Was I Always Going To Be Like This

Was I always going to be like this?

It's the question that shows up at 3am. When nothing else is working. Somewhere between despair and accusation.

This episode goes looking for a real answer — not reassurance, not false hope, but what the science actually says.

We go into genetics and what heritability really means for depression and anxiety. We go into epigenetics—the genuinely significant discovery that chronic stress and early experience can change how genes are expressed without changing your DNA. And we go into neuroplasticity—what the evidence shows about the brain's capacity to change and what that means for the question of whether any of this is fixed.

This is the most scientifically complex episode in the series so far. It doesn't offer a clean answer. But it offers something more honest than the question you started with.

Not Fixed, Still Here. Episode 4.

If anything in this episode brought something up for you, support is available 24/7. Call or text 988 or text HOME to 741741.

Genetics & Heritability 

Tabrizi et al.—Heritability and polygenic load for comorbid anxiety and depression—Translational Psychiatry (March 2025) 

Wray et al.—Genome-wide association analyses identify 44 risk variants for major depression—Nature Genetics (2018) 

Adams et al.—Genome-wide study of major depression in 685,808 diverse individuals—medRxiv (2024) 

Molecular Psychiatry — Genetic nurture effects in depressive and anxiety disorders (2025) 

Epigenetics 

Kretzschmar, Boldt, Targa — The genetics and epigenetics of mental health — Frontiers in Genetics (April 2024) 

Franklin et al.—Epigenetic regulation of brain development, plasticity, and response to early-life stress—Neuropsychopharmacology (2025) 

Talarowska — Epigenetic mechanisms in the neurodevelopmental theory of depression — PMC (2020) 

Frontiers in Psychiatry — From trauma to depression: epigenetic and molecular pathways (2025) Frontiers in Psychiatry — Clinical use of epigenetics in psychiatry (2025) 

Neuroplasticity 

Huizenga, Neuroplasticity and mental health: implications for depression and anxiety treatment, Journal of Cognitive Neuroscience (2025) 

Radulescu, Dragoi, Trifu—Neuroplasticity and depression: rewiring the brain's networks—Experimental and Therapeutic Medicine—PMC (2021) 

Journal of Neuropsychiatry and Clinical Neurosciences — The dynamic brain: neuroplasticity and mental health (2012 / updated 2025) 

Axis Mental Health—How neuroplasticity improves mental health (2026) 

Crisis Resources — Include in Every Episode Description 

Call or text 988 — Suicide and Crisis Lifeline (24/7, free, confidential) Text HOME to 741741 — Crisis Text Line (24/7, free, confidential) 

