Pub Date : 2025-12-20Epub Date: 2025-10-24DOI: 10.1016/j.pnpbp.2025.111530
Issa Wassouf , Nicolas Vibert , Julien Dampuré , Damien Doolub , Ghina Harika-Germaneau , Nicolas Langbour , Nematollah Jaafari
Patients suffering from obsessive-compulsive disorder (OCD) show an attentional bias towards pathology-related words. Electroencephalographic cognitive potentials were used to investigate how patients responded to words related to their obsessions and compulsions. Forty OCD patients with various levels of severity and treatment-resistance were included to assess links between word-evoked potentials and patients' clinical variables, and compared with 40 control participants. The P200 component evoked by both neutral and pathology-related words was greater in patients than in controls, suggesting that patients were more attentive overall. In the N400 time window, pathology-related words evoked less negative potentials than neutral words in OCD patients, suggesting that pathology-related words were particularly familiar to them and permanently pre-activated in their mental lexicon. Finally, correlations were detected between pathology severity and the profile of word-evoked potentials in the N400 time window, and between the patients' treatment resistance and the amplitude of late word-evoked positive potentials (P600).
{"title":"Cognitive electroencephalographic potentials evoked by words as markers of the severity of the pathology and resistance to treatment in obsessive-compulsive disorder.","authors":"Issa Wassouf , Nicolas Vibert , Julien Dampuré , Damien Doolub , Ghina Harika-Germaneau , Nicolas Langbour , Nematollah Jaafari","doi":"10.1016/j.pnpbp.2025.111530","DOIUrl":"10.1016/j.pnpbp.2025.111530","url":null,"abstract":"<div><div>Patients suffering from obsessive-compulsive disorder (OCD) show an attentional bias towards pathology-related words. Electroencephalographic cognitive potentials were used to investigate how patients responded to words related to their obsessions and compulsions. Forty OCD patients with various levels of severity and treatment-resistance were included to assess links between word-evoked potentials and patients' clinical variables, and compared with 40 control participants. The P200 component evoked by both neutral and pathology-related words was greater in patients than in controls, suggesting that patients were more attentive overall. In the N400 time window, pathology-related words evoked less negative potentials than neutral words in OCD patients, suggesting that pathology-related words were particularly familiar to them and permanently pre-activated in their mental lexicon. Finally, correlations were detected between pathology severity and the profile of word-evoked potentials in the N400 time window, and between the patients' treatment resistance and the amplitude of late word-evoked positive potentials (P600).</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111530"},"PeriodicalIF":3.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370484","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}
Pub Date : 2025-12-20Epub Date: 2025-11-11DOI: 10.1016/j.pnpbp.2025.111560
Yanan Su , Guangfei Li , Shanmei Wang , Dongmei Hao , Clara S. Li , Yiyao Ye-Lin , Xiaolin Wang , Ruolin Zhang , Lin Yang , Chiang-Shan R. Li
Background
Preterm birth involves structural brain changes and increases the risk of neurodevelopmental disorders, including social cognitive dysfunction as implicated in autism spectrum disorder (ASD). However, it remains unclear whether or how volumetric brain changes may impact the risk of social cognitive dysfunction in toddlers of preterm birth.
Methods
We curated data of 569 toddlers approximately 18 months of age, including 76 with preterm (PB) and 493 with term (TB) birth, from the developing Human Connectome Project. We processed the imaging data, collected at birth, and investigated group differences in gray matter volume (GMV) of the brain and eye-tracking data collected at 18 months as well as the interrelationships amongst birth age, GMVs, and eye-tracking markers of ASD.
Results
In a covariance analysis with age at scan, total intracranial volume, sex, and number of embryos at gestation as covariates, PB demonstrated higher GMV in bilateral superior temporal gyri (STG). Right STG GMV's were negatively correlated with birth age and positively with the proportion of looking at faces and mouths in PB, but not in TB. Further, path analyses suggested right STG GMV at birth as a marker of preferential face and mouth viewing in PB at 18 months.
Conclusions
The findings associate earlier birth age with atypical volumetrics of the right STG and eye gazing patterns in preterm children at 18 months. Longitudinal studies are needed to examine whether these neural and behavioral markers may reflect risks of social cognitive dysfunction in children with neurodevelopmental disorders, including ASD.
