Biological psychiatry global open science最新文献

{"title":"Has Deep Brain Stimulation Shown Its Full Potential in Treatment-Resistant Depression? A Scoping Review","authors":"Liene Puke ,&nbsp;Joelle Rosselet Amoussou ,&nbsp;Armin von Gunten ,&nbsp;Julien Elowe","doi":"10.1016/j.bpsgos.2025.100682","DOIUrl":"10.1016/j.bpsgos.2025.100682","url":null,"abstract":"<div><div>Major depressive disorder is increasingly conceptualized as a networkopathy involving dysfunction across brain networks rather than isolated regions. This perspective has supported the use of deep brain stimulation (DBS) in treatment-resistant depression (TRD), where conventional therapies have failed. In this scoping review, we examined peer-reviewed studies on bilateral DBS for TRD, with a focus on the relationship between stimulation targets, conceptual frameworks of depression, and clinical outcome measures. A comprehensive literature search was conducted in September 2024 across 6 bibliographic databases, supplemented by citation tracking strategies to identify additional relevant studies. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we screened and selected studies based on predefined eligibility criteria. The review identified significant variability in how TRD is defined, which brain targets are selected, and how these are associated with specific symptom dimensions. Anatomical targets varied widely, reflecting differing neurobiological rationales. While most studies assessed symptom severity using standardized scales such as the Montgomery–Åsberg Depression Rating Scale or Hamilton Depression Rating Scale, a minority of studies (8 of 48 [16.7%]) did not specify which symptom dimensions were expected to respond to DBS. Despite methodological heterogeneity, DBS appears promising for symptom alleviation in TRD. However, its clinical benefits remain to be fully established. The review highlights the need for greater standardization, including consistent definitions of TRD, clear symptom mapping, and improved integration of patient-reported and functional outcomes. Although most existing studies focus on bilateral stimulation, future work should also explore unilateral and multitarget approaches to advance toward more personalized neuromodulation strategies.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 3","pages":"Article 100682"},"PeriodicalIF":3.7,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disorder-Specific Genetic Effects Drive the Associations Between Psychopathology and Cognitive Functioning","authors":"Wangjingyi Liao ,&nbsp;Engin Keser ,&nbsp;Andrea Allegrini ,&nbsp;Kaili Rimfeld ,&nbsp;Robert Plomin ,&nbsp;Margherita Malanchini","doi":"10.1016/j.bpsgos.2025.100680","DOIUrl":"10.1016/j.bpsgos.2025.100680","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive functioning is a critical dimension of psychopathology that remains underinvestigated. Because cognitive deficits often transcend diagnostic boundaries, it has been challenging to delineate specific relationships between psychiatric disorders and cognitive functioning. Genetic research offers novel, powerful tools to disentangle shared (transdiagnostic) from disorder-specific effects, thereby opening new avenues for understanding how psychopathology relates to cognition.</div></div><div><h3>Methods</h3><div>We used genomic structural equation modeling to identify transdiagnostic and disorder-specific genetic risk. We derived polygenic scores in a longitudinal twin sample (<em>N</em> = 7764) to examine associations between genetic risk for psychopathology and domains of cognitive functioning across development.</div></div><div><h3>Results</h3><div>The results showed that relationships between psychopathology and cognition are primarily driven by disorder-specific genetic risk rather than by transdiagnostic factors. Associations differed across disorders and cognitive domains. Within-family analyses indicated that associations between genetic risk for psychopathology and cognition operated through distinct pathways. While for some disorders (e.g., attention-deficit/hyperactivity disorder), the effects could be attributed to confounding by environmental differences between nuclear families, for others (e.g., autism spectrum disorder), effects were robust to environmental confounding.