Journal of Psychopharmacology最新文献

{"title":"Compassionate use of esketamine intranasal in patients with severe major depressive disorder resistant to the treatment.","authors":"Luis Gutiérrez-Rojas, Julia Vendrell-Serres, J Antoni Ramos-Quiroga, Jon Iñaki Etxeandia-Pradera, Eduardo Aguilar, Ana Isabel De Santiago-Díaz, Daniel Hernández-Huerta, Vicente Tordera, Carlos Vázquez-Ventoso, Moisés Bolívar, Asunción Abril, Rubén Catalán-Barragán, Jesús García-Jiménez","doi":"10.1177/02698811241267837","DOIUrl":"10.1177/02698811241267837","url":null,"abstract":"<p><strong>Background: </strong>Treatment-resistant depression (TRD) is defined as the failure of at least two antidepressants in adequate doses and timing during a major depressive episode. Esketamine intranasal (ESK-IN) has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of TRD in combination with other antidepressants.</p><p><strong>Aims: </strong>To assess the effectiveness and tolerability of a sample of TRD patients who received treatment with ESK-IN as part of the compassionate use program.</p><p><strong>Methods: </strong>A retrospective, observational study was carried out on patients with a diagnosis of TRD enrolled in the early access program of ESK-IN in nine centers. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS) at four time points: baseline, 28, 90, and 180 days of treatment.</p><p><strong>Results: </strong>The sample included 71 patients (70% women) with a mean baseline MADRS score of 38.27 ± 5.9 and total or partial work disability rates of 85%. ESK-IN treatment was associated with a statistically and clinically significant reduction in the severity of depressive symptoms at all time points assessed. The presence of side effects was common but the majority were mild in severity and resolved after the observation period. Those patients who received psychotherapy in combination with ESK-IN showed a significantly lower MADRS score at 90 and 180 days than those patients who did not undergo psychotherapy.</p><p><strong>Conclusion: </strong>ESK-IN has proven to be effective and safe in a clinical sample of patients with severe TRD. To optimize clinical outcomes, the pharmacological treatment for TRD should always be integrated into a comprehensive therapeutic plan that encompasses strategies such as psychotherapy, social support, and family interventions.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"38-48"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902042","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":"Ketamine for treatment-resistant obsessive-compulsive disorder: Double-blind active-controlled crossover study.","authors":"Ben Beaglehole, Paul Glue, Shona Neehoff, Shabah Shadli, Neil McNaughton, Bridget Kimber, Chrissie Muirhead, Aroha de Bie, Rachel Day-Brown, Natalie J Hughes-Medlicott","doi":"10.1177/02698811241301215","DOIUrl":"10.1177/02698811241301215","url":null,"abstract":"<p><strong>Background: </strong>Obsessive-Compulsive Disorder (OCD) may respond to ketamine treatment.</p><p><strong>Aim: </strong>To examine the responsiveness and tolerability of treatment-refractory OCD to intramuscular (IM) ketamine compared to IM fentanyl.</p><p><strong>Methods: </strong>This was a randomised double-blind psychoactive-controlled study with single doses of racemic ketamine 0.5 mg/kg, 1.0 mg/kg or fentanyl 50 µg (psychoactive control). Pre-dosing with 4 mg oral ondansetron provided nausea prophylaxis. Eligible participants were aged between 18 and 50 years with severe treatment-resistant OCD. The primary efficacy measure was the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Tolerability was measured with the Clinician-Administered Dissociative States Scale (CADSS). Repeated measures analysis of variance with orthogonal polynomial trends was used to assess the effect of drug treatment on Y-BOCS and CADSS scores.</p><p><strong>Results: </strong>Twelve participants were randomised and 10 completed the study (7 females, 3 males, mean age 33 years). Two participants dropped out due to not tolerating dissociative effects associated with the study medication. The reductions in Y-BOCS scores were greater and statistically dose-related for both ketamine doses than fentanyl (dose [linear], <i>F</i>(1, 9) = 6.5, <i>p</i> = 0.031). Score changes for all treatments were maximal at 1-2 h with a steady separation of scores out to 168 h. Ketamine was associated with short-term dissociative and cardiovascular effects.</p><p><strong>Conclusions: </strong>We provide further preliminary evidence for the efficacy and tolerability of IM ketamine in an outpatient cohort of OCD. Additional work is required to establish the optimal dosing regimen and longer-term role of ketamine for OCD. These findings are encouraging given the well-known limitations that exist for treatments in this area.