Pub Date : 2025-10-30DOI: 10.1016/j.bpsgos.2025.100643
Rafael Navarro-González , Pedro Luque-Laguna , Rodrigo de Luis-García , Derek K. Jones , Kate Merritt , Anthony S. David
Background
Psychotic experiences (hallucinations and delusions: PEs) are linked to structural brain variation, but their relationship to magnetic resonance imaging (MRI)–derived brain age is unclear. We hypothesized that young adults reporting PEs would show an increased brain-age gap (predicted − chronological age) and that this gap would diverge over 10 years.
Methods
A multilayer perceptron (2628 training scans; age 6–50 years; mean absolute error = 4.3 years, R2 = 0.72) estimated brain age from T1-weighted MRIs in the ALSPAC (Avon Longitudinal Study of Parents and Children). Participants were scanned at around age 20 years (N = 245; 124 with PEs) and again at around 30 years (N = 279; 69 with PEs); 113 participants contributed both scans. Linear mixed-effects models tested case-control, severity, and time-by-group effects.
Results
At the initial time point, individuals with PEs showed a larger brain-age gap than control individuals (d [95% CI] = 0.70 [0.14 to 1.27]; q = .029). The brain-age gap showed a trend-level association with PE severity (d [95% CI] = 1.32 [0.00 to 2.64]; q = .098). At the follow-up, the group difference was nonsignificant (d [95% CI] = 0.22 [−0.08 to 0.51]; q = .153). No longitudinal case-control divergence reached significance, likely reflecting limited power.
Conclusions
Young adults who report PEs display an older-looking brain in early adulthood, consistent with atypical brain maturation. However, the gap does not clearly widen or contract by age 30. Multimodal, longitudinal cohorts spanning adolescence to midadulthood are needed to map psychosis-related atypical brain maturation.
{"title":"Increased Brain-Age Gap in Young Adults With Psychotic Experiences","authors":"Rafael Navarro-González , Pedro Luque-Laguna , Rodrigo de Luis-García , Derek K. Jones , Kate Merritt , Anthony S. David","doi":"10.1016/j.bpsgos.2025.100643","DOIUrl":"10.1016/j.bpsgos.2025.100643","url":null,"abstract":"<div><h3>Background</h3><div>Psychotic experiences (hallucinations and delusions: PEs) are linked to structural brain variation, but their relationship to magnetic resonance imaging (MRI)–derived brain age is unclear. We hypothesized that young adults reporting PEs would show an increased brain-age gap (predicted − chronological age) and that this gap would diverge over 10 years.</div></div><div><h3>Methods</h3><div>A multilayer perceptron (2628 training scans; age 6–50 years; mean absolute error = 4.3 years, <em>R</em><sup>2</sup> = 0.72) estimated brain age from T1-weighted MRIs in the ALSPAC (Avon Longitudinal Study of Parents and Children). Participants were scanned at around age 20 years (<em>N</em> = 245; 124 with PEs) and again at around 30 years (<em>N</em> = 279; 69 with PEs); 113 participants contributed both scans. Linear mixed-effects models tested case-control, severity, and time-by-group effects.</div></div><div><h3>Results</h3><div>At the initial time point, individuals with PEs showed a larger brain-age gap than control individuals (<em>d</em> [95% CI] = 0.70 [0.14 to 1.27]; <em>q</em> = .029). The brain-age gap showed a trend-level association with PE severity (<em>d</em> [95% CI] = 1.32 [0.00 to 2.64]; <em>q</em> = .098). At the follow-up, the group difference was nonsignificant (<em>d</em> [95% CI] = 0.22 [−0.08 to 0.51]; <em>q</em> = .153). No longitudinal case-control divergence reached significance, likely reflecting limited power.</div></div><div><h3>Conclusions</h3><div>Young adults who report PEs display an older-looking brain in early adulthood, consistent with atypical brain maturation. However, the gap does not clearly widen or contract by age 30. Multimodal, longitudinal cohorts spanning adolescence to midadulthood are needed to map psychosis-related atypical brain maturation.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100643"},"PeriodicalIF":3.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/j.bpsgos.2025.100646
Marta Korom , Mary Dozier , Hung-Wei Bernie Chen , Elisa Macera , Nim Tottenham , Jeffrey M. Spielberg
Background
In this study, we investigated the sustained causal effects of enhanced early caregiving quality on adolescent brain network properties approximately 11 years after families received an attachment-based parenting intervention.
Methods
Participants included 60 adolescents whose parents were referred by Child Protective Services (CPS) because of risk for child maltreatment and 35 adolescents from families without a CPS history (total N = 95). CPS-involved families were randomly assigned to either the target intervention (Attachment and Biobehavioral Catch-up [ABC]) (n = 31) or a control intervention (Developmental Education for Families [DEF]) (n = 29) before the infants turned 2. During adolescence (meanage = 13.4 years, SD = 0.37), participants underwent a 6-minute resting-state functional magnetic resonance imaging scan.
