Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Cortical structural alterations and thyroid autoantibodies underlying anxiety in major depressive disorder with comorbid Hashimoto's thyroiditis","authors":"Qinghua Zhai ,&nbsp;Wenyue Gong ,&nbsp;Azi Shen ,&nbsp;Yiwen Wang ,&nbsp;Haowen Zou ,&nbsp;Yinghong Huang ,&nbsp;Kaiyu Shi ,&nbsp;Shuai Zhao ,&nbsp;Rui Yan ,&nbsp;Zhijian Yao ,&nbsp;Qing Lu ,&nbsp;Jindan Wu","doi":"10.1016/j.pnpbp.2026.111613","DOIUrl":"10.1016/j.pnpbp.2026.111613","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is often accompanied by anxiety and may co-occur with Hashimoto's thyroiditis (HT), an autoimmune thyroid disease linked to mood disturbances. Patients with comorbid HT often present with more severe anxiety, yet the neurobiological mechanisms underlying this comorbidity remain unclear.</div></div><div><h3>Methods</h3><div>The study included 44 MDD patients without HT (MDDHT−), 45 MDD patients with comorbid HT (MDDHT+), 48 HT patients, and 80 healthy controls (HC). Participants completed self-report questionnaires, blood sampling, and MRI scans. MDD patients were additionally evaluated with the Hamilton Depression (HAMD-17) and Anxiety (HAMA) Rating Scales. Cortical morphology was analyzed with FreeSurfer. Generalized linear models were employed to examine the main and interactive effects of MDD and HT, controlling for age, sex, eTIV, education, and medication load index. Partial correlation analyses were conducted to explore associations between cortical alterations and clinical measures.</div></div><div><h3>Results</h3><div>Depression diagnosis was independently associated with reduced surface area in the left cuneus and pericalcarine gyrus, while HT was independently linked to reduced surface area in the left cuneus. Moreover, a significant interaction between depression and HT was observed in the surface area of the left middle temporal gyrus. In MDDHT+ patients, the left cuneus surface area was negatively correlated with anxiety/somatization factor and GAD-7 scores. Furthermore, Tg-Ab levels were positively correlated with anxiety/somatization factor and GAD-7 scores in the MDDHT+ group.</div></div><div><h3>Conclusion</h3><div>MDD and HT exert distinct effects on cortical surface area. These alterations, together with Tg-Ab levels, may jointly contribute to anxiety symptoms in MDDHT+ patients.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"145 ","pages":"Article 111613"},"PeriodicalIF":3.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019960","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":"Subgenual anterior cingulate cortex and antidepressant response to serotonergic and glutamatergic pharmacological treatments: a systematic review of neuroimaging studies","authors":"Rachel L. Sousa-Ho ,&nbsp;Ilya Demchenko ,&nbsp;Vanessa A. Baltazar ,&nbsp;Ishaan Tailor ,&nbsp;Benjamin T. Dunkley ,&nbsp;Tom A. Schweizer ,&nbsp;Sidney H. Kennedy ,&nbsp;Alexandre Boutet ,&nbsp;Andres M. Lozano ,&nbsp;Cherise R. Chin Fatt ,&nbsp;Manish K. Jha ,&nbsp;Katharine Dunlop ,&nbsp;Venkat Bhat","doi":"10.1016/j.pnpbp.2026.111616","DOIUrl":"10.1016/j.pnpbp.2026.111616","url":null,"abstract":"<div><div>Antidepressants are commonly prescribed for major depressive disorder (MDD), with evidence suggesting that their therapeutic effect may involve the normalization of structural and functional abnormalities within the subgenual anterior cingulate cortex (sgACC). This systematic review evaluates the neuroimaging literature to assess the relationship between longitudinal change in the sgACC structure, activity, functional connectivity, and metabolism with serotonergic and glutamatergic antidepressive agents. A search for relevant articles was conducted with an end date of July 29th 2024, through OVID (MEDLINE, Embase, APA PsychINFO). To be included in this systematic review, studies must have collected and reported neuroimaging data pertaining to the structure, function, or metabolism of the sgACC in participants with resistant or non-resistant MDD undergoing treatment with serotonergic or glutamatergic antidepressants. Twenty-one studies were included in the review. Two studies found that increased sgACC