Biology subjects

Jeon, P.

Publications and source records attributed to Jeon, P..

5 recordsLinked to original sources

bioRxiv2021

Myelin imaging of the basal forebrain in first-episode psychosis

Cholinergic dysfunction has been implicated in the pathophysiology of psychiatric disorders such as schizophrenia, depression, and bipolar disorder. The basal forebrain (BF) cholinergic nuclei, defined as cholinergic cell groups Ch1-3 and Ch4 (Nucleus Basalis of Meynert; NBM), provide extensive cholinergic projections to the rest of the brain. Here, we examined microstructural neuroimaging measures of the cholinergic nuclei in patients with untreated psychosis ([~] 31 weeks of psychosis, <2 defined daily dose of antipsychotics) and used Magnetic Resonance Spectroscopy (1H-MRS) and transcriptomic data to support our findings. We used a cytoarchitectonic atlas of the BF to map the nuclei and obtained measures of myelin (quantitative T1, or qT1 as myelin surrogate) and microstructure (axial diffusion; AxD). In a clinical sample (n=85; 29 healthy controls, 56 first-episode psychosis), we found significant correlations between qT1 and 1H-MRS-based dorsal anterior cingulate choline in healthy controls, while this relationship was disrupted in FEP. Case-control differences in qT1 and AxD were observed in the Ch1-3, with increased qT1 (reflecting reduced myelin content) and AxD (reflecting reduced axonal integrity). We found clinical correlates between left NBM qT1 with manic symptom severity, and AxD with negative symptom burden in FEP. Intracortical and subcortical myelin maps were derived and correlated with BF myelin. BF-cortical and BF-subcortical myelin correlations demonstrate known projection patterns from the BF. Using data from the Allen Human Brain Atlas, cholinergic nuclei showed significant enrichment for schizophrenia and depression-related genes. Cell-type specific enrichment indicated enrichment for cholinergic neuron markers as expected. Further relating the neuroimaging correlations to transcriptomics demonstrated links with cholinergic receptor genes and cell type markers of oligodendrocytes and cholinergic neurons, providing biological validity to the measures. These results provide genetic, neuroimaging, and clinical evidence for cholinergic dysfunction in schizophrenia and other psychiatric disorders such as depression.

neuroscience↗

bioRxiv2021

The in vitro and in vivo potency of CT-P59 against Delta and its associated variants of SARS-CoV-2

The Delta variant originally from India is rapidly spreading across the world and causes to resurge infections of SARS-CoV-2. We previously reported that CT-P59 presented its in vivo potency against Beta and Gamma variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on the Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal study. CT-P59 showed reduced antiviral activity but enabled neutralization against Delta, Epsilon, and Kappa variants in cells. In line with in vitro results, the mouse challenge experiment with the Delta variant substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against the Delta variant infection, hinting that CT-P59 has therapeutic potency for patients infected with Delta and its associated variants. HighlightsO_LICT-P59 exerts the antiviral effect on authentic Delta, Epsilon and Kappa variants in cell-based experiments. C_LIO_LICT-P59 showed neutralizing potency against variants including Delta, Epsilon, Kappa, L452R, T478K and P681H pseudovirus variants. C_LIO_LIThe administration of clinically relevant dose of CT-P59 showed in vivo C_LIO_LIprotection against Delta variants in animal challenge experiment. C_LI

microbiology↗

bioRxiv2019

Ultra-high field imaging of hippocampal neuroanatomy in first episode psychosis demonstrates receptor-specific morphometric patterning

