Molecular Psychiatry最新文献

{"title":"Clinical response to neurofeedback in major depression relates to subtypes of whole-brain activation patterns during training","authors":"Masaya Misaki, Kymberly D. Young, Aki Tsuchiyagaito, Jonathan Savitz, Salvador M. Guinjoan","doi":"10.1038/s41380-024-02880-3","DOIUrl":"https://doi.org/10.1038/s41380-024-02880-3","url":null,"abstract":"<p>Major Depressive Disorder (MDD) poses a significant public health challenge due to its high prevalence and the substantial burden it places on individuals and healthcare systems. Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) shows promise as a treatment for this disorder, although its mechanisms of action remain unclear. This study investigated whole-brain response patterns during rtfMRI-NF training to explain interindividual variability in clinical efficacy in MDD. We analyzed data from 95 participants (67 active, 28 control) with MDD from previous rtfMRI-NF studies designed to increase left amygdala activation through positive autobiographical memory recall. Significant symptom reduction was observed in the active group (<i>t</i> = −4.404, <i>d</i> = −0.704, <i>p</i> &lt; 0.001) but not in the control group (<i>t</i> = −1.609, <i>d</i> = −0.430, <i>p</i> = 0.111). However, left amygdala activation did not account for the variability in clinical efficacy. To elucidate the brain training process underlying the clinical effect, we examined whole-brain activation patterns during two critical phases of the neurofeedback procedure: activation during the self-regulation period, and transient responses to feedback signal presentations. Using a systematic process involving feature selection, manifold extraction, and clustering with cross-validation, we identified two subtypes of regulation activation and three subtypes of brain responses to feedback signals. These subtypes were significantly associated with the clinical effect (regulation subtype: <i>F</i> = 8.735, <i>p</i> = 0.005; feedback response subtype: <i>F</i> = 5.326, <i>p</i> = 0.008; subtypes’ interaction: <i>F</i> = 3.471, <i>p</i> = 0.039). Subtypes associated with significant symptom reduction were characterized by selective increases in control regions, including lateral prefrontal areas, and decreases in regions associated with self-referential thinking, such as default mode areas. These findings suggest that large-scale brain activity during training is more critical for clinical efficacy than the level of activation in the neurofeedback target region itself. Tailoring neurofeedback training to incorporate these patterns could significantly enhance its therapeutic efficacy.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"25 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADNP is essential for sex-dependent hippocampal neurogenesis, through male unfolded protein response and female mitochondrial gene regulation","authors":"Guy Shapira, Gidon Karmon, Gal Hacohen-Kleiman, Maram Ganaiem, Shula Shazman, Paschalis Theotokis, Nikolaos Grigoriadis, Noam Shomron, Illana Gozes","doi":"10.1038/s41380-024-02879-w","DOIUrl":"https://doi.org/10.1038/s41380-024-02879-w","url":null,"abstract":"<p>Essential for brain formation and protective against tauopathy, activity-dependent neuroprotective protein (ADNP) is critical for neurogenesis and cognitive functions, while regulating steroid hormone biogenesis. As such, de novo mutations in ADNP lead to syndromic autism and somatic ADNP mutations parallel Alzheimer’s disease progression. Furthermore, clinical trials with the ADNP fragment NAP (the investigational drug davunetide) showed efficacy in women suffering from the tauopathy progressive supranuclear palsy and differentially boosted memory in men (spatial) and women (verbal), exhibiting prodromal Alzheimer’s disease. While autism is more prevalent in boys and Alzheimer’s disease in women, both involve impaired neurogenesis. Here, we asked whether ADNP sex-dependently regulates neurogenesis. Using bromodeoxyuridine (BrdU) as a marker of neurogenesis, we identified two-fold higher labeling in the hippocampal sub-ventricular zone of ADNP-intact male versus female mice. <i>Adnp</i> haplo-insufficient (<i>Adnp</i>^<i>+/−</i>) mice or mice CRSIPR/Cas9-edited to