Chronic stress and cognitive dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: HPA axis dysregulation and hippocampal plasticity

Cognitive dysfunction is a common and disabling clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), often described by patients as “brain fog.” These symptoms typically manifest as difficulties in attention, memory, and concentration. Chronic stress has been proposed as an important contributing factor in ME/CFS. The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the stress response, and prolonged adverse stress may contribute to HPA axis dysregulation, including altered cortisol rhythmicity and impaired negative feedback regulation. Such dysregulation may be associated with cognitive dysfunction in ME/CFS through mechanisms involving neuroinflammatory responses, oxidative stress, and disturbances in neurotransmitter homeostasis. Studies suggest that these alterations may affect hippocampal structure and function, thereby contributing to impaired learning and memory processes. As a key brain region involved in cognition and stress regulation, the hippocampus may be implicated in the neurobiological mechanisms underlying cognitive dysfunction in ME/CFS. This review integrates current evidence on the potential role of HPA axis dysregulation and related neurobiological alterations in chronic stress-associated cognitive dysfunction in ME/CFS, with the aim of providing a theoretical basis for identifying potential intervention targets and informing strategies centered on HPA axis regulation.

Psychometric properties of Lithuanian translation of the self-report version of the Liebowitz social anxiety scale in young adult sample

BackgroundSocial anxiety disorder starts in adolescence or young adulthood and may have damaging effects on psychosocial development of the individual. Any intervention starts from assessment and the Liebowitz social anxiety scale with later developed self-report version is a valuable tool for practitioners for almost four decades. Even though the original version and adaptations have consistently demonstrated good reliability, there remains considerable debate regarding the factor structure. The aim is to test the factor structure and internal consistency of Lithuanian translation of the self-report version of the Liebowitz social anxiety scale (LSAS-SR) in a non-clinical young adult sample.MethodData of 452 young adults (mean age 21.3, 69.7% female) who volunteered participate in the study was used. Two factor solutions were tested: a single-factor model, with anxiety/fear and avoidance ratings loading on one factor, and a higher-order factor model, including two second-order scales (anxiety/fear scale and avoidance scale) and four first-order subscales (social interaction anxiety, performance anxiety, social interaction avoidance, performance avoidance). Internal consistency assessed using Cronbach’s alpha.ResultsLithuanian version has excellent internal consistency for the total score, scales and subscales, with Cronbach’s alfas ranging.85-.96. Confirmatory factor analysis shows that both tested models have acceptable data fit (RMSEA = .062-.067; CFI = .93-.94), however strong associations between (sub)scales, i.e. correlations exceeding.80, suggests that the use of scale and subscale scores may be less informative, especially in cross-sectional research, but could provide nuanced information in individual assessment.ConclusionFurther research on psychometric properties of Lithuanian versions of LSAS-SR should focus on verifying these results in a representative sample and in a clinical sample as well as testing the convergent and discriminant validity.

Experiences From an Internet-Delivered Treatment Program for Individuals With Obesity: Pilot Study