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"23-28"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750816","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":"Cognitive effects, pharmacokinetics, and safety of zuranolone administered alone or with alprazolam or ethanol in healthy adults in a phase 1 trial.","authors":"Joi Dunbar, David P Walling, Howard A Hassman, Rakesh Jain, Andy Czysz, Indrani Nandy, Victor Ona, Margaret K Moseley, Seth Levin, Paul Maruff","doi":"10.1177/02698811241282777","DOIUrl":"10.1177/02698811241282777","url":null,"abstract":"<p><strong>Background: </strong>Zuranolone is an oral, once-daily, 14-day treatment course approved for adults with postpartum depression in the United States.</p><p><strong>Aims: </strong>To assess cognitive effects, pharmacokinetics, and safety of zuranolone, alone or with alprazolam/ethanol.</p><p><strong>Methods: </strong>This was a phase 1, two-part, two-period, randomized, double-blind, placebo-controlled crossover trial. Participants received zuranolone 50 mg or placebo once daily for 9 days, and additionally received alprazolam (1 mg, Part A), ethanol (males: 0.7 g/kg; females: 0.6 g/kg, Part B), or corresponding placebo on days 1, 5, and 9. Within each part, participants received all treatment combinations. Cognition was assessed using a computerized test battery; pharmacokinetics and safety were also evaluated.</p><p><strong>Results: </strong>All participants (Part A, <i>N</i> = 24; Part B, <i>N</i> = 25) received ⩾1 dose of zuranolone/placebo. Compared to placebo, zuranolone produced small-to-moderate cognitive decline (Cohen's |<i>d</i>| = 0.126-0.76); effects were larger with alprazolam (Cohen's |<i>d</i>| = 0.523-0.93) and ethanol (Cohen's |<i>d</i>| = 0.345-0.88). Zuranolone coadministration with alprazolam (Cohen's |<i>d</i>| = 0.6-1.227) or ethanol (Cohen's |<i>d</i>| = 0.054-0.5) generally worsened cognitive decline when compared with zuranolone alone. Maximal pharmacodynamic effects occurred at approximately 5 h and were resolved by 12 h postbaseline. No pharmacokinetic interactions were observed. Incidence of adverse events was similar between groups; most events were mild or moderate in severity.</p><p><strong>Conclusion: </strong>A general small-to-moderate magnitude decline in cognition occurred with zuranolone alone. Coadministration with alprazolam/ethanol increased the magnitude, but not the duration, of effects compared with single-agent administration. Zuranolone prescribers and patients should be aware of the potential for increased central nervous system-depressant effects if coadministered with GABAergic active compounds such as alprazolam and ethanol.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1122-1136"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468382","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":"High-dose Vitamin-B6 reduces sensory over-responsivity.","authors":"Rebekah O Cracknell, Teresa Tavassoli, David T Field","doi":"10.1177/02698811241271972","DOIUrl":"10.1177/02698811241271972","url":null,"abstract":"<p><strong>Background: </strong>Sensory reactivity differences are experienced by between 5% and 15% of the population, often taking the form of sensory over-responsivity (SOR), in which sensory stimuli are experienced as unusually intense and everyday function is affected. A potential mechanism underlying over-responsivity is an imbalance between neural excitation and inhibition in which inhibitory influences are relatively weakened. Therefore, interventions that boost neural inhibition or reduce neural excitation may reduce SOR; Vitamin-B6 is the coenzyme for the conversion of excitatory glutamate to inhibitory gamma-aminobutyric acid (GABA), and in animal models, it both increases the concentration of GABA and reduces glutamate.</p><p><strong>Aims: </strong>To discover whether taking a high dose of Vitamin-B6 reduces SOR and other aspects of sensory reactivity.</p><p><strong>Methods: </strong>We recruited 300 adults (249 females) from the general population who completed the Sensory Processing 3-Dimensions Scale (SP-3D) first at baseline, and again following randomisation to either 1 month's supplementation with 100 mg Vitamin-B6, or one of two control conditions (1000 µg Vitamin-B12 or placebo). To focus on individuals who experience SOR, we analysed the effects of supplementation only on individuals with high baseline SOR scores (above the 87th percentile).</p><p><strong>Results: </strong>In individuals with SOR at baseline, Vitamin-B6 selectively reduced SOR compared to both placebo and Vitamin-B12. We also found that Vitamin-B6 selectively reduced postural disorder in individuals with high scores on this subscale at baseline, but there were no effects on the four remaining SP-3D subscales.</p><p><strong>Conclusions: </strong>Clinical trials and mechanistic studies should now be conducted in autism, attention deficit hyperactivity disorder and other groups with SOR.