volume in MDD patients at baseline was associated with better treatment outcomes with escitalopram and fluoxetine. Functional studies reported mixed findings, with counterbalanced evidence for increased, decreased, as well as unchanged activity in the sgACC after pharmacotherapy. Three metabolic imaging studies reported decreased sgACC metabolism post-treatment with fluoxetine and paroxetine, whereas two serotonin transporter (SERT) occupancy studies reported increased SERT occupancy post-treatment with escitalopram. Future studies should explore individual variability in sgACC modulation, possibly examining genetic, neurobiological, and clinical factors that influence sgACC response to antidepressant pharmacotherapy.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"145 ","pages":"Article 111616"},"PeriodicalIF":3.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020363","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":"Combination of brain injury and brain reserve promotes the neuroimaging evaluation of small vessel disease related cognitive impairment","authors":"Yuanzheng Wang ,&nbsp;Xu Han ,&nbsp;Yuewei Chen ,&nbsp;Mianxin Liu ,&nbsp;Ying Hu ,&nbsp;Yage Qiu ,&nbsp;Qun Xu ,&nbsp;Yao Wang ,&nbsp;Yan Zhou","doi":"10.1016/j.pnpbp.2026.111615","DOIUrl":"10.1016/j.pnpbp.2026.111615","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the advantage of combining brain injury and reserve in evaluation of cerebral small vessel disease (CSVD) related cognitive impairment.</div></div><div><h3>Design, settings, participants and measurements</h3><div>This was a single-center cross-sectional study. A total of 483 CSVD patients underwent structural MRI and cognitive testing. CSVD related imaging biomarkers including white matter hyperintensities (WMH), lacunar infarctions (LI), cerebral microbleeds (CMBs), and brain atrophy were quantitated. Brain reserve was assessed by intracranial volume (ICV). Structural network characteristics, including sparseness, redundancy, global efficiency (Eg), and local efficiency (Eloc) were calculated. High and low brain reserve were defined using the quartile method on ICV.</div></div><div><h3>Results</h3><div>The MoCA scores between the high and low reserve groups has a difference(23.35 ± 4.06 vs 21.73 ± 5.20, <em>t</em> = 2.38, <em>p</em> = 0.037). All of the CSVD related imaging biomarkers, ICV and brain structural network characteristics were significantly correlated with MoCA(<em>r</em> = 0.156, <em>p</em> = 0.002). ICV was positively associated with MoCA after controlling the other related variables(<em>r</em> = 0.145, <em>p</em> = 0.012; <em>r</em> = 0.128, <em>p</em> = 0.049). Compared with the low brain reserve group, the high brain reserve group had similar macroscopic brain damages, but better network configuration and better cognitive performance. Most brain injury biomarkers were significantly associated with cognitive function in the low brain reserve group, but not in the high brain reserve group. The mediation analysis shows that brain structural network sparseness(indirect effect = 0.0196, <em>p</em> &lt; 0.05), redundancy(indirect effect = 0.0155, p &lt; 0.05), and Eg(indirect effect = 0.0355, p &lt; 0.05) could play significant role in mediating effects on the relationship between ICV and MoCA, while Eloc(no significant mediating effect, <em>p</em> &gt; 0.05) did not show a significant mediating effect. Education, grey matter volume, ICV and network sparseness were significant contributors to MoCA within the best regression model.</div></div><div><h3>Conclusions</h3><div>Brain reserve protects cognitive function, potentially mediated in part through an optimized configuration of the brain structural network. The incorporation of conventional MRI biomarkers and brain structural network characteristics, encompassing both aspects of brain injury and reserve, holds promise for enhancing the clinical assessment of cognitive impairment related to CSVD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"145 ","pages":"Article 111615"},"PeriodicalIF":3.