{"title":"Gray matter volumes of the superior temporal gyrus link preterm birth and developmentally disordered eye gazing patterns in toddlers at eighteen months","authors":"Yanan Su , Guangfei Li , Shanmei Wang , Dongmei Hao , Clara S. Li , Yiyao Ye-Lin , Xiaolin Wang , Ruolin Zhang , Lin Yang , Chiang-Shan R. Li","doi":"10.1016/j.pnpbp.2025.111560","DOIUrl":"10.1016/j.pnpbp.2025.111560","url":null,"abstract":"<div><h3>Background</h3><div>Preterm birth involves structural brain changes and increases the risk of neurodevelopmental disorders, including social cognitive dysfunction as implicated in autism spectrum disorder (ASD). However, it remains unclear whether or how volumetric brain changes may impact the risk of social cognitive dysfunction in toddlers of preterm birth.</div></div><div><h3>Methods</h3><div>We curated data of 569 toddlers approximately 18 months of age, including 76 with preterm (PB) and 493 with term (TB) birth, from the developing Human Connectome Project. We processed the imaging data, collected at birth, and investigated group differences in gray matter volume (GMV) of the brain and eye-tracking data collected at 18 months as well as the interrelationships amongst birth age, GMVs, and eye-tracking markers of ASD.</div></div><div><h3>Results</h3><div>In a covariance analysis with age at scan, total intracranial volume, sex, and number of embryos at gestation as covariates, PB demonstrated higher GMV in bilateral superior temporal gyri (STG). Right STG GMV's were negatively correlated with birth age and positively with the proportion of looking at faces and mouths in PB, but not in TB. Further, path analyses suggested right STG GMV at birth as a marker of preferential face and mouth viewing in PB at 18 months.</div></div><div><h3>Conclusions</h3><div>The findings associate earlier birth age with atypical volumetrics of the right STG and eye gazing patterns in preterm children at 18 months. Longitudinal studies are needed to examine whether these neural and behavioral markers may reflect risks of social cognitive dysfunction in children with neurodevelopmental disorders, including ASD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111560"},"PeriodicalIF":3.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514507","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}
Pub Date : 2025-12-20Epub Date: 2025-11-06DOI: 10.1016/j.pnpbp.2025.111557
Joël Macoir , Fenise Selin Karalı , Samet Tosun
{"title":"Corrigendum to Leveraging Language and Cognitive Data for PPA Subtyping: A Systematic Review of AI-Based Approaches’ [Progress in Neuropsychopharmacology & Biological Psychiatry 142 (2025) 1–11/ 111514]","authors":"Joël Macoir , Fenise Selin Karalı , Samet Tosun","doi":"10.1016/j.pnpbp.2025.111557","DOIUrl":"10.1016/j.pnpbp.2025.111557","url":null,"abstract":"","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111557"},"PeriodicalIF":3.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472273","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}
Pub Date : 2025-12-20Epub Date: 2025-12-05DOI: 10.1016/j.pnpbp.2025.111569
Olga Yu. Fedorenko , Evgeniya G. Poltavskaya , Elena G. Kornetova , Maxim B. Freidin , Anna V. Bocharova , Anastasiya S. Boiko , Vadim A. Stepanov , Nikolay A. Bokhan , Svetlana A. Ivanova , Kuzma Strelnikov
Dopamine receptor inhibition underlies both the therapeutic and adverse effects of antipsychotics, but the mechanisms modulating these effects in patients with schizophrenia remain incompletely understood. Hyperprolactinemia (HPRL), a direct consequence of D2 dopamine receptor blockade, provides a unique clinical model to investigate how genetic variation in glutamatergic signaling influences the downstream effects of dopaminergic disruption. We hypothesized that polymorphisms in GRIN2A and GRIN2B, encoding NMDA glutamate receptor subunits, modify the neuroendocrine consequences of dopamine receptor inhibition. By studying antipsychotic-induced HPRL, we aimed to demonstrate that NMDA receptor genetic variants shape the functional outcomes of dopaminergic perturbation.
In a cross-sectional analysis of 536 schizophrenia patients, we measured prolactin levels—a sensitive biomarker of D2 receptor inhibition—and genotyped 23 GRIN2A/GRIN2B variants. Logistic regression assessed gene-drug relationships while controlling for clinical covariates.
NMDA receptor genetic variation significantly influenced susceptibility to HPRL, with distinct effects observed between antipsychotic classes with the highest effect for the typical antipsychotics, which are D2 dopamine receptor antagonists. This demonstrates that glutamatergic genotypes predict interindividual variability in the neuroendocrine response to dopamine receptor blockade.