present the most prevalent neurodevelopmental ADNP syndrome mutation, p.Tyr718* (Tyr) showed dramatic reductions in male BrdU incorporation, resulting in mutated females presenting higher labeling than males. Treatment with NAP compensated for the male reduction of BrdU labeling. Mechanistically, hippocampal RNAseq revealed male-specific Tyr down-regulation of endoplasmic reticulum unfolded protein response genes critical for sex-dependent organogenesis. Newly discovered mitochondrial accessibility of ADNP was inhibited by the Tyr718* mutation further revealing female-specific Tyr downregulation of mitochondrial <i>ATP6</i>. NAP moderated much of the differential expression caused by p.Tyr718*, accompanied by the down-regulation of neurotoxic, pro-inflammatory and pro-apoptotic genes. Thus, ADNP is a key regulator of sex-dependent neurogenesis that acts by controlling canonical pathways, with NAP compensating for fundamental ADNP deficiencies, striding toward clinical development targeting the ADNP syndrome and related neurodevelopmental/neurodegenerative diseases.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"2 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analysis of psychosis Biotypes: shared Ancestry-adjusted polygenic risk and unique genomic associations","authors":"Cuihua Xia, Ney Alliey-Rodriguez, Carol A. Tamminga, Matcheri S. Keshavan, Godfrey D. Pearlson, Sarah K. Keedy, Brett Clementz, Jennifer E. McDowell, David Parker, Rebekka Lencer, S. Kristian Hill, Jeffrey R. Bishop, Elena I. Ivleva, Cindy Wen, Rujia Dai, Chao Chen, Chunyu Liu, Elliot S. Gershon","doi":"10.1038/s41380-024-02876-z","DOIUrl":"https://doi.org/10.1038/s41380-024-02876-z","url":null,"abstract":"<p>The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed <i>post hoc</i> ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples. Applied to schizophrenia PRS, we found the Khera AAPRS method to show superior portability and comparable prediction accuracy as compared with the Ge method. The three Biotypes of psychosis disorders had similar AAPRSs across ancestries. In genomic analysis of Biotypes, 12 genes, and isoforms showed significant genomic associations with specific Biotypes in a Transcriptome-Wide Association Study (TWAS) of genetically regulated expression (GReX) in the adult brain and fetal brain. TWAS inflation was addressed by the inclusion of genotype principal components in the association analyses. Seven of these 12 genes/isoforms satisfied Mendelian Randomization (MR) criteria for putative causality, including four genes <i>TMEM140</i>, <i>ARTN</i>, <i>C1orf115</i>, <i>CYREN</i>, and three transcripts ENSG00000272941, ENSG00000257176, ENSG00000287733. These genes are enriched in the biological pathways of Rearranged during Transfection (RET) signaling, Neural Cell Adhesion Molecule 1 (NCAM1) interactions, and NCAM signaling for neurite out-growth. The specific associations with Biotypes suggest that pharmacological clinical trials and biological investigations might benefit from analyzing Biotypes separately.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"24 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OXTR-mediated signaling in astrocytes contributes to anxiolysis","authors":"Carl-Philipp Meinung, Laura Boi, Sareh Pandamooz, David Mazaud, Grégory Ghézali, Nathalie Rouach, Inga D. Neumann","doi":"10.1038/s41380-024-02870-5","DOIUrl":"https://doi.org/10.1038/s41380-024-02870-5","url":null,"abstract":"<p>Astrocytes are an indispensable part of signal processing within the mammalian brain. Thus, the mode of action of a neuropeptide such as oxytocin (OXT) can only be fully understood considering this integral part of the CNS. Here, we show that OXT regulates astrocytic gene expression, intracellular signaling and specific proteins both in vitro and in vivo. This translates into rapid regulation of astroglial structural and functional properties including cytoskeletal plasticity, coverage of synapses and gap-junction coupling. At the molecular level, we identify the previously undescribed Sp1-Gem signaling cascade as the key driver for these cell type-specific OXT effects. Finally at the behavioral level, we found in vivo that OXT requires astrocytes to exert its well described anxiolytic properties within the hypothalamic paraventricular nucleus. Thus, our study points to OXT receptor-expressing astrocytes as a critical component of the brain OXT system.