Dataset Information

Brain serotonin 4 receptor binding is inversely associated with verbal memory recall.

ABSTRACT:

Background

We have previously identified an inverse relationship between cerebral serotonin 4 receptor (5-HT ₄R) binding and nonaffective episodic memory in healthy individuals. Here, we investigate in a novel sample if the association is related to affective components of memory, by examining the association between cerebral 5-HT ₄R binding and affective verbal memory recall.

Methods

Twenty-four healthy volunteers were scanned with the 5-HT ₄R radioligand [¹¹C]SB207145 and positron emission tomography, and were tested with the Verbal Affective Memory Test-24. The association between 5-HT ₄R binding and affective verbal memory was evaluated using a linear latent variable structural equation model.

Results

We observed a significant inverse association across all regions between 5-HT ₄R binding and affective verbal memory performances for positive (p = 5.5 × 10^-4) and neutral (p = .004) word recall, and an inverse but nonsignificant association for negative (p = .07) word recall. Differences in the associations with 5-HT ₄R binding between word categories (i.e., positive, negative, and neutral) did not reach statistical significance.

Conclusion

Our findings replicate our previous observation of a negative association between 5-HT ₄R binding and memory performance in an independent cohort and provide novel evidence linking 5-HT ₄R binding, as a biomarker for synaptic 5-HT levels, to the mnestic processing of positive and neutral word stimuli in healthy humans.

SUBMITTER: Stenbæk DS

PROVIDER: S-EPMC5390847 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

Brain serotonin 4 receptor binding is inversely associated with verbal memory recall.

Stenbæk Dea S DS Fisher Patrick M PM Ozenne Brice B Andersen Emil E Hjordt Liv V LV McMahon Brenda B Hasselbalch Steen G SG Frokjaer Vibe G VG Knudsen Gitte M GM

Brain and behavior 20170317 4

<h4>Background</h4>We have previously identified an inverse relationship between cerebral serotonin 4 receptor (5-HT <sub>4</sub>R) binding and nonaffective episodic memory in healthy individuals. Here, we investigate in a novel sample if the association is related to affective components of memory, by examining the association between cerebral 5-HT <sub>4</sub>R binding and affective verbal memory recall.<h4>Methods</h4>Twenty-four healthy volunteers were scanned with the 5-HT <sub>4</sub>R rad ...[more]

PMID: 28413715

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Project description:ImportanceThe cerebral serotonin 4 (5-HT4) receptor is a promising novel target for treatment of major depressive disorder (MDD), and pharmacological stimulation of the 5-HT4 receptor has been associated with improved learning and memory in healthy individuals.ObjectiveTo map the neurobiological signatures of patients with untreated MDD compared with healthy controls and to examine the association between cerebral 5-HT4 receptor binding and cognitive functions in the depressed state.Design, setting, and participantsThis case-control study used baseline data from the NeuroPharm clinical depression trial in Denmark. Adult participants included antidepressant-free outpatients with a current moderate to severe depressive episode and healthy controls. All participants completed positron emission tomography (PET) scanning with [11C]SB207145 for quantification of brain 5-HT4 receptor binding, but only the patients underwent cognitive testing. Data analyses were performed from January 21, 2020, to April 22, 2022.Main outcomes and measuresThe main study outcome was the group difference in cerebral 5-HT4 receptor binding between patients with MDD and healthy controls. In addition, the association between 5-HT4 receptor binding and verbal memory performance in the patient group was tested. Other cognitive domains (working memory, reaction time, emotion recognition bias, and negative social emotions) were assessed as secondary outcomes.ResultsA total of 90 patients with untreated MDD (mean [SD] age, 27.1 [8.2] years; 64 women [71.1%]) and 91 healthy controls (mean [SD] age, 27.1 [8.0] years; 55 women [60.4%]) were included in the analysis. Patients with current MDD had significantly lower cerebral 5-HT4 receptor binding than healthy controls (-7.0%; 95% CI, -11.2 to -2.7; P = .002). In patients with MDD, there was a correlation between cerebral 5-HT4 receptor binding and verbal memory (r = 0.29; P = .02).Conclusions and relevanceResults of this study show that cerebral 5-HT4 receptor binding was lower in patients with MDD than in healthy controls and that the memory dysfunction in patients with MDD was associated with lower cerebral 5-HT4 receptor binding. The cerebral 5-HT4 receptor is a promising treatment target for memory dysfunction in patients with MDD.

