International Journal of Neuropsychopharmacology最新文献

{"title":"Oxytocin reduces methylphenidate-induced dorsal striatal dopamine release in male rhesus macaques.","authors":"Mary R Lee, Ehsan Shokri Kojori, William Dieckmann, Erick Singley, Julie A Mattison, Peter Herscovitch, Lorenzo Leggio","doi":"10.1093/ijnp/pyae056","DOIUrl":"https://doi.org/10.1093/ijnp/pyae056","url":null,"abstract":"<p><strong>Background: </strong>Oxytocin is being evaluated as potential treatment for psychostimulant use disorders. It is unknown what effect oxytocin has on dopamine signaling in response to psychostimulants in brain regions such as the striatum where oxytocin and dopamine interact to process natural rewards. We investigated the effect of oxytocin on striatal dopamine release stimulated by methylphenidate whose mechanism of action is analogous to that of cocaine.</p><p><strong>Method: </strong>We conducted an [11C] raclopride positron emission tomography study to assess striatal dopamine release in male rhesus macaques treated with oxytocin (80 IU) [administered via the intranasal (N=5) and intravenous (N=6) routes] followed by methylphenidate/[11C] raclopride.</p><p><strong>Results: </strong>Oxytocin delivered by both routes significantly reduced methylphenidate-stimulated dopamine release in the dorsal striatum (caudate/putamen). These effects were, in part, evidenced by a reduction in dorsal striatal [11C] raclopride binding potential (increased dopamine release) following oxytocin administration.</p><p><strong>Conclusion: </strong>The results provide translational and mechanistic evidence for the potential role of oxytocin as a treatment for psychostimulant use disorders.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Esketamine Nasal Spray on Cognition in Patients With Treatment-Resistant Depression: Results From Four Phase 3 Studies.","authors":"Randall L Morrison, Jaskaran Singh, Ella Daly, Maggie Fedgchin, Rachel Ochs-Ross, Keith Karcher, Rosanne Lane, Kim Cooper, Gerard Sanacora, Paul Maruff, Wayne C Drevets","doi":"10.1093/ijnp/pyae046","DOIUrl":"10.1093/ijnp/pyae046","url":null,"abstract":"<p><strong>Background: </strong>While esketamine is effective in treatment-resistant depression (TRD), detailed information about the effect of esketamine on cognition is relatively scarce. This analysis assessed the effect of short-term (3 double-blind [DB] studies: DB1, DB2, and DB4) or long-term maintenance treatment (DB3) with esketamine nasal spray (ESK) compared with a placebo (PBO) combined with active-comparator, on cognition in patients with TRD.</p><p><strong>Methods: </strong>Patients (DB1/DB2/DB3: [18-64 years, n = 747]; DB4: [65 years or older, n = 137]) with TRD received ESK (DB1/DB2/DB3: 56/84 mg; DB4: 28/56/84 mg) or PBO+newly initiated oral antidepressant (OAD) as per treatment schedules. Cognitive assessments-Cogstate battery and Hopkins Verbal Learning Test-Revised-were administered at baseline, Day 28/early withdrawal, and follow-up visits in DB1/DB2/DB4 and at 12-week intervals in the DB3 maintenance phase. Descriptive statistics were used to analyze ESK effects on cognition with effect sizes and 95% confidence intervals to express the nature and magnitude of treatment effects relative to active-comparator+PBO. Correlation between depression severity (Montgomery-Ǻsberg Depression Rating Scale scores [MADRS]) and cognition was assessed at baseline and endpoint(s).</p><p><strong>Results: </strong>At baseline, mild-to-moderate impairment in psychomotor function, attention, and memory (working and episodic) were evident. For each DB1/DB2/DB4, group mean performance in Z-scores for ESK+OAD and OAD+PBO groups on all cognitive tests remained similar or slightly improved from baseline at endpoint (Day 28) and follow-up assessments. Similarly, in DB3 (maintenance phase), both groups generally showed improvement in cognitive performance at endpoint(s). Correlations between MADRS scores and performance on the cognitive test battery were small at baseline and endpoint(s).</p><p><strong>Conclusions: </strong>This analysis did not identify evidence of negative effects on cognition following short-term or long-term maintenance treatment with ESK+OAD in patients with TRD.