scholarly journals Behavioural and Neurochemical Effects of Acute (±) 3,4 methylenedioxymethamphetamine (MDMA) in the Dopamine D1 Receptor Mutant Rat

2021 ◽  
Author(s):  
◽  
Hanna Squire
Keyword(s):  
Working Memory ◽  
Memory Performance ◽  
Memory Function ◽  
Experimental Studies ◽  
Reward Processing ◽  
D1 Receptor ◽  
D1 Receptors ◽  
Acute Effects ◽  
Skf 81297 ◽  
Fos Expression

<p>Rationale: (±) 3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) is a recreationally abused psychostimulant that leads to detrimental effects on memory performance. MDMA’s acute effects on memory are often attributed to a working memory impairment resulting from compromised serotonin systems. However, recent evidence from non-human animal experimental studies suggests that acute MDMA may impair memory performance through an MDMA-induced increase in dopamine (DA) release, leading to overstimulation of DA D1 receptors. The overstimulation of D1 receptors during acute MDMA exposure is thought to indirectly impair memory by increasing a subject’s susceptibility to proactive interference, leading to a perseverative pattern of responding during memory tasks.  Objective: This project investigates the hypothesis that acute MDMA impairs memory performance via overstimulation of D1 receptors. The acute actions of MDMA will be assessed using DA D1 mutant (DAD1-/-) rats which possess a selective down-regulation in functional DA D1 receptors. On the basis that acute MDMA impairs memory function via overstimulation of D1 receptors it is predicted that, compared to control rats, DAD1-/- rats will be protected from the acute memory deficits caused by MDMA. Due to the novelty of the DAD1-/- rat model, prior to the assessment of the acute effects of MDMA on memory performance in these rats, behavioural and neurochemical characterisations will be conducted.  Methods: Firstly, a behavioural characterisation was conducted to explore the tendencies of DAD1-/- rats, compared to controls, in a drug free state. Behaviours relevant for motivation and reward, movement, and memory were the focus of the behavioural investigation due to evidence suggesting a role for D1-like receptors in these functions. Secondly, a neurochemical assessment of DAD1-/- and controls rats in response to MDMA (3 mg/kg) was assayed using c-fos expression, a marker for neuronal activity, in several brain regions with known DA innervation. Thirdly, to assess the acute effects of MDMA on memory performance, DAD1-/- and control rats were trained on a spatial working memory T-maze task, delayed non-matching to position (DNMTP), over 25 sessions. Once trained, rats were administered either MDMA (1.5, 2.25 and 3 mg/kg) or saline fifteen minutes prior to testing on DNMTP, with all subjects experiencing all drug doses three time each. In addition, to further investigate the hypothesis that overstimulation of D1 receptors impairs memory performance, the effects of a D1 receptor agonist, SKF 81297 (0.5, 1, 1.5, 3, 4.5 mg/kg) on DNMTP performance were also assessed.  Results: The behavioural characterisation revealed that DAD1-/- rats are capable of performing many behaviours relevant for reward processing, movement and memory function. However, DAD1-/- rats were impaired with regard to some reward-related behaviours, such as the acquitision of lever pressing for sugar pellets. The assessment of c-fos expression demonstrated that DAD1-/- rats express less c-fos in the medial prefrontal cortex, striatum and nucleus accumbens compared to control rats following MDMA administration. Lastly, the effects of acute MDMA administration on memory performance were tested. During the third block of MDMA administration, control rats demonstrated decreased accuracy on the DMNTP task at both the 2.25 and 3 mg/kg doses. The decrease in accuracy during MDMA exposure in control rats was driven by an increase in perseverative errors. On the contrary, DAD1-/- rats were not impaired on the DNMTP task following acute MDMA at any of the doses tested. Administration of SKF 81297 did not lead to any systematic changes in performance, but at the 3 mg/kg dose DAD1-/- rats displayed increased accuracy compared to control rats.  Conclusions: DAD1-/- rats were protected from an MDMA-induced decrease in accuracy on the DNMTP task compared to control rats. This finding challenges the assumption that MDMA’s acute effects on memory performance are wholly due to serononergic mechanisms. Specifically, the current study provides evidence for the hypothesis that acute MDMA exposure impairs memory performance in rats.</p>

scholarly journals Behavioural and Neurochemical Effects of Acute (±) 3,4 methylenedioxymethamphetamine (MDMA) in the Dopamine D1 Receptor Mutant Rat

