Molecular Psychiatry最新文献

{"title":"Prenatal cannabis exposure is associated with alterations in offspring DNA methylation at genes involved in neurodevelopment, across the life course","authors":"Alexandra J. Noble, Alex T. Adams, Jack Satsangi, Joseph M. Boden, Amy J. Osborne","doi":"10.1038/s41380-024-02752-w","DOIUrl":"https://doi.org/10.1038/s41380-024-02752-w","url":null,"abstract":"<p>Prenatal cannabis exposure (PCE) is of increasing concern globally, due to the potential impact on offspring neurodevelopment, and its association with childhood and adolescent brain development and cognitive function. However, there is currently a lack of research addressing the molecular impact of PCE, that may help to clarify the association between PCE and neurodevelopment. To address this knowledge gap, here we present epigenome-wide association study data across multiple time points, examining the effect of PCE and co-exposure with tobacco using two longitudinal studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Christchurch Health and Development Study (CHDS) at birth (0 y), 7 y and 15–17 y (ALSPAC), and ~27 y (CHDS). Our findings reveal genome-wide significant DNA methylation differences in offspring at 0 y, 7 y, 15–17 y, and 27 y associated with PCE alone, and co-exposure with tobacco. Importantly, we identified significantly differentially methylated CpG sites within the genes <i>LZTS2, NPSR1, NT5E</i>, <i>CRIP2, DOCK8, COQ5</i>, and <i>LRP5</i> that are shared between different time points throughout development in offspring. Notably, functional pathway analysis showed enrichment for differential DNA methylation in neurodevelopment, neurotransmission, and neuronal structure pathways, and this was consistent across all timepoints in both cohorts. Given the increasing volume of epidemiological evidence that suggests a link between PCE and adverse neurodevelopmental outcomes in exposed offspring, this work highlights the need for further investigation into PCE, particularly in larger cohorts.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"4 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233516","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":"Increasing hexokinase 1 expression improves mitochondrial and glycolytic functional deficits seen in sporadic Alzheimer’s disease astrocytes","authors":"Simon M. Bell, Hollie Wareing, Francesco Capriglia, Rachel Hughes, Katy Barnes, Alexander Hamshaw, Liam Adair, Allan Shaw, Alicja Olejnik, Suman De, Elizabeth New, Pamela J. Shaw, Matteo De Marco, Annalena Venneri, Daniel J. Blackburn, Laura Ferraiuolo, Heather Mortiboys","doi":"10.1038/s41380-024-02746-8","DOIUrl":"https://doi.org/10.1038/s41380-024-02746-8","url":null,"abstract":"<p>Abnormalities in cellular metabolism are seen early in Alzheimer’s disease (AD). Astrocyte support for neuronal function has a high metabolic demand, and astrocyte glucose metabolism plays a key role in encoding memory. This indicates that astrocyte metabolic dysfunction might be an early event in the development of AD. In this paper we interrogate glycolytic and mitochondrial functional changes and mitochondrial structural alterations in patients’ astrocytes derived with a highly efficient direct conversion protocol. In astrocytes derived from patients with sporadic (sAD) and familial AD (fAD) we identified reductions in extracellular lactate, total cellular ATP and an increase in mitochondrial reactive oxygen species. sAD and fAD astrocytes displayed significant reductions in mitochondrial spare respiratory capacity, have altered mitochondrial membrane potential and a stressed mitochondrial network. A reduction in glycolytic reserve and glycolytic capacity is seen. Interestingly, glycolytic reserve, mitochondrial spare respiratory capacity and extracellular lactate levels correlated positively with neuropsychological tests of episodic memory affected early in AD. We identified a deficit in the glycolytic enzyme hexokinase 1 (HK1), and correcting this deficit improved the metabolic phenotype in sAD not fAD astrocytes. Importantly, the amount of HK1 at the mitochondria was shown to be reduced in sAD astrocytes, and not in fAD astrocytes. Overexpression of HK1 in sAD astrocytes increases mitochondrial HK1 levels. In fAD astrocytes HK1 levels were unaltered at the mitochondria after overexpression. This study highlights a clear metabolic deficit in AD patient-derived astrocytes and indicates how HK1, with its roles in both oxidative phosphorylation and glycolysis, contributes to this.