Molecular Psychiatry最新文献

{"title":"Gene expression profiles of endothelium, microglia and oligodendrocytes in hippocampus of post-stroke depression rat at single cell resolution","authors":"Cai Li, Wentao Li, Wenbin Wei, Qili Chen, Han Gao, Yanqing Zhao, Lingling Zhang, Li Ling, Hao Shen, Yifen Shen, Yihang Shen","doi":"10.1038/s41380-024-02810-3","DOIUrl":"https://doi.org/10.1038/s41380-024-02810-3","url":null,"abstract":"<p>Post-stroke depression (PSD) is a common but severe mental complication after stroke. However, the cellular and molecular understanding of PSD is still yet to be illustrated. In current study, we prepared PSD rat model (MD) via unilateral middle cerebral artery occlusion (MCAO) and chronic stress stimulation (DEPR), and isolated hippocampal tissues for single cell sequencing of 10x Genomics Chromium. First, we determined the presence of the increased cell population of endothelium and microglia and the compromised oligodendrocytes in MD compared to NC, MCAO and DEPR. The enriched functions of highly variable genes (HVGs) of endothelium and microglia suggested a reinforced blood-brain barrier in MD. Next, cell clusters of endothelium, microglia and oligodendrocytes were individually analyzed, and the subtypes with distinct functions were identified. The presence of expression profiles, intercellular communications and signaling pathways of these three cell populations of PSD displayed a similar but more aggressive appearance with DEPR compared to MCAO and NC. Taken together, this study characterized the specific gene profile of endothelium, microglia and oligodendrocytes of hippocampal PSD by single cell sequencing, emphasizing the crosstalk among them to provide theoretical basis for the in-depth mechanism research and drug therapy of PSD.</p><figure></figure>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"70 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal COVID-19 infection associated with offspring neurodevelopmental disorders","authors":"Lian Duan, Huamin Yin, Jiaxin Liu, Wenhang Wang, Peijun Huang, Li Liu, Jingling Shen, Zhendong Wang","doi":"10.1038/s41380-024-02822-z","DOIUrl":"https://doi.org/10.1038/s41380-024-02822-z","url":null,"abstract":"<p>Maternal COVID-19 infection increases the incidence of neurodevelopmental disorders (NDDs) in offspring, although the underlying mechanisms have not been elucidated. This study demonstrated that COVID-19 infection during pregnancy disrupted the balance of maternal and fetal immune environments, driving alterations in astrocytes, endothelial cells, and excitatory neurons. A risk score was established using 47 unique genes in the single-cell transcriptome of gestational mothers. The high risk score in CD4 proliferating T cell level served as an indicator for increased risk of offspring NDDs. Summary-based Mendelian randomization and phenome-wide association study analyses were conducted to identify the causal association of the transcriptional changes with the increased risk of offspring NDDs. Additionally, 10 drugs were identified as potential therapeutic candidates. Our findings support a model where the maternal COVID-19 infection changed the levels of CD4 proliferating T cells, leading to the alterations of astrocytes, endothelial cells, and excitatory neurons in offspring, contributing to the increased risk of NDDs in these individuals.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"147 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on “Perception of social inclusion/exclusion and response inhibition in adolescents with past suicide attempt: a multidomain task-based fMRI study.” by Gifuni et al.","authors":"Emilie Olié, Philippe Courtet","doi":"10.1038/s41380-024-02745-9","DOIUrl":"https://doi.org/10.1038/s41380-024-02745-9","url":null,"abstract":"<p>The fMRI study conducted by Gifuni et al. [1] investigates neural responses during social inclusion/exclusion tasks in suicide attempters compared to psychiatric and healthy controls. The authors highlight a significant finding regarding lower activation in the left insula during inclusion vs. control condition (i.e. passive viewing or implicit social exclusion (ISE)), in suicide attempters compared to the control groups. Additionally, they report that higher perception of social exclusion (measured by Need Threat Scale) is correlated with insular activity during inclusion-control contrast. Two critical observations merit consideration in light of these results for further investigation.