Early-treatment cerebral blood flow change as a predictive biomarker of antidepressant treatment response: evidence from the EMBARC clinical trial.

BACKGROUND: Major depressive disorder (MDD) is one of the most prevalent and disabling illnesses worldwide. Treatment of MDD typically relies on trial-and-error to find an effective approach. Identifying early response-related biomarkers that predict response to antidepressants would help clinicians to decide, as early as possible, whether a particular treatment might be suitable for a given patient. METHODS: Data were from the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial. A whole-brain, voxel-wise, mixed-effects model was applied to identify early-treatment cerebral blood flow (CBF) changes as biomarkers of treatment response. We examined changes in CBF measured with arterial spin labeling 1-week after initiating double-masked sertraline/placebo. We tested whether these early 1-week scans could be used to predict response observed after 8-weeks of treatment. RESULTS: Response to 8-week placebo treatment was associated with increased cerebral perfusion in temporal cortex and reduced cerebral perfusion in postcentral region captured at 1-week of treatment. Additionally, CBF response in these brain regions was significantly correlated with improvement in Hamilton Depression Rating Scale score in the placebo group. No significant associations were found for selective serotonin reuptake inhibitor treatment. CONCLUSIONS: We conclude that early CBF responses to placebo administration in multiple brain regions represent candidate neural biomarkers of longer-term antidepressant effects.

Mapping the neural mechanism that distinguishes between holistic thinking and analytic thinking.

Holistic and analytic thinking are two distinct modes of thinking used to interpret the world with relative preferences varying across cultures. While most research on these thinking styles has focused on behavioral and cognitive aspects, a few studies have utilized functional magnetic resonance imaging (fMRI) to explore the correlations between brain metrics and self-reported scale scores. Other fMRI studies used single holistic and analytic thinking tasks. As a single task may involve processing in spurious low-level regions, we used two different holistic and analytic thinking tasks, namely the frame-line task and the triad task, to seek convergent brain regions to distinguish holistic and analytic thinking using multivariate pattern analysis (MVPA). Results showed that brain regions fundamental to distinguish holistic and analytic thinking include the bilateral frontal lobes, bilateral parietal lobes, bilateral precentral and postcentral gyrus, bilateral supplementary motor areas, bilateral fusiform, bilateral insula, bilateral angular gyrus, left cuneus, and precuneus, left olfactory cortex, cingulate gyrus, right caudate and putamen. Our study maps brain regions that distinguish between holistic and analytic thinking and provides a new approach to explore the neural representation of cultural constructs. We provide initial evidence connecting culture-related brain regions with language function to explain the origins of cultural differences in cognitive styles.

Exploring kidney biopsy findings in congenital heart diseases: Insights beyond cyanotic nephropathy.

BACKGROUND: The association between congenital heart disease and chronic kidney disease is well known. Various mechanisms of kidney damage associated with congenital heart disease have been established. The etiology of kidneydisease has commonly been considered to be secondary to focal segmental glomerulosclerosis (FSGS), however, this has only been demonstrated in case reports and not in observational or clinical trials. AIM: To identify baseline and clinical characteristics, as well as the findings in kidney biopsies of patients with congenital heart disease in our hospital. METHODS: This is a retrospective observational study conducted at the Nephrology Department of the National Institute of Cardiology "Ignacio Chávez". All patients over 16 years old who underwent percutaneous kidney biopsy from January 2000 to January 2023 with congenital heart disease were included in the study. RESULTS: Ten patients with congenital heart disease and kidney biopsy were found. The average age was 29.00 years ± 15.87 years with pre-biopsy proteinuria of 6193 mg/24 h ± 6165 mg/24 h. The most common congenital heart disease was Fallot's tetralogy with 2 cases (20%) and ventricular septal defect with 2 (20%) cases. Among the 10 cases, one case of IgA nephropathy and one case of membranoproliferative glomerulonephritis associated with immune complexes were found, receiving specific treatment after histopathological diagnosis, delaying the initiation of kidney replacement therapy. Among remaining 8 cases (80%), one case of FSGS with perihilar variety was found, while the other 7 cases were non-specific FSGS. CONCLUSION: Determining the cause of chronic kidney disease can help in delaying the need for kidney replacement therapy. In 2 out of 10 patients in our study, interventions were performed, and initiation of kidney replacement therapy was delayed. Prospective studies are needed to determine the usefulness of kidney biopsy in patients with congenital heart disease.