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"24 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and acceptability of pharmacological interventions for tardive dyskinesia in people with schizophrenia or mood disorders: a systematic review and network meta-analysis","authors":"Marco Solmi, Michele Fornaro, Stefano Caiolo, Marialaura Lussignoli, Claudio Caiazza, Michele De Prisco, Niccolo Solini, Andrea de Bartolomeis, Felice Iasevoli, Giorgio Pigato, Cinzia Del Giovane, Andrea Cipriani, Christoph U. Correll","doi":"10.1038/s41380-024-02733-z","DOIUrl":"https://doi.org/10.1038/s41380-024-02733-z","url":null,"abstract":"<p>Tardive Dyskinesia (TD) can occur in people exposed to dopamine receptor antagonists (DRAs). Its clinical management remains challenging. We conducted a systematic review/random-effects network meta-analysis (NMA) searching PubMed/MEDLINE/PsycINFO/ClinicalTrials.gov/Cochrane Central Register (22/05/2023, pre-defined protocol https://osf.io/b52ae/), for randomized controlled trials (RCTs) of pharmacological/brain stimulation interventions for DRA-induced TD in adults with schizophrenia or mood disorders. Primary outcomes were TD symptom change (standardized mean difference/SMD) and all-cause discontinuation (acceptability-risk ratio/RR). Sensitivity analyses were conducted. Global, local inconsistencies, risk of bias (RoB-2 tool), and confidence in evidence (CINeMA) were measured. We included 46 trials (n = 2844, age = 52.89 ± 9.94 years, males = 59.8%, schizophrenia = 84.6%, mood disorders = 15.4%), all testing pharmacological interventions versus placebo. We identified three subnetworks. In network 1, several treatments outperformed placebo on TD symptoms with large effect sizes (k = 34, n = 2269), encompassing 22 interventions versus placebo, but 18 had 1 RCTs only, and 15 had n ≤ 20. High heterogeneity (I² = 57.1%; tau² = 0.0797), and global inconsistency (Q = 32.64; df = 14; p = 0.0032) emerged. No significant differences emerged in acceptability. When restricting analyses to treatments with trials with n &gt; 20 and &gt;1 RCT, only valbenazine (k = 5, SMD = −0.69; 95% CI = −1.00, −0.37) and vitamin E (k = 7, SMD = −0.49; 95% CI = −0.87, −0.11) were superior to placebo. Deutetrabenazine outperformed placebo considering AIMS score and in low risk of bias trials only and with a moderate effect size for 24/36 mg (k = 2, SMD = −0.57/−0.60). Confidence in findings was low for deutetrabenazine and valbenazine, very low for all others. In network 2 (k = 2, n = 63), switch to molindone (k = 1, n = 9) versus switch to haloperidol worsened TD (SMD = 1.68; 95% CI = 0.61,2.76). In network 3 (k = 3, n = 194), antipsychotic wash-out+placebo (k = 1, n = 25) versus TAU+placebo (k = 1, n = 27) worsened TD (SMD = 1.30; 95% CI = 0.36,2.23). Despite large effect sizes for some treatments with very low quality/confidence, when considering higher quality evidence only valbenazine or deutetrabenazine are evidence-based first-line treatments for TD, and potentially vitamin E as second-line. Switching to molindone and antipsychotic washout should be avoided. More treatment options and higher-quality trials are needed.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"66 9-10 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psilocybin increases emotional empathy in patients with major depression","authors":"J. Jungwirth, R. von Rotz, I. Dziobek, F. X. Vollenweider, K. H. Preller","doi":"10.1038/s41380-024-02875-0","DOIUrl":"https://doi.org/10.1038/s41380-024-02875-0","url":null,"abstract":"<p>Empathy plays a crucial role in interpersonal relationships and mental health. It is decreased in a variety of psychiatric disorders including major depression. Psilocybin, a promising candidate for treating depression, has been shown to acutely increase emotional empathy in healthy volunteers. However, no study has investigated this effect and its relevance for symptom improvement in a clinical population. This study examines the enduring effects of psilocybin-assisted therapy on empathy in depressed patients using a