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"59 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174970","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":"Transcriptomic profiles in major depressive disorder: the role of immunometabolic and cell-cycle-related pathways in depression with different levels of inflammation","authors":"Luca Sforzini, Moira Marizzoni, Chiara Bottanelli, Veronika Kunšteková, Valentina Zonca, Samantha Saleri, Melisa Kose, Giulia Lombardo, Nicole Mariani, Maria A. Nettis, Naghmeh Nikkheslat, Courtney Worrell, Zuzanna Zajkowska, Linda Pointon, Philip J. Cowen, Jonathan Cavanagh, Neil A. Harrison, Marco A. Riva, Valeria Mondelli, Edward T. Bullmore, Annamaria Cattaneo, Carmine M. Pariante","doi":"10.1038/s41380-024-02736-w","DOIUrl":"https://doi.org/10.1038/s41380-024-02736-w","url":null,"abstract":"<p>Transcriptomic profiles are important indicators for molecular mechanisms and pathways involved in major depressive disorder (MDD) and its different phenotypes, such as immunometabolic depression. We performed whole-transcriptome and pathway analyses on 139 individuals from the observational, case-control, BIOmarkers in DEPression (BIODEP) study, 105 with MDD and 34 controls. We divided MDD participants based on levels of inflammation, as measured by serum high-sensitivity C-reactive protein (CRP), in <i>n</i> = 39 ‘not inflamed’ (CRP &lt; 1 mg/L), <i>n</i> = 31 with ‘elevated CRP’ (1–3 mg/L), and <i>n</i> = 35 with ‘low-grade inflammation’ (&gt;3 mg/L). We performed whole-blood RNA sequencing using Illumina NextSeq 550 and statistical analyses with the Deseq2 package for R statistics (RUV-corrected) and subsequent pathway analyses with Ingenuity Pathway Analysis. Immunometabolic pathways were activated in individuals with CRP &gt; 1 mg/L, although surprisingly the CRP 1–3 group showed stronger immune activation than the CRP &gt; 3 group. The main pathways identified in the comparison between CRP &lt; 1 group and controls were cell-cycle-related, which may be protective against immunometabolic abnormalities in this ‘non-inflamed’ depressed group. We further divided MDD participants based on exposure and response to antidepressants (<i>n</i> = 47 non-responders, <i>n</i> = 37 responders, and <i>n</i> = 22 unmedicated), and identified specific immunomodulatory and neuroprotective pathways in responders (especially vs. non-responders), which could be relevant to treatment response. In further subgroup analyses, we found that the specific transcriptional profile of responders is independent of CRP levels, and that the inhibition of cell-cycle-related pathways in MDD with CRP &lt; 1 mg/L is present only in those who are currently depressed, and not in the responders. The present study demonstrates immunometabolic and cell-cycle-related transcriptomic pathways associated with MDD and different (CRP-based and treatment-based) MDD phenotypes, while shedding light on potential molecular mechanisms that could prevent or facilitate an individual’s trajectory toward immunometabolic depression and/or treatment-non-responsive depression. The recognition and integration of these mechanisms will facilitate a precision-medicine approach in MDD.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"27 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231407","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":"Spatio-temporal mechanisms of consolidation, recall and reconsolidation in reward-related memory trace","authors":"Adam Hamed, Miron Bartosz Kursa, Wiktoria Mrozek, Krzysztof Piotr Piwoński, Monika Falińska, Konrad Danielewski, Emilia Rejmak, Urszula Włodkowska, Stepan Kubik, Rafał Czajkowski","doi":"10.1038/s41380-024-02738-8","DOIUrl":"https://doi.org/10.1038/s41380-024-02738-8","url":null,"abstract":"<p>The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"105 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174967","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":"Schizophrenia is associated with altered DNA methylation variance","authors":"Dylan J. Kiltschewskij, William R. Reay, Murray J. Cairns","doi":"10.1038/s41380-024-02749-5","DOIUrl":"https://doi.org/10.1038/s41380-024-02749-5","url":null,"abstract":"<p>Varying combinations of genetic and environmental risk factors are thought to underpin phenotypic heterogeneity between individuals in psychiatric conditions such as schizophrenia. While epigenome-wide association studies in schizophrenia have identified extensive alteration of mean DNA methylation levels, less is known about the location and impact of DNA methylation variance, which could contribute to phenotypic and treatment response heterogeneity. To explore this question, we conducted the largest meta-analysis of blood DNA methylation variance in schizophrenia to date, leveraging three cohorts comprising 1036 individuals