Feasibility and Safety of Percutaneous Kidney Biopsy in Small Kidneys: Breaking the Paradigm.

INTRODUCTION: The percutaneous kidney biopsy (PKB) is an essential tool in nephrology; small kidney size has been a relative contraindication to PKB and there is limited data on the safety and utility of performing PKB in this setting. Our aim was to describe the complications of PKB in small kidneys and to assess if kidney biopsy results have an impact on medical decisions and outcomes. METHODS: This was a retrospective, descriptive, and observational study. Patients older than 16 years of age with a decreased kidney size (≤8 cm) and undergoing PKB of native kidneys from July 2019 to December 2022 were included. RESULTS: Twenty-five patients were included, 19 women and 6 men. The mean age was 42.3 ± 18.04. The mean kidney length was 7.56 ± 0.33 and the mean width was 4.2 cm. All patients received only 1 puncture, obtaining an average of 12 glomeruli. The mean blood urea nitrogen and serum creatinine were 36 mg/dL and 1.94 mg/dL, respectively and the mean Hgb (hemoglobin) was 12.87 ± 2.81 g/dL. Minor complications occurred in 5 patients, perirenal hematoma in 3 patients, hematuria in 1 patient, and hematoma plus hematuria in 1 patient. Histological examination showed FSGS, lupus nephritis, other Glomerular disease, crescentic glomerulonephritis, and tubulointerstitial nephritis in 36%, 20%, 16%, 16%, and 12% of the cases, respectively. Biopsy resulted in management modification in 64% of cases. In a bivariate analysis, kidney size was not associated with higher complication rates. CONCLUSIONS: PKB in small kidneys is a feasible and safe procedure when properly planned, providing an adequate sample in all cases, with an insignificant number of minor complications, and that is clinically relevant.

Shared and Specific Neural Correlates of Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder: A Meta-Analysis of 243 Task-Based Functional MRI Studies.

OBJECTIVE: To investigate shared and specific neural correlates of cognitive functions in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), the authors performed a comprehensive meta-analysis and considered a balanced set of neuropsychological tasks across the two disorders. METHODS: A broad set of electronic databases was searched up to December 4, 2022, for task-based functional MRI studies investigating differences between individuals with ADHD or ASD and typically developing control subjects. Spatial coordinates of brain loci differing significantly between case and control subjects were extracted. To avoid potential diagnosis-driven selection bias of cognitive tasks, the tasks were grouped according to the Research Domain Criteria framework, and stratified sampling was used to match cognitive component profiles. Activation likelihood estimation was used for the meta-analysis. RESULTS: After screening 20,756 potentially relevant references, a meta-analysis of 243 studies was performed, which included 3,084 participants with ADHD (676 females), 2,654 participants with ASD (292 females), and 6,795 control subjects (1,909 females). ASD and ADHD showed shared greater activations in the lingual and rectal gyri and shared lower activations in regions including the middle frontal gyrus, the parahippocampal gyrus, and the insula. By contrast, there were ASD-specific greater and lower activations in regions including the left middle temporal gyrus and the left middle frontal gyrus, respectively, and ADHD-specific greater and lower activations in the amygdala and the global pallidus, respectively. CONCLUSIONS: Although ASD and ADHD showed both shared and disorder-specific standardized neural activations, disorder-specific activations were more prominent than shared ones. Functional brain differences between ADHD and ASD are more likely to reflect diagnosis-related pathophysiology than bias from the selection of specific neuropsychological tasks.

Early-life prefrontal cortex inhibition and early-life stress lead to long-lasting behavioral, transcriptional, and physiological impairments.

