Use of prepubertal environment enrichment to prevent dopamine dysregulation in a neurodevelopmental rat model of schizophrenia risk

Zhu, Xiyu; Grace, Anthony A.

doi:10.1016/j.xpro.2022.101215

Cited by 3 publications

(2 citation statements)

References 33 publications

(54 reference statements)

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“…The difference in the timing of BDZ exposure is perhaps most relevant to note, as MAM rats were treated peripubertally compared to in young adulthood in our study. For example, environmental enrichment -which has previously demonstrated similar effects to diazepam in preventing the psychosis phenotype in the MAM model -is not effective when given postpubertally compared to peripubertally 33 . There are also much higher levels of heterogeneity between CHR-P individuals than in MAM rats.…”

Section: Discussionmentioning

confidence: 99%

Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High-Risk for Psychosis

Livingston,

De Micheli,

McCutcheon

et al. 2023

Preprint

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Background: Animal models indicate GABAergic dysfunction in the development of psychosis, and that benzodiazepine (BDZ) exposure can prevent the emergence of psychosis-relevant phenotypes. However, whether BDZ exposure influences the risk of psychosis in humans is unknown. Methods: This observational-cohort study used electronic health record data from 818 individuals at clinical high-risk for psychosis (CHR-P) to investigate whether BDZ exposure (including hypnotics e.g., zopiclone) reduces the risk of developing psychosis and adverse clinical outcomes. Cox proportional-hazards models were employed in both the whole-unmatched sample, and a propensity score matched (PSM) subsample. Results: 567 CHR-P individuals were included after data cleaning (105 BDZ-exposed, 462 BDZ-unexposed). 306 (54%) individuals were male, and the mean age was 22.3 years (SD 4.9). The BDZ-exposed and BDZ-unexposed groups differed on several demographic and clinical characteristics, including psychotic symptom severity. In the whole-unmatched sample, BDZ exposure was associated with increased risk of transition to psychosis (HR=1.61; 95%CI:1.03-2.52; P=0.037), psychiatric hospital admission (HR=1.93; 95%CI:1.13-3.29; P=0.017), home visit (HR=1.64; 95%CI:1.18-2.28; P=0.004), and A&E attendance (HR=1.88; 95%CI:1.31-2.72; P<0.001). However, after controlling for confounding-by-indication through PSM, BDZ exposure did not modulate the risk of any outcomes (all P>0.05). In analysis restricted to antipsychotic-naive individuals, BDZ exposure reduced the risk of transition to psychosis at trend-level (HR=0.59; 95%CI:0.32-1.08; P=0.089). Conclusions: BDZ exposure in CHR-P individuals was not associated with a reduction in the risk of psychosis transition or other adverse clinical outcomes. Results in the whole-unmatched sample suggest BDZ prescription may be more likely in CHR-P individuals with higher symptom severity.

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Section: Discussionmentioning

confidence: 99%

Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High-Risk for Psychosis

Livingston,

De Micheli,

McCutcheon

et al. 2023

Preprint

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“…EE is a behavioral paradigm that can stimulate cognitive function, and cognitive stimulation in rodents can be achieved by adding new items or rearranging existing items in the cage, thus positively affecting cognitive behavior (Zhu and Grace, 2022 ). EE can improve the positive, negative, and cognitive symptoms of MK-801 induced schizophrenia.…”

Section: Ee Improved the Cognitive Symptoms Of Schizophrenia Induced ...mentioning

confidence: 99%

The effects and mechanism of environmental enrichment on MK-801 induced cognitive impairment in rodents with schizophrenia

Tian

et al. 2022

Front. Cell. Neurosci.

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Schizophrenia is a severe mental disorder characterized by positive, negative, and cognitive symptoms. Cognitive symptoms are a kind of symptoms with high incidence and great impact on patients. There is no effective treatment in clinical practice. N-methyl-d-aspartic acid (NMDA) receptor hypofunction may be an important cause of cognitive symptoms. MK-801 (also named Dizocilpine), a noncompetitive antagonist of NMDA receptor, is often used to construct a model of NMDA receptor dysfunction. In terms of treatment, environmental enrichment (EE) as an environmental intervention can effectively improve the symptoms of cognitive impairment in rodents. In this paper, we first briefly introduce the background of cognitive symptoms and EE in schizophrenia, and then investigate the manifestations of MK-801 induced cognitive impairment, the improvement of EE on these cognitive impairments based on the MK-801 induced schizophrenia rodent models, and the possible mechanism of EE in improving cognitive symptoms. This article reviews the literature in recent years, which provides an important reference for MK-801 to construct a cognitive symptom model of schizophrenia and the mechanism of EE in improving cognitive symptoms of schizophrenia.

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Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High Risk for Psychosis

Livingston,

De Micheli,

McCutcheon

et al. 2024

Schizophrenia Bulletin

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Background and Hypothesis Animal models indicate GABAergic dysfunction in the development of psychosis, and that benzodiazepine (BDZ) exposure can prevent the emergence of psychosis-relevant phenotypes. However, whether BDZ exposure influences real-world clinical outcomes in individuals at clinical high risk for psychosis (CHR-P) is unknown. Study Design This observational cohort study used electronic health record data from CHR-P individuals to investigate whether BDZ exposure (including hypnotics, eg, zopiclone) reduces the risk of developing psychosis and adverse clinical outcomes. Cox proportional-hazards models were employed in both the whole-unmatched sample, and a propensity score matched (PSM) subsample. Study Results 567 CHR-P individuals (306 male, mean[±SD] age = 22.3[±4.9] years) were included after data cleaning. The BDZ-exposed (n = 105) and BDZ-unexposed (n = 462) groups differed on several demographic and clinical characteristics, including psychotic symptom severity. In the whole-unmatched sample, BDZ exposure was associated with increased risk of transition to psychosis (HR = 1.61; 95% CI: 1.03–2.52; P = .037), psychiatric hospital admission (HR = 1.93; 95% CI: 1.13–3.29; P = .017), home visit (HR = 1.64; 95% CI: 1.18–2.28; P = .004), and Accident and Emergency department attendance (HR = 1.88; 95% CI: 1.31–2.72; P < .001). However, after controlling for confounding-by-indication through PSM, BDZ exposure did not modulate the risk of any outcomes (all P > .05). In an analysis restricted to antipsychotic-naïve individuals, BDZ exposure reduced the risk of transition to psychosis numerically, although this was not statistically significant (HR = 0.59; 95% CI: 0.32–1.08; P = .089). Conclusions BDZ exposure in CHR-P individuals was not associated with a reduction in the risk of psychosis transition or adverse clinical outcomes. Results in the whole-unmatched sample suggest BDZ prescription may be more likely in CHR-P individuals with higher symptom severity.

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Use of prepubertal environment enrichment to prevent dopamine dysregulation in a neurodevelopmental rat model of schizophrenia risk

Cited by 3 publications

References 33 publications

Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High-Risk for Psychosis

Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High-Risk for Psychosis

The effects and mechanism of environmental enrichment on MK-801 induced cognitive impairment in rodents with schizophrenia

Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High Risk for Psychosis

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