En el presente trabajo se revisa la literatura referente a las interacciones entre enfermedad cardiovascular y depresión psiquiátrica . Se buscó determinar en que medida la presencia de depresión incrementa la mortalidad en pacientes con trastornos cardiovasculares y si es un factor de riesgo para la aparición de trastornos cardiovasculares . En pacientes cardiovasculares, la pre-sencia de depresión empeora el pronóstico, en función de la duración y severidad de la misma; este efecto esta mas claramente demostrado en los pacientes que sobreviven a un infarto de miocardio. Con una excepción, los estudios de mortalidad en poblaciones generales muestran un aumento del riesgo de mortalidad de causas cardiovasculares en individuos deprimidos en comparación con controles . Se ofrece una explicación fisiopatológica a los resultados observados y se revisan y recomiendan estrategias de reconocimiento y tratamiento de la depresión en pacientes cardiológicos.

Electroconvulsive therapy (ECT) remains the most effective intervention for treatment-resistant depression (TRD). We investigated whether cortico-limbic structural connectivity is associated with ECT response. Twenty-nine TRD patients underwent bifrontal ECT and baseline probabilistic tractography assessing connectivity between amygdala, anterior insula (aINS), orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), posterior ventrolateral (VLPFC) and dorsolateral prefrontal cortex (DLPFC), subgenual cingulate cortex (SGCC) and thalamus. Stronger connectivity within a subnetwork comprising bilateral OFC, bilateral aINS, left SGCC and right DLPFC was associated with poorer ECT response showing predictive value for treatment outcome. Conversely, thalamus-PCC connectivity is related to greater baseline severity and better ECT response. In TRD, depressive symptom scores negatively correlated with fronto-limbic-thalamic connectivity. Our findings highlight a fronto-limbic subnetwork whose hyperconnectivity may reflect maladaptive regulation limiting neuromodulation efficacy. In contrast, thalamic connectivity may act as a hub linking fronto-limbic and default mode network circuits, potentially facilitating receptive pathways supporting therapeutic response and guiding anatomically precise neuromodulation strategies.

Background:Depression is associated with risk for late-onset Alzheimer's disease (LOAD), but its underlying pathogenesis in at-risk individuals remains unclear. We examined multimodal imaging correlates of depressive symptoms in cognitively normal middle-aged offspring of patients with LOAD (O-LOAD) compared with control individuals without LOAD history up to a 4 th degree of kinship (HC). Methods:Participants (n=58; 52±3 years; 74% female) underwent assessment with the Beck Depression Inventory-II (BDI), structural MRI, resting-state fMRI, FDG-PET, and PiB-PET. Resting-state fMRI data were available for 28 O-LOAD and 24 HC; PET data for 24 O-LOAD and 22 HC. General linear models tested associations between imaging measures and BDI, including group interactions. Results:In O-LOAD, higher BDI scores were associated with reduced cortical thickness in the left postcentral gyrus. Resting-state fMRI revealed significant group-by-BDI interactions involving cingulate and orbitofrontal networks. In O-LOAD, greater depressive symptom severity was associated with reduced cingulate connectivity across distributed corticolimbic, prefrontal, insular, occipital, and cerebellar regions (β range -0.10 to -0.18). In HC, depressive symptoms were associated with reduced right orbitofrontal and somatosensory-medial orbitofrontal connectivity (β=-0.13), with divergent patterns of cingulate connectivity. FDG-PET showed no significant associations with depressive symptoms. PiB-PET demonstrated regionally specific associations between amyloid signal and BDI in HC, involving an inverse pattern in anterior and posterior insular cortices. Conclusions:Depressive symptoms in middle-aged individuals at familial risk for LOAD are associated with distinct structural and functional alterations, involving circuitry subserving salience and reward, and suggesting early network-level mechanisms linking affective symptoms with vulnerability to neurodegeneration.