Transcript

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SPEAKER_00 0:03

There is a question that most people who have struggled with mental health have asked themselves at some point. Usually at 3 a.m. Usually when nothing else is working, usually in a tone that is somewhere between despair and accusation. Was I always going to be like this? Is it in my DNA? Did I inherit this? Is it written somewhere in my biology that I was always going to end up here? Depressed, anxious, struggling, and nothing I do will fundamentally change that. That question deserves a real answer. Not reassurance, not false hope, but what the science actually says. Today we are going to go there. Still here. The podcast about mental health grounded in science and shaped by lived experience. I'm Torin, not a therapist, not a clinician, someone who has spent 20 years inside these questions, and this is what happens when I ask them out loud. This is episode 4, and it is the most scientifically complex episode we've done so far. We are going to look at genetics, epigenetics and neuroplasticity and what they actually tell us about whether biology decides our mental health. I want to flag something important before we begin. This episode covers three areas of science that are genuinely complex, actively research and not fully settled. I will tell you clearly what is well established, what is emerging and what is still contested. Hold it all with appropriate certainty. I want to start with what that 3 a.m. question actually contains because was I always going to be like this is not just one question, it is several. It is asking whether the suffering is inevitable, whether it is permanent, whether it is somehow written into who you are at a level that nothing, no therapy, no medication, no amount of work on yourself can touch. It is also underneath all of that asking whether any of it is your fault. Whether you are broken by design or broken by circumstance and whether the distinction even matters. The science I'm going to assert today does not fully resolve any of those questions, but it changes the frame around them significantly. Because what research into genetics, epigenetics and neuroplasticity has revealed increasingly in recent years, is that the relationship between biology and mental health is not a simple one-way street. It is a conversation between what you inherited, what you experienced, and what your brain is doing right now in response to both of those things. That is a more complicated picture than biology designs everything. But it is also more honest and it opens up possibilities that the simpler version closes it down. The usual frame before we go in. I am not a neurobiologist. I have studied this area extensively for my own understanding and I will be transparent about what the research shows and where it falls short. This episode covers three distinct concepts. They are related but not the same thing. Neuroplasticity the brain's capacity to change in response to experience, therapy and intervention. Each one of these is generally important to understanding the question we started with. Let's start with genetics. The question of whether mental health conditions run in families. The honest answer is yes they do, but what that means is more nuanced than the way it's usually understood. Scientists measure genetic contribution through something called heritability, the proportion of the variation in the trait that can be attributed to genetic differences between people in a given population. The most reliable way to study this is through twin studies, comparing how often identical twins who share virtually all their DNA both develop a condition versus non-identical twins who share about half their DNA. Health stability of depression and anxiety twin research Heritability of Depression 30-50% established across decades of twin research heritability of anxiety disorders 30-50% consistent across multiple large studies New Finding 2025 Helpability of Comorbid Anxiety and Depression together 79% study 12792 genotyped twins ages 38 to 85 1986 monozygotic and 1594 desigotic pairs. Key finding when anxiety and depression occur together the genetic contribution appears substantially greater than when either occurs alone. In plain terms, genes contribute meaningfully to the risk of diversifying depression or anxiety. Between a third and a half of that risk appears to have a genetic component. But here is what heritability does not mean. It does not mean that if you carry these genes you will definitely develop the condition. It means you are more likely to under certain conditions. The environment plays the other part. And it does not mean a single gene causes depression. Mental health conditions are polygenic, influenced by hundreds or thousands of small genetic variations, each contributing to a tiny amount to overall risk. Polygenic risk what the genome wide research shows. Genome wide association studies have identified forty four risk variants for major depression nature genetics twenty eighteen. A 2024 study identified six hundred and ninety-seven independent genetic associations with a major depression across six hundred and eighty five thousand eight hundred and eight diverse individuals. No single gene causes depression. Risk is distributed across hundreds of variants, each contributing a fraction of overall susceptibility. Depression PGS polygenic scores currently explain 0.27 to 2.2% of variance in depression outcomes in independent cohorts. Translation Genetic risk is real, measurable and disputed. It is not deterministic, it is prob probable it is probabilistic. Probabilistic not deterministic. That distinction matters enormously. Having a genetic predisposition to depression does not mean you are destined to be depressed. It means under certain conditions your risk is elevated. Which brings us to what those conditions are and that is where epigenetics come in. Epigenetics is one of the most significant developments in our understanding of mental health in recent decades. The word itself means above genetics and that is essentially what it describes. Epigenetics is the study of changes in how genes are expressed, turned on or turned off without any change to the underlying DNA sequence itself. In pen terms, your genes are not a fixed program that runs the same way regardless of what happens to you. Your experiences, your environment, your stress levels, what happened to you in childhood can change the way those genes behave. And some of those changes can be long lasting. Epigenetics and early life stress key findings Frontiers in Genetics 2024 Research Topic Summary Stress has severe consequences on the epigenome, the timing, intensity and number of events are critical for the severity of mental health symptoms. Neuropsychopharma Pharmacology 2025 review Environmental perturbations during development such as early life stress can become encoded in the epigenome. Evidence from human and animal studies has converged on long lasting epigenetic changes at key genes which confer functional changes in stress response. I want to stay with that for a moment. Long lasting epigenetic changes at key genes which confer functional changes in stress response. What that means in lived terms is this if you grew up in an environment of chronic stress or trauma, your body may have responded by changing the way certain genes related to stress response are expressed, not by changing your DNA, by changing the volume dial on certain genes, turning up the ones that keep you alert, vigilant, reactive, turning down the ones that help you return to calm. And those changes can persist. How epigenetic changes affect the brain? Epigenetic mechanisms