Marker Of Vulnerability Research Articles

The Predictive Power of Intraoperative EEG and Clinical Characteristics for Postoperative Delirium Following Cardiac Surgery

Introduction: Postoperative delirium is common and associated with poor postoperative outcomes. However, the predictive power of intraoperative electroencephalogram (EEG) features for postoperative delirium has not yet been well studied. Methods: Intraoperative EEG data from 261 patients who underwent major cardiac surgery were analyzed. Cases were identified using the Confusion Assessment Method. Predictive analytics for delirium outcome were performed using (1) only clinical data, (2) only EEG data, and (3) a combined list of important features from the first two stages. Results: Eleven percentage of participants experienced postoperative delirium. The patients were generally older and had lower physical and cognitive function. EEG models were found to be highly specific but less sensitive in identifying delirium cases. The combined EEG-clinical model performed comparably to the clinical-only model (AUC = 80%) but outperformed the EEG-only model (AUC = 56%). After adjusting for clinical covariates, only interhemispheric mutual information remained significantly associated with delirium (OR = 2.29, p = 0.03), with a positive correlation with delirium severity (ρ = 0.18, P ≤ 0.01). Conclusions: This study enhances our understanding of delirium neurophysiology by emphasizing the role of intraoperative EEG as a marker of brain vulnerability. Although EEG may not constitute a standalone biomarker of delirium, it holds promise for delirium risk stratification.

Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long-Term Cardiovascular Mortality.

Complement activation may promote atherosclerosis. Yet, data on the to which extent complement, and more specifically the alternative complement pathway, is activated in patients with carotid atherosclerosis and related to adverse outcome in these patients, are scarce. We measured, by ELISA, plasma levels of factor D, properdin, C3bBbP (C3 convertase), and factor H in patients with advanced carotid atherosclerosis in a Discovery (n=324) and in a Validation (n=206) cohort in relation to adverse outcome (mean follow-up 7.8 and 6.6 years, respectively). Our major findings were as follows. Compared with healthy controls, patients with carotid atherosclerosis had increased plasma levels of factor D, properdin, and C3bBbP (P<0.001), but not factor H, an inhibitor of the alternative complement pathway, compared with controls. Although patients with carotid atherosclerosis had elevated levels of properdin compared with controls, within these patients, low plasma levels of properdin (ie, <median levels of properdin in the patient group) were significantly associated with cardiovascular mortality. This was seen in both the Discovery (HR 2.31, P=0.019) and the Validation cohort (hazard ratio [HR], 2.81, P=0.014). In contrast to the low circulating levels, high intraplaque properdin levels (assessed by ELISA) correlated with markers of plaque vulnerability and symptomatology. We show a strong and independent association of low plasma properdin levels with cardiovascular mortality in 2 cohorts. Conversely, the plaque properdin levels linked to features of plaque vulnerability, potentially reflecting increased deposition at the site of inflammation or local production of properdin in the atherosclerotic lesion indicating local enhanced alternative complement pathway activation.

Cross-sectional and longitudinal association of sleep patterns and aneurysmal vulnerability biomarkers on high-resolution magnetic resonance vessel wall imaging

BackgroundAneurysm wall enhancement (AWE) on vessel wall imaging (VWI) scans is a robust biomarker for aneurysmal vulnerability. This study aimed to explore the association of different sleep patterns with AWE...

Smoking as a Marker of Comorbid Vulnerability Among Persons with Probable Posttraumatic Stress Disorder Who Engage in Hazardous Drinking

Background: Persons with posttraumatic stress disorder (PTSD) compared to those without evince high rates of hazardous drinking, or patterns of alcohol consumption that increase the risk for harmful consequences. One potential marker of vulnerability for PTSD-hazardous drinking comorbidity may be smoking behavior. Individuals with PTSD have a higher prevalence of smoking and smoke at higher rates. Smokers, compared to nonsmokers, are more apt to engage in hazardous alcohol use. Notably, there is a need to expand research on smoking in the context of PTSD and hazardous drinking to inform treatment of these morbidities. Objective: The present cross-sectional investigation sought to examine smoking status as a marker of risk among persons with probable PTSD who engage in hazardous drinking (N = 647; M age = 38.90 years, SD = 10.71; 51.2% female). Results: Results indicated that trauma-exposed smokers, compared to non-smokers, evinced greater severity of PTSD symptoms, depression, emotion regulation difficulties, hazardous drinking, and substance use problems, with small effect sizes. No statistically significant group differences were found for anxiety symptom severity. Secondary analyses among only smokers supported an interrelation between cigarette dependence and each of the criterion variables that demonstrated statistically significant group differences. Specifically, cigarette dependence was statistically significantly and incrementally related to PTSD symptom severity, depression, emotion regulation difficulties, more severe hazardous drinking, and a greater degree of substance use problems. Conclusions: Overall, the current investigation found that smoking status among persons with probable PTSD who engaged in hazardous drinking was associated with numerous indicators of mental health and substance use vulnerability.

