Written By: Vanessa Rosario Edited By: Evelyn Castro Introduction Going into my undergraduate studies as a Neuroscience major, I was intrigued by brain chemistry and shifts in mental disorders. Learning about what’s going on in my head became a major catalyst in studying mental illness from a biological perspective. My aspirations in pursuing a neuroscience career with specializations in mental health motivated me to research this topic. Depression and depressive disorders are usually viewed purely as a psychological concept, yet neurobiology plays a role in depression via its physical brain alterations. This paper explores the complex neurobiological landscapes in Major Depressive Disorder (MDD), Depression, and other depressive disorders. Macro-Level Shifts in Brain Activity Analyzing neural networks from contemporary research shows that depression is a profound failure of context-dependent adaptation. In their meta-analysis, Palmert et al. (2015) show that macro-level neurofunctional alterations in MDD depend on the specific task at hand. In simpler terms, Depression changes how the brain responds depending on what a person is doing. Interestingly, the researchers discovered that the brain has a split between thinking and emotional tasks. When the brain processes thinking tasks, such as trying to focus or remember things, its executive control networks conflict and fail to activate properly. Executive control networks are a large-scale system of brain regions that work in unison to manage complex thinking. In detail, the brain goes through a systematic failure to recruit executive control networks. The brain essentially functions beyond its limits to process basic cognitive tasks. Conversely, when the brain processes emotional tasks, such as processing feelings and stress, the amygdala and other emotional centers become dysregulated. Depression causes a whole networking problem as the brain loses its ability to function and switch gears between thinking and feeling. The neurobiology of depression can be described as a dynamic inability to modulate macro-level networks. The Evolution of Depression Neuroscience For decades, the mainstream belief about depression was simply reduced to a “chemical imbalance, " with those arguing that depression was a lack of essential neurotransmitters in the brain. To counter this thinking, Alexander Kaltenboeck and Catherine Harmer (2018) discuss in their review that our biological understanding and definition of the disorder have evolved from this streamlined view. We now recognize depression as a complex network disease and a sort of failure in synaptic plasticity. Synaptic plasticity plays a role in allowing us to think, feel, and move by passing chemical and electrical signals through synapses. In the modern day, the traditional pills that alter brain chemistry have been assisted by various interventions such as neurostimulation and other novel therapies. These new interventions are aimed at reducing neuroinflammation, which lessens the immune response in the brain and spinal cord. Neuroinflammation is simply the inflammation and swelling of the brain and spinal cord. Minimizing neuroinflammation can stop chemical attacks that alter an individual’s mood and energy and, in this context, affect depression’s emotional, reward, and memory centers. The evolution of depression neuroscience has completely transformed from the mainstream definition of chemical imbalances to a complex, network-based, explicit understanding. We are now using this new network of inflammatory science to spot severe depression in individuals. Molecular Biomarkers and Clinical Severity The network-based model is actively changing how we can identify severe depression in patients. The 2023 study by Li et al. (2023) researched how patients with Major Depressive Disorder had elevated levels of the protein called mature Brain-Derived Neurotrophic Factor (mBDNF). The mBDNF is a protein responsible for synaptic plasticity, fostering brain cell survival, growth, and adaptation. Research found that patients with the highest levels of suicidal ideation had elevated plasma levels of mBDNF and increasingly high inflammatory levels. This evidence suggests that psychological and inflammatory strain triggers the brain to a compensatory distress signal, which overwhelms the system with mBDNF as a physical attempt to protect and repair its failing networks. Depression through the biological lens uncovers physical pain inside. Conclusion Depression is a far more complex subject than a shortage of neurotransmitters like serotonin; it’s a dynamic network failure in the brain. The brain essentially struggles to switch between thinking and emotional regulation due to its aggravated neuroinflammation. A chronically hyperactive immune response in the central nervous system floods the brain with inflammatory chemicals that disrupt communication throughout the brain. The constant inflammatory stress forces the brain into an uphill battle to maintain baseline mood and cognitive function. Fortunately, there is hope and alternative methods to help manage depressive symptoms. When we reflect on how the brain floods itself with mBNDF counterparts to counteract inflammatory damage, we can recognize from a biological perspective that our brain is trying to fight back to heal itself. Depression is a psychological battle, but our brains are structurally made to adapt and rewire. By introducing tools to calm neuroinflammation and fix network communications, science is actively figuring out how to alleviate the brain’s broken circuits from depression. References Kaltenboeck, A., & Harmer, C. (2018). The neuroscience of depressive disorders: A brief review of the past and some considerations about the future. Brain and Neuroscience Advances, 2, 1–12. doi.org [1] Li, H., Zhao, M., Jiang, C., Zhao, H., Wu, C., Li, Y., Zhang, S., Xu, P., Mou, T., Xu, Y., & Huang, M. (2023). Elevated plasma levels of mature brain-derived neurotrophic factor in major depressive disorder patients with higher suicidal ideation. Journal of Clinical Medicine, 12(17), 5462. doi.org Palmer, S. M., Crewther, S. G., & Carey, L. M. (2015). A meta-analysis of changes in brain activity in clinical depression. Frontiers in Human Neuroscience, 8, 1045. doi.org [1]

Written By: Raquel Castro Ever wondered about ways to prevent or slow down the development of dementia due to a genetic predisposition, environmental factors, or simply due to a general concern? Recent research finds that having a healthy gut can also support a healthy brain, which may contribute to preventing dementia. Neurodegeneration is known as the death of brain cells, which is caused by neurodegenerative diseases (Przedborski et al., 2003). Neurodegenerative diseases commonly appear amongst older individuals depending on environmental or genetic factors. Neurodegenerative diseases include Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD), and Amyotrophic Lateral Sclerosis (ALS). The purpose of this article is to further dive into the benefits of probiotic supplementation, as a healthy brain is strongly associated with a healthy gut and can prevent further development of the specific neurodegenerative disorder known as Parkinson’s Disease (PD). What is Parkinson’s Disease (PD)? Parkinson’s Disease (PD) is a neurodegenerative disorder that is commonly associated with tremors, impaired gait, general slowness of motor movements, and limb stiffness. Additionally, non-motor symptoms associated with PD are: depression, anxiety, orthostatic hypotension, apathy, sleep disorders, hallucinations, and a loss of a sense of smell. Constipation, nausea, vomiting, delayed gastric emptying, hypersalivation, dysphagia, and gastroparesis are found to be associated with the symptoms of PD patients (Parkinson’s Foundation & Hsieh et al., 2020). What Are Probiotics? If you are unfamiliar with what probiotics are, chances are you have consumed them before! Probiotics are commonly found in yogurt, which contains healthy bacteria that support digestive health. It has been found that individuals with neurodegenerative diseases are more likely to have a lower number of healthy gut bacteria compared to healthy-brained individuals (Kesika et al., 2021, as cited in Xiang et al., 2022). Taking precautions like consuming probiotic supplements that contain the probiotic called Lactobacillus Plantarum can promote gut-brain health, as seen in Figures 1 and 2. Figure 1: Neuralli® MP – PS128 probiotic medical food ; Figure 2: BIOptimizers – Probiotic Breakthrough How May Probiotics Prevent Parkinson’s? Relevant research suggests that the progression of neurodegenerative diseases may be delayed by probiotic supplementation. Metabolites like γ-aminobutyric acid, commonly known as GABA, serotonin (5-HT), and dopamine work together to support the overall functioning and regulation of mood and cognitive functions (Clark et al., 2014; Dinan & Cryan, 2017, as cited in Xiang et al., 2022). PD is strongly associated with dopamine production and the gut microbiome. It has been found that certain probiotics such as Lactobacillus Plantarum PS128 contribute specifically to the production of dopamine neurons (Lu et al., 2021). Hsieh et al. (2020) discuss how there is a relationship between the brain and gastrointestinal (GI) dysfunctions. The researchers experimented on 10 genetically altered mice called MitoPark mice to test whether probiotic supplementation may support dopamine production and prevent the further deterioration of dopamine neurons. In this study, the researchers used a probiotic-food mixture consisting of six strains, including Lactobacillus Plantarum LP28 and Lactobacillus rhamnosus. This probiotic mixture was administered daily throughout a span of 24 weeks to the experimental group. The control group was given their regimen diet without including the probiotic mixture. To test if PD symptoms improved, biweekly, the mice would be required to participate in rotarod, balance beam, and gait analysis tests as shown in Figure 3. Figure 3: The experimental design to test the PD mice As a result, the researchers discovered that there was a significant improvement in the general motor symptoms and cognition presented in the treated PD mice, as shown in Figure 4. This resulted in the finding that the supplementation of probiotics resulted in long-term positive effects and slower neurodegeneration (Hsieh et al., 2020). Figure 4: There was an increased cell number found in the brains of the treated PD mice compared to the untreated PD mice. Not only has the supplementation of probiotics for treating PD been tested on mice, but it has also been tested on humans and showed significant long-term effects. Xiang et al. (2022) conducted a meta-analysis to determine whether neurodegenerative diseases, including PD, can effectively be treated among humans. The researchers searched for every potential combination of research papers including probiotics, cognitive functioning, and PD. These findings resulted in the researchers concluding that there was a significant cognitive difference and improvement in the treated individuals with a neurodegenerative disease compared to the untreated individuals. Improvements in gene expression, biochemical indicators, and clinical features also resulted from this, as shown in Figure 5. Figure 5: Primary findings of administering probiotics to patients with PD (Created in https://BioRender.com). Conclusion Neurodegeneration is a very unfortunate occurrence that affects people of a variety of backgrounds. Finding effective means to treat Parkinson’s Disease in any shape or form would be beneficial to every affected individual. Incorporating the supplementation of probiotics such as Neuralli® MP – PS128 probiotic medical food and BIOptimizers – Probiotic Breakthrough into one’s diet could help prevent the development of neurodegeneration. Further research must be conducted on this, as there has primarily been research on rodents compared to humans. The neuroscientific field is still developing, with hopes that advancements in brain health will become apparent. Works Cited Hsieh, T.-H., Kuo, C.-W., Hsieh, K.-H., Shieh, M.-J., Peng, C.-W., Chen, Y.-C., Chang, Y.-L., Huang, Y.-Z., Chen, C.-C., Chang, P.-K., Chen, K.-Y., & Chen, H.-Y. (2020). Probiotics alleviate the progressive deterioration of motor functions in a mouse model of parkinson’s disease. Brain Sciences, 10(4), 206. https://doi.org/10.3390/brainsci10040206 Lu, C.-S., Chang, H.-C., Weng, Y.-H., Chen, C.-C., Kuo, Y.-S., & Tsai, Y.-C. (2021). The add-on effect of lactobacillus plantarum PS128 in patients with parkinson’s disease: A pilot study. Frontiers in Nutrition, 8. https://doi.org/10.3389/fnut.2021.650053 Neurodegenerative diseases. Cleveland Clinic. (2026, April 14). https://my.clevelandclinic.org/health/diseases/24976-neurodegenerative-diseases What is parkinson’s? Parkinson’s Foundation. (n.d.). https://www.parkinson.org/understanding-parkinsons/what-is-parkinsons Xiang S, Ji J-L, Li S, Cao X-P, Xu W, Tan L and Tan C-C (2022) Efficacy and Safety of Probiotics for the Treatment of Alzheimer's Disease, Mild Cognitive Impairment, and Parkinson's Disease: A Systematic Review and Meta-Analysis. Front. Aging Neurosci. 14:730036. doi: 10.3389/fnagi.2022.730036

Written by: Jacinda Taggett Edited by: Kierstin Burt Scrolling, scrolling, scrolling. Endless scrolling. One or two seconds per image, video, or caption, then onto the next. I had grown up right when technology began its boom in the early-to-mid 2000s. In elementary school I loved watching movies in my free time. In middle school it was YouTube videos. High school began the Vine era. Finally, the latest trend of TikTok videos and Instagram Reels has plagued every social media platform possible. I think science communicators so far have done a good job at saying “too much dopamine is bad! We’re hurting our attention spans!” But does anyone really know why? If you asked someone why they spend less than one second on a TikTok video, they’ll likely just jokingly respond “my dopamine receptors are fried.” I guess that’s true in some sense… What is “binge-scrolling” really? Not to be confused with “doomscrolling,” the term binge-scrolling refers to the act of engaging in compulsive viewing of short-form digital content over extended, unplanned, periods of time. Think of platforms such as TikTok and Instagram that have now introduced the “infinite scroll” of their videos and feeds. You open up your phone to check a notification, then suddenly it’s been 3 hours later and you’ve been scrolling through your social media timelines. Why does this happen? Neuroscience of Reward and Uncertainty In order to understand binge-scrolling, you have to look into the brain regions known for reward and uncertainty– the dopamine pathways. Primarily we are looking at the mesolimbic pathway, which allows for motivation, action, and obviously reward! Whenever you engage with a funny, entertaining, or interesting piece of social media content, dopamine from the ventral tegmental area (VTA) projects to the ventral striatum. This process allows you to feel extra motivated and excited for the next piece of media. Then when you decide to scroll to the next video or infographic, your brain sends dopamine to the prefrontal cortex through the mesocortical pathway– essential for the evaluation of consequences. In decision-making psychology, we have the term “reward prediction error” that alludes to the act of dopaminergic activity from certain events, such as TikTok scrolling, influencing our behavior later on. It goes as follows: Unexpected Reward: You get a dopamine “boost” from watching a video that you were not intending to find amusing. Expected Reward: You scroll expecting a funny or interesting video to follow, so your brain increases dopamine in anticipation rather than the actual reward. Negative Prediction Error: You continue to scroll through your feed, and therefore get the dopaminergic pleasure from scrolling– but the dopamine activity in your brain decreases after experiencing a sad or disheartening video. Through this paradigm, social media has been able to hijack our reward systems by alternating between happy, sad, neutral videos. You always get the boost from scrolling, and the negative prediction error from videos you disliked are keeping you wanting more! Consequences and implications This phenomenon of binge-scrolling has detrimental implications on the mental wellbeing of our current and future generations. With every instance of instant scrolling, you are eliciting quick, repetitive, and rewarding behaviors, leading to a hijacked version of the dopaminergic regions of the brain. Thus, individuals that are binge-scrolling are in fact developing addictive behaviors and will therefore have similar neurological consequences (Ogun, 2025). The anticipation of the next scroll is more exciting and rewarding than the actual content itself (Shivam et al., 2023) leading this experience to be excessive forms of short dopamine bursts. Neurologically, this has implications for the dopamine receptors in our brain to become less effective primarily in cognitive functioning. We expect to see in the long-term poorer memory (Nguyen et al., 2025), weakened attention spans (Atienza et al., 2025), instability with mood and anxiety (Yousef et al., 2025), and the inability to perceive time (Fung et al., 2021). Future directions In terms of early intervention, there should be more emphasis in our communities about long-term, low-dopamine activities. This can include reading, going outside, and engaging in social interactions. Policy makers and public health professionals need to advocate for better social media practices, as the introduction of short-form content has made this phenomenon exponentially worse in conjunction with the natural progression of social media reliance. References Atienza, Justin & Perez, Ynnos Lincoln & Quinto, Loraine Mae. (2025). A Mixed Methods Study on Binge-Scrolling Behavior, Attention, and Memory Retention in Young Adults. 