Trauma
November 2, 2025
TLDR: Understanding Pre-Traumatic Stress Disorder - When Your Body Prepares for Trauma That Hasn't Happened
This article explores the emerging phenomenon of pre-traumatic stress disorder—a state where anticipatory anxiety creates biological changes before any actual trauma occurs. Key points include:
Uncertain future threats activate the same brain regions as actual dangers, keeping your nervous system in constant fight-or-flight
The HPA axis becomes dysregulated under chronic anticipatory stress, literally rewiring the brain to be more anxious
Epigenetic changes from ancestral trauma can be passed down across generations through DNA methylation
Chronic inflammation from stress and ultra-processed foods sensitizes the nervous system to threat
The hippocampus loses its ability to discriminate between safety and danger under prolonged stress
The biological evidence shows:
Inflammatory cytokines (IL-1β, IL-6, TNF-α) create a feedback loop between anticipatory stress and physical inflammation
Third and fourth-generation descendants of Holocaust survivors carry measurable epigenetic signatures of trauma
For every 10% increase in ultra-processed food consumption, there's an 11% higher risk of depression
Up to 27% of patients with major depression have neuroinflammation driving treatment resistance
Stress-related epigenetic changes may be reversible through therapy and lifestyle interventions
The article concludes that while the biology shows increasing sensitization, healing is possible through nervous system regulation, anti-inflammatory nutrition, and addressing both individual trauma and structural forces that perpetuate chronic stress.
[Read full article for the science behind pre-traumatic stress and evidence-based approaches to nervous system healing]
How Our Bodies Are Learning to Be Traumatized Before Anything Even Happens
I've noticed something troubling in my practice lately. People are showing up not just with the aftermath of trauma, but with what I can only describe as trauma before the fact. Their nervous systems are already activated, their threat detection systems already on high alert, and their bodies already responding as if something terrible has happened—when nothing has.
We call this anticipatory anxiety, but that phrase doesn't quite capture what's really going on at the biological level. What I'm witnessing is more accurately described as pre-traumatic stress disorder: a state where the brain and body have become so sensitized to potential threat that they exist in a perpetual state of preparing for trauma that may never come.
This state is typically due to the biological embedding of early life adversity (adverse experiences during developmental years) which is why I have advocated for nutrition-focused solutions. But many people are in pre-traumatic stress disorder without significant trauma histories, just from living in a polarized world (collective trauma).
What concerns me most—the biology shows it's getting worse.
When Your Brain Goes Offline Before Anything Happens
You know that feeling when you're scrolling through news headlines and your heart rate picks up? When you read about climate projections or political instability and suddenly you're thinking about stockpiling supplies or escape routes? That's not just worry—that's your nervous system responding to uncertain future threats the same way it would respond to a tiger in front of you.
Research shows that when we're faced with uncertainty about possible future threats, we literally can't avoid or mitigate the negative impact, which results in anxiety [1]. But here's what makes this particularly insidious: the neural systems recruited during uncertain threat anticipation involve the same frontocortical regions, extended amygdala, and periaqueductal gray that respond to certain threats [2].
Translation? Your brain treats thinking about bad things happening with nearly the same neurobiological response as actually experiencing them. This can impact sleep, which then impacts all dimensions of wellness.
In people with generalized anxiety disorder, the amygdala shows indiscriminately elevated activation during the anticipation of both neutral and aversive stimuli, reflecting a failure to down-regulate amygdala activity in response to safe cues [3]. It's like having a smoke alarm that goes off when you're cooking dinner, taking a shower, and sleeping—the alarm system itself has become the problem.
The Biology of Living in Tomorrow's Disaster
Let me walk you through what's happening in your body right now if you're living in this state of pre-traumatic stress.
Your hypothalamic-pituitary-adrenal (HPA) axis—the system responsible for your stress response—is designed to activate when you face real danger, pump out cortisol to give you energy and focus, and then shut down when the danger passes. But when you're constantly anticipating future threats, this system never truly shuts off.
Research demonstrates that even short-term restraint stress induces anxiety-like behaviors and structural changes in the basolateral amygdala ten days later [4]. And here's the kicker: inhibiting cortisol elevation during stress actually prevents these delayed anxiety responses and brain changes [4]. The stress hormone itself is literally rewiring your brain to be more anxious in the future.
Higher plasma levels of inflammatory cytokines—most consistently IL-1β, IL-6, and TNF-α—are correlated with greater depressive symptoms, and these cytokines sensitize the HPA axis, disrupt the negative feedback loop, and further propagate inflammatory reactions [5]. It's a vicious cycle: anticipatory stress triggers inflammation, inflammation makes you more sensitive to stress, which creates more anticipatory anxiety.
