The Neurological Basis of Anxiety

A person suffering from an anxiety disorder experiences neurology-based changes in mood and bodily functions that are discussed in more detail in this article.

As with anxiety, various personality traits and emotional responses are by-products of the interaction between our genetic coding and environmental influences. Our genes make us more receptive to some specific stimuli and play a role in developing the resilience to some other stimuli. Our brain is a plastic organ. Thus, the role of environmental factors in its development and casting cannot be negated.

Fear and stress are normal defensive reactions to threats that help our body to deal with challenges more efficiently. Anxiety is different from fear in that it is a set of emotional and somatic reactions to a future threat that may or may not be realistic. To some extent, having anxiety is a normal human reaction. However,  if it continues for a prolonged period, it may have an adverse effect on our daily life and health.

In the state of anxiety, worrying about the future makes it difficult to concentrate and leads to irritability. Somatic symptoms like palpation, sweating, and gastrointestinal changes are also common in this state. Anxiety is considered as a disorder if such symptoms persist over a period of six or more months.

Anxiety disorders are most prevalent among people with psychiatric disorders, affecting around 10% of the population at any given time. Nonetheless, only a small number of those suffering from anxiety disorders seek treatment. This can be partially explained by the difficulties in identifying the condition. General anxiety disorder, panic disorder, specific phobias, and social anxiety are some of the most common types of anxiety disorders.

What makes a person vulnerable to anxiety disorders?

The hereditary nature of various forms of anxiety disorders has been established through clinical and observational studies. Multiple studies have demonstrated that a person is at 3–5 times greater risk of developing anxiety disorders if such a condition is found among first-degree relatives. The importance of familial clustering in anxiety has been demonstrated by a number of twin studies. Other internal factors like certain personality traits also make a person more vulnerable to developing anxiety disorders.

Apart from internal factors, environmental factors may also make some people more anxious. These factors include exposure to stressful condition, drug or alcohol use, parenting style, and stressful life events.

Neuroanatomy of stress and anxiety

Higher cognitive centers in our brain are located in the prefrontal cortex. They are involved in thinking, planning, and social behavior. From an evolutionary perspective, the prefrontal cortex is the “newer” part of the brain that helps us to keep our emotional responses in check.

Most of the emotion processing takes place in more ancient parts of the cortex. These anatomical brain structures are collectively called the “limbic system”. One fundamental structure in the limbic system is the hippocampus that plays a vital role in the stress response and regulation of the hypothalamic–pituitary–adrenal (HPA) axis. Both hippocampal growth and neurogenesis play an essential role in the development of resiliency towards stress and anxiety.

But perhaps the most crucial part of the limbic system that plays a central role in the regulation of emotions is the amygdala. The amygdala is central to the formation of fear and anxiety-related memory and has been shown to be hyperactive in anxiety disorders. It is well connected with other brain structures like the hippocampus, thalamus, and hypothalamus.

Apart from anatomical changes, it is essential to understand that brain functionality or communication between various brain centers and networks takes place through neurotransmitters. In the case of emotional responses, gamma-aminobutyric acid (GABA) is known to have an inhibitory effect on emotions, while glutamate has an excitatory effect. The roles of serotonin, dopamine, and norepinephrine are also well documented in the pathogenesis of various emotional states. Other neurotransmitters that may play a role in the pathogenesis of anxiety disorders are cholecystokinin (CCK), galanin (Gal), neuropeptide Y (NPY), oxytocin (OT), vasopressin (AVP), and corticotrophin-releasing factor.

Neuroanatomical changes in stress

Most anxiety disorder cases develop in childhood, where the long-term and repetitive experience of anxiety leads to changes in specific brain structures that can be observed using neuroimaging. fMRI studies on generalized anxiety disorder (GAD) have shown a higher level of activity in the ventrolateral prefrontal cortex. Furthermore, a significant level of activity is seen in the amygdala, especially when a person is told to focus on his or her stress, as well changes in the cingular cortex and insular cortex.

During adolescence, there is an acceleration in the physical growth, along with changes in behavior, cognition, and emotional control. The development of the body during this period may result in permanent changes in various brain areas that can be implicated in the development of psychiatric disorders in adult life.

During adolescence, it might be easier to remodel various brain structures with the help of cognitive behavioral therapy or other modalities than in adults. Meanwhile, in adults, various therapeutic agents can be used to alter the biochemical structure of the brain.

For patients with anxiety disorders, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are often prescribed as the first line treatment. Other drugs that can be used to treat various anxiety disorders include monoamine oxidase inhibitors, tricyclic antidepressants, and benzodiazepines.

Despite the immense progress in our understanding of neuroanatomy and neuroendocrinology, not all cases of anxiety can currently be treated. However, the latest research on the subject has improved the selection of drugs available for various anxiety disorders. For instance, benzodiazepines are known to be more efficient in the treatment of panic disorders than GAD.

As neuroimaging technologies continue to evolve, a better understanding of the neurobiology of anxiety is bound to influence the way we treat anxiety and other related disorders.


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Image via Graehawk/Pixabay.

Viatcheslav Wlassoff, PhD

Viatcheslav Wlassoff, PhD, is a scientific and medical consultant with experience in pharmaceutical and genetic research. He has an extensive publication history on various topics related to medical sciences. He worked at several leading academic institutions around the globe (Cambridge University (UK), University of New South Wales (Australia), National Institute of Genetics (Japan). Dr. Wlassoff runs consulting service specialized on preparation of scientific publications, medical and scientific writing and editing (Scientific Biomedical Consulting Services).
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