Stress Accumulation, Depressive Symptoms, and Sleep Problems among Black Americans in the Rural South.

Centuries of systemic racism in the United States have led to Black Americans facing a disproportionate amount of life stressors. These stressors can have negative effects on mental and physical health, contributing to inequities throughout the lifespan. The current study used longitudinal data from 692 Black adults in the rural South to examine the ways in which neighborhood stress, financial strain, and interpersonal experiences of racial discrimination operate independently and in tandem to impact depressive symptoms and sleep problems over time. Findings provided strong support for univariate and additive stress effects and modest support for multiplicative stress effects. Results underscore how multiple stressors stemming from systemic racism can undermine health among Black Americans and highlight the need for further research on factors that promote well-being in the face of these stressors.

Racial Discrimination, Neural Connectivity, and Epigenetic Aging Among Black Women.

Importance: Racial discrimination increases the risk of adverse brain health outcomes, potentially via neuroplastic changes in emotion processing networks. The involvement of deep brain regions (brainstem and midbrain) in these responses is unknown. Potential associations of racial discrimination with alterations in deep brain functional connectivity and accelerated epigenetic aging, a process that substantially increases vulnerability to health problems, are also unknown. Objective: To examine associations of racial discrimination with brainstem and midbrain resting-state functional connectivity (RSFC) and DNA methylation age acceleration (DMAA) among Black women in the US. Design, Setting, and Participants: This cohort study was conducted between January 1, 2012, and February 28, 2015, and included a community-based sample of Black women (aged ≥18 years) recruited as part of the Grady Trauma Project. Self-reported racial discrimination was examined in association with seed-to-voxel brain connectivity, including the locus coeruleus (LC), periaqueductal gray (PAG), and superior colliculus (SC); an index of DMAA (Horvath clock) was also evaluated. Posttraumatic stress disorder (PTSD), trauma exposure, and age were used as covariates in statistical models to isolate racial discrimination-related variance. Data analysis was conducted between January 10 and October 30, 2023. Exposure: Varying levels of racial discrimination exposure, other trauma exposure, and posttraumatic stress disorder (PTSD). Main Outcomes and Measures: Racial discrimination frequency was assessed with the Experiences of Discrimination Scale, other trauma exposure was evaluated with the Traumatic Events Inventory, and current PTSD was evaluated with the PTSD Symptom Scale. Seed-to-voxel functional connectivity analyses were conducted with LC, PAG, and SC seeds. To assess DMAA, the Methylation EPIC BeadChip assay (Illumina) was conducted with whole-blood samples from a subset of 49 participants. Results: This study included 90 Black women, with a mean (SD) age of 38.5 (11.3) years. Greater racial discrimination was associated with greater left LC RSFC to the bilateral precuneus (a region within the default mode network implicated in rumination and reliving of past events; cluster size k = 228; t85 = 4.78; P < .001, false discovery rate-corrected). Significant indirect effects were observed for the left LC-precuneus RSFC on the association between racial discrimination and DMAA (ß [SE] = 0.45 [0.16]; 95% CI, 0.12-0.77). Conclusions and Relevance: In this study, more frequent racial discrimination was associated with proportionately greater RSFC of the LC to the precuneus, and these connectivity alterations were associated with DMAA. These findings suggest that racial discrimination contributes to accelerated biological aging via altered connectivity between the LC and default mode network, increasing vulnerability for brain health problems.

Racial Discrimination and Risk for Internalizing and Externalizing Symptoms Among Black Youths.

