Alfonso Martone, Chiara Possidente, Giuseppe Fanelli, Chiara Fabbri, Alessandro Serretti
{"title":"Genetic factors and symptom dimensions associated with antidepressant treatment outcomes: clues for new potential therapeutic targets?","authors":"Alfonso Martone, Chiara Possidente, Giuseppe Fanelli, Chiara Fabbri, Alessandro Serretti","doi":"10.1007/s00406-024-01873-1","DOIUrl":"10.1007/s00406-024-01873-1","url":null,"abstract":"<p><p>Treatment response and resistance in major depressive disorder (MDD) show a significant genetic component, but previous studies had limited power also due to MDD heterogeneity. This literature review focuses on the genetic factors associated with treatment outcomes in MDD, exploring their overlap with those associated with clinically relevant symptom dimensions. We searched PubMed for: (1) genome-wide association studies (GWASs) or whole exome sequencing studies (WESs) that investigated efficacy outcomes in MDD; (2) studies examining the association between MDD treatment outcomes and specific depressive symptom dimensions; and (3) GWASs of the identified symptom dimensions. We identified 13 GWASs and one WES of treatment outcomes in MDD, reporting several significant loci, genes, and gene sets involved in gene expression, immune system regulation, synaptic transmission and plasticity, neurogenesis and differentiation. Nine symptom dimensions were associated with poor treatment outcomes and studied by previous GWASs (anxiety, neuroticism, anhedonia, cognitive functioning, melancholia, suicide attempt, psychosis, sleep, sociability). Four genes were associated with both treatment outcomes and these symptom dimensions: CGREF1 (anxiety); MCHR1 (neuroticism); FTO and NRXN3 (sleep). Other overlapping signals were found when considering genes suggestively associated with treatment outcomes. Genetic studies of treatment outcomes showed convergence at the level of biological processes, despite no replication at gene or variant level. The genetic signals overlapping with symptom dimensions of interest may point to shared biological mechanisms and potential targets for new treatments tailored to the individual patient's clinical profile.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1637-1651"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valentina Rosolen, Luigi Castriotta, Marco Driutti, Umberto Albert, Fabio Barbone, Giulio Castelpietra
{"title":"Association between previous SARs-CoV-2 infection and new prescription of antidepressant drugs: a case-control study in Friuli Venezia Giulia region, Italy.","authors":"Valentina Rosolen, Luigi Castriotta, Marco Driutti, Umberto Albert, Fabio Barbone, Giulio Castelpietra","doi":"10.1007/s00406-024-01846-4","DOIUrl":"10.1007/s00406-024-01846-4","url":null,"abstract":"<p><strong>Purpose: </strong>A rise in affective and anxiety disorders and in antidepressant (AD) treatment during the COVID-19 pandemic has been extensively described, but few studies were provided at the individual level, further considering COVID-19 severity and vaccination status.</p><p><strong>Methods: </strong>Case-control study evaluating the association between the new use of ADs and a previous COVID-19 infection, in Friuli Venezia Giulia Region, Italy, from March 1, 2020, to July 19, 2022. Multiple conditional logistic regressions assess the association between a new AD use and a COVID-19 infection previous to the index date, stratified by gender, age and anti-COVID-19 vaccination status. Odds Ratios (OR) and 95% confidence intervals were reported.</p><p><strong>Results: </strong>COVID-19 was associated with AD treatment after the infection. The disease severity was positively associated with a growing risk of being dispensed an AD, with the highest risk in unvaccinated subjects previously hospitalised in ICU (OR = 28.77). The risk of using ADs after COVID-19 infection was higher in unvaccinated subjects aged 65 years and older, both females and males. The association between COVID-19 infection and AD dispensation in vaccinated subjects was not significant, with the exception of females aged 65 years and over.</p><p><strong>Conclusions: </strong>Anti-COVID-19 vaccination, especially among the elderly, might prevent post-COVID AD treatment. Clinicians should be aware that COVID-19 patients requiring hospitalisation are more likely to experience these symptoms, given their higher risk of being dispensed ADs. Future studies may benefit by analysing the incidence of both mental disorders and psychotropic treatment in post-COVID patients, considering socioeconomic factors and vaccination status.