2021 ◽  
Author(s):  
◽  
Hanna Squire
Keyword(s):  
Working Memory ◽  
Memory Performance ◽  
Memory Function ◽  
Experimental Studies ◽  
Reward Processing ◽  
D1 Receptor ◽  
D1 Receptors ◽  
Acute Effects ◽  
Skf 81297 ◽  
Fos Expression

<p>Rationale: (±) 3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) is a recreationally abused psychostimulant that leads to detrimental effects on memory performance. MDMA’s acute effects on memory are often attributed to a working memory impairment resulting from compromised serotonin systems. However, recent evidence from non-human animal experimental studies suggests that acute MDMA may impair memory performance through an MDMA-induced increase in dopamine (DA) release, leading to overstimulation of DA D1 receptors. The overstimulation of D1 receptors during acute MDMA exposure is thought to indirectly impair memory by increasing a subject’s susceptibility to proactive interference, leading to a perseverative pattern of responding during memory tasks.  Objective: This project investigates the hypothesis that acute MDMA impairs memory performance via overstimulation of D1 receptors. The acute actions of MDMA will be assessed using DA D1 mutant (DAD1-/-) rats which possess a selective down-regulation in functional DA D1 receptors. On the basis that acute MDMA impairs memory function via overstimulation of D1 receptors it is predicted that, compared to control rats, DAD1-/- rats will be protected from the acute memory deficits caused by MDMA. Due to the novelty of the DAD1-/- rat model, prior to the assessment of the acute effects of MDMA on memory performance in these rats, behavioural and neurochemical characterisations will be conducted.  Methods: Firstly, a behavioural characterisation was conducted to explore the tendencies of DAD1-/- rats, compared to controls, in a drug free state. Behaviours relevant for motivation and reward, movement, and memory were the focus of the behavioural investigation due to evidence suggesting a role for D1-like receptors in these functions. Secondly, a neurochemical assessment of DAD1-/- and controls rats in response to MDMA (3 mg/kg) was assayed using c-fos expression, a marker for neuronal activity, in several brain regions with known DA innervation. Thirdly, to assess the acute effects of MDMA on memory performance, DAD1-/- and control rats were trained on a spatial working memory T-maze task, delayed non-matching to position (DNMTP), over 25 sessions. Once trained, rats were administered either MDMA (1.5, 2.25 and 3 mg/kg) or saline fifteen minutes prior to testing on DNMTP, with all subjects experiencing all drug doses three time each. In addition, to further investigate the hypothesis that overstimulation of D1 receptors impairs memory performance, the effects of a D1 receptor agonist, SKF 81297 (0.5, 1, 1.5, 3, 4.5 mg/kg) on DNMTP performance were also assessed.  Results: The behavioural characterisation revealed that DAD1-/- rats are capable of performing many behaviours relevant for reward processing, movement and memory function. However, DAD1-/- rats were impaired with regard to some reward-related behaviours, such as the acquitision of lever pressing for sugar pellets. The assessment of c-fos expression demonstrated that DAD1-/- rats express less c-fos in the medial prefrontal cortex, striatum and nucleus accumbens compared to control rats following MDMA administration. Lastly, the effects of acute MDMA administration on memory performance were tested. During the third block of MDMA administration, control rats demonstrated decreased accuracy on the DMNTP task at both the 2.25 and 3 mg/kg doses. The decrease in accuracy during MDMA exposure in control rats was driven by an increase in perseverative errors. On the contrary, DAD1-/- rats were not impaired on the DNMTP task following acute MDMA at any of the doses tested. Administration of SKF 81297 did not lead to any systematic changes in performance, but at the 3 mg/kg dose DAD1-/- rats displayed increased accuracy compared to control rats.  Conclusions: DAD1-/- rats were protected from an MDMA-induced decrease in accuracy on the DNMTP task compared to control rats. This finding challenges the assumption that MDMA’s acute effects on memory performance are wholly due to serononergic mechanisms. Specifically, the current study provides evidence for the hypothesis that acute MDMA exposure impairs memory performance in rats.</p>

scholarly journals The role of dopamine D1 receptors in MDMA-induced memory impairments

