Healthy Control Individuals Research Articles

Amygdala Reactivity, Antidepressant Discontinuation, and Relapse

Antidepressant discontinuation substantially increases the risk of a depression relapse, but the neurobiological mechanisms through which this happens are not known. Amygdala reactivity to negative information is a marker of negative affective processes in depression that is reduced by antidepressant medication, but it is unknown whether amygdala reactivity is sensitive to antidepressant discontinuation or whether any change is related to the risk of relapse after antidepressant discontinuation. To investigate whether amygdala reactivity to negative facial emotions changes with antidepressant discontinuation and is associated with subsequent relapse. The Antidepressiva Absetzstudie (AIDA) study was a longitudinal, observational study in which adult patients with remitted major depressive disorder (MDD) and currently taking antidepressants underwent 2 task-based functional magnetic resonance imaging (fMRI) measurements of amygdala reactivity. Patients were randomized to discontinuing antidepressants either before or after the second fMRI measurement. Relapse was monitored over a 6-month follow-up period. Study recruitment took place from June 2015 to January 2018. Data were collected between July 1, 2015, and January 31, 2019, and statistical analyses were conducted between June 2021 and December 2023. The study took place in a university setting in Zurich, Switzerland, and Berlin, Germany. Of 123 recruited patients, 83 were included in analyses. Of 66 recruited healthy control individuals matched for age, sex, and education, 53 were included in analyses. Discontinuation of antidepressant medication. Task-based fMRI measurement of amygdala reactivity and MDD relapse within 6 months after discontinuation. Among patients with MDD, the mean (SD) age was 35.42 (11.41) years, and 62 (75%) were women. Among control individuals, the mean (SD) age was 33.57 (10.70) years, and 37 (70%) were women. Amygdala reactivity of patients with remitted MDD and taking medication did not initially differ from that of control individuals (t125.136 = 0.33; P = .74). An increase in amygdala reactivity after antidepressant discontinuation was associated with depression relapse (3-way interaction between group [12W (waited) vs 1W2 (discontinued)], time point [MA1 (first scan) vs MA2 (second scan)], and relapse: β, 18.9; 95% CI, 0.8-37.1; P = .04). Amygdala reactivity change was associated with shorter times to relapse (hazard ratio, 1.05; 95% CI, 1.01-1.09; P = .01) and predictive of relapse (leave-one-out cross-validation balanced accuracy, 67%; 95% posterior predictive interval, 53-80; P = .02). An increase in amygdala reactivity was associated with risk of relapse after antidepressant discontinuation and may represent a functional neuroimaging marker that could inform clinical decisions around antidepressant discontinuation.

EEG-based Signatures of Schizophrenia, Depression, and Aberrant Aging: A Supervised Machine Learning Investigation.

Electroencephalography (EEG) is a noninvasive, cost-effective, and robust tool, which directly measures in vivo neuronal mass activity with high temporal resolution. Combined with state-of-the-art machine learning (ML) techniques, EEG recordings could potentially yield in silico biomarkers of severe mental disorders. Pathological and physiological aging processes influence the electrophysiological signatures of schizophrenia (SCZ) and major depressive disorder (MDD). From a single-center cohort (N = 735, 51.6% male) comprising healthy control individuals (HC, N = 245) and inpatients suffering from SCZ (N = 250) or MDD (N = 240), we acquired resting-state 19 channel-EEG recordings. Using repeated nested cross-validation, support vector machine models were trained to (1) classify patients with SCZ or MDD and HC individuals and (2) predict age in HC individuals. The age model was applied to patient groups to calculate Electrophysiological Age Gap Estimation (EphysAGE) as the difference between predicted and chronological age. The links between EphysAGE, diagnosis, and medication were then further explored. The classification models robustly discriminated SCZ from HC (balanced accuracy, BAC = 72.7%, P < .001), MDD from HC (BAC = 67.0%, P < .001), and SCZ from MDD individuals (BAC = 63.2%, P < .001). Notably, central alpha (8-11 Hz) power decrease was the most consistently predictive feature for SCZ and MDD. Higher EphysAGE was associated with an increased likelihood of being misclassified as SCZ in HC and MDD (ρHC = 0.23, P < .001; ρMDD = 0.17, P = .01). ML models can extract electrophysiological signatures of MDD and SCZ for potential clinical use. However, the impact of aging processes on diagnostic separability calls for timely application of such models, possibly in early recognition settings.