These results provide the first clinical evidence in support of the hypothesis that NMDA receptor polymorphisms modulate the effects of dopaminergic inhibition in schizophrenia. Beyond HPRL, this dopamine-glutamate relationships paradigm may extend to other clinical outcomes of antipsychotic treatment, including therapeutic response and neurological side effects. Our findings underscore the importance of glutamatergic pathways in determining the functional consequences of dopamine receptor targeting.
{"title":"NMDA glutamate receptor polymorphisms modulate antipsychotic-induced hyperprolactinemia in schizophrenia","authors":"Olga Yu. Fedorenko , Evgeniya G. Poltavskaya , Elena G. Kornetova , Maxim B. Freidin , Anna V. Bocharova , Anastasiya S. Boiko , Vadim A. Stepanov , Nikolay A. Bokhan , Svetlana A. Ivanova , Kuzma Strelnikov","doi":"10.1016/j.pnpbp.2025.111569","DOIUrl":"10.1016/j.pnpbp.2025.111569","url":null,"abstract":"<div><div>Dopamine receptor inhibition underlies both the therapeutic and adverse effects of antipsychotics, but the mechanisms modulating these effects in patients with schizophrenia remain incompletely understood. Hyperprolactinemia (HPRL), a direct consequence of D2 dopamine receptor blockade, provides a unique clinical model to investigate how genetic variation in glutamatergic signaling influences the downstream effects of dopaminergic disruption. We hypothesized that polymorphisms in <em>GRIN2A</em> and <em>GRIN2B</em>, encoding NMDA glutamate receptor subunits, modify the neuroendocrine consequences of dopamine receptor inhibition. By studying antipsychotic-induced HPRL, we aimed to demonstrate that NMDA receptor genetic variants shape the functional outcomes of dopaminergic perturbation.</div><div>In a cross-sectional analysis of 536 schizophrenia patients, we measured prolactin levels—a sensitive biomarker of D2 receptor inhibition—and genotyped 23 <em>GRIN2A</em>/<em>GRIN2B</em> variants. Logistic regression assessed gene-drug relationships while controlling for clinical covariates.</div><div>NMDA receptor genetic variation significantly influenced susceptibility to HPRL, with distinct effects observed between antipsychotic classes with the highest effect for the typical antipsychotics, which are D2 dopamine receptor antagonists. This demonstrates that glutamatergic genotypes predict interindividual variability in the neuroendocrine response to dopamine receptor blockade.</div><div>These results provide the first clinical evidence in support of the hypothesis that NMDA receptor polymorphisms modulate the effects of dopaminergic inhibition in schizophrenia. Beyond HPRL, this dopamine-glutamate relationships paradigm may extend to other clinical outcomes of antipsychotic treatment, including therapeutic response and neurological side effects. Our findings underscore the importance of glutamatergic pathways in determining the functional consequences of dopamine receptor targeting.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111569"},"PeriodicalIF":3.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684522","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}
Pub Date : 2025-12-20Epub Date: 2025-11-27DOI: 10.1016/j.pnpbp.2025.111568
Miroslav N. Nenov , Lisa A. Briand
Nitric oxide synthase (NOS) plays a role in substance use related neurotoxicity and addictive phenotypes. Inhibition of nitric oxide (NO) production can prevent negative phenotypes associated with drugs intake. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. ADMA levels are regulated by dimethylarginine dimethylaminohydrolase type 1 (DDAH1). Numerous evidence suggests that drugs of abuse can increase DDAH1 levels, leading to reduction of ADMA levels, and in turn, causing neurotoxicity associated with NO overproduction. Yet, this data is sparse, and very little mechanistic evidence exists. Here, we review the literature on the impact of substances of abuse and social stress, as a condition implicated in addictive phenotypes, on DDAH1 levels in the brain. This review highlights five things: first, psychostimulants can increase brain DDAH1 levels and DDAH1-ADMA-NOS signaling axis could underlay neurotoxicity and addictive behaviors driven by psychostimulants. Second, opioids can also significantly increase brain DDAH1 levels, yet currently no mechanistic studies exist to determine the consequences of that increase. Three, the nicotine and alcohol studies are inconclusive as results are often complicated with comorbidities associated with cardiovascular impairments, liver toxicity and aging. Four, studies on cannabinoids are insufficient, more data is needed. Finally, social stress affects DDAH1 levels and anti-depressants can reverse this effect, but mechanistic data is lacking. In conclusion, proteomic, metabolomic and functional studies suggest that DDAH1 may play a role in addiction and conditions related to social stress. Further investigation is necessary to elucidate the specific function of DDAH1 in addiction and social stress phenotypes.
