Biology subjects

Marsland, A. L.

Publications and source records attributed to Marsland, A. L..

7 recordsLinked to original sources

bioRxiv2026

From the scanner to daily life: Neural expression of the Picture-Induced Negative Emotion Signature is associated with real-world daily and momentary negative affect in midlife adults

Functional magnetic resonance imaging (fMRI) is widely used to map brain systems that process affective stimuli and predict concurrent affective experiences in the scanner. However, the extent to which affect-related fMRI activity in the scanner predicts affective experiences in daily life remains unclear. This study examined whether a multivariate brain pattern previously validated to predict negative affect to emotional images during fMRI testing (the Picture-Induced Negative Emotion Signature; PINES) associates with daily negative affect measured over 7-10 days via daily diaries and ecological momentary assessment. Among 287 midlife adults, those exhibiting greater PINES pattern expression showed greater daily (end-of-day) and hourly negative affect. These findings were not explained by demographic factors and trait negative affect. A cross-validated whole-brain pattern of negative affect generalizes beyond the fMRI testing context to predict negative affect severity in daily life.

neuroscience↗

bioRxiv2026

Unraveling Tissue-Specific Molecular Signatures and Convergent Pathway Enrichments in Suicidal Behavior

Suicide is a leading cause of death worldwide, yet the biological mechanisms underlying suicide remain poorly understood. A clearer understanding at the molecular level is essential for developing objective biomarkers and targeted interventions. In this study, we used transcriptomic profiling to investigate gene expression patterns associated with suicidal thoughts and behaviors across peripheral blood (n=264) and postmortem brain tissue from two prefrontal regions (dorsolateral prefrontal cortex, DLPFC; subgenual anterior cingulate cortex, sgACC) of individuals with and without psychiatric illness (n=249). Peripheral analyses revealed broad transcriptional changes associated with suicidal thoughts and behaviors, marked by dysregulated immune-related and inflammatory processes. Longitudinal modeling further revealed gene co-expression modules that predicted future suicide attempts over a 12-month follow-up, highlighting processes related to apoptosis, mitochondrial function, and immune regulation. By contrast, transcriptomic analyses of postmortem tissue derived from the DLPFC and sgACC revealed largely suppressed neuroimmune activity. Gene co-expression analyses in the brain identified suicide-associated modules enriched for synaptic plasticity, oxidative stress, and neuroimmune function, some of which displayed regional specificity. Cross-tissue comparison showed minimal gene-level overlap between brain and blood, although shared pathway-level themes emerged in immune, sensory, and cellular stress processes. Taken together, these findings suggest that suicide is associated with distinct but functionally convergent transcriptional alterations across brain and blood. By integrating tissue-specific and systems-level molecular signatures, this work provides insight into the biological architecture of suicide and lays the groundwork for developing novel biomarkers and therapeutic targets to improve prevention and treatment outcomes.

neuroscience↗

bioRxiv2025

Community Socioeconomic Disadvantage relates to White Matter Hyperintensity Burden in Mid-to-Late Life Adults

BackgroundResiding in communities characterized by socioeconomic disadvantage may confer risk for neurodegenerative brain changes and future neuropathology. Based on prior evidence, this study tested the hypotheses that (1) community-level disadvantage would relate independently of individual-level socioeconomic position to white matter hyperintensities (WMHs), which reflect subclinical brain pathology that may presage later dementia; and (2) this association would be partly explained by blood pressure, cardiometabolic risk, and/or systemic levels of inflammation. These hypotheses were examined among otherwise healthy middle- and older-aged adults without clinical dementia at testing. MethodsParticipants were 388 adults aged 40-72 years (53% female; 12% non-White) whose street addresses were entered into the Neighborhood Atlas to compute Area Deprivation Index scores by census block. Participants also underwent high resolution (7 Tesla) brain imaging to assess total WMH volume normalized for intracranial volume, and assessment of blood pressure, cardiometabolic (adiposity, lipids, glucose and insulin), and inflammatory (interleukin-6 and C-reactive protein) risk factors. ResultsLinear regression models showed that higher community deprivation on the ADI associated with greater WMH volume, independently of age, sex, years of education and smoking. This association was largely independent of blood pressure, cardiometabolic risk and systemic inflammation. ConclusionThe present novel findings add to growing evidence that community disadvantage relates to preclinical neurodegenerative changes, which may contribute to accelerated brain and cognitive aging. Future work is warranted to better understand pathways that link residential environments to brain health and to identify targets for community and public policy interventions.

neuroscience↗

bioRxiv2024

Psychobiological regulation of plasma and saliva GDF15 dynamics in health and mitochondrial diseases