Early-life stress has been linked to multiple neurodevelopmental and neuropsychiatric deficits. Our previous studies have linked maternal presence/absence from the nest in developing rat pups to changes in prefrontal cortex (PFC) activity. Furthermore, we have shown that these changes are modulated by serotonergic signaling. Here we test whether changes in PFC activity during early life affect the developing cortex leading to behavioral alterations in the adult. We show that inhibiting the PFC of mouse pups leads to cognitive deficits in the adult comparable to those seen following maternal separation. Moreover, we show that activating the PFC during maternal separation can prevent these behavioral deficits. To test how maternal separation affects the transcriptional profile of the PFC we performed single-nucleus RNA-sequencing. Maternal separation led to differential gene expression almost exclusively in inhibitory neurons. Among others, we found changes in GABAergic and serotonergic pathways in these interneurons. Interestingly, both maternal separation and early-life PFC inhibition led to changes in physiological responses in prefrontal activity to GABAergic and serotonergic antagonists that were similar to the responses of more immature brains. Prefrontal activation during maternal separation prevented these changes. These data point to a crucial role of PFC activity during early life in behavioral expression in adulthood.

MVAR: A Mouse Variation Registry.

The Mouse Variation Registry (MVAR) resource is a scalable registry of mouse single nucleotide variants and small indels and variant annotation. The resource accepts data in standard Variant Call Format (VCF) and assesses the uniqueness of the submitted variants via a canonicalization process. Novel variants are assigned a unique, persistent MVAR identifier; variants that are equivalent to an existing variant in the resource are associated with the existing identifier. Annotations for variant type, molecular consequence, impact, and genomic region in the context of specific transcripts and protein sequences are generated using Ensembl's Variant Effect Predictor (VEP) and Jannovar. Access to the data and annotations in MVAR are supported via an Application Programming Interface (API) and web application. Researchers can search the resource by gene symbol, genomic region, variant (expressed in Human Genome Variation Society syntax), refSNP identifiers, or MVAR identifiers. Tabular search results can be filtered by variant annotations (variant type, molecular consequence, impact, variant region) and viewed according to variant distribution across mouse strains. The registry currently comprises more than 99 million canonical single nucleotide variants for 581 strains of mice. MVAR is accessible from https://mvar.jax.org.

The power of many brains: Catalyzing neuropsychiatric discovery through open neuroimaging data and large-scale collaboration.

Recent advances in open neuroimaging data are enhancing our comprehension of neuropsychiatric disorders. By pooling images from various cohorts, statistical power has increased, enabling the detection of subtle abnormalities and robust associations, and fostering new research methods. Global collaborations in imaging have furthered our knowledge of the neurobiological foundations of brain disorders and aided in imaging-based prediction for more targeted treatment. Large-scale magnetic resonance imaging initiatives are driving innovation in analytics and supporting generalizable psychiatric studies. We also emphasize the significant role of big data in understanding neural mechanisms and in the early identification and precise treatment of neuropsychiatric disorders. However, challenges such as data harmonization across different sites, privacy protection, and effective data sharing must be addressed. With proper governance and open science practices, we conclude with a projection of how large-scale imaging resources and collaborations could revolutionize diagnosis, treatment selection, and outcome prediction, contributing to optimal brain health.

Epigenome-wide association study identifies neonatal DNA methylation associated with two-year attention problems in children born very preterm.

Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from buccal swabs collected at NICU discharge using the Illumina MethylationEPIC Bead Array. Attention problems were assessed at 2 years of adjusted age using the attention problems subscale of the Child Behavior Checklist (CBCL). After adjustment for multiple testing, DNA methylation at 33 CpG sites was associated with child attention problems. Differentially methylated CpG sites were located in genes previously linked to physical and mental health, including several genes associated with ADHD in prior epigenome-wide and genome-wide association studies. Several CpG sites were located in genes previously linked to exposure to prenatal risk factors in the NOVI sample. Neonatal epigenetics measured at NICU discharge could be useful in identifying preterm children at risk for long-term attention problems and related psychiatric disorders, who could benefit from early prevention and intervention efforts.

GenomeMUSter mouse genetic variation service enables multitrait, multipopulation data integration and analysis.