Importance: Racial discrimination is a psychosocial stressor associated with youths' risk for psychiatric symptoms. Scarce data exist on the moderating role of amygdalar activation patterns among Black youths in the US. Objective: To investigate the association between racial discrimination and risk for psychopathology moderated by neuroaffective processing. Design, Setting, and Participants: This cohort study used longitudinal self-report and functional magnetic resonance imaging (fMRI) data from Black youth participants in the US from the Adolescent Brain Cognitive Development (ABCD) study. Data were analyzed from January 2023 to May 2024. Exposures: At time 1 of the current study (12 months after baseline), youths self-reported on their experiences of interpersonal racial discrimination and their feelings of marginalization. Amygdalar response was measured during an emotionally valenced task that included blocks of faces expressing either neutral or negative emotion. Main Outcomes and Measures: At 24 and 36 months after baseline, youths reported their internalizing (anxiety and depressive symptoms) and externalizing symptoms (aggression and rule-breaking symptoms). Results: A total of 1596 youths were a mean (SD) age of 10.92 (0.63) years, and 803 were female (50.3%). Families in the study had a mean annual income range of $25 000 to $34 999. Two factors were derived from factor analysis: interpersonal racial discrimination and feelings of marginalization (FoM). Using structural equation modeling in a linear regression, standardized ß coefficients were obtained. Neural response to faces expressing negative emotion within the right amygdala significantly moderated the association between FoM and changes in internalizing symptoms (ß = -0.20; 95% CI, -0.32 to -0.07; P < .001). The response to negative facial emotion within the right amygdala significantly moderated the association between FoM and changes in externalizing symptoms (ß = 0.24; 95% CI, 0.04 to 0.43; P = .02). Left amygdala response to negative emotion significantly moderated the association between FoM and changes in externalizing symptoms (ß = -0.16; 95% CI, -0.32 to -0.01; P = .04). Conclusions and Relevance: In this cohort study of Black adolescents in the US, findings suggest that amygdala function in response to emotional stimuli can both protect and intensify the affective outcomes of feeling marginalized on risk for psychopathology, informing preventive interventions aimed at reducing the adverse effects of racism on internalizing and externalizing symptoms among Black youths.

Moral injury, race-related stress and post-traumatic stress disorder in a trauma-exposed Black population.

BACKGROUND: Race-related stress (RRS) is an unrecognized source of moral injury (MI)-or the emotional and/or spiritual suffering that may emerge after exposure to events that violate deeply held beliefs. Additionally, MI has not been explored as a mechanism of risk for post-traumatic stress disorder (PTSD) in trauma-exposed civilians. We examined relations among exposure to potentially morally injurious events (moral injury exposure, MIE), related distress (moral injury distress, MID), and RRS in Black Americans. Potential indirect associations between RRS and PTSD symptoms via MID were also examined. METHODS: Black Americans (n = 228; 90.4% female; Mage = 31.6 years. SDage = 12.8 years) recruited from an ongoing study of trauma completed measures assessing civilian MIE and MID, RRS, and PTSD. Bivariate correlations were conducted with MIE and MID, and mediation analysis with MID, to examine the role of MI in the relationship between RRS and PTSD symptom severity. RESULTS: MIE was significantly correlated with cultural (r = 0.27), individual (r = 0.29), and institutional (r = 0.25) RRS; MID also correlated with cultural (r = 0.31), individual (r = 0.31), and institutional (r = 0.26) RRS (ps < 0.001). We found an indirect effect of RRS on PTSD symptoms via MID (ß = 0.10, p < 0.005). CONCLUSIONS: All types of RRS were associated with facets of MI, which mediated the relationship between RRS and current PTSD symptoms. MI may be a potential mechanism through which RRS increases the risk for PTSD in Black individuals.

The neurophysiological consequences of racism-related stressors in Black Americans.

Racism-related stressors, from experiences of both implicit and explicit racial discrimination to systemic socioeconomic disadvantage, have a cumulative impact on Black Americans' health. The present narrative review synthesizes peripheral (neuroendocrine and inflammation markers), psychophysiological (heart-rate variability, skin conductance), and neuroimaging (structural and functional) findings that demonstrate unique associations with racism-related stress. Emerging evidence reveals how racism-related stressors contribute to differential physiological and neural responses and may have distinct impacts on regions involved with threat and social processing. Ultimately, the neurophysiological effects of racism-related stress may confer biological susceptibility to stress and trauma-related disorders. We note critical gaps in the literature on the neurophysiological impact of racism-related stress and outline additional research that is needed on the multifactorial interactions between racism and mental health. A clearer understanding of the interactions between racism-related stress, neurophysiology, and stress- and trauma-related disorders is critical for preventative efforts, biomarker discovery, and selection of effective clinical treatments for Black Americans.