{"title":"Involvement of dimethylarginine dimethylaminohydrolase type 1 (DDAH1) in addiction and social stress phenotypes: Insights from proteomic, metabolomic and functional studies","authors":"Miroslav N. Nenov , Lisa A. Briand","doi":"10.1016/j.pnpbp.2025.111568","DOIUrl":"10.1016/j.pnpbp.2025.111568","url":null,"abstract":"<div><div>Nitric oxide synthase (NOS) plays a role in substance use related neurotoxicity and addictive phenotypes. Inhibition of nitric oxide (NO) production can prevent negative phenotypes associated with drugs intake. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. ADMA levels are regulated by dimethylarginine dimethylaminohydrolase type 1 (DDAH1). Numerous evidence suggests that drugs of abuse can increase DDAH1 levels, leading to reduction of ADMA levels, and in turn, causing neurotoxicity associated with NO overproduction. Yet, this data is sparse, and very little mechanistic evidence exists. Here, we review the literature on the impact of substances of abuse and social stress, as a condition implicated in addictive phenotypes, on DDAH1 levels in the brain. This review highlights five things: first, psychostimulants can increase brain DDAH1 levels and DDAH1-ADMA-NOS signaling axis could underlay neurotoxicity and addictive behaviors driven by psychostimulants. Second, opioids can also significantly increase brain DDAH1 levels, yet currently no mechanistic studies exist to determine the consequences of that increase. Three, the nicotine and alcohol studies are inconclusive as results are often complicated with comorbidities associated with cardiovascular impairments, liver toxicity and aging. Four, studies on cannabinoids are insufficient, more data is needed. Finally, social stress affects DDAH1 levels and anti-depressants can reverse this effect, but mechanistic data is lacking. In conclusion, proteomic, metabolomic and functional studies suggest that DDAH1 may play a role in addiction and conditions related to social stress. Further investigation is necessary to elucidate the specific function of DDAH1 in addiction and social stress phenotypes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111568"},"PeriodicalIF":3.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145642082","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}
Pub Date : 2025-12-20Epub Date: 2025-11-03DOI: 10.1016/j.pnpbp.2025.111552
Yi-Ling Chien , Chi Chen , Ming Hsien Hsieh , Susan Shur-Fen Gau
Backgrounds
Individuals with autism spectrum disorder (ASD) exhibit aberrant intrinsic connectivity and altered mismatch negativity responses. Both mismatch negativity and intrinsic connectivity are associated with pre-attentive mechanisms. However, the potential link between mismatch negativity and alterations in intrinsic connectivity in ASD has not been thoroughly explored. This study aimed to investigate the resting-state functional connectivity of the auditory network in ASD and examine its association with mismatch negativity and set-shifting performance.
Methods
This study recruited 75 ASD participants and 50 neurotypical controls (NAC). All participants underwent clinical assessments, mismatch negativity on the oddball paradigm, and resting-state functional MRI. We compared the resting-state brain connectivity of the auditory network between ASD and NAC using independent component analysis. We then examined correlations between this connectivity, mismatch negativity, and executive function measured by the Intra-Extra Dimensional Set Shift task (IED).
Results
The ASD group demonstrated resting-state hyperconnectivity between the auditory network and the regions of the posterior cingulate gyrus, left inferior frontal gyrus, right angular gyrus, and right caudate/thalamus. In ASD, the connectivity between the auditory network and the left inferior frontal gyrus was positively correlated with higher P3a amplitude and a greater number of completed stages on the IED task, indicating enhanced cognitive flexibility.
Conclusion
Findings suggest heightened functional connectivity between the auditory network and various brain regions in ASD. Specifically, connectivity to the left inferior frontal gyrus at rest may predict enhanced attention reorientation and cognitive flexibility in autistic individuals. Further research is warranted to elucidate these relationships.
