Cobbers on the Brain – Student Commentary on the Neurological Sciences

The Hidden Control Center of Your Metabolism

Posted on April 23, 2026 by cborrud / 0 Comment

Cayley Borrud Artstract made with ChatGPT

When you think of metabolic disease and metabolism, do you think of the brain?

One of the most important regulators of metabolism is the brain. Metabolic Syndrome triggers a constant state of low-grade inflammation in the hypothalamus. The hypothalamus is the region that manages energy balance and metabolism. It’s the control center for hunger and energy balance making it vital that the hypothalamus has reduced inflammation. First, there needs to be an understanding of how diet affects this important brain area.

Image sourced from Jamestown Spine

But, how do saturated fatty acids cause inflammation in the hypothalamus?

Image sourced from Pharmacy180

It starts with eating a saturated fatty acid such as pizza or ice-cream. The saturated fatty acid found in those foods, palmitic acid, is the most consumed fatty acid in the United States [2]. This activates signaling pathways and disrupts vital neuron populations [1]. Two of the most important neuronal populations involved are POMC neurons and AgRP neurons. POMC neurons help reduce appetite while AgRP neurons stimulate hunger when energy is needed. POMC and AgPR neuronal population disruptions lead to insulin and leptin resistance. This leptin and insulin resistance impairs the brains’ ability to sense nutritional cues which can then cause increased food intake and reduced energy expenditure [2]. While hypothalamic inflammation begins almost immediately, it’s very subtle. Unlike the inflammation seen in injury, this process chronic. Overtime, it disrupts the brains’ ability to interrupt hunger and fullness. Understanding these cellular interactions is vital for creating new medical strategies in combating metabolic syndrome.

Research has also shown that metabolic health may begin before birth. A maternal diet high in saturated fat may influence the developing hypothalamus of offspring. This could then increase future risk for obesity and metabolic syndrome [3]. Additionally, chronic sleep deprivation is also a major risk factor. Chronic sleep deprivation disrupts cortisol, ghrelin and leptin, therefore increasing hunger and insulin resistance [6].

What can be done to help this vital control center?

Understanding that metabolic health starts in the brain shifts the conversation from simple willpower to biological signaling. While overnutrition can cause this damage, certain factors like omega-3 fatty acids or exercise may help restore sensitivity and combat this silent inflammation [1]. Exercise can trigger anti-inflammatory signals that suppress the jammed pathways in the brain. Exercise also influences brain function by modulating the function of gut microbiota [4]. Also, Low movement decreases insulin sensitivity and reduces energy expenditure. Lower insulin sensitivity would also mean lower muscle glucose uptake [5]. Since muscle is one of the biggest regulators of blood sugar, it’s important that this system is modulated to help fight against metabolic disease.

Obesity is not simply a matter of calories. It’s deeply connected to the brains ability to regulate hunger and energy use. When the hypothalamus becomes inflamed, the body can lose its ability to accurately respond to cues of fullness therefore creating a cycle that promotes weight gain and insulin resistance. Factors such as diet, sleep deprivation and event maternal diet can influence this hidden control center. By focusing on the brain’s hypothalamic inflammation, we can work in the right direction against metabolic syndrome.

Sources:

Jais, A., & Brüning, J. C. (2017). Hypothalamic inflammation in obesity and metabolic disease.The Journal of Clinical Investigation,127(1), 24–32. https://doi.org/10.1172/JCI88878
skr42. (2024, August 19). Identifying ‘stealth’ sources of saturated fat, added sugar in the diet.Lombardi Comprehensive Cancer Center. https://lombardi.georgetown.edu/lombardi-stories/identifying-stealth-sources-of-saturated-fat-added-sugar-in-the-diet/
Alum, E. U., Aloh, H. E., Obasi, D. C., Okoroh, P. N., Aniokete, U. C., & Emeruwa, A. P. (2025). Maternal nutrition, toxicants, and epigenetic programming of obesity across generations.Diabetes, Metabolic Syndrome and Obesity,18, 4873–4911. https://doi.org/10.2147/DMSO.S579409
Sun, W., Wang, W., Zhang, Y., Liu, H., Li, L., Zhang, Y., & Liu, B. (n.d.). The brain-gut-muscle axis: A mechanism for exercise-mediated protection in brain aging.Frontiers in Aging Neuroscience,18, 1761832. https://doi.org/10.3389/fnagi.2026.1761832
Silva, F. M., Duarte-Mendes, P., Teixeira, A. M., Soares, C. M., & Ferreira, J. P. (2024). The effects of combined exercise training on glucose metabolism and inflammatory markers in sedentary adults: A systematic review and meta-analysis.Scientific Reports,14(1), 1936. https://doi.org/10.1038/s41598-024-51832-y
Liu, S., Wang, X., Zheng, Q., Gao, L., & Sun, Q. (2022). Sleep deprivation and central appetite regulation.Nutrients,14(24), 5196. https://doi.org/10.3390/nu14245196

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The Broken Thermostat: How Obesity Rewires Your Brain

Posted on April 22, 2026 by gkuehn / 0 Comment

When we talk about obesity, we usually don’t instantly think about the brain. Primary areas of concern usually consist of the heart, the joints, and the metabolic system to name a few. However, some of the most consequential changes happen in the brain, specifically in a small but mighty region called the hypothalamus. Furthermore, emerging research suggests that these brain changes aren’t just a consequence of carrying extra weight – they’re actively driving it.

Inflammation at the Control Center

A 2017 review by Jais and Brüning in the Journal of Clinical Investigation laid out a striking picture: a high-fat diet doesn’t just expand the waistline: it triggers inflammation deep in the brain, and it does so fast. Within days of starting a high-fat diet, before significant weight gain even occurs, the hypothalamus begins showing signs of inflammatory stress. Key signaling pathways involving JNK and IKK activate, leptin and insulin resistance develops at the neuronal level, and the brain’s ability to accurately read the body’s energy state starts to break down. [1]

The hypothalamus is essentially the thermostat of your metabolism. It receives signals from hormones like leptin and insulin that tell it how much fat you’re carrying and how much you’ve eaten, then adjusts hunger and energy expenditure accordingly. When diet-induced inflammation disrupts this feedback loop, the thermostat breaks. You eat more, burn less, and the cycle deepens.