Association of white matter hyperintensities and clinical vascular burden with depressive symptoms in Black older adults.

OBJECTIVES: Black older adults have a higher vascular burden compared to non-Hispanic White (NHW) older adults, which may put them at risk for a form of depression known as vascular depression (VaDep). The literature examining VaDep in Black older adults is sparse. The current study addressed this important gap by examining whether vascular burden was associated with depressive symptoms in Black older adults. METHODS: Participants included 113 Black older adults from the Healthy Brain Project, a substudy of the Health, Aging, and Body Composition Study. In multiple regression analyses, clinical vascular burden (sum of vascular conditions) and white matter hyperintensity (WMH) volume predicted depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale, controlling for demographic variables. Follow-up analyses compared the associations in the Black subsample and in 179 NHW older adults. RESULTS: Higher total WMH volume, but not clinically-defined vascular burden, predicted higher concurrent depressive symptoms and higher average depressive symptoms over 4 years. Similar associations were found between uncinate fasciculus (UF) WMHs and concurrent depressive symptoms and between superior longitudinal fasciculus WMHs and average depressive symptoms. The association between depressive symptoms and UF WMH was stronger in Black compared to NHW individuals. CONCLUSION: This research is consistent with the VaDep hypothesis and extends it to Black older adults, a group that has historically been underrepresented in the literature. Results highlight WMH in the UF as particularly relevant to depressive symptoms in Black older adults and suggest this group may be particularly vulnerable to the negative effects of WMH.

What, How, When, and Where: Spatiotemporal Water Quality Hazards of Cyanotoxins in Subtropical Eutrophic Reservoirs.

Though toxins produced during harmful blooms of cyanobacteria present diverse risks to public health and the environment, surface water quality surveillance of cyanobacterial toxins is inconsistent, spatiotemporally limited, and routinely relies on ELISA kits to estimate total microcystins (MCs) in surface waters. Here, we employed liquid chromatography tandem mass spectrometry to examine common cyanotoxins, including five microcystins, three anatoxins, nodularin, cylindrospermopsin, and saxitoxin in 20 subtropical reservoirs spatially distributed across a pronounced annual rainfall gradient. Probabilistic environmental hazard analyses identified whether water quality values for cyanotoxins were exceeded and if these exceedances varied spatiotemporally. MC-LR was the most common congener detected, but it was not consistently observed with other toxins, including MC-YR, which was detected at the highest concentrations during spring with many observations above the California human recreation guideline (800 ng/L). Cylindrospermopsin was also quantitated in 40% of eutrophic reservoirs; these detections did not exceed a US Environmental Protection Agency swimming/advisory level (15,000 ng/L). Our observations have implications for routine water quality monitoring practices, which traditionally use ELISA kits to estimate MC levels and often limit collection of surface samples during summer months near reservoir impoundments, and further indicate that spatiotemporal surveillance efforts are necessary to understand cyanotoxins risks when harmful cyanobacteria blooms occur throughout the year.

Cellular Iron Deficiency Disrupts Thyroid Hormone Regulated Gene Expression in Developing Hippocampal Neurons.

