International Journal of Neuropsychopharmacology最新文献

{"title":"Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers.","authors":"Priyanka Singh,&nbsp;Ankit Srivastava,&nbsp;Debleena Guin,&nbsp;Sarita Thakran,&nbsp;Jyoti Yadav,&nbsp;Puneet Chandna,&nbsp;Mamta Sood,&nbsp;Rakesh Kumar Chadda,&nbsp;Ritushree Kukreti","doi":"10.1093/ijnp/pyad001","DOIUrl":"10.1093/ijnp/pyad001","url":null,"abstract":"<p><strong>Background: </strong>The clinical heterogeneity in major depressive disorder (MDD), variable treatment response, and conflicting findings limit the ability of genomics toward the discovery of evidence-based diagnosis and treatment regimen. This study attempts to curate all genetic association findings to evaluate potential variants for clinical translation.</p><p><strong>Methods: </strong>We systematically reviewed all candidates and genome-wide association studies for both MDD susceptibility and antidepressant response, independently, using MEDLINE, particularly to identify replicated findings. These variants were evaluated for functional consequences using different in silico tools and further estimated their diagnostic predictability by calculating positive predictive values.</p><p><strong>Results: </strong>A total of 217 significantly associated studies comprising 1200 variants across 545 genes and 128 studies including 921 variants across 412 genes were included with MDD susceptibility and antidepressant response, respectively. Although the majority of associations were confirmed by a single study, we identified 31 and 18 replicated variants (in at least 2 studies) for MDD and antidepressant response. Functional annotation of these 31 variants predicted 20% coding variants as deleterious/damaging and 80.6% variants with regulatory effect. Similarly, the response-related 18 variants revealed 25% coding variant as damaging and 88.2% with substantial regulatory potential. Finally, we could calculate the diagnostic predictability of 19 and 5 variants whose positive predictive values ranges from 0.49 to 0.66 for MDD and 0.36 to 0.66 for response.</p><p><strong>Conclusions: </strong>The replicated variants presented in our data are promising for disease diagnosis and improved response outcomes. Although these quantitative assessment measures are solely directive of available observational evidence, robust homogenous validation studies are required to strengthen these variants for molecular diagnostic application.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"692-738"},"PeriodicalIF":4.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10599097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Neurons in Nucleus Tractus Solitarius Are Involved in Decrease of Heart Rate Variability and Development of Depression-Like Behaviors in Temporal Lobe Epilepsy.","authors":"Guliqiemu Aimaier,&nbsp;Kun Qian,&nbsp;Huateng Cao,&nbsp;Weifeng Peng,&nbsp;Zhe Zhang,&nbsp;Jing Ding,&nbsp;Xin Wang","doi":"10.1093/ijnp/pyad033","DOIUrl":"10.1093/ijnp/pyad033","url":null,"abstract":"<p><strong>Background: </strong>Diminished heart rate variability (HRV) has been observed in epilepsy, especially in epilepsy with depressive disorders. However, the underlying mechanism remains elusive.</p><p><strong>Methods: </strong>We studied HRV, spontaneous recurrent seizures, and depression-like behaviors in different phases of pilocarpine-induced temporal lobe epilepsy (TLE) in mice. Single-cell RNA sequencing analysis was used to identify various nerve cell subsets in TLE mice with and without depression. Differentially expressed gene (DEG) analysis was performed in epilepsy, depression, and HRV central control-related brain areas.</p><p><strong>Results: </strong>We found decreased HRV parameters in TLE mice, and alterations were positively correlated with the severity of depression-like behaviors. The severity of depression-like behaviors was correlated with the frequency of spontaneous recurrent seizure. Characteristic expression of mitochondria-related genes was significantly elevated in mice with depression in glial cells, and the enrichment analysis of those DEGs showed an enriched GABAergic synapse pathway in the HRV central control-related brain area. Furthermore, inhibitory neurons in the nucleus tractus solitarius, which is an HRV central control-related brain area, were specifically expressed in TLE mice combined with depression compared with those in mice without depression. A significantly enriched long-term depression pathway in DEGs from inhibitory neurons was found.