</p><p>Firstly, the decreased insula activation in suicide attempters may be associated with a general processing of negative states rather than a specific impact of social exclusion. Indeed, perception of social exclusion is correlated with insular activity but also with level of depression. Interestingly Caceda et al. [2] found a significant correlation between anterior insula response during inclusion-rest and depression severity.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"36 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of fampridine on working memory: a randomized controlled trial based on a genome-guided repurposing approach","authors":"Andreas Papassotiropoulos, Virginie Freytag, Nathalie Schicktanz, Christiane Gerhards, Amanda Aerni, Tamás Faludi, Ehssan Amini, Elia Müggler, Annette Harings-Kaim, Thomas Schlitt, Dominique J.-F. de Quervain","doi":"10.1038/s41380-024-02820-1","DOIUrl":"https://doi.org/10.1038/s41380-024-02820-1","url":null,"abstract":"<p>Working memory (WM), a key component of cognitive functions, is often impaired in psychiatric disorders such as schizophrenia. Through a genome-guided drug repurposing approach, we identified fampridine, a potassium channel blocker used to improve walking in multiple sclerosis, as a candidate for modulating WM. In a subsequent double-blind, randomized, placebo-controlled, crossover trial in 43 healthy young adults (ClinicalTrials.gov, NCT04652557), we assessed fampridine’s impact on WM (3-back d-prime, primary outcome) after 3.5 days of repeated administration (10 mg twice daily). Independently of baseline cognitive performance, no significant main effect was observed (Wilcoxon <i>P</i> = 0.87, r = 0.026). However, lower baseline performance was associated with higher working memory performance after repeated intake of fampridine compared to placebo (r_s = −0.37, <i>P</i> = 0.014, <i>n</i> = 43). Additionally, repeated intake of fampridine lowered resting motor threshold (F(1,37) = 5.31, <i>P</i> = 0.027, R²β = 0.01), the non-behavioral secondary outcome, indicating increased cortical excitability linked to cognitive function. Fampridine’s capacity to enhance WM in low-performing individuals and to increase brain excitability points to its potential value for treating WM deficits.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"127 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence of altered monoamine oxidase B, an astroglia marker, in early psychosis and high-risk state","authors":"Kankana Nisha Aji, Nittha Lalang, Christian Ramos-Jiménez, Reza Rahimian, Naguib Mechawar, Gustavo Turecki, Daniel Chartrand, Isabelle Boileau, Jeffrey H. Meyer, Pablo M. Rusjan, Romina Mizrahi","doi":"10.1038/s41380-024-02816-x","DOIUrl":"https://doi.org/10.1038/s41380-024-02816-x","url":null,"abstract":"<p>A novel radiotracer, [¹¹C]SL25.1188, targets monoamine oxidase-B (MAO-B) enzyme, found primarily in astrocytes, which metabolizes monoamines (including dopamine), particularly in subcortical regions. Altered astrocyte function in schizophrenia is supported by convergent evidence from post-mortem, genetic, transcriptomic, peripheral and preclinical findings. We aimed to test whether levels of MAO-B, an index of astrocyte function are low in the living brains of early psychosis and their high-risk states. Thirty-eight participants including antipsychotic-free/minimally exposed clinical participants with first-episode psychosis (FEP), clinical high-risk (CHR) individuals and healthy volunteers (HVs) underwent a 90-min positron emission tomography (PET) scan with [¹¹C]SL25.1188, to measure MAO-B <i>V</i>_T, an index of MAO-B concentration. Participants were excluded if tested positive on urine drug screen (except for cannabis). This study of 14 FEP (mean[SD] age, 25.7[5.7] years; 6 F), 7 CHR (mean[SD] age, 20.9[3.7] years; 4 F) and 17 HV (mean[SD] age, 31.2[13.9] years; 9 F) demonstrated significant group differences in regional MAO-B <i>V</i>_T (F_(2,37.42) = 