Results
Graph-theoretical analyses were completed with intervention status as the group-level predictor of interest. Adolescents who received the ABC intervention exhibited distinct global and local network properties compared with the DEF group. The ABC group demonstrated lower current-flow global efficiency and more hierarchical structure, indicating intervention-driven modulation of connectome-wide neurodevelopmental outcomes. Node-specific analyses also indicated intervention effects on clustering coefficients and communicability distances in frontal, limbic, and parietal cortices, suggesting nuanced effects of early interventions on local network properties. Exploratory moderation analyses revealed associations between brain network metrics and externalizing symptoms in the DEF group—indicative of neurobiological risk—that were absent in the ABC and low-risk groups.
Conclusions
The results suggest that the ABC intervention causally shapes the development of the resting-state connectome and associated regulatory health, offering insights into the neural pathways through which early enhanced care may get under the skin of at-risk adolescents.
{"title":"Causal Effects of Enhanced Parenting on Resting-State Graph Properties of Adolescents at Risk for Maltreatment","authors":"Marta Korom , Mary Dozier , Hung-Wei Bernie Chen , Elisa Macera , Nim Tottenham , Jeffrey M. Spielberg","doi":"10.1016/j.bpsgos.2025.100646","DOIUrl":"10.1016/j.bpsgos.2025.100646","url":null,"abstract":"<div><h3>Background</h3><div>In this study, we investigated the sustained causal effects of enhanced early caregiving quality on adolescent brain network properties approximately 11 years after families received an attachment-based parenting intervention.</div></div><div><h3>Methods</h3><div>Participants included 60 adolescents whose parents were referred by Child Protective Services (CPS) because of risk for child maltreatment and 35 adolescents from families without a CPS history (total <em>N</em> = 95). CPS-involved families were randomly assigned to either the target intervention (Attachment and Biobehavioral Catch-up [ABC]) (<em>n</em> = 31) or a control intervention (Developmental Education for Families [DEF]) (<em>n</em> = 29) before the infants turned 2. During adolescence (mean<sub>age</sub> = 13.4 years, SD = 0.37), participants underwent a 6-minute resting-state functional magnetic resonance imaging scan.</div></div><div><h3>Results</h3><div>Graph-theoretical analyses were completed with intervention status as the group-level predictor of interest. Adolescents who received the ABC intervention exhibited distinct global and local network properties compared with the DEF group. The ABC group demonstrated lower current-flow global efficiency and more hierarchical structure, indicating intervention-driven modulation of connectome-wide neurodevelopmental outcomes. Node-specific analyses also indicated intervention effects on clustering coefficients and communicability distances in frontal, limbic, and parietal cortices, suggesting nuanced effects of early interventions on local network properties. Exploratory moderation analyses revealed associations between brain network metrics and externalizing symptoms in the DEF group—indicative of neurobiological risk—that were absent in the ABC and low-risk groups.</div></div><div><h3>Conclusions</h3><div>The results suggest that the ABC intervention causally shapes the development of the resting-state connectome and associated regulatory health, offering insights into the neural pathways through which early enhanced care may get under the skin of at-risk adolescents.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100646"},"PeriodicalIF":3.7,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/j.bpsgos.2025.100645
Hugo Fleming , Martyna K. Stasiak , Isabel Lau , Annalise Whines , Sara Z. Mehrhof , Camilla L. Nord
Background
Signals from the body profoundly influence cognition. This process is known as interoception, and has been extensively studied in the cardiac, respiratory, and gastric domains; in contrast, metabolic influences remain poorly understood. Here, we focus on the link between glucose control and cognition, motivated by the observation that there is substantial, unexplained comorbidity between type 2 diabetes and depression. In rodents, insulin modulates dopamine signaling in the ventral striatum. We therefore hypothesized that, in humans, differences in glucose control would be associated with altered reward learning.
Methods
To test this hypothesis, we recruited 48 participants from the general population, who each completed a glucose tolerance test, a monetary reward learning task known to relate to dopamine function, and mental health questionnaires. We fitted an established reinforcement learning model to the task data to obtain computational parameters characterizing participants’ learning, and then examined the associations between these parameters and their glucose control.
Results
We discovered that poorer glucose control was associated with greater reliance on recent rewards during learning, which was in turn associated with higher levels of depression symptoms. There was also more modest evidence for the association between glucose control and depression symptoms.
Conclusions
Together, our results identify a specific neurocognitive process, reward learning, by which metabolic information may influence cognition, and which may explain the link between metabolic diseases such as type 2 diabetes and depression.