BACKGROUND: Developing neurons have high thyroid hormone and iron requirements to support their metabolically demanding growth. Early-life iron and thyroid-hormone deficiencies are prevalent and often coexist, and each independently increases risk of permanently impaired neurobehavioral function in children. Early-life dietary iron deficiency reduces thyroid-hormone concentrations and impairs thyroid hormone-responsive gene expression in the neonatal rat brain, but it is unclear whether the effect is cell-intrinsic. OBJECTIVES: This study determined whether neuronal-specific iron deficiency alters thyroid hormone-regulated gene expression in developing neurons. METHODS: Iron deficiency was induced in primary mouse embryonic hippocampal neuron cultures with the iron chelator deferoxamine (DFO) beginning at 3 d in vitro (DIV). At 11DIV and 18DIV, thyroid hormone-regulated gene messenger ribonucleic acid (mRNA)concentrations indexing thyroid hormone homeostasis (Hairless, mu-crystallin, Type II deiodinase, solute carrier family member 1c1, and solute carrier family member 16a2) and neurodevelopment (neurogranin, Parvalbumin, and Krüppel-like factor 9) were quantified. To assess the effect of iron repletion, DFO was removed at 14DIV from a subset of DFO-treated cultures, and gene expression and adenosine 5'-triphosphate (ATP) concentrations were quantified at 21DIV. RESULTS: At 11DIV and 18DIV, neuronal iron deficiency decreased neurogranin, Parvalbumin, and mu-crystallin, and by 18DIV, solute carrier family member 16a2, solute carrier family member 1c1, Type II deiodinase, and Hairless were increased, suggesting cellular sensing of a functionally abnormal thyroid hormone state. Dimensionality reduction with Principal component analysis reveals that thyroid hormone homeostatic genes strongly correlate with and predict iron status. Iron repletion from 14-21DIV did not restore ATP concentration, and Principal component analysis suggests that, after iron repletion, cultures maintain a gene expression signature indicative of previous iron deficiency. CONCLUSIONS: These novel findings suggest there is an intracellular mechanism coordinating cellular iron/thyroid hormone activities. We speculate this is a part of the homeostatic response to acutely match neuronal energy production and growth signaling. However, the adaptation to iron deficiency may cause permanent deficits in thyroid hormone-dependent neurodevelopmental processes even after recovery from iron deficiency.

C-reactive protein moderates associations between racial discrimination and ventromedial prefrontal cortex activation during attention to threat in Black American women.

Prior research has shown that racial discrimination (RD) impacts activation in threat network regions, including the ventromedial prefrontal cortex (vmPFC) and middle occipital cortex during attention to threat-relevant stimuli. However, little is known about the biological mechanisms that may modulate these effects; inflammation may be a pathway linking RD and threat network activation. As such, the current study aimed to explore whether systemic inflammation, measured by C-reactive protein (CRP) levels, may moderate the relationship between RD and activation in the vmPFC and middle occipital cortex during attention to threat. Blood samples for inflammatory marker (CRP) assays were obtained from forty Black American women (mean [SD] age, 39.93 [9.97] years; range, 22-58 years) recruited from an ongoing trauma study; participants also viewed threat-relevant stimuli as part of an attention task during fMRI. We found that CRP moderated the relationship between RD and vmPFC activation during attention to threat, such that participants with relatively higher concentrations of CRP ( ≥ 23.97 mg/L) demonstrated significant positive associations between RD and vmPFC activation [ß = 0.18, CI (0.04, 0.32), t = 2.65, p = 0.01]. No significant associations were observed for participants who showed moderate (10.89 mg/L) or low (0.20 mg/L) CRP concentrations. CRP did not moderate the relationship between RD and middle occipital cortex activation. Our data present a mechanism through which RD may influence immune system activation and, in turn, threat network activation. Inflammation may contribute to brain health vulnerabilities in Black Americans via its effects on threat circuits; this merits further investigation in large-scale studies.

Concentration of total microcystins associates with nitrate and nitrite, and may disrupt the nitrogen cycle, in warm-monomictic lakes of the southcentral United States.