4.56, <i>p</i> = 0.02, Cohen’s <i>f</i> = 0.49), controlling for tobacco (F _(1,37.42) = 5.37, <i>p</i> = 0.03) and cannabis use (F_(1,37.42) = 5.11, <i>p</i> = 0.03) with significantly lower MAO-B <i>V</i>_T in CHR compared to HV (Cohen’s <i>d</i> = 0.99). We report a significant cannabis effect on MAO-B <i>V</i>_T (F_(1,39.19) = 12.57, <i>p</i> = 0.001, Cohen’s <i>f</i> = 0.57), with a significant group-by-cannabis interaction (F_(2,37.30) = 3.82, <i>p</i> = 0.03, Cohen’s <i>f</i> = 0.45), indicating lower MAO-B <i>V</i>_T in cannabis-using clinical groups. Lower MAO-B <i>V</i>_T levels were more robust in striatal than cortical regions, in both clinical groups (F_(12,46.84) = 2.08, <i>p</i> = 0.04, Cohen’s <i>f</i> = 0.73) and in cannabis users (F_(6,46.84) = 6.42, p &lt; 0.001, Cohen’s <i>f</i> = 0.91). Lower MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP clinical populations. Lower MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"244 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and functional analyses of CTBP2 in anorexia nervosa and body weight regulation","authors":"Johanna Giuranna, Yiran Zheng, Matthäus Brandt, Sigrid Jall, Amrita Mukherjee, Soni Shankhwar, Simone Renner, Nirup Kumar Kurapati, Caroline May, Triinu Peters, Beate Herpertz-Dahlmann, Jochen Seitz, Martina de Zwaan, Wolfgang Herzog, Stefan Ehrlich, Stephan Zipfel, Katrin Giel, Karin Egberts, Roland Burghardt, Manuel Föcker, Katrin Marcus, Kathy Keyvani, Timo D. Müller, Frank Schmitz, Luisa Sophie Rajcsanyi, Anke Hinney","doi":"10.1038/s41380-024-02791-3","DOIUrl":"https://doi.org/10.1038/s41380-024-02791-3","url":null,"abstract":"<p>The C-terminal binding protein 2 (<i>CTBP2</i>) gene (translational isoforms: CTBP2-L/S, RIBEYE) had been identified by a cross-trait analysis of genome-wide association studies for anorexia nervosa (AN) and body mass index (BMI). Here, we did a mutation analysis in <i>CTBP2</i> by performing polymerase chain reactions with subsequent Sanger-sequencing to identify variants relevant for AN and body weight regulation and ensued functional studies. Analysis of the coding regions of <i>CTBP2</i> in 462 female patients with AN (acute or recovered), 490 children and adolescents with severe obesity, 445 healthy-lean adult individuals and 168 healthy adult individuals with normal body weight detected 24 variants located in the specific exon of RIBEYE. In the initial analysis, three of these were rare non-synonymous variants (NSVs) detected heterozygously in patients with AN (p.Arg72Trp - rs146900874; p.Val289Met -rs375685611 and p.Gly362Arg - rs202010294). Four NSVs and one heterozygous frameshift variant were exclusively detected in children and adolescents with severe obesity (p.Pro53Ser - rs150867595; p.Gln175Arg<i>fs</i>Ter45 - rs141864737; p.Leu310Val - rs769811964; p.Pro397Ala - rs76134089 and p.Pro402Ser - rs113477585). <i>Ribeye</i> mRNA was detected in mouse hypothalamus. No effect of fasting or overfeeding on murine hypothalamic <i>Ribeye</i> expression was determined. Yet, increased <i>Ribeye</i> expression was detected in hypothalami of leptin-treated <i>Lep</i>^<i>ob/ob</i> mice. This increase was not related to reduced food intake and leptin-induced weight loss. We detected rare and frequent variants in the <i>RIBEYE</i> specific exon in both patients with AN and in children and adolescents with severe obesity. Our data suggest <i>RIBEYE</i> as a relevant gene for weight regulation.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"37 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimaging-based variability in subtyping biomarkers for psychiatric heterogeneity","authors":"Zhenfu Wen, Mira Z. Hammoud, Carole E. Siegel, Eugene M. Laska, Duna Abu-Amara, Amit Etkin, Mohammed R. Milad, Charles R. Marmar","doi":"10.1038/s41380-024-02807-y","DOIUrl":"https://doi.org/10.1038/s41380-024-02807-y","url":null,"abstract":"<p>Neuroimaging-based subtyping is increasingly used to explain heterogeneity in psychiatric disorders. However, the clinical utility of these subtyping efforts remains unclear, and replication has been challenging. Here we examined how the choice of neuroimaging measures influences the derivation of neuro-subtypes and the consequences