ObjectiveThe hippocampus is considered a putative marker in schizophrenia with early volume deficits of select subfields. Certain subregions are thought to be more vulnerable due to a glutamate-driven mechanism of excitotoxicity, hypermetabolism, and then degeneration. Here, we explored whether hippocampal anomalies in first-episode psychosis (FEP) correlate with glutamate receptor density via a serotonin receptor proxy by leveraging structural neuroimaging, spectroscopy (MRS), and gene expression.\n\nMethodsHigh field 7T brain MR images were collected from 27 control, 41 FEP participants, along with 1H-MRS measures of glutamate. Automated methods were used to delineate the hippocampus and atlases of the serotonin receptor system were used to map receptor density across the hippocampus and subfields. We used gene expression data from the Allen Human Brain Atlas to test for correlations between serotonin and glutamate receptor genes.\n\nResultsWe found reduced hippocampal volumes in FEP, replicating previous findings. Amongst the subfields, CA4-dentate gyrus showed greatest reductions. Gene expression analysis indicated 5-HTR1A and 5-HTR4 receptor subtypes as predictors of AMPA and NMDA receptor expression, respectively. Volumetric differences in the subfields correlated most strongly with 5-HT1A (R=0.64, p=4.09E-03) and 5-HT4 (R=0.54, p=0.02) densities as expected, and replicated using previously published data from two FEP studies. Measures of individual structure-receptor alignment were derived through normative modeling of hippocampal shape and correlations to receptor distributions, termed Receptor-Specific Morphometric Signatures (RSMS). Right-sided 5-HT4 RSMS was correlated with glutamate (R=0.357, p=0.048).\n\nConclusionsWe demonstrate glutamate-driven hippocampal remodeling in FEP through a receptor-density gated mechanism, thus providing a mechanistic explanation of how redox dysregulation affects brain structure and symptomatic heterogeneity in schizophrenia.

neuroscience↗

bioRxiv2019

Early Treatment Response in First Episode Psychosis: A 7-Tesla Magnetic Resonance Spectroscopic Study of Glutathione and Glutamate

Early response to antipsychotic medications is one of the most important determinants of later symptomatic and functional outcomes in psychosis. Glutathione and glutamate have emerged as promising therapeutic targets for patients demonstrating inadequate response to dopamine-blocking antipsychotics. Nevertheless, the role of these neurochemicals in the mechanism of early antipsychotic response remains poorly understood. Using a longitudinal design and ultra-high field 7-Tesla magnetic resonance spectroscopy (MRS) protocol in 53 subjects, we report the association between dorsal anterior cingulate cortex glutamate and glutathione, with time to treatment response in drug-naive (34.6% of the sample) or minimally medicated first episode patients with non-affective psychosis. Time to response was defined as the number of weeks required to reach a 50% reduction in the PANSS-8 scores. Higher glutathione was associated with shorter time to response (F=4.86, P= .017), while higher glutamate was associated with more severe functional impairment (F=5.33, P= .008). There were no significant differences between patients and controls on measures of glutamate or glutathione. For the first time, we have demonstrated an association between higher glutathione and favourable prognosis in FEP. We propose that interventions that increase brain glutathione levels may improve outcomes of early intervention in psychosis.

neuroscience↗

bioRxiv2019

Glutamate and Dysconnection in the Salience Network: Neurochemical, Effective-connectivity, and Computational Evidence in Schizophrenia

In the dysconnection hypothesis, psychosis is caused by NMDA hypofunction resulting in aberrant network connectivity. Combining a cognitive-control task, functional magnetic resonance spectroscopy, and functional magnetic resonance imaging, we tested this hypothesis in the salience network of 20 first-episode psychosis (FEP) and 20 healthy control (HC) subjects. Across groups, glutamate concentration in the dorsal anterior cingulate cortex (dACC) was associated with higher and lower inhibitory connectivity in the dACC and in the anterior insula (AI) respectively. Crucially, glutamate concentration correlated negatively with the inhibitory influence on the excitatory neuronal population in the dACC of FEP subjects. Furthermore, aberrant computational parameters of the cognitive-control task performance were associated with aberrant inhibitory connections. Finally, the strength of connections from the dACC to the AI correlated negatively with severity of social withdrawal. These findings support a link between glutamate-mediated cortical disinhibition, deficits in effective connectivity, and computational performance in psychosis.

neuroscience↗