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THE EFFECTS OF STRESS ON THE BRAIN:

NEUROBIOLOGICAL MECHANISMS AND HORMONAL RESPONSES

Deborah Benoliel

Athabasca University

Biological Psychology PSYC 302

Dr. Audny Dypvik

September 2023
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The effects of stress on the brain: Neurobiological mechanisms and hormonal responses

Stress is a fundamental physiological response that dates back to our evolutionary history

(Taborsky et al., 2022). It enabled our ancestors to react swiftly in life-threatening situations,

mobilizing energy and resources to confront or flee from danger. Stress can be defined as the

result of demands the exceed the resources available to an individual (Hostinar et al. 2013). Mild

stressors are normal and present no harm while even enhance physical fitness (Taborsky et al.,

2022). In contrast, intense stressors can cause strain and damage to the human body (Chu et al.,

2022). In today’s times, constant demands of work, societal expectations, information overload,

and personal challenges can lead to chronic stress, disrupting homeostasis and mental health. In

the complex interaction between the human brain and the stress response, this paper seeks to

examine the profound neurobiological mechanisms that underlie how the brain reacts to stress.

We will explore the roles of key brain regions—the prefrontal cortex, amygdala, and

hippocampus—alongside the important influence of hormones, particularly cortisol,

norepinephrine, and epinephrine. Likewise, we will discuss the far-reaching effects of stress on

the human body, cognition and emotion, and overall mental well-being.

Introduction

Stressors are a common aspect of life, and in certain circumstances, the stress response

can be considered adaptive. When encountering typical stressors, the body readies itself to

confront the challenge. Physiologically, it undergoes adjustments and adaptations, including the

release of hormones like cortisol and adrenaline (Chu et al., 2022). Intense or repeated stressors,

or even ones that are perceived as such (Hostinar et al. 2013), can cause maladaptive response

which can lead to depression, anxiety and physical ailments including heart disease and cognitive
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regression (Nowacka-Chmielewska et al. 2022, Chu et al., 2022). Prolonged exposure to stress

hormones like cortisol can alter brain structure and function, affecting areas linked to emotions,

memory, and decision-making (Sroykham et al., 2019). This, in turn, heightens vulnerability to

mood disorders and reduces resilience in coping with life's ups and downs (Yaeger et al., 2020).

Recognizing the intricate interplay between stress and mental health emphasizes the urgency of

adopting stress-reduction techniques, seeking therapy, and building strong support systems to

safeguard our psychological well-being in an increasingly complex and demanding world.

Literature review

The Neurobiological Mechanism of Stress Response

The stress response is a finely tuned orchestration of various neurobiological mechanisms

that work together to prepare the body for immediate action in the face of perceived threats

(Joels et al., 2009). One key player in this process is the hypothalamic-pituitary-adrenal (HPA)

axis. When a stressor is detected, the hypothalamus releases corticotropin-releasing hormone

(CRH), which triggers the pituitary gland to release adrenocorticotropic hormone (ACTH).

ACTH then signals the adrenal glands to produce and release cortisol, the primary stress

hormone (Kalat, 2019). Cortisol plays a central role in mobilizing energy reserves and regulating

various physiological functions to enhance the body's ability to cope with stress. Cortisol will

elevate the sugar levels and increase available energy to address and fight the difficult situation

at hand (Hannibal et al., 2014). It may also enable the consolidation of memories created by

stressful experiences for future survival purpose and evasion of danger (Hannibal et al., 2014).

Extensive or frequent activation of the HPA axis can lead to chronic inflammation and general

physiological body pain (Hannibal et al., 2014).

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Prolonged exposure to high levels of cortisol and a flight or fight state are also related

with high brain activity and reduced cognition (Sroykham et al., 2019). In a study performed by

the aforecited researcher, Alzheimer patients showed greater exposure to cortisol had greater

neural atrophy in the hippocampal and amygdala leading to deficits in emotional regulation and

general cerebral circulation (Sroykham et al., 2019). In children, there is evidence that HPA axis

early reactivity to adversity in conjunction with genetic vulnerability can evolve into emotional

and behavioral disorders (Gunnar, 2022). This can be a result from childhood stressors, exposure

to violence or other experiences that younger people would have difficulty addressing or

processing and that remain unresolved (Gunnar, 2022).