10.13140/RG.2.2.27820.53126. Ogun, D. (2025). Neurobiological and behavioral correlates of excessive social media use in adolescents: Impact of social media use on adolescents. Journal of Surgery and Medicine, 9(10), 199–206. https://doi.org/10.28982/josam.8211 Fung, B. J., Sutlief, E., & Hussain Shuler, M. G. (2021). Dopamine and the interdependency of time perception and reward. Neuroscience and biobehavioral reviews, 125, 380–391. https://doi.org/10.1016/j.neubiorev.2021.02.030 Nguyen, L., Walters, J., Paul, S., Monreal Ijurco, S., Rainey, G. E., Parekh, N., Blair, G., & Darrah, M. (2025). Feeds, feelings, and focus: A systematic review and meta-analysis examining the cognitive and mental health correlates of short-form video use.Psychological Bulletin, 151(9), 1125–1146. https://doi.org/10.1037/bul0000498 Shivam Kalhan, Garrido, M. I., Hester, R., & A. David Redish. (2023). Reward prediction-errors weighted by cue salience produces addictive behaviours in simulations, with asymmetrical learning and steeper delay discounting. Neural Networks, 168, 631–651. https://doi.org/10.1016/j.neunet.2023.09.032 Yousef, A. M. F., Alshamy, A., Tlili, A., & Metwally, A. H. S. (2025). Demystifying the New Dilemma of Brain Rot in the Digital Era: A Review. Brain sciences, 15(3), 283. https://doi.org/10.3390/brainsci15030283

Malleeka Suy Neuroepigenetics…the word itself is a mouthful, but it doesn’t have to be a brainful. You probably know what “neuro” indicates, but what is “epigenetics”? Suppression and Amplification Contrary to popular belief, your genetics are not as static as you may think. Where you live and your life experiences can change how your genes are expressed. This is the field of epigenetics. These changes can express more or less of your genes, but the gene sequences themselves are not changed. These changes are achieved in many ways but generally involve the addition or removal of different chemical groups on genes with the help of certain proteins. DNA methylation, for example, utilizes enzymes called DNA methyltransferases (Dnmts) to attach a methyl group, or three hydrogens attached to a carbon, to DNA nucleotides (the building blocks of DNA) to “turn off” genes. Conversely, the process of histone acetylation “turns on” genes by attaching an acetyl group to a histone, the protein around which DNA is wound like a yo-yo. This “loosens” the DNA from the histone, allowing easier access for proteins and other factors to attach. Both methylation and acetylation are also reversible. Think of these processes as a light switch on our DNA! DNA methylation and histone acetylation are examples of epigenetic modifications. Methyl groups block gene readers, such as RNA Polymerase II (RNAPII), and other factors from binding to DNA and expressing genes. Acetyl groups “loosen” DNA and allow RNAPII and factors better access. Made on BioRender. In the Brain Changing the expression of certain genes alters the amount of proteins being produced, which can affect how certain parts of our body function. Neuroepigenetics specifically focuses on how epigenetic modifications shape the development and functioning of the human nervous system and brain. The development of the human central nervous system depends highly on DNA methylation and demethylation, or the removal of methyl groups from DNA. The foundations of the central nervous system are neurons, which are cells that signal your brain to think and move, and astrocytes, star-shaped cells that nourish neurons and support brain function (read here for more information on neurons, or here for more information on astrocytes). Both of these cells evolve from starter cells called neural progenitor cells—these NPCs first develop into neurons, then switch to develop into astrocytes (Qian et al, 2000; Sauvageot and Stiles, 2002). This switch is controlled by DNA methylation and demethylation of the glial fibrillary acidic protein (Gfap) gene via different Dnmts (Teter et al, 1994). Methylation of Gfap via Dnmt1 results in repressed expression, which correlates with neuron development (Teter et al, 1996; Takizawa et al, 2001; Fan et al, 2005). As you may have guessed, demethylation of Gfap thus corresponds with the development of astrocytes (Teter et al, 1996). Schematic of how methylation of Gfap plays a role in the development of neurons and astrocytes from neural progenitor cells (NPCs). Methylation of Gfap produces neurons, while demethylation of Gfap produces astrocytes. Made in BioRender. Methylation also affects learning and memory formation. Protein phosphatase 1 (PP1) is a gene that suppresses learning and memory; methylating PP1, therefore producing less PP1, allows for better memory maintenance, improves the efficacy of associative training, and enhances long-term potentiation (LTP), or the process of strengthening connections being made across brain cells (Genoux et al., 2002; Jouvenceau et al., 2006; Blitzere et al., 1998; Khan Academy). Subsequently, demethylation of the memory-promoting gene reelin suggests better memory maintenance and enhanced LTP (Miller and Sweatt, 2007). Methylation studies could thus play a huge role in memory retention, combatting aging and cognitive disorders. Too Much or Too Little? Neuroepigenetics acts like the checks and balances of the brain, so errors can cause a cascade of serious complications. Too little methylation where methylation should occur can cause severe cognitive lapses and developmental defects. Mutations in the Dnmt1 gene, for example, can cause improper folding of the Dnmt1 protein, leading to decreased activity, faulty DNA binding, and imbalanced methylation levels, where certain areas are more methylated than others (Klein et al., 2011). Certain mutations within Dnmt1 have also been linked to hereditary, sensory, and autonomic neuropathy type 1 (HSAN1), a neurodegenerative disease that presents with dementia, loss of hearing, and loss of sensation in the feet and hands (Klein et al., 20111). Similarly, mutations in the Dnmt3a gene cause Tatton-Brown-Rahman Syndrome (TBRS), a rare overgrowth syndrome characterized by tall stature, an enlarged head, intellectual disabilities, and distinct facial features (Tibben and Rothbart, 2025; TBRS Community). But too much methylation can pose problems as well: An increase in Dnmt1 and Dnmt3a expression is linked to human temporal lobe epilepsy (TLE) and recurrent seizures (Zhu et al., 2012). Varied acetylation levels have also been associated with Alzheimer’s disease (AD), a common neurodegenerative disease that results in progressive memory loss. Plaques and tangles of a protein called tau in specific brain regions increase the risk of developing AD (Mattson, 2004; Ballatore et al., 2007). While histone acetylases add acetyl groups to histones to increase gene expression, histone deacetylases (HDACs) remove them, resulting in tighter DNA packaging around histones and reduced gene expression. In postmortem brain samples from AD patients, an increased level of HDAC6 correlated with an increase in tau levels (Cooke et al., 2012). Methylation and acetylation, and their opposites, are thus crucial for healthy development and function. Schematic comparing a healthy brain to one with Alzheimer’s. In healthy brains, tau proteins stabilize microtubules, which act as “train tracks” for nutrient transport and neuronal communication. In Alzheimer’s brains, tau protein tangles form neurofibrillary tangles, collapsing the “tracks” and destabilizing the microtubules. Made in BioRender. The field of neuroepigenetics provides an exciting behind-the-scenes look at the development of the brain. Despite all that we know about the epigenetic mechanisms behind a healthy brain, it is not an easy fix. Epigenetics is a hotspot for hopes of treating diseases such as Alzheimer’s and neurological problems associated with aging. 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by Tate Madison & Anthony Thomas Abstract Social feedback is widely prevalent in college settings, often with negative implications of students’ sense of self, confidence, and mental health. This study aimed to explore the impact of perceived relationship readiness, alongside gender differences, on self-esteem. We hypothesized that participants told they were ready for a relationship would show higher self-esteem than those told they were not; and that men would show higher self-esteem than women and nonbinary/prefer not to say groups. This study consisted of two self-esteem evaluations and a relationship readiness condition. We analyzed data from 51 undergraduate participants, with the majority being female. Our hypotheses were tested with a two-way ANOVA. Perceived relationship readiness did not predict self-esteem in either men or women. Gender did not predict their self-esteem scores. Additionally, their interaction did not predict self-esteem. These results were found to be inconsistent with our hypotheses. The pattern of our results were trending towards significance, despite the low sample size. A main limitation of our study was low sample size and lack of participant diversity. Future research could investigate the implications of social feedback in dating on the mental health and psychological well-being of college students. Gender Differences in Perceived Relationship Readiness on Self-Esteem College is often a student's first real experience with dating and relationships. People often receive social feedback from their friends and possible romantic partners. Social feedback may have both positive and negative impacts on self-esteem, well-being, and social relationships. This study investigated the gender differences within the impact of perceived relationship readiness on self-esteem. We aimed to explore the impacts of social feedback in romantic relationship settings on self-worth and self-evaluation. Perceived Relationship Readiness Perceived relationship readiness in this study is the assumption from an outside source that someone is or is not ready for a relationship. Prior research suggests that social feedback or interactions can be tied to self-esteem, psychological well-being, and outcomes in relationships. Changes in self-esteem from social acceptance or rejection have been shown to guide social behavior (van Schie et al., 2023). This study found that increases in self-esteem due to positive evaluation was associated with increased social learning, but decreased non-social learning. A decrease in self-esteem due to negative evaluation was associated with decreased non-social learning as well. They concluded that increases in self-esteem due to positive evaluation can induce a shift in the inclination to use social versus non-social information. Similarly, research has shown that individuals with low self-esteem suffer from poor relationship well-being and benefit less from positive social feedback (Hoplock et al., 2019). In this study, participants with low self-esteem felt undeserving of positive social feedback, which undermined their relationship well-being. Self-perceptions of readiness have also been found to correlate between relationship status and psychological well-being. Tan et al. (2023) found that coupled individuals higher in commitment readiness reported greater levels of well-being than single individuals, whereas coupled individuals lower in commitment readiness reported lower levels compared to their single counterparts. Self-reported commitment readiness in this study was shown to impact overall psychological well-being, with differences in coupled versus single individuals. These findings suggest that social feedback, and especially that related to social feedback within relationships, may have a significant impact on self-esteem and overall well-being. Gender Gender differences in this study is examined as a factor influencing individuals’ responses to social feedback and self-evaluation. Prior research has suggested that men and women respond differently to social interactions and these have varying implications on their self-esteem. Ratliff (2013) found that men’s self-esteem was negatively impacted by their romantic partner’s success, and furthermore that their self-esteem was negatively impacted by thinking about a romantic partner’s success both when the success is and is not relative. Women’s implicit self-esteem was unaffected by partner performance. The gender differences presented in this study have implications for understanding social comparison in romantic relationships. Additionally, Muratori et al., (2026) found gender differences in self-esteem, narcissism, and externalizing problems in childhood. In boys, narcissism was positively associated with externalizing problems only among those with high self-esteem, and oppositely only in girls with low self-esteem. These findings indicate that gender plays an important role in how individuals respond to social feedback and interact with each other. Self Esteem Self-esteem in this study reflects how individuals evaluate their self-worth in response to social feedback and social interactions. Research has shown that social relationships and self-esteem reciprocally predict each other over time (Harris & Orth, 2020). The effect of self-esteem on relationships slightly varied, being stronger for general relationships than for specific partners and stronger for self-reported than for informant-reported relationship characteristics. This supports the influence of social relationships on self-esteem; and emphasizes that the link between social relationships and self-esteem is consistently reciprocal and reflects a positive feedback loop between the two. Social comparison and interpersonal relationships have