Background: The prevalence of obesity is a global health challenge, as obesity is associated with various comorbidities, reduced quality of life, and increased mortality. Providing effective treatment to improve health and quality of life for people with obesity is a major health care concern. Internet-delivered treatment (IDT) is an alternative treatment that increases patient accessibility and reachability; however, pilot testing is required before such interventions are evaluated in full-scale studies or implemented. Objective: This study aims to investigate the feasibility and user-friendliness of an IDT program for obesity (IDT-O); to evaluate body weight, dietary habits, physical activity, psychosocial functioning, and experiences of treatment in those who completed the 6-month treatment; and to investigate the dropouts’ experiences of the treatment. Methods: A prospective 1-year observational approach, evaluated through a multimethod research design, was adopted. Inclusion criteria were age 18 years and older, BMI of ≥30 kg/m, or BMI of 28‐29.9 kg/m with obesity-related comorbidity. Participants were offered a 6-month therapist-assisted IDT-O program providing evidence-based obesity treatment, behavioral and lifestyle support, and strategies to address weight stigma. BMI, participants’ dietary habits, self-reported physical activity, psychosocial functioning, experiences of treatment effects, and treatment satisfaction were measured before treatment and after 6 and 12 months. Dropouts were followed up through qualitative interviews. Results: A total of 20 participants (17 females and 3 male; mean age 44.2, SD 16.4 years) started the IDT-O program, and 35% (7/20) completed all 12 modules. Ten (8 females) out of 13 dropouts were interviewed. Both quantitative and qualitative findings showed that participants were generally satisfied with the content and design of the intervention. Those who completed the IDT-O lost some weight (mean 2.0%, 95% CI −1.09 to 5.13), reported improved dietary habits (effect size [ES] 0.25, 95% CI −0.51 to 1.00), increased physical activity (ES 0.93, 95% CI −0.08 to 1.87), and improved psychosocial functioning (distress: ES 0.43, 95% CI 0.‐0.37 to 1.19; avoidance: ES 0.67, 95% CI −0.18 to 1.48), 6 months after completing the treatment. The qualitative analysis of the interviews revealed “The programme was OK, but it does not suit everyone” as the main theme. The main themes were based on the 3 subthemes: “It wasn’t for me,” “There were good things,” and “There are things to improve.” Conclusions: The findings indicate that the IDT-O holds potential as a treatment for people with obesity, although one limitation is that only 35% (7/20) of the participants completed the pilot program. Improvements in lifestyle habits and psychosocial functioning were observed in those who completed the IDT-O, but these findings are preliminary and need to be confirmed in a more comprehensive study. The issue of nonadherence underscores the importance of both thoroughly assessing patients before treatment and further development of IDT-O programs. Trial Registration: ClinicalTrials.gov NCT04150445; https://clinicaltrials.gov/study/NCT04150445
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Interoceptive dysfunction and its neural correlates in schizophrenia: protocol for a cross-sectional multimodal MRI study

BackgroundInteroception—the perception and integration of internal bodily signals—is fundamental to emotion regulation, bodily self-awareness, and predictive coding. Emerging evidence suggests that interoceptive disturbances may contribute to core psychopathological features of schizophrenia. Our research group recently conducted a systematic review and meta-analysis demonstrating significant impairments in interoceptive accuracy and sensitivity among individuals with schizophrenia. However, the neural mechanisms underlying these deficits remain unclear.MethodsThis cross-sectional protocol will recruit 30 individuals with schizophrenia and 30 age- and sex-matched healthy controls. Participants will complete (1) behavioral interoceptive assessment using the heartbeat counting task; (2) subjective interoceptive questionnaires, including the Multidimensional Assessment of Interoceptive Awareness (MAIA) and the Body Perception Questionnaire (BPQ); (3) clinical symptom ratings (PANSS, HAM-A, HAM-D); and (4) cognitive testing (TMT, animal fluency, DSST). All participants will undergo multimodal MRI scanning, including structural T1-weighted imaging, resting-state fMRI, and diffusion tensor imaging. Neuroimaging data will be preprocessed and analyzed using DPABISurf, SPM12, and GRETNA. Expected Results: We anticipate that individuals with schizophrenia will show reduced interoceptive accuracy, altered subjective interoceptive awareness, and abnormal intrinsic neural activity and connectivity within interoception-related circuits, including the anterior insula, anterior cingulate cortex, amygdala, and thalamus. Structural abnormalities within thalamo-cortical pathways are also expected. Interoceptive deficits are hypothesized to correlate with symptom severity and cognitive performance.ConclusionsThis study will provide an integrated characterization of interoceptive dysfunction and its neural correlates in schizophrenia. Findings may advance understanding of bodily self-disturbance and emotional dysregulation and support the development of future interoception-focused therapeutic approaches.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2500110551.