{"title":"Correlation of auditory network hyperconnectivity with P3a amplitude and set-shifting in individuals with autism spectrum disorder","authors":"Yi-Ling Chien , Chi Chen , Ming Hsien Hsieh , Susan Shur-Fen Gau","doi":"10.1016/j.pnpbp.2025.111552","DOIUrl":"10.1016/j.pnpbp.2025.111552","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Individuals with autism spectrum disorder (ASD) exhibit aberrant intrinsic connectivity and altered mismatch negativity responses. Both mismatch negativity and intrinsic connectivity are associated with pre-attentive mechanisms. However, the potential link between mismatch negativity and alterations in intrinsic connectivity in ASD has not been thoroughly explored. This study aimed to investigate the resting-state functional connectivity of the auditory network in ASD and examine its association with mismatch negativity and set-shifting performance.</div></div><div><h3>Methods</h3><div>This study recruited 75 ASD participants and 50 neurotypical controls (NAC). All participants underwent clinical assessments, mismatch negativity on the oddball paradigm, and resting-state functional MRI. We compared the resting-state brain connectivity of the auditory network between ASD and NAC using independent component analysis. We then examined correlations between this connectivity, mismatch negativity, and executive function measured by the Intra-Extra Dimensional Set Shift task (IED).</div></div><div><h3>Results</h3><div>The ASD group demonstrated resting-state hyperconnectivity between the auditory network and the regions of the posterior cingulate gyrus, left inferior frontal gyrus, right angular gyrus, and right caudate/thalamus. In ASD, the connectivity between the auditory network and the left inferior frontal gyrus was positively correlated with higher P3a amplitude and a greater number of completed stages on the IED task, indicating enhanced cognitive flexibility.</div></div><div><h3>Conclusion</h3><div>Findings suggest heightened functional connectivity between the auditory network and various brain regions in ASD. Specifically, connectivity to the left inferior frontal gyrus at rest may predict enhanced attention reorientation and cognitive flexibility in autistic individuals. Further research is warranted to elucidate these relationships.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111552"},"PeriodicalIF":3.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453959","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}
Pub Date : 2025-12-20Epub Date: 2025-11-22DOI: 10.1016/j.pnpbp.2025.111565
Danica E. Johnson , Shakila Meshkat , Erica S. Kaczmarek , Jennifer S. Rabin , Ryan M. Brudner , Noah Chisamore , Zoe Doyle , Jordan Bawks , Jeremy Riva-Cambrin , Rodrigo B. Mansur , Orly Lipsitz , Roger S. McIntyre , Krista L. Lanctôt , Joshua D. Rosenblat
Background
Cognitive difficulties within treatment-resistant unipolar and bipolar depression (TRD; TRBD) often do not improve with conventional pharmacotherapies. Psilocybin-assisted psychotherapy (PAP) has shown promise as a novel intervention for TRD; however, few studies have assessed its effects on cognition in this population.
Methods
This retrospective post hoc analysis included 26 adults with TRD or TRBD from an open-label trial of PAP. Cognition was assessed with the Digit Symbol Substitution Test (DSST) and Trail Making Test Part A and B (TMT-A/B) at baseline, one-day, and two-weeks post-treatment. Linear mixed models (LMMs) evaluated change over time, and reliable change indices (RCIs) with binomial tests assessed whether the proportion of participants showing meaningful improvement exceeded chance.
Results
Significant improvements were observed on all cognitive measures over time (all p < .05). After adjusting for depressive symptoms, gains on the TMT-A (p < .001), TMT-B (p < .001), and TMTB – A (p = .005) remained significant. In contrast, DSST improvements were attenuated (p = .069). RCIs showed that 4.2 %–12.5 % of participants achieved meaningful improvement, but these rates did not significantly exceed chance expectations.
Conclusion
PAP was associated with modest, short-term improvements in performance on measures of processing speed and executive function among individuals with TRD. While these changes appeared independent of mood, they did not consistently exceed expected practice effects. These findings highlight the need for adequately powered, controlled trials to clarify whether observed cognitive changes reflect genuine procognitive effects of psilocybin or are attributable to non-specific influences such as test familiarity or concurrent mood improvements.