Hundreds of inbred mouse strains and intercross populations have been used to characterize the function of genetic variants that contribute to disease. Thousands of disease-relevant traits have been characterized in mice and made publicly available. New strains and populations including consomics, the collaborative cross, expanded BXD, and inbred wild-derived strains add to existing complex disease mouse models, mapping populations, and sensitized backgrounds for engineered mutations. The genome sequences of inbred strains, along with dense genotypes from others, enable integrated analysis of trait-variant associations across populations, but these analyses are hampered by the sparsity of genotypes available. Moreover, the data are not readily interoperable with other resources. To address these limitations, we created a uniformly dense variant resource by harmonizing multiple data sets. Missing genotypes were imputed using the Viterbi algorithm with a data-driven technique that incorporates local phylogenetic information, an approach that is extendable to other model organisms. The result is a web- and programmatically accessible data service called GenomeMUSter, comprising single-nucleotide variants covering 657 strains at 106.8 million segregating sites. Interoperation with phenotype databases, analytic tools, and other resources enable a wealth of applications, including multitrait, multipopulation meta-analysis. We show this in cross-species comparisons of type 2 diabetes and substance use disorder meta-analyses, leveraging mouse data to characterize the likely role of human variant effects in disease. Other applications include refinement of mapped loci and prioritization of strain backgrounds for disease modeling to further unlock extant mouse diversity for genetic and genomic studies in health and disease.

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

Chronic Mild Sleep Restriction Does Not Lead to Marked Neuronal Alterations Compared With Maintained Adequate Sleep in Adults.

BACKGROUND: Sleep restriction (SR) has been shown to upregulate neuronal reward networks in response to food stimuli, but prior studies were short-term and employed severe SR paradigms. OBJECTIVE: Our goal was to determine whether mild SR, achieved by delaying bedtimes by 1.5 h, influences neuronal networks responsive to food stimuli compared with maintained adequate sleep (AS) >7 h/night. METHODS: A randomized controlled crossover study with 2 6-wk phases, AS (≥7 h sleep/night) and SR (-1.5 h/night relative to screening), was conducted. Adults with AS duration, measured using wrist actigraphy over a 2-wk screening period, and self-reported good sleep quality were enrolled. Resting-state and food-stimulated functional neuroimaging (fMRI) was performed at the endpoint of each phase. Resting-state fMRI data analyses included a priori region-of-interest seed-based functional connectivity, whole-brain voxel-wise analyses, and network analyses. Food task-fMRI analyses compared brain activity patterns in response to food cues between conditions. Paired-sample t tests tested differences between conditions. RESULTS: Twenty-six participants (16 males; age 29.6 ± 5.3 y, body mass index 26.9 ± 4.0 kg/m2) contributed complete data. Total sleep time was 7 h 30 ± 28 min/night during AS compared with 6 h 12 ± 26 min/night during SR. We employed different statistical approaches to replicate prior studies in the field and to apply more robust approaches that are currently advocated in the field. Using uncorrected P value of <0.01, cluster ≥10-voxel thresholds, we replicated prior findings of increased activation in response to foods in reward networks after SR compared with AS (right insula, right inferior frontal gyrus, and right supramarginal gyrus). These findings did not survive more rigorous analytical approaches (Gaussian Random Field theory correction at 2-tailed voxel P < 0.001, cluster P < 0.05). CONCLUSIONS: The results suggest that mild SR leads to increased reward responsivity to foods but with low confidence given the failure to meet significance from rigorous statistical analyses. Further research is necessary to inform the mechanisms underlying the role of sleep on food intake regulation. This trial was registered at clinicaltrials.gov as NCT02960776.

The evolution of antimicrobial peptides in Chiroptera.

High viral tolerance coupled with an extraordinary regulation of the immune response makes bats a great model to study host-pathogen evolution. Although many immune-related gene gains and losses have been previously reported in bats, important gene families such as antimicrobial peptides (AMPs) remain understudied. We built an exhaustive bioinformatic pipeline targeting the major gene families of defensins and cathelicidins to explore AMP diversity and analyze their evolution and distribution across six bat families. A combination of manual and automated procedures identified 29 AMP families across queried species, with α-, ß-defensins, and cathelicidins representing around 10% of AMP diversity. Gene duplications were inferred in both α-defensins, which were absent in five species, and three ß-defensin gene subfamilies, but cathelicidins did not show significant shifts in gene family size and were absent in Anoura caudifer and the pteropodids. Based on lineage-specific gains and losses, we propose diet and diet-related microbiome evolution may determine the evolution of α- and ß-defensins gene families and subfamilies. These results highlight the importance of building species-specific libraries for genome annotation in non-model organisms and shed light on possible drivers responsible for the rapid evolution of AMPs. By focusing on these understudied defenses, we provide a robust framework for explaining bat responses to pathogens.