Cyanobacterial blooms and the toxins they produce pose a growing threat worldwide. Mitigation of such events has primarily focused on phosphorus management and has largely neglected the role of nitrogen. Previous bloom research and proposed management strategies have primarily focused on temperate, dimictic lakes, and less on warm-monomictic systems like those at subtropical latitudes. The in-lake conditions, concentration of total microcystins, and microbial functioning of twenty warm-monomictic lakes in the southcentral United States were explored in the spring and summer of 2021. Our data revealed widespread microcystins in lakes across this region, some of which exceeded regulatory limits. Microcystins were higher in the spring compared to the summer, indicating that warm-monomictic lakes, even across a large range of precipitation, do not follow the trends of temperate dimictic lakes. Microcystins were found in surface waters and bottom waters well below the photic zone, reflecting the persistence of these toxins in the environment. Principal components analyses showed a strong association between microcystins, nitrate + nitrite, and Planktothrix relative abundance and transcriptional activity. Many systems exhibited stronger denitrification in the spring, perhaps contributing to the decreased toxin concentrations in the summer. Counter to most sampled lakes, one lake with the highest concentration of total microcystins indicated nitrogen cycle disruption, including inhibited denitrification. These findings are relevant to mitigating cyanobacterial blooms and toxin production in warm-monomictic systems, and suggests a need to consider nitrogen, and not solely phosphorus, in nutrient management discussions.

A multiple-oscillator mechanism underlies antigen-induced Ca2+ oscillations in Jurkat T-cells.

T-cell receptor stimulation triggers cytosolic Ca2+ signaling by inositol-1,4,5-trisphosphate (IP3)-mediated Ca2+ release from the endoplasmic reticulum (ER) and Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC) channels gated by ER-located stromal-interacting molecules (STIM1/2). Physiologically, cytosolic Ca2+ signaling manifests as regenerative Ca2+ oscillations, which are critical for nuclear factor of activated T-cells-mediated transcription. In most cells, Ca2+ oscillations are thought to originate from IP3 receptor-mediated Ca2+ release, with CRAC channels indirectly sustaining them through ER refilling. Here, experimental and computational evidence support a multiple-oscillator mechanism in Jurkat T-cells whereby both IP3 receptor and CRAC channel activities oscillate and directly fuel antigen-evoked Ca2+ oscillations, with the CRAC channel being the major contributor. KO of either STIM1 or STIM2 significantly reduces CRAC channel activity. As such, STIM1 and STIM2 synergize for optimal Ca2+ oscillations and activation of nuclear factor of activated T-cells 1 and are essential for ER refilling. The loss of both STIM proteins abrogates CRAC channel activity, drastically reduces ER Ca2+ content, severely hampers cell proliferation and enhances cell death. These results clarify the mechanism and the contribution of STIM proteins to Ca2+ oscillations in T-cells.

Infant epigenetic aging moderates the link between Black maternal childhood trauma and offspring symptoms of psychopathology.

Although offspring of women exposed to childhood trauma exhibit elevated rates of psychopathology, many children demonstrate resilience to these intergenerational impacts. Among the variety of factors that likely contribute to resilience, epigenetic processes have been suggested to play an important role. The current study used a prospective design to test the novel hypothesis that offspring epigenetic aging - a measure of methylation differences that are associated with infant health outcomes - moderates the relationship between maternal exposure to childhood adversity and offspring symptomatology. Maternal childhood adversity was self-reported during pregnancy via the ACEs survey and the CTQ, which assessed total childhood trauma as well as maltreatment subtypes (i.e., emotional, physical, and sexual abuse). Offspring blood samples were collected at or shortly after birth and assayed on a DNA methylation microarray, and offspring symptomatology was assessed with the CBCL/1.5-5 when offspring were 2-4 years old. Results indicated that maternal childhood trauma, particularly sexual abuse, was predictive of offspring symptoms (ps = 0.003-0.03). However, the associations between maternal sexual abuse and offspring symptomatology were significantly attenuated in offspring with accelerated epigenetic aging. These findings further our understanding of how epigenetic processes may contribute to and attenuate the intergenerational link between stress and psychopathology.

Introduction to the Special Section on the International Society for Traumatic Stress Studies 38th Annual Meeting: Trauma as a transdiagnostic risk factor across the lifespan.