with schizophrenia and 954 non-psychiatric controls. Surprisingly, only a small proportion (0.1%) of the 213 variably methylated positions (VMPs) associated with schizophrenia (Benjamini-Hochberg FDR &lt; 0.05) were shared with differentially methylated positions (DMPs; sites with mean changes between cases and controls). These blood-derived VMPs were found to be overrepresented in genes previously associated with schizophrenia and amongst brain-enriched genes, with evidence of concordant changes at VMPs in the cerebellum, hippocampus, prefrontal cortex, or striatum. Epigenetic covariance was also observed with respect to clinically significant metrics including age of onset, cognitive deficits, and symptom severity. We also uncovered a significant VMP in individuals with first-episode psychosis (<i>n</i> = 644) from additional cohorts and a non-psychiatric comparison group (<i>n</i> = 633). Collectively, these findings suggest schizophrenia is associated with significant changes in DNA methylation variance, which may contribute to individual-to-individual heterogeneity.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"123 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174968","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":"Safety of psychotropic medications in pregnancy: an umbrella review","authors":"Nicholas Fabiano, Stanley Wong, Arnav Gupta, Jason Tran, Nishaant Bhambra, Kevin K. Min, Elena Dragioti, Corrado Barbui, Jess G. Fiedorowicz, Corentin J. Gosling, Samuele Cortese, Jasmine Gandhi, Gayatri Saraf, Risa Shorr, Simone N. Vigod, Benicio N. Frey, Richard Delorme, Marco Solmi","doi":"10.1038/s41380-024-02697-0","DOIUrl":"https://doi.org/10.1038/s41380-024-02697-0","url":null,"abstract":"<p>Weighing risks and benefits of the use of psychotropic medications during pregnancy remains a challenge worldwide. We systematically assessed the strength of associations between psychotropic medication use in pregnant people with mental disorders and various adverse health outcomes in both pregnant people and foetuses. Systematic reviews with meta-analyses of observational studies investigating the association between exposure to psychotropic medication in pregnancy and any adverse health outcomes were included. Credibility was graded into convincing, highly suggestive, suggestive, weak or not significant. Quality of the meta-analyses and of individual studies were assessed with A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) the Newcastle-Ottawa Scale (NOS), respectively. We considered 21 meta-analyses encompassing 17,290,755 participants (AMSTAR 2 high = 1, low = 12, or critically low = 8). Evidence was suggestive for: (1) preterm birth in pregnant people with either any mental disorder (equivalent odds ratio 1.62 (95% confidence interval 1.24–2.12) or depression (1.65 [1.34–2.02]) receiving antidepressants during any trimester of pregnancy; (2) small for gestational age for pregnant people with depression receiving a SSRI during any trimester of pregnancy (1.50 [1.19–1.90]); and (3) major congenital malformation (1.24 [1.09–1.40]) or cardiac malformations (1.28 [1.11–1.47]) in babies for pregnant people with depression or anxiety receiving paroxetine during first trimester of pregnancy. Additional associations were supported by weak evidence, or were not statistically significant. This umbrella review found no convincing or highly suggestive level of evidence of adverse health outcomes associated with psychotropic medication use in pregnant people with mental disorders.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"105 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174974","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":"Molecular and micro-architectural mapping of gray matter alterations in psychosis","authors":"Natalia García-San-Martín, Richard A. I. Bethlehem, Agoston Mihalik, Jakob Seidlitz, Isaac Sebenius, Claudio Alemán-Morillo, Lena Dorfschmidt, Golia Shafiei, Víctor Ortiz-García de la Foz, Kate Merritt, Anthony David, Sarah E. Morgan, Miguel Ruiz-Veguilla, Rosa Ayesa-Arriola, Javier Vázquez-Bourgon, Aaron Alexander-Bloch, Bratislav Misic, Edward T. Bullmore, John Suckling, Benedicto Crespo-Facorro, Rafael Romero-García","doi":"10.1038/s41380-024-02724-0","DOIUrl":"https://doi.org/10.1038/s41380-024-02724-0","url":null,"abstract":"<p>The psychosis spectrum encompasses a heterogeneous range of clinical conditions associated with abnormal brain development. Detecting patterns of atypical neuroanatomical maturation across psychiatric disorders requires an interpretable metric standardized by age-, sex- and site-effect. The molecular and micro-architectural attributes that account for