What makes this especially sobering is that it’s not just neurons involved. Microglia, astrocytes, and cells lining the blood-brain barrier all participate in — and amplify — this inflammatory cascade. Over time, chronic inflammation can even trigger the death of POMC neurons, the very cells responsible for suppressing appetite. The damage compounds quietly, long before it shows up on a scale.

The Good News: Some of This Is Reversible

Figure 1: Areas of the brain with significant change in activity following diet change

Here’s where things get more hopeful. Recent research into what happens to the brain after weight loss tells a more optimistic story. Following a structured weight loss intervention, activity decreased significantly in brain regions that are typically overactive in obesity – areas tied to food reward, taste processing, and decision-making around eating (figure 1). Critically, these changes didn’t show up after a 48-hour fast, meaning they weren’t just a side effect of short-term hunger. They appear to be genuine adaptations tied to actual reductions in body weight and fat mass. Leptin levels dropped alongside brain activity, suggesting the brain is recalibrating in response to a changed metabolic environment. [2]

The implications for eating behavior are significant. Less reactivity in reward-related brain regions could mean food simply becomes less compelling – less of a constant pull. Whether these changes help sustain weight loss long-term is still an open question, and researchers are careful to note the limitations of small study sizes.

Even more striking are findings from bariatric surgery research. Individuals with obesity showed measurably older brain ages compared to normal-weight peers – a marker of accelerated neurological aging. But after surgery and sustained weight loss, brain age improved by roughly three to six years over two years of follow-up. These weren’t subtle changes confined to one area; they were global, touching sensory, visual, and attention networks alike, and they correlated with lower BMI, better blood pressure, and improved insulin resistance. [3]

What This Means

Taken together, these findings reframe obesity not as a failure of willpower but as a condition that reshapes the very organ responsible for regulating appetite and behavior. The hypothalamus gets caught in a feedback loop where inflammation drives overeating, and overeating drives more inflammation. The brain, in a real sense, becomes organized around a higher weight set point.

But the brain is also adaptable. Weight loss – whether through lifestyle change or surgery – appears to walk some of those changes back. The thermostat can, at least partially, be reset. Understanding exactly how and why that happens may be one of the most important frontiers in obesity medicine.

(1) Jais, A.; Brüning, J. C. Hypothalamic Inflammation in Obesity and Metabolic Disease. J. Clin. Invest. 2017, 127 (1), 24–32. https://doi.org/10.1172/JCI88878.

(2) van Opstal, A. M.; Wijngaarden, M. A.; van der Grond, J.; Pijl, H. Changes in Brain Activity after Weight Loss. Obes. Sci. Pract. 2019, 5 (5), 459–467. https://doi.org/10.1002/osp4.363.

(3) Zeighami, Y.; Dadar, M.; Daoust, J.; Pelletier, M.; Biertho, L.; Bouvet-Bouchard, L.; Fulton, S.; Tchernof, A.; Dagher, A.; Richard, D.; Evans, A.; Michaud, A. Impact of Weight Loss on Brain Age: Improved Brain Health Following Bariatric Surgery. NeuroImage 2022, 259, 119415. https://doi.org/10.1016/j.neuroimage.2022.119415.

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More than the Munchies: How Cannabinoids Rewire Hunger in the Brain

Posted on April 20, 2026 by edoty / 0 Comment

Feature Image from Pexels

Our relationship with food intake and satiety is a complex system in the brain. Appetite is tightly regulated by a network of signals in the hypothalamus, which plays a large role in energy balance. When inflamed, the balance between food intake and energy expenditure is disrupted.[1]

Hypothalamic Inflammation:

The article linked here highlights that hypothalamic inflammation often develops in response to chronic exposure to high-fat and high-calorie diets. This inflammation interferes with how the brain processes signals related to hunger and fullness. Under normal conditions, hormones like leptin and insulin tell the hypothalamus when the body has enough energy stored. However, when inflammation is present, neurons become less responsive to these signals. This creates leptin or insulin resistance, resulting in the brain failing to recognize satiety. In turn, individuals may continue to feel hungry even when they have sufficient energy stored. Thus, hypothalamic inflammation is a pivotal component of metabolic disorders and obesity.[2]

Role of the Endocannabinoid System:

This imbalance also allows other systems to have a stronger influence on eating behavior. One of these is the endocannabinoid system. Rather than simply increasing appetite, cannabinoids act directly on hypothalamic circuits to reshape how hunger signals are produced and interpreted.

In the arcuate nucleus, cannabinoids promote food intake through two major mechanisms. They increase the release of neuropeptide Y (NPY), a strong appetite-stimulating signal, and they alter the function of POMC neurons. Normally, these neurons help suppress appetite by releasing α-MSH. However, when cannabinoids are present, they release β-endorphin instead, which promotes feeding through opioid signaling.[3] This is shows how cannabinoids don’t just amplify hunger, but alter the function of key neurons entirely.

This effect extends across multiple hypothalamic regions. In the paraventricular hypothalamus, cannabinoid signaling shifts the balance of neurotransmitters by increasing GABA, which stimulates eating, and decreasing serotonin, which promotes fullness. This region also works closely with ghrelin, a hormone that drives hunger and depends on the endocannabinoid system to function. In the lateral hypothalamus, cannabinoids excite neurons that release orexin and melanin-concentrating hormone, both of which increase motivation to seek out food and promote impulsive eating.[4]

These effects explained above are visualized here.

Source of Image: Hypothalamic cannabinoid signaling: Consequences for eating behavior – PMC

These biological mechanisms are exemplified when thinking about the use of cannabis, specifically THC, which is known to increase cravings, especially for high-fat, high-calorie foods. Interestingly, edible forms tend to produce a stronger and longer-lasting increase in appetite compared to inhaled forms, possibly because of prolonged effects on hunger-related hormones like ghrelin.[5]

Effect on Obesity:

The relationship between cannabis and body weight is not as straightforward as it might seem. Despite increased appetite, cannabis use alone is not strongly linked to weight gain and has even been associated with lower BMI, though this is not a causal relationship. However, when use becomes disordered, there is a greater risk of losing control over eating behaviors, and it may co-occur with eating disorders. Indirect factors, such as reduced physical activity, can also influence long-term outcomes associated with cannabinoid use.[6]

Final Thoughts:

Overall, appetite is not controlled by a single pathway but by a complex system. Hypothalamic inflammation can alter normal regulatory signals, and within that altered environment, the endocannabinoid system can significantly amplify hunger. Together, these processes show how deeply brain chemistry shapes something as mundane as eating.