in depression include DNA methylation, chemical attacks that affect gene expression, histone modification, changes to protein structures around DNA, non-coding RNA molecules that regulate gene activity in stress-related depression models, reduced histone acetylation in the prefrontal cortex and hippocampus correlates with downregulated expression of BDNS, brain-derived neurotrophic factor, a key protein supporting neuron growth and mood stabilization. Early childhood experiences accompanied by severe stresses considered a risk factor for depression in adult life or linked with changes in gene expression. These are established not speculative. This is significant for a specific reason. It means that the question is this biology or is this what happened to me may be a false distinction because what happened to you particularly in childhood became biology. It got encoded, it changed the way your genes express themselves. This is not a reason for despair, it is a reason for a different kind of understanding. Your suffering is not a personal feeling, it is not weakness, it is a biological response to a biological reality, even if that reality was created by experience rather than inherited directly. And here is where the third piece of science becomes important. Because if experience can change gene expression, can new experience change it back? The answer the research suggests is partially under the right conditions over time. That is neuroplasticity. Neuroplasticity is the brain's capacity to change in response to experience. It is not a new idea, but our understanding of it has expanded dramatically in recent years and its implications for mental health are significant. For most of the 20th century, the dominant view was that the adult brain was largely fixed. You were born with a certain number of neurons, they declined with age, and the basic architecture of the brain didn't fundamentally change after childhood. That view has been substantially revised. Neuroplasticity what the research now shows The brain retains the ability to form new synaptic connections, prune unused ones and create new neurons throughout life. This is particularly active in the hippocamp in the hippocampus, a region central to memory and emotional regulation. Depression has been linked to reduced neuroplasticity, atrophy of neurons in cortical and limbic regions, decreased dendrites and synapses in hippocampus, reduced brain matter volume, likely synaptic priming, and dendritic regression, not cell loss. FMOI studies show therapy can produce measurable brain damage, brain change, sorry, misspoke, CBC leads to increased prefrontal cortex activity and reduced amygdala hyperactivity, correlating with improved emotional regulation. These are structural measurable changes, not just symptom relief. Let me translate that into human terms. Depression is not just a feeling, it has a physical dimension, changes in the structure and function of specific brain regions, regions involved in mood, memory and emotional regulation. And the research now shows that those changes are not permanent. Therapy, particularly CBT, but increasingly other approaches to can produce measurable changes in how the brain functions. Scannable visible changes, not just feeling better, actual structural shifts. What can support neuroplasticity current evidence? Established evidence for neuroplastic benefits, psychotherapy, CBT and others, FMY confirmed changes, physical exercise promotes BDNF, supports hippocampal growth, SSLIs, antidepressants promote BDNF release, support synaptic connectivity, emerging evidence promising more research needed. Ketamine, rapid antidepressant effects of eye glutamate, receptor modulation, particularly for treatment resistant depression, sinocybine and MDMA assisted therapy, early clinical trials, some neuroplastic and epigenetic effects. EMDR Neurobiological Mechanisms under active investigation important caveat individual variability in neuroplastic responses is significant. What works for one person may not work for another or to the same degree. I want to be precise about the caveat at the bottom of that box. Individual variability in neuroplastic responses is significant. This is not a reason to give up, but it is a reason to Be honest about the limits of any single intervention. The brain can change, the evidence for that is real and growing, but how much it changes how quickly and in response to what varies considerably from person to person? Which means the answer to will this work for me is almost always we don't fully know yet, but there is a genuine reason to try. So let's come back to the question we started with. Does biology ultimately decide our brain chemistry to suffer from mental health? Here is the honest answer the one that the research supports without false comfort and without false despair. Partially yes, partially no, and the interaction between the two is where the most important science lives. Yes, genetics contributes meaningfully to risk between a third and a half of variation in depression and anxiety appears to be heritable. That is a real biological factor, it is not invented. But genetics are not deafening, they are probability and what activates that probability, what turns up the volume on genetic risk is often experience, specifically early experience. And that experience, the chronic stress, the trauma, the years of growing up in an environment that required your nervous system to stay on alert gets encoded. It becomes biology through epigenetic mechanisms that are real, measurable and documented. So when you ask was this already in my biology, the answer is some of it some of it was and some of it became biology because of what you went through. Neither of those things is your fault. And neither of them, and this is where neuropathicity matters, is permanently fixed. The brain retains the capacity to change slowly and with the right conditions and with significant individual variation, but genuinely the research is clear on this. That is not a promise of recovery. I am not making that promise. It will not be honest of me to make it. What it is is evidence that the question was I always going to be like this has a more complicated answer than the 3 a.m. voice in your head suggests. You are the product of change, experience and a brain that is still, even now responding and adapting. Not fixed, still here, still changing. I have spent years asking whether I was built for this, whether the difficulty was written into me, whether there was any point in trying to change something that was at its root biological. What the science I've shared today changed for me was not the answer. The answer is still complicated. What it changed was the question. Instead of was I always going to be like this, which closes everything down, the question becomes given everything I've inherited and everything I've experienced, what conditions would give my brain the best chance of updating? That is a more useful question, it is also I think a more honest one. Next episode we're going to ask whether our current therapeutic models are adequate, whether the systems designed to help people like us are actually built around the reality of our experience. It's the question that has been quietly running under every episode in this series. But for now that's enough. You can call or text 988 the Suicide and Crisis Lifeline 3 confidentials available 24 hours a day. Or text home to 741741 The Crisis Text Line also 3 confidential and available anytime. You can find this show wherever you listen to podcasts. If today's episode resonated, please show it to someone who might need it. I'm Toman, I'll be back for episode five. Take care of yourself.