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604480","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":"Efficacy and safety of lumateperone for bipolar depression and schizophrenia: a systematic review and meta-analysis.","authors":"Hanrui Peng, Kewen Yan, Shouhuan Liu, Xin Li, Xin Wang, Pu Peng, Xueyi Li, Min Wu, Huixue Xu, Qiuxia Wu, Tieqiao Liu, Zejun Li","doi":"10.1093/ijnp/pyae052","DOIUrl":"10.1093/ijnp/pyae052","url":null,"abstract":"<p><p>This study aimed to evaluate the efficacy and safety of lumateperone in treating bipolar disorder and schizophrenia. A comprehensive literature search was conducted across multiple databases and websites from inception to July 16, 2024, to identify both published and unpublished randomized controlled trials (RCTs). Meta-analyses were performed using random-effects or fixed-effects models depending on statistical heterogeneity. Relative risks (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to summarize the effects. Out of 931 records screened, 7 RCTs (four focusing on bipolar depression and 3 on schizophrenia) were eligible for inclusion. Lumateperone was efficacious in reducing depressive symptoms in bipolar depression (SMDs = -0.36, 95% CI: -.59 to -.13). In treating schizophrenia, lumateperone exhibited a lower combined SMD of -0.14 (95% CI: -.27 to 0, P = .051, I² = 49.6%), showing no significant difference from the placebo group, although the P-value approached significance. The lumateperone group showed significantly higher response rates compared with placebo in both bipolar depression (RRs = 1.27, 95% CI = 1.07 to 1.51) and schizophrenia (RRs = 1.44, 95% CI = 1.12 to 1.86). Common treatment-emergent adverse events included somnolence, dry mouth, dizziness, nausea, and headache (RRs = 1.30 to 3.29). Importantly, lumateperone did not significantly increase extrapyramidal symptoms (EPS, RRs = 1.46, 95% CI = .84 to 2.53). Lumateperone is effective in treating bipolar depression but does not significantly reduce symptom severity in schizophrenia. It has a favorable safety and tolerability profile. However, caution is warranted in interpreting these findings due to the limited number of studies included.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564019","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":"Epigenome-Wide DNA Methylation in Unipolar Depression: Predictive Biomarker of Antidepressant Treatment Response?","authors":"Miriam A Schiele, Oscar Crespo Salvador, Jan Lipovsek, Kathrin Schwarte, Pascal Schlosser, Peter Zwanzger, Volker Arolt, Bernhard T Baune, Anna Köttgen, Katharina Domschke","doi":"10.1093/ijnp/pyae045","DOIUrl":"10.1093/ijnp/pyae045","url":null,"abstract":"<p><strong>Background: </strong>Despite the well-documented efficacy of antidepressant agents for the treatment of major depressive disorder (MDD), initial treatment nonresponse rates are high. Recent years have seen an increase in research into predictive biomarkers toward improving diagnosis and individualized treatment. Among those, epigenetic mechanisms such as DNA methylation constitute promising candidate markers in predicting antidepressant treatment response in MDD. The present study sought to address epigenome-wide DNA methylation as a predictor of antidepressant treatment response in the largest sample to date of patients with MDD.</p><p><strong>Methods: </strong>Epigenome-wide DNA methylation was analyzed using the Infinium MethylationEPIC BeadChip in peripheral blood of n = 230 Caucasian patients with MDD receiving 6-week antidepressant treatment in a naturalistic in-patient setting as well as in a subsample of n = 107 patients primarily receiving continuous treatment with serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. Treatment response was assessed by means of the Hamilton Depression Scale.</p><p><strong>Results: </strong>No genome-wide significant hits were observed. Suggestive (P < 1E-5) epigenome-wide evidence was discerned for altered DNA methylation at 6 CpG sites (LOC102724467, LOC100506023, RSPO2, SAG, IL16, PRKCI) to predict response to naturalistic antidepressant treatment. In patients treated with serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors, differential DNA methylation at 11 CpGs, for example, mapping to the TIMP2, VDAC1, or SORL1 genes, was suggestively associated with treatment response.