Intraoperative Electroencephalogram Frontal Low Alpha Power for Predicting Postoperative Delirium in Elderly Patients after Orthopedic Surgery: A Prospective Cohort Study.

Postoperative delirium (POD) is a common complication with significant adverse effects in elderly patients. Electroencephalography (EEG) provides a promising approach for predicting the risk of POD. This study aims to elucidate the correlation between intraoperative EEG spectrum and the incidence of POD in elderly patients undergoing orthopedic surgery. A single-center prospective observational cohort study was conducted at Zhongda Hospital, Southeast University, from September 2022 to March 2023, registered on Chinese Clinical Trail Registry (ChiCTR2300069548). Among the 172 patients who underwent orthopedic surgery, 125 completed the study with available data. Preoperative baseline cognitive function was assessed using the mini-mental state examination (MMSE). An intraoperative 4-channel EEG was recorded. Total power spectra and power spectral density for beta, alpha, theta, and delta bands were calculated. Spectral edge frequency, burst suppression ratio, and patient state index were directly extracted from the EEG monitor. The primary outcome was POD, assessed using a 3-minute Diagnostic Interview for Confusion Assessment Method (CAM)-Defined Delirium scale or the CAM for the Intensive Care Unit. Patients were divided into POD and non-postoperative delirium (non-POD) groups. Logistic regression analysis was conducted to evaluate the independent predictive effect of intraoperative spectral distribution and other quantitative EEG data for POD. The incidence of delirium within 72 hours after surgery was 8.8%. Compared to the non-POD group, the POD group showed significantly lower absolute power in the beta [0.06 (0.03, 0.09) dB vs 0.14 (0.08, 0.26) dB, p < 0.001], alpha [0.41 (0.25, 0.71) dB vs 1.24 (0.55, 2.57) dB, p = 0.008], and theta [0.77 (0.44, 1.01) dB vs 1.19 (0.72, 2.02) dB, p = 0.035] bands. Logistic regression analysis identified several independent risk factors for POD, including lower intraoperative alpha power [odds ratio (OR) 10.210, 95% confidence interval (CI) 1.233-84.568, p = 0.031], advanced age (OR 7.713, 95% CI 1.022-58.204, p = 0.048), preoperative anemia (OR 6.636, 95% CI 1.091-40.358, p = 0.040), and preoperative depression (OR 10.089, 95% CI 1.029-98.909, p = 0.047). In contrast, higher preoperative MMSE scores appeared to be a protective factor for POD (OR 0.130, 95% CI 0.021-0.820, p = 0.030). Intraoperative EEG frontal low alpha power demonstrated a significant independent association with POD in elderly patients after orthopedic surgery. This parameter may serve as an intraoperative neurophysiological marker of cerebral vulnerability to POD. Additionally, advanced age, lower preoperative MMSE scores, preoperative anemia, and preoperative depression were independent risk factors for POD. Chinese Clinical Trial Registry (ChiCTR2300069548).

Multimodal neural correlates of childhood psychopathology.

Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development (ABCD) dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology (p) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples and robust to variations in analytical parameters. Although model parameters yielded statistically significant brain-behavior associations in unseen data, generalizability of the model was rather limited for all three latent components (r change from within- to out-of-sample statistics: LC1within = 0.36, LC1out = 0.03; LC2within = 0.34, LC2out = 0.05; LC3within = 0.35, LC3out = 0.07). Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.

Predictors of mortality among older adults discharged to or readmitted from a skilled nursing facility.