The case for fixing everything

The handsome new book Maintenance: Of Everything, Part One, by the tech industry legend Stewart Brand, promises to be the first in a series offering “a comprehensive overview of the civilizational importance of maintenance.” One of Brand’s several biographers described him as a mainstay of both counterculture and cyberculture, and with Maintenance, Brand wants us to understand that the upkeep and repair of tools and systems has profound impact on daily life. As he puts it, “Taking responsibility for maintaining something—whether a motorcycle, a monument, or our planet—can be a radical act.”

Radical how? This volume doesn’t say. In an outline for the overall work, Brand says his goal is to “end with the nature of maintainers and the honor owed them.”

The idea that maintainers are owed anything, much less honor, might surprise some readers. Actually, maintenance and repair have been hot topics in academia since the mid-2010s. I played some role in that movement as a cofounder of the Maintainers, a global, interdisciplinary network dedicated to the study of maintenance, repair, care, and all the work that goes into keeping the world going.

Brand is right, too, that maintainers haven’t gotten the laurels they deserve. Over the past few decades, scholars have shown that work from oiling tools to replacing worn parts to updating code bases all tends to be lower in status than “innovation.” Maintenance gets neglected in many organizational and social settings. (Just look at some American infrastructure!) And as the right-to-­repair movement has shown, companies in pursuit of greater profits have frequently locked us out of being able to do repairs or greatly reduced the maintainable life of their products. It’s hard to think of any other reason to put a computer in the door of a refrigerator.

Some of Brand’s earlier work helped inspire those insights. But his new book makes me think he doesn’t see things that way. For Brand, maintenance seems to be a solitary act, profound but more about personal success and fulfillment than tending to a shared world or making it better.


Born in 1938, Brand is 87 years old. A sense hangs over the book—with its battles against corrosion, rust, and decay, with its attempts to keep things going even as they inevitably falter—of someone looking over life and pondering its end. Maintenance: Of Everything connects to every stage of Brand’s life. It’s worth reviewing where it falls in that arc. Brand has always been interested in tools and fixing things, but rarely has he focused on the systems that need the most care. 

More than a half-century ago, Brand was a member of the Merry Pranksters, a countercultural, LSD-centered hippie collective famously led by Ken Kesey, the author of One Flew Over the Cuckoo’s Nest. In 1966, Brand co-produced the Trips Festival, where bands like the Grateful Dead and Big Brother and the Holding Company performed for thousands amid psychedelic light shows.

Brand’s Whole Earth Catalog had a vision that might feel progressive, but its libertarian, rugged-individualist philosophy of remaking civilization alone stood in contrast to more collective social change movements.

In some ways, the Trips Festival set a paradigm for the rest of his life’s work. Brand’s biographers have described him as a network celebrity—someone who got ahead by bringing people together, building coalitions of influential figures who could boost his signal. As Kesey put it in 1980, “Stewart recognizes power. And cleaves to it.” 

Brand applied this network logic to the undertaking he will always be best remembered for: the Whole Earth Catalog. First published in 1968 and aimed at hippies and members of the nascent back-to-the-land movement, the publication had the motto “Access to tools.” Its pages were full of Quonset huts, geodesic domes, solar panels, well pumps, water filters, and other technologies for life off the grid. It was a vision that might feel progressive or left-leaning, but the libertarian, rugged-individualist philosophy of eschewing corrupt systems and remaking civilization alone stood in contrast to the more collective movements pushing for deep social change at the time—like civil rights, feminism, and environmentalism.

That vision also led straight to the empowerment that came with new digital tools, and to Silicon Valley. In 1985, Brand published the Whole Earth Software Catalog, the last of the series, and also cofounded the WELL—the Whole Earth ’Lectronic Link, a pioneering online community famous for, among other things, facilitating the trade of Grateful Dead bootlegs. He also wrote a hagiographic book about the MIT Media Lab, known for its corporate-sponsored research into new communications tech. “The Lab would cure the pathologies of technology not with economics or politics but with technology,” Brand wrote. Again, not collective action, not policymaking: tools. And Brand then cofounded the Global Business Network, a group of pricey consulting futurists that further connected him to MIT, Stanford, and the Valley. Brand had literally helped bring about the modern digital revolution.