{"title":"Metabolism and the Mind: Investigating the Link Between Glucose Control and Reinforcement Learning in Humans","authors":"Hugo Fleming , Martyna K. Stasiak , Isabel Lau , Annalise Whines , Sara Z. Mehrhof , Camilla L. Nord","doi":"10.1016/j.bpsgos.2025.100645","DOIUrl":"10.1016/j.bpsgos.2025.100645","url":null,"abstract":"<div><h3>Background</h3><div>Signals from the body profoundly influence cognition. This process is known as interoception, and has been extensively studied in the cardiac, respiratory, and gastric domains; in contrast, metabolic influences remain poorly understood. Here, we focus on the link between glucose control and cognition, motivated by the observation that there is substantial, unexplained comorbidity between type 2 diabetes and depression. In rodents, insulin modulates dopamine signaling in the ventral striatum. We therefore hypothesized that, in humans, differences in glucose control would be associated with altered reward learning.</div></div><div><h3>Methods</h3><div>To test this hypothesis, we recruited 48 participants from the general population, who each completed a glucose tolerance test, a monetary reward learning task known to relate to dopamine function, and mental health questionnaires. We fitted an established reinforcement learning model to the task data to obtain computational parameters characterizing participants’ learning, and then examined the associations between these parameters and their glucose control.</div></div><div><h3>Results</h3><div>We discovered that poorer glucose control was associated with greater reliance on recent rewards during learning, which was in turn associated with higher levels of depression symptoms. There was also more modest evidence for the association between glucose control and depression symptoms.</div></div><div><h3>Conclusions</h3><div>Together, our results identify a specific neurocognitive process, reward learning, by which metabolic information may influence cognition, and which may explain the link between metabolic diseases such as type 2 diabetes and depression.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100645"},"PeriodicalIF":3.7,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.bpsgos.2025.100642
Kateryna Golovina , Mai Gutvilig , Ripsa Niemi , Christian Hakulinen
Background
Previous research has shown assortative mating across various psychiatric disorders; however, their definitions of partnership have often been limited, and the timing of relationship formation has been imprecise. In this study, we aimed to comprehensively examine assortative mating across the full spectrum of mental disorders using population-wide register data from Finland that include information on the formation of both marriages and cohabiting unions.
Methods
We used nationwide data on all cohabitations and marriages between 2000 and 2020 from the Finnish Population Register (n = 1,271,242 partnerships). Broad and specific categories of mental disorder diagnoses were retrieved from both primary and secondary health care registers in Finland. We calculated tetrachoric correlations between partners’ mental disorder diagnoses, considering only diagnoses received before the start of cohabitation or marriage.
Results
Assortative mating was observed across the full spectrum of mental disorders, with the strongest within-disorder correlations for schizophrenia, psychotic disorders, organic mental disorders, and intellectual disabilities (r > 0.50). Moderate correlations were found for mood and anxiety disorders. Adjusting for birth decade and excluding comorbidities slightly attenuated the associations but did not change the overall patterns.
Conclusions
This study suggests that assortative mating is prevalent in mental disorders. Assortative mating may contribute to the transmission and clustering of mental disorders within families, highlighting the importance of considering partner selection in mental health research and policy making.
{"title":"Assortative Mating Across the Full Spectrum of Mental Disorders: A Nationwide Finnish Register Study","authors":"Kateryna Golovina , Mai Gutvilig , Ripsa Niemi , Christian Hakulinen","doi":"10.1016/j.bpsgos.2025.100642","DOIUrl":"10.1016/j.bpsgos.2025.100642","url":null,"abstract":"<div><h3>Background</h3><div>Previous research has shown assortative mating across various psychiatric disorders; however, their definitions of partnership have often been limited, and the timing of relationship formation has been imprecise. In this study, we aimed to comprehensively examine assortative mating across the full spectrum of mental disorders using population-wide register data from Finland that include information on the formation of both marriages and cohabiting unions.</div></div><div><h3>Methods</h3><div>We used nationwide data on all cohabitations and marriages between 2000 and 2020 from the Finnish Population Register (<em>n</em> = 1,271,242 partnerships). Broad and specific categories of mental disorder diagnoses were retrieved from both primary and secondary health care registers in Finland. We calculated tetrachoric correlations between partners’ mental disorder diagnoses, considering only diagnoses received before the start of cohabitation or marriage.</div></div><div><h3>Results</h3><div>Assortative mating was observed across the full spectrum of mental disorders, with the strongest within-disorder correlations for schizophrenia, psychotic disorders, organic mental disorders, and intellectual disabilities (<em>r</em> > 0.50). Moderate correlations were found for mood and anxiety disorders. Adjusting for birth decade and excluding comorbidities slightly attenuated the associations but did not change the overall patterns.</div></div><div><h3>Conclusions</h3><div>This study suggests that assortative mating is prevalent in mental disorders. Assortative mating may contribute to the transmission and clustering of mental disorders within families, highlighting the importance of considering partner selection in mental health research and policy making.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100642"},"PeriodicalIF":3.7,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1016/j.bpsgos.2025.100611
Florian Freudenberg
{"title":"NO Time to Die: Nitric Oxide’s Ongoing Relevance in Mental Disorders","authors":"Florian Freudenberg","doi":"10.1016/j.bpsgos.2025.100611","DOIUrl":"10.1016/j.bpsgos.2025.100611","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100611"},"PeriodicalIF":3.7,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145365068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A common feature of cannabis use disorder (CUD) is an intense reactivity to cannabis cues, which are becoming increasingly visible due to the growth in its decriminalization, accessibility, and marketing of cannabis products. The brain’s automatic reactivity to cannabis cues can trigger craving and subsequent use. In this study, we aimed to test neural activity during cannabis cue reactivity in non–treatment-seeking individuals with moderate-to-severe CUD and past attempts to cut down/quit.