When Trauma Becomes Hereditary
Here's where it gets even more concerning. We now have compelling evidence that this sensitization doesn't just affect you—it can be passed down to your children and grandchildren through epigenetic mechanisms.
Studies in rodents show that exposure to extreme stress in males can affect brain, behavior, and sperm in the next generation, with changes in DNA methylation patterns that are transmitted to offspring [6]. In humans, research on Syrian refugees found differentially methylated positions associated with violence exposure across three generations, with most showing the same directionality in DNA methylation change across germline, prenatal, and direct exposures [7].
The Holocaust survivor studies are particularly instructive. Third and fourth-generation descendants of Holocaust survivors exhibit DNA methylation patterns associated with increased HPA axis reactivity—specifically, lower methylation in FKBP5 (suggesting delayed stress response shutdown) and higher methylation in NR3C1 (suggesting reduced ability to terminate stress response) [8]. These descendants carry what we might call "molecular echoes" of trauma they never directly experienced.
But here's what gives me hope: despite this elevated biological sensitivity to stress, these descendants often function within non-clinical psychological ranges [8]. The biology has been altered, but resilience is still possible (hint: nutrition helps). Some of these stress-related changes may even be reversible—combat veterans with PTSD who benefited from cognitive-behavioral psychotherapy showed treatment-induced changes in FKBP5 methylation [9].
The Inflammation Connection
One of the mechanisms driving this increasing sensitization is chronic low-grade inflammation. And this is where our modern lifestyle—and particularly our food environment—becomes relevant.
Research shows that inflammatory cytokines interfere with serotonin synthesis and reuptake, activate the HPA axis (increasing chronic stress), decrease brain-derived neurotrophic factor (impairing neurogenesis and synaptic plasticity), and increase amygdala reactivity, leading to exaggerated stress responses [10].
Peripheral inflammation exacerbates central neuroinflammation through several mechanisms including disruption of the blood-brain barrier, immune cell trafficking, and activation of glial cells, which then release cytokines and reactive oxygen species that dysregulate neurotransmitter systems [11].
What's driving this inflammation? Part of it is the ultra-processed food supply. For every 10% increase in ultra-processed food consumption relative to daily caloric intake, there's an 11% higher risk of depression [12]. These foods don't just lack nutrients—they actively promote inflammatory processes that sensitize your nervous system to threat.
But it's not just food. Chronic stress itself promotes prolonged psychophysiological activation through anxiety and rumination, which increases activity of cardiovascular, endocrinological, immunological, and neurovisceral systems, promoting the evolution of numerous physiological diseases [13].
The Perfect Storm
So here we are, living in a world that provides constant exposure to uncertain threats through 24/7 news cycles and social media, eating a food supply that promotes inflammation, experiencing chronic stressors around finances, relationships, and existential concerns, and potentially carrying epigenetic signatures of our ancestors' traumas.
Is it any wonder that we're seeing epidemic levels of anxiety and depression?
When the hippocampus-based pattern separation and prefrontal cortex-based cognitive control functions are impaired—which happens under chronic stress—we lose our ability to discriminate between threat and safety, leading to generalized fear responses [14]. We become unable to recognize when we're actually safe.
What This Means for Healing
Understanding the biology of pre-traumatic stress doesn't mean we're doomed. It means we need to take nervous system regulation seriously as a foundational intervention—not just for mental health, but for preventing the biological sensitization that makes future trauma more likely. This means:
Addressing inflammation at its roots. We can't ignore the role of nutrition in nervous system health. Moving away from ultra-processed foods toward whole, minimally processed foods isn't diet culture—it's acknowledging that what we eat directly affects our stress response systems.
Interrupting anticipatory anxiety cycles. When your brain is treating uncertain future threats as present dangers, you need practices that bring you back to the present moment—whether that's mindfulness, somatic experiencing, or simply spending time in nature.
Healing the HPA axis. This means adequate sleep, stress management practices, appropriate movement, and sometimes nutritional support for the systems that have become dysregulated. Exercise releases stress from the body and can help modulate inflammatory responses [15].
Recognizing intergenerational patterns. If you're carrying epigenetic signatures of ancestral trauma, understanding this can help you have compassion for your own nervous system's sensitivity. It's not your fault that your threat detection system is hypervigilant—but it is your responsibility to work with it.
The Larger Context
I want to be clear about something: this isn't just an individual problem. Yes, we need individual interventions, but we also need to acknowledge the structural forces that are creating this epidemic of pre-traumatic stress.
A society that profits from keeping people in states of fear and outrage through algorithmic amplification of threatening content is creating biological damage. A food system that produces cheap, inflammatory, ultra-processed foods is not just a matter of personal choice—it's a public health crisis with mental health consequences.