Physiological Regularity and Synchrony in Individuals with Gaming Disorder.

Individuals with gaming disorder (GD) show emotional dysregulation and autonomic dysfunction in daily life. Although studies have shown that the relaxation method of breathing exercise (BE) improves cardiopulmonary synchrony, the physiological regularity and synchrony of GD remain unclear. In this study, we investigated the regularities of pulse wave (PW), thoracic wall movement (TWM), and abdominal wall movement (AWM) using sample entropy (SE) and assessed the vascular-respiratory and TWM-AWM synchrony using cross-sample entropy (CSE). Twenty individuals with GD and 26 healthy control (HC) individuals participated in baseline, gaming, and recovery stages, both before and after BEs. The results showed that both groups had significantly higher SETWM, SEAWM, and CSETWM-AWM during gaming than baseline. Before BE, CSEPW-TWM and CSEPW-AWM during gaming were considerably higher in the GD group than in the HC group. Compared to before BE, both groups had decreased SETWM and CSETWM-AWM during gaming, particularly in the HC group. Online gaming may induce pulse wave and respiratory irregularities, as well as thoracic-abdominal wall movement asynchrony. Individuals with GD who engage in prolonged gaming periods may exhibit lower vascular-respiratory synchrony compared to the HC group. SETWM, SEAWM, CSETWM-AWM, CSEPW-TWM, and CSEPW-AWM may serve as biomarkers for assessing the risk of GD. BE may improve TWM regularity and vascular-respiratory synchrony during gaming, potentially alleviating addictive behavior.

A generalizable normative deep autoencoder for brain morphological anomaly detection: application to the multi-site StratiBip dataset on bipolar disorder in an external validation framework.

The heterogeneity of psychiatric disorders makes researching disorder-specific neurobiological markers an ill-posed problem. Here, we face the need for disease stratification models by presenting a generalizable multivariate normative modelling framework for characterizing brain morphology, applied to bipolar disorder (BD). We employed deep autoencoders in an anomaly detection framework, combined with a confounder removal step integrating training and external validation. The model was trained with healthy control (HC) data from the human connectome project and applied to multi-site external data of HC and BD individuals. We found that brain deviating scores were greater, more heterogeneous, and with increased extreme values in the BD group, with volumes prominently from the basal ganglia, hippocampus and adjacent regions emerging as significantly deviating. Similarly, individual brain deviating maps based on modified z scores expressed higher abnormalities occurrences, but their overall spatial overlap was lower compared to HCs. Our generalizable framework enabled the identification of subject- and group-level brain normative-deviating patterns, a step forward towards the development of more effective and personalized clinical decision support systems and patient stratification in psychiatry.

Provincial and connector qualities of somatosensory brain network hubs in bipolar disorder.

Brain network hubs are highly connected brain regions serving as important relay stations for information integration. Recent studies have linked mental disorders to impaired hub function. Provincial hubs mainly integrate information within their own brain network, while connector hubs share information between different brain networks. This study used a novel time-varying analysis to investigate whether hubs aberrantly follow the trajectory of other brain networks than their own. The aim was to characterize brain hub functioning in clinically remitted bipolar patients. We analyzed resting-state functional magnetic resonance imaging data from 96 euthymic individuals with bipolar disorder and 61 healthy control individuals. We characterized different hub qualities within the somatomotor network. We found that the somatomotor network comprised mainly provincial hubs in healthy controls. Conversely, in bipolar disorder patients, hubs in the primary somatosensory cortex displayed weaker provincial and stronger connector hub function. Furthermore, hubs in bipolar disorder showed weaker allegiances with their own brain network and followed the trajectories of the limbic, salience, dorsal attention, and frontoparietal network. We suggest that these hub aberrancies contribute to previously shown functional connectivity alterations in bipolar disorder and may thus constitute the neural substrate to persistently impaired sensory integration despite clinical remission.