Project description:Background: Patients with postacute anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis are often left with permanent memory impairments. Given that NMDA receptors are essential to memory encoding, and encoding processes have been suggested to contribute to the success of memory retrieval, we investigate whether postacute anti-NMDA receptor encephalitis leads to abnormal brain activation during verbal memory encoding and its potential effects on subsequent memory retrieval performance. Methods: To address this issue, this study recruited 21 adult patients with anti-NMDA receptor encephalitis past the acute stage and 22 healthy controls (HCs). Functional magnetic resonance imaging (fMRI) data were collected when they completed an episodic memory task. Results: At the neural level, the patients showed higher brain activation than the HCs in the bilateral hippocampus/parahippocampus (HG/PHG), right superior temporal gyrus (STG), and right thalamus during memory encoding. At the behavioral level, the patients showed worse memory retrieval performance than the HCs. Importantly, greater brain activation in the left HG/PHG during memory encoding was significantly associated with worse memory retrieval performance among the patients. Conclusion: Our findings indicate that postacute anti-NMDA receptor encephalitis is likely related to altered brain activation during memory encoding. Particularly, less memory retrieval performance often observed in patients with postacute anti-NMDA receptor encephalitis may result from abnormal activation in HG during encoding. These observations may enhance our understanding of NMDA receptor dysfunction in the human brain. Impact statement Patients with anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis are often left with permanent memory impairments. In this study, brain activation during verbal memory encoding and its potential effects on subsequent memory retrieval performance are addressed using 21 adult patients with postacute anti-NMDA receptor encephalitis and 22 healthy controls. Greater brain activation in the left hippocampus/parahippocampus during memory encoding was significantly associated with worse memory retrieval performance among the patients. These observations enhance our understanding of NMDA receptor dysfunction in the human brain.

Project description:ObjectiveMemory dysfunction is prevalent in many neurological disorders and can have a significant negative impact on quality of life. The genetic contributions to memory impairment in epilepsy, particularly temporal lobe epilepsy (TLE), remain poorly understood. Here, we compare the brain transcriptome between TLE patients with and without verbal memory impairments to identify genes and signaling networks important for episodic memory.MethodsBrain tissues were resected from 23 adults who underwent dominant temporal lobectomy for treatment of pharmacoresistant epilepsy. To control for potential effects of APOE on memory, only those homozygous for the APOE ε3 allele were included. A battery of memory tests was performed, and patients were stratified into two groups based on preoperative memory performance. The groups were well matched on demographic and disease-related variables. Total RNA-Seq and small RNA-Seq were performed on RNA extracted from the brain tissues. Pathway and integrative analyses were subsequently performed.ResultsWe identified 1092 differentially expressed transcripts (DETs), with the majority (71%) being underexpressed in brain tissues from patients with impaired memory compared to those from patients with intact memory. Enrichment analysis revealed overrepresentation of genes in pathways pertaining to brain-related neurological dysfunction, including a subset associated with neurodegenerative diseases, memory, and cognition (APP, MAPT, PINK1). Despite including patients with identical APOE genotypes, we identify APOE as a differentially expressed gene associated with memory status. Small RNA-Seq identified four differentially expressed microRNAs (miRNAs) that were predicted to target a subset (22%) of all DETs. Integrative analysis showed that these miRNA-predicted DET targets impact brain-related pathways and biological processes also pertinent to memory and cognition.SignificanceTLE-associated memory status may be influenced by differences in gene expression profiles within the temporal lobe. Upstream processes influencing differential expression signatures, such as miRNAs, could serve as biomarkers and potential treatment targets for memory impairment in TLE.

Dataset Information

Brain serotonin 4 receptor binding is inversely associated with verbal memory recall.

Background

Methods

Results

Conclusion

Publications

Brain serotonin 4 receptor binding is inversely associated with verbal memory recall.

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