</p><p><strong>Conclusions: </strong>Our study reported correlations between HRV and epilepsy-depression comorbidity in different phases of TLE. More importantly, we found that HRV central control-related inhibitory neurons are involved in the development of depression in TLE, providing new insights into epilepsy comorbid with depression.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"669-679"},"PeriodicalIF":4.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ba/5b/pyad033.PMC10586034.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cucurbitacin B Exerts Significant Antidepressant-Like Effects in a Chronic Unpredictable Mild Stress Model of Depression: Involvement of the Hippocampal BDNF-TrkB System.","authors":"Jian-Bin Ge, Bo Jiang, Tian-Shun Shi, Wei-Yu Li, Wei-Jia Chen, Bao-Lun Zhu, Zheng-Hong Qin","doi":"10.1093/ijnp/pyad052","DOIUrl":"10.1093/ijnp/pyad052","url":null,"abstract":"<p><strong>Background: </strong>Although depression has been a serious neuropsychiatric disorder worldwide, current antidepressants used in clinical practice have various weaknesses, including delayed onset and low rates of efficacy. Recently, the development of new antidepressants from natural herbal medicine has become one of the important research hotspots. Cucurbitacin B is a natural compound widely distributed in the Cucurbitaceae and Cruciferae families and has many pharmacological activities. The present study aimed to investigate whether cucurbitacin B possess antidepressant-like effects in mice.</p><p><strong>Methods: </strong>The antidepressant-like effects of cucurbitacin B on mice behaviors were explored using the forced swim test, tail suspension test, open field test, sucrose preference test, and a chronic unpredictable mild stress model of depression together. Then, western blotting and immunofluorescence were used to examine the effects of cucurbitacin B on the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling cascade and neurogenesis in the hippocampus of mice. Furthermore, BDNF-short hairpin RNA, K252a, and p-chlorophenylalanine methyl ester were adopted together to determine the antidepressant mechanism of cucurbitacin B.</p><p><strong>Results: </strong>It was found that administration of cucurbitacin B indeed produced notable antidepressant-like effects in mice, which were accompanied with significant promotion in both the hippocampal BDNF-TrkB pathway and neurogenesis. The antidepressant mechanism of cucurbitacin B involves the hippocampal BDNF-TrkB system but not the serotonin system.</p><p><strong>Conclusions: </strong>Cucurbitacin B has the potential to be a novel antidepressant candidate.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"680-691"},"PeriodicalIF":4.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10388710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of mTORC1 Signaling Cascade in Hippocampus and Medial Prefrontal Cortex Is Required for Antidepressant Actions of Vortioxetine in Mice.","authors":"Wei-Yu Li,&nbsp;Tian-Shun Shi,&nbsp;Jie Huang,&nbsp;Yan-Mei Chen,&nbsp;Wei Guan,&nbsp;Bo Jiang,&nbsp;Cheng-Niu Wang","doi":"10.1093/ijnp/pyad017","DOIUrl":"10.1093/ijnp/pyad017","url":null,"abstract":"<p><strong>Background: </strong>Although thought of as a multimodal-acting antidepressant targeting the serotonin system, more molecules are being shown to participate in the antidepressant mechanism of vortioxetine. A previous report has shown that vortioxetine administration enhanced the expression of rapamycin complex 1 (mTORC1) in neurons. It has been well demonstrated that mTORC1 participates in not only the pathogenesis of depression but also the pharmacological mechanisms of many antidepressants. Therefore, we speculate that the antidepressant mechanism of vortioxetine may require mTORC1.