Background: Repetitive negative thinking (RNT), particularly its brooding aspect, is a prominent feature in Major Depressive Disorder (MDD) with and without comorbid anxiety. Error processing, an adaptive cognitive operation, seems to be impaired in individuals with exaggerated RNT. This study measured a post-error neural response, error-related negativity (ERN), during an inhibitory task to examine the mechanism underlying the relationship between RNT and faulty error processing. Methods: We examined current MDD patients with (n = 61) and without comorbid anxiety disorders (COM; n = 38), propensity-matched into High- or Low-RNT groups according to Ruminative Response Scale Brooding subscale scores. Using 32-channel electroencephalography (EEG) during a stop-signal task, we measured baseline-corrected ERN amplitude at FCz 0-100 ms after an incorrect response. A between-subjects ANOVA was conducted with group (High RNT, Low RNT) and comorbidity (MDD, COM) as factors. Results: A significant group-by-comorbidity interaction (eta(2) = 0.07) was found, with MDD participants exhibiting high RNT revealing smaller (more positive) ERN amplitudes compared to their COM counterparts with high RNT (d = 0.77) and MDD participants with low RNT (d = 0.92). Conclusions: Non-anxious individuals with MDD and high RNT showed blunted post-error neural responses, potentially indicating a diminished adaptive neural mechanism for recognizing and correcting errors. However, the presence of comorbid anxiety disorders in individuals with high RNT appears to counteract this reduction, potentially through an enhanced neural response to errors, thereby maintaining a higher level of error-processing activity. Further understanding of these relationships is essential for developing targeted interventions for MDD, with particular focus on the detrimental impact of brooding RNT.

Background: Repetitive negative thinking (RNT) in major depressive disorder (MDD) involves persistent focus on negative self-related experiences. Resting-state fMRI shows that the functional connectivity (FC) between the insula and the superior temporal sulcus is critical to RNT intensity. This study examines how insular FC patterns differ between resting-state and RNT-induction in MDD and healthy participants (HC). Methods: Forty-one individuals with MDD and twenty-eight HCs (total n=69) underwent resting-state and RNT-induction fMRI scans. Seed-to-whole brain analysis using insular subregions as seeds was performed. Results: No diagnosis-by-run interaction effects were observed across insular subregions. MDD participants showed greater FC between bilateral anterior, middle, and posterior insular regions and the cerebellum (z = 4.31 to 6.15). During RNT-induction, both MDD and HC participants demonstrated increased FC between bilateral anterior and middle insula and key brain regions, including prefrontal cortices, parietal lobes, posterior cingulate cortex, and medial temporal gyrus, encompassing the STS (z = 4.47 to 8.31). Higher trait-RNT was associated with increased FC between the right dorsal anterior and middle insula and regions in the DMN and salience network in MDD participants (z = 4.31 to 6.15). Greater state-RNT scores were linked to increased FC in similar insular regions, the bilateral angular gyrus and right middle temporal gyrus (z = 4.47 to 8.31). Conclusions: Hyperconnectivity in insula subregions during active rumination, especially involving the DMN and salience network, supports theories of heightened self-focused and negative emotional processing in depression. These findings emphasize the neural basis of RNT when actively elicited in MDD.

Current efforts to establish anatomically precise and causal deep brain circuit-symptom relationships to predict surgical responses require the insertion of intracranial electrodes. In the present study (ClinicalTrials.gov NCT05697172) we examined whether low-intensity focused ultrasound (LIFU; FDA Q220192) could modulate the white matter tracts in the anterior limb of the internal capsule (ALIC), a common surgical target for the treatment of refractory depression. We based our human study on the in vitro observation that ultrasound attenuates conduction in myelinated axons by operating mechanosensitive potassium channels in nodes of Ranvier. We employed a cross-over, randomized, sham-controlled, double-blind design to establish the ability of LIFU (80 s; 0.5 MHz; estimated peak tissue energy 2.26 Watt/cm2; 10

This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing (16S) and shallow shotgun sequencing (WGS) were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and Neurocomputational Mechanisms of Affiliation and Personality Study Center for Biomedical Research Excellence (NeuroMAP CoBRE) cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. Though the effect sizes were larger in females than males, similar trends emerged for both sexes. These findings encourage future research on the gut microbiota’s role in NPD and its interactions with pharmacological treatments.

BACKGROUND:The macro-social and environmental conditions in which people live, such as the level of a country's development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults. METHODS:We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country's level of development and inequality. RESULTS:Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain. CONCLUSIONS:Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants' brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.