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020646","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":"Repeated adenosine A1 receptor antagonism rewires ventral hippocampus-ventral tegmental area transmission and enhances stress-coping responses","authors":"Ornella Valenti ,&nbsp;Karin Mueller ,&nbsp;Jae-Won Yang ,&nbsp;Hilal Bulut ,&nbsp;Katarzyna Anna Rekawek ,&nbsp;Stefan Boehm","doi":"10.1016/j.pnpbp.2026.111609","DOIUrl":"10.1016/j.pnpbp.2026.111609","url":null,"abstract":"<div><div>Despite decades of research, antidepressant therapies are ineffective in many patients, and the rewiring of neuronal networks during depression has remained largely unexplored. Emerging evidence indicates that unbalanced inhibition/ excitation and dysregulations of ventral tegmental area (VTA) dopamine (DA) neuron activity are correlated with depression. Recently, caffeine and adenosine receptor antagonists were found to modulate VTA DA neuron activity, and investigations in both, humans and rodents, indicate that these receptors might serve as targets to treat depression.</div><div>We employed a system-oriented approach and electrophysiology measurements to explore the impact of the adenosine A1 receptor antagonist DPCPX on the ventral hippocampus (vHPC)-VTA circuit and its ability to affect behavioral responses in forced swim and elevated plus maze tests.</div><div>A single exposure to DPCPX reduced VTA DA neuron activity at doses known to elicit anxiety. With repeated exposure, a lower dose of DPCPX sufficed to stabilize DA neuron firing via vHPC and to prevent an influence of tetrahydrodeoxycorticosterone or forced swim task (FST), but not of elevated plus maze (EPM), on VTA DA neuron activity. Vice versa, repeated DPCPX enhanced active stress coping behavior in FST, but failed to exert an action in EPM.</div><div>Our data indicate that repeated A1R antagonism in vHPC can rewire the vHPC – NAc – VTA circuitry to enhance stress resilience by orchestrating VTA DA neuron activity. As reinforced stress resilience may boost antidepressant therapy, A1 receptor antagonism may prove to be a promising strategy in the fight against major depressive disorder.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"145 ","pages":"Article 111609"},"PeriodicalIF":3.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991885","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":"Long-term impact of embryonic ethanol exposure on gene expression and executive functions in zebrafish","authors":"Romério de Oliveira Lima Filho ,&nbsp;Ricardo Gabriel de Lima Bisneto ,&nbsp;Beatriz Silva do Nascimento ,&nbsp;Heloysa Araujo-Silva ,&nbsp;Silvia Regina Batistuzzo de Medeiros ,&nbsp;Eduardo Pacheco Rico ,&nbsp;Ana Carolina Luchiari","doi":"10.1016/j.pnpbp.2026.111612","DOIUrl":"10.1016/j.pnpbp.2026.111612","url":null,"abstract":"<div><div>This study explores the long-term effects of embryonic ethanol exposure on cognitive functions and gene expression in zebrafish (<em>Danio rerio</em>). We hypothesized that ethanol exposure during a critical developmental stage would lead to deficits in executive functions, such as working memory and behavioral flexibility, as well as alterations in neurodevelopmental gene expression. Zebrafish embryos were exposed to ethanol for 2 h at 24 hpf (hours post fertilization), and behavior was assessed at the fry (15 days post-fertilization), juvenile (45 dpf), and adult (90 dpf) stages. The Y-FMP behavioral test revealed impairments in behavioral flexibility and working memory, indicated by increased repetitive strategy in the juvenile phase and reduced alternation strategy in adult individuals. Molecular analyses showed downregulation of genes responsible for neurodevelopment and also dopaminergic signaling, suggesting that ethanol exposure disrupts critical developmental pathways. Despite partial recovery of gene expression in the juvenile stage, cognitive deficits persisted, highlighting the long-term impact of embryonic ethanol exposure. This study underscores the need for early diagnostic and intervention strategies for individuals affected by Fetal Alcohol Spectrum Disorders (FASD) and calls for further research on biomarkers to distinguish FASD from other neurodevelopmental disorders. In conclusion, our findings demonstrate that embryonic ethanol exposure significantly impacts cognitive functions and gene expression pattern in zebrafish, mirroring the challenges faced by individuals with FASD. These results contribute to the understanding of the neurodevelopmental consequences of prenatal ethanol exposure and reinforce the importance of preventing ethanol consumption during pregnancy.