Previous studies have shown that patients who are readmitted to the hospital from a skilled nursing facility (SNF) have a higher mortality rate. The objective of this study is to determine factors associated with high mortality rate for older adults who require hospital readmission while on presumed short stay in SNF to trigger a goals-of-care discussion. Retrospective study of 847 patients aged 65 and above who were discharged from 1 large urban academic medical center to multiple SNF in 2019. Charts of 847 patients admitted to SNF after an acute hospital stay were reviewed; their overall 1-year mortality rate was 28.3%. The 1-year mortality rate among individuals readmitted to the hospital within 30 days of discharge to SNF was 50%, whereas for those who did not require readmission, the rate was 22%. For the most common diagnostic categories of nervous system, and musculoskeletal, patients with readmission to hospital within 30 days of discharge to SNF had a roughly threefold higher 1-year mortality rate. Worse frailty score on hospital readmission, poor nutrition, and weight loss were the most impactful individual factors carrying a higher degree of mortality of up to 83%. Hospital discharge to SNF and readmission from SNF within 30 days, further decline in functional status, and malnutrition characterize high-risk groups that should trigger care preference and prognostic discussions with patients as these events may be markers of vulnerability and are associated with high 1-year mortality rates.

Abstract 4136597: Atherosclerotic plaque healing as a marker of plaque vulnerability: Insight from intracoronary polarization-sensitive optical frequency domain imaging

Background: Collagen is the major extracellular matrix that imparts mechanical strength to fibrous caps covering fibroatheromas. Intracoronary polarimetry with polarization-sensitive (PS) optical frequency domain imaging (OFDI) measures polarization properties, such as birefringence and depolarization (Figure 1). Birefringence is elevated in collagen and collagen-synthesizing smooth muscle cells, while depolarization is increased by the presence of macrophages and lipid/necrotic cores. Purpose: This study aimed to investigate polarimetric signatures of coronary lesions with healed coronary plaques (HCP) in patients with ACS and chronic coronary syndrome (CCS). Furthermore, we aimed to investigate diagnostic value for birefringence and depolarization of ACS culprit lesions discriminating from CCS target lesions. Methods: We conducted a single center prospective registry of intracoronary PS-OFDI imaging in patients with coronary artery disease (n = 50). A total of 862 OFDI frames selected from culprit or target lesions were analyzed. Coronary plaque phenotypes were assessed using conventional OFDI imaging. HCP was defined as plaques with one or more layers of different optical density and a clear demarcation from underlying components on intensity images. Birefringence and depolarization of the newer intima was measured in cross-sectional images. Birefringence and depolarization of ACS- and CCS-lesions were compared using a generalized estimating equation model. Receiver operating characteristic (ROC) analysis was used to investigate the diagnostic performance of polarimetric signatures for identifying ACS-lesions. Results: Compared to CCS-lesions, ACS-lesions featured significantly higher lipid-burden index and maximum lipid arc (both p &lt; 0.05). Compared to the CCS-lesions, ACS-lesions exhibited significantly lower birefringence (p &lt; 0.05) and higher depolarization (p &lt; 0.05). In the ROC analysis for differentiating ACS-lesions from CCS-lesions, area under the curves (AUC) for birefringence and depolarization were 0.712 and 0.672, respectively. In the multivariable ROC analysis in diagnosing ACS lesions, combination of birefringence with depolarization improved the AUC to 0.755 (p ＝ 0.025). Conclusions: Intracoronary polarimetry provides quantitative assessment of plaque composition in patients. Further research is warranted to investigate whether birefringence can serve as a marker of healing failure following plaque rupture and erosion.

Neuroinflammation, Stress-Related Suicidal Ideation, and Negative Mood in Depression

Brain translocator protein 18k Da (TSPO) binding, a putative marker of neuroinflammatory processes (eg, gliosis), is associated with stress and elevated in depressed and suicidal populations. However, it is unclear whether neuroinflammation moderates the impact of daily life stress on suicidal ideation and negative affect, thereby increasing risk for suicidal behavior. To examine the association of TSPO binding in participants with depression with real-world daily experiences of acute stress-related suicidal ideation and negative affect, as well as history of suicidal behavior and clinician-rated suicidal ideation. Data for this cross-sectional study were collected from June 2019 through July 2023. Procedures were conducted at a hospital-based research center in New York, New York. Participants were recruited via clinical referrals, the Columbia University research subject web portal, and from responses to internet advertisements. Of 148 participants who signed informed consent for study protocols, 53 adults aged 18 to 60 years who met DSM-5 diagnostic criteria for current major depressive disorder completed procedures with approved data and were enrolled. Participants were free of schizophrenia spectrum disorders, active physical illness, cognitive impairment, and substance intoxication or withdrawal at the time of scan. All participants underwent positron emission tomography imaging of TSPO binding with 11C-ER176 and concurrent arterial blood sampling. A weighted average of 11C-ER176 total distribution volume (VT) was computed across 11 a priori brain regions and made up the primary outcome measure. Clinician-rated suicidal ideation was measured via the Beck Scale for Suicidal Ideation (BSS). A subset of participants (n = 21) completed 7 days of ecological momentary assessment (EMA), reporting daily on suicidal ideation, negative affect, and stressors. In the overall sample of 53 participants (mean [SD] age, 29.5 [9.8] years; 37 [69.8%] female and 16 [30.2%] male), 11C-ER176 VT was associated at trend levels with clinician-rated suicidal ideation severity (β, 0.19; 95% CI, -0.03 to 0.39; P = .09) and did not differ by suicide attempt history (n = 15; β, 0.18; 95% CI, -0.04 to 0.37; P = .11). Exploratory analyses indicated that presence of suicidal ideation (on BSS or EMA) was associated with higher 11C-ER176 VT (β, 0.21; 95% CI, 0.01 to 0.98; P = .045). In 21 participants who completed EMA, 11C-ER176 VT was associated with greater suicidal ideation and negative affect during EMA periods with stressors compared with nonstress periods (β, 0.12; SE, 0.06; 95% CI, 0.01 to 0.23; P = .03 and β, 0.19; SE, 0.06; 95% CI, 0.08 to 0.30; P < .001, respectively). TSPO binding in individuals with depression may be a marker of vulnerability to acute stress-related increases in suicidal ideation and negative affect. Continued study is needed to determine the causal direction of TSPO binding and stress-related suicidal ideation or negative affect and whether targeting neuroinflammation may improve resilience to life stress in patients with depression.

Genetic and Neurodevelopmental Markers in Schizophrenia-Spectrum Disorders: Analysis of the Combined Role of the CNR1 Gene and Dermatoglyphics.

Background: Dermatoglyphic pattern deviances have been associated with schizophrenia-spectrum disorders (SSD) and are considered neurodevelopment vulnerability markers based on the shared ectodermal origin of the epidermis and the central nervous system. The endocannabinoid system participates in epidermal differentiation, is sensitive to prenatal insults and is associated with SSD. Objective: We aimed to investigate whether the Cannabinoid Receptor 1 gene (CNR1) modulates the dermatoglyphics-SSD association. Methods: In a sample of 112 controls and 97 patients with SSD, three dermatoglyphic markers were assessed: the total palmar a-b ridge count (TABRC), the a-b ridge count fluctuating asymmetry (ABRC-FA), and the pattern intensity index (PII). Two CNR1 polymorphisms were genotyped: rs2023239-T/C and rs806379-A/T. We tested: (i) the CNR1 association with SSD and dermatoglyphic variability within groups; and (ii) the CNR1 × dermatoglyphic measures interaction on SSD susceptibility. Results: Both polymorphisms were associated with SSD. The polymorphism rs2023239 modulated the relationship between PII and SSD: a high PII score was associated with a lower SSD risk within C-allele carriers and a higher SSD risk within TT-homozygotes. This result indicates an inverse relationship between the PII and the SSD predicted probability conditional to the rs2023239 genotype. Conclusions: These novel findings suggest the endocannabinoid system's role in the development and variability of dermatoglyphic patterns. The identified interaction encourages combining genetic and dermatoglyphics to assess neurodevelopmental alterations predisposing to SSD in future studies.

Associations between intraindividual reaction time variability, baseline respiratory sinus arrhythmia, and trait impulsivity in males with substance use disorders

Trait impulsivity, characterized by the tendency to act without adequate consideration of potential consequences in pursuit of immediate rewards, is a recognized vulnerability marker for substance use disorders (SUDs). Cognitive control deficits are implicated in the manifestation of high trait impulsivity, and intraindividual reaction time variability (IIRTV), an indicator of cognitive control, may influence trait impulsivity. Baseline respiratory sinus arrhythmia (RSA) reflects vagal tone, serves as an index of physiological self-regulation, which has been demonstrated to be related to trait impulsivity. However, it is unclear whether IIRTV is associated with trait impulsivity and whether it interacts with baseline RSA to influence trait impulsivity. A total of 113 males with SUDs participated (Mage=46.04years, SD=11.53) in this study. Trait impulsivity was assessed using a self-report questionnaire, IIRTV was measured through a two-choice oddball task, and baseline RSA was obtained through the collection of electrocardiogram (ECG) data. The results indicated that IIRTV interacted with baseline RSA to influence trait impulsivity. These findings suggested that cognitive control indexed by IIRTV, might represent a central nervous correlate of trait impulsivity, and that it interacted with vagal tone indexed by baseline RSA, to influence trait impulsivity.

Examining associations between brain morphology in late childhood and early alcohol or tobacco use initiation in adolescence: findings from a large prospective cohort

A prominent challenge in understanding neural consequences of substance use involves disentangling predispositional risk factors from resulting consequences of substance use. Existing literature has identified pre-existing brain variations as vulnerability markers for substance use throughout adolescence. As early initiation of use is an important predictor for later substance use problems, we examined whether pre-existing brain variations are associated with early initiation of use. In the Generation R Study, a prospective population-based cohort, brain morphology (gray matter volume, cortical thickness and surface area) was assessed at ages 10 and 14 using neuroimaging. In the second wave, participants reported on alcohol and tobacco use initiation. From a base study population (N=3019), we examined the longitudinal (N=2218) and cross-sectional (N=1817) association between brain morphology of frontolimbic regions of interest known to be associated with substance use risk, and very early (age < 13) alcohol/tobacco use initiation. Additionally, longitudinal and cross-sectional associations were examined with a brain surface-based approach. Models were adjusted for age at neuroimaging, sex and relevant sociodemographic factors. No associations were found between brain morphology (ages 10 and 14) and early alcohol/tobacco use initiation (<13 years). Sex-specific analyses suggested a cross-sectional association between smaller brain volume and early initiated tobacco use in girls. Our findings are important for interpreting studies examining neural consequences of substance use in the general population. Future longitudinal studies are needed to specify whether these findings can be extended to initiation and continuation of alcohol/tobacco use in later stages of adolescence.

Basic self-disturbance in adolescents at risk of psychosis: temporal stability investigated by the experience sampling method in a mixed method study.

Basic self-disturbance (BSD), also called anomalous self-experiences (ASEs), are core phenotypic markers for schizophrenia spectrum disorders and a prepsychotic vulnerability marker considered to be temporally stable (trait-phenomenon). Studies of BSD in children and adolescents are lacking. To be clinically useful, we need to know more about the characteristics and temporal development of BSD in prepsychotic phases. This study used a smartphone application measuring the occurrence and subjective intensity of ASEs in the daily life of 27 help-seeking adolescents (12-18 years) repeatedly over a period of 6 months. A total of 5223 unique application-reports based on individually selected and verbatim descriptions of personal core ASEs were analysed by mixed methods. The intensity of ASEs, within subjects and between subjects and irrespective of time intervals or baseline scores obtained by the Examination of Anomalous Self-Experience (EASE) were relatively stable with a mean variability of 1.25 (0.4) SD. Participants with low EASE total scores at baseline had a significantly lower score on ASE intensity than those with high baseline EASE total scores at baseline (mean 2.42 vs 3.42, p=0.046). In this study, ASEs were not reported as essentially fluctuating experiences but as almost constantly present, demonstrating BSD as a mainly trait phenomenon in prepsychotic phases in persons under the age of 18. Considering the continuous experience of BSD and its predictive value for psychosis development, ASEs should be targeted and monitored to the same extent as other prepsychotic features.

Association of non-HDL cholesterol with plaque burden and composition of culprit lesion in acute coronary syndrome. An intravascular ultrasound-virtual histology study

Lipids play key role in coronary atherosclerosis. The role of non-high-density lipoprotein cholesterol (non-HDL-C) in atherosclerotic plaques using intravascular imaging remains unclear. This study aimed to assess its relationship with coronary plaque features using intravascular ultrasound (IVUS) in acute coronary syndrome (ACS). A total of 601 patients divided into two groups: normal non-HDL-C≤130mg/dl (n=410) and high non-HDL cholesterol >130mg/dl (n=191). IVUS performed before coronary intervention. Mean age 53.18±12.29 years. No significant differences in hypertension, diabetes, and smoking between groups. Plaque burden was significantly higher among normal versus high non-HDL-C groups (79.59±9.98% vs. 81.61±5.39%; p=0.001). At minimal luminal site, fibrofatty percentage was higher in normal non-HDL-C group (p=0.027), while necrotic core greater in high non-HDL-C group (p=0.033). Segmental analysis, necrotic core was significantly higher in percentage (p=0.006) and volumes (p=0.011) in normal versus high non-HDL-C groups. Total cholesterol (r=0.099, p=0.015), LDL-C (r=0.081, p=0.046), triglycerides (r=0.083, p=0.041),and non-HDL-C (r=0.099, p=0.015) positively correlated with plaque burden. Total cholesterol (r=0.115, p=0.005), LDL-C (r=0.107, p=0.009), and non-HDL-C (r=0.105, p=0.010) positively correlated with necrotic core volume. Linear regression analysis showed age and non-HDL-C as predictors of higher plaque burden. Multiple linear regression analysis; age, body mass index, and non-HDL-C were predictors of larger necrotic core volume. Non-HDL-C levels were positively associated with plaque burden, measure of extent of atherosclerosis. It is closely associated with and is a predictor of necrotic core volume; a marker of plaque vulnerability. This IVUS study demonstrates potential role of non-HDL-C in causation of plaque in ACS.

Locus coeruleus microstructural integrity is associated with vigilance vulnerability to sleep deprivation.

Insufficient sleep compromises cognitive performance, diminishes vigilance, and disrupts daily functioning in hundreds of millions of people worldwide. Despite extensive research revealing significant variability in vigilance vulnerability to sleep deprivation, the underlying mechanisms of these individual differences remain elusive. Locus coeruleus (LC) plays a crucial role in the regulation of sleep-wake cycles and has emerged as a potential marker for vigilance vulnerability to sleep deprivation. In this study, we investigate whether LC microstructural integrity, assessed by fractional anisotropy (FA) through diffusion tensor imaging (DTI) at baseline before sleep deprivation, can predict impaired psychomotor vigilance test (PVT) performance during sleep deprivation in a cohort of 60 healthy individuals subjected to a rigorously controlled in-laboratory sleep study. The findings indicate that individuals with high LC FA experience less vigilance impairment from sleep deprivation compared with those with low LC FA. LC FA accounts for 10.8% of the variance in sleep-deprived PVT lapses. Importantly, the relationship between LC FA and impaired PVT performance during sleep deprivation is anatomically specific, suggesting that LC microstructural integrity may serve as a biomarker for vigilance vulnerability to sleep loss.

P18: BDNF levels and affective disorders as a marker of vulnerability to developing cognitive impairment in the Chilean adult population

Summary: Disorders related to progressive cognitive decline constituting an important cause of global death and disability-adjusted life years because conditions are also associated to impairment of several brain functions, psychological and behavioral changes, regardless of economic status. Brain-derived neurotrophic factor (BDNF) is a neurotrophin highly relevant in memory, learning and neuroplasticity processes in adults. The amount of plasma BDNF has been considered to partly reflect its secretion in the brain. Its deficiency is associated with affective disorders and neurodegenerative pathologies such as Alzheimer disease and Parkinson’sdisease.The aim of this study was to identify quantifiable biomarkers (serum levels of BDNF) and clinical marker (state of depression and anxiety) that allow early detection of cognitive impairment risk. We made an analytic and transversal study with a representative sample (n:307) of the population over 50 years old in the south of Chile (X region). We determine the cognitive condition of the population by applying cognitive functionality tests, such as the minimental status examination (MMSE) test and identify demographic and psychosocial characteristics that constitute impairment cognitive risk. Subsequently, we determined depression status (scale of Yesavage) and anxiety status (Beck inventory), and finally we made a quantitative determination of human BDNF at the blood level using ELISA technique.Our results revealed that 26.7% of the participants exhibited some degree of cognitive impairment, being higher in women (55.7%) with average age of 70,7. A 18,2% of subjects manifested indicators of depression and 33,2% have a very hight level of anxiety. The correlation analysis revealed a significant positive correlation between MMSE test (p &lt; 0.001) and both BDNF plasma levels (p &lt; 0.001) and education level (p &lt; 0.001) scores. The results additionally indicated a negative correlation between cognitive functions and age range/anxiety state, suggesting low age level/hight level of anxiety in subjects with more pronounced cognitive decline (p &lt; 0.001),. In consistent, the results of our study point towards decreases plasma BDNF levels and hight levels of anxiety in cognitive impairment subjects compared with cognitive normal subjects, which may be due to the early and middle stages of neurodegeneration process.

No significant alteration in white matter microstructure in first-degree relatives of patients with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is characterized by structural alteration within white matter tissues of cortico-striato-thalamo-cortical, temporal and occipital circuits. However, the presence of microstructural changes in the white matter tracts of unaffected first-degree relatives of patients with OCD as a vulnerability marker remains unclear. Therefore, here, diffusion-tensor magnetic resonance imaging (DTI) data were obtained from 29 first-degree relatives of patients with OCD and 59 healthy controls. We investigated the group differences in FA using whole-brain analysis (DTI analysis). For additional regions of interest (ROI) analysis, we focused on the posterior thalamic radiation and sagittal stratum, shown in recent meta-analysis of patients with OCD. In both whole-brain and ROI analyses, using a strict statistical threshold (family-wise error rate [FWE] corrected p<.05 for whole-brain analyses, and p<.0125 (0.05/4) with Bonferroni correction for ROI analyses), we found no significant group differences in FA. Subtle reductions were observed in the anterior corona radiata, forceps minor, cingulum bundle, and corpus callosum only when a lenient statistical was applied (FWE corrected p<.20). These findings suggest that alterations in the white matter microstructure of first-degree relatives, as potential vulnerability markers for OCD, are likely subtle.

MULTIMODAL NEURAL CORRELATES OF CHILDHOOD PSYCHOPATHOLOGY.

Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology (p) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples, supporting generalizability, and robust to variations in analytical parameters. Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.

Examining the Complex Mismatch Negativity in Early Phase Psychosis Using the Dual Rule Paradigm.

Using electroencephalography (EEG) to examine the simple mismatch negativity (MMN), a marker of auditory cortex function, has been of great interest in the exploration of biomarkers for psychotic illness. Despite many studies reporting MMN deficits in chronic schizophrenia, there are inconsistent reports of MMN reductions in the early phases of psychotic illness, suggesting the MMN elicited by traditional paradigms may not be a sensitive enough measure of vulnerability to be used as a biomarker. Recently, a more computationally complex measure of auditory cortex function (the complex mismatch negativity; cMMN) has been hypothesized to provide a more sensitive marker of illness vulnerability. The current study employed a novel dual rule paradigm, in which two pattern rules are established and violated, to examine the cMMN in 14 individuals with early phase psychosis (EPP, < 5 years illness) and 15 healthy controls (HC). Relationships between cMMN waveforms, symptom severity, and measures of functioning were explored. We found reductions of cMMN amplitudes at the site of maximal amplitude in EPP (p = .017) with large effect sizes (Hedges' g = 0.96). This study is an early step in the exploration of the cMMN as a biomarker for psychosis. Our results provide evidence that the dual rule cMMN paradigm shows promise as a method for cMMN elicitation that captures more subtle neurofunctional changes in the early stages of illness.

Hippocampal temporal dynamics and spatial heterogeneity unveil vulnerability markers in the offspring of bipolar patients.

Bipolar disorder (BD) is a highly heritable disorder characterized by emotion dysregulation and recurrent oscillations between mood states. Despite the proven efficacy of early interventions, vulnerability markers in high-risk individuals are still lacking. BD patients present structural alterations of the hippocampus, a pivotal hub of emotion regulation networks composed of multiple subregions with different projections. However, the hippocampal dynamic functional connectivity (dFC) in BD remains unclear. We aim to investigate whether the dFC of hippocampal subdivisions differentiates BD patients, offspring of BD patients (BDoff), and healthy controls (HC); and whether it correlates with symptoms differently between these groups. We studied for the first time the dFC of the hippocampus through a cutting-edge micro-co-activation patterns (μCAPs) analysis of resting-state functional MRI data of 97 subjects (26 BD, 18 BDoff, 53 HC). μCAPs allow a data-driven differentiation within the seed region. dFC between the hippocampal body and a somatomotor-μCAP was lower both in BD patients (p-valueFDR:0.00015) and in BDoff (p-valueFDR:0.020) than in HC. Inversely, dFC between the hippocampal head and a limbic-μCAP was higher in BD patients than in HC (p-valueFDR: 0.005). Furthermore, the correlations between a frontoparietal-μCAP and both depression and emotion dysregulation symptoms were significantly higher in BD than HC (p-valueFDR <0.02). Overall, we observed alterations of large-scale functional brain networks associated with decreased cognitive control flexibility and disrupted somatomotor, saliency, and emotion processing in BD. Interestingly, BDoff presented an intermediate phenotype between BD and HC, suggesting that dFC of hippocampal subregions might represent a marker of vulnerability to BD.