these deviations in brain structure from typical neurodevelopment are still unknown. Here, we aggregate structural magnetic resonance imaging data from 38,696 healthy controls (HC) and 1256 psychosis-related conditions, including first-degree relatives of schizophrenia (SCZ) and schizoaffective disorder (SAD) patients (<i>n</i> = 160), individuals who had psychotic experiences (<i>n</i> = 157), patients who experienced a first episode of psychosis (FEP, <i>n</i> = 352), and individuals with chronic SCZ or SAD (<i>n</i> = 587). Using a normative modeling approach, we generated centile scores for cortical gray matter (GM) phenotypes, identifying deviations in regional volumes below the expected trajectory for all conditions, with a greater impact on the clinically diagnosed ones, FEP and chronic. Additionally, we mapped 46 neurobiological features from healthy individuals (including neurotransmitters, cell types, layer thickness, microstructure, cortical expansion, and metabolism) to these abnormal centiles using a multivariate approach. Results revealed that neurobiological features were highly co-localized with centile deviations, where metabolism (e.g., cerebral metabolic rate of oxygen (CMRGlu) and cerebral blood flow (CBF)) and neurotransmitter concentrations (e.g., serotonin (5-HT) and acetylcholine (α₄β₂) receptors) showed the most consistent spatial overlap with abnormal GM trajectories. Taken together these findings shed light on the vulnerability factors that may underlie atypical brain maturation during different stages of psychosis.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"17 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142171064","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":"Large-scale brain connectivity changes following the administration of lysergic acid diethylamide, d-amphetamine, and 3,4-methylenedioxyamphetamine","authors":"Mihai Avram, Lydia Fortea, Lea Wollner, Ricarda Coenen, Alexandra Korda, Helena Rogg, Friederike Holze, Patrick Vizeli, Laura Ley, Joaquim Radua, Felix Müller, Matthias E. Liechti, Stefan Borgwardt","doi":"10.1038/s41380-024-02734-y","DOIUrl":"https://doi.org/10.1038/s41380-024-02734-y","url":null,"abstract":"<p>Psychedelics have recently attracted significant attention for their potential to mitigate symptoms associated with various psychiatric disorders. However, the precise neurobiological mechanisms responsible for these effects remain incompletely understood. A valuable approach to gaining insights into the specific mechanisms of action involves comparing psychedelics with substances that have partially overlapping neurophysiological effects, i.e., modulating the same neurotransmitter systems. Imaging data were obtained from the clinical trial NCT03019822, which explored the acute effects of lysergic acid diethylamide (LSD), d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 28 healthy volunteers. The clinical trial employed a double-blind, placebo-controlled, crossover design. Herein, various resting-state connectivity measures were examined, including within-network connectivity (integrity), between-network connectivity (segregation), seed-based connectivity of resting-state networks, and global connectivity. Differences between placebo and the active conditions were assessed using repeated-measures ANOVA, followed by post-hoc pairwise t-tests. Changes in voxel-wise seed-based connectivity were correlated with serotonin 2 A receptor density maps. Compared to placebo, all substances reduced integrity in several networks, indicating both common and unique effects. While LSD uniquely reduced integrity in the default-mode network (DMN), the amphetamines, in contrast to our expectations, reduced integrity in more networks than LSD. However, LSD exhibited more pronounced segregation effects, characterized solely by decreases, in contrast to the amphetamines, which also induced increases. Across all substances, seed-based connectivity mostly increased between networks, with LSD demonstrating more pronounced effects than both amphetamines. Finally, while all substances decreased global connectivity in visual areas, compared to placebo, LSD specifically increased global connectivity in the basal ganglia and thalamus. These findings advance our understanding of the distinctive neurobiological effects of psychedelics, prompting further exploration of their therapeutic potential.