This article serves as an introduction to the special section in the Journal of Traumatic Stress related to the 38th annual meeting of the International Society for Traumatic Stress Studies, held in Atlanta, Georgia (USA) in November 2022. The theme of this meeting, "Trauma as a Transdiagnostic Risk Factor Across the Lifespan," provided an opportunity to recognize the far-reaching impact of trauma and how traumatic experiences can become embedded into the mind, body, and societal spirit. This introductory article outlines the importance of harnessing multiple perspectives to address these wide-ranging sequelae of trauma and provides an overview of the series of contributions to the special section.

Cellular Iron Deficiency Disrupts Thyroid Hormone Regulated Gene Expression in Developing Hippocampal Neurons.

Background: Developing neurons have high thyroid hormone and iron requirements to support their metabolism and growth. Early-life iron and thyroid hormone deficiencies are prevalent, often coexist, and increase the risk of permanently impaired neurobehavioral function in children. Early-life dietary iron deficiency reduces thyroid hormone levels and impairs thyroid hormone-responsive gene expression in the neonatal rat brain. Objective: This study determined whether neuronal-specific iron deficiency alters thyroid hormone-regulated gene expression in developing neurons. Methods: Iron deficiency was induced in primary mouse embryonic hippocampal neuron cultures with the iron chelator deferoxamine (DFO) beginning at 3 days in vitro (DIV). At 11DIV and 18DIV, mRNA levels for thyroid hormone-regulated genes indexing thyroid hormone homeostasis (Hr, Crym, Dio2, Slco1c1, Slc16a2) and neurodevelopment (Nrgn, Pvalb, Klf9) were quantified. To assess the effect of iron repletion, DFO was removed at 14DIV from a subset of DFO-treated cultures and gene expression and ATP levels were quantified at 21DIV. Results: At 11DIV and 18DIV, neuronal iron deficiency decreased Nrgn, Pvalb, and Crym, and by 18DIV, Slc16a2, Slco1c1, Dio2, and Hr were increased; collectively suggesting cellular sensing of a functionally abnormal thyroid hormone state. Dimensionality reduction with Principal Component Analysis (PCA) reveals that thyroid hormone homeostatic genes strongly correlate with and predict iron status (Tfr1 mRNA). Iron repletion from 14-21DIV restored neurodevelopmental genes, but not all thyroid hormone homeostatic genes, and ATP concentrations remained significantly altered. PCA clustering suggests that cultures replete with iron maintain a gene expression signature indicative of previous iron deficiency. Conclusions: These novel findings suggest there is an intracellular mechanism coordinating cellular iron/thyroid hormone activities. We speculate this is a part of homeostatic response to match neuronal energy production and growth signaling for these important metabolic regulators. However, iron deficiency may cause permanent deficits in thyroid hormone-dependent neurodevelopmental processes even after recovery from iron deficiency.

Shift-and-persist coping and health among rural African American adolescents.

This study examines whether shift-and-persist coping, a coping strategy defined by accepting challenges and remaining hopeful for the future, is associated with psychosocial and physical health and/or moderates the effects of contextual stress (i.e., racial discrimination, financial strain) on health among African American adolescents living in the rural Southeastern United States. Participants (N = 299, 56% boys, Mage = 12.91) completed measures of shift-and-persist coping, contextual stress, and psychosocial and physical health. Shift-and-persist coping was generally associated with better health but did not buffer the effects of contextual stress. Results suggest that shift-and-persist coping may serve as a source of resilience among African American adolescents living in a context where many experience heightened contextual stress.

Intergenerational Transmission of Depression: Examining the Roles of Racism and Trauma Among Black Mothers and Youth.