randomized, placebo-controlled design. Fifty-one depressed patients were randomly assigned to receive a single dose of psilocybin (0215 mg/kg body weight) or a placebo embedded in a 4-week psychological support intervention. Empathy was measured using the Multifaceted Empathy Test at baseline and 2 days, 1 week, and 2 weeks after substance administration. Changes in empathy were compared between treatment conditions. Patients who received psilocybin showed significant improvements in explicit emotional empathy driven by an increase in empathy towards positive stimuli compared to the placebo group for at least two weeks. This study highlights the potential of psychedelics to enhance social cognition in individuals living with depression and contributes to a better understanding of the psychological mechanisms of action of psychedelics. Further studies are necessary to investigate the interaction between social cognition and clinical efficacy.</p><p>The trial is registered on clinicaltrials.gov (Identifier: NCT03715127) and KOFAM (Identifier: SNCTP000003139).</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"56 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fast-spiking parvalbumin-positive interneurons: new perspectives of treatment and future challenges in dementia","authors":"Xiaorong Zhang, Moxin Wu, Lin Cheng, Wa Cao, Ziying Liu, Seung-Bum Yang, Min-Sun Kim","doi":"10.1038/s41380-024-02756-6","DOIUrl":"https://doi.org/10.1038/s41380-024-02756-6","url":null,"abstract":"<p>Central nervous system parvalbumin-positive interneurons (PV-INs) are crucial and highly vulnerable to various stressors. They also play a significant role in the pathological processes of many neuropsychiatric diseases, especially those associated with cognitive impairment, such as Alzheimer’s disease (AD), vascular dementia (VD), Lewy body dementia, and schizophrenia. Although accumulating evidence suggests that the loss of PV-INs is associated with memory impairment in dementia, the precise molecular mechanisms remain elusive. In this review, we delve into the current evidence regarding the physiological properties of PV-INs and summarize the latest insights into how their loss contributes to cognitive decline in dementia, particularly focusing on AD and VD. Additionally, we discuss the influence of PV-INs on brain development, the variations in their characteristics across different types of dementia, and how their loss affects the etiology and progression of cognitive impairments. Ultimately, our goal is to provide a comprehensive overview of PV-INs and to consider their potential as novel therapeutic targets in dementia treatment.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"7 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neuroendocrinology of stress and the importance of a proper balance between the mineralocorticoid and glucocorticoid receptors","authors":"Philip W. Gold,&nbsp;Ma-Li Wong","doi":"10.1038/s41380-024-02686-3","DOIUrl":"10.1038/s41380-024-02686-3","url":null,"abstract":"","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"30 1","pages":"1-3"},"PeriodicalIF":9.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41380-024-02686-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826497","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":"Electroconvulsive therapy-specific volume changes in nuclei of the amygdala and their relationship to long-term anxiety improvement in depression","authors":"Yuzuki Ishikawa, Naoya Oishi, Yusuke Kyuragi, Momoko Hatakoshi, Jinichi Hirano, Takamasa Noda, Yujiro Yoshihara, Yuri Ito, Jun Miyata, Kiyotaka Nemoto, Yoshihisa Fujita, Hiroyuki Igarashi, Kento Takahashi, Shingo Murakami, Hiroyuki Kanno, Yudai Izumi, Akihiro Takamiya, Junya Matsumoto, Fumitoshi Kodaka, Kazuyuki Nakagome, Masaru Mimura, Toshiya Murai, Taro Suwa","doi":"10.1038/s41380-024-02874-1","DOIUrl":"https://doi.org/10.1038/s41380-024-02874-1","url":null,"abstract":"<p>Electroconvulsive therapy (ECT) is one of the most effective treatments for depression. ECT induces volume changes in the amygdala, a key center of anxiety. However, the clinical relevance of ECT-induced changes in amygdala volume remains uncertain. We hypothesized that nuclei-specific amygdala volumes and anxiety