also been shown to have implications on self-esteem (Mann & Blumberg, 2022). Feared possible selves are an imagined, unwanted version of who you might become. This study found the relationship between gender and feared possible selves to be significant; women reported more feared possible selves related to interpersonal relationships than men. These findings suggest that self-esteem is dynamic and highly influenced by social feedback. Study overview This study aimed to address the gender differences within the impact of perceived relationship readiness on self-esteem for which there is no existing literature yet. Participants completed a survey containing two self-esteem evaluations and a relationship readiness condition. The conditions read short blurbs stating the participant is either ready for a relationship and positive affirmations or that the participant is not ready and encourage them to take time to reflect prior to pursuing one. Their self-esteem was tested before and after the readiness conditions, being scored in similar manners. We hypothesized that participants who were told they were ready for a relationship would have higher self-esteem than participants who were told they were not ready for a relationship. Concurrently we also hypothesised that men in both relationship readiness conditions would have higher self-esteem than women & nonbinary/prefer not to say groups. We expect men in the readiness condition to have the highest self-esteem and women in the no-readiness condition to have the lowest self-esteem. Methods Participants We had 64 total undergraduate students who participated in our survey. We excluded 13 participants due to outside circumstances such as 1 participant not filling out their age, as well as 9 participants not filling out the entirety of the survey. We also cut the 3 non-binary/prefer not to say participants from our data, due to the fact that their data wasn’t sufficient enough to use.The remaining 51 participants are undergraduate students who range from ages 19-23. The majority of our participants were women, women being 71% and men being 29%. With our participants, 64.71% were Caucasian, 13.73% were Asian, 11.76% were African American, 7.84% were Multiethinic, and 1.96% were Hispanic, Latino, or Spanish Origin. There were 4 that self described their race. Most participants were Psychology majors, but we also had participants that were Engineering majors, Communications majors, and Economics majors. Design This research has two independent variables and one dependent variable for a 2x2 ANOVA study design. The first independent variable was perceived relationship readiness. The second independent variable was gender. The dependent variable for our study was self-esteem. Procedure Participants who consented to participate in the study began to answer demographic questions. Demographics consisted of age, gender, race/ethnicity, and major. Participants first encountered the pre-test. They responded to 18 questions in regard to relationships, friendships, emotional intelligence/maturity, and self-esteem. The self-esteem questions came from the Rosenberg Self-Esteem Scale (Rosenberg, 1979). Participants responded to all 10 of the questions in order, with filler questions in between about relationships, friendships, and emotional intelligence/maturity. The pre-test served as what they believed to decide their relationship readiness. After completing the pre-test, participants were randomly assigned to a readiness condition. Participants in the Readiness Condition read a short blurb saying their responses showed they’re ready for a relationship and relevant positive affirmations. Participants in the ‘Not Ready’ condition read a short blurb saying that, based on their responses, they do not seem ready for a relationship, and encouraged them to take their time for reflection and growth. Following the readiness conditions, participants completed a post-test. The post test consisted of a shortened version of the Rosenberg Self-Esteem scale. It was six questions in randomized order. Ethical Process Participants read the conditions of consent, and either selected “I consent” or “I do not consent”. Participants who did not consent were taken to the end of the survey. At the end of the questionnaire, participants were taken to a debriefing page that thanked the participants, informed them that the condition they were assigned to was random and not representative of their actual chosen responses, and had a short summary of our study purpose. Materials Pre-test self-esteem This was an 18-item questionnaire using the 10-item Rosenberg self-esteem scale (Rosenberg, 1979) which included statements such as :“ 1. On the whole, I am satisfied with myself.”. To avoid suspicion, filler questions were also added with statements such as: “I have a good relationship with my parents”. They were then asked to rank each statement from 1 (strongly agree) to 4 (strongly disagree). To see full scale, go to Appendix A. Relationship Readiness Conditions Participants either encountered the relationship ready condition or the not ready for relationship condition, randomly assigned after the pre-test. This was done to ensure a clear difference in measuring self-esteem before and after the condition. Readiness Condition. “Based on your responses, you seem to be ready for a relationship. You seem emotionally mature, as well as open to maintaining and developing healthy relationships. Good luck out there, hope you find the one!” Not Ready Condition. “Based on your responses, you do not seem ready for a relationship. You should try to do some reflection and growth before attempting to pursue a relationship. Take your time!” Post-test self-esteem This was a shortened questionnaire of the 10 item Rosenberg self-esteem scale (Rosenberg, 1979) which included statements such as: “I wish I could have more respect for myself.” To further decrease suspicion, we used a shortened questionnaire in a randomized order. They were then asked to rank each statement from 1 (strongly agree) to 4 (strongly disagree). To see full scale, go to Appendix B. Results Analysis techniques For this study, we completed a 2 x 2 ANOVA to understand the effects of perceived relationship readiness on self-esteem with gender as a subject variable. In addition, we calculated two Cronbach’s alphas to assess the reliability of our pre and post-test (Rosenberg Self-Esteem scale) scales. We found the Cronbach’s alpha for both pre-test results (ɑ = 0.86) and post-test results (ɑ = 0.78). Both scales had a high score above ɑ = .75 and therefore had good reliability. Self-Esteem We hypothesized that men would have higher self-esteem than women. Concurrently, we hypothesized that participants in the ready condition would have higher self-esteem than participants in the no-readiness condition. We expected men in the readiness condition to have the highest self-esteem and women in the no-readiness condition to have the lowest self-esteem. To measure the effect of perceived readiness condition on self-esteem we calculated the difference between self-esteem scores before receiving feedback and after. These hypotheses were tested with a two-way ANOVA predicting self-esteem from gender and relationship readiness condition. Gender did not significantly predict self-esteem F (1,47) = 0.74, p = 0.4. Additionally, the not ready condition did not predict self-esteem Readiness Condition F(1,47) = 2.13, p = 0.15. The not ready condition and gender did not interact to predict self-esteem F(1,47) = 0.26, p = 0.61. These results were inconsistent with our hypothesis. For the visual results, see Figure 1. Figure 1 - Self-Esteem Difference Figure 1. Mean differences in self-esteem scores across gender and readiness conditions. The two-way ANOVA revealed no significant main effects for gender or readiness condition, and no significant interaction between the readiness condition and gender. Discussion Over the course of this study, we examined gender differences within the effects of perceived relationship readiness on self-esteem. We originally hypothesized that participants in the ready condition would have a higher self-esteem than participants in the not ready condition. Additionally, we hypothesized that male participants would have higher self-esteem than their female counterparts. Finally, we hypothesized that male participants in the ready condition would have the highest self-esteem, while female participants in the not ready condition would have the lowest self-esteem. Overall, our hypotheses were inconsistent with our results, with none showing significance, with the perceived readiness condition not predicting self-esteem in either men or women. Additionally, the gender of participants did not predict their self-esteem scores, consistent with the null hypothesis. Perceived relationship readiness condition and gender did not separately, nor did their interaction, predict self-esteem. Limitations One limitation of this study is its small sample size. We were only able to analyze data from 51 participants. With such a small sample, it is difficult to accurately identify significant relationships in our data. Within this sample we had 15 male participants and 36 female participants. This is a drastic difference in gendered participants. With a larger sample size and a more even gender distribution within our participant sample, this would likely increase the accuracy of our results. Additionally, there were issues around data collection which further lead to a reduced participant sample size. For example, while 64 participants originally took the survey, we had to exclude 13 participants’ data, mainly due to incompleteness of the survey. We also had to discard 3 non-binary/prefer not to say participants, due to their number not being sufficient enough for use and analysis. Our results were trending towards significance, and this study redone with a larger population could possibly show significance. Another limitation of this study is its online format. Participants may have less of an emotional reaction to perceived relationship readiness given to them by a computer algorithm, compared to a person giving them feedback face-to-face. Participants may have more care receiving feedback from a person than a computer. Additionally, they may be more likely to believe the credibility of their social feedback if they think it’s from a person assessing them. Participants may not have believed their readiness condition and that contributed to the lack of change in their self esteem. Future Research Future research within this topic could investigate the impact of other social feedback, especially surrounding romantic relationships, on self-esteem, but given from a real person, as many people may be indifferent to a computer’s feedback from a short written survey. This alternative study could consist of a brief conversation and interview-style survey with more open-ended questions. This would allow the participants to potentially form a greater connection with their evaluator and possibly seek their approval, causing more emotional impact and an increased impact to their self-esteem. Moreover, this study could be repeated but with a larger age demographic, compared to solely undergraduate students. This may increase the generalizability of the results, and possibly have implications for dating and self-esteem in educational settings . Conclusion This study touches on the personal implications and feelings surrounding social feedback in college students. College is an extremely social environment and romantic relationships become increasingly prevalent in people's lives. With further research, studies could contribute to increased self-esteem, mental health, and psychological well-being among college students. Knowledge on how romantic relationships impact the self is crucial for healthy dating practices and personal wellness. Through further research, we can contribute to a healthier social environment for college students. References Harris, M. A., & Orth, U. (2020). The link between self-esteem and social relationships: A meta-analysis of longitudinal studies. Journal of Personality and Social Psychology, 119(6), 1459–1477. https://doi.org/10.1037/pspp0000265 Hoplock, L. B., Stinson, D. A., Marigold, D. C., & Fisher, A. N. (2019). Self-esteem, epistemic needs, and responses to social feedback. Self and Identity, 18(5), 467–493. https://doi.org/10.1080/15298868.2018.1471414 Mann, R. B.; Blumberg, F. Adolescents and social media: The effects of frequency of use, self-presentation, social comparison, and self esteem on possible self imagery. Acta Psychologica. 2022, 228, 1–8. https://doi.org/10.1016/j.actpsy.2022.103629. Muratori, P.; Bertacchi, I.; Buonanno, C.; Levantini, V.; Pannunzi, L.; Coppola, G. The role of gender in the relationship between narcissism, self-esteem, and externalizing problems in children. European Journal of Developmental Psychology. 2025, 1–14. https://doi.org/10.1080/17405629.2025.2585983. Ratliff, K. A., & Oishi, S. (2013). Gender differences in implicit self-esteem following a romantic partner’s success or failure. Journal of Personality and Social Psychology, 105(4), 688–702. https://doi.org/10.1037/a0033769 Rosenberg, M. (1979). Rosenberg self-esteem scale (RSE). In APA.org (pp. 61–62). American Psychological Association. https://www.apa.org/obesity-guideline/rosenberg-self-esteem.pdf Tan, K., Ho D, & Agnew, C. R. (2023). Relationship status and psychological well-being: Initial evidence for the moderating effects of commitment readiness. Journal of Happiness Studies, 24, 2563-2581. https://doi.org/10.1007/s10902-023-00692-w van Schie, C., Cook, J. L., Elzinga, B., & Ly, V. (2023). A boost in self-esteem after positive social evaluation predicts social and non-social learning. Royal Society Open Science, 10(5), 230027. https://doi.org/10.1098/rsos.230027 Appendix A Self-Esteem Pre-Test _____ 1. On the whole, I am satisfied with myself. I have a good relationship with my parents. _____ 2. At times, I think I am no good at all. (R) _____ 3. I feel that I have a number of good qualities. I think the world would be better if more people were like me. _____ 4. I am able to do things as well as most other people. I have good quality friends. _____ 5. I do not have much to be proud of. (R) _____ 6. I certainly feel useless at times. (R) I have high standards for a partner. I find it easy to open up. _____ 7. I feel that I'm a person of worth. I make friends easily. _____ 8. I wish I could have more respect for myself. (R) I am satisfied with my life. _____ 9. All in all, I am inclined to think that I am a failure. (R) _____ 10. I take a positive attitude toward myself. I regularly spend time with myself. Note. Respondents indicate the degree to which they relate to the statements on a 4-point scale (1 = Strongly agree, 2 = Agree, 3 = Disagree, 4 = Strongly disagree). Numbered questions are part of the Rosenberg scale. (R) indicates that the item is reverse-scored. Appendix B Self-Esteem Post-Test _____ 1. I wish I could have more respect for myself. (R) _____ 2. I feel that I have a number of good qualities. _____ 3. On the whole, I am satisfied with myself. _____ 4. I certainly feel useless at times. (R) _____ 5. I take a positive attitude toward myself. _____ 6. I do not have much to be proud of. (R) Note. Respondents indicate the degree to which they relate to the statements on a 4-point scale (1 = Strongly agree, 2 = Agree, 3 = Disagree, 4 = Strongly disagree). (R) indicates that the item is reverse-scored. Figure 1 - Self-Esteem Difference Figure 1. Mean differences in self-esteem scores across gender and readiness conditions. The two-way ANOVA revealed no significant main effects for gender or readiness condition, and no significant interaction between the readiness condition and gender.