[1] Alexander Jais and Jens C. Brüning, “Hypothalamic Inflammation in Obesity and Metabolic Disease,” The Journal of Clinical Investigation 127, no. 1 (2017): 24–32, https://doi.org/10.1172/JCI88878.

[2] Jais and Brüning, “Hypothalamic Inflammation in Obesity and Metabolic Disease.”

[3] Magen N. Lord and Emily E. Noble, “Hypothalamic Cannabinoid Signaling: Consequences for Eating Behavior,” Pharmacology Research & Perspectives 12, no. 5 (2024): e1251, https://doi.org/10.1002/prp2.1251.

[4] Lord and Noble, “Hypothalamic Cannabinoid Signaling.”

[5] Kasey P. S. Goodpaster, “Cannabis, Weight, and Weight-Related Behaviors,” Current Obesity Reports 14, no. 1 (2025): 40, https://doi.org/10.1007/s13679-025-00633-z.

[6] Goodpaster, “Cannabis, Weight, and Weight-Related Behaviors.”

Disease/Health

Can Exercise Rewire How We Remember Stress?

Posted on April 17, 2026 by jnanyong / 0 Comment

Why Do Some Stressful Memories Stay?

Have you ever wondered why your brain holds onto a stressful moment like a high-definition movie, while other memories just fade away? We know that stress can shape powerful memories by changing how the brain functions at a molecular level. These changes, especially in the hippocampus, help us adapt to future challenges.

However, not everyone responds to stress in the same way. Some people develop overwhelming, persistent memories, while others recover more easily. This raises an important question: what controls how strongly stress is encoded in the brain? Emerging research suggests that exercise, through its effects on GABA, may be a key piece of the puzzle.

How Stress Becomes Memory

When we experience stress, the body releases glucocorticoid hormones (like cortisol), which travel to the brain and interact with regions involved in memory, particularly the hippocampus. At the same time, neural activity increases through pathways like theERK-MAPK signaling pathway.

These two systems – hormonal and neural – don’t act independently. Indeed, they interact to trigger a cascade of events inside neurons that ultimately leads to changes in gene expression. [1]

One of the key mechanisms involved is epigenetic modification. Think of it as your brain “bookmarking” its most stressful experiences so it can find them quickly later on. In this case, stress causes specific changes to histone proteins (such as H3S10p – K14ac), which open up sections of DNA and allow certain genes – like c-Fos and Erg-1 – to be expressed. [1]

These genes are critical for consolidating memory, essentially helping the brain store the stressful experience for the long term.

Figure 1(right): An image of how stress activates both glucocorticoid receptors and neural signaling pathways to drive gene expression and memory formation. [1]

Why Anxiety Changes the Outcome

Even though these mechanisms exist in everyone, their effects aren’t the same across individuals. One major factor that shapes this response is anxiety level, which is closely tied to the neurotransmitter GABA.

GABA acts as the brain’s primary inhibitory signal—it helps keep neural activity in check. When GABA levels are high, neurons are less likely to become overactive. When GABA levels are low, the brain becomes more excitable and more reactive to stress.

The paper highlights that GABAergic signaling plays a critical role in regulating how strongly stress activates the hippocampus, particularly in the dentate gyrus. [1]

This means that:

Lower GABA activity → stronger stress signaling → stronger memory formation.
Higher GABA activity → reduced stress signaling → more controlled memory encoding.

This helps explain why individuals with higher anxiety may foirm stringer, more persistent stress-related memories.

Exercise and GABA: A Protective Mechanism

This is where exercise comes in and where things get really interesting.

The paper reports that long-term voluntary exercise increases the expression of GAD67, an enzyme responsible for synthesizing GABA. [1] In other words, exercise may actually increase the brain’s ability to produce GABA.

This shift has important downstream effects. Increased GABA strengthens inhibitory control in the hippocampus, which reduces neuronal excitability. As a result, key stress-related signaling pathways – like ERK-MAPK – are less strongly activated.

Studies in a paper by Reul, 2014 showed that exercised animals had:

Reduced activation of ERK-MAPK signaling
Lower levels of stress-induced gene expression (like c-Fos)
A dampened molecular response to stress [2]

What this suggests is that exercise doesn’t stop stress from occurring, but it changes how intensely the brain responds to it.

Why This Matters

These findings go beyond basic neuroscience – they have real implications for mental health. Conditions like PTSD are often linked to overactive stress responses and persistent memory formation. If exercise can increase GABA levels and reduce the intensity of these processes, it may serve as a powerful, accessible way to build resilience.

More broadly, this research highlights something important: our experiences don’t just shape our minds psychologically – the reshape them biologically as well. And through behavior like exercise, we may have more control over that process than we think.

Bibliography

[1]

M. H. M. Reul, “Making Memories of Stressful Events: A Journey Along Epigenetic, Gene Transcription, and Signaling Pathways,” Front. Psychiatry, vol. 5, 2014, doi: 10.3389/fpsyt.2014.00005.

[2]

“Neuroscience Pinpoints Unique Way Exercise Fights Depression | Psychology Today.” Accessed: Apr. 14, 2026. [Online]. Available: https://www.psychologytoday.com/us/blog/the-athletes-way/201602/neuroscience-pinpoints-unique-way-exercise-fights-depression

Community/Disease/Health

Genes, Memory, and Fear: The Science Behind PTSD

Posted on April 15, 2026 by edoty / 0 Comment

Feature Image from Pexels

The brain is constantly changing in response to our experiences. The article linked here emphasizes this by showing how patterns of neural activity are translated into lasting changes in brain structure and function. These processes are correlated to learning and memory formation. When neurons are activated by experiences such as learning something new or encountering stress, they trigger intracellular signaling pathways that ultimately alter gene expression. These changes lead to modifications in synaptic strength, allowing the brain to store information over time and associate the emotions felt during an experience with our long-term memory of such events.[1]

Mental Health Connections:

Importantly, the article connects these processes to mental health, explaining that when these memory systems become dysregulated, they can contribute to disorders like anxiety disorders and post-traumatic stress disorder. In these conditions, fear-related memories can become overly strong or persist longer than they should.[2]

Immediate Early Genes:

Building on this foundation, immediate early genes (IEGs) play a critical role in linking neural activity to these long-term changes. IEGs are among the first genes activated when a neuron receives a signal from its environment.[3] As transcription factors, they control the expression of other genes. Through this process, they can affect long-term cellular responses.[4]

IEGs are especially important in learning and memory because they drive the molecular changes underlying synaptic plasticity. By regulating the production of proteins involved in synaptic growth and strengthening, they help stabilize the neural connections formed during pivotal experiences. This makes them essential for memory consolidation, where short-term information is transformed into long-term storage.[5]

Key IEG Examples:

Two important examples of IEGs are c-Fos and Egr1. c-Fos is rapidly expressed in response to strong neuronal stimulation, with transcription occurring within minutes. Its promoter contains two key regulatory elements: the serum response element (SRE), which responds to cytoplasmic calcium, and the cAMP response element (CRE), which is linked to nuclear calcium signaling. c-Fos has a dual role. In the nucleus, it acts as a transcription factor, forming complexes with Jun proteins to regulate late effector genes that produce structural and synaptic proteins necessary for long-term. In the cytoplasm, it supports membrane formation and neurite outgrowth by activating lipid synthesis. These functions make c-Fos especially important for long-term memory formation.[6]

Egr1 (early growth response 1) is another crucial IEG that is activated by when we experience something for the first time. It plays a foundational role in learning by helping initiate long-term potentiation (LTP), a key mechanism underlying strengthened synaptic connections. Beyond memory, Egr1 also guides cell growth, differentiation, and tissue repair.[7]

IEGs and PTSD:

IEGs are also directly tied to emotional memory and mental health. The article highlights that persistent fear memories depend on activity in genes like c-Fos. For example, blocking c-Fos expression in the hippocampus can disrupt the consolidation and persistence of fear memories, while reducing Egr1 in the amygdala impairs both contextual and cued fear memories.[8] These findings suggest that the same molecular systems that allow us to learn from new experiences contribute to disorders such as Post-Traumatic Stress Disorder when dysregulated.

[1] Johannes M. H. M. Reul, “Making Memories of Stressful Events: A Journey Along Epigenetic, Gene Transcription, and Signaling Pathways,” Frontiers in Psychiatry 5 (January 2014): 5, https://doi.org/10.3389/fpsyt.2014.00005.

[2] Reul, “Making Memories of Stressful Events.”

[3] “The EGR1 Gene’s Role in Health, Disease, and Medicine,” Biology Insights, June 29, 2025, https://biologyinsights.com/the-egr1-genes-role-in-health-disease-and-medicine/.

[4] “Immediate Early Genes – Knowledge and References,” Taylor & Francis, accessed March 31, 2026, https://taylorandfrancis.com/knowledge/Engineering_and_technology/Biomedical_engineering/Immediate_early_genes/.

[5] Pavel P. Tregub et al., “Brain Plasticity and Cell Competition: Immediate Early Genes Are the Focus,” Cells 14, no. 2 (2025): 143, https://doi.org/10.3390/cells14020143.

[6] “C-Fos – an Overview | ScienceDirect Topics,” accessed March 31, 2026, https://www.sciencedirect.com/topics/neuroscience/c-fos.

[7] Biology Insights, “The EGR1 Gene’s Role in Health, Disease, and Medicine.”

[8] Francisco T. Gallo et al., “Immediate Early Genes, Memory and Psychiatric Disorders: Focus on c-Fos, Egr1 and Arc,” Frontiers in Behavioral Neuroscience 12 (April 2018), https://doi.org/10.3389/fnbeh.2018.00079.

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Why Traumatic Memories Stick

Posted on April 15, 2026 by gkuehn / 0 Comment

Gannon Kuehn’s Artstract #2 generated by ChatGPT

We’ve been struggling to name what trauma does to the mind for a long time. Civil War soldiers called it “soldier’s heart” — a cardiovascular condition, they thought, brought on by the stress of combat. WWI veterans were told they had “shell shock,” initially assumed to be literal brain damage from artillery blasts, until doctors noticed identical symptoms in soldiers who’d never been near an explosion. [1] After WWII it became “battle fatigue.” The name kept changing because the phenomenon was always slightly beyond our grasp. It wasn’t until 1980, pushed forward by a convergence of Vietnam veterans, Holocaust survivors, and sexual trauma survivors, that PTSD was formally recognized as a diagnosis. The DSM had actually dropped its predecessor diagnosis entirely in 1968. [1]

That long, halting history matters because it shapes how we think about the disorder today. PTSD isn’t one thing. The DSM-5 recognizes a dissociative subtype, characterized by feeling detached from oneself or from reality, alongside the standard diagnosis. [2] The ICD-11 goes further, formally recognizing Complex PTSD — typically following prolonged or repeated trauma — as a distinct condition, though the DSM hasn’t followed suit. [3] Researchers have also identified subtypes that don’t appear in any diagnostic manual: a “threat-reactivity” profile dominated by fear and hypervigilance, strongly associated with combat; and a “dysphoric” profile dominated by depression and emotional numbing, which appears more tied to pre-existing genetic vulnerability than to the type of trauma experienced. [4]

That last point raises an obvious question: if two people go through the same event and one develops PTSD while the other doesn’t, what’s actually different between them? The answer, neuroscience is beginning to show, is partly molecular.

A 2014 paper by Johannes Reul at the University of Bristol traced what happens in the brain during and after a psychologically stressful event, at the level of individual neurons. [5] When we encounter something threatening, the adrenal glands release stress hormones that travel to the hippocampus — the brain region central to memory formation. Reul’s team found that in a specific subset of hippocampal neurons, these stress hormones interact with a signaling pathway normally associated with learning to trigger a cascade of changes inside the cell (Figure 1).

Figure 1: Cascade that alters how memory is encoded.

The cascade ends at the DNA itself: proteins that control which genes are accessible get chemically modified, switching on genes that drive long-term changes in how those neurons function. The stressful experience, in other words, leaves a physical mark on the genome of specific brain cells — a mark that shapes how the memory is encoded and stored.

Crucially, Reul’s research found that this process is gated by anxiety. The neurotransmitter GABA normally acts as an inhibitory brake on these neurons. When anxiety is high and GABAergic inhibition is correspondingly low, the neurons are more easily activated and the full molecular cascade is more likely to fire. In animal studies, drugs that boost GABA activity blunted the stress response at the molecular level; drugs that suppress it amplified the response dramatically. Voluntary exercise, which Reul’s group also studied, appeared to increase GABA synthesis over time and reduce the intensity of stress-induced molecular changes — a possible mechanism behind exercise’s well-documented benefits for anxiety and mood.