OBJECTIVE: Racism is a multifaceted system of oppression that disproportionately harms Black mothers and children across the lifespan. Despite reliable evidence that racism is associated with worse mental health outcomes (eg, increased depressive symptoms), less is known about potential intergenerational effects of Black mothers' experiences of racism on children's mental health, as well as how traumatic experiences influence these pathways. In this cross-sectional quantitative study, we aimed (1) to replicate the finding that maternal experiences of racism are associated with both maternal and child depression; (2) to identify whether maternal experiences of racism are indirectly associated with child depression via the effect of maternal depression; and (3) to test whether the indirect effect of racism on child depression via maternal depression is conditioned on maternal trauma. METHOD: Black mothers and their children (N = 148 dyads) were recruited from an urban hospital and were interviewed about their experiences of racism, trauma, and mental health symptoms. The mothers' average age was 35.16 years (SD = 8.75) and the children's average age was 10.03 years (SD = 1.51). RESULTS: First, we found that maternal experiences of racism were associated with more severe maternal depression (r = 0.37, p < .01) as well as more severe child depression (r = 0.19, p = .02). Second, we found that maternal experiences of racism were indirectly associated with child depression through the effect of maternal depression (ab = 0.76, 95% CI = 0.26, 1.37). Third, we found that maternal trauma exposure moderated this indirect effect such that, at relatively lower levels of maternal trauma exposure, the indirect effect of maternal experiences of racism on child depression was nonsignificant (ωlow = -0.05, 95% CI = -0.50, 0.45), whereas at relatively higher levels of maternal trauma exposure, the indirect effect of maternal experiences of racism on child depression was statistically significant (ωhigh= .65, 95% CI = 0.21, 1.15). CONCLUSION: These findings suggest that the indirect effect of maternal experiences of racism on child depression through the effect of maternal depression depends on the degree of maternal trauma exposure. This study advances the literature by shedding light on key processes that can explain the intergenerational effects of racism as well as contextual factors that can exacerbate racism's downstream consequences across generations.

Disruptive lysosomal-metabolic signaling and neurodevelopmental deficits that precede Purkinje cell loss in a mouse model of Niemann-Pick Type-C disease.

Purkinje cell (PC) loss occurs at an early age in patients and animal models of Niemann-Pick Type C (NPC), a lysosomal storage disease caused by mutations in the Npc1 or Npc2 genes. Although degeneration of PCs occurs early in NPC, little is known about how NPC1 deficiency affects the postnatal development of PCs. Using the Npc1nmf164 mouse model, we found that NPC1 deficiency significantly affected the postnatal development of PC dendrites and synapses. The developing dendrites of Npc1nmf164 PCs were significantly deficient in mitochondria and lysosomes. Furthermore, anabolic (mTORC1) and catabolic (TFEB) signaling pathways were not only perturbed but simultaneously activated in NPC1-deficient PCs, suggesting a loss of metabolic balance. We also found that mice with conditional heterozygous deletion of the Phosphatase and Tensin Homolog Deleted on Chromosome 10 gene (Pten-cHet), an inhibitor of mTORC1, showed similar early dendritic alterations in PCs to those found in Npc1-deficient mice. However, in contrast to Npc1nmf164 mice, Pten-cHet mice exhibited the overactivation of the mTORC1 pathway but with a strong inhibition of TFEB signaling, along with no dendritic mitochondrial reductions by the end of their postnatal development. Our data suggest that disruption of the lysosomal-metabolic signaling in PCs causes dendritic and synaptic developmental deficits that precede and promote their early degeneration in NPC.

Strengthening couple functioning promotes resilience to COVID-19-related stressors among Black Americans.

The COVID-19 pandemic resulted in substantial hardship for Black Americans, leading to increased stress and mental health difficulties. We used longitudinal data from the Protecting Strong African American Families (ProSAAF) intervention study to test the hypothesis that improved couple functioning following ProSAAF participation would serve as a constructed resilience resource during the pandemic, buffering the impact of elevated pandemic-related stressors on change in depressive symptoms. We found that COVID-19-related stress predicted change in depressive symptoms from prepandemic to during the pandemic, that ProSAAF predicted improved couple functioning, and that positive change in couple functioning buffered the impact of pandemic stressors on change in depressive symptoms. These effects resulted in a significant indirect buffering effect of ProSAAF on the association between COVID-19-related stress and change in depressive symptoms through its effects on change in couple functioning. The results suggest that relationship intervention may increase resilience to unanticipated community-wide stress and promote mental health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Indirect Effects of Racial Discrimination on Health Outcomes Through Prefrontal Cortical White Matter Integrity.