Methods
The study examined 65 individuals with moderate-to-severe CUD and 43 control participants, with a functional magnetic resonance imaging cannabis cue-reactivity task and assessment of mental health and substance use as well as cognitive testing. Group differences in neural responses to cannabis cue reactivity were examined, adjusting for age and sex; correlations with cannabis use characteristics and mental health variables were assessed, accounting for recent substance use.
Results
Compared with control participants, individuals with CUD showed greater brain activity during cannabis cue reactivity in the superior/middle occipital, medial/lateral orbitofrontal cortex, anterior/posterior cingulate, cerebellar, hippocampus, and middle temporal and lateral parietal cortices (p < .05; cluster k > 10, familywise error corrected). Greater occipital/cerebellar activity correlated with greater subjective arousal toward cannabis images and cannabis withdrawal scores, while anterior cingulate/inferior parietal activity negatively correlated with urinary level of 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol:creatinine (ps < .05).
Conclusions
Exposure to cannabis cues can elicit greater activity within salience evaluation/attention, motivation, and disinhibition pathways of addiction neurocircuitry in people with moderate-to-severe CUD, consistent with prominent neuroscientific theories of addiction and findings with other substances. Interventions that can suppress brain activity in salience and attention circuits during cannabis cue reactivity may help reduce craving and subsequent use.
大麻使用障碍（CUD）的一个共同特征是对大麻的强烈反应，由于大麻产品的非犯罪化、可及性和营销的增长，这种反应越来越明显。大脑对大麻的自动反应会引发对大麻的渴望和随后的使用。在这项研究中，我们旨在测试中度至重度CUD患者在大麻线索反应期间的神经活动，这些患者没有寻求治疗，过去曾尝试减少/戒烟。方法对65例中重度CUD患者和43例对照患者进行功能性磁共振成像大麻线索反应任务、心理健康和物质使用评估以及认知测试。研究了大麻线索反应的神经反应组差异，并根据年龄和性别进行了调整；评估了大麻使用特征和心理健康变量之间的相关性，考虑到最近的物质使用情况。结果与对照组相比，CUD患者在大麻线索反应过程中，在枕上/枕中、眶额内侧/外侧皮层、扣带前部/后部、小脑、海马、颞叶中部和顶叶外侧皮层表现出更大的大脑活动（p < 0.05；聚类k >； 10，家庭误差校正）。枕叶/小脑活动越活跃，对大麻图像和大麻戒断评分的主观唤醒程度越高，而前扣带/下顶叶活动与尿中11- no -9-羧基-Δ9-tetrahydrocannabinol：肌酐水平呈负相关（ps < 0.05）。结论暴露于大麻线索可引起中重度CUD患者成瘾神经回路的显着性评价/注意、动机和去抑制通路的更大活动，这与著名的成瘾神经科学理论和其他物质的研究结果一致。在大麻线索反应期间，可以抑制大脑突出和注意回路活动的干预措施可能有助于减少渴望和随后的使用。
{"title":"The Neurocircuitry of Cannabis Cue Reactivity in Cannabis Use Disorder: A Functional Neuroimaging Study","authors":"Valentina Lorenzetti , Hannah Sehl , Arush Honnedevasthana Arun , Eugene McTavish , Adam Clemente , Hannah Thomson , Marianna Quinones-Valera , Alexandra Gaillard , Emillie Beyer , Diny Thomson , Janna Cousijn , Izelle Labuschagne , Peter Rendell , Gill Terrett , Chao Suo , Lisa-Marie Greenwood , Victoria Manning , Govinda Poudel","doi":"10.1016/j.bpsgos.2025.100638","DOIUrl":"10.1016/j.bpsgos.2025.100638","url":null,"abstract":"<div><h3>Background</h3><div>A common feature of cannabis use disorder (CUD) is an intense reactivity to cannabis cues, which are becoming increasingly visible due to the growth in its decriminalization, accessibility, and marketing of cannabis products. The brain’s automatic reactivity to cannabis cues can trigger craving and subsequent use. In this study, we aimed to test neural activity during cannabis cue reactivity in non–treatment-seeking individuals with moderate-to-severe CUD and past attempts to cut down/quit.</div></div><div><h3>Methods</h3><div>The study examined 65 individuals with moderate-to-severe CUD and 43 control participants, with a functional magnetic resonance imaging cannabis cue-reactivity task and assessment of mental health and substance use as well as cognitive testing. Group differences in neural responses to cannabis cue reactivity were examined, adjusting for age and sex; correlations with cannabis use characteristics and mental health variables were assessed, accounting for recent substance use.