Author: Alyssa Lee Editor: Keoni Andrews Introduction When you picture a brain cell, a "neuron" is likely what comes to mind. Historically, neurons have dominated the spotlight within neuroscience research. However, these famous cells would be unable to function without the presence of the "stars of the brain"- astrocytes. Astrocytes are the most populous macroglia in the central nervous system (CNS). Following their initial discovery by Rudolf Virchow in 1858, they were viewed as mere support staff, playing passive roles in supporting neuronal function. Recent advancements have radically redefined these macroglia. Today, astrocytes are recognised as necessary regulators of CNS health, playing active roles in synapse regulation, information processing within neuronal circuits and the formation/maintenance of the blood brain barrier (BBB) (Gradisnik & Velnar, 2023; Sofroniew & Vinters, 2010). The multifunctional behaviour of these cells have earned them the label of the ‘housekeepers’ of the CNS as they play vital roles in both physiological homeostasis and the immune response in pathological states (Verkhratsky et al., 2021). When the Stars Dim: Astrocytes dysfunction Astrocytes are vital for overall CNS health. When they become dysfunctional or enter a state of prolonged reactivity, they actively contribute to the development and progression of various neurological or neuropsychiatric disorders. In neurodegenerative diseases such as Alzheimer’s disease (AD), initially astrocytes attempt to protect the brain by assisting in amyloid-beta plaque clearance. However, after prolonged activity, they transform into a reactive, proinflammatory phenotype, producing cytokines that exacerbate disease progression (Kim et al., 2026; Kim et al., 2024). Restoring normal astrocytic function has been shown to help in the recovery of neuronal hyperactivity in AD, highlighting these cells as a major therapeutic target (Shah et al., 2022). The health of astrocyte populations are also critical in neuropsychiatric contexts. Lima et al. (2014), modelled astrocyte pathology by poisoning astrocytes in the prefrontal cortex using an astrocyte specific toxin. Resulting in a decrease of astrocyte density, manifesting as schizophrenia-like cognitive symptoms, such as impaired working memory. These examples highlight the importance astrocytes have in the CNS and how without their proper functioning issues arise. A Tale of Two Matter Types: Astrocyte Heterogeneity Astrocytes are complex cells and are highly heterogeneous on a morphological, genetic and functional level (Holt, 2023). A key part of this complexity is their spatial organisation, allowing them to carry out highly specialised, region-specific functions, a trait mapped as early as the prenatal stage (Schroeder et al., 2025). Traditionally, astrocytes can be classified into two basic morphological subtypes based on their neuroanatomical location: protoplasmic astrocytes and fibrous astrocytes, found in Fig 1 (Miller & Raff, 1984). Table 1. A summary of Protoplasmic and Fibrous Astrocytes, highlighting their Location, Morphology and Primary Role. Protoplasmic Astrocytes Fibrous astrocytes Location Gray Matter (GM) White Matter (WM) Morphology Central soma. “Bushy” appearance, highly branched with primary and secondary/tertiary processes Soma to one side. Straight, non-branched processes ending in small projections Primary Role Regulating neurotransmission, maintaining the BBB, CNS homeostasis Production and maintenance of the myelin sheath Figure 1. Tracings of protoplasmic and fibrous astrocytes. Protoplasmic astrocytes are highly branched with primary and secondary processes (branches), which split into many terminal processes (leaflets). Fibrous astrocytes are less branched with only primary processes that split into perinodal processes. The soma of protoplasmic astrocytes are found within the centre of the cell whereas the soma of fibrous astrocytes are found more towards the left with the length of the primary processes extending to the right. Image by Verkhratsky et al. (2021) Protoplasmic astrocytes and neurotransmission Found widely distributed in the gray matter, protoplasmic astrocytes are critical for regulating synaptic transmission (Corkrum et al., 2020; Liu et al., 2021). Their endfeet ensheaths the synaptic terminals of neurons, forming the "tripartite synapse", a physiological model allowing bidirectional communication between the astrocyte and the pre- and post-synaptic neurons, shown in Fig 2. Through the tripartite synapse, protoplasmic astrocytes actively regulate neurotransmitters, such as glutamate. While essential for normal brain processing and neuroplasticity, excess glutamate can cause excitotoxicity (de Ceglia et al., 2023; Pal, 2021). To prevent this, astrocytes express specialized membrane transporters (EAAT1 and EAAT2) that sweep up excess glutamate, degrade it into glutamine, and release it back for neuronal reuse (Adermark et al., 2022), shown in Fig 2. The reuptake and recycling cycle is vital as a disruption of neurotransmitter homeostasis, such as an excess in glutamate can lead to excessive Ca2+ influx in the postsynaptic neuron causing extreme neuronal firing and excitotoxicity (Teleanu et al., 2022). Beyond simple uptake, they also actively release gliotransmitters, including glutamate, D-serine and ATP via Ca2+ regulated exocytosis to influence cognitive processing and synaptic plasticity (Harada et al., 2015; Sahlender et al., 2014). Furthermore, their endfeet enclose capillaries in the brain to form the outermost layer of the blood brain barrier (BBB), which allows them to regulate blood flow aligned with synaptic demand (Chiareli et al., 2021). Fibrous astrocytes and myelination In contrast, fibrous astrocytes populate the white matter (WM). Although currently less researched than their gray matter (GM) counterparts, current evidence identifies them as key regulators of the production and maintenance of the myelin sheath. Their perinodal processes communicate with the nodes of Ranvier and interact with myelinating oligodendrocytes along the white matter tracks, facilitating the production and maintenance of myelin to actively support neuronal connectivity (Sofroniew & Vinters, 2010; Stogsdill et al., 2023). Additionally, astrocytes secrete promyelinating factors and regulate the maturation and migration of oligodendrocyte progenitor cells (Molina-Gonzalez & Miron, 2019), allowing for the proper development of myelin. Dynamic Responses to Brain Injury Astrocyte heterogeneity is not only apparent in their different functions but also in their response to neuroplasticity - changes in the brain. Astrocyte heterogeneity also dictates how the brain heals. During recovery from an ischemic stroke, gray matter astrocytes induce angiogenesis (new blood vessel formation), while white matter astrocytes do not (Gleichman et al., 2025). Furthermore, mechanical injury causes fibrous astrocytes to simplify their structures, while protoplasmic astrocytes do the opposite, becoming increasingly complex and branched (Sun & Jakobs, 2012). Figure 2. A diagram of the tripartite synapse (pre- and post-synaptic neuron and astrocyte) illustrating how astrocytes regulate glutamate neurotransmission. Glutamate (brown circles) is released in vesicles from the presynaptic terminal via exocytosis. The glutamate receptor on the astrocytes sense an excess of glutamate in the extrasynaptic space which triggers the reuptake of glutamate via express glutamate transporters excitatory amino acid transporter 1 (EAAT1) and transporters excitatory amino acid transporter 2 (EAAT2). The rest of the glutamate is taken up by the postsynaptic neuron. Glutamate taken up by the astrocyte is degraded into glutamine and released into the extrasynaptic space for neuronal uptake. Created using BioRender Heterogeneity within GM and WM brain regions The complexity deepens when looking within these broad categories. White matter astrocytes can be further divided by gene expression, as some are dedicated to axonal support, while others focus on cell proliferation (Bocchi et al., 2025). 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Written by: Jacinda Taggett I was recently featured in The Boston Globe about a comment on hot dogs. This experience got me wondering… why do we crave hot dogs in the summertime? Well to really understand the craving, you need to know the psychological and neurobiological reasoning behind comfort foods. What is “comfort food?” When comfort food was first introduced, it was linked to an unhealthy diet that provided maximal pleasure but minimal nutritional value. In the psychological and sociological context, researchers defined it as having 5 main components: nostalgia, convenience, physical comfort, indulgence, and belonging. When you think about how sales of hot dogs are rising currently, they fit all of the criteria for comfort food from the colloquial to the academic. The neurobiology of high-fat, high-sugar foods Whenever Americans think about guilty pleasures in their diet, they think of hamburgers, ice cream, and nonetheless hot dogs! As is inferred since the origination of the term, comfort foods are typically high in fats and high in sugars. Neuroscientists have seen in both animals and humans that after consuming these high-fat, high-sugar foods, there are short-lived dopamine boosts into the same regions of the brain that are known for reinforcing pleasurable behaviors (Atar, 2026). Additionally, it has been shown throughout various studies that fatty foods are seen as reported in higher frequency during stressful periods of life– such as intense work weeks or during exams season. This is due to the fats in the food temporarily suppressing the HPA axis– our primary stress-response system– and therefore promoting a feeling of solace during an already stressful time (Gibson, 2012). The psychology of foods that provide comfort Although there are studies backing the neurobiological mechanisms of comfort foods, there are psychological studies showcasing that part of the pleasure comes from expectation. Psychologists have studied this topic not via eating but via drawing or describing their comfort food preferences, which still showed improvements in mood and allows us to infer that part of the psychological benefit is coming from expectation. On top of this, there was a study last year that focused on the different expectations people might experience when deciding to eat comfort food, and saw that although most people use it to manage negative emotions or alleviate boredom, it was actually highly endorsed that pleasure and reward was the main motivator for indulging in comfort food (Wu, Vartanian & Faasse, 2025). Instead of knowing that this food will make us feel better long-term, it’s instead a short-lived dopamine boost and deep down we understand that (Wagner et al., 2014). So… why do we crave comfort foods? Since the 60s, comfort food has shifted from strictly being unhealthy foods to being any type of food that brings solace during tough times. There was a great review by Dr. Lucy M. Long that describes how the pandemic introduced this shift– particularly through social and outlet media (Long, 2022). I think that modern food marketing has reflected this, as now individuals view comfort food as more nostalgic or more convenient than simply unhealthy. Living in America, especially in the Greater Boston area, you might remember eating hot dogs throughout the summertime, during your favorite sports game, or spending time with family and friends. On the same idea as nostalgia, there is almost a sense of community that comes from eating hot dogs with friends, family, or sports fans. It is essentially embedded into our culture to indulge in hot dogs solely in large gatherings, therefore we will see a high rise of hot dog consumption during peak summertime. References Atar A. Neurobiological Consequences of High-Fat High-Sugar Diets on the Mesocorticolimbic System: a Narrative Review. Curr Nutr Rep 15, 6 (2026). https://doi.org/10.1007/s13668-026-00729-5 Gibson EL. The psychobiology of comfort eating: implications for neuropharmacological interventions. Behav Pharmacol. 2012 Sep;23(5-6):442-60. doi: 10.1097/FBP.0b013e328357bd4e. PMID: 22854304. Long LM. How the Pandemic Redefined Comfort Food: American Individualism, Culinary Relativism, and Shifting Moralities. Popular Culture Studies Journal. 10(1) 2022: 1-18. Wu F, Vartanian LR, Faasse K. Why Do We Eat Comfort Food? Exploring Expectations Regarding Comfort Food and Their Relationship with Comfort Eating Frequency. Nutrients. 2025 Jul 8;17(14):2259. doi: 10.3390/nu17142259. PMID: 40732884; PMCID: PMC12297910. Wagner HS, Ahlstrom B, Redden JP, Vickers Z, Mann T. The myth of comfort food. Health Psychol. 2014 Dec;33(12):1552-7. doi: 10.1037/hea0000068. Epub 2014 Aug 18. PMID: 25133833.

By Emma Reid Edited By: Keoni Andrews Cover Image from Mohamed M on Unsplash From scrolls to bound volumes to electronic novels, books have changed with each turn of the century — and with the rise of modernization comes a new medium: audiobooks. Audiobooks are defined as recordings of works, such as magazines or books, being read out loud. Originally, audiobooks were invented for the blind community by the American Foundation for the Blind, where recordings of books were printed onto vinyls for individual use (Theot, 2017). However, emerging technology has given easier access to these audio recordings — skyrocketing their popularity to the general public. Now, services such as Audible have millions of users listening to audiobooks every day (Singh, 2023). This available change for book consumption has sparked a heated debate over the last several years: do audiobooks count as reading? With the lack of a visual pathway found in typical reading patterns, many argue that they do not (Engle, 2025). However, neuroscience suggests something different. While their sensory pathways differ, these two processes share many neural features, including the way they perceive and comprehend language. This isn't to say that reading and listening to books are the same, but is there even a need for them to be? Often we frame this question under the guise of what counts as 'real reading,' but with deeply rooted traditions and scientifically backed cognitive benefits, both audiobooks and reading deserve to be understood on their own terms. The Neuroscience Behind Reading and Listening While they seem simple, reading and listening are far more complex than instantaneously understanding words. When the brain encounters a word, whether read or heard, the same core language networks activate, making these two processes more neurologically similar than they seemingly appear. Reading comprises four main processes: visual, phonological, semantic, and syntactic processing. Both visual and phonological processes are involved in the physical appearance of a word, while semantic and syntactic processing are involved in its definition. When all of these mechanisms align, the brain is able to recognize, refine, and predict information from a word within milliseconds. Visual processing is done in the occipital lobe, where visual information from our eyes, such as letters and words, gets properly interpreted in the brain (Cohen et al., 2004). Phonological processing maps letters to sounds, a skill crucial in understanding how words are pronounced (Mathur et al., 2020). Think back to when your teacher made you rhyme words like “bat” and “hat” together — those exercises were strengthening phonological processing. Together, these two processes handle the physical recognition of a word. For listening, this recognition happens differently. Sound waves travel into the ear and are eventually converted into electrical nerve impulses, which are carried to the auditory cortex in the temporal lobe (How Do We Hear?, n.d.). Here, vowels, consonants, prefixes, and suffixes are all processed by their specific sounds in order for the brain to register a complete, fully-formed word (Saenz & Langers, 2014). This is the place where reading and listening intersect. Once a word is recognized, by either pathway, semantic and syntactic processing take over. Semantic processing involves a wide network of neural connections that pulls a word's associated features, such as sound, shape, motion, and sensation, from multiple cortical regions and unifies them into a single concept (Chen et al., 2020 and Reilly et al, 2017). This is why when you read or hear the word "apple", your brain conjures not just the image of the fruit, but also its scent, taste, and sound all at once. Syntactic processing then extracts meaning from the sentences those words form, drawing on past experiences with grammar to generate instantaneous comprehension (Fedorenko, 2025). Both of these processes, along with phonological processing, become active the moment the brain detects a word, whether spoken or read (Mineo, 2026). The pathway to the brain may differ, but the neural architecture that processes language remains the same. Different Cognitive Experiences, Equal Cultural Value Since the neural networks responsible for comprehending words remain largely similar, it’s easy to conclude that reading and listening to books are the same. In fact, most scientists would agree. Yet many people insist that audiobooks are still not equal with their physical counterparts. This conflict suggests a bigger question at large — one that peels back the science to reveal the deeper cultural values we unconsciously and intrinsically hold. The question itself, “do audiobooks count as reading?”, inadvertently accepts the premise that