{"title":"Cognitive outcomes following psilocybin-assisted therapy in treatment-resistant depression: A post-hoc analysis of a randomized, waitlist-controlled trial","authors":"Danica E. Johnson , Shakila Meshkat , Erica S. Kaczmarek , Jennifer S. Rabin , Ryan M. Brudner , Noah Chisamore , Zoe Doyle , Jordan Bawks , Jeremy Riva-Cambrin , Rodrigo B. Mansur , Orly Lipsitz , Roger S. McIntyre , Krista L. Lanctôt , Joshua D. Rosenblat","doi":"10.1016/j.pnpbp.2025.111565","DOIUrl":"10.1016/j.pnpbp.2025.111565","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive difficulties within treatment-resistant unipolar and bipolar depression (TRD; TRBD) often do not improve with conventional pharmacotherapies. Psilocybin-assisted psychotherapy (PAP) has shown promise as a novel intervention for TRD; however, few studies have assessed its effects on cognition in this population.</div></div><div><h3>Methods</h3><div>This retrospective post hoc analysis included 26 adults with TRD or TRBD from an open-label trial of PAP. Cognition was assessed with the Digit Symbol Substitution Test (DSST) and Trail Making Test Part A and B (TMT-A/B) at baseline, one-day, and two-weeks post-treatment. Linear mixed models (LMMs) evaluated change over time, and reliable change indices (RCIs) with binomial tests assessed whether the proportion of participants showing meaningful improvement exceeded chance.</div></div><div><h3>Results</h3><div>Significant improvements were observed on all cognitive measures over time (all <em>p</em> < .05). After adjusting for depressive symptoms, gains on the TMT-A (<em>p</em> < .001), TMT-B (p < .001), and TMTB – A (<em>p</em> = .005) remained significant. In contrast, DSST improvements were attenuated (<em>p</em> = .069). RCIs showed that 4.2 %–12.5 % of participants achieved meaningful improvement, but these rates did not significantly exceed chance expectations.</div></div><div><h3>Conclusion</h3><div>PAP was associated with modest, short-term improvements in performance on measures of processing speed and executive function among individuals with TRD. While these changes appeared independent of mood, they did not consistently exceed expected practice effects. These findings highlight the need for adequately powered, controlled trials to clarify whether observed cognitive changes reflect genuine procognitive effects of psilocybin or are attributable to non-specific influences such as test familiarity or concurrent mood improvements.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111565"},"PeriodicalIF":3.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598173","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}
Pub Date : 2025-12-20Epub Date: 2025-11-08DOI: 10.1016/j.pnpbp.2025.111556
P. de la Higuera-Gonzalez , A. Galvez-Merlin , B. Marcos-Diaz , A. Calvo , A. Carrasco-Diaz , W. Ayad-Ahmed , P. Mola-Cardenes , A. de la Torre-Luque , F. Ruiz-Guerrero , F. Polo-Montes , J.L. Carrasco-Perera , L. Beato-Fernandez , A. Gomez-del Barrio , M. Diaz-Marsa
Introduction
Difficulties in interpersonal interactions have been related to Social Cognition (SC) impairments in eating disorders (EDs). However, results do not account for differences between restrictive (rED) and purgative (pED) profiles and are just based on decoding tasks. This study assessed SC by Theory of Mind (ToM) abilities in ToM decoding and inference tasks between rED and pED patients and healthy women and its relationship with clinical variables.
Method
37 rED patients, 42 pED patients and 34 controls were evaluated using the Movie for the Assessment of Social Cognition (MASC) -ToM inference abilities- and the Reading the Mind in the Eyes revised version (RMET-R) - ToM decoding abilities-. Age, body mass index (BMI) and disorder's duration were considered as clinical variables. ANCOVA analyses were carried out to analyse differences between groups, controlling for impulsivity as a covariate. Group relationships between ToM and clinical variables were analysed through linear regression models.
Results
pED showed lower correct MASC responses (p < .01) and more overmentalising errors (p < .05) than controls, and for rED, differences overmentalising errors were close to significance (p = .051). For RMET-R, differences were related to impulsivity. Age (p < .01) and BMI p < .05) were related with correct MASC responses.
Conclusions
Patients with EDs show difficulties in ToM inference abilities, especially those with a purgative profile, with poorer performance related to clinical severity indices such as weight and age. Differences in ToM decoding appear to be related to impulsivity rather than clinical diagnosis.