</div></div><div><h3>Results</h3><div>Compared with control participants, individuals with CUD showed greater brain activity during cannabis cue reactivity in the superior/middle occipital, medial/lateral orbitofrontal cortex, anterior/posterior cingulate, cerebellar, hippocampus, and middle temporal and lateral parietal cortices (<em>p</em> < .05; cluster <em>k</em> > 10, familywise error corrected). Greater occipital/cerebellar activity correlated with greater subjective arousal toward cannabis images and cannabis withdrawal scores, while anterior cingulate/inferior parietal activity negatively correlated with urinary level of 11-Nor-9-carboxy-Δ<sup>9</sup>-tetrahydrocannabinol:creatinine (<em>p</em>s < .05).</div></div><div><h3>Conclusions</h3><div>Exposure to cannabis cues can elicit greater activity within salience evaluation/attention, motivation, and disinhibition pathways of addiction neurocircuitry in people with moderate-to-severe CUD, consistent with prominent neuroscientific theories of addiction and findings with other substances. Interventions that can suppress brain activity in salience and attention circuits during cannabis cue reactivity may help reduce craving and subsequent use.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100638"},"PeriodicalIF":3.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-10DOI: 10.1016/j.bpsgos.2025.100627
Dwight L. Evans , Sergei Spitsin , Kevin G. Lynch , Chelsea D. Voytek , Menvekeh G. Daramay , Elizabeth A. Hembree , Danielle Fiore , Robert Gross , J. Cobb Scott , Steven D. Douglas , Michael E. Thase
Background
This study was a randomized controlled trial investigating the effects of a selective serotonin reuptake inhibitor (SSRI) and improvement in depressive symptoms on innate immunity and inflammation in people with HIV (PWH).
Methods
The mean 17-item Hamilton Depression Rating Scale (HAMD-17) score at baseline was 19.1 for the sample (N = 108). Eligible participants were randomized to 10 weeks of double-blind therapy with either SSRI (escitalopram) or placebo. All participants concurrently received computer-assisted cognitive behavioral therapy (CCBT). Peripheral blood was obtained from each participant at baseline and at weeks 2, 4, and 10, and intracellular interferon gamma (IFN-γ) in natural killer (NK) cells, lytic units per 107 NK cells (LUNKs), interleukin 6 (IL-6), and C-reactive protein (CRP) were measured.
Results
Participants showed substantial reduction in depressive symptoms during study with final HAMD-17 score of 8.00 (average decrease of 11.0 units). However, there was no statistically significant effect of treatment, whether viewed as a group × time interaction (F1,166 = 0.00, p = .976) or as a main effect for group (F1,667 = 0.50, p = .479). There were no statistically significant differences between the groups on the immune parameters over time. There was little evidence that the magnitude of symptom improvement was associated with changes in immune measures.
Conclusions
Our study did not demonstrate superiority of treatment with SSRI+CCBT versus placebo+CCBT. Patients in both arms showed improvement of depression symptoms, which did not correlate with changes in immune markers. We found no evidence of decreased inflammation (IL-6, CRP) or immune restoration (LUNKs or intracellular IFN-γ) following treatment with CCBT with or without active escitalopram. While antidepressant treatment is indicated for PWH with depression, we observed no evidence of direct immunologic benefits.
