattern separation. In this Review, we discuss recent advances in the understanding of this process and evaluate the caveats and limitations of linking across animal and human studies. We summarize clinical and translational studies using methods that are sensitive to pattern separation impairments, an approach that stems from the fact that the hippocampus is a major site of disruption in many brain disorders. We critically evaluate the assumptions that guide fundamental and translational studies in this area. Finally, we suggest guidelines for future research and offer ways to overcome potential interpretational challenges to increase the utility of pattern separation as a construct that can further understanding of both memory processes and brain disease.

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“…label them as 'similar'). A similar dissociation between intact recognition memory performance and impaired lure discrimination emerged in psychiatric and neurological disorders as well (Schizophrenia: 22,23 Early multiple sclerosis: 24 ).…”

Section: Lure Discrimination As Behavioral Indicator Of Pattern Separmentioning

confidence: 68%

Pupil size changes signal hippocampus-related memory functions

Pajkossy

Szöllősi

Racsmány

2020

Sci Rep

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A major task of episodic memory is to create unique, distinguishable representations of highly overlapping perceptual inputs. Several studies on this basic function have shown that it is based on the intact functioning of certain subregions of the hippocampus and is among the most sensitive behavioral indicators of mild cognitive impairment (MCI) and dementia. Here we assessed pupil dilation associated with performance in a widely used recognition paradigm that aims to uncover the intactness of fine-graded mnemonic discrimination. A sample of healthy undergraduate students was used. First, we showed that the correct discrimination between highly similar lure items and target items elicit larger pupil response than correct target identification. Second, we found that mnemonic discrimination is associated with larger pupil response in general as compared to target identification, regardless of whether the response was correct or not. These results suggest the pupil changes differentiate mnemonic discrimination and memory identification processes in recognition performance.

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RETRACTED: Mnemonic Discrimination Deficits in First-Episode Psychosis and a Ketamine Model Suggests Dentate Gyrus Pathology Linked to N-Methyl-D-Aspartate Receptor Hypofunction

Abstract: We observed a mnemonic discrimination deficit but intact recognition in both datasets. Our findings suggest a tentative mechanistic link between dentate gyrus dysfunction in first-episode psychosis and N-methyl-D-aspartate receptor hypofunction.

Cited by 27 publications

References 73 publications

Neurometabolic correlates of 6 and 16 weeks of treatment with risperidone in medication-naive first-episode psychosis patients

Neurometabolic correlates of 6 and 16 weeks of treatment with risperidone in medication-naive first-episode psychosis patients

Integrating new findings and examining clinical applications of pattern separation

Pupil size changes signal hippocampus-related memory functions

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