This connects the molecular picture back to the clinical one. Higher baseline anxiety means a lower threshold for triggering the memory-consolidation cascade, which may explain why anxious individuals face elevated risk for PTSD after trauma. It also suggests why the “dysphoric” research subtype — with its roots in pre-existing biology rather than trauma — might represent a distinct pathway into the disorder altogether.

For over a century, PTSD cycled in and out of official recognition, framed alternately as weakness, neurological damage, or simple failure to adjust. The 1968 DSM dropped the diagnosis entirely. What research like Reul’s provides is something that advocacy alone couldn’t: a biological explanation for why traumatic memory is different from ordinary memory. It isn’t a failure of resilience; it’s the product of specific, powerful processes in the brain that, under the right conditions, encode experience with unusual and sometimes lasting permanence. Understanding those processes is the first step toward one day being able to interrupt them.

(1) VA.gov | Veterans Affairs. https://www.ptsd.va.gov/understand/what/history_ptsd.asp (accessed 2026-04-14).

(2) Treatment (US), C. for S. A. Exhibit 1.3-4, DSM-5 Diagnostic Criteria for PTSD. https://www.ncbi.nlm.nih.gov/books/NBK207191/ (accessed 2026-04-14).

(3) VA.gov | Veterans Affairs. https://www.ptsd.va.gov/professional/treat/essentials/complex_ptsd.asp (accessed 2026-04-14).

(4) Sumner, J. A.; Kubzansky, L. D.; Roberts, A. L.; Chen, Q.; Rimm, E. B.; Koenen, K. C. Not All Posttraumatic Stress Disorder Symptoms Are Equal: Fear, Dysphoria, and Risk of Developing Hypertension in Trauma-Exposed Women. Psychol. Med. 2020, 50 (1), 38–47. https://doi.org/10.1017/S0033291718003914.

(5) Reul, J. M. H. M. Making Memories of Stressful Events: A Journey Along Epigenetic, Gene Transcription, and Signaling Pathways. Front. Psychiatry 2014, 5, 5. https://doi.org/10.3389/fpsyt.2014.00005.

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When the Brain Won’t Let Go: Understanding PTSD

Posted on April 14, 2026 by jwolf6 / 0 Comment

Featured image created by Julia Wolf and Microsoft CoPilot

The Science of PTSD

Not all stress is processed the same way by the brain. While many experiences are eventually filed away and lose their intensity, traumatic events can become deeply embedded, continuing to influence thoughts and emotions long after they occur. This starts with the body’s stress response. During a traumatic event, stress hormones like cortisol are released and travel to areas of the brain that handle emotion and memory, including the hippocampus and amygdala. These hormones don’t just signal that something important is happening, they actively shape how that experience is stored. Inside neurons, they activate receptors that set off signaling cascades, such as the ERK-MAPK pathway, which play a key role in forming long-term memories [1].

What’s happening at this stage goes beyond simple memory storage. Stress can influence how genes are turned on or off without altering the DNA sequence itself, a process known as epigenetics. This involves changes to histones, the proteins that DNA wraps around. When these proteins are modified, certain genes become easier to access, allowing the brain to strengthen connections between neurons involved in that memory. In other words, the experience becomes biologically “prioritized.” This system is normally beneficial because it helps us recognize and respond to danger in the future. However, in PTSD, this process becomes overactive. The brain may reinforce the memory too strongly, making it difficult to move past the event. Instead of fading, the memory is repeatedly reactivated, which can show up as flashbacks, nightmares, or persistent feelings of threat [1].

Anxiety further intensifies this cycle. Under typical conditions, the brain uses inhibitory signals, largely controlled by the neurotransmitter GABA, to keep stress responses in check. When anxiety is elevated, this braking system becomes less effective. As a result, stress-related activity in the brain increases, making traumatic memories more likely to be strongly encoded and easily triggered [1].

To learn more about the mechanisms involved in stress and PTSD, click here!

Comorbidities with PTSD

PTSD rarely occurs on its own. In fact, 80% of individuals with PTSD have at least one additional mental health condition, these comorbidities can significantly worsen outcomes, including functional impairments, reduced quality of life, and relationship problems [2].

Anxiety disorders are among the most common comorbid conditions. Disorders such as generalized anxiety disorder, panic disorder, and social anxiety frequently overlap with PTSD, largely because they share underlying features like hyperarousal, irritability, and difficulty concentrating. Generalized anxiety disorder, in particular, affects about 11.1-31.6% of individuals with pTSD and is strongly related to the hyperarousal symptom cluster. These shared symptoms reflect similar disruptions in the brain’s stress-response systems [3].

Figure 2. Overview of common PTSD symptoms group into categories [9].

Major depressive disorder is also highly prevalent, affecting roughly half of individuals with PTSD. Both conditions share symptoms such as sleep disturbances, loss of interest in activities, and impaired concentration. When PTSD and depression occur together, individuals often experience more severe cognitive difficulties and are at greater risk for suicide. Additionally, early life stress, such as childhood adversity or abuse, increases the likelihood of developing both conditions, and having both disorders is associated with poorer treatment outcomes and more treatment dropout[4].

Substance use disorders are another major concern. Individuals with PTSD are two to four times more likely to develop substance use issues, and about 34.4% of those with PTSD also meet the criteria for at least one substance use disorder, most commonly alcohol use disorders. This is often explained by the self-medication hypothesis, which suggests that individuals use substances to cope with or numb distressing symptoms like intrusive memories or constant anxiety. However, this can create a cycle that worsens both conditions and leads to additional complications such as health problems and adhering to treatment [5].

Sleep disturbances are extremely common in PTSD and can further add to symptoms. Many individuals experience chronic insomnia or frequent nightmares, and some even develop a fear of sleep due to the possibility of reliving traumatic experiences. In veterans with PTSD, obstructive sleep apnea has been reported at rates of 43-75% [6], and about 90% of individuals experience insomnia symptoms, with around 40% meeting criteria for clinical insomnia. These disruptions not only worsen mental health but also interfere with physical recovery and overall functioning.