symptoms in depression could explain the clinical correlates of ECT-induced volume changes. To test this hypothesis, we enrolled patients with depression who underwent ECT (N = 20) in this multicenter observational study and collected MRI data at three time points: before and after treatment and a 6-month follow-up. Patients who received medication (N = 52), cognitive behavioral therapy (N = 63), or transcranial magnetic stimulation (N = 20), and healthy participants (N = 147) were included for comparison. Amygdala nuclei were identified using FreeSurfer and clustered into three subdivisions to enhance reliability and interpretability. Anxiety symptoms were quantified using the anxiety factor scores derived from the Hamilton Depression Rating Scale. Before treatment, basolateral and basomedial subdivisions of the right amygdala were smaller than those of healthy controls. The volumes of the amygdala subdivisions increased after ECT and decreased during the follow-up period, but the volumes at 6-month follow-up were larger than those observed before treatment. These volume changes were specific to ECT. Long-term volume changes in the right basomedial amygdala correlated with improvements in anxiety symptoms. Baseline volumes in the right basolateral amygdala correlated with long-term improvements in anxiety symptoms. These findings demonstrate that clinical correlates of ECT-induced amygdala volume changes are existent, but in a nucleus and symptom-specific manner.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"122 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute cannabidiol administration reduces alcohol craving and cue-induced nucleus accumbens activation in individuals with alcohol use disorder: the double-blind randomized controlled ICONIC trial","authors":"Sina Zimmermann, Anton Teetzmann, Joscha Baeßler, Lena Schreckenberger, Judith Zaiser, Marlen Pfisterer, Manuel Stenger, Patrick Bach","doi":"10.1038/s41380-024-02869-y","DOIUrl":"https://doi.org/10.1038/s41380-024-02869-y","url":null,"abstract":"<p>Although alcohol use disorder (AUD) is highly prevalent, only a few medications are approved for its treatment leaving much room for improvement. Cannabidiol (CBD) might be a particularly promising candidate, with preclinical data suggesting that CBD is effective in targeting AUD symptoms and disease processes that drive alcohol use and relapse, due to its anti-craving, stress-reducing, and anti-compulsive effects. Here we report data from the double-blind randomized controlled ICONIC trial that compared the effects of a single dose of 800 mg cannabidiol against placebo (PLC) in N = 28 individuals with AUD. Cue-induced nucleus accumbens (NAc) activation, alcohol craving during a combined stress- and alcohol cue exposure session, as well as craving during an fMRI alcohol cue-reactivity task and CBD plasma levels served as outcomes. Individuals receiving CBD showed lower bilateral cue-induced NAc activation (<i>t</i>_{<i>left</i>_NAc(23)} = 4.906, <i>p</i> &lt; 0.001, d = 1.15; <i>t</i>_{right_NAc (23)} = 4.873, <i>p</i> &lt; 0.001, d = 1.13) and reported significantly lower alcohol craving after a combined stress- and alcohol cue exposure session (<i>F</i>_group(1,26) = 4.516, <i>p</i> = 0.043, eta² = 0.15) and during the fMRI cue-reactivity task (<i>F</i>_group(1,24) = 6.665, <i>p</i> = 0.015, eta² = 0.23). CBD levels were significantly higher in the CBD group (<i>t</i>₍₂₅₎ = 3.808, <i>p</i> &lt; 0.001, d = 1.47) and showed a significant negative association with alcohol craving during the cue exposure experiment (<i>r</i> = −0.394, <i>p</i>_FDR = 0.030) and during fMRI (<i>r</i> = −0.389, <i>p</i>_FDR = 0.030), and with left and right NAc activation (<i>r</i>_left__NAc = −0.459, <i>p</i>_FDR = 0.030; <i>r</i>_right__NAc = −0.405, <i>p</i>_FDR = 0.030). CBD’s capacity to reduce stress- and cue-induced alcohol craving and to normalize NAc activation – a region critical to the pathophysiology of AUD – contribute to understanding the neurobiological basis of its clinical effects and support its potential as a treatment option for AUD. Clinical Trials Registry: DRKS00029993.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"1 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}