</p><p><strong>Conclusions: </strong>The present results provide preliminary evidence for altered DNA methylation patterns to be associated with antidepressant treatment response in MDD. Provided significant replication in independent and larger samples, the present findings might in the future aid in clinical decision-making toward more individualized and thus more efficacious treatments of MDD.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377918","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":"Correction to: Identification of Phosphodiesterase-7A (PDE7A) as a Novel Target for Reducing Ethanol Consumption in Mice.","authors":"","doi":"10.1093/ijnp/pyae049","DOIUrl":"10.1093/ijnp/pyae049","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":"27 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582979","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":"Behavioral and neurophysiological signatures of cognitive control in humans and rats.","authors":"Samantha R Linton, Ty Lees, Ann Iturra-Mena, Brian D Kangas, Genevieve Nowicki, Rachel Lobien, Gordana Vitaliano, Jack Bergman, William A Carlezon, Diego A Pizzagalli","doi":"10.1093/ijnp/pyae050","DOIUrl":"10.1093/ijnp/pyae050","url":null,"abstract":"<p><strong>Background: </strong>Deficits in cognitive control are implicated in numerous neuropsychiatric disorders. However, relevant pharmacological treatments are limited, likely due to weak translational validity of applicable preclinical models used. Neural indices derived from electroencephalography may prove useful in comparing and translating the effects of cognition-enhancing drugs between species. In the current study, we aimed to extend our previous cross-species results by examining if methylphenidate (MPH) modulates behavioral and neural indices of cognitive control in independent cohorts of humans and rats.</p><p><strong>Methods: </strong>We measured continuous electroencephalography data from healthy adults (n = 25; 14 female) and Long Evans rats (n = 22; 8 female) and compared both stimulus- and response-locked event-related potentials and spectral power measures across species, and their MPH-related moderation following treatment with vehicle (placebo) or 1 of 2 doses of MPH.</p><p><strong>Results: </strong>Across both species, linear mixed effects modeling confirmed the expected Flanker interference effect on behavior (eg, accuracy) and response-related event-related potentials. Unexpectedly, in contrast to past work, we did not observe any task-related effects on the spectral power of rodents. Moreover, MPH generally did not modulate cognitive control of either species, although some species-specific patterns offer insight for future research.</p><p><strong>Conclusions: </strong>Collectively, these findings in independent human and rodent subjects replicate some of our previously reported behavioral and neurophysiological patterns partly consistent with the notion that similar neural mechanisms may regulate cognitive control in both species. Nonetheless, these results showcase an approach to accelerate translation using a coordinated between-species platform to evaluate pro-cognitive treatments.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500008","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":"Upregulation of Phosphodiesterase 7A Contributes to Concurrent Pain and Depression via Inhibition of cAMP-PKA-CREB-BDNF Signaling and Neuroinflammation in the Hippocampus of Mice.","authors":"Shi-Cai Chen, Yan-Han Chen, Yan Song, Shu-Hua Zong, Ming-Xia Wu, Wei Wang, Hao Wang, Feng Zhang, Yan-Meng Zhou, Hai-Yang Yu, Han-Ting Zhang, Fang-Fang Zhang","doi":"10.1093/ijnp/pyae040","DOIUrl":"10.1093/ijnp/pyae040","url":null,"abstract":"<p><strong>Background: </strong>Phosphodiesterases (PDEs) are enzymes that catalyze the hydrolysis of cyclic adenosine monophosphate AMP (cAMP) and/or cyclic guanosine monophosphate (cGMP). PDE inhibitors can mitigate chronic pain and depression when these disorders occur individually; however, there is limited understanding of their role in concurrent chronic pain and depression. We aimed to evaluate the mechanisms of action of PDE using 2 mouse models of concurrent chronic pain and depression.