Simultaneously, the sympathetic nervous system is activated, resulting in the release of

norepinephrine and epinephrine (adrenaline) from the adrenal medulla (Chu et al., 2022). These

stress hormones prepare the body for "fight-or-flight" responses by increasing heart rate,

redirecting blood flow to vital organs, and sharpening sensory perception. This heightened state

of alertness enables quick decision-making and rapid responses to potential dangers (Wei et al.,

2023).

Neurotransmitters, the brain's chemical messengers, also play a crucial role in the stress

response. Glutamate, an excitatory neurotransmitter, becomes more prevalent during stress,

promoting heightened neural activity and enhancing attention and memory (Kalat, 2019). On the

other hand, gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, works to

counteract the excitatory effects of glutamate, promoting relaxation and dampening the stress

response (Kalat, 2019). The balance between these neurotransmitters influences an individual's

cognitive and emotional processing, shaping how they perceive and respond to stressors (Duman

et al., 2019). In their clinical experiment, Duman et al., (2019) demonstrate a correlation between
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alterations of glutamate and GABA on synapse and behavioral responses, including induction of

depressive-like effects and symptoms.

The Brain Regions and Response to Stress

The brain's response to stress involves a dynamic interaction among several key regions,

each contributing to different aspects of the stress experience. The prefrontal cortex (PFC),

known for its role in higher-order cognitive functions, is greatly impacted by stress. Chronic

stress can impair executive functions and decision-making abilities, compromising an

individual's capacity to plan, reason, and self-regulate (Wei et al., 2023). The PFC also plays a

crucial role in emotional regulation, and its dysfunction is linked to heightened susceptibility to

stress-related disorders such as depression and anxiety, where emotional control becomes

compromised (Chu et al.2022). Furthermore, childhood trauma was shown to increase

internalized and externalized behaviors in adolescents and young adults (Wei et al., 2023). This

corroborates well with earlier findings as reported by…..

The amygdala, often referred to as the brain's "fear center," is central to the perception of

threats and the initiation of fear and anxiety responses (Kalat, 2019). Under stress, the

amygdala's activity increases, leading to heightened threat perception and an enhanced emotional

response to stressors. This heightened reactivity can have significant implications for emotional

disorders and trauma-related conditions, as heightened amygdala activity is often observed in

individuals with conditions such as post-traumatic stress disorder (PTSD) (Yaeger et al., 2020).

Reappraisal is a cognitive technique that centers on the interaction between the prefrontal

cortex (PFC) and the amygdala in the brain. The PFC, responsible for logical reasoning, aids

individuals in reinterpreting and reframing stressful situations, while the amygdala, known for
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its emotional processing, plays a vital role in recalibrating emotional responses to these

stressors. The strength of the connection between the PFC and the amygdala serves as a

determinant of an individual's ability to perform effective reappraisal (Kalat, 2019). A healthy

neural link facilitates a smoother transition from initial emotional reactions to more rational and

constructive perspectives. ultimately enhancing one's capacity to cope with and manage stress.

This dynamic interplay underscores the importance of the brain's wiring in shaping our

emotional responses and coping strategies in the face of adversity.

The hippocampus, a region crucial for memory formation and learning, is also deeply

affected by stress. Chronic stress can lead to reduced neurogenesis (the birth of new neurons) in

the hippocampus, impacting memory consolidation and retrieval (Hannibal et al., 2014). This can

result in long-term adverse effects on learning abilities and cognitive flexibility. Moreover, the

hippocampus is associated with conditions like PTSD, where traumatic experiences may disrupt

its normal functioning and contribute to flashbacks and memory disturbances (Yaeger et al.,

2020). Hippocampal degeneration can compound the effect of inflammation on the experience

of pain and depression (Hannibal et al., 2014).

Understanding the connection of these brain regions in the stress response sheds light on

the intricate neural mechanisms underlying stress-related disorders. The intricate interplay

between the prefrontal cortex, amygdala, and hippocampus helps shape our cognitive and

emotional responses to stressors, influencing our capacity to adapt, cope, and recover from

stressful experiences. Studies of older population show a significant correlation between

neurodegeneration to depression and anxiety (Sroykham et al., 2019).

