Pub Date : 2026-01-24DOI: 10.1016/j.pnpbp.2026.111617
Shakeel Ahmed Ansari, Faez Iqbal Khan, Asim Muhammad Alshanberi, Mohammad Zubair Alam, Muhammad Saboor, Ghulam Md Ashraf
Schizophrenia is a severe psychiatric disorder that occurs more frequently in males than in females. Males typically show symptoms earlier in life, while females tend to develop symptoms later, with a peak after menopause. Men have a higher incidence rate, but the overall prevalence is similar between genders. Several studies have identified potential biopsychosocial reasons for these differences. The "estrogen hypothesis," which suggests a neuroprotective effect of estrogen in women, has gained support despite limited evidence for genetic and neurodevelopmental factors. Differences based on symptoms have also been connected to distinct psychological vulnerabilities in men and women. Emerging research indicates that genetic and neurodevelopmental factors may play a less significant role in female schizophrenia compared to males. In this context, the estrogen hypothesis, which proposes a neuroprotective role for estrogen, has gained attention as a possible explanation for sex-related differences in disease expression and progression. These gender-based differences in schizophrenia might reflect variations in symptom profiles that are influenced by underlying psychological and neurobiological vulnerabilities unique to each sex. A thorough investigation of these gender-specific mechanisms is necessary to deepen understanding of the causes and to develop more personalized and effective treatments.
{"title":"Gender-specific perspectives in schizophrenia: Recent advances and future directions.","authors":"Shakeel Ahmed Ansari, Faez Iqbal Khan, Asim Muhammad Alshanberi, Mohammad Zubair Alam, Muhammad Saboor, Ghulam Md Ashraf","doi":"10.1016/j.pnpbp.2026.111617","DOIUrl":"10.1016/j.pnpbp.2026.111617","url":null,"abstract":"<p><p>Schizophrenia is a severe psychiatric disorder that occurs more frequently in males than in females. Males typically show symptoms earlier in life, while females tend to develop symptoms later, with a peak after menopause. Men have a higher incidence rate, but the overall prevalence is similar between genders. Several studies have identified potential biopsychosocial reasons for these differences. The \"estrogen hypothesis,\" which suggests a neuroprotective effect of estrogen in women, has gained support despite limited evidence for genetic and neurodevelopmental factors. Differences based on symptoms have also been connected to distinct psychological vulnerabilities in men and women. Emerging research indicates that genetic and neurodevelopmental factors may play a less significant role in female schizophrenia compared to males. In this context, the estrogen hypothesis, which proposes a neuroprotective role for estrogen, has gained attention as a possible explanation for sex-related differences in disease expression and progression. These gender-based differences in schizophrenia might reflect variations in symptom profiles that are influenced by underlying psychological and neurobiological vulnerabilities unique to each sex. A thorough investigation of these gender-specific mechanisms is necessary to deepen understanding of the causes and to develop more personalized and effective treatments.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111617"},"PeriodicalIF":3.9,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055017","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 : 2026-01-23DOI: 10.1016/j.pnpbp.2026.111622
Chengwen Liu , Shulin Fang , Chang Cheng , Pan Lin , Daifeng Dong , Shuqiao Yao , Weijun Situ , Xiang Wang
Background
Major depressive disorder (MDD) is frequently accompanied by suicidal ideation (SI), which has been linked to functional disruptions in brain regions involved in emotion regulation, including the key amygdala. However, the temporal dynamics of amygdala-based functional connectivity in MDD patients with SI remain unclear.
Methods
First-episode MDD patients with SI (n = 53), without SI (NSI, n = 27), and healthy controls (HCs, n = 58) who underwent resting-state functional magnetic resonance imaging were included. Co-activation pattern (CAP) analysis was employed to characterize amygdala connectivity dynamics. Five distinct network states were identified and corresponding dynamic metrics were analyzed with respect to clinical characteristics, and support vector machine (SVM) classification was applied to classify individuals based on aberrant CAP features.
Results
Both SI and NSI groups showed increased dominance of the affective network (AN) co-activated with the amygdala compared to HCs, with a positive correlation to anxiety symptoms. Notably, SI group exhibited decreased occurrence rate and resilience of a transient network state, predominantly involving the default mode network (DMN) and reward network (RN), which was negatively correlated with SI severity. SVM classification achieved robust performance in distinguishing SI individuals from NSI and HC based on dynamic CAP metrics.
