Translational Psychiatry最新文献

{"title":"Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction.","authors":"Bettina Habelt, Dzmitry Afanasenkau, Cindy Schwarz, Kevin Domanegg, Martin Kuchar, Carsten Werner, Ivan R Minev, Rainer Spanagel, Marcus W Meinhardt, Nadine Bernhardt","doi":"10.1038/s41398-024-03189-z","DOIUrl":"10.1038/s41398-024-03189-z","url":null,"abstract":"<p><p>Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. To test this, we applied our recently developed biocompatible neuroprosthesis to measure prefrontal neural function in a well-established rat model of alcohol addiction and relapse. We monitored neural oscillations and event-related potentials in awake alcohol-dependent rats during abstinence and following treatment with psilocybin or LY379268, agonists of the serotonin 2A receptor (5-HT_2AR), and the metabotropic glutamate receptor 2 (mGluR2), that are known to reduce prefrontal dysfunction and relapse. Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. Psilocybin and LY379268 were able to restore these impairments. Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract. In summary, we provide prefrontal markers indicative of relapse and treatment response, especially for psychedelic drugs.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"486"},"PeriodicalIF":5.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid effects of valproic acid on the fetal brain transcriptome: implications for brain development and autism.","authors":"Susan G Dorsey, Evelina Mocci, Malcolm V Lane, Bruce K Krueger","doi":"10.1038/s41398-024-03179-1","DOIUrl":"10.1038/s41398-024-03179-1","url":null,"abstract":"<p><p>There is an increased incidence of autism among the children of women who take the anti-epileptic, mood-stabilizing drug, valproic acid (VPA) during pregnancy; moreover, exposure to VPA in utero causes autistic-like symptoms in rodents and non-human primates. Analysis of RNA-seq data obtained from E12.5 fetal mouse brains 3 hours after VPA administration to the pregnant dam revealed that VPA rapidly and significantly increased or decreased the expression of approximately 7,300 genes. No significant sex differences in VPA-induced gene expression were observed. Expression of 399 autism risk genes was significantly altered by VPA as was expression of 258 genes that have been reported to modulate fetal brain development but are not otherwise linked to autism. Expression of genes associated with intracellular signaling pathways, neurogenesis, and excitation-inhibition balance as well as synaptogenesis, neuronal fate determination, axon and dendritic development, neuroinflammation, circadian rhythms, and epigenetic modulation of gene expression was dysregulated by VPA. Notably, at least 40 genes that are known to regulate embryonic neurogenesis were dysregulated by VPA. The goal of this study was to identify mouse genes that are: (a) significantly up- or downregulated by VPA in the fetal brain and (b) associated with autism and/or known to play a role in embryonic neurodevelopmental processes, perturbation of which has the potential to alter brain connectivity and, consequently behavior, in the adult. The genes meeting these criteria provide potential targets for future hypothesis-driven studies to elucidate the proximal causes of errors in brain connectivity underlying neurodevelopmental disorders such as autism.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"482"},"PeriodicalIF":5.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of CACNB4 overexpression on dendritic spine density in both sexes and relevance to schizophrenia.","authors":"Emily M Parker, Nathan L Kindja, Rebecca A DeGiosio, Ryan B Salisbury, Josh M Krivinko, Claire E J Cheetham, Matthew L MacDonald, Weijia Fan, Bin Cheng, Robert A Sweet","doi":"10.1038/s41398-024-03181-7","DOIUrl":"10.1038/s41398-024-03181-7","url":null,"abstract":"<p><p>The voltage-gated calcium channel (VGCC) subunit complex is comprised of the α1 subunit, the ion-permeable channel, and three auxiliary subunits: β, α₂δ, and γ. β is the most extensively studied auxiliary subunit and is necessary for forward trafficking of the α1 subunit to the plasma membrane. VGCCs mediate voltage-dependent movement of calcium ions into neuronal cytoplasm, including at dendrites, where intracellular calcium spikes initiate signaling cascades that shape the structural plasticity of dendritic spines. Genetic studies strongly implicate calcium signaling dysfunction in the etiology of neurodevelopmental disorders including schizophrenia. Dendritic spine density is significantly decreased in schizophrenia in the primary auditory cortex where it is driven by the loss of small spines, and small spine loss associated with increased peptide levels of ALFDFLK found in the VGCC β subunit β4. Overexpressing the gene that encodes