Biology subjects

Slavich, G. M.

Publications and source records attributed to Slavich, G. M..

5 recordsLinked to original sources

bioRxiv2026

Inflammatory Proteins are Highly Variable During a Natural Stressor: A Call for Intensive Longitudinal Blood Microsampling

Much research investigates how inflammation might play a role in stress-mediated diseases such as heart disease and depression. However, standard longitudinal designs often have measurement lags of months or years between assessments. This status quo is at odds with evidence that inflammatory biology and stress are both highly dynamic and would require much shorter time lags to quantify change as it naturally occurs, with minimal risk of confounding or effects diluting over time. Inspired by the use of intensive longitudinal data collection in psychological research, this study collected high frequency (every 3 days) blood microsamples over 22 days as 86 incoming college students transitioned onto campus (total observations = 622 blood samples). Samples were analyzed for CRP, TNF-, IFN-{gamma}, IL-1{beta}, IL-2, IL-4, IL-6, IL-10, IL-12p70, and IL-17A. Results using both bivariate correlation and intra-class correlation coefficients (which can be used for future power analyses for longitudinal research with these proteins) demonstrate low reliability. Notably, hierarchical linear models demonstrated that, even at this frequency of assessment, most proteins were characterized by less than 6% stable between-person differences. These results provide compelling evidence that investment in intensive longitudinal data collection of immune proteins is critical for understanding how inflammatory biology might function in psychosocial models of risk and resilience.

immunology↗

bioRxiv2025

Neural Predictors of Functional Genomic Responses to Negative Social Evaluation in Adolescent Females

BackgroundSocial stress--particularly when experienced during adolescence, can have a lasting impact on health and well-being. Among other key biological pathways, inflammatory and innate immune signaling appear to play important roles in linking stress to physical and mental health problems. Individual differences in sensitivity to social threats may leave certain people more vulnerable to stress and its harmful sequelae than others, and a growing body of research has found that stress sensitivity is reflected in neural activity throughout the threat network. However, few studies have investigated whether heightened neural sensitivity to social threats is related to acute changes in immune and neuroendocrine pathways relevant to health, particularly among those for whom the effects of stress may be especially impactful. MethodIn the current research, 52 adolescent females (MAge = 14.90, SD = 1.35) participated in a functional magnetic resonance imaging study to examine brain activity and functional connectivity during a social evaluation task. Nearly half of the sample (n = 22) were identified as having a maternal history of depression. Blood samples were collected prior to the task, as well as 35 and 65 min. after the task began, and were used for transcriptional profiling. ResultsThe primary analyses tested whether threat network activity and connectivity predicted the magnitude of change in gene expression from baseline to the follow-up time points. Results revealed robust shifts in expression of genes in innate immune pathways in response to the task (e.g., hypoxia inducible factor-1, interferon signaling). Although activity across the entire threat network was related to individual differences in gene expression, anterior cingulate cortex-insula and insula-ventromedial prefrontal cortex connectivity were most consistently related to up- and down-regulation of immune pathways, respectively. These patterns were further moderated by differences in maternal depression history. ConclusionResults demonstrate that individual differences in threat network activity may have important implications for biological responses to social threat among adolescent females. In turn, these findings both provide insights into neural signatures of social stress vulnerability and the biological pathways that may contribute to poorer health outcome among those most vulnerable to stress.

neuroscience↗

bioRxiv2024

Shared and unique lifetime stressor characteristics and brain networks predict adolescent anxiety and depression

BackgroundExposure to major life stressors and aberrant brain functioning have been related to anxiety and depression, especially during adolescence. However, whether these associations differ based on the specific characteristics of the stressors experienced, and/or the functional networks engaged, remains unclear. MethodsWe used baseline lifetime stressor exposure and resting-state functional magnetic resonance imaging data from a longitudinal sample of 150 adolescents enriched for anxiety and depressive disorders. We examined the cumulative lifetime stressor frequency and severity of five stressor characteristics: physical danger, interpersonal loss, humiliation, entrapment, and role change/disruption. Anxiety and depression symptoms were assessed at three time points: baseline, 6-month and 12-month follow-ups. Linear mixed-effect models tested if the lifetime frequency and severity of these stressor characteristics and functional connectivity within and between frontoparietal, default, and ventral attention networks at baseline predicted anxiety and depression symptoms at three time points. ResultsLifetime frequency and severity of humiliation and entrapment predicted both anxiety and depression symptoms. Lifetime frequency and severity of entrapment exposures predicted anxiety and depression symptoms after accounting for baseline depression and anxiety symptoms, respectively. Resting-state functional connectivity between default, frontoparietal and ventral attention networks did not predict either anxiety or depression symptoms after correcting for multiple comparisons. ConclusionsOur study highlights lifetime exposures to humiliation and entrapment stressors as central stressor characteristics predictive of prospective anxiety and depression symptoms in adolescence. Our results also suggest that resting-state functional connectivity within and between default, frontoparietal and ventral attention networks may be relatively weak predictors of prospective anxiety and depression symptoms in adolescence.

neuroscience↗

bioRxiv2024

Dynamic Human Gut Microbiome and Immune Shifts During an Immersive Psychosocial Therapeutic Program

BackgroundDepression is a leading cause of disability worldwide yet its underlying factors, particularly microbial associations, are poorly understood. MethodsWe examined the longitudinal interplay between the microbiome and immune system in the context of depression during an immersive psychosocial intervention. 142 multi-omics samples were collected from 52 well-characterized participants before, during, and three months after a nine-day inquiry-based stress reduction program. ResultsWe found that depression was associated with both an increased presence of putatively pathogenic bacteria and reduced microbial beta-diversity. Following the intervention, we observed reductions in neuroinflammatory cytokines and improvements in several mental health indicators. Interestingly, participants with a Prevotella-dominant microbiome showed milder symptoms when depressed, along with a more resilient microbiome and more favorable inflammatory cytokine profile, including reduced levels of CXCL-1. ConclusionsOur findings reveal a protective link between the Prevotella-dominant microbiome and depression, associated with a less inflammatory environment and moderated symptoms. These insights, coupled with observed improvements in neuroinflammatory markers and mental health from the intervention, highlight potential avenues for microbiome-targeted therapies in depression management.

microbiology↗

bioRxiv2020

Glutamatergic adaptation to stress in medial prefrontal cortex underlies risk and resilience for pessimistic beliefs

Stress is a major risk factor for the development of mental illness, including major depressive disorder (MDD), yet the underlying biological mechanisms remain unclear. Particular challenges lie in disentangling adaptive versus maladaptive responses to repeated stress exposure. Preclinically, stress-induced changes in glutamatergic function have been frequently observed in the medial prefrontal cortex (mPFC), a key region for mediating adaptive stress responses. Here, we examined stress-induced changes in mPFC glutamate using magnetic resonance spectroscopy (MRS) in four human samples varying in perceived stress exposure. Changes in mPFC glutamate following an acute stressor were reliably moderated by recent perceived stress in healthy controls. This adaptive glutamate response was absent in unmedicated individuals with MDD and was associated with excessively pessimistic beliefs as assessed via ecological momentary assessments over a 1-month follow-up period. Taken together, these data provide novel evidence for glutamatergic adaptation to stress in mPFC that is significantly disrupted in MDD.

neuroscience↗