His attention then turned toward its upkeep. Brand’s 1994 book, How Buildings Learn: What Happens After They’re Built, argued against high-modernist architectural ideas. Nearly all buildings eventually get remade, he argued, but he especially favored cheap, simple structures that inhabitants could easily retool to suit changing needs. In some ways, Brand was recapitulating the liberated—or libertarian—philosophy of the Whole Earth Catalog: People can remake their world, if they have access to tools. In a chapter titled “The Romance of Maintenance,” he asked readers to see the beauty, value, and occasional pleasures of fixer-uppers of all kinds.

This chapter was a touchstone for many of us in the academic subfield of maintenance studies. Researchers in disciplines like history, sociology, and anthropology, as well as artists and practitioners in fields like libraries, IT, and engineering, all started trying to understand the realities and, yes, romance of maintenance and repair. Brand joined and contributed to Listservs, attended conferences, chatted with intellectual leaders. So it’s a bit uncharitable when he writes that his new book is “the first to look at maintenance in general.” He knows better. The real question, though, is what his work has to teach us that others have not said before. In this first volume, the answer is unclear.


Maintenance: Of Everything, Part One is an odd book. If so much of Brand’s thinking has been about access to tools, he now asks, in a more extended way: How are our tools maintained? But where Brand began his career with a catalogue, in this volume we get … what? A digest? An almanac? An encyclopedia? Its form and riotous variety fit no genre easily. 

The book has two chapters. The first, “The Maintenance Race,” recounts the story of three men who took part in the Golden Globe, a round-the-world race for solo sailors held in 1968. Each of the sailors, Brand explains, had a different philosophy of maintenance. One neglected it and hoped for the best. He died. Another thought of and prepared for everything in advance, and while he didn’t win the race, he completed it and once held the record for the “world’s longest recorded nonstop solo sailing voyage.” The final sailor won and did so through heroic acts of perseverance; his style was “Whatever comes, deal with it,” Brand explains. Structured like a fairy tale and unremittingly romantic, the story—like most of the anecdotes in the book—focuses on the derring-do of vigorous white guys. The strategy is no secret. Brand’s outline explains: “Start with a dramatic contest of maintenance styles under life-critical conditions—a true story told as a fable.” This myth is meant to inspire. 

The second chapter, “Vehicles (and Weapons),” is over 150 pages long. It has five sections, multiple subsections, five subsections designated “digressions,” one called a “subdigression,” two “postscripts,” and several “footnotes” that are not footnotes in a formal sense but, rather, further addenda. At times, it all feels like notes for a future work. Brand makes no apology for the book’s woolliness. “All I can offer here,” he writes, “is to muse across a representative of maintenance domains and see what emerges.” Perhaps the most charitable reading of the potpourri is that it represents the return of a Merry Prankster, offering us a riotous varied light show. It’s a good book to leave on a table and occasionally open to a random page for entertainment. But it often seems as if it does not know what it wants to say or be. 

“Vehicles (and Weapons)” begins by paraphrasing two famous works of maintenance philosophy, Robert M. Pirsig’s Zen and the Art of Motorcycle Maintenance and Matthew B. Crawford’s Shop Class as Soulcraft. Maintenance involves both “problem finding” and “problem solving.” While much repair work is marked by anxiety, impatience, and boredom, it also offers positive values and outcomes. “Motorcycle maintainers take heart from what they repair for—the glory of the ride,” Brand writes. 

The beauty and triumph of cheapness is a running theme throughout the work, harking back to How Buildings Learn. Henry Ford’s Model T won out over early electric vehicles and hugely expensive luxury vehicles like Rolls-Royce’s Silver Ghost because it was cheap and easier to maintain. The three most popular cars in human history—the Ford Model T, the Volkswagen Bug, and the Lada “Classic” from Russia—all privileged cheapness, “retained their basic design for decades, and … invited repair by the owner.” Or, to be fair, maybe demanded it? For every hobbyist who delighted in being able to self-reliantly keep a VW running, there must have been thousands who appreciated how cheap it was and hated that it broke a lot. Brand never points to social research, like surveys, that might help us know people’s feelings on such matters.