the voltage-gated calcium channel subunit β4, CACNB4, selectively reduced small spine density in vitro. In the current study we extended this observation in an intact mammalian system within a relevant neurodevelopmental context. We overexpressed CACNB4 in early development, assessed spine density and morphology in adult male and female mouse cortex, and characterized β1-4 protein levels and β4 protein-protein interactions. Overexpression reduced small spine density in females. This effect was not dependent on the estrous stage. Instead, it corresponded to sex differences in the murine β4 interactome. The VGCC subunit β1b was significantly enriched in the β4 interactome of male relative to female mice, and thus may have served to mitigate VGCC overexpression-mediated spine loss in male mice.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"484"},"PeriodicalIF":5.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology.","authors":"Kenneth Shinozuka, Katarina Jerotic, Pedro Mediano, Alex T Zhao, Katrin H Preller, Robin Carhart-Harris, Morten L Kringelbach","doi":"10.1038/s41398-024-03187-1","DOIUrl":"10.1038/s41398-024-03187-1","url":null,"abstract":"<p><p>Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three hierarchical levels of analysis: (1) subjective experience (phenomenology), (2) neuroimaging and (3) molecular pharmacology. Phenomenologically, medium and high doses of LSD yield significantly higher ratings of visionary restructuralisation than psilocybin on the 5-dimensional Altered States of Consciousness Scale. Our neuroimaging results reveal that, in general, psychedelics significantly strengthen between-network functional connectivity (FC) while significantly diminishing within-network FC. Pharmacologically, LSD induces significantly more inositol phosphate formation at the 5-HT_2A receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT_2A, 5-HT_2C, or D₂ receptors, relative to the 5-HT_1A receptor. Our meta-analyses link DMT, LSD, and psilocybin to specific neural fingerprints at each level of analysis. The results show a highly non-linear relationship between these fingerprints. Overall, our analysis highlighted the high heterogeneity and risk of bias in the literature. This suggests an urgent need for standardising experimental procedures and analysis techniques, as well as for more research on the emergence between different levels of psychedelic effects.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"485"},"PeriodicalIF":5.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study.","authors":"Marvin S Meiering, David Weigner, Matti Gärtner, Luisa Carstens, Christian Keicher, Rita Hertrampf, Christian F Beckmann, Maarten Mennes, Andreas Wunder, Anne Weigand, Simone Grimm","doi":"10.1038/s41398-024-03191-5","DOIUrl":"10.1038/s41398-024-03191-5","url":null,"abstract":"","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"483"},"PeriodicalIF":5.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized use of ketamine and esketamine for treatment-resistant depression.","authors":"Gustavo C Medeiros, Isabella Demo, Fernando S Goes, Carlos A Zarate, Todd D Gould","doi":"10.1038/s41398-024-03180-8","DOIUrl":"10.1038/s41398-024-03180-8","url":null,"abstract":"<p><p>A large and disproportionate portion of the burden associated with major depressive disorder (MDD) is due to treatment-resistant depression (TRD). Intravenous (R,S)-ketamine (ketamine) and intranasal (S)-ketamine (esketamine) are rapid-acting antidepressants that can effectively treat TRD. However, there is variability in response to ketamine/esketamine, and a personalized approach to their use will increase success rates in the treatment of TRD. There is a growing literature on the precision use of ketamine in TRD, and the body of evidence on esketamine is still relatively small. The identification of reliable predictors of response to ketamine/esketamine that are easily translatable to clinical practice is urgently needed. Potential clinical predictors of a robust response to ketamine include a pre-treatment positive family history of alcohol use disorder and a pre-treatment positive history of clinically significant childhood trauma. Pre-treatment versus post-treatment increases in gamma power in frontoparietal brain regions, observed in electroencephalogram (EEG) studies, is a promising brain-based biomarker of response to ketamine, given its time of onset and general applicability. Blood-based biomarkers have shown limited usefulness, with small-effect increases in brain-derived neurotrophic factor (BDNF) being the most consistent indicator of ketamine response. The severity of treatment-emergent dissociative symptoms is typically not associated with a response either to ketamine or esketamine. Future studies should ensure that biomarkers and clinical variables are obtained in a similar manner across studies to allow appropriate comparison across trials and to reduce the signal-to-noise ratio. Most predictors of response to ketamine/esketamine have modest effect sizes; therefore, the use of multivariate predictive models will be needed.