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"145 ","pages":"Article 111612"},"PeriodicalIF":3.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991837","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":"Traumatic-like fear memory recall causes persistent morphine conditioned place preference in drug withdrawn male mice","authors":"Claire Leconte,&nbsp;Virginie Beray-Berthat,&nbsp;Fanny Saulnier,&nbsp;Derin Reha Ulusoy,&nbsp;Amanda Patricia Sales,&nbsp;Matilde Donzelli,&nbsp;Laura Marques,&nbsp;Isabelle Nondier,&nbsp;Corinne Canestrelli,&nbsp;Florence Noble,&nbsp;Raymond Mongeau","doi":"10.1016/j.pnpbp.2026.111611","DOIUrl":"10.1016/j.pnpbp.2026.111611","url":null,"abstract":"<div><div>Post-traumatic stress disorders (PTSD) can lead to substance use disorders (SUD), and in particular opioid dependence. Although preclinical models of the literature focused on traumatic stress-induced potentiation of opioid dependence acquisition, none studied the effect of fear memories during opioid withdrawal. The goal of this study was thus to develop and describe a preclinical model of the PTSD/SUD comorbidity during this critical period in adult male mice. Classically, the traumatic-like memory was acquired by fear conditioning and was followed by morphine-conditioned place preference (CPP) to acquire the associative memory linked to the drug-reinforcing effect. Departing from this approach, we evaluated the effect of a stress on drug-induced CPP using regular re-exposures to a conditioned fear stimulus recall (FR), immediately followed by CPP tests, several days after the last morphine injection (from the 5th to the 21st day). Our data indicated that FR sessions induce a persistent morphine CPP, that is absent in morphine withdrawn mice not subjected to FR. This effect was prevented when antalarmin, a corticotropin-releasing factor receptor 1 antagonist, was administered during morphine withdrawal before each FR. Persistent morphine-induced CPP was concomitant with a FR-induced <em>kappa</em> opioid receptor mRNA upregulation in the prefrontal cortex, while <em>mu</em> opioid receptor mRNA expression was enhanced in control morphine withdrawn mice, an effect absent, however, in withdrawn mice subjected to FR. Surprisingly, in the amygdala, endogenous opioid-related mRNA expression changes in relation with the long-term persistence of drug-induced CPP were few, but Next Generation Sequencing revealed differential expression of numerous microRNAs in that brain area between morphine-control vs morphine-FR mice. The present study thus proposes an innovative behavioral model of the PTSD/SUD-like comorbidity with biological modulations in both the prefrontal cortex and the amygdala, paving the way to develop adapted treatments for this comorbidity in clinics.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"145 ","pages":"Article 111611"},"PeriodicalIF":3.9,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967895","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":"High-fat diet-induced obesity enhances stress vulnerability and promotes a PTSD-like phenotype in rats","authors":"Carmit Cohen ,&nbsp;Joseph Zohar ,&nbsp;Doron Todder ,&nbsp;Hagit Cohen","doi":"10.1016/j.pnpbp.2025.111596","DOIUrl":"10.1016/j.pnpbp.2025.111596","url":null,"abstract":"<div><div>The association between post-traumatic stress disorder (PTSD) and subsequent obesity is well-established in humans, however, whether obesity exacerbates vulnerability to PTSD remains underexplored. To investigate this, we employed a rat model fed either a high-fat diet (HFD; 60 % kcal from fat) or a control diet (CD). After confirming significant body mass index differences between HFD and CD groups, rats were exposed to predator scent stress (PSS) or a sham-PSS control. Behavioral phenotyping was conducted using the elevated plus maze (EPM) and