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1147-1156"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046812","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":"Aspirin may be more suitable for patients with major depression: Evidence from two-sample Mendelian randomization analysis.","authors":"Haohao Zhu, Yucai Qu, Qin Zhou, Zhiqiang Du, Zhenhe Zhou, Ying Jiang","doi":"10.1177/02698811241282613","DOIUrl":"10.1177/02698811241282613","url":null,"abstract":"<p><strong>Objective: </strong>Utilizing two-sample Mendelian randomization (TSMR) analysis, this study aims to explore the potential bidirectional causal relationship between common nonsteroidal anti-inflammatory drugs (paracetamol, ibuprofen, aspirin) and major depression (MD) from a genetic standpoint.</p><p><strong>Methods: </strong>We employed summarized data from a Genome-Wide Association Study (GWAS) of European populations. The inverse variance weighted (IVW) method was used for TSMR analysis; outcomes were evaluated based on <i>p</i>-value, OR (Odds Ratio), and 95% confidence interval (95% CI).</p><p><strong>Results: </strong>From a genetic perspective, the study found that the use of paracetamol and ibuprofen increased the risk of MD (IVW (MRE): OR = 2.314, 95% CI: 1.609-3.327; <i>p</i> = 6.07E-06) and (IVW (MRE): OR = 2.308, 95% CI: 1.780-3.653; <i>p</i> = 0.002), respectively. No significant causal relationship was found between aspirin and MD (<i>p</i> > 0.05). Reverse TSMR analysis found that MD increased the genetic predisposition to use paracetamol, ibuprofen, and aspirin (IVW (MRE): OR = 1.042, 95% CI: 1.030-1.054, <i>p</i> = 3.07E-12), (IVW (FE): OR = 1.015, 95% CI: 1.007-1.023, <i>p</i> = 1.13E-04), (IVW (MRE): OR = 1.019, 95% CI: 1.009-1.030, <i>p</i> = 4.22E-04), respectively. Other analytical methods and sensitivity analyses further supported the robustness and reliability of these findings.</p><p><strong>Conclusion: </strong>This study provides preliminary genetic evidence through bidirectional TSMR analysis that MD increases the genetic predisposition to use paracetamol, ibuprofen, and aspirin, aiding clinicians in devising preventive strategies against the misuse of non-steroidal anti-inflammatory drugs. Moreover, we found that the use of paracetamol and ibuprofen increases the risk of MD, whereas aspirin did not. This suggests a crucial clinical implication: clinicians treating MD patients could opt for the relatively safer aspirin over paracetamol and ibuprofen.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1137-1146"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348920","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":"Evaluation of the sedative-motor effects of novel GABAkine imidazodiazepines using quantitative observation techniques in rhesus monkeys.","authors":"Dishary Sharmin, Daniela Rüedi-Bettschen, Laís F Berro, Jemma E Cook, Jaren A Reeves-Darby, Tanya Pareek, Md Yeunus Mian, Farjana Rashid, Lalit Golani, Eliseu da Cruz Moreira-Junior, Donna M Platt, James M Cook, James K Rowlett","doi":"10.1177/02698811241286760","DOIUrl":"10.1177/02698811241286760","url":null,"abstract":"<p><strong>Background: </strong>Benzodiazepines bind to γ-aminobutyric acid type A (GABA_A) receptor subtypes identified by different α subunits (i.e., α1GABA_A, α2GABA_A, α3GABA_A, and α5GABA_A). Sedative-motor effects of benzodiazepines are thought to involve α1GABA_A and α3GABA_A subtypes.</p><p><strong>Aims: </strong>We evaluated observable measures of sedative-motor effects and species-typical behaviors in monkeys following acute administration of novel GABAkines (positive allosteric modulators of GABA_A receptors), with varying degrees of selective efficacy at different GABA_A receptor subtypes. We predicted that the induction of sedative-motor effects would depend on the degree of α1GABA_A and α3GABA_A efficacy.</p><p><strong>Methods: </strong>Adult female rhesus monkeys (<i>N</i> = 4) were implanted with chronic indwelling i.v. catheters. Quantitative behavioral observation was conducted by trained observers following administration of multiple doses of the conventional benzodiazepine alprazolam and the GABAkines MP-III-80 (preferential efficacy at α2/α3/α5GABA_A subtypes), KRM-II-81, MP-III-24 (both with preferential efficacy for α2/α3GABA_A subtypes), and MP-III-22 (preferential potency and efficacy for α5GABA_A subtypes).</p><p><strong>Results: </strong>As with alprazolam, all GABAkines induced significant levels of mild sedation (\"rest/sleep posture\"). Deep sedation was observed with alprazolam, MP-III-80, and MP-III-22; motoric effects (observable ataxia) were obtained with alprazolam, KRM-II-81, and MP-III-22 only. Surprisingly, the order of potency for rest/sleep posture was significantly associated only with potency at α5GABA_A subtypes.