本研究是一项随机对照试验，旨在研究选择性血清素再摄取抑制剂（SSRI）和抑郁症状的改善对HIV （PWH）患者先天免疫和炎症的影响。方法样本（108例）17项汉密尔顿抑郁评定量表（HAMD-17）基线平均得分为19.1分。符合条件的参与者被随机分配到SSRI（艾司西酞普兰）或安慰剂的10周双盲治疗。所有参与者同时接受计算机辅助认知行为治疗（CCBT）。在基线和第2周、第4周和第10周采集每位参与者的外周血，并测量自然杀伤（NK）细胞中的细胞内干扰素γ (IFN-γ)、每107个NK细胞（LUNKs）的溶解单位、白细胞介素6 （IL-6）和c反应蛋白（CRP）。结果受试者抑郁症状明显减轻，最终HAMD-17评分为8.00分（平均下降11.0分）。然而，无论是作为组间交互作用（f1166 = 0.00, p = .976）还是作为组内主要作用（f1667 = 0.50, p = .479），治疗均无统计学显著影响。各组间免疫参数随时间变化无统计学差异。几乎没有证据表明症状改善的程度与免疫措施的改变有关。结论我们的研究并未证明SSRI+CCBT治疗优于安慰剂+CCBT治疗。两组患者均表现出抑郁症状的改善，这与免疫标记物的变化无关。我们没有发现在CCBT治疗后炎症（IL-6， CRP）或免疫恢复（lunk或细胞内IFN-γ）减少的证据。虽然抗抑郁治疗适用于伴有抑郁症的PWH，但我们没有观察到直接免疫益处的证据。
{"title":"A Placebo-Controlled Randomized Trial of the Effects of Escitalopram on Depressive Symptoms and Immune Function in People With HIV","authors":"Dwight L. Evans , Sergei Spitsin , Kevin G. Lynch , Chelsea D. Voytek , Menvekeh G. Daramay , Elizabeth A. Hembree , Danielle Fiore , Robert Gross , J. Cobb Scott , Steven D. Douglas , Michael E. Thase","doi":"10.1016/j.bpsgos.2025.100627","DOIUrl":"10.1016/j.bpsgos.2025.100627","url":null,"abstract":"<div><h3>Background</h3><div>This study was a randomized controlled trial investigating the effects of a selective serotonin reuptake inhibitor (SSRI) and improvement in depressive symptoms on innate immunity and inflammation in people with HIV (PWH).</div></div><div><h3>Methods</h3><div>The mean 17-item Hamilton Depression Rating Scale (HAMD-17) score at baseline was 19.1 for the sample (<em>N</em> = 108). Eligible participants were randomized to 10 weeks of double-blind therapy with either SSRI (escitalopram) or placebo. All participants concurrently received computer-assisted cognitive behavioral therapy (CCBT). Peripheral blood was obtained from each participant at baseline and at weeks 2, 4, and 10, and intracellular interferon gamma (IFN-γ) in natural killer (NK) cells, lytic units per 10<sup>7</sup> NK cells (LUNKs), interleukin 6 (IL-6), and C-reactive protein (CRP) were measured.</div></div><div><h3>Results</h3><div>Participants showed substantial reduction in depressive symptoms during study with final HAMD-17 score of 8.00 (average decrease of 11.0 units). However, there was no statistically significant effect of treatment, whether viewed as a group × time interaction (<em>F</em><sub>1,166</sub> = 0.00, <em>p</em> = .976) or as a main effect for group (<em>F</em><sub>1,667</sub> = 0.50, <em>p</em> = .479). There were no statistically significant differences between the groups on the immune parameters over time. There was little evidence that the magnitude of symptom improvement was associated with changes in immune measures.</div></div><div><h3>Conclusions</h3><div>Our study did not demonstrate superiority of treatment with SSRI+CCBT versus placebo+CCBT. Patients in both arms showed improvement of depression symptoms, which did not correlate with changes in immune markers. We found no evidence of decreased inflammation (IL-6, CRP) or immune restoration (LUNKs or intracellular IFN-γ) following treatment with CCBT with or without active escitalopram. While antidepressant treatment is indicated for PWH with depression, we observed no evidence of direct immunologic benefits.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100627"},"PeriodicalIF":3.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Various cognitive and emotional factors shape our perception of time. Notably, individuals experiencing depressive symptoms often report changes in their time perception, characterized by a phenomenon termed depressive time dilation, or a subjective slowing of temporal flow. However, research on this topic has yielded conflicting and inconclusive findings, leaving the mechanisms behind altered time perception in depression largely unknown. In this study, we aim to explore the neural dynamics underlying the influence of emotional experiences on time perception in relation to depressive symptomatology.
Methods
A total of 120 university students participated in a retrospective time estimation task after watching either sad or neutral emotion-eliciting videos. Moreover, participants’ electroencephalographic (EEG) activity was recorded for the whole duration of the experiment by means of a high-density EEG cap. The severity of depressive symptoms was assessed using the Patient Health Questionnaire-9.
Results
Our findings revealed notable differences between individuals with depressive symptoms and healthy control individuals. Specifically, emotional modulation influenced time estimations exclusively in healthy control individuals. Moreover, individuals with depressive symptoms exhibited a significant relationship between beta band power and retrospective time estimations, specifically after watching the neutral video.
Conclusions
These results suggest that cognitive processes related to depression may disrupt the link between emotions and time perception. Overall, our study contributes to a deeper understanding of the interplay between emotional experience, cognitive processes, and time perception in individuals with depressive symptoms.