Psicosis como manifestación inicial de encefalitis autoinmune contra los receptores N-metil-D-aspartato (ECR-NMDA): reporte de caso / Psychosis as first manifestation of autoimmune encephalitis against N-methyl-D-aspartate receptors (ECR-NMDA). Case Report

RESUMEN Se presenta el caso de un varón de 21 años hospitalizado en el servicio de psiquiatría de un hospital general con historia de alteraciones de pensamiento, percepción y conducta, y que tuvo un intento suicida. En la unidad de hospitalización, el paciente presentó una evolución tórpida, incluyendo la aparición de movimientos involuntarios y un progresivo trastorno sensorial que determinó su traslado a la unidad de cuidados intermedios del servicio de medicina interna. Después de exámenes de laboratorio, apoyo de imágenes y evaluación por diferentes especialidades, el diagnóstico final fue el de un cuadro compatible con encefalitis anti-receptor NMDA.

ABSTRACT The case of a 21-year-old man, hospitalized in the psychiatric service of a general hospital with a history of abnormal thought, perception, and behavioral processes, reaching a suicidal attempt, is presented. In the psychiatric hospitalization unit, he experienced a torpid clinical course, including the appearance of involuntary movements and a progressive sensory disorder that led to his transfer to the Intermediate Care Unit of the Internal Medicine Service. After laboratory tests, imaging support and evaluation by different medical specialties, the final diagnosis was a clinical picture compatible with NMDA anti-receptor encephalitis.

Aberrant resting-state functional connectivity of the globus pallidus interna in first-episode schizophrenia.

BACKGROUND: The striatal-pallidal pathway plays an important role in cognitive control and modulation of behaviors. Globus pallidus interna (GPi), as a primary output structure, is crucial in modulating excitation and inhibition. Studies of GPi in psychiatric illnesses are lacking given the technical challenges of examining this small and functionally diverse subcortical structure. METHODS: 71 medication-naïve first episode schizophrenia (FES) participants and 73 healthy controls (HC) were recruited at the Shanghai Mental Health Center. Clinical symptoms and imaging data were collected at baseline and, in a subset of patients, 8 weeks after initiating treatment. Resting-state functional connectivity of sub-regions of the GP were assessed using a novel mask that combines two atlases to create 8 ROIs in the GP. RESULTS: Baseline imaging data from 63 FES patients and 55 HC met quality standards and were analyzed. FES patients exhibited less negative connectivity and increased positive connectivity between the right anterior GPi and several cortical and subcortical areas at baseline compared to HC (PFWE < 0.05). Positive functional connectivity between the right anterior GPi and several brain areas, including the right dorsal anterior cingulate gyrus, was associated with severity of positive symptoms (PFWE < 0.05) and predicted treatment response after 8 weeks (n = 28, adjusted R2 = 0.486, p < 0.001). CONCLUSIONS: Our results implicate striatal-pallidal-thalamic pathways in antipsychotic efficacy. If replicated, these findings may reflect failure of neurodevelopmental processes in adolescence and early adulthood that decrease functional connectivity as an index of failure of the limbic/associative GPi to appropriately inhibit irrelevant signals in psychosis.

New species of the Spiny Mouse genus Neacomys (Cricetidae, Sigmodontinae) from northwestern Ecuador.

Neacomys is a genus of small spiny or bristly sigmodontine rodents that are common components of mammalian faunas in multiple biomes on Central and South America. Recent studies on this group have demonstrated that there is cryptic diversity yet to be discovered within currently recognized species that have not received comprehensive revisions, as well as in areas that have been overlooked. Here we ratify this assertion by describing a new species previously misidentified as the Narrow-footed Spiny Mouse (Neacomystenuipes) from the Chocó biogeographic region in northwestern Ecuador, Neacomysmarci Brito & Tinoco, sp. nov. Distinctiveness of this entity is supported by the combination of the following morphological characters: small size (head-body length 65-85 mm); long tail (69-126% longer than head-body length); pale buff-colored but gray-based belly fur; white throat; hypothenar pad usually absent; long nasals; and a condylar process higher than the coronoid process. Likewise genetic distance analyses and phylogenetic reconstructions based on cytochrome-b (Cytb) sequence data indicate a clear divergence from typical populations of N.tenuipes, and a sister relationship between them. The results presented here increase the diversity of Neacomys to 24 species, placing it among the most diverse genera within the sigmodontine rodents.