{"title":"Social cognition in women with eating disorders: Differences between the restrictive and purgative profiles","authors":"P. de la Higuera-Gonzalez , A. Galvez-Merlin , B. Marcos-Diaz , A. Calvo , A. Carrasco-Diaz , W. Ayad-Ahmed , P. Mola-Cardenes , A. de la Torre-Luque , F. Ruiz-Guerrero , F. Polo-Montes , J.L. Carrasco-Perera , L. Beato-Fernandez , A. Gomez-del Barrio , M. Diaz-Marsa","doi":"10.1016/j.pnpbp.2025.111556","DOIUrl":"10.1016/j.pnpbp.2025.111556","url":null,"abstract":"<div><h3>Introduction</h3><div>Difficulties in interpersonal interactions have been related to Social Cognition (SC) impairments in eating disorders (EDs). However, results do not account for differences between restrictive (rED) and purgative (pED) profiles and are just based on decoding tasks. This study assessed SC by Theory of Mind (ToM) abilities in ToM decoding and inference tasks between rED and pED patients and healthy women and its relationship with clinical variables.</div></div><div><h3>Method</h3><div>37 rED patients, 42 pED patients and 34 controls were evaluated using the Movie for the Assessment of Social Cognition (MASC) -ToM inference abilities- and the Reading the Mind in the Eyes revised version (RMET-R) - ToM decoding abilities-. Age, body mass index (BMI) and disorder's duration were considered as clinical variables. ANCOVA analyses were carried out to analyse differences between groups, controlling for impulsivity as a covariate. Group relationships between ToM and clinical variables were analysed through linear regression models.</div></div><div><h3>Results</h3><div>pED showed lower correct MASC responses (<em>p</em> < .01) and more overmentalising errors (<em>p</em> < .05) than controls, and for rED, differences overmentalising errors were close to significance (<em>p</em> = .051). For RMET-R, differences were related to impulsivity. Age (<em>p</em> < .01) and BMI <em>p</em> < .05) were related with correct MASC responses.</div></div><div><h3>Conclusions</h3><div>Patients with EDs show difficulties in ToM inference abilities, especially those with a purgative profile, with poorer performance related to clinical severity indices such as weight and age. Differences in ToM decoding appear to be related to impulsivity rather than clinical diagnosis.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111556"},"PeriodicalIF":3.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490899","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}
Pub Date : 2025-12-20Epub Date: 2025-11-02DOI: 10.1016/j.pnpbp.2025.111555
Florian W. Adraoui , Maëlle Violas , Geoffrey Viardot , Kenza Hettak , Samuel Tugler , Eric Delpy , Anne Maurin , Philippe L'Hostis , Christophe Drieu La Rochelle , Kevin Carvalho
Treating people with schizophrenia still represents a major challenge for neuropsychiatric drug development companies. While available atypical antipsychotics are mainly effective on positive symptoms of schizophrenia, their effects on cognitive and social-cognitive deficits remain insufficient and poorly characterized. For instance, a modest improvement of cognitive functions has been described following clozapine treatment. Nevertheless, it remains unclear whether this outcome is due to a direct effect on the neural circuits underlying cognition or to an indirect effect mediated by an overall reduction in positive symptoms. To address this question, we sought to measure mismatch negativity (MMN) responses in telemetered rats. MMN constitutes an electroencephalography-based biomarker of sensory, pre-attentional and predictive coding processes, functions whose disruptions highly influence certain aspects of patients' cognitive symptoms. MMN was measured under N-methyl-d-aspartate receptor (NMDAr) pharmacological inhibition by MK-801 (dizocilpine), a model based on the glutamatergic hypothesis of schizophrenia, and we tested whether clozapine could improve MMN under this condition or not. We found that MK-801 dose-dependently reduced the MMN peak amplitude in rats, aligning with the MMN response deficit seen in schizophrenia patients. Strikingly, clozapine was able to mitigate this electrophysiological deficit, an unprecedented observation that has the potential to inspire new treatment strategies aimed towards unaddressed schizophrenia symptoms.