Beyond mental health, PTSD is also linked to a range of physical health conditions. Chronic activation of stress pathways can contribute to cardiovascular issues such as high blood pressure, as well as metabolic problems like type 2 diabetes and obesity. Individuals with PTSD also report higher rates of chronic pain conditions, including fibromyalgia, migraines, and arthritis, showing how deeply stress can affect the entire body [8].

Why This Matters

Understanding the science behind PTSD changes how we think about it. Rather than viewing it as simply a psychological issue, it becomes clear that PTSD is rooted in real, measurable biological processes involving brain signaling, gene expression, and long-term changes in how the brain functions. This perspective helps reduce stigma by showing that PTSD is not a sign of weakness, but the result of the brain’s attempt to adapt to overwhelming stress. It also shows why treatment can be complex, especially when multiple conditions occur together. Effective care often needs to address not just the traumatic memory itself, but also related issues like anxiety, depression, sleep disturbances, and physical health.

Most importantly, this research opens the door for better treatments. By targeting the underlying biological mechanisms, such as stress hormone systems, brain signaling pathways, and even epigenetic changes, scientists and clinicians can develop more precise and effective ways to help individuals recover.

References

[1] J. M. H. M. Reul, “Making Memories of Stressful Events: A Journey Along Epigenetic, Gene Transcription, and Signaling Pathways,” Frontiers in Psychiatry, vol. 5, 2014, doi: https://doi.org/10.3389/fpsyt.2014.00005.

[2] U.S. Department Of Veterans Affairs, “VA.gov | Veterans Affairs,” Va.gov, 2014. https://www.ptsd.va.gov/professional/treat/cooccurring/index.asp

[3] M. Price and K. van Stolk-Cooke, “Examination of the interrelations between the factors of PTSD, major depression, and generalized anxiety disorder in a heterogeneous trauma-exposed sample using DSM 5 criteria,” Journal of Affective Disorders, vol. 186, pp. 149–155, Nov. 2015, doi: https://doi.org/10.1016/j.jad.2015.06.012.

[4] J. Flory and R. Yehuda, “Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations,” Treatment of Affective Dysfunction in Challenging Contexts, vol. 17, no. 2, pp. 141–150, Jun. 2015, doi: https://doi.org/10.31887/dcns.2015.17.2/jflory.

[5] J. L. McCauley, T. Killeen, D. F. Gros, K. T. Brady, and S. E. Back, “Posttraumatic Stress Disorder and Co-Occurring Substance Use Disorders: Advances in Assessment and Treatment,” Clinical Psychology: Science and Practice, vol. 19, no. 3, pp. 283–304, Sep. 2012, doi: https://doi.org/10.1111/cpsp.12006.

[6] P. Gehrman, “Sleep Problems in Veterans with PTSD – PTSD: National Center for PTSD,” Va.gov, 2014. https://www.ptsd.va.gov/professional/treat/cooccurring/sleep_problems_vets.asp

[7] G. G. Werner, D. Riemann, and T. Ehring, “Fear of sleep and trauma-induced insomnia: A review and conceptual model,” Sleep Medicine Reviews, vol. 55, p. 101383, Feb. 2021, doi: https://doi.org/10.1016/j.smrv.2020.101383.

[8] K. Jankowksi, “VA.gov | Veterans Affairs,” Va.gov, Mar. 02, 2023. https://www.ptsd.va.gov/professional/treat/cooccurring/ptsd_physical_health.asp

[9] Cleveland Clinic, “Post-Traumatic stress disorder (PTSD),” Cleveland Clinic, 2023. https://my.clevelandclinic.org/health/diseases/9545-post-traumatic-stress-disorder-ptsd

Uncategorized

PTSD: A Historical Advantage Turned to a Modern Day Demon

Posted on April 12, 2026 by ehunt4 / 0 Comment

Artstract created by: Eli Hunt through use of Google Gemini

Post-Traumatic Stress Disorder (PTSD) is a debilitating mental health condition caused by experiencing or witnessing a traumatic event. Most people think of PTSD being a condition associated with mostly former military members, while this is a population at risk for

developing PTSD, it can be developed by anyone from any traumatic event, not just war. Some other events that put people at risk of developing PTSD are car accidents, sexual assault, natural disasters or violent crimes. This leads to symptoms that can include nightmares, flashbacks, hypervigilance, negative mood and avoidance of reminders. The mechanisms behind the development of PTSD are unique to other forms of memory development, and these adaptions have contributed to the survival and advancement of humans. To get a better understanding of PTSD and how it affects a person, look here.

Modern day humans, especially those of us who are fortunate enough to live in wealthier societies, are not subject to nearly as much trauma and we live lives more or less free from traumatic stress. When you think of ancient humans, who are subject to predation, dangerous terrain, unknown territory, and other tribes of humans, they were subject to

trauma on a daily basis. The mechanisms behind PTSD work to the benefit of these humans as if they remember where a traumatic event took place or common patterns involved in it, this could help them survive. So as sick as it can be to think of PTSD being a beneficial human adaptation in a modern context, when you wind it back a few thousand years, PTSD has theoretically helped humans to survive into today. To better understand PTSD in this context we need to know how it works.

The Mechanisms Behind PTSD

The place in the brain primarily responsible for memory is the hippocampus. Within the hippocampus are receptors called glucocorticoid receptors. When we are experiencing stress, our bodies release glucocorticoids, which bind to the glucocorticoid receptors. To understand the next part of the pathway we need to back up a little bit and talk about a pair of genes, these genes are called c-Fos and Egr-1. These genes are essentially what tells the hippocampus to prioritize remembering this stimuli, leading to those traumatic memories leaving such a strong impact. These genes are locked behind a hypothetical vault that is unlocked through a histone called H3S10p-K14ac. This key to the vault is something that needs to be made, and glucocorticoid receptors play an essential role to this formation.

The role that glucocorticoid receptors play are small but essential. They act as a scaffold in

the ERK/MAPK pathway that leads to the creation of H3S10p-K14ac. When NMDA receptors activate, allowing a calcium influx to take place in the cell, it leads to the activation of this pathway. In order to create H3S10p-K14ac, ERK needs to activate MSK1/2, which is the kinase that leads to the creation of H3S10p-K14ac. This is where glucocorticoid receptors come in. When glucocorticoid receptors are activated, they act as scaffold between ERK and MSK1/2, allowing for the activation of MSK1/2. MSK1/2 then creates H3S10p-K14ac, which then unlocks the vault containing c-Fos and Egr-1. These genes then create the traumatic memory.