2020 ◽  
Author(s):  
Hanna Squire ◽  
Jiun Youn ◽  
Bart Ellenbroek ◽  
David Harper
Keyword(s):  
Working Memory ◽  
Spatial Working Memory ◽  
Memory Performance ◽  
Experimental Studies ◽  
D1 Receptor ◽  
D1 Receptors ◽  
Memory Impairments ◽  
Perseverative Errors ◽  
Drug Doses ◽  
Task Accuracy

(±) 3,4-methylenedioxymethamphetamine (MDMA) is a recreationally abused psychostimulant that impairs memory performance. This effect is often attributed to a working memory impairment resulting from compromised serotonin systems. However, recent evidence from non-human animal experimental studies suggests that acute MDMA may indirectly impair memory performance through overstimulation of dopamine (DA) D1 receptors, which increases perseverative responding during memory tasks. This hypothesis was explored using DA D1 mutant (DAD1-/-) rats which possess a selective down-regulation in functional D1 receptors. Adult male Wistar DAD1-/- rats and wild type controls were trained over 25 sessions on a spatial working memory T-maze task, delayed non-matching to position (DNMTP). Once trained, the rats were administered MDMA (1.5, 2.25 and 3 mg/kg) or saline fifteen minutes prior to testing on DNMTP with all subjects experiencing all drug doses and saline three times. We predicted that controls would demonstrate decreased task accuracy following MDMA, driven by an increase in perseverative errors. In contrast, we predicted that DAD1-/- rats would be protected from MDMA-induced perseverative errors due to their reduced D1 receptor function. As predicted, during the third block of MDMA administration, control rats demonstrated decreased task accuracy following 2.25 and 3 mg/kg doses, driven by an increase in perseverative errors. In addition, DAD1-/- rats were protected from MDMA-induced task deficits. These findings challenge the assumption that MDMA’s acute effects on memory performance are predominantly due to serotonergic mechanisms and provide support for the hypothesis that acute MDMA impairs memory performance in rats via overstimulation of D1 receptors by increasing perseverative behaviour.

scholarly journals Behavioral and neural signatures of working memory in childhood

2019 ◽  
Author(s):  
Monica D. Rosenberg ◽  
Steven A. Martinez ◽  
Kristina M. Rapuano ◽  
May I. Conley ◽  
Alexandra O. Cohen ◽  
...  
Keyword(s):  
Working Memory ◽  
Individual Differences ◽  
Fluid Intelligence ◽  
Short Term Memory ◽  
Memory Performance ◽  
Memory Function ◽  
The United States ◽  
Reward Processing ◽  
Stop Signal Task ◽  
Back Task

AbstractWorking memory function changes across development and varies across individuals. The patterns of behavior and brain function that track individual differences in working memory during development, however, are not well understood. Here we establish associations between working memory, cognitive abilities, and functional MRI activation in data from over 4,000 9–10-year-olds enrolled in the Adolescent Brain Cognitive Development study, an ongoing longitudinal study in the United States. Behavioral analyses reveal robust relationships between working memory, short-term memory, language skills, and fluid intelligence. Analyses relating out-of-scanner working memory performance to memory-related fMRI activation in an emotional n-back task demonstrate that frontoparietal activity in response to an explicit memory challenge indexes working memory ability. Furthermore, this relationship is domain-specific, such that fMRI activation related to emotion processing during the emotional n-back task, inhibitory control during a stop-signal task, and reward processing during a monetary incentive delay task does not track memory abilities. Together these results inform our understanding of the emergence of individual differences in working memory and lay the groundwork for characterizing the ways in which they change across adolescence.

scholarly journals A Neurofunctional Domains Approach to Evaluate D1/D5 Dopamine Receptor Partial Agonism on Cognition and Motivation in Healthy Volunteers With Low Working Memory Capacity