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"481"},"PeriodicalIF":5.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant encoding of event saliency in the orbitofrontal cortex following loss of the psychiatric-associated circular RNA, circHomer1.","authors":"Amber J Zimmerman, Jason P Weick, Grigorios Papageorgiou, Nikolaos Mellios, Jonathan L Brigman","doi":"10.1038/s41398-024-03188-0","DOIUrl":"10.1038/s41398-024-03188-0","url":null,"abstract":"<p><p>CircHomer1 is an activity-dependent circular RNA (circRNA) isoform produced from back-splicing of the Homer1 transcript. Homer1 isoforms are well-known regulators of homeostatic synaptic plasticity through post-synaptic density scaffold regulation. Homer1 polymorphisms have been associated with psychiatric diseases including schizophrenia (SCZ) and bipolar disorder (BD). Postmortem tissue from patients with SCZ and BD displayed reduced circHomer1 levels within the orbitofrontal cortex (OFC), a region that tracks event saliency important for modulating behavioral flexibility. While dysregulation of circHomer1 expression has recently been identified across multiple psychiatric and neurodegenerative disorders and is associated with impaired behavioral flexibility in mice, it is unknown whether circHomer1 can induce electrophysiological signatures relevant to cognitive dysfunction in these disorders. To examine the role of circHomer1 in neuronal signaling, we bilaterally knocked down circHomer1 in the OFC of C57BL/6 J male mice and recorded neural activity from the OFC during a touchscreen reversal learning task then measured molecular changes of synaptic regulators following knockdown. Knockdown of circHomer1 within the OFC induced choice-dependent changes in multiunit firing rate and local field potential coordination and power to salient stimuli during reversal learning. Further, these electrophysiological changes were associated with transcriptional downregulation of glutamatergic signaling effectors and behavioral alterations leading to impaired cognitive flexibility. CircHomer1 is a stable biomolecule, whose knockdown in rodent OFC produces lasting electrophysiological and transcriptional changes important for efficient reversal learning. This is, to our knowledge, the first demonstration of a psychiatric-associated circRNA contributing to electrophysiological, transcriptional, and behavioral alterations relevant to psychiatric phenotypes.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"480"},"PeriodicalIF":5.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reverse phase protein array-based investigation of mitochondrial genes reveals alteration of glutaminolysis in the parahippocampal cortex of people who died by suicide.","authors":"Fanni Dóra, Tamara Hajdu, Éva Renner, Krisztina Paál, Alán Alpár, Miklós Palkovits, Christos Chinopoulos, Arpád Dobolyi","doi":"10.1038/s41398-024-03137-x","DOIUrl":"10.1038/s41398-024-03137-x","url":null,"abstract":"<p><p>A moderating hub between resting state networks (RSNs) and the medial temporal lobe (MTL) is the parahippocampal cortex (PHC). Abnormal activity has been reported in depressed patients and suicide attempters in this region. Alterations in neuronal mitochondrial function may contribute to depression and suicidal behavior. However, little is known about the underlying molecular level changes in relevant structures. Specifically, expressional changes related to suicide have not been reported in the PHC. In this study, we compared the protein expression levels of genes encoding tricarboxylic acid (TCA) cycle enzymes in the PHC of adult individuals who died by suicide by reverse phase protein array (RPPA), which was corroborated by qRT-PCR at the mRNA level. Postmortem human brain samples were collected from 12 control and 10 suicidal individuals. The entorhinal cortex, which is topographically anterior to the PHC in the parahippocampal gyrus, and some other cortical brain regions were utilized for comparison. The results of the RPPA analysis revealed that the protein levels of DLD, OGDH, SDHB, SUCLA2, and SUCLG2 subunits were significantly elevated in the PHC but not in other cortical brain regions. In accordance with these findings, the mRNA levels of the respective subunits were also increased in the PHC. The subunits with altered levels are implicated in enzyme complexes involved in the oxidative decarboxylation branch of glutamine catabolism. These data suggest a potential role of glutaminolysis in the pathophysiology of suicidal behavior in the PHC.