BACKGROUND:Substance use disorders (SUDs) pose significant societal challenges, and underlying mechanisms remain poorly understood. Work within the growing field of computational psychiatry has begun to offer novel insights into these underlying mechanisms, including impairments in learning from negative outcomes and less deterministic decision-making, among others. However, the longitudinal stability and predictive utility of these computational measures remain underexplored, limiting their clinical applicability. METHODS:A confirmatory longitudinal study was conducted with 144 participants (75 with SUDs and 69 healthy comparisons [HCs]) from the Tulsa 1000 project. Participants completed a three-armed bandit task at baseline and 1-year follow-up. Computational modeling assessed parameters including learning rates and action precision, among others. Bayesian and frequentist approaches tested group differences, stability, and associations with symptom severity (Drug Abuse Screening Test [DAST] scores). Machine learning analyses also evaluated out-of-sample predictive accuracy when combining this sample with an earlier exploratory dataset (83 SUDs, 48 HCs). RESULTS:Computational measures showed moderate stability over 1 year (ICC range: 0.4-0.58). Learning rates for losses were consistently lower in individuals with SUDs than HCs (posterior probability > 0.99), replicating prior findings. Baseline computational parameters did not significantly predict follow-up DAST scores. Out-of-sample classification achieved modest accuracy (59 %, AUC = 0.62). CONCLUSION:Findings confirm moderate longitudinal stability and group differences in computational parameters, supporting their mechanistic relevance but raising questions about their predictive value. This highlights the need for experimental designs and enhanced reliability in computational psychiatry. Future work should integrate neurophysiological measures and dimensional approaches to improve clinical relevance.

OBJECTIVE:The authors sought to determine whether an inflammatory challenge with lipopolysaccharide (LPS) differentially impacts symptoms of anhedonia in participants with major depressive disorder with high (≥3 mg/L) and low (≤1.5 mg/L) serum C-reactive protein (CRP) concentrations. METHODS:Sixty-eight participants with major depressive disorder were randomly assigned, in a 1:1 ratio, to receive LPS (0.8 ng/kg body weight) or placebo (saline) in a parallel-group double-blind design. Participants were stratified according to baseline CRP concentrations, yielding four groups: high-CRP LPS (N=13), low-CRP LPS (N=19), high-CRP placebo (N=13), and low-CRP placebo (N=19). Blood was sampled at baseline, at 1, 1.5, 3.5, 6, and 24 hours, and 1 week after LPS or saline administration, with concurrent assessment of psychological outcomes. The primary outcome measure was the Snaith-Hamilton Pleasure Scale (SHAPS), and the primary contrast of interest was the change between baseline and 1.5 hours (peak of the inflammatory response) in the high-CRP versus low-CRP groups receiving LPS. Secondary outcomes included the Montgomery-Åsberg Depression Rating Scale (MADRS) and serum levels of three cytokines: interleukin-6 (IL-6), IL-10, and tumor necrosis factor (TNF). Data were analyzed with linear mixed models. RESULTS:Significantly greater increases in self-reported anhedonia (on the SHAPS) and IL-6 levels were observed between baseline and 1.5 hours in the high-CRP versus low-CRP LPS groups. There were no significant differences for TNF and IL-10. The MADRS was not administered at 1.5 hours; secondary analyses showed a significant group-by-condition-by-time interaction driven by a greater decrease in MADRS scores between baseline and 24 hours in the high-CRP group. CONCLUSIONS:Depressed individuals with systemic inflammation appeared to be biologically primed to respond more strongly to inflammatory stimuli, and psychologically, this sensitization impacted the symptom of anhedonia, the primary outcome.

Major depressive (MDD) and borderline personality disorders (BPD) are highly prevalent and frequently comorbid psychiatric conditions, both characterized by emotion dysregulation yet likely arising from distinct etiologies. Nonetheless, the specific features of autonomic central-peripheral relationships in these disorders remain poorly understood. We investigated the association between brain structure and vagal activity, and explored the resting-state functional connectivity of brain regions found to be associated with vagal tone, in 19 MDD, 18 BPD and 20 healthy controls (HC). We found that the cortical thinning in the right lateral occipital region was associated with increased parasympathetic tone in BPD, a relationship not observed in MDD. Moreover, in BPD, this region was functionally connected to the anterior insula and prefrontal areas, linked to the central autonomic system and emotion regulation processes. Accordingly, this region was also linked to emotion dysregulation in BPD. Our findings highlight distinct central-peripheral autonomic integration in these disorders and emphasize the occipital region's structural and functional involvement in emotional and autonomic regulation in BPD. Further research is needed to clarify how occipital structure and function, well as vagal activity, may contribute as potential biomarkers for BPD.