Neuroinflammation affects up to 27% of patients with major depressive disorder and is associated with a more severe, chronic, and treatment-resistant trajectory [16]. This isn't some abstract concept—this is real suffering that has biological mechanisms we can measure and, potentially, intervene on.
Moving Forward
Here's what I know from working with people every day: the nervous system is remarkably plastic. Just as repeated exposure to uncertain threats can sensitize us, repeated experiences of safety can help recalibrate our threat detection systems. This is known as resilience.
Anticipatory traumatic reaction can be measured and includes feelings related to future threat, preparatory thoughts and actions, and disruption to daily activities [17]. Recognizing this pattern in yourself is the first step toward addressing it.
The work isn't easy. It requires us to be hard on systems that create and profit from chronic stress while being soft on ourselves and each other as we navigate these systems. It requires us to challenge simplistic narratives about mental health while acknowledging the very real biological mechanisms at play.
And it requires us to remember this: just because the biology shows increasing sensitization doesn't mean we're helpless. The reward system can help us recognize and exploit rewards within contexts of chronic stress exposure, permitting more positive appraisals and optimal stress responding [18]. Even in the midst of all this, joy and connection and meaning are possible.
We're not just fighting post-traumatic stress anymore. We're working to prevent pre-traumatic stress—to stop the cascade before it starts, to heal the systems that have been sensitized, and to create conditions where nervous systems can learn what safety actually feels like.
That's the work ahead. And it's work worth doing. Perhaps we do it one bite at a time…
References
Grupe DW, Nitschke JB. Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective. Nat Rev Neurosci. 2013;14(7):488-501.
Shackman AJ, Fox AS. Anxiety and the neurobiology of temporally uncertain threat anticipation. J Neurosci. 2020;40(41):7949-7957.
Fullana MA, Albajes-Eizagirre A, Soriano-Mas C, et al. Fear extinction in the human brain: A meta-analysis of fMRI studies in healthy participants. Neurosci Biobehav Rev. 2018;88:16-25.
Roozendaal B, Hernandez A, Cabrera SM, et al. Genomic glucocorticoid receptor effects guide acute stress-induced delayed anxiety and basolateral amygdala spine plasticity in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2023;128:110859.
Beurel E, Toups M, Nemeroff CB. The bidirectional relationship of depression and inflammation: double trouble. Neuron. 2020;107(2):234-256.
Yehuda R, Lehrner A. Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms. World Psychiatry. 2018;17(3):243-257.
Ryan Noel S, Francis OJ, Krause SJ, et al. Epigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees. Sci Rep. 2025;15(1):3644.
Weiss DS, Rosenthal S, Weinstock R, et al. From trauma to resilience: psychological and epigenetic adaptations in the third generation of holocaust survivors. Sci Rep. 2025;15(1):8236.
Yehuda R, Daskalakis NP, Bierer LM, et al. Holocaust exposure induced intergenerational effects on FKBP5 methylation. Biol Psychiatry. 2016;80(5):372-380.
Miller AH, Haroon E, Raison CL, Felger JC. Inflammation-related functional and structural dysconnectivity as a pathway to psychopathology. Biol Psychiatry. 2022;93(5):405-418.
Medina-Rodriguez EM, Beurel E. Blood brain barrier and inflammation in depression. Neurobiol Dis. 2022;175:105926.
Lane MM, Gamage E, Travica N, et al. Ultra-processed food consumption and mental health: A systematic review and meta-analysis of observational studies. Nutrients. 2022;14(13):2568.
Brosschot JF, Gerin W, Thayer JF. The perseverative cognition hypothesis: a review of worry, prolonged stress-related physiological activation, and health. J Psychosom Res. 2006;60(2):113-124.
Kalisch R, Russo SJ, Müller MB. Neurobiology and systems biology of stress resilience. Physiol Rev. 2024;104(3):1205-1263.
Marsland AL, Walsh C, Lockwood K, John-Henderson NA. The effects of acute psychological stress on circulating and stimulated inflammatory markers: a systematic review and meta-analysis. Brain Behav Immun. 2017;64:208-219.
Köhler-Forsberg O, Lydholm CN, Hjorthøj C, et al. Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials. Acta Psychiatr Scand. 2019;139(5):404-419.
Palgi Y, Shrira A, Hamama-Raz Y, et al. Anticipatory traumatic reaction: outcomes arising from secondary exposure to disasters and large-scale threats. Br J Psychiatry. 2017;211(2):102-107.
Nestler EJ, Russo SJ. Neurobiological basis of stress resilience. Neuron. 2024;112(12):1911-1929.