All of this information may be confusing, so lets try looking at it through a historical context. An ancient caveman is out for a hunt when all of a sudden their group gets attacked by a saber-toothed tiger. During the vicious attack, the caveman’s brain releases glucocorticoids

which then bind to the glucocorticoid receptors. As the saber-toothed tiger is roaring at our caveman’s hunting party, the caveman’s brain is creating memories normally through the ERK/MAPK pathway, but the memories aren’t any stronger than normal. Following the activation of glucocorticoid receptors, ERK can activate MSK1/2 and create H3S10p-K14ac. After the saber-toothed tiger sinks it’s teeth into the bounty of their successful hunt, the hunting party is just beginning to fight back. The party successfully fights back against the tiger, and are able to salvage some of their hunt. As our caveman continues to walk back to their cave, H3S10p-K14ac is unlocking the vault containing the c-Fos and Egr-1 gene, and as he is reflecting on the traumatic event, these genes then create the memory and it is engrained stronger than a normal memory.

Next time our caveman is out on a hunt, he is remembering the attack and is hypervigilant for another saber-toothed tiger attack and is prepared to fight back. He also remembers where not to go to lower the chances of encountering a tiger. This allows him and his tribe to survive and the development of a traumatic memory works in their favor. In a modern context, say a car accident, this doesn’t have the same evolutionary advantage. Chances are, someone is very unlikely to experience multiple traumatic car accidents, so having such an engrained memory that leads to behavioral changes does not increase ones odds for survival, rather it just causes them distress. This is how an adaptation that was historically beneficial for survival has backfired in a modern context. All the information here has been simplified and summarized from this article, if you are interested in getting a deeper scientific understanding of PTSD it is a great place to start.

(1) The Economist, The war in Ukraine shows how technology is changing the battlefield, https://www.economist.com/special-report/2023/07/03/the-war-in-ukraine-shows-how-technology-is-changing-the-battlefield

(2) Look and Learn, Saber-Toothed Tiger Attack Image, https://www.lookandlearn.com/history-images/A829569/Sabre-tooth-tiger-attacking-Homoerectus

Primary Source: Reul J. M. (2014). Making memories of stressful events: a journey along epigenetic, gene transcription, and signaling pathways. Frontiers in psychiatry, 5, 5. https://doi.org/10.3389/fpsyt.2014.00005

Disease/Health/Hot topics

Science of Trauma: How Stress Hardwires the Brain

Posted on April 9, 2026 by kleppke / 0 Comment

Feature image created by K. Leppke with help of ChatGPT

The Story of a Stressful Memory

Why do some moments fade while others remain stuck within the memory? The answer centers around brain stress hormones, neural signaling, and DNA packaging processes working together to wire these experiences into our memory. Stressful experiences create powerful memories that, evolutionarily, helped us adapt to our environments and be successful. When we experience something stressful, our body releases glucocorticoid hormones, like cortisol [1]. These hormones travel to the brain, especially to the hippocampus, where they help build memories.

Figure 1: Glucocorticoids help form traumatic memories by strengthening the encoding and retrieval of the traumatic memory. This increases the likelihood of vivid re-experiences of that memory. During reconsolidation glucocorticoids reinforce this memory every time it is retrieved, making it more stable. This cycle boosts the emotional intensity and persistence of the traumatic memory [7].

Glucocorticoids interact with brain cells to activate a powerful signaling cascade, called the ERK-MAPK pathway [1]. This pathway passes extracellular information into the nucleus, where DNA is. However, sometimes the memories that form in this process become too strong, contributing to disorders like anxiety and PTSD. Therefore, understanding the mechanism behind these memories is crucial for understanding both resilience and vulnerability to various disorders.

Memory & Genetics

Memories are stored through changes in brain cells, but don’t alter the DNA sequence itself. The brain uses epigenetics, which are chemical modifications that control how genes are turned on or off. In stressed neurons, signaling cascades lead to modifications on proteins called histones, which control packaging of DNA. Two specific changes occur with these histones [1]:

Phosphorylation on S10
Acetylation on K14

Together, these changes are referred to as H3S10p-K14ac and they open up the DNA. This is what allows certain genes to be activated. Two important genes that are activated are important for memory formation and are in the group called immediate early genes (IEGs). These genes are[1]:

c-Fos
Egr-1

Therefore, PTSD and anxiety disorders can be examined on a genetic level. Both are influenced by many genetic variants that collectively increase risk for the development of these disorders. Genetic variants associated with anxiety also relate to structural changes in the brain, such as a reduced volume in the amygdala, which directly effects fear conditioning [2]. The genetic predisposition for PTSD often overlaps with genes that influence personality traits, meaning those at risk are often risk-takers, have poor organization, increased self doubt, and are unstable [3].

Figure 2: This figure shows how genetic and environmental factors contribute to anxiety and PTSD. A significant portion of risk, between 30–60% [4], is genetic for anxiety and 30-40% [5] of risk for PTSD is genetic. They have shared key genes like FKBP5, BDNF, and COMT that influence stress response, memory, and emotional regulation. PTSD and anxiety disorders arise from inherited biological pathways and life experiences, specifically exposure to stress or trauma (figure created by GoogleNotebook) [6].

Learning & Emotions Through Stress

Through experimentation with rats, researchers found that strong memories of the stressful event lead to learning and adaptation to that event in the future. They found that if these scenarios occur, they are key to this process:

If glucocorticoid signaling is blocked the memory doesn’t form properly
If the ERK-MAPK pathway is disrupted the memory formation fails
If epigenetic changes don’t occur the learned adaptation won’t occur either

Anxiety levels change how strongly memories form. Therefore, emotional state shapes the biology of memory. GABA, a neurotransmitter which calms signaling, regulates this system. Research has found antianxiety drugs to reduce memory based gene activation. Anxiety inducing drugs amplify these molecular responses, promoting memory formation. This suggests that more anxious people may form stronger stress memories.

Conclusion

Memories are being actively built in the brain by specific hormone and molecular pathways, which epigenetically change the brain to prepare for similar situations in the future. Stressful experiences help us learn and survive through these memories. When the system becomes overactive, it can lead to anxiety disorders and PTSD. This causes these memories to seem like active stress situations, rather than a past experience which can be drawn on for learning or adaptation. Therefore, understanding these mechanisms could lead to better treatments that target memory formation at its roots, and decrease the stress levels the brain puts on itself through these mechanisms.