Conclusion
These findings highlight heightened temporal instability of the AN and associated excessive anxious mood in MDD, while the diminished dominance of the amygdala–DMN-RN coupling indicates impairments in self-referential and reward processing in MDD patients with SI. Overall, disruptions in amygdala-based network dynamics may implicate neurobiological substrates underlying emotional dysregulation and elevated suicide risk in MDD.
Trial registration
The registration number is ChiCTR2000031931 and date of registration is April 15th 2020.
{"title":"Disrupted resting-state amygdala connectivity dynamics in major depressive disorder with suicidal ideation: Implications for emotional dysregulation and suicide risk","authors":"Chengwen Liu , Shulin Fang , Chang Cheng , Pan Lin , Daifeng Dong , Shuqiao Yao , Weijun Situ , Xiang Wang","doi":"10.1016/j.pnpbp.2026.111622","DOIUrl":"10.1016/j.pnpbp.2026.111622","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is frequently accompanied by suicidal ideation (SI), which has been linked to functional disruptions in brain regions involved in emotion regulation, including the key amygdala. However, the temporal dynamics of amygdala-based functional connectivity in MDD patients with SI remain unclear.</div></div><div><h3>Methods</h3><div>First-episode MDD patients with SI (<em>n</em> = 53), without SI (NSI, <em>n</em> = 27), and healthy controls (HCs, <em>n</em> = 58) who underwent resting-state functional magnetic resonance imaging were included. Co-activation pattern (CAP) analysis was employed to characterize amygdala connectivity dynamics. Five distinct network states were identified and corresponding dynamic metrics were analyzed with respect to clinical characteristics, and support vector machine (SVM) classification was applied to classify individuals based on aberrant CAP features.</div></div><div><h3>Results</h3><div>Both SI and NSI groups showed increased dominance of the affective network (AN) co-activated with the amygdala compared to HCs, with a positive correlation to anxiety symptoms. Notably, SI group exhibited decreased occurrence rate and resilience of a transient network state, predominantly involving the default mode network (DMN) and reward network (RN), which was negatively correlated with SI severity. SVM classification achieved robust performance in distinguishing SI individuals from NSI and HC based on dynamic CAP metrics.</div></div><div><h3>Conclusion</h3><div>These findings highlight heightened temporal instability of the AN and associated excessive anxious mood in MDD, while the diminished dominance of the amygdala–DMN-RN coupling indicates impairments in self-referential and reward processing in MDD patients with SI. Overall, disruptions in amygdala-based network dynamics may implicate neurobiological substrates underlying emotional dysregulation and elevated suicide risk in MDD.</div></div><div><h3>Trial registration</h3><div>The registration number is ChiCTR2000031931 and date of registration is April 15th 2020.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"145 ","pages":"Article 111622"},"PeriodicalIF":3.9,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047363","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 : 2026-01-23DOI: 10.1016/j.pnpbp.2026.111621
B Romeo, E Kervadec, B Fauvel, L Strika-Bruneau, P Mathieu, A Amirouche, A Bezo, R Hacquet, P Piolino, A Benyamina
Introduction: The intensity of the psychedelic experience has been shown to be associated with its clinical efficacy. This study aims to investigate the factors that may influence the level of altered consciousness during naturalistic psychedelic use, which serves as a proxy for the intensity of the psychedelic experience.
Methods: A retrospective online survey was conducted on individuals who reported a psychedelic experience. Demographic data, intensity of the psychedelic experience as assessed by the Altered States of Consciousness questionnaire (5D-ASC and its 11 subscales) and characteristics of the psychedelic experience were documented.
Results: A total of 804 participants were included in this study. Significant predictors of 5D-ASC scores following a psychedelic experience included the intended purpose of the experience (with spiritual/religious, therapeutic, and self-exploratory intentions exerting a greater influence than recreational intentions); the type of substance (with dissociative and serotonergic psychedelics associated with stronger effects than entactogens); the estimated dose (with moderate, high, and very high doses yielding greater effects relative to very low doses); as well as participants' age at the time of the experience and their gender.