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The Role of Hormones in Stress Response

The brain's response to stress involves complex hormonal mechanisms that influence

various brain regions, contributing to both adaptation and dysregulation in which the hormone

cortisol plays a pivotal role. It helps regulate metabolism and the immune response, redirecting

energy toward immediate needs during stress (Hannibal et al., 2014). However, prolonged

elevation of cortisol levels can impair memory consolidation and retrieval, potentially

contributing to cognitive issues in chronic stress. Likewise, Luo and his colleagues (2023)

demonstrate that early life-stress can induce social-related impairment in later years. In the

aforementioned study, Luo et al. separated young mice for 3 weeks from their mother post-natal

which resulted in social impairment and hypoactivity in the anterior cingulate cortex. They also

report orexin as mediating and enhancing the diminished social ability in the young mice (Luo et

al., 2023).

Norepinephrine and epinephrine, also known as adrenaline, provide immediate arousal

and enhance attention focus during stressful situations (Kalat, 2019). This heightened state of

alertness can be beneficial in the short term but may have long-term implications for stress-

related disorders, as sustained high levels of these neurotransmitters can strain the brain (Chu et

al., 2022). Orexin, a recently discovered neuropeptide/hormone (Yaeger et al., 2020) contributes

to arousal, appetite and reward seeking behavior. More recently, research has shown that orexin

is helpful to managing stress and regulating mood. However, orexin seems reciprocally

dysregulated by depression, anxiety and stress related conditions (Jazmine et al., 2020) which

often further exacerbates adverse conditions.

Stress significantly influences neuroplasticity, the brain's ability to change and adapt.

Chronic stress can lead to detrimental impacts on synaptic connections and structural changes in
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the brain (Joel et al., 2009). These alterations may correlate with mood disorders, as structural

changes in areas like the prefrontal cortex and hippocampus are associated with conditions like

depression and anxiety. Widespread inflammation instigated by stress may produce autoimmune

hypersensitivity and oxidative or free radical damage (Hannibal et al., 2014).

The concept of allostatic load refers to the wear and tear on the brain and body resulting

from chronic stress. Over time, this can lead to the development of stress-related health issues

and disorders. Stress is a known contributor to conditions such as depression, anxiety, and PTSD,

all of which involve alterations in brain function and structure. Furthermore, stress has profound

effects on the immune system, weakening its ability to defend against infections and potentially

exacerbating existing health problems. Some studies have identified females as more vulnerable

to stress related psychological dysfunction, presenting with clos to twice the rate of males of

affective disorder diagnosis (Yaeger, J. D. W. et al., 2020). Recognizing the multifaceted impact

of stress on the brain and the body underscores the importance of stress management and the

development of coping strategies to mitigate its long-term consequences.

The Coping Mechanisms

Coping with stress involves various mechanisms, each influenced by genetics, early-life

experiences, and individual resilience (Hostinar et al., 2013). Genetics can predispose individuals

to varying stress responses; some may inherently possess greater emotional resilience, while

others may be more susceptible to stress-related disorders based on genetic factors. Furthermore,

the interplay of gene X experience in early years greatly shape the physiological and emotional

response in adulthood (Gunnar, 2021)

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Mindfulness, meditation, and cognitive-behavioral techniques offer powerful tools for

managing stress (Tungtong, 2023). These practices encourage self-awareness, emotional

regulation, and the cultivation of a resilient mindset. Mindfulness, for instance, promotes living

in the present moment, reducing the rumination on past or future stressors. In a cross-sectional

study of cancer patients, Tungtong and his team (2023) assess the ability of reappraisal in the

participants due to mindfulness or rumination practices. Mindfulness correlates with a more

positive affect as it supports an individual's ability to reassess stressful situations. Furthermore,

participants appeared to "decenter" by shifting their focus from the stressful situation towards

adopting a broader mindset. This shift may include acknowledging other potential positive

aspects of the situation and adopting a more balanced reaction to it (Tungtong, 2023)

Similarly, engaging in regular physical activity benefits the central nervous system

(CNS), improving mood and enhancing cognitive function, such as memory and learning

(Nowacka-Chmielewska et al., 2022). It is also associated with increased production of

substances that promote brain health while reducing inflammation. Recent studies show that

energy demands of exercising stimulates cellular bioenergetics, a process that removes damaged

neurons and cells in the CNS, thereby reducing inflammation (Nowacka-Chmielewska et al.,

2022). Additionally, regular physical activity boosts the ability to handle stress effectively

(Leckman, 2014). Ultimately, early detection of stress and the integration of stress management

education into pain rehabilitation can support effective pain management, reduce the risk of

chronic and depressive symptoms, decrease disability, and enhance overall quality of life

(Hannibal et al., 2014).