</p><p><strong>Methods: </strong>C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) to induce chronic neuropathic pain or injected with complete Freund's adjuvant (CFA) to induce inflammatory pain, and both animals showed depression-like behavior. First, we determined the change in PDE expression in both animal models. Next, we determined the effect of PDE7 inhibitor BRL50481 or hippocampal PDE7A knockdown on PSNL- or CFA-induced chronic pain and depression-like behavior. We also investigated the role of cAMP-protein kinase A (PKA)-cAMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling and neuroinflammation in the effect of PDE7A inhibition on PSNL- or CFA-induced chronic pain and depression-like behavior.</p><p><strong>Results: </strong>This induction of chronic pain and depression in the 2 animal models upregulated hippocampal PDE7A. Oral administration of PDE7 inhibitor, BRL50481, or hippocampal PDE7A knockdown significantly reduced mechanical hypersensitivity and depression-like behavior. Hippocampal PDE7 inhibition reversed PSNL- or CFA-induced downregulation of cAMP and BDNF and the phosphorylation of PKA, CREB, and p65. cAMP agonist forskolin reversed these changes and caused milder behavioral symptoms of pain and depression. BRL50481 reversed neuroinflammation in the hippocampus in PSNL mice.</p><p><strong>Conclusions: </strong>Hippocampal PDE7A mediated concurrent chronic pain and depression in both mouse models by inhibiting cAMP-PKA-CREB-BDNF signaling. Inhibiting PDE7A or activating cAMP-PKA-CREB-BDNF signaling are potential strategies to treat concurrent chronic pain and depression.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286426","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":"Working Memory Performance Predicts, but Does Not Reduce, Cocaine and Cannabinoid Seeking in Adult Male Rats.","authors":"Sierra J Stringfield, Erin K Kirschmann, Mary M Torregrossa","doi":"10.1093/ijnp/pyae048","DOIUrl":"10.1093/ijnp/pyae048","url":null,"abstract":"<p><strong>Background: </strong>Cognitive deficits reflecting impaired executive function are commonly associated with psychiatric disorders, including substance use. Cognitive training is proposed to improve treatment outcomes for these disorders by promoting neuroplasticity within the prefrontal cortex, enhancing executive control, and mitigating cognitive decline due to drug use. Additionally, brain derived neurotrophic factor (BDNF) can facilitate plasticity in the prefrontal cortex and reduce drug-seeking behaviors. We investigated whether working memory training could elevate BDNF levels in the prefrontal cortex and if this training would predict or protect against cocaine or cannabinoid seeking.</p><p><strong>Methods: </strong>Adult male rats were trained to perform a \"simple\" or \"complex\" version of a delayed-match-to-sample working memory task. Rats then self-administered cocaine or the synthetic cannabinoid WIN55,212-2 and were tested for cued drug seeking during abstinence. Tissue from the prefrontal cortex and dorsal hippocampus was analyzed for BDNF protein expression.</p><p><strong>Results: </strong>Training on the working memory task enhanced endogenous BDNF protein levels in the prelimbic prefrontal cortex but not the dorsal hippocampus. Working memory training did not impact self-administration of either drug but predicted the extent of WIN self-administration and cocaine seeking during abstinence.</p><p><strong>Conclusions: </strong>These results suggest that working memory training promotes endogenous BDNF but does not alter drug-seeking or drug-taking behavior. However, individual differences in cognitive performance before drug exposure may predict vulnerability to future drug use.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketamine Prevents Inflammation-Induced Reduction of Human Hippocampal Neurogenesis via Inhibiting the Production of Neurotoxic Metabolites of the Kynurenine Pathway.","authors":"Gargi Mandal, Madeline Kirkpatrick, Silvia Alboni, Nicole Mariani, Carmine M Pariante, Alessandra Borsini","doi":"10.1093/ijnp/pyae041","DOIUrl":"10.1093/ijnp/pyae041","url":null,"abstract":"<p><strong>Background: </strong>Understanding the precise mechanisms of ketamine is crucial for replicating its rapid antidepressant effects without inducing psychomimetic changes. Here, we explore whether the antidepressant-like effects of ketamine enantiomers are underscored by protection against cytokine-induced reductions in hippocampal neurogenesis and activation of the neurotoxic kynurenine pathway in our well-established in vitro model of depression in a dish.