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"479"},"PeriodicalIF":5.8,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased prefrontal glutamatergic function is associated with a reduced astrocyte-related gene expression in treatment-resistant depression.","authors":"Masataka Wada, Shinichiro Nakajima, Shiori Honda, Mayuko Takano, Keita Taniguchi, Saki Homma, Risako Ueda, Yui Tobari, Yu Mimura, Shinya Fujii, Masaru Mimura, Yoshihiro Noda","doi":"10.1038/s41398-024-03186-2","DOIUrl":"10.1038/s41398-024-03186-2","url":null,"abstract":"<p><p>Glutamatergic dysfunction is involved in the pathophysiology of treatment-resistant depression (TRD). However, few physiological studies have evaluated its pathophysiology in vivo in individuals with TRD. Transcranial magnetic stimulation-electroencephalography (TMS-EEG) techniques can assess intracortical facilitation (ICF), which reflects glutamatergic neurophysiological function in specific cortical regions. The objectives of this study were (1) to compare glutamatergic receptor-mediated function as indexed with ICF TMS-EEG in the dorsolateral prefrontal cortex (DLPFC) between participants with TRD and healthy controls (HCs) and (2) to explore the relationships between cell-specific gene expression levels and the group difference in glutamatergic neural propagation using virtual histology approach. Sixty participants with TRD and thirty HCs were examined with ICF TMS-EEG measure (80 single-pulse TMS and paired-pulse ICF) in the left DLPFC. Both sensor and source-level ICF measures were computed to compare them between the TRD and HC groups. Furthermore, we conducted spatial correlation analyses interregionally between ICF glutamatergic activity and cell-specific gene expression levels employing the Allen Human Brain Atlas dataset. DLPFC-ICF at the sensor level was not significantly different between the two groups, whereas DLPFC-ICF at the source level was reduced in the TRD group compared with the HC group (p = 0.026). Moreover, the reduced ICF signal propagation of TRD correlated with astrocyte-specific gene expression level (p < 0.0001). The glutamatergic neural activities indexed by ICF in the left DLPFC were decreased in participants with TRD. Additionally, a relative reduction in glutamatergic signal propagation originating from the DLPFC in TRD may be associated with astrocytic abnormality.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"478"},"PeriodicalIF":5.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naltrexone blocks alcohol-induced effects on kappa-opioid receptors in the plasma membrane.","authors":"Sho Oasa, Erdinc Sezgin, Yuelong Ma, David A Horne, Mihajlo D Radmilović, Tijana Jovanović-Talisman, Rémi Martin-Fardon, Vladana Vukojević, Lars Terenius","doi":"10.1038/s41398-024-03172-8","DOIUrl":"10.1038/s41398-024-03172-8","url":null,"abstract":"<p><p>Naltrexone (NTX), a homolog of the opiate antidote naloxone, is an orally active long-acting general opioid receptor antagonist used in the treatment of opiate dependence. NTX is also found to relieve craving for alcohol and is one of few FDA-approved medications for treatment of alcohol use disorder (AUD). While it was early on established that NTX acts by blocking the binding of endogenous opioid peptide ligands released by alcohol, experimental evidence emerged that could not be fully accounted for by this explanation alone, suggesting that NTX may have additional modes of action. Mu- and kappa-opioid receptors (MOP and KOP, respectively) are structurally related G-protein-coupled receptors (GPCRs), but they are anatomically differently distributed and functionally distinct, often mediating opposite responses, with MOP typically promoting euphoria and reward, while KOP is associated with dysphoria and aversive states. While the actions of NTX on MOP are extensively characterized, the interactions with KOP are not. Here, we used sensitive fluorescence-based methods with single-molecule sensitivity to study in live cells the influence of alcohol (ethanol, EtOH) on KOP and the interaction between KOP and NTX. Our data show that alcohol, at relevant concentrations (10-40 mM), alters KOP interactions with the lipid environment in the plasma membrane. The counteracting effects of NTX are exerted by both its canonical action on KOP and its hitherto unrevealed effects on the lateral dynamics and organization of lipids in the plasma membrane. The KOP-specific antagonist LY2444296, in clinical trial for major depressive disorder (MDD), blocks KOP but does not show the full action profile of NTX. The therapeutic effect of NTX treatment in AUD may in part be due to direct actions on KOP and in part due to its effect on the surrounding lipid environment.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"477"},"PeriodicalIF":5.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}