</div></div><div><h3>Conclusions</h3><div>In contrast to psychiatric symptoms, which are most effectively predicted by transdiagnostic genetic risk, our findings highlight the need to consider disorder-specific genetic effects when examining associations between psychopathology and cognition. Focusing solely on transdiagnostic risk is unlikely to capture the full complexity of these relationships or enhance our understanding of the distinct cognitive profiles associated with psychopathology.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100680"},"PeriodicalIF":3.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motivational Significance of Control Failures as a Window on Risk for Problematic Alcohol Involvement","authors":"Bruce D. Bartholow","doi":"10.1016/j.bpsgos.2025.100658","DOIUrl":"10.1016/j.bpsgos.2025.100658","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100658"},"PeriodicalIF":3.7,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theta Oscillations Assessed From a Passive Auditory Oddball Paradigm in Individuals at Clinical High-Risk for Psychosis and Healthy Control Individuals: Associations with Clinical Outcomes and Mismatch Negativity","authors":"Jessica P.Y. Hua ,&nbsp;Brian J. Roach ,&nbsp;Holly K. Hamilton ,&nbsp;Peter M. Bachman ,&nbsp;Aysenil Belger ,&nbsp;Ricardo E. Carrión ,&nbsp;Erica Duncan ,&nbsp;Jason K. Johannesen ,&nbsp;Gregory A. Light ,&nbsp;Margaret Niznikiewicz ,&nbsp;Jean Addington ,&nbsp;Carrie E. Bearden ,&nbsp;Kristin S. Cadenhead ,&nbsp;Diana O. Perkins ,&nbsp;William S. Stone ,&nbsp;Elaine F. Walker ,&nbsp;Scott W. Woods ,&nbsp;Tyrone D. Cannon ,&nbsp;Daniel H. Mathalon","doi":"10.1016/j.bpsgos.2025.100664","DOIUrl":"10.1016/j.bpsgos.2025.100664","url":null,"abstract":"<div><h3>Background</h3><div>Reduced mismatch negativity (MMN) is a widely replicated schizophrenia biomarker. Time-frequency analyses suggest that deficient phase synchrony and/or power of electroencephalography (EEG) event-related oscillations, especially theta, contribute to MMN deficits in schizophrenia. Whether theta oscillations assessed from a passive auditory oddball paradigm are abnormal in clinical high-risk for psychosis (CHR-P) individuals and whether these oscillations predict CHR-P clinical outcomes remain unclear. These questions were addressed using data from NAPLS2 (North American Prodrome Longitudinal Study 2).</div></div><div><h3>Methods</h3><div>EEG was recorded from 77 CHR-P individuals who converted to psychosis (CHR-Cs), 238 CHR-P nonconverters (CHR-NCs) who completed a 24-month follow-up, and 241 healthy control (HC) individuals. Theta oscillations elicited by standard and deviant tones were calculated. Theta (4–6 Hz) intertrial phase coherence (ITC) and total power were compared between groups and evaluated as predictors of time to psychosis conversion in the full CHR-P sample. Furthermore, analyses of covariance were used to assess whether theta deficits persisted while covarying for MMN.</div></div><div><h3>Results</h3><div>The CHR-C group, relative to the HC and CHR-NC groups, had reduced theta ITC for standards and deviants (<em>p</em>s &lt; .029) and reduced total power for standards and deviants relative to the HC group (<em>p</em> = .021). Reduced theta ITC for standards and deviants predicted earlier psychosis conversion. The previously reported deficit in MMN amplitude in the CHR-C group was no longer significant after accounting for theta ITC or total power averaged across stimuli (<em>p</em>s &gt; .187), but this was not true for theta ITC or total power deviant-standard difference scores (<em>p</em>s &lt; .039).</div></div><div><h3>Conclusions</h3><div>These results implicate abnormalities in microcircuit generators of theta oscillations in CHR-P individuals at highest risk.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100664"},"PeriodicalIF":3.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the Poles: What the Transcranial Magnetic Stimulation Evidence Tells Us About Bipolar Depression","authors":"Véronique Desbeaumes Jodoin","doi":"10.1016/j.bpsgos.2025.100657","DOIUrl":"10.1016/j.bpsgos.2025.100657","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100657"},"PeriodicalIF":3.