{"title":"Clozapine mitigates MK-801-induced mismatch negativity impairment in a rat electroencephalography study: relevance for schizophrenia drug development","authors":"Florian W. Adraoui , Maëlle Violas , Geoffrey Viardot , Kenza Hettak , Samuel Tugler , Eric Delpy , Anne Maurin , Philippe L'Hostis , Christophe Drieu La Rochelle , Kevin Carvalho","doi":"10.1016/j.pnpbp.2025.111555","DOIUrl":"10.1016/j.pnpbp.2025.111555","url":null,"abstract":"<div><div>Treating people with schizophrenia still represents a major challenge for neuropsychiatric drug development companies. While available atypical antipsychotics are mainly effective on positive symptoms of schizophrenia, their effects on cognitive and social-cognitive deficits remain insufficient and poorly characterized. For instance, a modest improvement of cognitive functions has been described following clozapine treatment. Nevertheless, it remains unclear whether this outcome is due to a direct effect on the neural circuits underlying cognition or to an indirect effect mediated by an overall reduction in positive symptoms. To address this question, we sought to measure mismatch negativity (MMN) responses in telemetered rats. MMN constitutes an electroencephalography-based biomarker of sensory, pre-attentional and predictive coding processes, functions whose disruptions highly influence certain aspects of patients' cognitive symptoms. MMN was measured under <em>N</em>-methyl-<span>d</span>-aspartate receptor (NMDAr) pharmacological inhibition by MK-801 (dizocilpine), a model based on the glutamatergic hypothesis of schizophrenia, and we tested whether clozapine could improve MMN under this condition or not. We found that MK-801 dose-dependently reduced the MMN peak amplitude in rats, aligning with the MMN response deficit seen in schizophrenia patients. Strikingly, clozapine was able to mitigate this electrophysiological deficit, an unprecedented observation that has the potential to inspire new treatment strategies aimed towards unaddressed schizophrenia symptoms.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111555"},"PeriodicalIF":3.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446299","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}
Pub Date : 2025-12-20Epub Date: 2025-11-03DOI: 10.1016/j.pnpbp.2025.111551
Zhangwei Lv , Haobo Zhang , Yuhan Fan , Yuanyuan Chen , Yuxian Wei , Xu Lei
Insomnia disorder is a heterogeneous psychiatric condition characterized by differences in psychological traits and neurobiological mechanisms, necessitating precise phenotyping for targeted interventions. This clinical control study, part of a two-year multicenter research project, examined differences in sleep parameters, psychological characteristics, and morphometric similarity (MS) patterns between insomnia phenotypes classified by objective total sleep time (oTST). The study enrolled 997 adult patients with insomnia disorder, of whom 270 underwent MRI scanning. Participants were categorized into insomnia with objective normal sleep duration (INSD) and insomnia with objective short sleep duration (ISSD) based on oTST measured using a wearable forehead sleep recorder. Primary outcomes included sleep parameters (e.g., wake after sleep onset and rapid eye movement percentage), psychological characteristics (e.g., rumination), and MS patterns assessed through MS mapping. Results showed that the ISSD phenotype showed shorter wake after sleep onset, lower eye movement sleep (REM) percentage, and higher non-REM stage 2 percentage, whereas the INSD phenotype exhibited greater sleep perception bias and more fragmented sleep. Additionally, ISSD showed higher global MS and distinct regional MS patterns, including lower MS in the right middle temporal gyrus and higher MS in the right postcentral gyrus. It also exhibited decoupling with the visual network and de-differentiation with the ventral attention and default mode networks. These findings reveal distinct neurobiological mechanisms underlying insomnia phenotypes and highlight the need for phenotype-based interventions.
{"title":"Global and regional morphometric similarity in insomnia with objective short sleep duration","authors":"Zhangwei Lv , Haobo Zhang , Yuhan Fan , Yuanyuan Chen , Yuxian Wei , Xu Lei","doi":"10.1016/j.pnpbp.2025.111551","DOIUrl":"10.1016/j.pnpbp.2025.111551","url":null,"abstract":"<div><div>Insomnia disorder is a heterogeneous psychiatric condition characterized by differences in psychological traits and neurobiological mechanisms, necessitating precise phenotyping for targeted interventions. This clinical control study, part of a two-year multicenter research project, examined differences in sleep parameters, psychological characteristics, and morphometric similarity (MS) patterns between insomnia phenotypes classified by objective total sleep time (oTST). The study enrolled 997 adult patients with insomnia disorder, of whom 270 underwent MRI scanning. Participants were categorized into insomnia with objective normal sleep duration (INSD) and insomnia with objective short sleep duration (ISSD) based on oTST measured using a wearable forehead sleep recorder. Primary outcomes included sleep parameters (e.g., wake after sleep onset and rapid eye movement percentage), psychological characteristics (e.g., rumination), and MS patterns assessed through MS mapping. Results showed that the ISSD phenotype showed shorter wake after sleep onset, lower eye movement sleep (REM) percentage, and higher non-REM stage 2 percentage, whereas the INSD phenotype exhibited greater sleep perception bias and more fragmented sleep. Additionally, ISSD showed higher global MS and distinct regional MS patterns, including lower MS in the right middle temporal gyrus and higher MS in the right postcentral gyrus. It also exhibited decoupling with the visual network and de-differentiation with the ventral attention and default mode networks. These findings reveal distinct neurobiological mechanisms underlying insomnia phenotypes and highlight the need for phenotype-based interventions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111551"},"PeriodicalIF":3.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454008","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}
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