CXCL12 Gene Polymorphisms and Serum Levels: Associations with Multiple Sclerosis Prevalence and Clinical Parameters in Lithuania.

Our study aimed to investigate the associations between CXCL12 rs1029153, rs1801157, and rs2297630 single-nucleotide polymorphisms (SNPs), CXCL12 protein levels, MS prevalence, and clinical parameters. This study included 250 individuals diagnosed with MS and 250 sex- and age-matched healthy control individuals from Lithuania. The SNPs were genotyped with real-time PCR-based assays. The CXCL12 protein concentration was evaluated in serum using the ELISA method. Of the studied CXCL12 SNPs, we found that the rs1801157 CT genotype in the males was associated with 2.3 times reduced MS odds when compared with the CC genotype according to the overdominant and codominant models (p = 0.011 and p = 0.012, respectively). There was a tendency, which did not reach adjusted statistical significance, for a lower CXCL12 protein concentration in the healthy individuals with the rs1801157 CT genotype (p = 0.028). Sensory symptoms were rarer in the women with the rs1801157 TT genotype (p = 0.004); however, this genotype was also associated with a shorter MS disease duration (p = 0.007). CXCL12 rs1801157 was associated with reduced odds of MS occurrence in the male individuals. In women, rs1801157 was associated with a sensory symptom prevalence.

Investigating the Relationship Between Serum Thyroid Hormone and Vitamin D Levels in Women with Melasma

Patches and macules of hyperpigmentation characterize melasma, a prevalent condition of skin pigmentation. Known risk factors for melasma include a genetic predisposition, sun exposure, and pregnancy. Melasma may have a connection to thyroid issues, according to previous research. Considering that vitamin D influences and promotes melanocytes' melanin formation, this study sought to examine the correlation between thyroid problems, blood vitamin D levels, and melasma in female patients seen at Al-Mahmoudiya Hospital. Both Wood's light investigation and clinical evaluation by seasoned dermatologists verified the melasma diagnosis. There were 80 participants in total, with 40 assigned to the melasma group and 40 to the control group. Their ages and sexes were matched. In all groups, blood samples were taken to assess levels of TSH, Anti-TPO, T3, T4, and vitamin D. Melasma patients' clinical pigmentation severity was assessed using the standard mMASI score. I used SPSS (IBM Statistical Package for the Social Sciences) version 21 to conduct the statistical analysis. Melasma patients were more likely to have thyroid problems (50%) and lower vitamin D serum levels (47.5%), compared to the control group (27.5%) and healthy individuals (40%). The levels of thyroid hormone (T3) and vitamin D were found to be considerably higher in the case group as compared to the control group (P&lt;0.05). A relationship was found between Anti-TPO and mMASI Score (P&lt; 0.05) when the relationship between age, thyroid hormones, vitamin D, and mMASI Score was investigated. Melasma and pigmentation intensity are linked to thyroid autoimmune diseases. The most prevalent clinical form of melasma is the centro facial variant as well.

Neuroimaging analysis reveals distinct cerebral perfusion responses to fasting-postprandial metabolic switching in Alzheimer's disease patients.

Extended fasting-postprandial switch intermitting time has been shown to affect Alzheimer's disease (AD). Few studies have investigated the cerebral perfusion response to fasting-postprandial metabolic switching (FMS) in AD patients. We aimed to evaluate the cerebral perfusion response to FMS in AD patients. In total, 30 AD patients, 32 mild cognitive impairment (MCI) patients, and 30 healthy control individuals (HCs) were included in the quantification of cerebral perfusion via cerebral blood flow (CBF). The cerebral perfusion response to FMS was defined as the difference (ΔCBF) between fasting and postprandial CBF. Patients with AD had a regional negative ΔCBF in the anterior temporal lobe, part of the occipital lobe and the parietal lobe under FMS stimulation, whereas HCs had no significant ΔCBF. The AD patients had lower ΔCBF values in the right anterior temporal lobe than the MCI patients and HCs. ΔCBF in the anterior temporal lobe was negatively correlated with cognitive severity and cognitive reserve factors in AD patients. AD patients exhibited a poor ability to maintain cerebral perfusion homeostasis under FMS stimulation. The anterior temporal lobe is a distinct area that responds to FMS in AD patients and negatively correlates with cognitive function.