{"title":"Emotional Blunting and Time Estimation in Depression","authors":"Francesca Mura , Vincenzo Catrambone , Gaetano Valenza , Virginie Van Wassenhove , Giovanna Mioni , Claudio Gentili","doi":"10.1016/j.bpsgos.2025.100626","DOIUrl":"10.1016/j.bpsgos.2025.100626","url":null,"abstract":"<div><h3>Background</h3><div>Various cognitive and emotional factors shape our perception of time. Notably, individuals experiencing depressive symptoms often report changes in their time perception, characterized by a phenomenon termed depressive time dilation, or a subjective slowing of temporal flow. However, research on this topic has yielded conflicting and inconclusive findings, leaving the mechanisms behind altered time perception in depression largely unknown. In this study, we aim to explore the neural dynamics underlying the influence of emotional experiences on time perception in relation to depressive symptomatology.</div></div><div><h3>Methods</h3><div>A total of 120 university students participated in a retrospective time estimation task after watching either sad or neutral emotion-eliciting videos. Moreover, participants’ electroencephalographic (EEG) activity was recorded for the whole duration of the experiment by means of a high-density EEG cap. The severity of depressive symptoms was assessed using the Patient Health Questionnaire-9.</div></div><div><h3>Results</h3><div>Our findings revealed notable differences between individuals with depressive symptoms and healthy control individuals. Specifically, emotional modulation influenced time estimations exclusively in healthy control individuals. Moreover, individuals with depressive symptoms exhibited a significant relationship between beta band power and retrospective time estimations, specifically after watching the neutral video.</div></div><div><h3>Conclusions</h3><div>These results suggest that cognitive processes related to depression may disrupt the link between emotions and time perception. Overall, our study contributes to a deeper understanding of the interplay between emotional experience, cognitive processes, and time perception in individuals with depressive symptoms.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100626"},"PeriodicalIF":3.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-08DOI: 10.1016/j.bpsgos.2025.100629
Ashraf Mahmud , Giovanni Hernandez , Fatme Abboud , Cecilia Flores
Background
Elevated expression of the guidance cue receptor gene DCC in the adult prefrontal cortex (PFC) is a hallmark of major depressive disorder. DCC receptors regulate neuronal connectivity and plasticity in adulthood. In male mice, Dcc knockout in the PFC promotes resilience to behavioral dysregulation following chronic social defeat stress (CSDS), whereas Dcc upregulation increases susceptibility. However, the underlying mechanisms remain to be elucidated.
Methods
We combined CSDS, behavioral tests (i.e., social interaction, nestlet shredding, and dark-light tests), retrograde neuronal tracing, and quantitative neuroanatomical analysis in adult male mice (N = 90) to investigate whether DCC receptors contribute to stress susceptibility/resilience by remodeling dendritic spine architecture of selective PFC neuronal networks.
Results
CSDS reduced both mature and newly formed spines on the apical, but not basal, dendrites of PFC pyramidal neurons. This effect was prevented by downregulating DCC receptors in these neurons, a manipulation that also prevented depression-like behaviors, suggesting a mechanistic link. DCC-expressing neurons in the PFC predominantly projected to the nucleus accumbens, and social defeat stress induced dendritic spine loss specifically in projections from the infralimbic PFC. Notably, knockout of DCC receptors in infralimbic PFC neurons projecting to the nucleus accumbens shell protected against stress-induced social avoidance.
Conclusions
DCC receptors may influence susceptibility or resilience to social stress–induced depression-like behaviors by altering the apical dendritic architecture of PFC pyramidal neurons, particularly those projecting to the nucleus accumbens shell. This mechanism may be at play in the neurobiology of depression, pointing to DCC receptors as promising therapeutic targets.
