Beyond The Nerves: The Science Of Anxiety And Our Brain

Anxiety disorders are the most common type of mental illness, affecting approximately 20% of adults and 25% of adolescents in the US.¹ ‘Anxiety’ is defined by the American Psychological Association (APA) as “feelings of tension, worried thoughts, and physical changes.”

Anxiety is an important emotion for survival. It is a normal, healthy response in new and unfamiliar situations. However, these feelings are often debilitating for those with anxiety disorders and interfere with their daily lives.

Although the exact causes are unknown, research has suggested that anxiety disorders may be related to dysfunction in certain areas of the brain² and potential changes in signaling and connectivity between brain regions.³

Understanding the science of anxiety is important: How our brain responds, what our body tries to tell us, and what scientists say. Knowing the cues and realizing that anxiety is more than ‘just nerves’ is important in understanding how to best manage your anxiety. Read on to learn what we know about anxiety and evidence-based tips to reduce it.

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We make it easy for you to participate in a clinical trial for Anxiety, and get access to the latest treatments not yet widely available - and be a part of finding a cure.

How does the brain respond to anxiety?

Fear is usually a response to potential short-term threats and prepares the body to cope with danger through activating the body’s fight-or-flight response.

When you see or hear potential danger, this information is relayed to the amygdala, the region of the brain which assesses information received from your surroundings and plays a key role in your fear response.⁴ The amygdala connects to many different brain regions including the hypothalamus. The hypothalamus releases numerous hormones which communicate with the rest of the body and coordinate the stress response.

The sympathetic nervous system is responsible for the body’s fight-or-flight response and innervates different parts of the body. It provides a burst of energy to prepare the whole body for intense physical activity by releasing two key stress hormones (catecholamines):

  • Epinephrine (adrenaline)

  • Norepinephrine (noradrenaline)

Together, these hormones lead to bodily changes that prepare you to confront or flee danger. The chain reaction can result in the following events:

This response is incredibly efficient and can happen before you realize it. If the threat or potential danger is still present after the initial response, the increase in catecholamines triggered by that response activates a second component of the brain – the hypothalamic–pituitary–adrenal (HPA) axis.⁵

The HPA axis is a system that involves the hypothalamus and pituitary gland of the brain, and the adrenal glands attached to the top of each kidney.

A hormone called ‘corticotropin-releasing factor’ (CRF) is released from the hypothalamus. CRF binds to receptors on the pituitary gland, releasing adrenocorticotropic hormone (ACTH).⁶ Ultimately, this stimulates the adrenal glands in the kidneys to release cortisol – the stress hormone.

This hormone circulates through the body for a few hours after encountering the potential threat before it begins inhibiting the release of ACTH and CRF through negative feedback mechanisms.

To counteract the stress response, the parasympathetic nervous system controls the 'rest-and-digest' response. This acts as a counterbalance to the sympathetic nervous system by releasing neurotransmitters (chemical messengers) to help the body relax. The neurotransmitters circulate throughout the body to promote the following effects:

When the response becomes a problem

Short-term anxiety is a normal experience, but chronic activation of the stress response with high levels of stress hormones can affect physical and mental well-being.

Anxiety disorders are associated with amygdala hypersensitivity and prolonged HPA axis activation. This can make you more sensitive to threats and false alarms. High levels of stress hormones can lead to physiological changes such as:⁷

  • Increased blood pressure: This can raise the risk of stroke and heart attack

  • Depressed immune system: Inflammation responses are reduced, thus leading to reduced function of immune responses

  • Decreased rate of wound healing and tissue repair: White blood cell actions are limited, thereby increasing the risk of further tissue damage

  • Increased buildup of fat tissue: Cortisol increases appetite, which may cause increased calorie intake

An increasing amount of evidence suggests a relationship between anxiety and structural degeneration of several key brain regions, such as the prefrontal cortex. Using imaging techniques, scientists have shown that chronic stress can selectively impair attention control and connectivity in a brain network involved in shifting attention.⁸

Another study involving brain-imaging techniques appears to agree with these findings as the researchers found that accumulated levels of stress were associated with reduced size in certain areas of the prefrontal cortex.⁹ A common area that was affected was the medial prefrontal cortex; a region believed to regulate stress and emotional arousal. This study suggested that these changes in the prefrontal cortex could play a role in depression, addiction, and other stress-related disorders.