Other sections recount how Americans created interchangeable parts (enabling not only cheap mass production but also easy maintenance), examine how maintenance works with assault rifles and in war, and track the history of technical manuals from the early modern period to the age of YouTube. These stories are solid, but they’re also well known to students of technology, and nearly all are recycled from the work of others, featuring many large block quotes. The volume breaks little new ground. 

Brand treats maintenance as an unalloyed good. But the field of maintenance studies has moved on, burrowing into the domain’s ironies, complexities, and difficulties. A simple example: In most cases, it is environmentally far better to retire and recycle an internal-combustion vehicle and buy an electric one than to keep the polluting beast going forever. Maintaining a gas-guzzler or a coal-­burning power plant isn’t a radical act but a regressive one. Also, maintenance can become a life-breaking burden on the poor, and it falls inequitably on the shoulders of women and people of color. Keeping existing systems going can be a way of avoiding tough, necessary change—like making technological systems more accessible for people with disabilities. In this volume, Brand is uninterested in such difficult trade-offs. He avoids any question of how politics shapes these issues, or how they shape politics.

This avoidance comes out most clearly in a section of “Vehicles (and Weapons)” that talks about Elon Musk—a character of “unique mastery,” Brand informs us. He tells us that Bill Gates once shorted Tesla’s stock, only to lose $1.5 billion. The lesson is clear: Elon won. 

In what political and social vision is money the best way to keep the score? Brand rightly points out that electric vehicles have fewer moving parts and, in that sense, are more maintainable than internal-combustion vehicles. He celebrates Musk most of all because his products “have all proven to be game changers in part because they combine ingenious design with surprisingly low cost.” Again, it’s Brand’s “cheap, available tools” hypothesis. But there’s a real superficiality and lack of follow-through in thinking here: Teslas remain luxury vehicles whose sales have slumped since federal tax subsidies disappeared. The company has faced several right-to-repair lawsuits; there’s even a law review article on the topic. Musk is in no sense a maintenance hero. Yet Brand writes that with his companies, “Musk may have done more practical world saving than any other business leader of his time.” By the time Brand was writing this book, the controversies surrounding Musk for at least flirting with antisemitism, racism, sexism, authoritarianism, and more were quite clear. About this, the book says not a word.

book cover
Maintenance: Of Everything, Part One
Stewart Brand
STRIPE PRESS, 2026

For sure, Brand needn’t agree with Musk’s critics, but failing to even broach the subject is tone deaf and out of touch. Others have argued that Silicon Valley’s “Move fast and break things” mentality undermines healthy maintenance. Brand doesn’t raise the idea—even to dismiss it. 

It could be that with Maintenance: Of Everything, Part One Brand is just getting going; that in subsequent volumes he’ll have something more coherent to say; that he’ll raise really hard questions and try to answer them. But given his track record, we might reasonably doubt it. Kesey said Brand cleaves to power; he certainly doesn’t question it. 

Lee Vinsel is an associate professor of science, technology, and society at Virginia Tech and host of Peoples & Things, a podcast about human life with technology.

Acute Physiological and Emotional Responses to a Brief 24-Minute Yoga Session: Randomized Exploratory Pilot Study With Waitlist Comparison