</p><p><strong>Methods: </strong>Two mouse models of depression (chronic social defeat stress and chronic unpredictable mild stress) and western blotting were first used together to examine whether vortioxetine administration produced reversal effects against the chronic stress-induced downregulation in the whole mTORC1 signaling cascade in both the hippocampus and medial prefrontal cortex (mPFC). Then, LY294002, U0126, and rapamycin were used together to explore whether the antidepressant effects of vortioxetine in mouse models of depression were attenuated by pharmacological blockade of the mTORC1 system. Furthermore, lentiviral-mTORC1-short hairpin RNA-enhanced green fluorescence protein (LV-mTORC1-shRNA-EGFP) was adopted to examine if genetic blockade of mTORC1 also abolished the antidepressant actions of vortioxetine in mice.</p><p><strong>Results: </strong>Vortioxetine administration produced significant reversal effects against the chronic stress-induced downregulation in the whole mTORC1 signaling cascade in both the hippocampus and mPFC. Both pharmacological and genetic blockade of the mTORC1 system notably attenuated the antidepressant effects of vortioxetine in mice.</p><p><strong>Conclusions: </strong>Activation of the mTORC1 system in the hippocampus and mPFC is required for the antidepressant actions of vortioxetine in mice.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"655-668"},"PeriodicalIF":4.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/68/pyad017.PMC10586031.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9257699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Comparison of Ulotaront (SEP-363856) and Ralmitaront (RO6889450): Two TAAR1 Agonist Candidate Antipsychotics.","authors":"Richard Ågren,&nbsp;Nibal Betari,&nbsp;Marcus Saarinen,&nbsp;Hugo Zeberg,&nbsp;Per Svenningsson,&nbsp;Kristoffer Sahlholm","doi":"10.1093/ijnp/pyad049","DOIUrl":"10.1093/ijnp/pyad049","url":null,"abstract":"<p><strong>Background: </strong>Trace amine-associated receptor-1 (TAAR1) agonists have been proposed as potential antipsychotics, with ulotaront and ralmitaront having reached clinical trials. While ulotaront demonstrated efficacy in a recent Phase II trial, a corresponding study studies of ralmitaront failed to show efficacy as a monotherapy or as an adjunct to atypical antipsychotics. In addition to TAAR1 agonism, ulotaront is a partial agonist at the serotonin 1A receptor (5-HT1AR). However, little is known about ralmitaront.</p><p><strong>Methods: </strong>We compared ulotaront and ralmitaront at TAAR1, 5-HT1AR, and dopamine D2 using luciferase complementation-based G protein recruitment, cAMP accumulation, and G protein-coupled inward rectifier potassium channel activation assays.</p><p><strong>Results: </strong>Ralmitaront showed lower efficacy at TAAR1 in G protein recruitment, cAMP accumulation, and GIRK activation assays. Moreover, ralmitaront lacked detectable activity at 5-HT1AR and dopamine D2.</p><p><strong>Conclusions: </strong>Compared with ulotaront, ralmitaront shows lower efficacy and slower kinetics at TAAR1 and lacks efficacy at 5-HT1AR. These data may be relevant to understanding differences in clinical profiles of these 2 compounds.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"599-606"},"PeriodicalIF":4.8,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/29/3a/pyad049.PMC10519813.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9954363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rolipram Ameliorates Memory Deficits and Depression-Like Behavior in APP/PS1/tau Triple Transgenic Mice: Involvement of Neuroinflammation and Apoptosis via cAMP Signaling.","authors":"Yi-Fan Cong,&nbsp;Fu-Wang Liu,&nbsp;Li Xu,&nbsp;Shuang-Shuang Song,&nbsp;Xu-Ri Shen,&nbsp;Dong Liu,&nbsp;Xue-Qin Hou,&nbsp;Han-Ting Zhang","doi":"10.1093/ijnp/pyad042","DOIUrl":"10.1093/ijnp/pyad042","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer disease (AD) and depression often cooccur, and inhibition of phosphodiesterase-4 (PDE4) has been shown to ameliorate neurodegenerative illness. Therefore, we explored whether PDE4 inhibitor rolipram might also improve the symptoms of comorbid AD and depression.</p><p><strong>Methods: </strong>APP/PS1/tau mice (10 months old) were treated with or without daily i.p. injections of rolipram for 10 days. The animal groups were compared in behavioral tests related to learning, memory, anxiety, and depression. Neurochemical measures were conducted to explore the underlying mechanism of rolipram.