References

[1] Reul, J. M. H. M. (2014). Making Memories of Stressful Events: A Journey Along Epigenetic, Gene transcription, and Signaling Pathways. Front. Psychiatry 5.

[2] Vander Merwe, C., Jahanshad, N., Cheung, J. W., Mufford, M., Groenewold, N. A., Koen, N., Ramesar, R., Dalvie, S., ENIGMA Consortium PGC-PTSD, Knowles, J. A., Hibar, D. P., Nievergelt, C. M., Koenen, K. C., Liberzon, I., Ressler, K. J., Medland, S. E., Morey, R. A., Thompson, P. M., & Stein, D. J. (2019). Concordance of genetic variation that increases risk for anxiety disorders and posttraumatic stress disorders and that influences their underlying neurocircuitry. Journal of affective disorders, 245, 885–896. https://doi.org/10.1016/j.jad.2018.11.082

[3] Gottschalk, M. G., & Domschke, K. (2017). Genetics of generalized anxiety disorder and related traits. Dialogues in clinical neuroscience, 19(2), 159–168. https://doi.org/10.31887/DCNS.2017.19.2/kdomschke

[4] Domschke, K., & Maron, E. (2013). Genetic factors in anxiety disorders. Modern trends in pharmacopsychiatry, 29, 24–46. https://doi.org/10.1159/000351932

[5] DiCorato, A. (2024). Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nature Genetics. DOI: 10.1038/s41588-024-01707-9.

[6] Fox-Gaffney, K. A., & Singh, P. K. (2025). Genetic and Environmental Influences on Anxiety Disorders: A Systematic Review of Their Onset and Development. Cureus, 17(3), e80157. https://doi.org/10.7759/cureus.80157

[7] Dominique J. (2007). Glucocorticoid-induced reduction of traumatic memories: implications for the treatment of PTSD. Progress in Brain Research; Elsevier. Pages 239-247. https://doi.org/10.1016/S0079-6123(07)67017-4.

Health/Hot topics

Neurological Imprints: Adolescent Addiction

Posted on April 2, 2026 by cborrud / 0 Comment

Cover Image Artstract designed by Cayley Borrud with the use of ChatGPT

Adolescence is often a rocky time full of firsts and figuring out identity. But what if in that volatile time, a teen decides to try vaping? It’s wrapped in colorful packaging, advertised to youth and the most used Tabacco product in youths [4]. How bad could just trying it be?

Image sourced from Alamy

The Neuroscience of Addiction

E-cigarettes are designed to make the person crave more. It alters the brains reward center through the disruption of metabotropic glutamate receptors (mGluRs). The paper by Mozafari et. al explains how mGluRs are very involved in addiction. The absence of this vital receptor leads to increased glutamate. Glutamate is a neurotransmitter that drives the drug seeking behavior. It strengthens the circuits in the brain which would normally be a good thing however, the circuits that it is strengthening in this case would be the memories of the substance [1].

The brain could have structural changes such as increased dendritic spine density in the prefrontal cortex that can contribute to the formation of the ‘memory’ of vaping [3]. This is particularly a problem because it can make adolescents more likely to develop more addictions due to that rewiring of the brain. It also makes it much harder to stop their addiction since a non-fully developed brain is more likely to develop permanent addictions that follow them well into their adulthood [5].

Image sourced from Baker Institute

What started as curiosity driven experimentation would now be an addiction. This addiction can happen faster in teens than adults and it can greatly affect attention, impulse control and anxiety. The brain chemistry of the developing brain can change so rapidly that before nicotine is even consumed daily, withdrawal symptoms can appear [4].

The brain circuits involved in the development of addictions are constantly changing during adolescence which can lead to more risky behaviors [5]. What started as experimenting with e-cigarettes can quickly turn into experimentation and abuse of drugs and alcohol.

In adolescence, the dopamine signaling pathway is particularly sensitive and this pathway doesn’t reach full maturity until after adolescence [2]. This means that when a substance such as nicotine is taken, there would be a stronger reinforcement and quicker learned addictive behaviors [5]. The teenage brain is creating associations that vaping means reward and that association is the memory that’s hard to forget.

Now, let’s say, that teenager was able to stop vaping with the help of therapy and family support. That addictive pathway is still there and ready to be activated in moments of vulnerability or even from environmental cues associated with that nicotine memory [4]. Their brain is permanently changed. Unfortunately, adolescents don’t generally know that their actions are permantely changing their brain.

Image sourced from The American Psychiatric Association

Teens are biologically primed to become addicted therefore there needs to be more awareness and actions taken to protect them. There needs to be an urgency to protect teens before experimentation turns into long term consequences. By prioritizing prevention, regulation, and education, we can help protect developing brains during one of the most vulnerable stages of life.

Sources:

Mozafari, R., Karimi-Haghighi, S., Fattahi, M., Kalivas, P., & Haghparast, A. (2023). A review on the role of metabotropic glutamate receptors in neuroplasticity following psychostimulant use disorder.Progress in Neuro-Psychopharmacology & Biological Psychiatry, 124, 110735. https://doi.org/10.1016/j.pnpbp.2023.110735
Suri, D., Zanni, G., Mahadevia, D., Chuhma, N., Saha, R., Spivack, S., Pini, N., Stevens, G. S., Ziolkowski-Blake, A., Simpson, E. H., Balsam, P., Rayport, S., & Ansorge, M. S. (2023). Dopamine transporter blockade during adolescence increases adult dopamine function, impulsivity, and aggression.Molecular Psychiatry, 28(8), 3512–3523. https://doi.org/10.1038/s41380-023-02194-w
Brown, R. W., & Kolb, B. (2001). Nicotine sensitization increases dendritic length and spine density in the nucleus accumbens and cingulate cortex.Brain Research, 899(1–2), 94–100. https://doi.org/10.1016/s0006-8993(01)02201-6
(2024, October 17).E-cigarette use among youth. Smoking and Tobacco Use. https://www.cdc.gov/tobacco/e-cigarettes/youth.html
Adolescents are neurologically more vulnerable to addictions | yale news. (2003, June 18). https://news.yale.edu/2003/06/18/adolescents-are-neurologically-more-vulnerable-addictions