Background: Wellness tourism increasingly incorporates short yoga sessions for stress management, yet evidence on their immediate physiological and emotional responses remains limited. Objective: This exploratory pilot study aimed to generate preliminary data on acute physiological and emotional responses to a single 24-minute yoga session (breathing, postures, and meditation) compared with quiet sitting in novice practitioners. Methods: In this single-center, randomized waitlist-controlled exploratory pilot study (1:1 allocation), 19 university-affiliated adults with self-reported daily stress and no prior guided yoga experience were allocated to an immediate 24-minute yoga session (n=10) or quiet sitting (n=9). The primary outcome was change in salivary cortisol from baseline to postintervention. Secondary outcomes included salivary alpha-amylase, heart rate (Apple Watch [Apple Inc], subset n=12), and real-time emotional indices (stress, calmness, and concentration) measured by a commercial single-channel electroencephalogram (EEG) device (Kansei Analyzer [Dentsu ScienceJAM], subset n=8). Data were analyzed using change scores relative to the breathing phase, with between-group comparison performed by independent tests or multivariable linear regression adjusted for age, sex, and baseline values as appropriate. Results: No significant between-group differences were observed for salivary cortisol or alpha-amylase. In the yoga group, heart rate increased during postures and remained mildly elevated during meditation relative to the breathing phase, consistent with mild physical exertion. Exploratory individual EEG analyses suggested reduced stress and increased concentration during breathing and meditation phases in some participants. Conclusions: In this small exploratory pilot study, a single 24-minute yoga session did not significantly alter salivary stress biomarkers at the group level. However, it induced measurable cardiovascular activation and heterogeneous EEG-derived emotional responses. These hypothesis-generating findings demonstrate marked interindividual variability, suggesting the need for larger validation studies with improved control conditions.
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From peripheral initiation to central integration: a narrative review of the antihypertensive mechanisms of acupuncture in regulating autonomic nervous system homeostasis

Essential Hypertension (EH) is one of the most prevalent chronic cardiovascular diseases, imposing a significant burden on healthcare systems worldwide due to its high rates of disability and mortality. Long-term elevation of blood pressure leads to multi-organ damage in the heart, brain, and kidneys, resulting in severe complications such as coronary heart disease, stroke, and chronic kidney disease. Current treatment for hypertension primarily relies on pharmacological interventions. Although antihypertensive drugs have achieved notable success in controlling blood pressure, challenges remain, including poor long-term medication adherence, side effects, and inadequate blood pressure control in some patients with resistant hypertension. In parallel, acupuncture, a key modality of traditional Chinese medicine, has demonstrated unique advantages in hypertension management in recent years. Characterized by its holistic regulatory effects and minimal side effects, acupuncture is recognized by the World Health Organization as a recommended complementary and alternative therapy for hypertension, although its precise mechanisms remain incompletely understood. This review aims to summarize the “peripheral-central synergy” antihypertensive mechanism of acupuncture in regulating autonomic nervous system (ANS) homeostasis. Studies indicate that acupuncture primarily modulates autonomic homeostasis through the following pathways: (1) activating peripheral nerve fibers to convert physical stimulation into complex bioelectrical signals; (2) regulating synaptic neurotransmitter release and the expression of related membrane receptors; (3) modulating the synaptic microenvironment; (4) regulating the NTS-CVLM-RVLM neural circuit; and (5) modulating the HPA axis neuro-endocrine circuit. Through in-depth analysis, this review elucidates the multi-level and multi-dimensional impact of acupuncture therapy on primary hypertension, providing stronger evidence and a theoretical foundation for its clinical application.

Evaluation of anxiety levels and stress coping methods of pregnant women after the Kahramanmaraş earthquake

ObjectiveNatural disasters can cause serious psychological pressures on women during pregnancy. How the mental health of pregnant women is affected after major disasters such as earthquakes and what coping methods come into play in this process is an important research topic. This study aimed to evaluate the anxiety levels and stress coping strategies of pregnant women who experienced the February 6, 2023 Kahramanmaraş earthquake.MethodsThis cross-sectional descriptive study was carried out within four months after the earthquake. A total of 118 pregnant women were included. Participants were grouped according to pregnancy trimester. Anxiety level was assessed with the Beck Anxiety Inventory and coping strategies with the Brief COPE Scale. Earthquake exposure data, including building damage and loss of relatives, were collected via structured survey.ResultsThe mean Beck Anxiety score was 15.9 ± 12.8. A significant difference was observed between trimesters (H = 19.09, p < 0.001), with anxiety declining from the first to the third trimester. Religious coping (ρ = 0.42, p < 0.001), acceptance (ρ = 0.36, p < 0.001), and behavioral avoidance (ρ = 0.36, p < 0.001) were positively correlated with anxiety. Positive reinterpretation and development showed a significant negative correlation with anxiety (ρ = −0.32, p < 0.001). Building damage category was not significantly associated with anxiety (p = 0.80).ConclusionAnxiety in post-earthquake pregnant women differs according to trimester, and individual coping styles are associated with anxiety levels. Within the scope of the variables measured in this study, positive reinterpretation showed the strongest negative association with anxiety. Approaches supporting cognitive flexibility should be prioritized in perinatal mental health interventions.