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166276","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":"Nicotine dependence and incident psychiatric disorders: prospective evidence from US national study","authors":"Guillaume Airagnes, Marina Sánchez-Rico, Amélia Deguilhem, Carlos Blanco, Mark Olfson, Charles Ouazana Vedrines, Cédric Lemogne, Frédéric Limosin, Nicolas Hoertel","doi":"10.1038/s41380-024-02748-6","DOIUrl":"https://doi.org/10.1038/s41380-024-02748-6","url":null,"abstract":"<p>We examined the prospective associations between nicotine dependence and the likelihood of psychiatric and substance use disorders in the general adult population. Participants came from a nationally representative sample of US adults aged 18 years or older, who were interviewed 3 years apart in the National Epidemiologic Survey on Alcohol and Related Conditions (Wave 1, 2001–2002; Wave 2, 2004–2005). The primary analyses were limited to 32,671 respondents (13,751 male (47.9% weighted); mean age of 45 years (SD = 0.18)) who were interviewed in both waves. We used multiple regression and propensity score matching (PSM) to estimate the strength of independent associations between nicotine dependence related to the use of tobacco products at Wave 1 and incident psychiatric disorders at Wave 2. Psychiatric disorders were measured with a structured interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV). All analyses adjusted for multiple potential confounders, including childhood (family history of substance use disorders, parental loss, vulnerable family environment), early-adolescence (self-esteem, social deviance, conduct disorder), late-adolescence (education, personality and psychiatric disorders), adulthood (divorce, stressful life events, social deviance, quality of life, history of alcohol or other substance use disorder), and sociodemographic factors. Multiple regression analysis and PSM converged in indicating that nicotine dependence was associated with significantly increased incidence of any psychiatric disorder (OR = 1.39(95%CI:1.20;1.60)), including substance use disorders (OR = 1.91(95%CI:1.47;2.47)), and anxiety disorders (OR = 1.31(95%CI:1.06;1.62)). Population Attributable Risk Proportions were substantial, ranging from 12.5%(95%CI:8.10;17.0) for any psychiatric disorder to 33.3%(95%CI:18.7;48.0) for any other drug use disorder. Supplementary analyses also indicated significant associations between nicotine dependence and persistence of psychiatric and substance use disorders among patients having a disorder at Wave 1. In the general adult population, nicotine dependence is associated with an increased likelihood for several psychiatric and substance use disorders. Given its high prevalence, these findings have important public health implications.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"82 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166277","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":"Whole-brain turbulent dynamics predict responsiveness to pharmacological treatment in major depressive disorder","authors":"Anira Escrichs, Yonatan Sanz Perl, Patrick M. Fisher, Noelia Martínez-Molina, Elvira G-Guzman, Vibe G. Frokjaer, Morten L. Kringelbach, Gitte M. Knudsen, Gustavo Deco","doi":"10.1038/s41380-024-02690-7","DOIUrl":"https://doi.org/10.1038/s41380-024-02690-7","url":null,"abstract":"<p>Depression is a multifactorial clinical syndrome with a low pharmacological treatment response rate. Therefore, identifying predictors of treatment response capable of providing the basis for future developments of individualized therapies is crucial. Here, we applied model-free and model-based measures of whole-brain turbulent dynamics in resting-state functional magnetic resonance imaging (fMRI) in healthy controls and unmedicated depressed patients. After eight weeks of treatment with selective serotonin reuptake inhibitors (SSRIs), patients were classified as responders and non-responders according to the Hamilton Depression Rating Scale 6 (HAMD6). Using the model-free approach, we found that compared to healthy controls and responder patients, non-responder patients presented disruption of the information transmission across spacetime scales. Furthermore, our results revealed that baseline turbulence level is positively correlated with beneficial pharmacological treatment outcomes. Importantly, our model-free approach enabled prediction of which patients would turn out to be non-responders. Finally, our model-based approach provides mechanistic evidence that non-responder patients are less sensitive to stimulation and, consequently, less prone to respond to treatment. Overall, we demonstrated that different levels of turbulent dynamics are suitable for predicting response to SSRIs treatment in depression.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"47 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160662","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}