Long-lasting effects of post-traumatic stress disorder in Yazidi women living in Northern Iraqi camps

The severity of post-traumatic stress disorder and its long-lasting effects among the Yazidi population has not yet been investigated. ObjectivesThis study evaluated the impact of PTSD severity and chronicity on physiological and anthropometric parameters in women survivors of the genocide-related events after the so-called Islamic State of Iraq and Syria (ISIS) attack in 2014. MethodsThe diagnosis PTSD was assessed using PTSD Checklist for DSM-5 (PCL-5). Participants were divided into: External control (healthy individuals living outside the camps), Internal control (healthy individuals living in the camps), and PTSD group (individuals diagnosed with PTSD). The PTSD group was subdivided according to chronicity <2 years, 2–5 years, and >5 years and subdivided according to PTSD severity into “Moderate”, “Severe” and “Extreme”. Systolic blood pressure (SBP), diastolic blood pressure (DBP), blood oxygen saturation (SPO2) and heart rate (HR) were evaluated. Weight, height and waist circumference were measured. Body mass index (BMI) and waist-to-height ratio (WHtR) were calculated. ResultsThe PTSD group showed significant increases in SBP, DBP, heart rate, BMI, WC, weight, and WHtR compared to the control groups. SPO2 values decreased in the PTSD group. As the disease progressed, there were further increases in SBP, DBP, heart rate, BMI, WC, WHtR, and weight. Similar increases were observed with the severity of the disease. ConclusionOur data indicates that a long-term impact on physiological and anthropometric parameters is present in women diagnosed with PTSD which might be aggravated by the severity and chronicity of the disease.

Altered functional connectivity and spatiotemporal dynamics in individuals with sleep disorders.

Idiopathic hypersomnia (IH) is a sleep disorder characterized by highly disruptive symptoms. Like narcolepsy type 1, a well-characterized sleep disorder, individuals with IH suffer from excessive daytime sleepiness, though there is little overlap in metabolic or neural biomarkers across these two disorders. This lack of common pathophysiology, combined with the clear overlap in symptoms presents an ideal paradigm for better understanding the impact of IH on an individual's functional activity and organization, and potentially, the underlying pathophysiology. This study examines the observed functional connectivity in patients with IH, and patients with narcolepsy type 1 (NT1) against healthy control individuals. Static functional connectivity is compared, as are quasi-periodic patterns, acquired from the BOLD timecourse, for all groups. In addition to baseline data comparison, the study also included a post-nap condition, where the individuals included in this analysis napped for at least 10 minutes prior to the scanning session, to explore why individuals with IH do not feel refreshed after a nap like individuals with NT1 do. Assessing the groups' spatiotemporal patterns revealed key differences across both disorders and conditions: static connectivity revealed at baseline higher subcortical connectivity in the NT1 group. There was also observably less connectivity in the IH group both at baseline and post-nap, though none of these static analyses survived multiple comparisons correction to reach significance. The QPP results however found significant differences in the IH group in key networks, particularly the DAN/FPCN correlation is significantly different at baseline vs. post-nap, a trend not observed in either the control or NT1 groups. The DAN and FPCN are drastically altered both at baseline and post-nap when compared to the other groups, and may likely be a disorder-specific result. This study demonstrates that key networks for arousal are more heavily disrupted in IH patients, who are less affected by a nap, confirmed through both subject reporting and functional evidence through spatiotemporal patterns.