2020 ◽  
Vol 23 (5) ◽  
pp. 287-299
Author(s):  
Rita Balice-Gordon ◽  
Garry D Honey ◽  
Christopher Chatham ◽  
Estibaliz Arce ◽  
Sridhar Duvvuri ◽  
...  
Keyword(s):  
Working Memory ◽  
Adverse Events ◽  
Partial Agonist ◽  
Working Memory Capacity ◽  
Dose Range ◽  
Specific Treatment ◽  
Memory Capacity ◽  
Dopamine D1 Receptor ◽  
Reward Processing ◽  
D1 Receptor

Abstract Background Dopamine D1 receptor signaling plays key roles in core domains of neural function, including cognition and reward processing; however, many questions remain about the functions of circuits modulated by dopamine D1 receptor, largely because clinically viable, selective agonists have yet to be tested in humans. Methods Using a novel, exploratory neurofunctional domains study design, we assessed the safety, tolerability, pharmacodynamics, and pharmacokinetics of PF-06412562, a selective D1/D5R partial agonist, in healthy male volunteers who met prespecified criteria for low working memory capacity. Functional magnetic resonance imaging, electrophysiologic endpoints, and behavioral paradigms were used to assess working memory, executive function, and motivation/reward processing following multiple-dose administration of PF-06412562. A total of 77 patients were assigned PF-06412562 (3 mg twice daily and 15 mg twice daily) or placebo administered for 5 to 7 days. Due to the exploratory nature of the study, it was neither powered for any specific treatment effect nor corrected for multiple comparisons. Results Nominally significant improvements from baseline in cognitive endpoints were observed in all 3 groups; however, improvements in PF-06412562–treated patients were less than in placebo-treated participants. Motivation/reward processing endpoints were variable. PF-06412562 was safe and well tolerated, with no serious adverse events, severe adverse events, or adverse events leading to dose reduction or temporary discontinuation except for 1 permanent discontinuation due to increased orthostatic heart rate. Conclusions PF-06412562, in the dose range and patient population explored in this study, did not improve cognitive function or motivation/reward processing more than placebo over the 5- to 7-day treatment period. ClinicalTrials.gov Identifier NCT02306876

Ecstasy use and higher-level cognitive functions: weak effects of ecstasy after control for potential confounds

2008 ◽  
Vol 38 (9) ◽  
pp. 1319-1330 ◽  
Author(s):  
G. Bedi ◽  
J. Redman
Keyword(s):  
Working Memory ◽  
Cognitive Functions ◽  
Verbal Memory ◽  
Drug Users ◽  
Memory Performance ◽  
Memory Function ◽  
Inverse Association ◽  
Cross Sectional ◽  
Cohort Design ◽  
Larger Sample

BackgroundAlthough there have been several reports linking ecstasy use with lowered cognitive function, much previous research suffers from substantial methodological limitations. The present study aimed to examine associations between ecstasy use and higher-level cognitive functions, using a larger sample size than most previous research and better controlling for a range of potential confounds.MethodA cross-sectional cohort design assessed 45 currently abstinent ecstasy polydrug users (EP), 48 cannabis polydrug users (CP) and 40 legal drug users (LD). Standardized neuropsychological tests were used to measure attention, verbal, visual and working memory and executive function. Prospective memory function was also assessed.ResultsIt was not possible to discriminate between groups on the basis of the cognitive functions assessed. Regression analyses showed an inverse association between lifetime dose of ecstasy and verbal memory performance. A combination of drug-use variables, including measures of ecstasy use, contributed to prediction of attention/working memory. However, individual associations were small, explaining 1–6% of variance in cognitive scores.ConclusionsAlthough the results suggest that heavy use of ecstasy is associated with some lowering of higher-level cognitive functions, they do not indicate a clinical picture of substantial cognitive dysfunction.

scholarly journals Quantifying the inverted U: A meta-analysis of prefrontal dopamine, D1-receptors, and working memory

2021 ◽  
Author(s):  
Matthew A. Weber ◽  
Mackenzie M. Conlon ◽  
Hannah R. Stutt ◽  
Linder Wendt ◽  
Patrick Ten Eyck ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Function ◽  
Memory Performance ◽  
Meta Analysis ◽  
Quantitative Relationship ◽  
D1 Receptors ◽  
Hyperactivity Disorder ◽  
Human Disorders ◽  
High Level ◽  
And Behavior