acoustic startle response (ASR) to classify stress response profiles, supplemented by the forced swim test to assess depressive-like behavior and the Morris water maze to evaluate spatial learning and memory. Neural cytoarchitecture and molecular mechanisms were examined via Golgi-Cox staining and immunohistochemistry, targeting shared modulators of the orexigenic and anxiolytic systems in the hippocampus and hypothalamus. Our findings reveal that HFD-induced obesity promotes a PTSD-like phenotype, exacerbates depressive-like behavior, and impairs spatial learning and memory acquisition. Morphological alterations in the hippocampus and amygdala of HFD-fed rats resembled those in PSS-exposed CD-fed rats, regardless of stress exposure, suggesting common neurostructural changes. Furthermore, HFD-induced obesity modulated region-specific expression of neuropeptide Y (NPY), NPY-Y1 receptor, and glucocorticoid receptor immunoreactivity in hippocampal and hypothalamic nuclei. These results underscore a bidirectional interplay between diet-induced obesity and stress-related disorders, highlighting the critical role of the orexigenic and anxiolytic systems and their neurobiological underpinnings in mediating these effects.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111596"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835301","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":"Effects of intermittent theta- burst stimulation on emotion anticipation and processing in depression- investigating behavioral, electrodermal and neural activity","authors":"Wiebke Struckmann ,&nbsp;Magdalena Wlad ,&nbsp;Jörgen Rosén ,&nbsp;David Fällmar ,&nbsp;Robert Bodén ,&nbsp;Jonas Persson ,&nbsp;Malin Gingnell","doi":"10.1016/j.pnpbp.2026.111606","DOIUrl":"10.1016/j.pnpbp.2026.111606","url":null,"abstract":"<div><h3>Background</h3><div>Depression is characterized by disturbed emotion processing. Repetitive transcranial magnetic stimulation, and its development intermittent theta- burst stimulation (iTBS), induces brain network changes and is an emerging treatment alternative for depression. In this sham- controlled study, we aimed at studying the effects of iTBS on emotion anticipation and processing in depression.</div></div><div><h3>Methods</h3><div>42 patients with depression were allocated to receive active or sham iTBS treatment. Before treatment (baseline) and four weeks after baseline (follow- up), participants underwent functional magnetic resonance imaging (fMRI) scanning with simultaneous recordings of skin conductance responses (SCR). During scanning, participants were presented to an emotion anticipation and processing paradigm. Behavioral data (symptom ratings and ratings of emotional stimuli) were also collected.</div></div><div><h3>Results</h3><div>There were no differences in behavioral, skin conductance or neural activity after active, compared with sham, treatment. However, across groups, SCRs to positive anticipation increased and SCRs to negative processing decreased at follow- up. Additionally, amygdala and right insula reactivity to negative processing, and right amygdala reactivity to positive processing, decreased at follow- up. Increased ACC activity after active treatment to positive anticipation and processing was correlated with decreased anhedonia symptoms.</div></div><div><h3>Conclusions</h3><div>Active, compared with sham, iTBS treatment does not affect behavioral, skin conductance or neural activity to emotion anticipation and processing in depression. However, across treatment groups, changes occur with time, perhaps reflecting normalization processes or partial treatment effect of sham iTBS. The ACC seems to be involved in the treatment mechanism of iTBS.