reading is the gold standard of society. While it can be argued that the difficulty in learning how to read over how to speak is greater and thus requiring more attention, the focus on reading guides us to accept it as a fundamental marker of status rather than preference. However, listening has its own rich cultural history — one that drives it to act as an important subset of many social foundations. It predates reading by millenia, making it one of the earliest skills humans have ever known. In early civilizations, oral storytelling was the primary form of record-keeping and information exchange, along with generating bonding rituals between communal members (The Ancient Origins, 2026). Even though the oral preservation of information has changed in popularity over time, there was once a deep dependence on this skill for generations. Additionally, there are still many present-day benefits to transferring information via verbal communication, especially for those who cannot read in a typical manner. For people with dyslexia, visual impairments, or demanding schedules, audiobooks aren't a short cut — they're the optimal format to gain new knowledge. In general, experts agree that engaging in intellectually-stimulating content is important for brain health, so there is little need to diminish one approach over the other (Zickl, 2026). Instead of ranking these modalities based on intellectual legitimacy, we should start viewing these mediums by their content rather than their surface-level context. Audiobooks aren’t reading—they’re listening—but that doesn’t make them less than. Without listening, much of history, knowledge, and everyday conversations would not exist. Although listening shares a similar neural experience to reading, it is still its own cognitively rich, culturally ancient, and neurologically legitimate act. The goal shouldn’t be to prove that audiobooks are as good as or even better than reading — it should stop them from needing to be. Reading and listening will never be the same, but both allow people to take part in an activity everyone reserves the right to enjoy. References Chen, Y., Huang, L., Chen, K., Ding, J., Zhang, Y., Yang, Q., Lv, Y., Han, Z., & Guo, Q. (2020). White matter basis for the hub-and-spoke semantic representation: Evidence from semantic dementia. Brain, 143(4), 1206–1219. https://doi.org/10.1093/brain/awaa057 Cohen, L., Lehéricy, S., Henry, C., Bourgeois, M., Larroque, C., Sainte-Rose, C., Dehaene, S. and Hertz-Pannier, L. (2004). Learning to read without a left occipital lobe: Right-hemispheric shift of visual word form area. Annals of Neurology, 56, 890–894. https://doi.org/10.1002/ana.20326 Engle, E. (2025, December 1). Does listening to an audiobook count as reading? The New York Times. https://www.nytimes.com/2025/12/01/learning/does-listening-to-an-audiobook-count-as-reading.html Fedorenko, E. (2025). Neuroscience of syntax. In M. C. Frank & A. Majid (Eds.), Open Encyclopedia of Cognitive Science. MIT Press. https://doi.org/10.21428/e2759450.d858c2df How do we hear? (n.d.). National Institute on Deafness and Other Communication Disorders. https://www.nidcd.nih.gov/health/how-do-we-hear Mathur, A., Schultz, D., & Wang, Y. (2020). Neural bases of phonological and semantic processing in early childhood. Brain Connectivity, 10(5), 212–223. https://doi.org/10.1089/brain.2019.0728 Mineo, L. (2026, March 2). Audiobooks don't really count as reading? Think again. Harvard Gazette. https://news.harvard.edu/gazette/story/2026/03/audiobooks-dont-really-count-as-reading-think-again/ Reilly, J., Garcia, A., & Binney, R. J. (2016). Does the sound of a barking dog activate its corresponding visual form? An fMRI investigation of modality-specific semantic access. Brain and Language, 159, 45–59. https://doi.org/10.1016/j.bandl.2016.05.006 Saenz, M., & Langers, D. R. M. (2014). Tonotopic mapping of human auditory cortex. Hearing Research, 307, 42–52. https://doi.org/10.1016/j.heares.2013.07.016 Singh, S. (2023, June 13). How many people use Audible? User stats & data (2025). eReader.blog. https://ereader.blog/audible-users/ The Archaeologist. (2026). The ancient origins of storytelling. https://www.thearchaeologist.org/blog/the-ancient-origins-of-storytelling Thoet, A. (2017, November 22). A short history of the audiobook, 20 years after the first portable digital audio device. PBS NewsHour. https://www.pbs.org/newshour/arts/a-short-history-of-the-audiobook-20-years-after-the-first-portable-digital-audio-device Zickl, D. (2026, June 11). Do audiobooks offer the same cognitive benefits as reading? MSU Health Care. https://healthcare.msu.edu/news/2026-06-11-Do-audiobooks-offer-the-same-cognitive-benefits-as-reading.html

Written by - Nitya Thakur Abstract Early relationships play a central role in shaping neural systems involved in emotion regulation, threat processing, and social bonding (Feldman, 2017; Gunnar & Quevedo, 2007). Attachment theory proposes that bonds formed between infants and caregivers give rise to internal working models, enduring mental representations that guide expectations of closeness, safety, and emotional availability in later relationships. Neurobiological research has extended this framework, demonstrating that early caregiving experiences influence the development of key brain regions and systems, including the amygdala, prefrontal cortex, anterior cingulate cortex (ACC), and the hypothalamic–pituitary–adrenal (HPA) axis. This review synthesizes findings from attachment theory, developmental neuroscience, and adult relationship research to examine how early relational environments contribute to patterns of emotional and interpersonal functioning. Although early caregiving does not determine later outcomes, it represents a significant developmental influence on how individuals experience and regulate intimacy throughout the lifespan. Introduction Most people do not think of their earliest relationships as neurological events. Yet research in developmental psychology and social neuroscience suggests that the first bonds formed with caregivers play a foundational role in shaping how the brain later interprets closeness, trust, and emotional safety (Hernández Pacheco, 2026). Many individuals notice patterns in their relationships that feel stubborn and deeply personal: some move through intimacy with ease, while others live in quiet fear of abandonment or find themselves retreating whenever someone gets too close. These patterns rarely feel chosen. Psychological research suggests they may originate much earlier in development than most people expect and that they may be written, at least partially, into the biology of the brain. From the earliest stages of life, humans depend on caregivers not only for physical survival but also for emotional regulation itself. Infants arrive in the world without the neural machinery to manage their own distress; they rely on the people around them to soothe, attune, and restore a sense of safety. Over thousands of such co-regulatory interactions, the brain begins to learn what relationships are, whether closeness is safe or threatening, whether distress will be met with comfort or left unacknowledged, and whether other people can be trusted. These lessons do not stay abstract. They shape the structure and sensitivity of neural systems that will govern emotional life for decades. Attachment theory, first proposed by John Bowlby, offers a framework for understanding how early relational experience becomes encoded in the developing mind. Bowlby argued that infants form emotional bonds with caregivers that function as a secure base for exploration and development and that through repeated interactions, children develop internal working models, mental representations of the self and others that guide how they approach intimacy across the lifespan (Bowlby, 1969). What began as a theory of infancy has since expanded into one of the most empirically supported frameworks in relational psychology, extended to adult romantic love and deepened by decades of neurobiological research. This review examines what that research has revealed. It traces the path from early caregiving experience to adult relationship behavior through the lens of neuroscience, asking what actually happens in the brain when a child is held or ignored, soothed or left to cry, or loved consistently or inconsistently. The goal is not to blame caregivers or to reduce the complexity of human relationships to biology. It is to take seriously a possibility that is both humbling and hopeful: that how we learned to love, we can, given the right conditions, learn again. Foundations of Attachment Theory Attachment theory begins with a deceptively simple claim: humans are biologically prepared to form strong emotional bonds with caregivers because proximity to a protective adult increases the probability of survival. John Bowlby, working at the intersection of psychoanalysis and ethology, argued that attachment behaviors, crying, clinging, and reaching are not signs of weakness or dependency but an adaptive system shaped by evolution (Bowlby, 1969). The infant who stays close to the caregiver is the infant more likely to survive. Bowlby's central contribution was the concept of the internal working model: repeated interactions with a caregiver, including experiences of comfort, inconsistency, or lack of responsiveness, contribute to the development of mental representations of relationships. When caregiving is consistent and responsive, children tend to learn that distress can be regulated and that closeness is safe. In contrast, when caregiving is unpredictable, rejecting, or emotionally unavailable, children may develop models characterized by uncertainty, avoidance, or heightened vigilance (Bowlby, 1973). Importantly, these models persist beyond childhood and continue to influence expectations and behavior in later relationships. Mary Ainsworth provided attachment theory with its empirical foundation through the Strange Situation, a laboratory procedure in which infants were briefly separated from their caregivers and observed upon reunion (Ainsworth et al., 1978). This work identified three primary attachment patterns: secure, anxious-ambivalent, and avoidant. Securely attached infants used their caregiver as a reliable source of reassurance; although they showed distress upon separation, they were able to regulate their emotions and quickly calm upon reunion. Anxious-ambivalent infants displayed heightened distress and difficulty settling, suggesting uncertainty about the availability of comfort. Avoidant infants appeared emotionally disengaged, minimizing expressions of distress and proximity-seeking behavior, likely reflecting adaptation to caregiving environments in which bids for closeness were not consistently met. The extension of these patterns into adult romantic life emerged through the work of Hazan and Shaver (1987), who proposed that romantic love functions as an attachment process in which the same behavioral systems activated in infant–caregiver bonds are reengaged in adult intimacy. Their research found that the distribution of secure, anxious, and avoidant attachment styles in a large adult sample closely mirrored distributions observed in infancy and that these styles were associated with distinct patterns of relationship functioning. Securely attached individuals reported higher relationship satisfaction, greater trust, and more effective conflict resolution, whereas anxiously attached individuals experienced heightened fear of abandonment and emotional volatility, and avoidant individuals showed discomfort with closeness and reduced emotional expression. Subsequent research has replicated these patterns across diverse samples and methodologies, demonstrating that attachment style is associated with relationship satisfaction, stability, communication patterns, and emotion regulation (Mikulincer & Shaver, 2007). Neural Systems Underlying Attachment If attachment theory explains why early relationships matter, neuroscience is beginning to explain how. The brain does not passively receive experience; it is shaped by it, particularly during infancy and early childhood, when processes such as synaptogenesis, synaptic pruning, and myelination occur at especially high rates. Repeated relational experiences during this period do not simply form memories, they shape the sensitivity and connectivity of neural systems involved in emotional processing and regulation, including the amygdala, prefrontal cortex, and the HPA axis. These systems play a central role in threat detection, stress response, and the regulation of affect, with long-term implications for emotional and interpersonal functioning. Central to threat detection and emotional processing is the amygdala, an almond-shaped structure in the medial temporal lobe that is critically involved in identifying emotionally salient and potentially threatening cues in the social environment. Research on early adversity consistently demonstrates that stressful or disrupted caregiving can alter amygdala reactivity, increasing sensitivity to interpersonal threat across development (Tottenham et al., 2010). This heightened sensitivity may be especially evident in close relationships, where ambiguous cues, such as delayed responses, shifts in tone, or reduced communication, can be interpreted as threatening. Behaviors that appear disproportionate from an outside perspective may thus reflect adaptive responses shaped by earlier experiences in which relational uncertainty was reliably associated with distress. Working in coordination with the amygdala is the prefrontal cortex, particularly its medial regions, which are involved in evaluating social information and regulating emotional responses. Whereas the amygdala detects emotional salience, the prefrontal cortex supports interpretation, contextualization, and top-down regulation. Research on both parent–child and adult social regulation demonstrates that supportive relationships can reduce neural threat responses, with the presence of a trusted partner functioning as an external regulatory resource (Coan et al., 2006). In a now-classic fMRI study, Coan and colleagues showed that married women anticipating mild electric shock exhibited significantly reduced activity in threat-related neural systems when holding their spouse's hand, with effects moderated by relationship quality. This finding suggests that secure attachment is not merely emotionally supportive but plays a critical role in moment-to-moment biological regulation. The anterior cingulate cortex (ACC) also plays a key role in processing the distress associated with social rejection and exclusion. In a landmark neuroimaging study using a virtual ball-tossing paradigm, Eisenberger et al. (2003) found that social exclusion activated the dorsal ACC, a region typically associated with the experience of physical pain, and that ACC activity correlated positively with self-reported distress. These findings suggest that the brain processes threats to social connection through mechanisms closely linked to those involved in physical danger, providing a neurobiological basis for the profound emotional impact of rejection and interpersonal loss. Attachment is further supported by neurochemical systems, particularly oxytocin, which promotes social affiliation, bonding, and coordinated caregiving (Feldman, 2017). Research has demonstrated that oxytocin functions across parental, romantic, and filial bonds and plays a role in synchronizing the physiological states of individuals in close relationships. Together, these systems, the amygdala, prefrontal cortex, ACC, and associated neurochemical networks, do not constitute a single 'love center' in the brain. Rather, attachment is a distributed process that emerges from the interaction of systems involved in detecting social salience, regulating distress, and reinforcing social bonds. Early Caregiving and Brain Development The neurobiological systems described above do not arrive fully formed; they develop over time, with early caregiving serving as a central influence on their organization. During infancy and early childhood, children have a limited capacity for self-regulation and rely on caregivers to help modulate distress. In this context, caregiving functions as an external regulatory system: through thousands of repeated co-regulatory interactions, children gradually internalize the capacity to manage their own emotional states (Feldman, 2017; Hofer, 1994). The HPA axis, the body's primary stress-response system, is a key mechanism through which caregiver–child co-regulation of stress occurs. When a child is frightened or distressed, the HPA axis coordinates a physiological stress response by releasing cortisol and mobilizing the body for action. Caregivers who respond with soothing, proximity, and predictability help regulate this response, buffering the child's stress system and preventing excessive or chronic activation. Research on early adversity has shown that neglectful or abusive caregiving can disrupt this regulatory process, altering the calibration of the HPA axis and shaping cortico-limbic functioning, that is, the interaction between cortical regions such as the prefrontal cortex and limbic structures such as the amygdala, in ways that persist into adulthood (Gunnar & Quevedo, 2007). Studies of amygdala–prefrontal connectivity provide direct evidence of how early caregiving shapes neural development. The functional connection between these regions, central to regulating emotional responses, tolerating uncertainty, and preventing escalation of distress, appears sensitive