</p><p><strong>Conclusions: </strong>GABAkines with preferential efficacy at α2/α3GABA_A and/or α5GABA_A subtypes engendered sedative-motor effects in monkeys, although only compounds with α5GABA_A activity engendered deep sedation. Moreover, the significant relationship between potency obtained with in vitro electrophysiology data and the rest/sleep posture measure suggests a role for the α5GABA_A subtype in this milder form of sedation.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1157-1169"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391349","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":"Optimizing the individual dosing of paroxetine in major depressive disorder with therapeutic drug monitoring.","authors":"Lingjun Zhong, Linlin Hu, Yinghui Li, Tianyu Wang, Suzhen Chen, Yuanyue Gao, Yonggui Yuan, Hua Shao","doi":"10.1177/02698811241278779","DOIUrl":"10.1177/02698811241278779","url":null,"abstract":"<p><strong>Introduction: </strong>Previous studies have examined the correlation between paroxetine concentrations and therapeutic efficacy in patients diagnosed with major depressive disorder (MDD), but findings have been contradictory.</p><p><strong>Aims: </strong>This study aimed to investigate the relationships among plasma concentrations, severity of symptoms, and adverse drug reactions (ADRs) to optimize individual dosing.</p><p><strong>Methods: </strong>Eighty-seven MDD patients, after completing treatment with paroxetine, were divided into low-concentration (LC, <i>n</i> = 38), medium-concentration (MC, <i>n</i> = 27), and high-concentration (HC, <i>n</i> = 22) groups, based on cutoff value concentrations with the 50% response rate and the laboratory alert level from the 2017 consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology. The severity of depression and anxiety was evaluated using a 17-item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA), respectively. Dosage, plasma concentrations, scale scores, and ADRs were recorded across the three groups at different treatment stages to define the therapeutic reference range.</p><p><strong>Results: </strong>The 4-week plasma concentration of paroxetine (65.00 ng/mL) could predict the clinical response in MDD patients at 8 weeks. Symptom relief in patients with 4-week paroxetine concentrations ranging from 65.00 to 120.00 ng/mL at 8 weeks was greater than in those with concentrations below 65.00 ng/mL, with no significant difference observed above this range. In addition, more cases of liver injury and weight gain were observed in patients with high paroxetine concentrations.</p><p><strong>Conclusion: </strong>Our results support that early paroxetine concentration may predict clinical efficacy and the incidence of ADRs, thus improving individual dosing regimens for MDD patients.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1063-1070"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348922","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":"Unidentified <i>CYP2D6</i> genotype does not affect pharmacological treatment for patients with first episode psychosis.","authors":"Emma Y De Brabander, Thérèse van Amelsvoort, Roos van Westrhenen","doi":"10.1177/02698811241279022","DOIUrl":"10.1177/02698811241279022","url":null,"abstract":"<p><strong>Background: </strong>Research on the pharmacogenetic influence of hepatic <i>CYP450</i> enzyme 2D6 (<i>CYP2D6</i>) on metabolism of drugs for psychosis and associated outcome has been inconclusive. Some results suggest increased risk of adverse reactions in poor and intermediate metabolizers, while others find no relationship. However, retrospective designs may fail to account for the long-term pharmacological treatment of patients. Previous studies found that clinicians adapted risperidone dose successfully without knowledge of patient <i>CYP2D6</i> phenotype.</p><p><strong>Aim: </strong>Here, we aimed to replicate the results of those studies in a Dutch cohort of patients with psychosis (<i>N</i> = 418) on pharmacological treatment.</p><p><strong>Method: </strong>We compared chlorpromazine-equivalent dose between <i>CYP2D6</i> metabolizer phenotypes and investigated which factors were associated with dosage. This was repeated in two smaller subsets; patients prescribed pharmacogenetics-actionable drugs according to published guidelines, and risperidone-only as done previously.</p><p><strong>Results: </strong>We found no relationship between chlorpromazine-equivalent dose and phenotype in any sample (complete sample: <i>p</i> = 0.3, actionable-subset: <i>p</i> = 0.82, risperidone-only: <i>p</i> = 0.34). Only clozapine dose was weakly associated with <i>CYP2D6</i> phenotype (<i>p</i> = 0.03).</p><p><strong>Conclusion: </strong>Clinicians were thus not intuitively adapting dose to <i>CYP2D6</i> activity in this sample, nor was <i>CYP2D6</i> activity associated with prescribed dose. Although the previous studies could not be replicated, this study may provide support for existing and future pharmacogenetic research.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1111-1121"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348925","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":"Influence of panic disorder and paroxetine on brain functional hubs in drug-free patients.","authors":"Yingying Zhang, Haohao Yan, Yiding Han, Xiaoxiao Shan, Huabing Li, Feng Liu, Ping Li, Jingping Zhao, Wenbin Guo","doi":"10.1177/02698811241278780","DOIUrl":"10.1177/02698811241278780","url":null,"abstract":"<p><strong>Background: </strong>The effects of panic disorder (PD) and pharmacotherapy on brain functional hubs in drug-free patients, and the utility of their degree centrality (DC) in diagnosing and predicting treatment response (TR) for PD, remained unclear.</p><p><strong>Aims: </strong>This study aimed to assess the effects of PD and paroxetine on brain functional hubs in drug-free patients and to identify neuroimaging biomarkers for diagnosing and predicting TR in patients with PD.</p><p><strong>Methods: </strong>Imaging data from 54 medication-free PD patients and 54 matched healthy controls (HCs) underwent DC and functional connectivity (FC) analyses before and after a 4-week paroxetine treatment. Diagnosis and prediction of TR models for PD were constructed using support vector machine (SVM) and support vector regression (SVR), with DC as features.</p><p><strong>Results: </strong>Patients with PD showed aberrant DC and FC in the anterior cingulum, temporal, and occipital areas compared with HCs at baseline. After treatment, DC of the patients increased in the calcarine cortex, lingual gyrus, and cerebellum IV/V, along with improved clinical symptoms. Utilizing voxel-wise DC values at baseline, the SVM effectively distinguished patients with PD from HCs with an accuracy of 83.33%. In SVR, the predicted TR significantly correlated with the observed TR (correlation coefficient (<i>r</i>) = 0.893, Mean Squared Error = 0.009).</p><p><strong>Conclusion: </strong>Patients with PD exhibited abnormal DC and FC, notably in the limbic network, temporal, and occipital regions. Paroxetine ameliorated patients' symptoms while altering their brain FC. SVM and SVR models, utilizing baseline DC, effectively distinguished the patients from HCs and accurately predicted TR.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1083-1094"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289781","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":"Associative memory in alcohol-related contexts: An fMRI study with young binge drinkers.","authors":"Rui Pedro Serafim Rodrigues, Sónia Silva Sousa, Eduardo López-Caneda, Natália Almeida-Antunes, Alberto Jacobo González-Villar, Adriana Sampaio, Alberto Crego","doi":"10.1177/02698811241282624","DOIUrl":"10.1177/02698811241282624","url":null,"abstract":"<p><strong>Background: </strong>Alcohol-related cues are known to influence craving levels, a hallmark of alcohol misuse. Binge drinking (BD), a pattern of heavy alcohol use, has been associated with cognitive and neurofunctional alterations, including alcohol attentional bias, memory impairments, as well as disrupted activity in prefrontal- and reward-related regions. However, literature is yet to explore how memories associated with alcohol-related cues are processed by BDs, and how the recall of this information may influence their reward processing.</p><p><strong>Aims: </strong>The present functional magnetic resonance imaging (fMRI) study aimed to investigate the neurofunctional signatures of BD during an associative memory task.</p><p><strong>Method: </strong>In all, 36 university students, 20 BDs and 16 alcohol abstainers, were asked to memorize neutral objects paired with either alcohol or non-alcohol-related contexts. Subsequently, neutral stimuli were presented, and participants were asked to classify them as being previously paired with alcohol- or non-alcohol-related contexts.</p><p><strong>Results: </strong>While behavioral performance was similar in both groups, during the recall of alcohol-related cues, BDs showed increased brain activation in two clusters including the thalamus, globus pallidus and dorsal striatum, and cerebellum and occipital fusiform gyrus, respectively.</p><p><strong>Conclusion: </strong>These findings suggest that BDs display augmented brain activity in areas responsible for mental imagery and reward processing when trying to recall alcohol-related cues, which might ultimately contribute to alcohol craving, even without being directly exposed to an alcohol-related context. These results highlight the importance of considering how alcohol-related contexts may influence alcohol-seeking behavior and, consequently, the maintenance or increase in alcohol use.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"972-985"},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381157","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}