Corticotropin-Releasing Factor and Somatostatin Neurons in the Central Amygdala Mediate Dynamic Defensive Behaviors during Fear Extinction

Traumatic experiences can result in heightened fear responses to trauma-associated stimuli. These symptoms can be difficult to extinguish, so identifying neuronal targets for facilitating fear extinction is critical. Many studies investigating fear learning in mice measure conditioned fear via freezing, but other defensive behaviors, such as flight, can also be present during conditioning. The central amygdala (CEA) mediates conditioned freezing and flight responses via corticotropin-releasing factor-positive (CRF+) and somatostatin-positive (SOM+) neuron populations. However, it is unknown how these populations regulate changes in freezing and flight responses as fear extinction is learned. Thus, we investigated the roles of CRF+ and SOM+ CEA neurons in modulating defensive behaviors during extinction. To elicit dynamic defensive responses in male and female mice, we used a modified pavlovian conditioned flight paradigm that paired an aversive footshock with a serial compound stimulus (SCS) consisting of tone followed by white noise (WN), resulting in freezing during the tone that rapidly transitioned into flight (escape jumping and darting) during WN. We used optogenetics in CRF-Cre and SOM-Cre mice to selectively excite and inhibit CRF+ and SOM+ CEA populations during WN presentation within extinction. Within early extinction, CRF+ inhibition reduced WN-evoked jumping and led to subsequent context-specific reduction in tone-evoked freezing. During extinction, SOM+ excitation replaced early WN-evoked flight with freezing, and both SOM+ excitation and inhibition reduced WN-evoked darting. Collectively, these data demonstrate modulation of jumping and darting behaviors within extinction via CRF+ and SOM+ CEA activity. These findings suggest mechanisms of attenuating multiple defensive behaviors during extinction.

Synaptic remodeling and the female depression exposome: a mini-review of neuroendocrine, epigenetic, and social determinants

Depression is a multifactorial, chronic disorder and represents a leading cause of disability, with women exhibiting nearly twice the lifetime prevalence compared to men. Growing evidence indicates that this disparity cannot be explained by hormonal or psychosocial factors, but rather by dynamic interactions between environmental exposures, neuroendocrine signaling, and epigenetic regulation across development. This mini-narrative review aimed to examine how sex-specific exposome components interact with epigenetic mechanisms and synaptic remodeling processes to influence vulnerability to Major Depressive Disorder in women. The reviewed evidence demonstrates that fluctuations in ovarian hormones modulate HPA axis responsivity, neuroinflammatory signaling, and glutamatergic transmission through epigenetic regulation of stress-responsive genes such as NR3C1, SLC6A4, and BDNF, consequently influencing synaptic remodeling within corticolimbic circuits. Environmental and social exposures, particularly early-life adversity and psychosocial stressors, further interact with microglial activation and chromatin remodeling to produce long-lasting alterations in hippocampal and prefrontal plasticity. Collectively, these findings support a model in which sex-dependent neuroendocrine sensitivity amplifies exposome-driven epigenetic programming across the lifespan. Future research directions emerging from this synthesis include longitudinal life-course studies integrating multi-omic biomarkers, quantitative exposome assessment, and neuroimaging approaches to identify modifiable environmental targets and advance precision, sex-informed preventive and therapeutic strategies in depression.