The Neurobiology of Anxiety

Mood and anxiety disorders are believed to stem from an imbalance among neurons in the brain’s emotional hubs instead of areas responsible for higher thought processes. They are situated in the frontal lobe, which is said to be the most recently evolved part of our brains. Furthermore, evidence shows that the brain mechanisms engaged during exposure to potentially dangerous stimuli are shared among mammals, indicating a common evolutionary advantage of having an efficient threat response system.

Two Systems

For many years, people have believed that mammals possess an inborn “fear system” within their brains which activates both the physical and mental sensations of fear when faced with danger. However, recent studies suggest a “two systems” framework is more likely; one circuit produces conscious emotions while the other triggers behavioral and bodily reactions to hazardous situations.

Distinguishing between two systems, one primarily cortical and one involving subcortical regions such as the amygdala, is a helpful construct to understand how brain mechanisms give rise to normal and abnormal feelings of fear and anxiety. Both axes in this framework operate distinctly, with one responsible for conscious emotion while another primarily works nonconsciously.

A potential danger activates the amygdala’s lateral nucleus, which triggers defensive behaviours like freezing and physiological reactions due to its connection to the amygdala’s central nucleus. Further, avoidance responses are regulated from the lateral amygdala to the basal amygdala and then to the nucleus accumbens. Although these pathways predominantly work on a subcortical level, some cortical areas still influence them. For instance, connections from both the ventromedial prefrontal cortex and hippocampus direct how defensive reactions initiated by conditioned fear are extinguished within the amygdala.

The amygdala and the BNST (bed nucleus of the stria terminalis) detect potential risks and activate circuits which lead to fear and anxiety. Fear is an outcome of the amygdala’s indirect influence, while anxiety results from the BNST’s role in a defence circuit that detects uncertain threats. In both cases, their activation triggers signals, ultimately facilitating subjective feelings of trepidation and worry.

Rather than being caused by the same subcortical circuits that underpin defensive reactions, feelings of fear or anxiety may have their roots in neural pathways located within the higher-order association cortex. These regions are involved with cognitive activities like concentration and short-term memory, encompassing both parts of the lateral and medial prefrontal cortex and portions of the parietal neocortex.

Studies suggest that conscious awareness may be particularly linked to areas in the lateral prefrontal cortex, as it is interconnected with various other cortical regions and has a strong presence in primates and humans. In addition, research indicates that activity in the insula – another frontal region – may be related to the conscious experience of bodily sensations, which may trigger perturbations or forms of anxiety from interoceptive stimuli.


When faced with acute challenges, a stress response may initially be an adaptive option; however, when such short-term effects are repeatedly experienced over time, they can result in chronic maladaptive stress responses. Such chronic distress influences neurological and psychological factors and behavioural systems when confronted by actual or anticipated danger. Moreover, enduring stress gradually strains one’s biological equilibrium, leading to various health issues like generalized anxiety disorder due to the increasing allostatic load costing the body.


Early-life experiences, genetics, and stress history all play a role in determining an individual’s resilience to cumulative stress. For example, childhood trauma or life experiences can increase the risk of depression or anxiety disorders. In addition, genetic and environmental factors such as family stress can reduce one’s tolerance for allostatic load produced by continual strain, thus increasing the chances of developing a psychiatric disorder like anxiety.

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