to caregiving quality during early development. Children raised in environments characterized by chronic unpredictability or emotional unavailability show altered patterns of amygdala–prefrontal connectivity compared to those raised in more responsive environments (Gee et al., 2013). These differences reflect meaningful variation in the brain's regulatory architecture, not merely temperamental differences, and have documented implications for how individuals experience and manage emotional stress in later life. What emerges from this body of research is a developmental framework in which early caregiving shapes not only beliefs about relationships but also the neural systems through which emotional experiences are processed and regulated. A child who learns that distress will be met with care also learns that closeness can reduce threat. A child who experiences inconsistent caregiving may develop heightened sensitivity to uncertainty and a tendency toward vigilance in relationships. In this view, attachment is not deterministic, but it exerts a significant influence on both psychological and biological processes, shaping how individuals experience, interpret, and regulate intimacy across development. Attachment Patterns in Adult Romantic Relationships These developmental patterns become especially evident in adult romantic relationships, where intimacy and vulnerability reactivate the internal working models formed in early life. As a result, romantic experiences are shaped not only by the present partner but also by accumulated relational history. Securely attached adults tend to navigate intimacy with relative ease. They generally expect that others will be available and responsive, communicate more directly during conflict, and use relationships as genuine sources of support rather than as tests to be survived (Mikulincer & Shaver, 2007). They are not without insecurities or fears, but their baseline expectation of relationships tilts toward safety. Anxious attachment presents differently. Adults with this pattern often experience relationships as requiring heightened monitoring, including increased sensitivity to signs of distance, frequent reassurance-seeking, and a tendency to interpret ambiguity as potential rejection. From a neurobiological perspective, these patterns are consistent with evidence that heightened amygdala reactivity is associated with increased sensitivity to interpersonal threat, particularly in individuals with anxious attachment styles (Gillath et al., 2005; Mikulincer & Shaver, 2007). When prefrontal regulatory systems develop in the context of inconsistent caregiving, uncertainty in romantic relationships may not only be emotionally distressing but also physiologically activating, as the HPA axis responds to relational ambiguity as it would to genuine threat. Avoidant attachment operates differently but is no less shaped by developmental history. Avoidant individuals tend to minimize emotional needs, value self-sufficiency, and withdraw when intimacy becomes intense (Mikulincer & Shaver, 2007; Fraley & Shaver, 2000). On the surface this can appear as emotional indifference, but attachment research suggests it reflects a learned regulatory strategy, one developed in response to caregiving environments where bids for closeness went unmet or were met with rejection (Ainsworth et al., 1978; Main, 1990). Avoidance is not the absence of a need for connection. It is a way of managing that need under conditions where expressing it felt too costly. What makes this framework both sobering and generative is its insistence that these patterns are not fixed personality traits but organized strategies, coherent responses to the relational environments in which people developed. Research on 'earned' or acquired attachment security suggests that individuals who report difficult attachment histories can still achieve secure functioning through new relational experiences, including in psychotherapy, in stable long-term relationships, and in other contexts that provide sustained emotional safety (Roisman et al., 2002). The brain that learned a particular way of loving can, under the right conditions, learn again. Conclusion Early relationships shape far more than childhood memory. They shape the psychological and biological systems through which individuals will experience love for the rest of their lives. Attachment theory provides a framework for understanding why: through repeated interactions with caregivers, children build internal working models that carry forward their expectations of closeness, safety, and emotional availability. Neuroscience reveals the mechanism: these relational experiences tune the amygdala's sensitivity, the prefrontal cortex's regulatory capacity, the ACC's responsiveness to social pain, the HPA axis's stress calibration, and the brain's broader orientation toward intimacy. Critically, however, none of these outcomes is fixed. Early experience is a powerful developmental influence, but it is not a life sentence. The emerging literature on earned attachment security, neuroplasticity, and the therapeutic relationship all point toward the same conclusion: with the right relational conditions, whether found in a stable partnership, in skilled psychotherapy, or in communities of sustained care, the internal working models forged in childhood can be revised. Understanding the neuroscience of early attachment is not an invitation to fatalism. It is an invitation to take seriously what human beings need from one another and what becomes possible when those needs are met. References Ainsworth, M. 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Written by: Olivia Mickles Edited By: Keoni Andrews When the body can no longer be trusted to perform its most basic function, breathing, then psychological stability becomes deeply intertwined with physical survival. Severe asthma is a chronic lung disease that affects around 262 million people worldwide and caused about 455,000 deaths in 2019 alone (World Health Organization, 2024). It can develop at any age, sometimes present at birth usually from genetic predisposition, or can be triggered by smoking, pollution, obesity, or other medical conditions. Asthma occurs when the airways become hyperresponsive and inflamed, constricting the muscle around the airways, making it more difficult to breathe. Symptoms can range from mild to severe, including coughing, wheezing, shortness of breath, and chest tightness, leading to a life of uncertainty, restriction, and avoidance. Breathing should be an automatic given, so when this process is challenged by asthma, an individual must learn to be open to grieving the parts of life made risky or unavailable for them. In order to face and regulate their anxiety to not live in a state of constant hypervigilance, and to build resilience to get through the bad days without letting asthma become their identity. Dealing with severe asthma through the lenses of grief, anxiety, and resilience all have in common that an individual must constantly battle the desire to have full control over their body, environment, and circumstances while actually having little to no control over the greater factors that influence their condition. Therefore, severe asthma is not only a physiological condition, but a deeply psychological and social experience shaped by non-finite grief, heightened anxiety, and the resilience of individuals and their communities. Understanding the bidirectional relationships between emotional processes and asthma reveals that improving quality of life requires not only addressing the airways, but the lived emotional realities of those affected. Asthma produces a unique form of grief that cannot be reconciled because the source of loss persists and cannot be put to an end. This is often referred to as non-finite loss, or the enduring loss precipitated by a negative life event that usually retains a physical presence, psychological presence, or both. It has to do with a crisis of one’s self-identity or experience that creates a sense of disconnection from mainstream life (Bruce & Schultz, 2002). Chronic illness is a form of ongoing, non-finite loss as it restricts individuals from being able to comfortably participate in various aspects of a “normal” functioning world. For someone with severe asthma, they must take medication (e.g. budesonide formotorol) in the morning and at night, obligating them to allot time for that each day, and obligating them to schedule their lives around taking their medication. One cannot simply rush out in the morning or go out with friends at night without their medication, which is not commonly carried on one’s person all day. It is important to note that in this context, “medication” does not refer to the albuterol “rescue” inhaler that all asthmatics should have on them at all times; it is a much stronger corticosteroid that is necessary to reduce severe airway inflammation. Severe asthmatics also face the challenge of rearranging their lives when their symptoms flare and finding a balance of continuing with daily life duties while taking care of their health. The results of flare-ups could be mild, such as sleep loss, anxiety, and shortness of breath, or severe, such as chest tightness or an asthma attack (World Health Organization, 2024), resulting in feeling a loss of physical freedom, unpredictability in an area of life where the majority of the population faces no threat, and a loss of a “normal” identity. These issues, however, are not ones that doctors can commonly provide aid for. Professionals are so familiar with the breadth, depth, and content of their knowledge that they can easily underestimate the emotional impact of the information the patient is receiving and overestimate what an individual, or the parent of a child, understands (Bruce and Schultz, 2002). For example, I was diagnosed with severe asthma when I was seven years old, and my parents did not know anything about the condition. As kind and knowledgeable as my doctor was, I ended up taking a half dose of medication every day for almost a year, and struggled greatly, because the instructions were not clearly explained to my parents. I also did not fully understand what asthma was on a biological and physical level until I looked it up myself, almost ten years into my diagnosis, when I realized I did not actually know what was going on in my body. Therefore, doctors, in my opinion, should undergo training on how to explain diagnoses to patients clearly and effectively while also considering their emotional wellbeing. Chronic diseases are not discussed often in terms of grief and loss, but asthmatics miss out on enjoying so many social, athletic, and outdoor opportunities, along with a sense of normalcy and freedom, due to their condition, which only gets increasingly painful as the years pile on. If we are to acknowledge our grief, it is important to familiarize ourselves with the Five Gates of Grief, each of which helps us to understand how the many ways we can experience loss influence our lives (Weller, 2015). The gate that resonates most with grief and asthma is called Everything We Love, We Will Lose, and includes the notion that lingering illness can activate a feeling of loss. Prolonged sickness can lead to one lamenting the life they once knew and enjoyed, and leaving them to feel diminished, drained, vulnerable, and betrayed by their body, “as though we no longer have a foundation beneath us for living fully” (Weller, 2015). As a severe asthmatic, the word “betrayed” fits so well with my experience of thinking “why me?” and “it’s so unfair”. The condition requires so much time, thought, and energy every single day so it is difficult not to grieve the memory of running freely at recess in elementary school, or of being able to go places without the constant worry of “what if something triggers a flare-up or attack?” and “do I have my medicine on me?”. However, Weller powerfully states, “But we are not meant to go back”, and says that one must acknowledge that they have been uprooted by their illness and is now in a completely new place than before, unable to turn back, and forced to change. If one does not change and allows themself to be pulled into their metaphorical, or literal, grave, they will never leave the grief behind to face a more complex self that is both beautiful and in pain. Embracing that, he says, is how to embrace the rocky terrain of life. This kind of grief is not only a non-finite outcome; it is also a trigger. Although the cause of asthma is mostly biological, grief may initiate or intensify it. Researcher Levitan performed a case study of six patients in his practice whose asthma suddenly began during a period of mourning. It was suggested that the intensity of their grief was a key psychological factor that promoted the onset of asthma, and it was proposed that the unusual intensity of emotion along with the patient's inability to control their emotions associated with mourning were what was responsible. It was therefore hypothesized that when the intensity of emotion reaches a certain degree, the parasympathetic nervous system gets overstimulated, and the individual is stuck in a state of hyperarousal, which could potentially trigger asthma to develop as a stress response (Levitan, 1985). Levitan also made note of a past study done by Knapp and Nemetz (1957) that found that asthmatic patients often present with melancholic personality features, a depressed mood, and a sense of hopelessness, and that 10% of asthma attacks, in the contexts studied, occurred immediately after feelings of sadness. So, not only does having asthma create a sense of grief and sadness in asthmatics, it is also exacerbated by that grief and sadness. I definitely have recognized this relationship since my symptoms, of chest tightness and shortness of breath, noticeably flare after feeling intense depressive emotions for long periods of time. Finally, crying and laughing are also especially strong triggers as noted by health care professionals, and myself from experience, because the overactivation of the immune system, along with heavy breathing or hyperventilation, releases hormones that trigger the airway muscles to tighten (National Jewish Health, 2017). So, severe asthma makes even therapeutic and stress-releasing emotional responses, like crying and laughing, cause for concern, which could make an asthmatic feel very frustrated and isolated. Anxiety is a basic human response to uncertainty, and Chorpita and Barlow (1998) explain that early life experiences with diminished control could lead to an increased vulnerability to it. Severe asthma creates an environment that is riddled with opportunities for anxiety to manifest, especially in children who are still developing their perceived locus of control, while asthmatics should be aware of their triggers, symptom flare-ups and attacks are not always predictable and can happen for reasons out of one's control. However, one cannot just not go outside, attend social events, or express emotions, so this bidirectional relationship between asthma and anxiety can cause further problems like avoidance, excessive worry, anxiety attacks, or more common flare-ups in everyday circumstances due to nervous system hyperarousal. This is why Chorpita and Barlow (1998) highlighted the importance of a strong family support system for young people, because more responsive, less intrusive parents make a child feel more in control and safe in their environment. If a child is born with severe asthma and does not feel that they can depend on anyone for support or safety, their anxiety will increase, which further intensifies their symptoms. How does this relationship between asthma and anxiety work exactly? A recent study used fMRI to show that certain brain circuits, specifically the anterior cingulate cortex and insula, are activated in response to an inhaled antigen, a substance that triggers an immune response, generating brain signals that are associated with and predictive of airway inflammation. When an antigen was inhaled, mast cells, the “first responders” of our immune system, released histamine and leukotrienes, pro-inflammatory mediators that drive asthma and inflammation, causing a bronchospasm, or the immediate tightening of muscles lining the airways. This effect was seen over the course of six hours, with lung function declining from ~100% to ~50% due to increasing inflammation of the airways. Additionally in this study, researchers found that both acute and chronic stress do not cause inflammation, but intensify it if already present by increasing cortisol levels, which enhances inflammation. So, if an asthmatic's symptoms flare because of uncontrollable inflammation or inhalation of an antigen that causes inflammation, which are common, they will likely feel stress because their health is at risk, and that stress will only exacerbate inflammation, making symptoms worse (Busse, 2012). Asthma and anxiety are in a vicious cycle with each other, making anxiety physiologically embedded in the body, and the mind able to shape one’s breathing capacity. It is difficult not to feel so much loss of control over something the majority of the world does not even need to think about. The psychological burden of anxiety on asthma extends beyond symptom management; it shapes how individuals interpret and live with their condition every day. Many people strive to maximize their quality of life, yet having mental or medical conditions, or both, can make this far more challenging to accomplish. A recent study showed that individuals with severe asthma had worse