Background American Indians (AIs) experience chronic stressors that may be associated with disproportionate prevalence rates of major depressive disorder (MDD). Stress affects mental health through increased inflammatory processes and has been associated with increased risk of MDD and disruptions to reward processing. In this study, we investigated the role of inflammation in reward-processing disruptions among AI individuals with lifetime MDD, a population at heightened risk due to chronic stressors. Methods Participants (N = 73) completed a monetary incentive delay task during simultaneous electroencephalography and functional magnetic resonance imaging. Blood samples were analyzed for proinflammatory (tumor necrosis factor [TNF], interleukin 6 [IL-6], C-reactive protein [CRP]) and anti-inflammatory (IL-10) biomarkers. Depression severity was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression scale. Covariates were included and assessed using self-report measures. Results Regression analyses revealed that elevated TNF concentrations and sex were associated with reduced activation across subregions of the basal ganglia during gain anticipation. Similarly, TNF and CRP concentrations, as well as medication, were associated with reduced activation within basal ganglia subregions across loss anticipation. IL-10, IL-6, and P300 showed limited predictive value for neural responses. Conclusions These findings suggest that inflammation may contribute to reward-processing disruptions by impairing striatal function in a sample with lifetime MDD. The observed associations underscore the importance of inflammation’s potential role in and association with the pathophysiology of MDD, particularly in contexts of chronic stress. This study highlights the need to address the disproportionate mental health burden in AI communities through a biopsychosocial approach.

Major Depressive Disorder (MDD) poses a significant public health challenge due to its high prevalence and the substantial burden it places on individuals and healthcare systems. Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) shows promise as a treatment for this disorder, although its mechanisms of action remain unclear. This study investigated whole-brain response patterns during rtfMRI-NF training to explain interindividual variability in clinical efficacy in MDD. We analyzed data from 95 participants (67 active, 28 control) with MDD from previous rtfMRI-NF studies designed to increase left amygdala activation through positive autobiographical memory recall. Significant symptom reduction was observed in the active group (t=-4.404, d=-0.704, p<0.001) but not in the control group (t=-1.609, d=-0.430, p=0.111). However, left amygdala activation did not account for the variability in clinical efficacy. To elucidate the brain training process underlying the clinical effect, we examined whole-brain activation patterns during two critical phases of the neurofeedback procedure: activation during the self-regulation period, and transient responses to feedback signal presentations. Using a systematic process involving feature selection, manifold extraction, and clustering with cross-validation, we identified two subtypes of regulation activation and three subtypes of brain responses to feedback signals. These subtypes were significantly associated with the clinical effect (regulation subtype: F=8.735, p=0.005; feedback response subtype: F=5.326, p=0.008; subtypes' interaction: F=3.471, p=0.039). Subtypes associated with significant symptom reduction were characterized by selective increases in control regions, including lateral prefrontal areas, and decreases in regions associated with self-referential thinking, such as default mode areas. These findings suggest that large-scale brain activity during training is more critical for clinical efficacy than the level of activation in the neurofeedback target region itself. Tailoring neurofeedback training to incorporate these patterns could significantly enhance its therapeutic efficacy.

Repetitive negative thinking (RNT) involves a passive, repetitive focus on distressing thoughts that manifests as rumination - a repetitive focus on symptoms of distress - and worry - concern about potential future negative outcomes. While these processes often co-occur in mental disorders, their distinct neural mechanisms remain undetermined.

Adverse childhood experiences (ACEs) negatively affect the function and structure of emotion brain circuits, increasing the risk of various psychiatric disorders. It is unclear if ACEs show disorder specificity with respect to their effects on brain structure. We aimed to investigate whether the structural brain effects of ACEs differ between patients with major depression (MDD) and borderline personality disorder (BPD). These disorders share many symptoms but likely have different etiologies. To achieve our goal, we obtained structural 3T-MRI images from 20 healthy controls (HC), 19 MDD patients, and 18 BPD patients, and measured cortical thickness and subcortical gray matter volumes. We utilized the Adverse Childhood Experiences (ACE) questionnaire to quantify self-reported exposure to childhood trauma. Our findings suggest that individuals with MDD exhibit a smaller cortical thickness when compared to those with BPD. However, ACEs showed a significantly affected relationship with cortical thickness in BPD but not in MDD. ACEs were found to be associated with thinning in cortical regions involved in emotional behavior in BPD, whereas HC showed an opposite association. Our results suggest a potential mechanism of ACE effects on psychopathology involving changes in brain structure. These findings highlight the importance of early detection and intervention strategies.