Growth Differentiation Factor 15 (GDF15) is a protein that reflects mitochondrial energetic stress and is linked to physical and mental health symptoms, aging, and mortality. Here, we tested the hypothesis that GDF15 is a stress-responsive biomarker through a series of observational and experimental studies. We report four main findings. First, in the UK Biobank (n=53,026) and Framingham Heart Study (FHS) Offspring (n=3,460) cohorts, plasma GDF15 levels were elevated in individuals with symptoms of depression and anxiety. In the FHS cohort, GDF15 was also higher in participants exposed to chronic psychosocial stressors, including lower educational attainment, lower family income, and higher job strain. Second, plasma GDF15 levels in the FHS cohort correlated positively with epigenetic clocks measuring biological aging and effect sizes of GDF15 associations with psychosocial stressors were comparable to those observed for the clocks. Third, in a two-participant intensive-sampling study (n=112 days), saliva GDF15 showed a robust awakening response similar to established stress-related hormones. However, it exhibited a distinct negative pattern, peaking at waking and declining by 42-92% within 30-45 minutes. Finally, in two laboratory experiments (n=148), acute social-evaluative stress significant increased GDF15 levels in plasma and saliva within minutes. Together, these findings suggest that psychosocial stress may contribute to mitochondrial energetic stress indexed by GDF15, with implications for aging and health. This work opens new avenues for using GDF15 as a non-invasive biomarker to study the biological embedding of stress and its impact on aging trajectories. Significance statementGrowth Differentiation Factor 15 (GDF15) is a circulating protein elevated with mitochondrial energetic stress, aging, and diseases. Our findings show that GDF15 is elevated with depressive and anxiety symptoms and in those exposed to chronic psychosocial stress. Elevated plasma GDF15 also correlates with accelerated biological aging, as measured by epigenetic clocks. The effect sizes linking GDF15 to psychosocial stressors were comparable to those observed for the epigenetic clocks. Saliva GDF15 shows a robust negative awakening response characterized by elevated levels at awakening before declining within 30-45 minutes. Acute social-evaluative stress induced increase in plasma and saliva GDF15. Together, these findings suggest GDF15 can be used to study the energetic mechanisms for the biological embedding of stress across the lifespan.

physiology↗

bioRxiv2022

Glucocorticoid and adrenergic receptor distribution across human organs and tissues: a map for stress transduction

ObjectivePsychosocial stress is transduced into disease risk through energy-dependent release of hormones that affect target organs, tissues, and cells. The magnitude of the physiological stress responses reflects both systemic levels of these hormones and the sensitivity of target tissues to their effects. Thus, differential expression of receptors across organs likely contributes to stress transduction. Here we provide a quantitative whole-body map of glucocorticoid and adrenergic receptor expression. MethodsWe systematically examined gene expression levels for the glucocorticoid receptor (GR), - and {beta}-adrenergic receptors (AR-1B, AR-2B AR-{beta}2, and AR-{beta}3), across 55 different organs using the Human Protein Atlas dataset. We also leveraged the Human Proteome Map and MitoCarta3.0 data to examine receptor protein levels and, given the energy-dependence of the stress response, the link between stress hormone receptor density and mitochondrial pathways. Finally, we tested the functional interplay between GR activation and AR expression in living human cells. ResultsThe GR was expressed ubiquitously across all investigated organ systems. Immune tissues and cells expressed the highest GR RNA and protein levels. In contrast, AR subtypes showed lower and more localized expression patterns. Co-regulation was found between GR and AR-1B, as well as between AR-1B and AR-2B. In human fibroblasts, activating the GR selectively increased AR-{beta}2 (3.6-fold) and AR-1B (2.2-fold) expression, confirming their interaction. Consistent with the energetic cost of stress responses, GR and AR expression were positively associated with the expression of key mitochondrial pathways. ConclusionOur results provide a cartography of GR and AR expression across the human body. Tissue-specific stress hormone receptor expression patterns could make specific organ systems more responsive to the sustained, energetically expensive, neuroendocrine signaling pathways triggered by chronic psychosocial stress.

cell biology↗

bioRxiv2021

Leukocyte cytokine responses in adult patients with mitochondrial DNA defects

Patients with oxidative phosphorylation (OxPhos) defects causing mitochondrial diseases appear particularly vulnerable to infections. Although OxPhos defects modulate cytokine production in vitro and in animal models, little is known about how circulating leukocytes of patients with inherited mitochondrial DNA (mtDNA) defects respond to acute immune challenges. In a small cohort of healthy controls (n=21) and patients (n=12) with either the m.3243A>G mutation or single, large-scale mtDNA deletions, we examined: i) cytokine responses (IL-6, TNF-, IL-1{beta}) in response to acute lipopolysaccharide (LPS) exposure, and ii) sensitivity to the immunosuppressive effects of glucocorticoid signaling (dexamethasone) on cytokine production. In dose-response experiments to determine the half-maximal effective LPS concentration (EC50), relative to controls, leukocytes from patients with mtDNA deletions showed 74 - 79% lower responses for IL-6 and IL-1{beta} (pIL-6=0.031, pIL-1{beta}=0.009). Moreover, IL-6 response to LPS in presence of GC was also blunted in cells from patients with mtDNA deletions (pIL-6=0.006), but not in leukocytes from patients with the m.3243A>G mutation. Overall, these ex vivo data provide preliminary evidence that some systemic OxPhos defects may compromise immune cytokine responses and glucocorticoid sensitivity. Further work in larger cohorts is needed to define the nature of immune dysregulation in patients with mitochondrial disease, and their potential implications for disease phenotypes.

immunology↗

bioRxiv2018

Acute Psychological Stress Triggers Circulating Cell-Free Mitochondrial DNA

Intrinsic biological mechanisms transduce psychological stress into physiological adaptation, but the role of mitochondria and mitochondrial DNA (mtDNA) in this process has not been defined in humans. Here, we show that similar to physical injury, psychological stress triggers elevation in circulating cell- free mtDNA (ccf-mtDNA). Healthy midlife adults exposed on two separate occasions to a brief psychological challenge exhibit a 2-3-fold increase in ccf-mtDNA, with no change in nuclear DNA levels, establishing the magnitude and specificity to ccf-mtDNA. In cell-based studies, we show that glucocorticoid signaling - a consequence of psychological stress in humans - is sufficient to induce mtDNA extrusion in a time frame consistent with human psychophysiology. Collectively, these findings provide the first evidence that psychological stress induces ccf-mtDNA and implicate glucocorticoid signaling as a trigger for ccf-mtDNA release. Further work is needed to examine the functional significance of psychological stress-induced ccf-mtDNA as a mitokine in humans.

molecular biology↗