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1685-1692"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aticaprant, a kappa opioid receptor antagonist, and the recovered 'interest and pleasure' in the concept of major depressive disorder.","authors":"Koen Demyttenaere","doi":"10.1007/s00406-024-01851-7","DOIUrl":"10.1007/s00406-024-01851-7","url":null,"abstract":"<p><p>Lack of positive mood and anhedonia probably are the most specific depressive symptoms. Anhedonia is a multifaceted concept: the clinical language describes anticipatory/consummatory anhedonia and sensory/social anhedonia while the cognitive neuroscience language describes readiness for reward, energy expenditure to attain reward, updating reward presence and value. Mounting evidence supports the potential of kappa-opioid receptor (KOR) antagonists as novel pharmacotherapies for major depressive disorder : aticaprant is a potent, selective, short-acting KOR antagonist. The fast-fail approach evaluated the impact of aticaprant on the brain circuitry hypothesized to mediate anhedonia and significantly increased fMRI activation in the ventral striatal activation during reward anticipation as compared to placebo; the aticaprant induced changes in the self-reported psychological measures of anhedonia were rather inconsistent. The recently reported results of a phase 2a randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of aticaprant, co-administered to an oral SSRI/SNRI antidepressant in depressed patients who had an inadequate response to 1 or 2 antidepressants. The improvement from baseline favoured the co-administration of aticaprant over the co-administration of placebo at all time points (during 6 weeks), and this was confirmed by higher response rates with aticaprant. A mid-split of patients with higher or lower than median anhedonia also showed that the patients with higher baseline anhedonia had the largest decrease on the MADRS. Tolerability and safety were reassuring. These promising results of the co-administration of aticaprant to an SSRI/SNRI in depressed patients with prominent anhedonia support he further investigation of aticaprant in larger trials.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1593-1597"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simone Grimm, Stefan Just, Rene Fuertig, Jennifer B Dwyer, Vikas M Sharma, Andreas Wunder
{"title":"TRPC4/5 inhibitors: Phase I results and proof of concept studies.","authors":"Simone Grimm, Stefan Just, Rene Fuertig, Jennifer B Dwyer, Vikas M Sharma, Andreas Wunder","doi":"10.1007/s00406-024-01890-0","DOIUrl":"10.1007/s00406-024-01890-0","url":null,"abstract":"<p><p>Transient receptor potential canonical (TRPC) ion channels are expressed in areas of the brain responsible for processing emotion and mood and have been implicated in the pathophysiology of internalizing disorders such as major depressive disorder and anxiety disorders. This review outlines the rationale for targeting TRPC ion channels for drug development, with specific focus on TRPC4 and TRPC5. We provide preclinical evidence that the lack of TRPC4 and TRPC5 channels or its pharmacological inhibition attenuate fear and anxiety without impairing other behaviors in mice. We also report on clinical studies of BI 1358894, a small molecule inhibitor of TRPC4/5 ion channels, demonstrating reduced psychological and physiological responses to induced anxiety/panic-like symptoms in healthy volunteers. Furthermore, we highlight an imaging study that investigated the acute effects of BI 1358894 and showed reduced activation in several brain regions involved in emotional processing. We conclude that these findings demonstrate a critical role for TRPC4 and TRPC5 in emotional processing, even though it remains an open question if the biological signatures of TRPC4/5 inhibition reported here translate into clinical efficacy and indicate that a TRPC4/5 inhibitor might provide a more effective treatment of internalizing disorders.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1599-1610"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Calum D Moulton, Mantas Malys, Christopher W P Hopkins, Anna S Rokakis, Allan H Young, Nick Powell
{"title":"Activation of the interleukin-23/Th17 axis in major depression: a systematic review and meta-analysis.","authors":"Calum D Moulton, Mantas Malys, Christopher W P Hopkins, Anna S Rokakis, Allan H Young, Nick Powell","doi":"10.1007/s00406-024-01864-2","DOIUrl":"10.1007/s00406-024-01864-2","url":null,"abstract":"<p><p>The interleukin-23/Th17 axis is a promising modifiable target for depression. However, its association with depression has not been systematically evaluated. We systematically searched four databases (EMBASE, Web of Science, Pubmed and PsycINFO) for studies comparing patients with major depression and healthy controls for plasma/serum levels of Th17 cells and their canonical cytokines (interleukin-17A [IL-17A], IL-22, granulocyte macrophage colony stimulating factor [GM-CSF]). We also compared counts of Th1, Th2 and Th9 cells between depressed/non-depressed patients and their respective canonical cytokines. We performed random-effects meta-analysis of the standardised mean difference (SMD) in immune measures between groups. Risk of bias was assessed using the Newcastle-Ottawa scale. Of 3154 studies screened, 36 studies were included in meta-analysis. Patients with depression had elevated IL-17A compared to controls (SMD = 0.80 [95% CI 0.03 to 1.58], p = 0.042), an association moderated by antidepressant use (Z = 2.12, p = 0.034). Patients with depression had elevated GM-CSF (SMD = 0.54 [95% CI 0.16 to 0.91], p = 0.0047), and a trend towards higher Th17 counts (SMD = 0.44 [- 0.01 to 0.88], p = 0.052). Whilst the Th2-associated cytokine IL-5 was elevated in depression (SMD = 0.36 [95% CI 0.05 to 0.66], p = 0.02), Th2 cell counts (p = 0.97), Th1 cell counts (p = 0.17) and interferon-γ (p = 0.22) were not. Data for Th9 cells, IL-9 and IL-22 were insufficient for meta-analysis. Respectively, 22, 25 and 5 studies were good, fair and poor in quality. Patients with major depression show peripheral over-activation of the IL-23/Th17 axis. Future interventional studies should test whether this is a modifiable target for depression.