{"title":"Stress-Induced Dysregulation of the Guidance Cue Receptor DCC Alters Corticolimbic Circuit Architecture","authors":"Ashraf Mahmud , Giovanni Hernandez , Fatme Abboud , Cecilia Flores","doi":"10.1016/j.bpsgos.2025.100629","DOIUrl":"10.1016/j.bpsgos.2025.100629","url":null,"abstract":"<div><h3>Background</h3><div>Elevated expression of the guidance cue receptor gene <em>DCC</em> in the adult prefrontal cortex (PFC) is a hallmark of major depressive disorder. DCC receptors regulate neuronal connectivity and plasticity in adulthood. In male mice, <em>Dcc</em> knockout in the PFC promotes resilience to behavioral dysregulation following chronic social defeat stress (CSDS), whereas <em>Dcc</em> upregulation increases susceptibility. However, the underlying mechanisms remain to be elucidated.</div></div><div><h3>Methods</h3><div>We combined CSDS, behavioral tests (i.e., social interaction, nestlet shredding, and dark-light tests), retrograde neuronal tracing, and quantitative neuroanatomical analysis in adult male mice (<em>N</em> = 90) to investigate whether DCC receptors contribute to stress susceptibility/resilience by remodeling dendritic spine architecture of selective PFC neuronal networks.</div></div><div><h3>Results</h3><div>CSDS reduced both mature and newly formed spines on the apical, but not basal, dendrites of PFC pyramidal neurons. This effect was prevented by downregulating DCC receptors in these neurons, a manipulation that also prevented depression-like behaviors, suggesting a mechanistic link. DCC-expressing neurons in the PFC predominantly projected to the nucleus accumbens, and social defeat stress induced dendritic spine loss specifically in projections from the infralimbic PFC. Notably, knockout of DCC receptors in infralimbic PFC neurons projecting to the nucleus accumbens shell protected against stress-induced social avoidance.</div></div><div><h3>Conclusions</h3><div>DCC receptors may influence susceptibility or resilience to social stress–induced depression-like behaviors by altering the apical dendritic architecture of PFC pyramidal neurons, particularly those projecting to the nucleus accumbens shell. This mechanism may be at play in the neurobiology of depression, pointing to DCC receptors as promising therapeutic targets.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100629"},"PeriodicalIF":3.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-30DOI: 10.1016/j.bpsgos.2025.100624
Priscila Dib Gonçalves , James O. Woodruff , Maria Olivia Pozzolo Pedro , Milenna T. van Dijk , Emilie Bruzelius , Silvia S. Martins , Gretchen Bandoli , Alexandra Potter , Leigh-Anne Cioffredi , Ardesheer Talati , Matthew D. Albaugh
Understanding the impact of prenatal cannabis exposure (PCE) on brain development is increasingly important given rising cannabis use during pregnancy. Many existing reviews on this topic are more than 5 years old and may not reflect recent social shifts that could impact cannabis use during pregnancy; they also have not utilized the recently available large longitudinal datasets for more robust and population-representative investigations. In this narrative review, we aim to provide an updated and expanded examination of the associations between PCE and magnetic resonance imaging (MRI)–based brain outcomes from in utero development to adolescence. We included studies published after 2019 that used at least one of the following measures: structural MRI, diffusion-weighted imaging, resting-state fMRI, and/or task-based fMRI. Across 9 studies that met criteria, 1 study focused on MRI outcomes in utero, 2 in infancy, and 6 in early adolescence, and only 3 studies included MRI and behavior outcomes. PCE was linked to differences in frontal, parietal, and temporal areas, spanning from in utero to adolescence across multiple MRI modalities. However, in the current state of the literature, detecting a consistent trend on PCE’s impact on MRI findings was not possible. Furthermore, we found several divergences in study design: varying approaches to assessment (e.g., self-report vs. urine toxicology); difficulties in accounting for prenatal exposure to multiple substances; limited information on timing, frequency, potency, or mode of consumption; and the influence of parental or postnatal factors. Future research should implement designs that can rigorously capture the abovementioned elements to permit replication and eventual meta-analyses on this critical topic.
{"title":"Investigating Links Between Prenatal Cannabis Exposure and Brain Development Using Magnetic Resonance Imaging Techniques: A Narrative Review","authors":"Priscila Dib Gonçalves , James O. Woodruff , Maria Olivia Pozzolo Pedro , Milenna T. van Dijk , Emilie Bruzelius , Silvia S. Martins , Gretchen Bandoli , Alexandra Potter , Leigh-Anne Cioffredi , Ardesheer Talati , Matthew D. Albaugh","doi":"10.1016/j.bpsgos.2025.100624","DOIUrl":"10.1016/j.bpsgos.2025.100624","url":null,"abstract":"<div><div>Understanding the impact of prenatal cannabis exposure (PCE) on brain development is increasingly important given rising cannabis use during pregnancy. Many existing reviews on this topic are more than 5 years old and may not reflect recent social shifts that could impact cannabis use during pregnancy; they also have not utilized the recently available large longitudinal datasets for more robust and population-representative investigations. In this narrative review, we aim to provide an updated and expanded examination of the associations between PCE and magnetic resonance imaging (MRI)–based brain outcomes from in utero development to adolescence. We included studies published after 2019 that used at least one of the following measures: structural MRI, diffusion-weighted imaging, resting-state fMRI, and/or task-based fMRI. Across 9 studies that met criteria, 1 study focused on MRI outcomes in utero, 2 in infancy, and 6 in early adolescence, and only 3 studies included MRI and behavior outcomes. PCE was linked to differences in frontal, parietal, and temporal areas, spanning from in utero to adolescence across multiple MRI modalities. However, in the current state of the literature, detecting a consistent trend on PCE’s impact on MRI findings was not possible. Furthermore, we found several divergences in study design: varying approaches to assessment (e.g., self-report vs. urine toxicology); difficulties in accounting for prenatal exposure to multiple substances; limited information on timing, frequency, potency, or mode of consumption; and the influence of parental or postnatal factors. Future research should implement designs that can rigorously capture the abovementioned elements to permit replication and eventual meta-analyses on this critical topic.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100624"},"PeriodicalIF":3.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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