What Causes Anxiety?
And how to help manage it.
Hey Rewire Collective!
Welcome to this weeks’ newsletter! It’s 2025, so we’re normalizing talking about anxiety. Let’s dig into the neurobiology.
Anxiety - A Fear-Based Human Emotion
Anxiety can be thought of as a fear response1. Fear is a central motivator in humans, and evolutionarily serves a lot of purposes, from not being eaten by another animal to not starving to death1. However, when this fear response becomes exaggerated and elicited from a minor stimulus, it is pathological – or disruptive to everyday life1. Pathological fear, or anxiety, is central to different anxiety disorders, which are the most prevalent mental health conditions worldwide2.
A useful way to think about anxiety is it can be ‘adaptive’ or ‘maladaptive’2. Adaptive anxiety is typically helpful to a situation, allowing us to change our behaviour to changing environments. It does not disrupt our work, social, or family lives. Maladaptive anxiety is when the anxiety response becomes disproportionate to the environment, or when the anxiety persists despite a resolution to conflict.
Side note, but I highly recommend the Inside Out films when trying to understand emotions and anxiety.
But the line between adaptive and maladaptive anxiety is not always clear. And the way we categorise different types of anxiety does not always correlate to the underlying neurobiology. Currently, we categorise the type of anxiety someone has based on their symptoms: anxiety in social situations = social anxiety3. However, the fact that people on the same treatment with the same disorder respond differently suggests there are different underlying brain differences even in the same disorder4. So, rather than talk about different types of anxiety, I am going to talk about different brain systems.
Systems involved in maladaptive anxiety2:
Negative valence, otherwise known as assigning negative emotions and reactions to stimulus. In anxiety disorders, we see increased activation in this system compared to neurotypicals. We also see changes in how uncertain and ambiguous threats are processed. Finally, we see changes in attention networks – how we are focusing on negative stimulus and looking out for it.
Increased activation in response to acute threats.
There are two pathways involved in responding to acute threats: the direct and indirect paths. The direct pathway sends information from the thalamus to the amygdala. The amygdala assesses the threat and activates the hypothalamus to get us ready for fight or flight. The indirect pathway includes our frontal cortex and hippocampus, which look at the threat in more detail and assign it an emotion, which then changes our cognition and behavioural response. Overactivation of both these pathways is common in phobia disorders (expecting outcomes in response to specific stimuli to be worse than they are). Overactivation in these pathways also occurs in generalised anxiety disorder (expecting outcomes to be worse than they are in general).
Changes in processing ambiguous or distant threats.
This is down to the bed nucleus of the stria terminalis (BNST). The BNST is connected to areas like the amygdala, hippocampus, and hypothalamus. We see increased BNST activity in individuals with generalised anxiety disorder compared with neurotypical individuals.
Changes in attentional networks.
The insula is a key player in attention networks. It is especially good at recognizing bodily signals. Individuals with generalised anxiety have increased insula activity, showing that they are more aware of internal stimuli.
Positive valence is how we process and assign positive emotion to stimuli. The ventral striatum is key to this system. However, this is understudied in anxiety, mainly because it is not diagnostically considered a symptom of anxiety. However, we see decreased response to rewards and disrupted reward learning in individuals with anxiety.
Cognitive systems help us control ourselves and form memories. These are all affected by anxiety, but haven’t been studied as much as negative valence. The main region identified in these systems is the dorsolateral prefrontal cortex (dlPFC). In the short term, individuals have excessive activation of the dlPFC, meaning they are overfocused on tasks. However, across a longer time, there is overall reduced dlPFC activity, causing impaired working memory.
Social systems help us interact in the world with others. We see that people with anxiety have biases in how they perceive social cues, have heightened sensitivity to social rejection, and have altered self-referential processing (they way we think about ourselves). Major brain regions involved in these processes include the premotor cortex, superior temporal sulcus, temporoparietal junction, and fusiform face area.
So when we’re talking about fixing anxiety, we’re really talking about rewiring a lot of different brain pathways and circuits. I don’t say that to scare you, but rather to encourage you: these things take time, and effort, and you’re doing your best! These things won’t change overnight, so keep going!
What can we do to help us manage anxiety?
First, let’s talk to a professional. Someone with a medical education and experience in the clinical setting (AKA not me).
Some things that we know are helpful and a professional might recommend:
Cognitive behavioural therapy – this type of therapy focuses on understanding how our thoughts influence our behaviours which in turn influence our thoughts. It aims to intervene on both thoughts/beliefs and behaviours, to help reduce anxiety. Studies show that CBT reduces social anxiety by improving connectivity between the fusiform face area and amygdala2. We also see in young people with anxiety that activity in the cognitive control circuity normalises after CBT2.
Social skills training – can be integrated into CBT to help with social anxiety.
Medication* – these are known as anxiolytics, and the most common ones are selective serotonin reuptake inhibitors (SSRIs) which are also used in depression. To be completely real with you, it’s not very clear why serotonin works in anxiety. It works on a lot of different systems and is known as a ‘feel-good’ chemical for a reason, but I don’t think we have a clear reason for why these work.
If you are experiencing mild anxiety, things that can be helpful are:
*I know some people are resistant towards the idea of medicine for anxiety, and mental health disorders in general. Especially if we don’t fully understand why serotonin works. I am not in any way trying to convince you in one way or the other, I just want you to be informed. We just talked about a whole lot of brain systems that are changed in anxiety disorders. And sometimes a good way to fix a biological problem can be medicine, even if just for a short time. From my conversations with therapists, medicine is most successful when accompanied by CBT, so that you can rewire your thought patterns with the added support of a serotonin boost. It doesn’t mean you’ll be on the medicine forever, but can help the process of rewiring.*
Until Next Week,
Nicole x
P.S. Leave a comment with requests for future newsletters (parenting and burnout coming up soon)!
References
https://www.nature.com/articles/s41583-024-00880-4?fromPaywallRec=false
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. (APA, 2013).