No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis

Lee, Maria; Fatouros‐Bergman, Helena; Plavén-Sigray, Pontus; Victorsson, P; Sellgren, Carl M.; Erhardt, Sophie; Flyckt, Lena; Farde, Lars; Červenka, Simon

doi:10.1038/s41537-021-00176-x

Cited by 4 publications

(4 citation statements)

References 54 publications

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“…Failure to maintain the glutamate-GABA balance may be related to schizophrenia, epilepsy, and anxiety[ 29 ]. Glutamate-GABA regulates the neuronal excitation-inhibition balance, which can cause neurodegenerative diseases and cognitive impairment[ 30 ]. Reversing GABA imbalance, inhibiting the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, and inhibiting the release of interleukin-6 and tumor necrosis factor-alpha can improve cognitive impairment[ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Cognitive dysfunction in schizophrenia patients caused by down-regulation of γ-aminobutyric acid receptor subunits

Chen,

Zhou,

et al. 2024

World J Psychiatry

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BACKGROUND The expression pattern of gamma aminobutyric acid (GABA) receptor subunits are commonly altered in patients with schizophrenia, which may lead to nerve excitation/inhibition problems, affecting cognition, emotion, and behavior. AIM To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments. METHODS This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period. The expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance spectroscopy. The recognized cognitive battery tool, the MATRICS Consensus Cognitive Battery, was used to evaluate the scores for various dimensions of cognitive function. The correlation between GABA receptor subunit downregulation and schizophrenia was also analyzed. RESULTS Significant differences in GABA receptor subunit levels were found between the case and control groups (P < 0.05). A significant difference was also found between the case and control groups in terms of cognitive function measures, including attention/alertness and learning ability (P < 0.05). Specifically, as the expression levels of GABRA1 (α1 subunit gene), GABRB2 (β2 subunit gene), GABRD (δ subunit), and GABRE (ε subunit) decreased, the severity of the patients’ condition increased gradually, indicating a positive correlation between the downregulation of these 4 receptor subunits and schizophrenia (P < 0.05). However, the expression levels of GABRA5 (α5 subunit gene) and GABRA6 (α6 subunit gene) showed no significant correlation with schizophrenia (P > 0.05). CONCLUSION Downregulation of the GABA receptor subunits is positively correlated with schizophrenia. In other words, when GABA receptor subunits are downregulated in patients, cognitive impairment becomes more severe.

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Section: Discussionmentioning

confidence: 99%

Cognitive dysfunction in schizophrenia patients caused by down-regulation of γ-aminobutyric acid receptor subunits

Chen,

Zhou,

et al. 2024

World J Psychiatry

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“…The DA system was prevalent in both vertebrates and invertebrates and performs more of a neurotransmitter function. In vertebrates, DA was involved in many functions, including locomotion [ 53 , 54 , 55 ], cognition [ 56 , 57 , 58 ] and development [ 59 , 60 ]. In each temperature group of this experiment, the DAC of rotifers decreased significantly with the increase in CPZ concentration, and there was a concentration–response relationship between CPZ concentration and DAC.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Antipsychotic Chlorpromazine on the Survival, Reproduction and Population Growth Other Than Neurotransmitters of Zooplankton in Light of Global Warming

Feng

Zhang

Gao

et al. 2022

IJERPH

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Global warming and environmental pollution have created a unique combination of abiotic and biotic stresses to zooplankton. However, little information is available on the effects of antipsychotic drugs commonly used to treat psychosis, such as chlorpromazine (CPZ), on non-target aquatic organisms in light of global warming. This study investigated how dopamine concentrations (DAC), acute toxicity and chronic toxicity of Brachionus calyciflorus changed in response to CPZ and gradually increasing temperatures. The results showed that the concentration range of rotifer DAC was 1.06~2.51 ng/g. At 18, 25 and 32 °C, the 24 h LC50 was 1.795, 1.242 and 0.833 mg/L, respectively. Compared to the control, exposure to CPZ significantly decreased life expectancy at hatching, the net reproduction rate, generation time, population growth rate and dopamine concentration of B. calyciflorus in all three temperatures (p < 0.05). The toxicity of CPZ to rotifers was increased by high temperature. These findings indicated that CPZ is highly toxic to rotifers, displaying high ecological risks to aquatic ecosystems.

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“…In addition to the literature search, we also included our own cognitive data collected within the Karolinska Schizophrenia Project (KaSP; antipsychotic drug–naive patients with FEP and age- and sex-matched controls), parts of which have been published elsewhere 24 , 25 (eMethods 3 in Supplement 1 ).…”

Section: Methodsmentioning

confidence: 99%

Cognitive Function and Variability in Antipsychotic Drug–Naive Patients With First-Episode Psychosis

Lee,

Cernvall,

Borg

et al. 2024

JAMA Psychiatry

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ImportanceCognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated.ObjectiveTo provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls.Data SourcesIn this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022.Study SelectionOriginal studies reporting data on cognitive function in antipsychotic drug–naive patients with first-episode psychosis (FEP) were included.Data Extraction and SynthesisData were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias.Main Outcomes and MeasuresThe main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability.ResultsFifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = −1.16; 95% CI, −1.35 to −0.98; verbal learning: Hedges g = −1.08; 95% CI, −1.28 to −0.88; visual learning: Hedges g = −1.05; 95% CI, −1.27 to −0.82; working memory: Hedges g = −1.04; 95% CI, −1.35 to −0.73; attention: Hedges g = −1.03; 95% CI, −1.24 to −0.82; reasoning/problem solving: Hedges g = −0.90; 95% CI, −1.12 to −0.68; executive function: Hedges g = −0.88; 95% CI, −1.07 to −0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92).Conclusions and RelevanceResults of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.

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No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis

Cited by 4 publications

References 54 publications

Cognitive dysfunction in schizophrenia patients caused by down-regulation of γ-aminobutyric acid receptor subunits

Cognitive dysfunction in schizophrenia patients caused by down-regulation of γ-aminobutyric acid receptor subunits

Inhibitory Effects of Antipsychotic Chlorpromazine on the Survival, Reproduction and Population Growth Other Than Neurotransmitters of Zooplankton in Light of Global Warming

Cognitive Function and Variability in Antipsychotic Drug–Naive Patients With First-Episode Psychosis

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