Conclusion: Our findings indicate that the intensity of psychedelic experiences is influenced by a multifaceted interplay of pharmacological, individual, and contextual factors. The close correspondence between determinants of mystical experiences and altered states of consciousness suggests that experiential intensity may reflect a shared underlying neurobiological sensitivity, rather than being specific to a given phenomenological category.
{"title":"Modulators of altered states of consciousness across psychedelic, dissociative, and entactogen use: A retrospective naturalistic study using the 5D-ASC.","authors":"B Romeo, E Kervadec, B Fauvel, L Strika-Bruneau, P Mathieu, A Amirouche, A Bezo, R Hacquet, P Piolino, A Benyamina","doi":"10.1016/j.pnpbp.2026.111621","DOIUrl":"10.1016/j.pnpbp.2026.111621","url":null,"abstract":"<p><strong>Introduction: </strong>The intensity of the psychedelic experience has been shown to be associated with its clinical efficacy. This study aims to investigate the factors that may influence the level of altered consciousness during naturalistic psychedelic use, which serves as a proxy for the intensity of the psychedelic experience.</p><p><strong>Methods: </strong>A retrospective online survey was conducted on individuals who reported a psychedelic experience. Demographic data, intensity of the psychedelic experience as assessed by the Altered States of Consciousness questionnaire (5D-ASC and its 11 subscales) and characteristics of the psychedelic experience were documented.</p><p><strong>Results: </strong>A total of 804 participants were included in this study. Significant predictors of 5D-ASC scores following a psychedelic experience included the intended purpose of the experience (with spiritual/religious, therapeutic, and self-exploratory intentions exerting a greater influence than recreational intentions); the type of substance (with dissociative and serotonergic psychedelics associated with stronger effects than entactogens); the estimated dose (with moderate, high, and very high doses yielding greater effects relative to very low doses); as well as participants' age at the time of the experience and their gender.</p><p><strong>Conclusion: </strong>Our findings indicate that the intensity of psychedelic experiences is influenced by a multifaceted interplay of pharmacological, individual, and contextual factors. The close correspondence between determinants of mystical experiences and altered states of consciousness suggests that experiential intensity may reflect a shared underlying neurobiological sensitivity, rather than being specific to a given phenomenological category.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111621"},"PeriodicalIF":3.9,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047350","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 : 2026-01-19DOI: 10.1016/j.pnpbp.2026.111614
Shaun G. Hong , Dasom Lee , Taewon Kim , Minhee Kim , Deung Hyun Kang , Soo-Hee Choi
Background
This study aimed to leverage advanced radiomics analysis of resting-state functional magnetic resonance imaging (rs-fMRI) data to investigate the potential of radiomics in distinguishing patients with social anxiety disorder (SAD) from healthy controls and identifying distinct subtypes within patients.
Methods
We analyzed the rs-fMRI data from 147 participants (78 controls, 69 patients) using three rs-fMRI metrics: regional homogeneity, fractional amplitude of low-frequency fluctuations, and degree centrality. From each of these metrics, we extracted 91 radiomics and mean signals from the amygdala, hippocampus, insula, and medial/ventromedial prefrontal cortex (mPFC/vmPFC). We employed machine learning algorithms for classification and utilized Subtype and Stage Inference (SuStaIn) model to identify disease subtypes and symptom progression.
Results
Classification using radiomics from individual regions, particularly the left amygdala (accuracy: 84.3%), right hippocampus (74.2%), and mPFC (74.1%), significantly outperformed classification using mean signals from all regions (52.2%). Furthermore, the right hippocampal-based SuStaIn model revealed two distinct subtypes of SAD, social anxiety-led and general anxiety-led, with the former demonstrating more severe comorbid symptoms and poorer prognosis.
Conclusions
Radiomics features from rs-fMRI effectively classified patients with SAD and revealed clinically meaningful subtypes through SuStaIn modeling. These findings demonstrate the value of quantitative imaging approaches that capture subtle functional patterns and underscore the potential of disease-progression modeling for understanding heterogeneity in SAD.