BACKGROUND: Racial discrimination is consistently associated with adverse health outcomes and has been linked to structural decrements in brain white matter. However, it is unclear whether discrimination-related neuroplastic changes could indirectly affect health outcomes. Our goal was to evaluate indirect associations of racial discrimination on health outcomes through white matter microstructure in a sample of trauma-exposed Black women. METHODS: A trauma study in an urban hospital setting recruited 79 Black women who received a history and physical examination to assess medical disorders (compiled into a summed total of disorder types). Participants reported on experiences of racial discrimination and underwent diffusion tensor imaging; fractional anisotropy values were extracted from white matter pathways previously linked to racial discrimination (corpus callosum, including the body and genu; anterior cingulum bundle; and superior longitudinal fasciculus) and entered into mediational models. RESULTS: Indirect effects of racial discrimination on medical disorders through left anterior cingulum bundle fractional anisotropy were significant (ß = 0.07, SE = 0.04, 95% CI [0.003, 0.14]) after accounting for trauma and economic disadvantage. Indirect effects of racial discrimination on medical disorders through corpus callosum genu fractional anisotropy were also significant (ß = 0.08, SE = 0.04, 95% CI [0.01, 0.16]). CONCLUSIONS: Racial discrimination may increase risk for medical disorders via neuroplastic effects on microstructural integrity of stress-sensitive prefrontal white matter tracts. Racial discrimination-related changes in these tracts may affect health behaviors, which, in turn, influence vulnerability for medical disorders. These data highlight the connections between racial discrimination, prefrontal white matter connections, and incidence of medical disorders in Black Americans.

Beliefs and Perceived Barriers Regarding Psychedelic-assisted Therapy in a Pilot Study of Service Members and Veterans With a History of Traumatic Brain Injury.

INTRODUCTION: Posttraumatic stress disorder (PTSD) and depression are common in service members and veterans, and the response to currently available treatments is often modest at best. Recent studies suggest potential benefit with psychedelic-assisted therapies (PATs), particularly 3,4-methylenedioxymethamphetamine-assisted therapy for PTSD and psilocybin-assisted therapy for depression. This study examined beliefs and perceived barriers regarding PAT among service members and veterans to inform the delivery of these treatments if they are approved by the FDA. MATERIALS AND METHODS: Twenty-one service members and veterans (67% male, 81% White, and 43% active duty) with a history of traumatic brain injury and co-occurring cognitive and psychological symptoms completed a measure assessing baseline knowledge and views of PAT, read a brief psychoeducation regarding PAT, and then responded to questions related to their beliefs and perceived barriers to PAT. RESULTS: Before psychoeducation, participants reported a neutral view of psychedelic drugs (M = 2.76; range: 1-5), PAT (M = 3.33), and interest in PAT (M = 3.10). After psychoeducation, participants reported a significantly more positive view of psychedelic drugs (M = 3.24, P = .014) and interest in PAT (M = 3.67, P = .016). Overall, participants indicated that they would support PAT availability in medical settings if proven beneficial (M = 4.52; 5 = "agree strongly") and they would support a loved one engaging in PAT (M = 4.29). The most frequently reported health concerns were concern of long-term effects (43%), fear of losing their mind (33%), fear of personality changes (33%), and fear of traumatic brain injury complications (24%). The most frequently endorsed barriers were time commitment, transportation, financial concerns, work, and childcare (33%-19%), with 48% reporting no barriers. CONCLUSIONS: This is the first study to explore beliefs and perceived barriers regarding PAT among service members and veterans. These results indicate that military populations may be interested in PAT, particularly if psychoeducation and outreach regarding these treatments occurred. If FDA approved, it will be important to facilitate command support and address logistical barriers to ensure appropriate access within military contexts.