</p><p><strong>Results: </strong>Rolipram attenuated cognitive decline as well as anxiety- and depression-like behaviors. These benefits were attributed at least partly to the downregulation of amyloid-β, Amyloid precursor protein (APP), and Presenilin 1 (PS1); lower tau phosphorylation; greater neuronal survival; and normalized glial cell function following rolipram treatment. In addition, rolipram upregulated B-cell lymphoma-2 (Bcl-2) and downregulated Bcl-2-associated X protein (Bax) to reduce apoptosis; it also downregulated interleukin-1β, interleukin-6, and tumor necrosis factor-α to restrain neuroinflammation. Furthermore, rolipram increased cAMP, PKA, 26S proteasome, EPAC2, and phosphorylation of ERK1/2 while decreasing EPAC1.</p><p><strong>Conclusions: </strong>Rolipram may mitigate cognitive deficits and depression-like behavior by reducing amyloid-β pathology, tau phosphorylation, neuroinflammation, and apoptosis. These effects may be mediated by stimulating cAMP/PKA/26S and cAMP/exchange protein directly activated by cAMP (EPAC)/ERK signaling pathways. This study suggests that PDE4 inhibitor rolipram can be an effective target for treatment of comorbid AD and depression.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"585-598"},"PeriodicalIF":4.8,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519811/pdf/pyad042.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9861430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction of: Regional Differences in Brain-Derived Neurotrophic Factor Levels and Dendritic Spine Density Confer Resilience to Inescapable Stress.","authors":"","doi":"10.1093/ijnp/pyad036","DOIUrl":"10.1093/ijnp/pyad036","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"654"},"PeriodicalIF":4.8,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519807/pdf/pyad036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10217849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress Hormone Dynamics Are Coupled to Brain Serotonin 4 Receptor Availability in Unmedicated Patients With Major Depressive Disorder: A NeuroPharm Study.","authors":"Gunild M Vulpius,&nbsp;Kristin Köhler-Forsberg,&nbsp;Brice Ozenne,&nbsp;Søren V Larsen,&nbsp;Arafat Nasser,&nbsp;Claus Svarer,&nbsp;Nic Gillings,&nbsp;Sune H Keller,&nbsp;Martin B Jørgensen,&nbsp;Gitte M Knudsen,&nbsp;Vibe G Frokjaer","doi":"10.1093/ijnp/pyad041","DOIUrl":"10.1093/ijnp/pyad041","url":null,"abstract":"<p><strong>Background: </strong>A prominent finding in major depressive disorder (MDD) is distorted stress hormone dynamics, which is regulated by serotonergic brain signaling. An interesting feature of the cerebral serotonin system is the serotonin 4 receptor (5-HT4R), which is lower in depressed relative to healthy individuals and also has been highlighted as a promising novel antidepressant target. Here, we test the novel hypothesis that brain 5-HT4R availability in untreated patients with MDD is correlated with cortisol dynamics, indexed by the cortisol awakening response (CAR). Further, we evaluate if CAR changes with antidepressant treatment, including a selective serotonin reuptake inhibitor, and if pretreatment CAR can predict treatment outcome.</p><p><strong>Methods: </strong>Sixty-six patients (76% women) with a moderate to severe depressive episode underwent positron emission tomography imaging with [11C]SB207145 for quantification of brain 5-HT4R binding using BPND as outcome. Serial home sampling of saliva in the first hour from awakening was performed to assess CAR before and after 8 weeks of antidepressant treatment. Treatment outcome was measured by change in Hamilton Depression Rating Scale 6 items.</p><p><strong>Results: </strong>In the unmedicated depressed state, prefrontal and anterior cingulate cortices 5-HT4R binding was positively associated with CAR. CAR remained unaltered after 8 weeks of antidepressant treatment, and pretreatment CAR did not significantly predict treatment outcome.</p><p><strong>Conclusions: </strong>Our findings highlight a link between serotonergic disturbances in MDD and cortisol dynamics, which likely is involved in disease and treatment mechanisms. Further, our data support 5-HT4R agonism as a promising precision target in patients with MDD and disturbed stress hormone dynamics.