{"title":"Radiomics-based classification and inference of subtypes and stages in social anxiety disorder using resting-state functional images","authors":"Shaun G. Hong , Dasom Lee , Taewon Kim , Minhee Kim , Deung Hyun Kang , Soo-Hee Choi","doi":"10.1016/j.pnpbp.2026.111614","DOIUrl":"10.1016/j.pnpbp.2026.111614","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to leverage advanced radiomics analysis of resting-state functional magnetic resonance imaging (rs-fMRI) data to investigate the potential of radiomics in distinguishing patients with social anxiety disorder (SAD) from healthy controls and identifying distinct subtypes within patients.</div></div><div><h3>Methods</h3><div>We analyzed the rs-fMRI data from 147 participants (78 controls, 69 patients) using three rs-fMRI metrics: regional homogeneity, fractional amplitude of low-frequency fluctuations, and degree centrality. From each of these metrics, we extracted 91 radiomics and mean signals from the amygdala, hippocampus, insula, and medial/ventromedial prefrontal cortex (mPFC/vmPFC). We employed machine learning algorithms for classification and utilized Subtype and Stage Inference (SuStaIn) model to identify disease subtypes and symptom progression.</div></div><div><h3>Results</h3><div>Classification using radiomics from individual regions, particularly the left amygdala (accuracy: 84.3%), right hippocampus (74.2%), and mPFC (74.1%), significantly outperformed classification using mean signals from all regions (52.2%). Furthermore, the right hippocampal-based SuStaIn model revealed two distinct subtypes of SAD, social anxiety-led and general anxiety-led, with the former demonstrating more severe comorbid symptoms and poorer prognosis.</div></div><div><h3>Conclusions</h3><div>Radiomics features from rs-fMRI effectively classified patients with SAD and revealed clinically meaningful subtypes through SuStaIn modeling. These findings demonstrate the value of quantitative imaging approaches that capture subtle functional patterns and underscore the potential of disease-progression modeling for understanding heterogeneity in SAD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"145 ","pages":"Article 111614"},"PeriodicalIF":3.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019944","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 : 2026-01-19DOI: 10.1016/j.pnpbp.2026.111613
Qinghua Zhai , Wenyue Gong , Azi Shen , Yiwen Wang , Haowen Zou , Yinghong Huang , Kaiyu Shi , Shuai Zhao , Rui Yan , Zhijian Yao , Qing Lu , Jindan Wu
Background
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.
Methods
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.
Results
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.
Conclusion
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.
{"title":"Cortical structural alterations and thyroid autoantibodies underlying anxiety in major depressive disorder with comorbid Hashimoto's thyroiditis","authors":"Qinghua Zhai , Wenyue Gong , Azi Shen , Yiwen Wang , Haowen Zou , Yinghong Huang , Kaiyu Shi , Shuai Zhao , Rui Yan , Zhijian Yao , Qing Lu , 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}
Pub Date : 2026-01-19DOI: 10.1016/j.pnpbp.2026.111616
Rachel L. Sousa-Ho , Ilya Demchenko , Vanessa A. Baltazar , Ishaan Tailor , Benjamin T. Dunkley , Tom A. Schweizer , Sidney H. Kennedy , Alexandre Boutet , Andres M. Lozano , Cherise R. Chin Fatt , Manish K. Jha , Katharine Dunlop , Venkat Bhat
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.
抗抑郁药通常用于重度抑郁症（MDD），有证据表明其治疗效果可能涉及亚属前扣带皮层（sgACC）结构和功能异常的正常化。本系统综述评估了神经影像学文献，以评估sgACC结构、活性、功能连通性和代谢与血清素和谷氨酸能抗抑郁药的纵向变化之间的关系。通过OVID （MEDLINE, Embase, APA PsychINFO）搜索相关文章，截止日期为2024年7月29日。要纳入本系统综述，研究必须收集和报告与耐药或非耐药MDD患者接受血清素能或谷氨酸能抗抑郁药治疗时sgACC的结构、功能或代谢有关的神经影像学数据。本综述纳入了21项研究。两项研究发现，重度抑郁症患者基线时sgACC体积增加与艾司西酞普兰和氟西汀治疗效果较好相关。功能研究报告了不同的结果，药物治疗后sgACC活性增加、减少和不变的平衡证据。三项代谢成像研究报告氟西汀和帕罗西汀治疗后sgACC代谢降低，而两项血清素转运体（SERT）占用研究报告艾司西酞普兰治疗后SERT占用增加。未来的研究应该探索sgACC调节的个体差异，可能检查影响sgACC对抗抑郁药物治疗反应的遗传、神经生物学和临床因素。
{"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 , Ilya Demchenko , Vanessa A. Baltazar , Ishaan Tailor , Benjamin T. Dunkley , Tom A. Schweizer , Sidney H. Kennedy , Alexandre Boutet , Andres M. Lozano , Cherise R. Chin Fatt , Manish K. Jha , Katharine Dunlop , 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}
Pub Date : 2026-01-19DOI: 10.1016/j.pnpbp.2026.111615
Yuanzheng Wang , Xu Han , Yuewei Chen , Mianxin Liu , Ying Hu , Yage Qiu , Qun Xu , Yao Wang , Yan Zhou
Objectives
To investigate the advantage of combining brain injury and reserve in evaluation of cerebral small vessel disease (CSVD) related cognitive impairment.