Dopamine in the prefrontal cortex can be disrupted in human disorders that affect cognitive function such as Parkinson's disease (PD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia. Dopamine has a powerful effect on prefrontal circuits via the D1-type dopamine receptor (D1DR). It has been proposed that prefrontal dopamine has "inverted U-shaped" dynamics, with optimal dopamine and D1DR signaling required for optimal cognitive function. However, the quantitative relationship between prefrontal dopamine and cognitive function is not clear. Here, we conducted a meta-analysis of published manipulations of prefrontal dopamine and the effects on working memory, a high-level executive function in humans, primates, and rodents that involves maintaining and manipulating information over seconds to minutes. We reviewed 646 papers and found that 75 studies met criteria for inclusion. Our quantification of effect sizes for dopamine, D1DRs, and behavior revealed a negative quadratic slope. This is consistent with the proposed inverted U-shape of prefrontal dopamine and D1DRs and working memory performance, explaining 10% of the variance. Of note, the inverted quadratic fit was much stronger for prefrontal D1DRs alone, explaining 26% of the variance, compared to prefrontal dopamine alone, explaining 10% of the variance. Taken together, these data, derived from a variety of manipulations and systems, demonstrate that optimal prefrontal dopamine signalling is linked with higher cognitive function. Our results provide insight into the fundamental dynamics of prefrontal dopamine, which could be useful for pharmacological interventions targeting prefrontal dopaminergic circuits, and into the pathophysiology of human brain disease.

scholarly journals Can pharmacological enhancement of the placebo effect be a novel therapy for working memory impairments?

2018 ◽  
Author(s):  
Weihua Zhao ◽  
Benjamin Becker ◽  
Shuxia Yao ◽  
Xiaole Ma ◽  
Juan Kou ◽  
...  
Keyword(s):  
Working Memory ◽  
Mental Disorders ◽  
Placebo Effect ◽  
Memory Performance ◽  
Memory Function ◽  
Controlled Clinical Trial ◽  
Expectancy Effects ◽  
Nocebo Effect ◽  
Novel Therapy ◽  
Wide Range

AbstractWorking memory is considered as a core aspect of cognitive function and its impairment in a wide range of mental disorders has resulted in it being considered as an important transdiagnostic feature. To date pharmacological and behavioural strategies for augmenting working memory have achieved only moderate success. Here we have taken a different approach by combining expectancy effects with intranasal oxytocin as an adjunct given previous evidence that it may enhance placebo effects. In a randomised controlled clinical trial we demonstrate that while working memory performance is not influenced by expectancy per se when it is given in conjunction with oxytocin performance in terms of accuracy can be significantly enhanced following positive expectancy induction (placebo effect) and impaired following negative expectancy induction (nocebo effect). Thus combining expectancy effects with intranasal oxytocin may represent a radical new approach for improving working memory function in mental disorders.

scholarly journals Chemogenetic actuator drugs impair prefrontal cortex-dependent working memory in rhesus monkeys

2019 ◽  
Author(s):  
Nicholas A. Upright ◽  
Mark G. Baxter
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Rhesus Monkeys ◽  
Memory Performance ◽  
Memory Function ◽  
Muscarinic Acetylcholine Receptor ◽  
Designer Drugs ◽  
Delayed Response ◽  
Response Task ◽  
Delayed Response Task