Risk factors

The causes of anxiety are multifactorial and complicated. However, several causes and risk factors are thought to contribute to anxiety development:¹⁰

  • Traumatic life experiences

  • Abuse

  • Genetics

  • Medical conditions

  • Certain medications

  • Significant life changes

  • The presence of other mental health disorders

  • Ongoing stressors

Evidence-based tips for managing anxiety

Although the long-term effects of stress and anxiety sound daunting, it doesn’t have to be that way forever. The brain is a highly resilient organ. The brain can change based on experience through neuroplasticity, which allows a significant degree of regrowth and regeneration.¹¹

Knowing how to manage anxiety is an important step towards relief. Here are some treatments that have been proven beneficial based on peer-reviewed scientific evidence:

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs), a treatment for depression, are also considered to be an effective treatment for anxiety disorders.¹² This type of drug reduces the reuptake of the neurotransmitter serotonin and increases its activity in the brain.

SSRIs are relatively safer and more tolerable than other drug options. However, individual response and potential adverse effects will largely depend on the individual and the type of SSRI.

SSRIs help reduce the symptoms of anxiety in many patients.¹³ How long you should take SSRIs should be discussed with your doctor. It may depend on the individual, the severity of the condition, response to treatment, and other components of the management plan.

Cognitive behavior therapy

Cognitive behavior therapy (CBT) is considered the ‘gold standard’ in therapy for anxiety disorders. It aims to change negative thinking patterns and habits, which may underlie anxiety.¹⁴

A CBT practitioner will work in a structured, collaborative manner with the individual to understand their attitudes, behaviors, thought processes, and how these may influence anxiety.

CBT is an adaptive form of therapy that can be personalized and is effective both as a standalone treatment or when combined with medication. CBT may incorporate techniques to help patients desensitize to triggers that cause anxiety.

Exposure therapy is one type of CBT that involves repeated, graded exposure to triggers or situations that may lead to anxious behaviors. Through repeated exposure, this type of therapy helps individuals overcome avoidance and develop new ways of confronting fears.

Multiple scientific reviews support the effectiveness of CBT for anxiety disorders, including generalized anxiety disorder¹⁵ and panic disorders.¹⁶

Mindfulness-based cognitive therapy

Mindfulness-based cognitive therapy (MBCT) is a type of psychotherapy that incorporates elements of CBT and meditative practices to help an individual change behaviors and unhelpful thoughts that perpetuate anxiety.

By implementing active-awareness techniques, MBCT teaches people to consciously pay attention to their current mood, thought patterns, and attitudes in a non-judgmental manner.

Both CBT and MBCT have proven effective for anxiety disorders, as studies have noted significant reductions in anxiety and depressive symptoms over a period of time.¹⁷ For some individuals, therapy may be combined with medication, depending on factors including:

  • Individual preferences and goals

  • Response to treatment

  • Severity of symptoms

Lifestyle changes

Lifestyle changes can play an important role in reducing anxiety and chronic stress. These may include dietary adjustments, improving exercise habits, or increasing the frequency of doing enjoyable activities.

Exercise

Exercise is often the first lifestyle change recommended by professionals. Research has shown exercise to be protective against physical symptoms of anxiety.¹⁸

Exposure to moderate- or high-intensity physical activity helps increase tolerance to anxiety symptoms while decreasing anxiety sensitivity. This may be through lowering the reactivity of the sympathetic nervous system and the HPA axis.¹⁹

While research is ongoing to establish the link between anxiety and exercise, patients are highly encouraged to stay physically active regularly to help reduce the severity of symptoms.