Design, settings, participants and measurements
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.
Results
The MoCA scores between the high and low reserve groups has a difference(23.35 ± 4.06 vs 21.73 ± 5.20, t = 2.38, p = 0.037). All of the CSVD related imaging biomarkers, ICV and brain structural network characteristics were significantly correlated with MoCA(r = 0.156, p = 0.002). ICV was positively associated with MoCA after controlling the other related variables(r = 0.145, p = 0.012; r = 0.128, p = 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, p < 0.05), redundancy(indirect effect = 0.0155, p < 0.05), and Eg(indirect effect = 0.0355, p < 0.05) could play significant role in mediating effects on the relationship between ICV and MoCA, while Eloc(no significant mediating effect, p > 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.
Conclusions
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.
{"title":"Combination of brain injury and brain reserve promotes the neuroimaging evaluation of small vessel disease related cognitive impairment","authors":"Yuanzheng Wang , Xu Han , Yuewei Chen , Mianxin Liu , Ying Hu , Yage Qiu , Qun Xu , Yao Wang , 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> < 0.05), redundancy(indirect effect = 0.0155, p < 0.05), and Eg(indirect effect = 0.0355, p < 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> > 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}
Pub Date : 2026-01-14DOI: 10.1016/j.pnpbp.2026.111609
Ornella Valenti , Karin Mueller , Jae-Won Yang , Hilal Bulut , Katarzyna Anna Rekawek , Stefan Boehm
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.
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.
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.
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.
{"title":"Repeated adenosine A1 receptor antagonism rewires ventral hippocampus-ventral tegmental area transmission and enhances stress-coping responses","authors":"Ornella Valenti , Karin Mueller , Jae-Won Yang , Hilal Bulut , Katarzyna Anna Rekawek , 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}
Pub Date : 2026-01-13DOI: 10.1016/j.pnpbp.2026.111612
Romério de Oliveira Lima Filho , Ricardo Gabriel de Lima Bisneto , Beatriz Silva do Nascimento , Heloysa Araujo-Silva , Silvia Regina Batistuzzo de Medeiros , Eduardo Pacheco Rico , Ana Carolina Luchiari
This study explores the long-term effects of embryonic ethanol exposure on cognitive functions and gene expression in zebrafish (Danio rerio). 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.
{"title":"Long-term impact of embryonic ethanol exposure on gene expression and executive functions in zebrafish","authors":"Romério de Oliveira Lima Filho , Ricardo Gabriel de Lima Bisneto , Beatriz Silva do Nascimento , Heloysa Araujo-Silva , Silvia Regina Batistuzzo de Medeiros , Eduardo Pacheco Rico , 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}
Pub Date : 2026-01-11DOI: 10.1016/j.pnpbp.2026.111611
Claire Leconte, Virginie Beray-Berthat, Fanny Saulnier, Derin Reha Ulusoy, Amanda Patricia Sales, Matilde Donzelli, Laura Marques, Isabelle Nondier, Corinne Canestrelli, Florence Noble, Raymond Mongeau
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 kappa opioid receptor mRNA upregulation in the prefrontal cortex, while mu 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.
{"title":"Traumatic-like fear memory recall causes persistent morphine conditioned place preference in drug withdrawn male mice","authors":"Claire Leconte, Virginie Beray-Berthat, Fanny Saulnier, Derin Reha Ulusoy, Amanda Patricia Sales, Matilde Donzelli, Laura Marques, Isabelle Nondier, Corinne Canestrelli, Florence Noble, 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}
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