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moving Beyond Self-Report in Characterizing Drug Addiction: Using Drug-Biased Behavior to Predict Treatment Completion and Dropout in Heroin-Primary, Medication-Maintained Opioid Use Disorder","authors":"Natalie McClain ,&nbsp;Ahmet O. Ceceli ,&nbsp;Kathryn Drury ,&nbsp;Greg Kronberg ,&nbsp;Eric L. Garland ,&nbsp;Nelly Alia-Klein ,&nbsp;Rita Z. Goldstein","doi":"10.1016/j.bpsgos.2025.100667","DOIUrl":"10.1016/j.bpsgos.2025.100667","url":null,"abstract":"<div><h3>Background</h3><div>Drug addiction is accompanied by enhanced salience attributed to drug over nondrug cues. This bias can be objectively measured and is reliable but underutilized in informing clinical end points, where self-report measures are most commonly used, with limited success.</div></div><div><h3>Methods</h3><div>We investigated whether behavioral picture choice (laboratory-simulated measure of drug seeking) and verbal fluency (drug and nondrug words generated) revealed drug-biased processing in 59 individuals with opioid use disorder (iOUDs) compared with 29 healthy control (HC) individuals; assessed twice, we also inspected the test-retest reliability of these tools. All iOUDs were heroin primary, abstinent (160.58 ± 188.18 days), and stabilized on medication for OUD at an inpatient treatment facility at baseline. Then, we tested whether, compared with self-report measures, these drug-biased behavioral measures could better predict prospective outcome measures in the iOUDs, i.e., study treatment completion as further validated using dropout from inpatient treatment.</div></div><div><h3>Results</h3><div>Results revealed that the iOUDs exhibited higher drug choice (<em>p</em>s &lt; .036) and drug fluency (<em>p</em> = .008) compared with the HC individuals; task performance demonstrated the strong test-retest reliability of these measures. Controlling for cognitive demographics, the self-report drug-use severity and craving measures did not show significant associations with study treatment completion (|β| &lt; 0.47, <em>p</em>s &gt; .290), but drug-biased choice did (β = −0.75, <em>p</em> = .036; model comparison: Δ<em>R</em>² = 0.10, <em>p</em> = .027). Importantly, these results were validated using inpatient treatment dropout as the outcome (drug-biased choice: β = 0.81, <em>p</em> = .049; model comparison: Δ<em>R</em>² = 0.11, <em>p</em> = .035).</div></div><div><h3>Conclusions</h3><div>This study is the first to demonstrate reliable drug-biased choice and fluency in iOUDs. Compared with traditional self-reported drug-use and craving measures, the objective drug-biased cognitive behavioral measure was a significant predictor of treatment-related outcomes.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100667"},"PeriodicalIF":3.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral and Prefrontal Circuit Deficits in a Newly Developed Setbp1 Haploinsufficiency Mouse Model","authors":"MacKenzie A. Howard,&nbsp;Mendee A. Geist,&nbsp;Gregory J. Ordemann,&nbsp;Alena Kizimenko,&nbsp;Dominic M. Balice,&nbsp;F. Isaac Guillén,&nbsp;Emmanuella Bassey,&nbsp;Polina Lyuboslavsky,&nbsp;Audrey C. Brumback","doi":"10.1016/j.bpsgos.2025.100666","DOIUrl":"10.1016/j.bpsgos.2025.100666","url":null,"abstract":"<div><h3>Background</h3><div>SET binding protein 1 (<em>SETBP1</em>) regulates the cell cycle, gene transcription, and other vital intracellular processes. <em>SETBP1</em> loss-of-function variants cause the neurodevelopmental disorders <em>SETBP1</em>-haploinsufficiency disorder and <em>SETBP1</em>-related disorders (<em>SETBP1</em>-HD and <em>SETBP1</em>-RD), which are characterized by attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability/developmental delay, and other neurological disabilities. Here we sought to characterize behavioral, physiological, and cell morphology phenotypes of a newly developed mouse model of <em>SETBP1</em>-HD.</div></div><div><h3>Methods</h3><div>We used open field, 3-chamber, and Y-maze behavioral tests to measure activity, social interest, and spatial learning, respectively. We used whole-cell current clamp recordings from medial prefrontal cortex (mPFC) layer-5 extratelencephalic projection neurons in ex vivo slices to measure cell intrinsic and spike properties. We used morphological reconstruction to measure dendritic arborization in recorded neurons.