Diet

Some research indicates that a healthy diet may reduce the risk of anxiety.²⁰ Food influences the gut microbiome, which can influence amygdala function and, as a result, the stress response and anxiety.

Highly processed foods are thought to influence these receptors by increasing inflammatory factors, which can worsen anxiety symptoms. Nicotine, caffeine, alcohol, and other stimulants can also trigger the adrenal glands to release adrenaline.²¹ Thus, patients are recommended to either lower their intake or avoid these foods entirely.

Although dietary changes alone can improve a person’s mood, they may be more effective with other treatments, such as regular exercise or medication. As it takes some time for these changes to take effect, patience is encouraged.

Stress management

Identifying and understanding sources of ongoing stress can help you relieve some pressure and develop strategies to manage your stressors. Whether it be work, relationships, financial difficulties, or other lifestyle aspects, acknowledging your stressors are key to finding out the best way to handle your stress.

Certain techniques to help identify and manage stressors include:

  • Keeping a stress journal

  • Sorting your stressors into categories – which ones are out of your control? Which ones can you control and eliminate?

  • Reviewing your lifestyle – are you taking on too much? Can you hand over tasks to others?

  • Connecting with friends and family – talking about your stressors with trusted people can help improve your resilience to stress²²

  • Getting restful sleep

Stress is a natural reaction to life events. However, prolonged stress and not taking time for yourself to relax can lead to physical and mental health problems.

When to see a doctor

While any time is a good time to see a doctor when you’re feeling anxious, if you find that the anxiety lingers or is having a significant impact on your life, then it’s a good idea to make an appointment.

You will most likely need to answer a few questions about your medical history and symptoms.

If appropriate, your doctor may refer you to a trained mental health professional such as a psychiatrist or psychologist for further assessment.

The lowdown

Anxiety is a common emotion and is a natural response to potential dangers. However, for those with anxiety disorders, anxiety can become overwhelming and impact your well-being and ability to function.

While short-term anxiety is a normal part of life, you don’t have to live with constant fear and worry. With the rapid progression of mental health research and the support of mental health professionals, many effective treatments are available to help you get back on track.

  1. Facts and statistics | Anxiety & Depression Association of America

  2. Neurobiological aspects of social anxiety disorder (2009)

  3. The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology (2009)

  4. Amygdala activity, fear, and anxiety: Modulation by stress (2010)

  5. The hypothalamic-pituitary-adrenal axis: Development, programming actions of hormones, and maternal-fetal interactions (2021)

  6. Physiology, adrenocorticotropic hormone (ACTH) (2021)

  7. The impact of stress on body function: A review (2017)

  8. Psychosocial stress reversibly disrupts prefrontal processing and attentional control (2008)

  9. Cumulative adversity and smaller gray matter volume in medial prefrontal, anterior cingulate, and insula regions (2012)

  10. Risk factors for the onset of panic and generalised anxiety disorders in the general adult population: A systematic review of cohort studies (2014)

  11. Dynamic brains and the changing rules of neuroplasticity: Implications for learning and recovery (2017)

  12. Selective serotonin reuptake inhibitors (2021)

  13. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology (2014)

  14. Cognitive behavior therapy (2021)

  15. Psychological treatment of generalized anxiety disorder: A meta-analysis (2014)

  16. Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta‐analysis (2016)

  17. Mindfulness-based cognitive therapy for generalized anxiety disorder (2008)

  18. Exploring exercise as an avenue for the treatment of anxiety disorders (2012)

  19. Effects of exercise and physical activity on anxiety (2013)

  20. Association of food groups with depression and anxiety disorders (2019)

  21. Complementary medicine, exercise, meditation, diet, and lifestyle modification for anxiety disorders: A review of current evidence (2012)

  22. Social support and resilience to stress (2007)

Have you considered clinical trials for Anxiety?

We make it easy for you to participate in a clinical trial for Anxiety, and get access to the latest treatments not yet widely available - and be a part of finding a cure.

Joining community groups and exercise programs for my condition made me feel empowered – but I want to be part of finding a cure.
Peter, 64

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