for clinical delineation. On a clinically heterogeneous dataset (total <i>n</i> = 566) that included controls (<i>n</i> = 268) and cases (<i>n</i> = 298) of psychiatric conditions, including individuals diagnosed with post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and comorbidity of both (PTSD&amp;TBI), we identified neuro-subtypes among the cases using either structural, resting-state, or task-based measures. The neuro-subtypes for each modality had high internal validity but did not significantly differ in their clinical and cognitive profiles. We further show that the choice of neuroimaging measures for subtyping substantially impacts the identification of neuro-subtypes, leading to low concordance across subtyping solutions. Similar variability in neuro-subtyping was found in an independent dataset (<i>n</i> = 1642) comprised of major depression disorder (MDD, <i>n</i> = 848) and controls (<i>n</i> = 794). Our results suggest that the highly anticipated relationships between neuro-subtypes and clinical features may be difficult to discover.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"3 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripartum allopregnanolone blood concentrations and depressive symptoms: a systematic review and individual participant data meta-analysis","authors":"Georgios Schoretsanitis, Lauren M. Osborne, Inger Sundström-Poromaa, Elizabeth S. Wenzel, Jennifer L. Payne, Corrado Barbui, Chiara Gastaldon, Kristina M. Deligiannidis","doi":"10.1038/s41380-024-02747-7","DOIUrl":"https://doi.org/10.1038/s41380-024-02747-7","url":null,"abstract":"<p>Neuroactive steroids including allopregnanolone are implicated in the pathophysiology of peripartum depressive symptoms (PDS). We performed a systematic review searching PubMed/Embase/PsychInfo/Cinhail through 08/2023 (updated in 07/2024), and conducted a random-effects meta-analysis of studies comparing allopregnanolone blood concentrations in women with versus without PDS at various timepoints during the 2^nd and 3^rd trimester and the postpartum period, calculating standardized mean differences (SMDs) and 95% confidence intervals (CIs). Meta-regression and subgroup analyses included age, diagnoses of affective disorders before pregnancy, antidepressant treatment, analytical methods, and sample type. Study quality was assessed using the Newcastle-Ottawa-scale. The study protocol was registered on PROSPERO (registration number CRD42022354495). We retrieved 13 studies with 2509 women (<i>n</i> = 849 with PDS). Allopregnanolone concentrations did not differ between women with versus without PDS at any timepoint (<i>p</i> &gt; 0.05). Allopregnanolone concentrations assessed during pregnancy did not differ for women with versus without PDS at postpartum follow-up (<i>p</i> &gt; 0.05). Subgroup analyses indicated higher allopregnanolone concentrations in women with versus without PDS at gestational weeks 21–24 and 25–28 (SMD = 1.07, 95% CI = 0.04, 2.11 and SMD = 0.92, 95% CI = 0.26, 1.59 respectively). Moreover, we reported differences between studies using mass-spectrometry combined with chromatography versus immunoassays at gestational weeks 25–28 (<i>p</i> = 0.01) and plasma versus serum samples at gestational weeks 21–24 (<i>p</i> = 0.005). Study quality was rated as poor, good, and fair for two, one and ten studies respectively. PDS were not associated with differences for allopregnanolone concentrations. The use of heterogenous peripartum time points, study cohorts, depression symptom measures and analytical methods has hampered progress in elucidating neuroactive steroid signaling linked to PDS.