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1653-1673"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rafting toward a depression biomarker.","authors":"Mark M Rasenick","doi":"10.1007/s00406-025-02071-3","DOIUrl":"10.1007/s00406-025-02071-3","url":null,"abstract":"<p><p>The journey from the cytoskeleton and G protein signaling to a framework that might provide a simple blood diagnostic for depression as well as a harbinger of individual antidepressant response, has been convoluted, occasionally frustrating, but ultimately rewarding. Herein, I provide a travelogue of sorts on our progress toward this end, and also chart a course toward the goal of providing a simple, quantitative and objective, biomarker-driven assessment tool that reflects the neurobiology of depressed mood.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1675-1683"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Barbara D'Aiello, Deny Menghini, Silvia Di Vara, Pietro De Rossi, Stefano Vicari
{"title":"Predictors of Methylphenidate response in children and adolescents with ADHD: the role of sleep disturbances.","authors":"Barbara D'Aiello, Deny Menghini, Silvia Di Vara, Pietro De Rossi, Stefano Vicari","doi":"10.1007/s00406-024-01932-7","DOIUrl":"10.1007/s00406-024-01932-7","url":null,"abstract":"<p><p>Sleep Disturbances (SD) have been linked to children and adolescents with ADHD, impacting its progression and outcomes. Methylphenidate (MPH), a commonly used stimulant medication for ADHD treatment, has been observed to potentially influence SD as a side effect, while SD can in turn potentially affect the response to MPH. This study aimed to explore the potential role of SD on MPH response in children and adolescents with ADHD. At this aim, 43 children and adolescents with ADHD received a single dose of MPH and were assessed for attention before and after medication administration. As expected, the administration of MPH resulted in improved attention levels. Our data indicate that patients with higher SD experienced greater benefits from the medication, stabilizing Reaction Times Variability (VRTs). This suggests that SD might influence the response to MPH, with individuals exhibiting higher SD deriving more advantages from the treatment. In addition, we found that other factors, such as externalizing problems and IQ, interact with each other and with SD, influencing the response to stimulant medication. Early detection of SD, along with the study of cognitive and emotional-behavioral characteristics, could assist clinicians in predicting the effectiveness of MPH therapy in children and adolescents with ADHD. However, further research is necessary to gain a deeper understanding of the role of SD and other factors in the long-term effects of MPH.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1705-1713"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gerrit Burkhardt, Simon E Blackwell, Miaoxi Chen, Lisa Feldmann, Jonas Björklund, Esther Dechantsreiter, Lucia Bulubas, Stephan Goerigk, Daniel Keeser, Peter Falkai, Ellen Greimel, Peter Bechmann, Gerd Schulte-Körne, Alkomiet Hasan, Wolfgang Strube, Frank Padberg
{"title":"Intermittent theta burst stimulation in adolescents and young adults with depressive disorders: protocol of a randomized, sham-controlled study with a sequential Bayesian design for adaptive trials.","authors":"Gerrit Burkhardt, Simon E Blackwell, Miaoxi Chen, Lisa Feldmann, Jonas Björklund, Esther Dechantsreiter, Lucia Bulubas, Stephan Goerigk, Daniel Keeser, Peter Falkai, Ellen Greimel, Peter Bechmann, Gerd Schulte-Körne, Alkomiet Hasan, Wolfgang Strube, Frank Padberg","doi":"10.1007/s00406-024-01926-5","DOIUrl":"10.1007/s00406-024-01926-5","url":null,"abstract":"<p><p>Intermittent theta burst stimulation (iTBS), a variant of repetitive transcranial magnetic stimulation (rTMS), is an established treatment for adults with major depressive disorder (MDD). Due to its favorable safety profile, iTBS is also a promising early intervention in the transition phase from adolescence to early adulthood, but this has not been systematically investigated to date. Thus, the EARLY-BURST trial investigates the efficacy and safety of iTBS over the left dorsolateral prefrontal cortex (lDLPFC) in treatment-seeking young patients (age 16-26 years) with depressive disorders (i.e. major depressive disorder, persistent depressive disorder, bipolar depression), allowing for relevant co-morbidities. Participants have not received antidepressant or antipsychotic medication during the last 12 months except for short-term (< 2 weeks) on-demand medication. The trial will employ a novel sequential Bayesian, randomized, double-blind, parallel-group, sham-controlled design. Up to 90 patients at two clinical sites (Munich, Augsburg) will be randomized 1:1 to the treatment groups, with sequential analyses starting after 26 patients in each group completed the treatment. The primary outcome will be the difference in depression severity at week 6 (post-treatment visit) between active iTBS and sham iTBS, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). The trial is planned to be expanded towards a three-arm leapfrog design, contingent on securing additional funding. Thus, in addition to potentially providing evidence of iTBS's efficacy in adolescents and young adults with depressive disorders, the EARLY-BURST trial aims at setting the stage for subsequent platform trials in this dynamic research field, where novel adaptive study designs are required to meet the need for rapidly testing promising new vs established rTMS protocols.Trial registration: DRKS00033313.