mental and physical health related quality of life (HRQoL) with corresponding higher anxiety scores than individuals without asthma. Severe asthma patients also expressed stronger beliefs about the essential nature of their medication than those without the condition, and reported having high anxiety over accessibility to medication as well as its side effects. As corticosteroids are required by all chronic asthmatics to be able to breathe twelve hours at a time, it is something they could not live a day without; yet taking corticosteroids daily, especially from young, can lead to mild to moderate side effects. One known side effect is stunted growth, so, for example, I was projected to be about 5’ 10”, but then started twice-daily corticosteroids at age seven, and now I am 5’ 4”. It would therefore be beneficial to integrate psychological resilience techniques into asthma treatment to reduce anxiety and lower worry regarding managing the disease and treatment. This addition could also improve the issue of poor adherence to treatment, caused by high anxiety and subsequent suspicion, which could improve an individual’s quality of life. (Rönnebjerg et al., 2023). Taking mental HRQoL seriously in individuals with chronic diseases like asthma is so important because some common symptoms in anxiety disorders include feeling hopeless, worthless, scared, and alone, leading to individuals becoming isolated, taking part in substance abuse or self-harm, engaging in medical neglect, and exhibiting a wide range of other destructive behaviors. By addressing this “dark side” of the disease, doctors can not only treat patients with medication, but also with anxiety-reducing and calm-inducing interventions that promote self-compassion and teach individuals how to ground themselves in times of distress (Rönnebjerg et al., 2023). If healthcare professionals aim to lower anxiety levels for those with severe asthma, not only would symptoms and quality of life improve, but also greater structural problems. People with generalized anxiety disorder (GAD) have had a major negative social and economic impact on society due to decreased work productivity and an extreme increase in health care utilization (Wittchen, 2002). This has cost the United States approximately $42 billion. They illustrate that GAD is already a significant burden for people without other physical or mental conditions, so if you combine GAD with a potentially life-threatening condition, those individuals are likely to go to the hospital and other doctors far more often and have far worse work performance. The article also covers the various SSRIs, SNRIs, and other medications that one can take to manage their anxiety, but they all come with varying rates of success and side effects, so an asthmatic may avoid these medications because they already take strong corticosteroids that come with their own side effects. This is another reason why non-pharmaceutical interventions should be put in place for people with chronic illnesses, to avoid having more drugs pulsing through their system, and to teach effective grounding and self-compassion techniques that make a lasting psychological difference and build resilience. Resilience is the ability to understand what one does and does not have control over, and to adapt through challenging situations to come out having grown and learned. Resilience is not about not feeling pain; it is about knowing how to hold your pain and strength in balance. A study done by Baker (2019) examined the relationship between self-compassion and depression, anxiety, and resilience in people with epilepsy (PWE), another chronic illness that generates higher levels of grief and uncertainty. It is suggested that many components of self-compassion, like treating oneself with kindness and recognizing common humanity, can reduce depression, anxiety, and feelings of marginalization and stigma that PWE feel as a result of their condition. Self-compassion was also shown to reduce the amount of time spent ruminating and preoccupying oneself with fear of evaluation from others, further lowering depression and anxiety levels. It is easy to ruminate over one’s poor physical health and what others may think, especially with very noticeable and anxiety-inducing conditions like epilepsy and asthma, but doing so can lead to self deprecating or hopeless thoughts that make one feel alone in their struggles or avoidant of the good life has to offer. Therefore, highly self-compassionate individuals experience more positive than negative automatic thoughts, which leads to less worry, which can lower anxiety. Finally, Baker (2019) showed that self-compassion increased resilience in PWE because they are already familiar with facing high levels of adversity, and, so, resilience was easily recognized as a valuable skill to protect against the negative factors of the condition. Resilience, however, does not need to be found or created alone; it can be structurally dispersed in communities. Asthma, especially pediatric asthma, is a leading global health concern that disproportionately affects children in low-income areas with stressors such as air pollution, allergens, and psychosocial stress, as these factors can aggravate symptoms and hinder treatment management. A series of case studies done by Lichtveld et al. (2026) examined the relationship between childhood asthma and community resilience and how environmental and social stressors determine asthma risk and management. Various implications to create resilience were identified and discussed, with one being having health care professionals educate communities, families, and individuals affected by asthma about the biological pathways that are affected by changes in the environment. This can include information similar to that presented by Busse (2012) regarding how pollutants have a direct negative effect on airway inflammation, and how the effects can be mitigated by actions like purchasing affordable home air-filtration systems and reducing the use of aerosol propellants. Education can also be extended to public health professionals and policy makers about asthma triggers and possible interventions to foster community resilience and improve general health. An implication of this could be creating dedicated asthma counseling groups out of community health workers who provide asthma trigger and symptom screening in schools, clinics, and other community settings. They could also alert families to common triggers such as pets, mold, dust, and smoking in the home, and then also how to reduce those triggers to make their environment more asthma-friendly. This intervention costs those benefiting from it almost nothing, so it would be practical to implement in low-income areas, and it allows families to build relationships with the community health workers, so, if medical assistance is ever needed, they know where to go, and who can help them. Overall, Lichtveld et al. (2026) highlight the severity of childhood asthma and that adverse health outcomes are strongly influenced by community-level moderators, such as social support, community assets, access to healthcare, and environmental influences. Not all communities have the same support or resources, therefore interventions must be put in place to close this gap, or else vulnerable populations will continue to struggle more than they should. Resilience in the context of severe asthma is not about the ability to cope, but about the process of reclaiming a sense of control over one’s body, finding meaning in life other than avoiding having an attack, and finding stability in an uncertain world. Grief and anxiety feed off the unstable and chronic nature of asthma, yet resilience can be a counterforce that allows people to adapt and live happily without having to deny their struggles and pain. By implementing interventions to improve social support and self-efficacy in communities, families, and individuals, physical and mental health related quality of life for those with severe asthma can improve. Grief, anxiety, and resilience are often seen today as individual matters, but research has also shown that one is really better off when they treat their grievances and growth as a collective process. In summary, severe asthma is a complex condition that millions of people suffer from worldwide, which is integrated with emotional pain and struggle. As one person among the millions, I resonate strongly with the asthmatic individuals discussed in the literature on the topic of grief, anxiety, resilience,and severe asthma. There will always be a ribbon of grief running through who I am because I am subtly, and often invisibly, struggling to keep up with the non-asthmatic population. However, I have come to realize that being resilient against my asthma is not about not caring or pretending it does not exist, it is about unapologetically allowing my condition to be a part of my identity. I have been aiming to not allow my anxiety, general and specifically health-related, to get in the way of my happiness or be an excuse to avoid living a full life, but, as described above, it can be extremely difficult to fight fears of the unknown. Breathing, to asthmatics, is something that must be fought for every single day, so, to truly support individuals with severe asthma, we must move beyond only caring about whether or not those diagnosed with the condition can breathe and attend to the emotional realities that shape every breath taken and that are shaped by every breath lost. References World Health Organization. (2024). Asthma. World Health Organization; World Health Organization. https://www.who.int/news-room/fact-sheets/detail/asthma Bruce, E., & Schultz, C. (2002). Non-finite loss and challenges to communication between parents and professionals. British Journal of Special Education, 29, 9-13. Weller, F. (2015). The wild edge of sorrow (ch. 3, pp. 23-70). Berkeley, CA: North Atlantic Books. Knapp PH. Nemetz SJ: Sources of tension in bronchial asthma. Psychosom Med 19:466- 485,1957. Levitan. H. (1985). Onset of asthma during intense mourning. Psychosomatics, 26(12), 939-941. https://doi.org/10.1016/S0033-3182(85)72759-4 Emotional Triggers for Childhood Asthma |How to Reduce Risk. (2017). National Jewish Health. https://www.nationaljewish.org/conditions/pediatric-asthma/overview/triggers/emotions Busse, W. W. (2012). The Brain and Asthma: What Are the Linkages? Allergy and the Nervous System, 98, 14-31. https://doi.org/10.1159/000336495 Wittchen, H.-U. (2002). Generalized Anxiety Disorder: Prevalence, burden, and cost to society. Depression and Anxiety, 16, 162-171. Chorpita, B. F., & Barlow, D. H. (1998). The development of anxiety: The role of control in the early environment. Psychological Bulletin, 124, 3-21. Rönnebjerg, L., Axelsson, M., Hannu Kankaanranta, & Ekerljung, L. (2023b). Health-related quality of life, anxiety, depression, beliefs of medication and self-efficacy in individuals with severe asthma – a population-based study. Journal of Asthma, 1–12. https://doi.org/10.1080/02770903.2023.2248512 Lichtveld, M. Y., Heimke, K. K., Dietz, L. J., Wahid, F. A., Buchanich, J. M., Earle, B. C., Noah, T. L. (2026). Childhood Asthma and Community Resilience. Pediatric Pulmonology, 61(2). https://doi.org/10.1002/ppul.71513 Baker, D. A., Caswell, H. L., & Eccles, F. J. (2019). Self-compassion and depression, anxiety, and resilience in adults with epilepsy. Epilepsy & Behavior, 90, 154-161.

Malleeka Suy Image from Google Images Planetoid, humanoid, organoid–these words sound like the makings of a great futuristic space odyssey. Perhaps so, but one of these sci-fi-sounding elements represents a rapidly advancing avenue of research that could address age-old challenges in neuroscience: Organoids. Creating and transplanting these man-made organs into humans is much more advanced than you might think, and they are illuminating a path towards a better understanding of brain functions, diseases, and cures. What are Organoids? Organoids are self-assembling mini-3D structures cultured, or grown, from stem cells, to bear striking structural, genetic, and functional similarities to their human counterparts. Organoid research began in the early 1900s, mostly involving the isolation of preexisting cells. In 1975, keratinocytes (skin cells that produce keratin), and fibroblasts (connective tissue cells), were successfully cultured together to grow human skin colonies (Rheinwatd and Green, 1975). This discovery advanced studies involving skin grafts, dermatological conditions, and drug testing, and would ultimately lead to the isolation and reconstruction of many other organs. Simplified organoid pipeline using iPSCs. Created in BioRender. A significant landmark in organoid research was the discovery and isolation of stem cells. The most popular stem cells used for organoid culturing are embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ESCs are unspecialized cells collected directly from early-stage embryos, while iPSCs are unspecialized cells reprogrammed from specialized adult cells, such as skin or liver cells. You can think of unspecialized cells like a ‘blank slate’; given the appropriate growth conditions, researchers can develop them into any specialized cell and construct any organoid of their choice. In 2009, Toshiro Sato, then a postdoctoral researcher at the Hubrecht Institute in Utrecht, cultured what is widely considered the first organoid. Sato used single stem cells to form small intestines similar to those found in the human body, complete with villi protrusions for nutrient absorption and crypts, where new intestinal stem cells grow (Sato et al., 2009). Since then, organoid culturing protocols have been developed for all types of organoids, which have become excellent models in many biomedical applications, including regenerative research, disease modeling, and personalized medicine (Yang et al., 2023). Brain Organoids The first brain organoids, also termed cerebral organoids or cortical organoids, were developed in 2013 by developmental neurobiologist Madeline Lancaster, who developed a protocol for brain tissue culturing and growth as part of her post-doctorate work at the Institute of Molecular Biotechnology of the Austrian Academy of Science. Lancaster and other scientists started by isolating and culturing a class of embryonic cells that differentiate to form the nervous system. These cells make up a structure called the neuroectoderm and serve as the “building block” of the organoid Lancaster developed. The cells quickly grew in specialized environments that triggered developmental cues within the cells and supplied necessary nutrients for neural growth. By days 20-30, defined brain regions had formed (Lancaster et al., 2013). Staining experiments also confirmed that brain regions within the organoid grew in a similar manner to corresponding regions in human brains: Although the regions were distinct and separate, they still influenced the growth and development of one another (Lancaster et al., 2013). So far, cerebral organoids displayed similar patterns of distinct brain region development and growth interactions in comparison to human-developing brains. These findings marked an important step towards accurately modeling the human brain, as well as exploring the similarities and differences in human neurodevelopment in comparison to other species. As Lancaster exclaimed in an interview with Cell Stem Cell, “For the first time we can now ask, what makes our brains special or different?” (Lancaster, Interview with Cell Stem Cell, 2017). The use of cerebral organoids also fills a large gap in using animals as models for studying human brain disorders. In the case of microcephaly, a neurological condition in which an infant’s head is much smaller than usual, mouse models with the disorder do not fully display the same traits as affected humans, making it challenging to analyze (Farcy et. al., 2022). Lancaster hoped that cerebral organoids could be used as a model for neurodevelopmental disorders by utilizing iPSCs from a patient with severe microcephaly to model the diseased brain. The resulting organoids displayed smaller neural tissues and few progenitor regions for neuron production–features consistent with the reduced brain size seen in microcephaly patients (Lancaster et al., 2013). With further experimentation, Lancaster and her team also identified a possible cause of the smaller brain displayed by microcephaly patients. In cell division, a weblike spindle aligns to separate chromosomes. Lancaster noticed that in the division of radial glial cells, the primary progenitor cells for neurons, many of the spindles were vertical or slanted, as opposed to horizontal. This led to a faulty expansion of neural stem cells and the development of a smaller brain (Lancaster et al., 2013). This could also explain why mice do not display human-like microcephaly traits, as mice do not undergo the same level of neural cell expansion as humans do (Lancaster et. al., 2013). With Lancaster’s discoveries, brain organoids have become widely used in research on neurological disorders, including Alzheimer’s disease, Rett syndrome, and Zika virus (Zhang et al., 2024; Samsarasinghe et al., 2021; Esper et al., 2022). Cortical organoids also hold significant promise for tackling brain injury response and treatment, a notorious challenge for researchers and clinicians. Scientists have managed to successfully transplant human brain organoids grown on culture dishes into mouse brains–complete with neuron differentiation, axon growth, and synaptic communication across the transplanted portions to the host (Mansour et al., 2018). This organoid grafting method is an invaluable tool in modeling disease within a living animal system, as well as neural circuit reconstruction. For example, a study from the Perelman School of Medicine at the University of Pennsylvania utilized organoid grafting to successfully integrate iPSC brain organoids into mice that suffered damage to the visual cortex, the part of the brain responsible for processing visual information. Not only did the grafts have a survival rate of 82% three months after being transplanted, but neurons also increasingly matured within these grafts and displayed similar signal firing rates compared to those from the host brain portions (Jgamadze et al., 2023). The visual cortex neurons of the organoid also responded with similar levels to host brain neurons during both exposure to on-and-off light stimulation and when light was shone in different positions (Jgamadze et al., 2023). The long-term survival rate, consistent neuronal activities, and adaptive responsiveness to visual stimuli suggested that brain organoids can successfully integrate and communicate with preexisting networks. These researchers are illuminating exciting avenues for brain circuitry function and response, with the possibility of neural regeneration on the horizon. The Horizon for Organoids A feat of biomolecular and cellular efforts, organoids have vastly advanced many fields of scientific research. However, much still needs to be improved within organoid formation itself. Because of their relatively short life span, most organoids, especially those derived from pluripotent stem cells, can only represent fetal tissue rather than mature adult tissue, leading to research skewed towards early-human brain development (Yang et al. 2023). Brain organoids also lack many crucial components and processes of a human brain, such as microglia (immune cells of the central nervous system), vascularization (the process of forming new blood vessels), and rely heavily on culture media for sufficient nutrient and oxygen supply (Urrestizala-Arenaza et al., 2024; Lancaster, Interview with Cell Stem Cell, 2017). This leads to an inner necrotic core in the brain organoid, or a “dead zone” of cells caused by limited oxygen and nutrient diffusion, making it challenging to form a fully accurate model of the brain. However, scientists have been on the move to address these problems. For example, researchers have found a way to coax the expression of genes that promote microglia development and vascularization, allowing functional maturation of the organoid and reducing the necrotic core (Cakir et al., 2019; Cakir et al., 2022). Blood vessel organoids could also be used as brain organoid vascularization to bring in nutrients to the brain via blood circulation–a twofold organoid technique (Wimmer et al., 2019). Brain and blood vessel organoids combined to form a vascularized brain organoid. Created in BioRender. With fine-tuning these aspects comes a push and pull of progress and drawbacks, but it is well worth the time and investment. From understanding neurodevelopmental defects to treating traumatic injury, organoids have allowed for further ventures into subfields of neuroscience previously inaccessible. The prospects for organoid use also stretch beyond biological research, with applications extending into anthropology, engineering, and computer science. By culturing the perfect organoid, society is well on its way toward turning scientific hopes and dreams into reality. References Cakir, B., Tanaka, Y., Kiral, F. R., Xiang, Y., Dagliyan, O., Wang, J., Lee, M., Greaney, A. M., Yang, W. S., DuBoulay, C., Kural, M. H., Patterson, B., Zhong, M., Kim, J., Bai, Y., Min, W., Niklason, L. E., Patra, P., & Park, I. (2022). Expression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids. Nature Communications, 13(1), 1-15. https://doi.org/10.1038/s41467-022-28043-y Cakir, B., Xiang, Y., Tanaka, Y., Kural, M. H., Parent, M., Kang, Y., Chapeton, K., Patterson, B., Yuan, Y., He, C., Raredon, M. S., Dengelegi, J., Kim, K., Sun, P., Zhong, M., Lee, S., Patra, P., Hyder, F., Niklason, L. E., . . . Park, I. (2019). Engineering of human brain organoids with a functional vascular-like system. 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By Emma Reid Image by Braňo from Unsplash Introduction Microorganisms are one of the most abundant and diverse life forms on Earth—scientists currently estimate that the human body alone is home to about one trillion microbial cells (NSF, 2021). These microorganisms have played a critical role in the development of modern medicine, from antibiotics to vaccines to even genetic therapies. In recent years, scientists have focused on a powerful genetic tool derived from microbial immune systems: clustered regularly interspaced short palindromic repeats or CRISPR. CRISPR has rapidly revolutionized genetic research, and has even offered up new avenues for treating previously incurable genetic diseases in patients. Overview of CRISPR In the 1980s, CRISPR was first discovered inside the immune systems of bacteria (Ishino et al., 1987). When a bacterium survives viral infection, fragments of the invading viral DNA are integrated into the bacterial genome. These stored viral sequences enable the bacterium to recognize and defend against future infections more quickly and efficiently than the first time. When the same viral DNA is detected in the bacterium again, CRISPR-associated (Cas) proteins spring into action. The Cas proteins are guided to the virus, where they induce double stranded breaks in the viral DNA. Without properly functioning DNA, the virus dies (Addgene CRISPR History). Despite its decades-long presence in the scientific community, the use of CRISPR as a gene editing tool was not discovered until the mid-2010s. Researchers Jennifer Doudna and Emmanuelle Charpentier collaborated together to devise a system composed of CRISPR, Cas proteins, and RNA (Jinek et al., 2012). The result yielded a programmable gene-editing system to target specific sections in DNA in complex organisms, such as humans (Addgene CRISPR History). Figure 1. An overview of target recognition and DNA cleavage for CRISPR/Cas9 systems. The Cas9 protein (blue) is guided to the target sequence (green) in the organism’s genome through guide RNA (red). Cas9 binds to the targeted DNA sequence, where the DNA is unwound and then cleaved at the target site. Cas9 unbinds from the DNA once the cleavage is complete. Figure adapted from Addgene. Mechanism of CRISPR in Human Cells The application of CRISPR in human cells is significantly more complicated than in bacterial systems. While bacterial genomes contain millions of base pairs, the human genome contains billions of base pairs. This difference makes it much more difficult to target specific sequences in the human genome—a challenge that has historically limited gene therapy. However, modern CRISPR technology addresses this limitation through its unique molecular and customizable design. In CRISPR-based gene editing, a Cas protein—most commonly Cas9—is paired with a synthetic guide RNA (gRNA). The guide RNA is engineered by the researchers to be complementary to a specific target DNA sequence within the genome. Once introduced into a cell, the guide RNA directs the Cas9 protein to the desired location in the DNA, where Cas9 creates a double-stranded break. Without the guide RNA present, Cas9 would cut the DNA in a nonspecific pattern. In order to stay alive, cells must be able to repair themselves. Because of this, cells possess intrinsic DNA repair mechanisms that are activated following DNA damage. Therefore, after CRISPR-induced cleavage at the specific DNA site, the cell will activate these mechanisms and begin to repair itself. Scientists can exploit these repair processes to alter genetic information to their desired goal. One scientific approach involves completely removing a certain genetic sequence to deactivate and disable protein expression of that gene entirely. Another method includes researchers providing a DNA template sequence for the cell to use during repairs, which would insert the desired DNA sequence into the genome. This method can result in eliciting specific phenotypes in the organism to study the function of a specific gene, or replacing mutated genetic sequences with healthy functioning versions (Salanga & Salanga, 2021).The latter is often the goal of CRISPR-based therapies. CRISPR and Its Ethical Controversies Despite its positives, several technical challenges and ethical concerns surrounding CRISPR still remain, including off-target effects, delivery efficiency, and long-term safety. Ethical concerns have also played a major role in shaping the conflict surrounding CRISPR procedures in humans. In 2018, the announcement of the first genetically edited human embryos brought these concerns to the forefront. This project altered the genome of twin IVF embryos to insert a mutation that would protect the embryos from the HIV virus. The edits made were done using germline editing—a type of genetic editing where the changes are passed from parent to offspring. Germline editing remains controversial in the scientific community for its heritable properties, leaving the ethics of the project in question by many. Although the study resulted in two successful and healthy births, the work was internationally condemned, and several of the researchers involved were later convicted of illegal medical practices (Scientific American, 2020). Despite these criticisms, the project demonstrated the success of embryonic CRISPR/Cas9 editing in human subjects. This research trial ultimately intensified global discussion regarding the responsible use of gene-editing in humans. Some researchers oppose gene editing entirely, as the novelty of the technology can lead to unpredicted consequences in humans. Others argue that the technology could be the key to preventing devastating genetic diseases before birth. Some middle-ground scientists commonly propose a compromise between the two sides: restricting CRISPR applications to somatic cells—non-reproductive cells—only to ensure that genetic modifications made in an individual are not passed on to future generations without their consent. Clinical Progress and Therapeutic Successes Despite ongoing ethical debates, CRISPR technology has demonstrated significant clinical potential. Multiple human clinical trials for CRISPR-based treatments are currently underway—most with encouraging results. For instance, CRISPR-based therapies have been shown to reduce cholesterol and triglyceride levels by approximately 50% in individuals with inherited lipid disorders (Cleveland Clinic, 2025). Additionally, immunotherapies incorporated with CRISPR have shown improved therapeutic potential compared to traditional cancer treatments by enhancing immune cell targeting of solid tumors and malignant blood cancers (Khan et al., 2016). In early 2025, a landmark achievement further demonstrated the therapeutic promise of CRISPR. A human infant was successfully treated using a personalized CRISPR-based therapy for severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare and life-threatening metabolic disorder (Musunuru et al., 2025; Children’s Hospital of Philadelphia, 2025). CPS1 deficiency disrupts the urea cycle, preventing the conversion of toxic ammonia into urea in the liver. Once ammonia accumulates, patients experience severe neurological and organ damage, often leading to infant death. Researchers at the Perelman School of Medicine at the University of Pennsylvania developed a base-editing therapy that precisely targeted the genetic variants responsible for the disorder. The treatment was delivered using lipid nanoparticles designed to transport the CRISPR components to liver cells via the bloodstream. The patient, referred to as KJ, experienced no adverse side effects and demonstrated improved metabolic stability and immune resilience (Musunuru et al., 2025). Ultimately, KJ represents the first human patient to ever receive personalized CRISPR therapy as a medical treatment, making this a revolutionary discovery for clinical progress. Significance of CRISPR-Based Therapies Cases such as KJ’s demonstrate how CRISPR introduces alternative treatment options for patients who cannot benefit from conventional medicine. In the case of CPS1 deficiency, the primary treatment option is liver transplantation. However, infants who are often too young and medically unstable to undergo such an invasive procedure are left without access to standard care. But CRISPR offers a minimally invasive option for younger patients, reducing their risk and potential side effects. In addition, CRISPR corrects the underlying genetic cause rather than simply managing symptoms alone as with transplantation. More broadly, CRISPR enables a shift toward personalized medicine, in which therapies are tailored to an individual’s unique genetic profile. This approach has the potential to improve quality of life and extend patient survival across a wide range of genetic disorders (Ahmed et al., 2026). Ultimately, CRISPR can become a powerful, life-saving tool for future patients with complex medical diagnoses and unique health circumstances that cannot be treated with standard medical practices. The Future of CRISPR Although the technology behind CRISPR is relatively new, its impact on biomedical research and medicine has been transformative. The ability to precisely target and modify disease-causing genes has already reduced symptom severity and improved life outcomes for patients with genetic disorders. As the technology continues to evolve, the applications and accessibility of CRISPR are expected to expand even further. Recent innovations include researchers at Stanford University integrating artificial intelligence with CRISPR to improve guide RNA design and prediction of off-target effects (Stanford Medicine, 2025). AI-assisted CRISPR can increase accessibility for scientists with little experience in gene-editing technologies, ultimately making the treatment more accessible for patients. Such advancements may accelerate research, improve patient safety, and broaden the adoption of CRISPR therapies in healthcare. Additionally, ongoing clinical trials continue to explore CRISPR’s potential to treat a wide range of rare and common genetic diseases. With the success of KJ’s treatment, researchers are now looking towards applying CRISPR towards diseases such as sickle cell anemia and Huntington's Disease. Even though technical and ethical challenges remain, CRISPR represents one of the most promising tools in modern medicine, offering new hope for conditions once considered untreatable. References Ahmed, R., Alghamdi, W. N., Alharbi, F. R., Alatawi, H. D., Alenezi, K. M., Alanazi, T. F., & Elsherbiny, N. M. (2025). CRISPR/Cas9 system as a promising therapy in thalassemia and sickle cell disease: A systematic review of Clinical Trials. Molecular Biotechnology, 68(1), 23–32. https://doi.org/10.1007/s12033-025-01368-x Cleveland Clinic first-in-human trial of CRISPR gene-editing therapy shown to safely lower cholesterol and triglycerides. Cleveland Clinic. (2025, November 8). https://newsroom.clevelandclinic.org/2025/11/08/cleveland-clinic-first-in-human-trial-of-crispr-gene-editing-therapy-shown-to-safely-lower-cholesterol-and-triglycerides CRISPR history and development for Genome Engineering. Addgene. (n.d.). https://www.addgene.org/crispr/history/ Ishino, Y., Shinagawa, H., Makino, K., Amemura, M., & Nakata, A. (1987). Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. Journal of bacteriology, 169(12), 5429–5433. https://doi.org/10.1128/jb.169.12.5429-5433.1987 Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science (New York, N.Y.), 337(6096), 816–821. https://doi.org/10.1126/science.1225829 Joseph, A. (2024, February 20). CRISPR babies scientist sentenced to 3 years in prison. Scientific American. https://www.scientificamerican.com/article/crispr-babies-scientist-sentenced-to-3-years-in-prison/ Kay, C. (2025, September 16). AI-powered CRISPR could lead to faster gene therapies, Stanford Medicine Study finds. News Center. https://med.stanford.edu/news/all-news/2025/09/ai-crispr-gene-therapy.html Khan, F. A., Pandupuspitasari, N. S., Chun-Jie, H., Ao, Z., Jamal, M., Zohaib, A., Khan, F. A., Hakim, M. R., & ShuJun, Z. (2016). CRISPR/Cas9 Therapeutics: A Cure for cancer and other genetic diseases. Oncotarget, 7(32), 52541–52552. https://doi.org/10.18632/oncotarget.9646 Musunuru, K., Grandinette, S. A., Wang, X., Hudson, T. R., Briseno, K., Berry, A. M., Hacker, J. L., Hsu, A., Silverstein, R. A., Hille, L. T., Ogul, A. N., Robinson-Garvin, N. A., Small, J. C., McCague, S., Burke, S. M., Wright, C. M., Bick, S., Indurthi, V., Sharma, S., … Ahrens-Nicklas, R. C. (2025). Patient-specific in vivo gene editing to treat a rare genetic disease. New England Journal of Medicine, 392(22), 2235–2243. https://doi.org/10.1056/nejmoa2504747 Salanga, C. M., & Salanga, M. C. (2021). Genotype to Phenotype: CRISPR Gene Editing Reveals Genetic Compensation as a Mechanism for Phenotypic Disjunction of Morphants and Mutants. International journal of molecular sciences, 22(7), 3472. https://doi.org/10.3390/ijms22073472 Seven degrees from one trillion species of microbes. NSF. (2021, August 4). https://www.nsf.gov/news/seven-degrees-one-trillion-species-microbes World’s first patient treated with personalized CRISPR gene editing therapy at Children’s Hospital of Philadelphia | Children’s Hospital of Philadelphia. (2025, May 15). https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital