The physiology of the fear response

To diagnose panic disorder from other differential diagnoses and be able use exposure and habituation effectively, a thorough understanding of the physiology of the fear response is essential. Being able to explain to patients what is actually happening within the body and the function of each arousal symptom is a critical success factor for engaging patients in treatment.

Often however time given to this information is limited in training due to time constraints, the condensing of curricula into shorter time frames, or a lack of physiology background and expertise that has developed over time. Worryingly, out of date, poor quality or lazy explanations of anxiety and the fear response exist in many self-help materials in circulation; even those from seemingly reputable sources and those newly published can have these problems. Many encourage safety seeking behaviours, such as distraction or do not adhere to the essential conditions. Some are also interpreted as patronising under focus group review for containing cartoons and illustrations, or being too basic in their approach. Practitioners can fall into the trap of not accurately explaining why a symptom happens, only that it occurs as a result (and let’s face it, most patients with panic disorder are acutely aware of that, but are misinterpreting their cause and consequences and unsure why their body responds in this way).

Most patients have already heard of arousal and fight and flight and they know that as previous hunter gathers, this response was helpful to us then. The response however is not a legacy from that time, we still very much need it. We share the arousal response with all other vertebrates and evolution has not removed it since Palaeolithic times, because of its important function to this day. We also never stepped out of our cave and saw dinosaurs, we were not on the planet at the same time and the great majority of hominis did not even live in caves, they were nomadic. It also tells the patient nothing about their symptoms in particular and what their purpose is in a way that informs treatment appropriately. We also do not have a steady stream of adrenalin in our bodies all the time as some materials reviewed state - or habituation simply wouldn’t work!, We have the ability to produce it on response to a perceived threat trigger. Our blood also does not ‘divert’ from its usual route around the body to the arms and legs, flow is prioritised there, on its normal course through vasodialation and vasoconstriction.

To aid with this, we have provided a thorough overview of the physiology of the fear response in the following pages and how this then applies to panic disorder. Whilst this information is not required to be relayed to the patient in full, we would strongly argue that it is a necessary level of physiological awareness for a clinician working in a CBT way to have, to ensure that assessments, information giving, selection of suitable resources and rationales given are improved.

The physiology of the fear response

As humans, we share the physiology of the fear response with other vertebrates. We are certainly not unique in our responses as humans. The fear response evolved to keep species safe. It enables us to avert danger quickly by reflexes such as jumping out of the way of an oncoming car, before we have even begun to experience the anxiety affects of the emotion of fear. In fact, the word emotion in Latin literally means emotus/emovere - to act, to move away, remove, agitate. Therefore it implies a verb, an action being implicit. In the case of fear, the action being to quickly move to respond to the threat in one of the fear cascade defences: freeze, flight, fight, flop or faint.

The nervous system in the body is divided into the central nervous system (the brain and the spine) and the peripheral nervous system. The nervous systems are in constant communication with each other through afferent (sensory) and efferent (motor) neuron activity and respond to what is happening across each area of the body. The peripheral nervous system is sub-divided into the somatic nervous system (which carries sensory information and controls skeletal muscle contractions, voluntary movement), the enteric nervous system (the gut, which has over 100 million nerve cells and is often described as the second brain. It is there that serotonin is produced. It also plays a key role in mediating the body’s immune system) and finally, the autonomic nervous system (which provides involuntary regulation of processes that lie outside of conscious control and require no conscious awareness such as breathing and heartbeat regulation, blinking, blood flow, stomach acid secretion etc.). The autonomic nervous system is the nervous system that most clinicians are aware of as having responsibility for the adrenalin response. It is composed of the sympathetic and parasympathetic systems, which have to work together in balance with each other to maintain a stable environment in the body. The parasympathetic system is responsible for ‘rest, digest, feeding and breeding’ and is active most of the time when there is no threat to respond to. It conserves resources and helps to maintain normal body functions. It is this system that steps back in to slow the

The defensive fear cascade: freeze, flight, fight, faint and flop

heart, breathing and blood flow as well as our pupil constriction when a threat has passed. The sympathetic system is involuntary by nature, it is the system that is activated when there is a stress, threat or danger trigger. It tells the body to produce adrenalin on response to the trigger, arousal occurs and then sets of a chain of autonomic, involuntary changes in the body to prepare to respond to the specific situation of the threat (also known as the ‘fear defence cascade’ within the anatomy and physiology literature. The arousal enables the individual to prepare to either actively respond by flight (run to safety), fight (attack to defend life), or more passive responses, freeze (put defence on hold to assess or hide), flop (tonic immobility when there is significant threat to life and escape or fight is not possible, where consciousness is maintained), or faint (where consciousness is lost, termed collapsed immobility by Kozlowska et al, 2015).

These changes are mediated by the neural circuits (the amygdala, hypothalamus, spinal cord, periaqueductal gray - the nucleus that plays a critical role in autonomic function, the ventral and dorsal medulla - part of the brain stem that deals with autonomic function and the ventral pontine tegmentum). The important thing to remember is that they are autonomic changes on response to a perceived threat, not choices made under voluntary conscious control. They happen within approximately 1/300 of a second to move the body to prepare for action and set of chain reactions of physical changes to meet the relevant cascade demands.

A way I developed within teaching to explain the physiology of fear cascade responses is to use a rabbit and a fox.

The fox, rabbit and the defence cascades:

danger, the field is otherwise empty. There is food to eat there and he is near his warren, where his female pair and a social group of other rabbits reside in the next field. The rabbit would not have adrenalin currently in its bloodstream. Its parasympathetic nervous system would be activated and things in the body in balance, the rabbit would be in the rest, digest, feeding and breeding’ state. Now, imagine scenario 1. The rabbit looks up and a fox is in the distance. Sensory information processing sends a signal to the amygdala in the limbic system where the arousal response begins, this is area of the brain that deals with emotional processing. It interprets the sensory data and sounds the alarm via a signal to the hypothalamus. The hypothalamus is control centre of the brain which will communicate with the rest of the body through the autonomic nervous system. It will trigger the adrenal glands above the kidneys to produce the adrenal medulla hormones - epinephrine (adrenalin) and norepinephrine (noradrenalin). Arousal has now begun and is the first step needed for the defence cascade to be activated. A series of autonomic physical, behavioural and cognitive

changes take place to prepare the rabbit for respond to the threat, even before he has begun to feel the physical effects of fear or fully process what is happening. Adrenalin will increase heart rate and flow to the brain and muscles. It will spike blood sugar by converting glycogen stores to glucose in the liver to enable it to be used as fuel. It will bind to receptors in the lung muscle cells, resulting in faster breathing. The lungs open additional pockets to enable more oxygen to be taken in with each breath.

Blood vessels are triggered to respond. The route blood takes within the body does not divert its usual course. Blood pumps up from the heart, through the brain and down and around the body, then back up to the heart. To aid the oxygenated blood reaching the arms and legs, vasodialation of blood vessels to these key areas takes place enabling the blood to get there faster, with vasoconstriction of non essential pathways minimising flow there to the level needed to maintain the area. Muscle cells contract to enable perspiration to keep the body cool, if active defence is required and insulin production is inhibited. The noradrenalin will enable vasoconstriction, narrowing of the blood vessels to increase blood pressure. The autonomic nervous system will then initiate one of the fear defence cascades. All of this will occur before the rabbit has even had time to consciously process the threat.

The fox in this scenario is at least two fields away in the distance and doesn’t yet seem to be moving in the rabbits direction. Does it make sense to flight, fight, faint, flop or freeze? What do you think you would you do if you were the rabbit? Remember that the response here is involuntary and autonomic. The rabbit (like other mammals, including humans) would ordinarily freeze first. Freezing occurs in the context of a predatory threat, context or discrete cues (Kozlowska et al, 2015). The purpose of this is to stay as still as possible and assess if it has been seen or not, be attentive to the threat, scan the environment and further prepare to respond. It also makes sense to not move and expend energy if it is not needed yet. Movement may make the situation worse, making the fox notice it and take chase, so freezing decreases the likelihood of being detected. In a freeze based response, sympathetic and

parasympathetic components are co-activated. Vagal inhibition opposes the sympathetic activation to enable the freezing response and make covert the effects of arousal. This prevents external expression of arousal symptoms. The primary autonomic changes are aimed to assist the rabbit to stay as still as possible, the muscles tense further with a heightened muscle tone specific to a freeze response. Focus of attention is now on the threat (the fox).

When the threat is further away, a freeze based response makes sense, it enables time to further prepare or assess when you cannot flee to safety (without making it worse) and you cannot fight it, as the threat is in the distance/future and not imminent. The main anxiety disorder where the threat is located in the future is obviously GAD which has a primary autonomic arousal response of freeze with the threat. Some other anxiety disorders also show situational specific freeze based responses along with fight or flight in other situations, due to the proximity of the threat when it is not imminent, compared with alternating times of active defence responses (fight/flight) when the threat is more imminent. This includes social anxiety disorder and health anxiety disorder for example. So the purpose of funnelling in the assessment is to gather specific recent examples and look at the autonomic, behavioural and cognitive symptom cluster at key time points to see if the response differs according to the situation and proximity of the threat the patient is in. Now, imagine scenario 2. The rabbit is happily in the field, looks up and this time, the fox is only one field away and appears to be looking in the rabbits direction. Arousal will be initiated again as before, this time followed by an active defence response appropriate for the situation rather than freeze. The rabbit is in imminent risk of harm as the threat is closer and higher, it will need to take aversive action to try to escape, to flee to a place of safety. When faced with an imminent threat, it makes sense that escaping the threat, fleeing to a place of safety when able to do so, is the better option to fighting. Sympathetic arousal activation is maintained and further amplified in an active defence response, motor networks remain activated, heart rate and respiration increase, sympathetic efferents inhibit digestive function in the gut, vasoconstriction of blood vessels that supply the salivary glands takes place (this can lead to a dry mouth, as in turn can the switch made to breathing through the mouth to take in more oxygen). The body will prepare for the rabbit to run, it wants to maintain the increased cardiac activation and energy to escape. The vasodialation and increased blood flow can make the person feel unsteady as it takes the route up and through the brain and can also lead to feelings of pins and needles or tingling sensations. Interestingly, fight or flight active responses have been shown to also initiate analgesia to block pain signals in the spinal cord in case of injury. Sweating can be initiated from the contract muscles under the skin to reduce body temperature as it increases through exertion

of running. The focus of the rabbits attention will be widened as its pupils dilate, it needs to focus on the exit from the field and also on the threat, the fox. A good way of thinking about this focus of attention is like watching the lead cyclist in a velodrome race. He needs to look at the finish line (his exit) but also spends a large part of the race looking back at his competitor behind him to ensure he has not caught up or will overtake him). An example of a flight response in panic disorder is any time the patient undertakes a behaviour to escape from their feelings of fear, for example physically leaving a situation before they planned, such as dropping their shopping and running out of a supermarket, or by adapting behaviour to leave a situation more quickly, for example by taking the shortest queue. Panic patients often report that they look and plan for exits and escape strategies, in case they need them. It is important to ask about these adaptations within assessment by asking for examples of situations and what they do to manage their symptoms. . Now, imagine scenario 3. This time when the rabbit looks up, the fox it is within a few meters distance and can cause imminent harm. The rabbit cannot run away quickly enough, it wouldn’t make it on time and is cornered. This time, a fight response will be used. A fight response is an active fight for its survival. From a physiological perspective, it shares the same symptoms as flight, an active defence. One noticeable change is focus of attention, now locked onto the threat (the fox). An example of a fight response within humans would be either attacking or lashing out or in an anxiety provoking situation a patient cannot escape from, a resulting peak of symptoms within a few minutes, leading to a full panic attack. Now imagine scenario 4, this time, when the rabbit looks up, the fox is right there, it cannot escape and it is not able to fight to defend itself (imagine in this situation the fox has it cornered, is far bigger a threat to the rabbit and the rabbit cannot fight back and likely survive). The flop response, tonic immobility, is a last ditched attempt to preserve life. It occurs when fight or flight is switched off and has a different physiological presentation. Sympathetic activity is withdrawn. In a flop

response, the animal or person loses control of its muscles initially and involuntarily ‘flops’ to the floor, but unlike faint, remains conscious. After the initial loss of muscle control, rigidity is present, Paralysis of the muscles occurs, meaning movement becomes temporarily suspended, which mimics rigor mortis. Rigor mortis is a post-mortem stiffening of the muscles due to chemical changes in their myofibrils. The function of a flop response is to deactivate the predators natural instinct to kill it. If the rabbit is already dead, the fox will (like most predators) carry the prey to a place of safety to eat it - or bury it for later, where he too is not at risk from a predator of his own. In a flop response, the rabbit will appear dead, it will not be responsive to touch, as such, it offers no resistance to the fox and will not scratch or bite, meaning he can carry it away to his den without much resistance. When able, the rabbit can then make one last escape attempt when the fox releases control of it and run. There are numerous examples of this within the animal world, across mammals, insects, fish, reptiles and birds. Many can be seen on videos posted to You Tube of lucky animals appearing dead, but escaping from the jaws of a predator at the last moment. This state used to be (cruelly) often invoked in pet rabbits by well meaning owners, by turning them on their backs and tickling their tummies. They would go rigid and people would think it was cute and the rabbit was happy. The rabbit however thought its life was in imminent danger from their owner, was immobilised and trying to prevent being killed. Luckily, these days the majority of rabbit owners know this is not ethical!

In humans, this response is seen only in extreme situations where there is significant imminent risk to life and fight or flight is either not possible or would significantly increase risk of mortality. It comes with disassociation and de-realisation from the situation as cognitive processing is interrupted. Patients usually report feeling numb, with little or no memory of specifics of what happened. The flop response enables the person to get through the incident with the chance of least injury or resistance. The collapse and immobility protect from injury to vital organs and maintain blood flow to the brain.

The flop defence response is seen with traumatic incidents in PTSD cases, such as situations experienced in war and conflict, terrorist or other violent attacks or in cases of sexual assault. Often the person describes feeling guilt or shame, that their ‘body let them down’ for not fighting back, but report not being able to move or being ‘paralysed with fear.

In our final scenario, there is no fox, but our rabbit has traumatically injured itself and is bleeding. The faint response is seen particularly in humans, although is shared with some animals. It is a passive immobility response, sometimes referred to as collapsed immobility or vasovagal syncope. Fainting is a consequence of fear response leading to a temporary loss of consciousness. This

response occurs specifically in blood, injection and injury phobia. Physiologically it is a variant of tonic immobility with greater loss of blood flow to the brain. It has been seen as part of the fear cascade for some time and reports of fainting responses can be found going back across history (Bracha, 2004). The faint is caused by bradycardia-induced hypoxia. After the initial arousal response increases heart rate and blood pressure, a sudden drop in blood pressure from this initial spike level occurs, due to a rapid surge of parasympathetic response. This causes a temporary decrease in blood flow to the brain, resulting in fainting and loss of consciousness (known as syncope). Regulated blood flow to the brain is required constantly, the sudden drop in blood pressure from the physiological response to the fear is a shock response. This defence response is believed to be to protective against high levels of blood loss. Major injury and trauma resulting in blood loss can be quickly fatal and lead to haemorrhagic shock. The fear defence cascades, along with the cognitive themes of each disorder (such as catastrophic misinterpretation of bodily sensations of arousal as a sign of imminent harm in panic disorder) are essential to have in mind in an assessment. To gather specific situational examples of the patients fear, clustering the autonomic, behavioural and cognitive changes that take place for the patient. Think when funnelling, what is the fox/ threat they fear and when it is present, how doe the autonomic, behavioural and cognitive symptoms cluster?, Where is the fox/threat they fear, in the distance/future or up close there and then?, Does it remain one defence cascade or change depending on situational variables? Is it future focused threat like in GAD, or imminent fear of harm, like in panic disorder? Does it vary in autonomic response depending on the situation, for example the difference between worrying about a future event in social anxiety and the lead up to it, versus being at a social event like a party or work presentation.