</div></div><div><h3>Results</h3><div><em>Setbp1</em>^{<em>+/−</em>} mice exhibited hyperactivity, decreased social interest, and increased olfactory exploration in behavioral tests. Ex vivo electrophysiology revealed hypoexcitability in layer-5 extratelencephalic projection neurons in the mPFC. Morphological reconstruction revealed changes to the way branch points and length are distributed within the apical dendritic arbor of these prefrontal pyramidal neurons without changes in overall length or branch number.</div></div><div><h3>Conclusions</h3><div>These data show that <em>Setbp1</em>^{<em>+/−</em>} mice exhibit phenotypes parallel to the ADHD and ASD that are common in patients with <em>SETBP1</em>-HD. Additionally, we identified cellular changes to a key control center for attention, social behavior, and cognitive function that may elucidate the mechanism that underlies the neuropsychiatric disabilities of this disorder.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100666"},"PeriodicalIF":3.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"μ Opioid Modulation of Sensorimotor Functional Connectivity in Autism: Insights From a Pharmacological Neuroimaging Investigation Using Tianeptine","authors":"Mihail Dimitrov ,&nbsp;Nichol M.L. Wong ,&nbsp;Sydney Leaman ,&nbsp;Lucas G.S. França ,&nbsp;Ioannis Valasakis ,&nbsp;Jason He ,&nbsp;David J. Lythgoe ,&nbsp;James L. Findon ,&nbsp;Robert H. Wichers ,&nbsp;Vladimira Stoencheva ,&nbsp;Dene M. Robertson ,&nbsp;Sarah Blainey ,&nbsp;Glynis Ivin ,&nbsp;Štefan Holiga ,&nbsp;Mark D. Tricklebank ,&nbsp;Dafnis Batalle ,&nbsp;Declan G.M. Murphy ,&nbsp;Gráinne M. McAlonan ,&nbsp;Eileen Daly","doi":"10.1016/j.bpsgos.2025.100663","DOIUrl":"10.1016/j.bpsgos.2025.100663","url":null,"abstract":"<div><h3>Background</h3><div>Reproducible patterns of atypical functional connectivity (FC) of sensorimotor and higher-order networks have previously been identified in the autistic brain. However, the neurosignaling pathways underpinning these differences remain unclear. The μ opioid system is involved in sensory processing as well as social and reward behaviors and has been implicated in autism, suggesting a potential role in shaping the autistic brain. Therefore, we tested the hypothesis that there is atypical involvement of the μ opioid system in these networks in autism.</div></div><div><h3>Methods</h3><div>We used a placebo-controlled, double-blind, randomized, crossover study design to compare the effects of a single dose of the μ opioid receptor agonist tianeptine in autistic (<em>n</em> = 20) and nonautistic (<em>n</em> = 21) males on FC of sensorimotor and frontoparietal networks.</div></div><div><h3>Results</h3><div>We found that tianeptine increased FC of a sensorimotor network previously characterized by atypically low FC in autism. The connectivity of the frontoparietal network was not significantly shifted.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that μ opioid neurosignaling may contribute to functional brain differences in the sensorimotor network in autism. Given that sensorimotor system alterations are thought to be central to autism and contribute to other core autistic features, as well as adaptability and mental health, further research is warranted to explore the translational potential of μ opioid modulation in autism.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100663"},"PeriodicalIF":3.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Brain Activity Associated With Intermittent Rhythmic Delta/Theta Activity: A Transdiagnostic Electroencephalography–Functional Magnetic Resonance Imaging Resting-State Study","authors":"Bernd Feige ,&nbsp;Katharina von Zedtwitz ,&nbsp;Isabelle Matteit ,&nbsp;Andrea Schlump ,&nbsp;Volker A. Coenen ,&nbsp;Kathrin Nickel ,&nbsp;Kimon Runge ,&nbsp;Harald Prüss ,&nbsp;Alexander Rau ,&nbsp;Marco Reisert ,&nbsp;Swantje Matthies ,&nbsp;Katharina Domschke ,&nbsp;Simon J. Maier ,&nbsp;Ludger Tebartz van Elst ,&nbsp;Dominique Endres","doi":"10.1016/j.bpsgos.2025.100661","DOIUrl":"10.1016/j.bpsgos.2025.100661","url":null,"abstract":"<div><h3>Background</h3><div>Intermittent rhythmic delta/theta activity (IRDA/IRTA) detected via electroencephalography (EEG) has been implicated in the pathophysiology of neuropsychiatric illnesses. Therefore, a combined EEG and functional magnetic resonance imaging (fMRI) approach was applied in a transdiagnostic group of patients with different causalities, i.e., autoimmune-mediated (in suspected autoimmune psychiatric syndromes [APS]) and primary psychiatric (borderline personality disorder [BPD]) causalities, as well as in healthy control (HC) participants, to characterize the brain regions functionally correlated with IRDA/IRTA.