Social support, a significant coping mechanism, has protective effects on mental health

(Gunnar, 2021). Strong social networks provide emotional validation and practical assistance
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during challenging times (Luo et al., 2023). The mere presence of social support can attenuate

the physiological response to stress, reducing its negative impact (Hostinar et al. 2013). In

contrast, loneliness has been identified as a robust negative predictor of overall wellness (Luo F.

et al., 2023). Experience is said to be important in what Hostinar and his colleagues (2013) call

social buffering. Previously secure relationships will serve as the most effective source of

support for an individual during their current period of stress (Hostinar et al., 2013). In his

conclusion of literature review, Leckman (2014) urges caregivers and parents to decrease severe

punishment and encourages positive and enriching childhood experiences, anticipating a

decrease in various biomarkers linked to neuro inflammation.

Resilience is a core coping mechanism to stress. It involves the capacity to bounce back

from adversity and adapt positively to life's challenges. Resilient individuals tend to exhibit

greater emotional strength, problem-solving abilities, and a more optimistic outlook, all of which

bolster their ability to navigate and recover from stressful situations (Philips, 2019). In their

study of emotional and psychological well-being during the COVID pandemic, Luo and his

colleagues (2023) identify resilience as involving determination, hope and calm. Countries in

which these characteristics were more present reported greater psychological well-being despite

the stressful reality the world was in (Luo et al., 2023).

Oxytocin (Hostinar et al. 2013)

Understanding these coping mechanisms highlights the complexity of managing stress

and emphasizes the importance of developing a diverse toolkit to mitigate its impact. Genetics,

early-life experiences and environmental realities lay the foundation, while mindfulness, social

support, and resilience can be cultivated and honed to build effective stress coping strategies for

improved mental well-being. It is important to likewise recognize the possible positive effects of
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stress on exposing youth to challenge and possibly engaging them in metacognition and choice

of how they react and reappraise the situation (Philips, 2019). It is only through challenge that

progress and growth occurs.

Discussion

This paper delves into the effects of stress on the brain, exploring neurobiological

mechanisms and hormonal responses. Stress, a physiological response rooted in our evolutionary

history, can be adaptive but also poses risks when chronic or intense. Key brain regions like the

prefrontal cortex, amygdala, and hippocampus are discussed, revealing how stress can impair

cognitive functions, emotional regulation, and memory, contributing to conditions such as

depression and anxiety. Hormonal responses, including cortisol, norepinephrine, and

epinephrine, are examined for their role in preparing the body for the "fight-or-flight" response

and their potential long-term consequences. The concept of allostatic load is introduced,

highlighting the cumulative toll of chronic stress on both the brain and the body, with certain

individuals, including females, being more vulnerable. Coping mechanisms like mindfulness,

physical activity, social support, and resilience are explored as crucial tools for managing stress

and enhancing mental well-being, alongside the genetic and early-life factors shaping an

individual's stress response. In summary, this paper underscores the complexity of stress's impact

on the brain and emphasizes the importance of stress management techniques and coping

strategies to mitigate its enduring consequences on mental health.

Future research could explore methods for identifying individuals who are particularly

susceptible to adverse reactions resulting from chronic stress. This exploration might involve the

utilization of objective measures of cortisol levels, attainable through blood or urine samples,

providing a valuable biomarker for stress response assessment. Additionally, the development
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and application of coping scales can be instrumental in pinpointing those most vulnerable to the

detrimental effects of stress, paving the way for proactive models of stress management

education tailored to individual needs. Indeed, investigating the creation of a preventative model

for stress overload would not only be beneficial to individuals but also serve as a valuable

contribution to society's overall well-being, potentially reducing the prevalence of stress-related

health issues and enhancing mental resilience.

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