The gut microbiome and serum metabolome are altered and interrelated in patients with intracranial atherosclerotic stenosis

ObjectivesTo evaluate the relationship among the gut microbiome, serum metabolites and the Intracranial atherosclerosis stenosis. Materials and methodsIntegrated analysis of 16S rDNA sequencing of fecal samples and untargeted serum metabolomics was applied to identify alterations in the gut microbiome and serum metabolome in 29 Intracranial atherosclerosis stenosis patients and 29 healthy control individuals. ResultsCompared to healthy control individuals, the abundances of forty-five genera and one hundred seventy-seven metabolites were significantly altered in Intracranial atherosclerosis stenosis patients. At the species level, the Intracranial atherosclerosis stenosis group exhibited higher abundances of Bacteroidetes and lower abundances of Megaphaera and Muribacoccaceae. Microbial functional prediction analysis revealed enhanced activity of bacterial chemotaxis and oxidative phosphorylation within the Intracranial atherosclerosis stenosis group. In terms of metabolomic findings, the levels of dulcitol were significantly increased in the Intracranial atherosclerosis stenosis group. The levels of specific metabolites within the phosphatidylcholine and lysophosphatidylcholine families, such as PC (14:0e/24:4) and LPC 20:5, were increased, while the levels of certain other specific metabolites were decreased. Dysregulation of certain pathways, such as unsaturated fatty acid metabolism, arginine and proline metabolism may be involved in the development of Intracranial atherosclerosis stenosis. Correlation analysis of the gut microbiome and metabolites revealed a positive correlation between Bacteroides and multiple metabolites, such as Acar 12:3 and PC (8:0/22:6). ConclusionsOur analysis revealed that Bacteroides is a key bacterial genus in gut dysbiosis and may be related to the development of Intracranial atherosclerosis stenosis.

Attributional style in Borderline personality disorder is associated with self-esteem and loneliness

BackgroundAttributions are the processes by which individuals explain the causes of positive and negative events. A maladaptive attributional style has been associated with reduced self-esteem, psychosocial functioning, and mental health. Although many psychosocial interventions target an individual’s attributional style in mental disorders, studies of its alterations in Borderline Personality Disorder (BPD) are sparse. This study aimed to investigate the attributional style in patients with BPD in comparison to healthy control individuals (HC) and its association with self-esteem and psychosocial functioning.MethodsThe participants (32 patients with a diagnosis of BPD, 32 HC, groups were balanced for sex, age and education) assessed their attributional style in regard to locus of control, stability and globality for positive and negative scenarios. Attributional style was compared between groups and linked to self-reports of self-esteem, loneliness and psychosocial functioning in different social domains while controlling for BPD and depressive symptom severity.ResultsIndividuals diagnosed with BPD reported a maladaptive attributional style for both positive and negative events. This was found to be strongly related with lower self-esteem and higher levels of loneliness, but not with psychosocial dysfunctions assessed in different social domains. The severity of BPD and depressive symptoms did not fully explain the association of attributional style with self-esteem and loneliness. In contrast, correcting for acute psychopathology actually strengthened the relationship between self-esteem and maladaptive inferring causality for positive events.ConclusionThe differential association of attributional style for positive and negative events with self-esteem and psychosocial functioning highlights the importance of considering the different facets of inferring causality during psychosocial interventions. Our findings suggest that the significance of cognitive alterations may change with remission of acute BPD and depressive psychopathology, depending on the valence of an event.

Association between serotonin transporter gene polymorphism and obsessive–compulsive disorder in the Egyptian population

BackgroundObsessive–compulsive disorder (OCD) is a debilitating disorder that has multifactorial etiology including genetic, neurobiological, cognitive, and environmental influences. Genetic studies have focused on the genes of the serotonin system. This study aimed to look for the possible relation between the polymorphism in the promotor region of the serotonin transporter gene and obsessive–compulsive disorder in the Egyptian population.ResultsThis study included 94 OCD patients and 116 healthy control individuals. Blood samples were collected from all participants for DNA extraction and genotyping. The assessment of patients was done by application of the structured clinical interview according to DSM-V, the dimensional Yale-Brown Obsessive–Compulsive Scale. There was an association between serotonin transporter gene polymorphism and OCD development. The carriage of the short allele was a risk factor for having OCD.ConclusionObsessive–compulsive disorder is associated with serotonin transporter gene polymorphism. This will contribute to considering the genetic information of patients for the prediction of best drug response and tolerability by personalizing the choice of treatment.

Hippocampal Availability of the α7 Nicotinic Acetylcholine Receptor in Recent-Onset Psychosis

Studies using human postmortem tissue and imaging with positron emission tomography (PET) support a low hippocampal availability of the α7 nicotinic acetylcholine receptor (α7-nAChR) in psychotic conditions, particularly in schizophrenia or schizoaffective disorder (nonaffective psychosis). If validated further, the finding may have implications for clinical diagnosis and treatment. To test for lower availability of the α7-nAChR in the hippocampus of individuals with recent-onset psychosis compared with healthy control individuals and its association with lower cognitive performance or higher psychotic symptom burden within recent-onset psychosis. In this cross-sectional study, healthy individuals without history of psychosis and patients within 10 years of a first onset of psychotic disorder were recruited from the greater Baltimore, Maryland, and Washington, DC, area. Fluorine 18-labeled ASEM ([18F] ASEM) PET data were acquired from participants enrolled between March 1, 2014, and July 31, 2023, from an academic research institution. Data acquired between March 1, 2014, and January 31, 2018 (n = 26), were published as a pilot study and were combined with new data acquired between January 1, 2019, and July 31, 2023 (n = 33). Regional [18F]ASEM total distribution volume (VT) that measures α7-nAChR availability, global cognition composite score, and total scores on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. A total of 59 participants (30 women [51%]; mean [SD] age, 25.5 [5.2] years), including 35 with recent-onset psychosis and 24 healthy controls, completed the study. In age-adjusted analyses, lower hippocampal [18F]ASEM VT was found in individuals with recent-onset psychosis (mean [SE], 17.87 [0.60]) compared with healthy controls (mean [SE], 19.82 [0.73]) (P = .04). In addition, [18F]ASEM VT was lower in individuals with nonaffective psychosis (mean [SE], 16.30 [0.83]) compared with healthy controls (P = .006) or those with affective psychosis (mean [SE], 19.34 [0.80]) (P = .03). Across recent-onset psychosis and after controlling for age, lower hippocampal [18F]ASEM VT was associated with more positive (r = -0.44; P = .009) but not negative symptoms, and higher hippocampal VT was associated with better global cognition composite score (r = 0.38; P = .03). In this cross-sectional study of individuals with recent-onset psychosis compared with healthy controls, a lower hippocampal α7-nAChR availability was found in recent-onset psychosis, and its availability was lower in those with nonaffective vs affective psychosis. Further study of the association between low availability of the α7-nAChR and recent-onset psychosis is warranted toward informing diagnostic or therapeutic strategies related to these findings.

DNA Methylation of PXDN Is Associated with Early-Life Adversity in Adult Mental Disorders.

Early-life adversity (ELA) is characterized by exposure to traumatic events during early periods of life, particularly involving emotional, sexual and/or physical adversities during childhood. Mental disorders are strongly influenced by environmental and lifestyle-related risk factors including ELA. However, the molecular link between ELA and the risk of an adult mental disorder is still not fully understood. Evidence is emerging that long-lasting changes in the epigenetic processes regulating gene expression, such as DNA methylation, play an important role in the biological mechanisms linking ELA and mental disorders. Based on a recent study, we analyzed the DNA methylation of a specific CpG site within the gene PXDN-cg10888111-in blood in the context of ELA across a set of psychiatric disorders, namely Borderline Personality Disorder (BPD), Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD), and its potential contribution to their pathogenesis. We found significant hypermethylation in mentally ill patients with high levels of ELA compared to patients with low levels of ELA, whereas cg10888111 methylation in healthy control individuals was not affected by ELA. Further investigations revealed that this effect was driven by the MDD cohort. Providing a direct comparison of cg10888111 DNA methylation in blood in the context of ELA across three mental disorders, our results indicate the role of PXDN regulation in the response to ELA in the pathogenesis of mental disorders, especially MDD. Further studies will be needed to validate these results and decipher the corresponding biological network that is involved in the transmission of ELA to an adult mental disorder in general.

Investigating Anxiety and Depression in Chronic Urticaria: Cause or Effect?

Background: Chronic urticaria is a complex multifactorial dermatological disease characterized by wheals lasting more than 6 consecutive weeks. The resultant physical discomfort from chronic urticaria may worsen the patient’s quality of life. Emotional manifestations are shown to occur in these patients, among which, depression and anxiety are the two most common conditions. Accordingly, this study evaluates the role of anxiety and depression in the course of chronic urticaria. Materials and Methods: A total of 170 adult patients with chronic urticaria and 50 healthy adults were asked to complete the questionnaires to be evaluated for the presence of any stigma regarding anxiety and depression. The inclusion criteria were individuals 18 years of age and above, and suffering from chronic urticaria. Results: The mean age of healthy individuals (control group) was 38.255±13.44 years. Most of the patients (74%) were female. Anxiety was found in 59.5% of the patients with chronic urticaria and 42% of healthy control individuals (P=0.029). Depression was found in 17.6% of patients with chronic urticaria and 6% of healthy individuals (P=0.022). Conclusion: A strong relationship exists between chronic urticaria and emotional conditions, including anxiety and depression exists.

Functional and structural abnormalities of thalamus in individuals at early stage of schizophrenia

BackgroundThalamic abnormalities in schizophrenia are recognized, alongside cognitive deficits. However, the current findings about these abnormalities during the prodromal period remain relatively few and inconsistent. This study applied multimodal methods to explore the alterations in thalamic function and structure and their relationship with cognitive function in first-episode schizophrenia (FES) patients and ultra-high-risk (UHR) individuals, aiming to affirm the thalamus's role in schizophrenia development and cognitive deficits. Methods75 FES patients, 60 UHR individuals, and 60 healthy controls (HC) were recruited. Among the three groups, gray matter volume (GMV) and functional connectivity (FC) were evaluated to reflect the structural and functional abnormalities in the thalamus. Pearson correlation was used to calculate the association between these abnormalities and cognitive impairments. ResultsNo significant difference in GMV of the thalamus was found among the abovementioned three groups. Compared with HC individuals, FES patients had decreased thalamocortical FC mostly in the thalamocortical triple network, including the default mode network (DMN), salience network (SN), and executive control network (ECN). UHR individuals had similar but milder dysconnectivity as the FES group. Furthermore, FC between the left thalamus and right putamen was significantly correlated with execution speed and attention in the FES group. ConclusionsOur findings revealed decreased thalamocortical FC associated with cognitive deficits in FES and UHR subjects. This improves our understanding of the functional alterations in thalamus in prodromal stage of schizophrenia and the related factors of the cognitive impairment of the disease. Trial registrationClinicalTrials.govNCT03965598; https://clinicaltrials.gov/ct2/show/NCT03965598.

The characteristics of WM in individuals with depressive tendencies: A functional near-infrared spectroscopy (fNIRS) study

Individuals with depressive tendencies are considered to be at high risk for the onset of depressive disorders. Currently, most research focuses on the impairment of working memory in patients with depression, while there is less attention paid to the WM of individuals with depressive tendencies, and their neural mechanisms underlying it are poorly understood. Therefore, this study focuses on the characteristics and neural mechanisms of WM in individuals with depressive tendencies. This study uses functional near-infrared spectroscopy (fNIRS) to monitor the concentration of Oxy-Hb in the prefrontal cortex and employs the n-back paradigm, designing three levels of load: 0, 1, and 2, to examine the characteristics of WM and its neural mechanisms in individuals with depressive tendencies. Behavioral results show that the accuracy rates of individuals with depressive tendencies is significantly lower than that of healthy individuals, and under the 0-back condition, the reaction time of individuals with depressive tendencies is significantly higher than that of healthy control individuals. Near-infrared results indicate that the activation level in the frontal pole and the dorsal lateral prefrontal cortex of individuals with depressive tendencies is significantly lower than that of healthy control individuals. The β values of channels 2, 7, and 9 are significantly negatively correlated with the Beck Depression Inventory scores of the participants. The results suggest that the reduced activation of the frontal pole and dorsal lateral prefrontal cortex in individuals with depressive tendencies leads to poorer WM performance compared to healthy control individuals. This is a rare brain evidence of the characteristics of WM in individuals with depressive tendencies, which can provide a deeper understanding of the WM characteristics of individuals with depressive tendencies.

METABOLIC AND BIOENERGETIC ALTERATIONS ARE ASSOCIATED WITH INFECTION SUSCEPTIBILITY IN SURVIVORS OF SEVERE TRAUMA: AN EXPLORATORY STUDY.

Background : Trauma and blood loss are frequently associated with organ failure, immune dysfunction, and a high risk of secondary bacterial lung infections. We aim to test if plasma metabolomic flux and monocyte bioenergetics are altered in association with trauma and related secondary infections. Methods : Plasma samples were collected from trauma patients at three time points: days 0, 3, and 7 postadmission. Metabolites (140) were measured in plasma from trauma survivors ( n = 24) and healthy control individuals (HC, n = 10). Further analysis within the trauma cohort included subsets of trauma/infection-negative (TIneg, n = 12) and trauma/infection-positive patients (TIpos, n = 12). The bioenergetic profile in monocytes was determined using mitochondrial and glycolytic stress tests. Results : In the trauma cohort, significant alterations were observed in 29 metabolites directly affecting 11 major metabolic pathways, while 34 metabolite alterations affected 8 pathways in 9, versus TIneg patients. The most altered metabolic pathways included protein synthesis, the urea cycle/arginine metabolism, phenylalanine, tyrosine, tryptophan biosynthesis, and carnitine compound family. In monocytes from trauma patients, reduced mitochondrial indices and loss of glycolytic plasticity were consistent with an altered profile of plasma metabolites in the tricarboxylic acid cycle and glycolysis. Conclusions : Our study highlights that the metabolic profile is significantly and persistently affected by trauma and related infections. Among trauma survivors, metabolic alterations in plasma were associated with reduced monocyte bioenergetics. These exploratory findings establish a groundwork for future clinical studies aimed at enhancing our understanding of the interplay between metabolic/bioenergetic alterations associated with trauma and secondary bacterial infections.

Compositional characteristics of the gut microbiome in patients with uremia.

During acute or chronic uremia, the cumulative harmful effects of uremic toxins result in numerous health problems and, ultimately, mortality. Previous research has identified that uremic retention solutes originate from the gut microbiome, indicating that uremia may be closely associated with gut microbiome dysbiosis. To deepen our understanding of the compositional characteristics of the gut microbiome in patients with uremia and thereby promote precision medicine in the treatment of uremia, we conducted a study of the compositional characteristics of the gut microbiome in 20 patients with uremia. The gut microbiome diversity of uremic patients and the control group showed certain differences. Nonmetric multidimensional scaling analysis showed that the beta diversity of the gut microbiome of uremic patients was significantly different from that of the healthy control individuals, with a distinct clustering effect in the uremic patient group, and it also showed a similarly distinct clustering effect in the healthy control group. The Chao1 index and Sobs index were significantly lower in the uremic patient group than in the healthy control group (P < 0.05). By analyzing the composition and abundance distribution of the gut microbiome in the uremic patient group and healthy control group, we found that the relative abundance of the gut microbiome constituents Fusobacteriota, Enterobacteriaceae, Oscillospirales, Ruminococcaceae, and Lachnospiraceae was significantly increased in the intestines of uremic patients. We also detected the rare taxa Erysipelotrichaceae, which was present only in the uremic patient group. Predictive functional analysis suggested that an increased abundance of Ruminococcaceae and Lachnospirales, which are associated with indoxyl sulfate and phenylacetyl glutamine, and an increased abundance of Oscillospirales, which is associated with pyruvate metabolism, in uremic patients may strongly influence the gut environment according to renal function, resulting in dysbiosis associated with uremic toxin production. Rare taxa such as Erysipelotrichaceae have been suggested to be detrimental to intestinal disease. Further research into these gut microbiomes may provide new ideas for the prevention and treatment of uremia with the gut microbiome.