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111606"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907274","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":"Complex relationship between endocannabinoids, fatty acid amide hydrolase, and stress reactivity in human intrusive memories of analogue trauma","authors":"Madeline A. Jarvis ,&nbsp;Allison Matthews ,&nbsp;Ken Chia Min Hsu ,&nbsp;Emma Nicholson ,&nbsp;Khalisa Amir Hamzah ,&nbsp;Natalie Turner ,&nbsp;Daniel V. Zuj ,&nbsp;David Nichols ,&nbsp;Kim Felmingham ,&nbsp;Luke J. Ney","doi":"10.1016/j.pnpbp.2026.111610","DOIUrl":"10.1016/j.pnpbp.2026.111610","url":null,"abstract":"<div><div>The endocannabinoid system has been shown to be involved in posttraumatic stress disorder-like behaviours in animal and human subjects. However, to date no studies have tested the relationship between blood markers of endocannabinoid signalling and intrusive memory development in humans. Across two studies, we tested the relationship between endocannabinoid genotypes, blood markers of endocannabinoids AEA and 2-AG, and intrusive memories of violent imagery and film clips. In study 1, we found a significant effect of rs324420 genotype on explicit memory recall, with A allele carriers (indicative of higher AEA) recalling fewer negative memories. Post-task AEA was negatively associated with explicit recall but not intrusive memories, though post-task AEA and 2-AG did interact with rs324420 to predict intrusive memory frequency. In study 2, stress induced changes in AEA but not 2-AG were negatively associated with intrusive memory frequency. In summary, we found evidence that AEA is involved in explicit and intrusive memories of negative stimuli. Evidence from both studies suggests that lower AEA is associated with higher explicit and intrusive memories. These findings support animal literature and have implications for targeted treatments for negative memory symptomology in posttraumatic stress disorder.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111610"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977470","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":"Cross-trial prediction of treatment response to transcranial direct current stimulation in patients with major depressive disorder","authors":"Gerrit Burkhardt ,&nbsp;Stephan Goerigk ,&nbsp;Lucia Bulubas ,&nbsp;Esther Dechantsreiter ,&nbsp;Daniel Keeser ,&nbsp;Ulrike Vogelmann ,&nbsp;Katharina von Wartensleben ,&nbsp;Johannes Wolf ,&nbsp;Christian Plewnia ,&nbsp;Andreas Fallgatter ,&nbsp;Berthold Langguth ,&nbsp;Claus Normann ,&nbsp;Lukas Frase ,&nbsp;Peter Zwanzger ,&nbsp;Thomas Kammer ,&nbsp;Carlos Schönfeldt-Lecuona ,&nbsp;Daniel Kamp ,&nbsp;Malek Bajbouj ,&nbsp;Nikolaos Koutsouleris ,&nbsp;Andre R. Brunoni ,&nbsp;Frank Padberg","doi":"10.1016/j.pnpbp.2025.111600","DOIUrl":"10.1016/j.pnpbp.2025.111600","url":null,"abstract":"<div><div>Machine-learning (ML) classification may offer a promising approach for treatment response prediction in patients with major depressive disorder (MDD) undergoing non-invasive brain stimulation. This analysis aims to develop and validate such classification models based on easily attainable sociodemographic and clinical information across two randomized controlled trials on transcranial direct-current stimulation (tDCS) in MDD. Using data from 246 patients with MDD from the randomized-controlled DepressionDC and ELECT-TDCS trials, we employed an ensemble machine learning strategy to predict treatment response to either active tDCS or sham tDCS/placebo, defined as ≥50 % reduction in the Montgomery-Åsberg Depression Rating Scale at 6 weeks. Separate models for active tDCS and sham/placebo were developed in each trial and evaluated for external validity across trials and for treatment specificity across modalities. In the DepressionDC trial, models achieved a balanced accuracy of 63.5 % for active tDCS and 62.5 % for sham tDCS in predicting treatment responders. Baseline self-rated depression was consistently ranked as the most informative feature. However, response prediction in the ELECT-TDCS trial and across trials was not successful. Our findings suggest that ML models based on easily attainable sociodemographic and clinical variables can yield modest improvements in predicting individual tDCS response, but performance remains insufficient for clinical application and will require refinement and external validation in larger, more comprehensively phenotyped cohorts.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111600"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145851584","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}