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1827-1838"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ludovic C Dormegny-Jeanjean, Clément de Crespin de Billy, Camille Pierrat, Olivier Mainberger, Benoit Schorr, Alexandre Obrecht, Hippolyte Arcay, Augustin Moreau, Ilia Humbert, Francesco Scarlatti, Gilles Bertschy, Paulo Loureiro de Sousa, Julien Lamy, Sebastien Weibel, Lionel Landré, Jack R Foucher
{"title":"Individualizing rTMS in treatment-resistant depression from patient-specific perfusion abnormalities a proof-of-concept randomized trial in comparison to standard rTMS and tDCS.","authors":"Ludovic C Dormegny-Jeanjean, Clément de Crespin de Billy, Camille Pierrat, Olivier Mainberger, Benoit Schorr, Alexandre Obrecht, Hippolyte Arcay, Augustin Moreau, Ilia Humbert, Francesco Scarlatti, Gilles Bertschy, Paulo Loureiro de Sousa, Julien Lamy, Sebastien Weibel, Lionel Landré, Jack R Foucher","doi":"10.1007/s00406-025-02027-7","DOIUrl":"10.1007/s00406-025-02027-7","url":null,"abstract":"<p><strong>Background: </strong>Studies examining treatment-resistant depression (TRD) as a group implicitly assume that these conditions share similar pathophysiological features, like left prefrontal hypoactivity, and should respond to standardized treatments like repetitive transcranial magnetic stimulation (S-rTMS) or transcranial direct current stimulation (tDCS). Recent advances in arterial spin labeling functional MRI (ASL-fMRI) revealed that subject-specific perfusion abnormalities may be more heterogeneous than expected. Individualized rTMS protocols (I-rTMS) could alleviate such abnormalities and establish their relevance.</p><p><strong>Methods: </strong>iADAPT was a randomized, cross-over trial comparing I-rTMS with active comparators (S-rTMS and tDCS) on brain perfusion, assessed with ASL-fMRI, and single blind clinical evaluation. Patient-specific abnormalities were determined from three ASL-fMRI sessions. I-rTMS multi-target interventions targeted all reachable bi-frontal abnormalities, upregulating hypoperfusions and downregulating hyperperfusions. S-rTMS and tDCS were placed on F3. rTMS interventions used neuronavigation and a robotic targeting device. Each arm included 20 sessions over two weeks.</p><p><strong>Results: </strong>Twenty-two patients with TRD were included and analyzed. While at the group level they presented subgenual cingulate hyperperfusion, they presented heterogeneous prefrontal perfusion abnormalities individually. I-rTMS was the only intervention to have specific effects on brain perfusion, showing perfusion reductions compatible with the disengagement of negative emotional systems, e.g. subgenual cingulate, anterior insula.</p><p><strong>Conclusions: </strong>Paradoxically, I-rTMS induced more reproducible remote effects on cerebral perfusion than S-rTMS, while the I-rTMS protocol differed considerably between participants. These results suggest that the heterogeneities observed in ASL-MRI at the individual level are significant and may have the potential to inform individualized treatment.</p><p><strong>Clinicaltrials: </strong>gov no NCT02863380, registered on 2016-08-05.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1809-1825"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synaptic basis of rapid antidepressant action.","authors":"Ege T Kavalali, Lisa M Monteggia","doi":"10.1007/s00406-024-01898-6","DOIUrl":"10.1007/s00406-024-01898-6","url":null,"abstract":"<p><p>The discovery of ketamine's rapid antidepressant action has generated intense interest in the field of neuropsychiatry. This discovery demonstrated that to alleviate the symptoms of depression, treatments do not need to elicit substantive alterations in neuronal circuitry or trigger neurogenesis, but rather drive synaptic plasticity mechanisms to compensate for the underlying pathophysiology. The possibility of a rapidly induced antidepressant effect makes therapeutic pursuit of fast-acting neuropsychiatric medications against mood disorders plausible. In the meantime, the accumulating clinical as well as preclinical observations raise critical questions on the nature of the specific synaptic plasticity events that mediate these rapid antidepressant effects. This work has triggered the current growing interest in alternative psychoactive compounds that are thought to have similar properties to ketamine and its action. This review covers our insight into these questions based on the work our group has conducted on this topic in the last decade.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1539-1546"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}