GenomeMUSter mouse genetic variation service enables multi-trait, multi-population data integration and analyses.

Hundreds of inbred laboratory mouse strains and intercross populations have been used to functionalize genetic variants that contribute to disease. Thousands of disease relevant traits have been characterized in mice and made publicly available. New strains and populations including the Collaborative Cross, expanded BXD and inbred wild-derived strains add to set of complex disease mouse models, genetic mapping resources and sensitized backgrounds against which to evaluate engineered mutations. The genome sequences of many inbred strains, along with dense genotypes from others could allow integrated analysis of trait - variant associations across populations, but these analyses are not feasible due to the sparsity of genotypes available. Moreover, the data are not readily interoperable with other resources. To address these limitations, we created a uniformly dense data resource by harmonizing multiple variant datasets. Missing genotypes were imputed using the Viterbi algorithm with a data-driven technique that incorporates local phylogenetic information, an approach that is extensible to other model organism species. The result is a web- and programmatically-accessible data service called GenomeMUSter ( https://muster.jax.org ), comprising allelic data covering 657 strains at 106.8M segregating sites. Interoperation with phenotype databases, analytic tools and other resources enable a wealth of applications including multi-trait, multi-population meta-analysis. We demonstrate this in a cross-species comparison of the meta-analysis of Type 2 Diabetes and of substance use disorders, resulting in the more specific characterization of the role of human variant effects in light of mouse phenotype data. Other applications include refinement of mapped loci and prioritization of strain backgrounds for disease modeling to further unlock extant mouse diversity for genetic and genomic studies in health and disease.

Updated Review and Clinical Recommendations for the Diagnosis and Treatment of Patients with Retroperitoneal Sarcoma by the Spanish Sarcoma Research Group (GEIS).

Soft tissue sarcomas (STS) are an uncommon and biologically heterogeneous group of tumors arising from mesenchymal cells. The incidence is estimated at five cases per 100,000 people per year. Retroperitoneal sarcomas (RPS) account for 10-15% of all STS, and their management depends on their anatomical characteristics and histotype. Due to their very low incidence, it is recommended that RPS be treated in reference centers and evaluated by an experienced multidisciplinary team (MDT). In Spain, the Spanish Group for Research in Sarcomas (GEIS) brings together experts from various specialties to promote research on sarcomas and improve treatment results. This paper summarizes the GEIS recommendations for the diagnosis, treatment, and follow-up of patients with RPS.

A systematic review of digital interventions for smoking cessation in patients with serious mental illness.

Tobacco smoking is highly prevalent among patients with serious mental illness (SMI), with known deleterious consequences. Smoking cessation is therefore a prioritary public health challenge in SMI. In recent years, several smoking cessation digital interventions have been developed for non-clinical populations. However, their impact in patients with SMI remains uncertain. We conducted a systematic review to describe and evaluate effectiveness, acceptability, adherence, usability and safety of digital interventions for smoking cessation in patients with SMI. PubMed/MEDLINE, EMBASE, CINAHL, Web of Science, PsychINFO and the Cochrane Tobacco Addiction Group Specialized Register were searched. Studies matching inclusion criteria were included and their information systematically extracted by independent investigators. Thirteen articles were included, which reported data on nine different digital interventions. Intervention theoretical approaches ranged from mobile contingency management to mindfulness. Outcome measures varied widely between studies. The highest abstinence rates were found for mSMART MIND (7-day point-prevalent abstinence: 16-40%). Let's Talk About Quitting Smoking reported greater acceptability ratings, although this was not evaluated with standardized measures. Regarding usability, Learn to Quit showed the highest System Usability Scale scores [mean (s.d.) 85.2 (15.5)]. Adverse events were rare and not systematically reported. Overall, the quality of the studies was fair to good. Digitally delivered health interventions for smoking cessation show promise for improving outcomes for patients with SMI, but lack of availability remains a concern. Larger trials with harmonized assessment measures are needed to generate more definitive evidence and specific recommendations.