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"244 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Projection-specific circuits of retrosplenial cortex with differential contributions to spatial cognition","authors":"Xiaoxiao Lin, Ali Ghafuri, Xiaojun Chen, Musab Kazmi, Douglas A. Nitz, Xiangmin Xu","doi":"10.1038/s41380-024-02819-8","DOIUrl":"https://doi.org/10.1038/s41380-024-02819-8","url":null,"abstract":"<p>Retrosplenial cortex (RSC) is a brain region involved in neuropsychiatric and neurodegenerative disorders. It has reciprocal connections with a diverse set of cortical and subcortical brain regions, but the afferent structure and behavioral function of circuits defined by its projection-specific sub-populations have yet to be determined. The corticocortical connections between RSC and secondary motor cortex (M2), as well as corticothalamic connections between RSC and anterodorsal thalamus (AD) have been hypothesized to function as semi-independent, but parallel pathways that impact spatial information processing in distinct ways. We used retrograde and anterograde viral tracers and monosynaptic retrograde rabies virus to quantitatively characterize and compare the afferent and efferent distributions of retrosplenial neuron sub-populations projecting to M2 and AD. AD-projecting and M2-projecting RSC neurons overlap in their collateral projections to other brain regions, but not in their projections to M2 and AD, respectively. Compared with AD-projecting RSC neurons, M2-projecting RSC neurons received much greater afferent input from the dorsal subiculum, AD, lateral dorsal and lateral posterior thalamus, and somatosensory cortex. AD-projecting RSC neurons received greater input from the anterior cingulate cortex and medial septum. We performed chemogenetic inhibition of M2- and AD-projecting RSC neurons and examined its impact on object-location memory, object-recognition, open-field exploration, and place-action association. Our findings indicate that inhibition of M2-projecting RSC neurons impairs object location memory as well as place-action association, while the RSC to AD pathway impacts only object-location memory. The findings indicate that RSC is composed of semi-independent circuits distinguishable by their afferent/efferent distributions and differing in the cognitive functions to which they contribute.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"80 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortico-limbic volume abnormalities in late life depression are distinct from β amyloid and white matter pathologies","authors":"R. Scott Mackin, Emma Rhodes, Michelle Kassel, Maria Kryza-Lacombe, Emily Burns, David Bickford, Ruth Morin, Duygu Tosun, Susan Landau, Meryl A. Butters, Paul Aisen, Rema Raman, Andrew J. Saykin, Arthur Toga, Robert Koeppe, Clifford Jack, Michael W. Weiner, Craig Nelson, Philip S. Insel","doi":"10.1038/s41380-024-02677-4","DOIUrl":"https://doi.org/10.1038/s41380-024-02677-4","url":null,"abstract":"<p>This study was conducted to clarify patterns of cortico-limbic volume abnormalities in late life depression (LLD) relative to non-depressed (ND) adults matched for amyloid β (Aβ) deposition and to evaluate the relationship of volume abnormalities with cognitive performance. Participants included 116 LLD and 226 ND. Classification accuracy of LLD status was estimated using area under the receiver operator characteristic curve. Twenty-one percent of LLD and ND participants were Aβ positive and the groups did not differ on white matter hyperintensity volume (WMH (logscale); β = 0.12, <i>p</i> = 0.28). Compared to ND, the LLD group exhibited significantly lower bilateral volume in the lateral orbitofrontal cortex, hippocampus, accumbens area, superior temporal lobe, temporal pole, and amygdala after multiple comparison correction (<i>p</i> &lt; 0.009 for all). Cortico-limbic volumes significantly improved classification of LLD beyond demographic characteristics, Aβ status, and WMH (AUC_Vol = 0.71, AUC_WMH, _Aβ = 0.62, AUC difference, 0.09 [0.03 to 0.15]). LLD exhibited poorer performance on measures of global cognition, set shifting, and verbal learning and memory relative to ND. Cognitive function was positively associated with cortico-limbic volumes and these relationships did not differ by group. Secondary analyses with an ND sample additionally matched for Mild Cognitive Impairment (MCI) diagnosis showed a similar but attenuated pattern of volume abnormalities. Overall, our results support LLD as being associated with cortico-limbic volume abnormalities that are distinct from Aβ and white matter pathologies and that these volume abnormalities are important factors associated with cognitive dysfunction in LLD.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"94 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}