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"639-648"},"PeriodicalIF":4.8,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10297706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aromatase Inhibition and Electroconvulsive Seizures in Adolescent Rats: Antidepressant and Long-Term Cognitive Sex Differences.","authors":"Sandra Ledesma-Corvi,&nbsp;M Julia García-Fuster","doi":"10.1093/ijnp/pyad047","DOIUrl":"10.1093/ijnp/pyad047","url":null,"abstract":"<p><strong>Background: </strong>We recently showed sex differences in the antidepressant-like potential of electroconvulsive seizures (ECS) in adolescent rats; whereas it worked for male rats, it was inefficacious in females. Because sex steroids might be important modulators of these sex disparities, we evaluated the role of estrogens in the differential response induced by adolescent ECS. Moreover, given the literature suggesting certain cognitive sequelae from ECS exposure, we aimed at evaluating its long-term safety profile in adulthood.</p><p><strong>Methods: </strong>Adolescent Sprague-Dawley rats were pretreated with letrozole (1 mg/kg/day) or vehicle (1 mL/kg/day) for 8 days (i.p.) and treated during the last 5 days (3 hours later) with ECS (95 mA, 0.6 s, 100 Hz) or SHAM. Antidepressant-like responses were measured in the forced swim test, and long-term cognitive performance was assessed in the Barnes maze.</p><p><strong>Results: </strong>During adolescence, whereas ECS alone exerted an antidepressant-like response in male rats, its combination with letrozole permitted ECS to also induce efficacy in females. Moreover, adolescent ECS treatment improved cognitive performance in adulthood although exclusively in male rats.</p><p><strong>Conclusions: </strong>Adolescent ECS demonstrated an antidepressant-like potential together with certain long-term beneficial cognitive effects but exclusively in male rats. For females, efficacy was restricted to a situation in which the biosynthesis of estrogens was reduced. Therefore, estrogens and/or testosterone levels play a crucial role in the sex disparities induced by ECS in Sprague-Dawley rats. Based on this study and on the literature supporting its safety, ECS should be encouraged for use in cases of treatment-resistant depression during adolescence, while adhering to sex-specific considerations.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"607-615"},"PeriodicalIF":4.8,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9957886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Neurofilament Light Chain With the Antidepressant Effects of Low-Dose Ketamine Infusion Among Patients With Treatment-Resistant Depression.","authors":"Wei-Chen Lin,&nbsp;Tung-Ping Su,&nbsp;Cheng-Ta Li,&nbsp;Hui-Ju Wu,&nbsp;Ya-Mei Bai,&nbsp;Yu-Li Liu,&nbsp;Pei-Chi Tu,&nbsp;Mu-Hong Chen","doi":"10.1093/ijnp/pyad045","DOIUrl":"10.1093/ijnp/pyad045","url":null,"abstract":"<p><strong>Background: </strong>The role of neurofilament light chain (NFL) in treatment-resistant depression (TRD) is unclear. Whether baseline NFL concentrations are associated with the antidepressant effects of low-dose ketamine infusion has not been determined.</p><p><strong>Methods: </strong>The NFL concentrations of 71 patients with TRD and 17 healthy controls were assessed. Patients with TRD were randomly administered a single infusion of 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were assessed before infusion and sequentially at postinfusion timepoints (after 240 minutes and after 2-7 and 14 days) using the Hamilton Depression Rating Scale (HDRS).</p><p><strong>Results: </strong>After adjustment for age, sex, and body mass index, patients with TRD were more likely to have higher concentrations of NFL than healthy controls (P < .001). A generalized estimating equation model with adjustments for infusion group, age, sex, body mass index, and baseline HDRS scores showed that baseline NFL concentrations were positively associated with subsequent HDRS scores following low-dose ketamine infusion (P = .038).</p><p><strong>Discussion: </strong>Higher concentrations of NFL were observed among patients with TRD compared with healthy controls. Baseline NFL concentrations may predict the antidepressant effects of low-dose ketamine infusion.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"649-653"},"PeriodicalIF":4.8,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4f/81/pyad045.PMC10519806.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}