</div></div><div><h3>Methods</h3><div>Overall, 135 EEG-fMRI datasets met the quality criteria, including 33 patients with suspected APS, 59 cases with BPD, and 43 HC participants. fMRI data were obtained using ultrafast MR encephalography and analyzed using AFNI. IRDA/IRTA events were separated from artifacts using independent component analysis and detected algorithmically. Brain regions (clusters) significantly correlated with IRDA/IRTA were first determined in all participants. Clusters occurring across all groups were classified as consensus areas. The groups were also analyzed individually, adding disease- or disorder-specific clusters not overlapping with the consensus areas.</div></div><div><h3>Results</h3><div>Eleven consensus areas were identified across the 3 groups: 5 of them showed increased activity (Brodmann area [BA] 43-right [r], BA 2-left [l], BA 4-r, BA 18-r, BA 26/29/30-r), and 6 had reduced activity (BA 39-l, BA 10-l, BA 23-l, BA 19-l, BA 10-r, BA 18-l). The APS group showed 5 additional clusters, all with reduced activity (BAs 39-r, 1/3-r, 8-r, 4-l, 21-r). The BPD group showed one further cluster with increased activity (BA 17-l).</div></div><div><h3>Conclusions</h3><div>In this study, IRDA/IRTA-related brain activity changes across the groups were identified, with excitatory brain activity especially in fronto-centro-temporal brain areas with similarities to the salience network. Additional disease- or disorder-specific changes were discovered in APS and BPD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100661"},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-Based Electroencephalography Phenotyping Uncovers Distinct Neurocomputational Mechanisms Underlying Learning Impairments Across Psychopathologies","authors":"Nadja R. Ging-Jehli ,&nbsp;Rachel Rac-Lubashevsky ,&nbsp;Krishn Bera ,&nbsp;Megan A. Boudewyn ,&nbsp;Cameron S. Carter ,&nbsp;Molly A. Erickson ,&nbsp;James M. Gold ,&nbsp;Steven J. Luck ,&nbsp;J. Daniel Ragland ,&nbsp;Andrew P. Yonelinas ,&nbsp;Angus W. MacDonald III ,&nbsp;Deanna M. Barch ,&nbsp;Michael J. Frank","doi":"10.1016/j.bpsgos.2025.100660","DOIUrl":"10.1016/j.bpsgos.2025.100660","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD), bipolar disorder (BP), and schizophrenia (SCZ) involve learning impairments with poorly understood mechanisms. Understanding both the similarities and differences in these mechanisms is important to guide the development of new, targeted interventions.</div></div><div><h3>Methods</h3><div>A total of 255 participants diagnosed with MDD (<em>n</em> = 54), BP (<em>n</em> = 47), or SCZ (<em>n</em> = 67) or without any clinical diagnoses (control [CTRL]) (<em>n</em> = 87) performed an associative learning task. Computational modeling quantified the mechanistic interplay between working memory (WM) and reinforcement learning (RL). The latent RL and WM signatures in the electroencephalography (EEG) dynamics showed shared and distinct neurocognitive mechanisms underlying learning.</div></div><div><h3>Results</h3><div>All clinical groups showed learning impairments at the behavioral level. Model-based EEG analyses linked these impairments to distinct patterns in the dynamic interplay between latent RL and WM mechanisms, contrasting with the typical patterns observed in the CTRL group. SCZ was characterized by reduced neural markers of WM, weakening the cooperative influence of WM onto RL (reduced WM recruitment), and reduced integration of negative feedback. Conversely, MDD was characterized by reduced reciprocal influence of RL onto WM, reducing the tendency to upregulate WM contribution with reward history (impaired WM management). Finally, BP was characterized by deficits in both WM and RL recruitment, along with higher WM decay.</div></div><div><h3>Conclusions</h3><div>Behavioral learning impairments that seem similar across clinical groups can be linked to distinct neurocognitive mechanisms via integrative neurocomputational modeling. Our approach provides insights into the interplay of underlying learning mechanisms and how they manifest differently across psychopathologies.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100660"},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}