AbstractThe most common chemogenetic neuromodulatory system, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is no longer sensitive to acetylcholine. It is crucial in studies using these systems to test the potential effects of DREADD actuators prior to any DREADD transduction, so that effects of DREADDs can be attributed to the chemogenetic system rather than the actuator drug. We investigated working memory performance after injections of three DREADD agonists, clozapine, olanzapine, and deschloroclozapine, in male rhesus monkeys tested in a spatial delayed response task. Performance at 0.1 mg/kg clozapine and 0.1 mg/kg deschloroclozapine did not differ from mean performance after vehicle in any of the four subjects. Administration of 0.2 mg/kg clozapine impaired working memory function in three of the four monkeys. Two monkeys were impaired after administration of 0.1 mg/kg olanzapine and two monkeys were impaired after the 0.3 mg/kg dose of deschloroclozapine. We speculate that the unique neuropharmacology of prefrontal cortex function makes the primate prefrontal cortex especially vulnerable to off-target effects of DREADD actuator drugs with affinity for endogenous monoaminergic receptor systems. These findings underscore the importance of within-subject controls for DREADD actuator drugs to confirm that effects following DREADD receptor transduction are not due to the actuator drug itself, as well as validating the behavioral pharmacology of DREADD actuator drugs in the specific tasks under study.Significance StatementChemogenetic technologies, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), allow for precise and remote manipulation of neuronal circuits. In the present study, we tested monkeys in a spatial delayed response task after injections of three actuator drugs – clozapine, olanzapine, and deschloroclozapine. We found that monkeys showed significant working memory impairments after 0.2 mg/kg clozapine, 0.1 mg/kg olanzapine, and 0.3 mg/kg deschloroclozapine compared to vehicle performance. In monkeys that showed impairments, these deficits were particularly apparent at longer delay periods. It is imperative to validate the drugs and dosages in the particular behavioral test to ensure any behavior after DREADD transduction can be attributed to activation of the receptors and not administration of the actuator drug itself.

scholarly journals Naturalistic coding of working memory in primate prefrontal cortex

2020 ◽  
Author(s):  
Megan Roussy ◽  
Rogelio Luna ◽  
Lyndon Duong ◽  
Benjamin Corrigan ◽  
Roberto A. Gulli ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Memory Performance ◽  
Memory Function ◽  
Nmda Receptor Antagonist ◽  
Inhibitory Neurons ◽  
Natural Behavior ◽  
Neuronal Populations ◽  
Memory Representations ◽  
Decoding Accuracy

SummaryThe primate lateral prefrontal cortex (LPFC) is considered fundamental for temporarily maintaining and manipulating mental representations that serve behavior, a cognitive function known as working memory1. Studies in non-human primates have shown that LPFC lesions impair working memory2 and that LPFC neuronal activity encodes working memory representations3. However, such studies have used simple displays and constrained gaze while subjects held information in working memory3, which put into question their ethological validity4,5. Currently, it remains unclear whether LPFC microcircuits can support working memory function during natural behavior. We tested macaque monkeys in a working memory navigation task in a life-like virtual environment while their gaze was unconstrained. We show that LPFC neuronal populations robustly encode working memory representations in these conditions. Furthermore, low doses of the NMDA receptor antagonist, ketamine, impaired working memory performance while sparing perceptual and motor skills. Ketamine decreased the firing of narrow spiking inhibitory interneurons and increased the firing of broad spiking cells reducing population decoding accuracy for remembered locations. Our results show that primate LPFC generates robust neural codes for working memory in naturalistic settings and that such codes rely upon a fine balance between the activation of excitatory and inhibitory neurons.

Fractionation of Verbal Memory Impairment in Schizophrenia and Schizophreniform Psychosis

2007 ◽  
Vol 41 (9) ◽  
pp. 732-739 ◽  
Author(s):  
Stephen J. Wood ◽  
Aleks U. Tarnawski ◽  
Tina M. Proffitt ◽  
Warrick J. Brewer ◽  
Greg R. Savage ◽  
...  
Keyword(s):  
Working Memory ◽  
Associative Learning ◽  
Verbal Memory ◽  
Memory Performance ◽  
Memory Function ◽  
Verbal Working Memory ◽  
First Episode ◽  
Story Recall ◽  
Associate Learning ◽  
The Impact

Objectives: The characterization, aetiology, and course of verbal memory deficits in schizophrenia remain ill defined. The impact of antipsychotic medications is also unclear. The purpose of the present paper was to investigate verbal memory performance in established schizophrenia (SZ) and first-episode schizophreniform psychosis (FE). Method: Performances of 32 SZ and 33 FE patients were compared to those of 47 healthy volunteers on measures of verbal working memory, verbal associative learning and story recall. Results: Story recall deficits, but not deficits in working memory or paired associate learning, were demonstrated by both patient groups. Patients treated with typical neuroleptics had more impairment in associative learning with arbitrary word pairings than those treated with atypicals, regardless of patient group. Conclusions: The results are consistent with the notion that some neuropsychological impairment is present at the time of psychosis onset and that this impairment is non-progressive. However, deficits may be specific to subclasses of memory function.

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