</p><p><strong>Methods: </strong>We used the fetal hippocampal progenitor cell line (HPC0A07/03C) to investigate ketamine's impact on cytokine-induced reductions in neurogenesis in vitro. Cells were treated with interleukin- 1beta (IL-1b) (10 ng/mL) or IL-6 (50 pg/mL), alone or in combination with ketamine enantiomers arketamine (R-ketamine, 400 nM) or esketamine (S-ketamine, 400 nM) or antidepressants sertraline (1 mM) or venlafaxine (1 mM).</p><p><strong>Results: </strong>Resembling the effect of antidepressants, both ketamine enantiomers prevented IL-1b- and IL-6-induced reduction in neurogenesis and increase in apoptosis. This was mediated by inhibition of IL-1b-induced production of IL-2 and IL-13 by R-ketamine and of IL-1b-induced tumor necrosis factor-alpha by S-ketamine. Likewise, R-ketamine inhibited IL-6-induced production of IL-13, whereas S-ketamine inhibited IL-6-induced IL-1b and IL-8. Moreover, both R- and S-ketamine prevented IL-1b-induced increases in indoleamine 2,3-dioxygenase expression as well as kynurenine production, which in turn was shown to mediate the detrimental effects of IL-1b on neurogenesis and apoptosis. In contrast, neither R- nor S-ketamine prevented IL-6-induced kynurenine pathway activation.</p><p><strong>Conclusions: </strong>Results suggest that R- and S-ketamine have pro-neurogenic and anti-inflammatory properties; however, this is mediated by inhibition of the kynurenine pathway only in the context of IL-1b. Overall, this study enhances our understanding of the mechanisms underlying ketamine's antidepressant effects in the context of different inflammatory phenotypes, ultimately leading to the development of more effective, personalized therapeutic approaches for patients suffering from depression.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286425","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":"Evidence for the Contribution of the miR-206/BDNF Pathway in the Pathophysiology of Depression.","authors":"Ya-Bin Zheng, Xiang Jin","doi":"10.1093/ijnp/pyae039","DOIUrl":"10.1093/ijnp/pyae039","url":null,"abstract":"<p><p>Depression is a complex disorder with substantial impacts on individual health and has major public health implications. Depression results from complex interactions between genetic and environmental factors. Epigenetic mechanisms, including DNA methylation, microRNAs (miRNAs), and histone modifications, can produce heritable phenotypic changes without a change in DNA sequence and recently were proven to mediate lasting increases in the risk of depression following exposure to adverse life events. Of these, miRNAs are gaining attention for their role in the pathogenesis of many stress-associated mental disorders, including depression. One such miRNA is microRNA-206 (miR-206), which is a critical candidate for increasing the susceptibility to stress. Although miR-206 is thought to be a typical muscle-specific miRNA, it is expressed throughout the brain, particularly in the hippocampus and prefrontal cortex. Until now, only a few studies have been conducted on rodents to understand the role of miR-206 in stress-related abnormalities in neurogenesis. However, the precise underlying molecular mechanism of miR-206-mediated depression-like behaviors remains largely unknown. Here, we reviewed recent advances in the field of biomedical and clinical research on the role of miR-206 in the pathogenesis of depression from studies using different tissues and various experimental designs and described how abnormalities in miR-206 expression in these tissues can affect neuronal functions. Moreover, we focused on studies investigating the brain-derived neurotrophic factor (BDNF) as a functional target of miR-206, where miR-206 has been implicated in the pathogenesis of depression by suppressing the expression of the BDNF. In summary, these studies confirm the existence of a tight correlation between the pathogenesis of depression and the miR-206/BDNF pathway.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107199","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}