Anxiety Disorders - Clinical Case Series #9
Adapted/Edited by Dr Gurjot Brar from "Evolution and Psychiatry: Clinical Cases" by Prof. Henry O'Connell
Welcome to the ninth in our clinical case series, exploring common mental disorders through the lens of evolutionary psychiatry. A ‘problem-based learning’ (PBL) approach is taken with learning outcomes defined at the outset, followed by several clinical encounters with fictional scenarios, interspersed with theory responding to the learning objectives. This method has emerged globally in medical curricula and has a good evidence base in medical education promoting self-directed learning. We hope you enjoy this format and look forward to your feedback.
This case series will often refer to key principles defined in the following article published in July 2023 which serves as a primer:
Anxiety Disorders
Learning Objectives
1. List the main anxiety disorders and outline their core clinical features, epidemiology, aetiology, pathophysiology and management.
2. Outline how evolutionary perspectives can be utilized in conceptualizing anxiety disorders.
3. Outline how therapy for anxiety disorders can be enhanced by adopting an evolutionary perspective.
An urgent referral from accident and emergency
Dr Jane Kelly is the Liaison Psychiatrist for the City Hospital. This is a new service and Dr Kelly has been in post for just one year. She has a wide remit, providing psychiatric consultation to the medical and surgical wards and the accident and emergency department. Dr Kelly has kept a close track on her clinical activity over the past year and has been able to use the data to persuade hospital management to fund posts for a Clinical Psychologist and Clinical Nurse Specialist to join her in developing the service. She finds that her medical and other colleagues at the hospital have limited understanding of psychiatric disorders, so a key role for her new team will be raising awareness and providing education on psychiatric disorders encountered in the hospital.
At the end of a long week on the wards, Dr Kelly is planning to spend Friday afternoon in her office finishing paperwork before going home. She has just started on her reports when her secretary enters with a referral from the accident and emergency department. ‘It’s a referral on Mary Dunne, marked urgent, again’. Dr Kelly looks at the referral letter and sighs. This is the third Friday afternoon in succession that she’s received an urgent referral on this patient.
The details of the referral are the same as before:
“47 year old married mother of three presenting with chest pain and palpitations. ECG and Troponin levels normal. Cardiac causes outruled. Advised to monitor for further symptoms and return if symptoms recur. Family history of myocardial infarction (father). Psychiatry referral.”
Dr Kelly sighs when she reads the referral. ‘Why do they advise her to monitor for symptoms? That’s just compounding the whole problem for her.’ she says to herself herself as she descends in the elevator. She follows the corridor to accident and emergency and finds Mrs Dunne in a cubicle, looking exhausted and slightly embarrassed. On this occasion she is accompanied by her sister. ‘I’m sorry to have to drag you down again Dr Kelly. They said I have to see you before I go home. This is my sister Emily. She gets similar episodes so I thought it might be helpful for you to meet her too’. Emily adds: ‘It’s nice to meet you Dr Kelly. I have obsessive compulsive disorder, panic disorder and a whole range of phobias. We could give you enough material for a conference!’ Dr Kelly smiles warmly and takes Mrs Dunne’s hand: ‘I know how terrifying these experiences are for you. And thank you Emily for coming in today. Let’s see if I can help’.
Dr Kelly is familiar with the background from her assessments of Mrs Dunne over the past two weeks. Mrs Dunne has a long history of Generalized Anxiety Disorder (GAD) and she has developed Panic Disorder over the past year. She had a difficult childhood. Her father died when she was aged 14, suffering a massive myocardial infarction in their home, which she and her sister witnessed. Mrs Dunne’s mother soon after began ‘suffering with her nerves’. As a result, Mrs Dunne and her sister Emily had to fend for themselves, spending much of their time staying with other family members. When they did stay with their mother they found her to be constantly worried and on edge. They remember how she barely left the house after their father died as she was conscious of people looking at her, making comments about her and pitying her. They also remember how during thunder storms that she would become even more anxious than usual and she would make her daughters hide under a bed, in case the house was hit by lightning.
Despite these early difficulties, Mary Dunne went on to complete a college degree and subsequently worked in administration. Her problems with anxiety seemed to fade into the background when she married and had her children. This was a largely stable time in her life. However, since her eldest child went away to college, she has been worrying about him and fearing that he may start taking drugs or that something bad may happen to him.
Learning Objective 1:
List the main anxiety disorders and outline their core clinical features, epidemiology, aetiology, pathophysiology and management.
The term ‘anxiety disorders’ refers to an extremely wide range of conditions, including generalized anxiety disorder, panic disorder, agoraphobia, post-traumatic stress disorder, anxiety related to physical illness, phobias and obsessive compulsive disorder. Anxiety is a core feature of all of these disorders and specific disorders can be seen as fear responses arising as a result of different situations. Specific and social phobias usually have their onset in childhood. GAD, panic disorder and agoraphobia tend to develop later in adolescence or early adulthood.
These disorders are very common, with lifetime prevalence for any anxiety disorder ranging from 14-29% and frequent (74%) comorbidity for more than one anxiety disorder. GAD and panic disorder tend to be highly associated, with individuals being 12.3 times to have both compared to individuals without GAD. Aetiology is multifactorial and includes genetic factors (30-40% heritability) and life experiences, with the risk of anxiety disorders in women being twice that of men (Kessler et al., 2010; Michael et al., 2007). Having an anxiety disorder is also associated with a substantially increased risk of depression, lifetime risk of any mood disorder ranges from 3.45-5.83 (Merikangas & Swanson, 2010). GAD and depression in particularl appear closely associated as the same genetic variations predispose individuals to either (Middeldorp et al., 2005; Taylor et al., 2019).
Management includes medication with antidepressants (primarily serotonin specific reuptake inhibitors or SSRIs) and focused psychotherapy such as cognitive behavioural therapy (CBT). CBT has been found to have a moderately beneficial effect against all types of anxiety disorder compared to a placebo drug (Cohen’s d = 0.57); the same is true of pharmacotherapy (e.g., sertraline, d = 0.54; venlafaxine, d = 0.50) (Bandelow et al., 2015).
Additionally, exercise (Ströhle, 2019), metacognitive therapy (Normann et al., 2014) and mindfulness-based therapy (Rodrigues et al., 2017) also show promise.
‘My body is sending off false alarms about danger?’
Dr Kelly finishes her assessment and has a discussion with Mary and her sister Emily. During the course of their discussion, they have multiple questions for Dr Kelly: ‘Is this anxiety problem genetic?’ ‘Did we pick it up from seeing our mother suffering?’ ‘If there isn’t any cardiac reason for Mary’s symptoms, then why does she sometimes feel like her heart is going to explode?’
Dr Kelly addresses the questions as well as she can. She prescribes Sertraline and explains how this will help reduce the frequency and severity of Mrs Dunne’s panic attacks. She tells them that she will arrange for Mary to have Cognitive Behavioural Therapy, to begin next week.
Dr Kelly then decides to offer some evolutionary explanations for Mary’s symptoms (see learning objective below). Mary and her sister are clearly very interested in this explanation. ‘So you’re saying this is very common and it’s like my body is sending off false alarms about danger?’
Dr Kelly finishes and writes up her case notes. Then she meets with the accident and emergency doctor who made the referral. Again, she decides to take a few minutes to explain to him how the evolutionary perspective can be helpful in explaining anxiety and panic symptoms to patients. He listens carefully and smiles: ‘I think if we took this approach to managing cases like Mrs Dunne’s then they wouldn’t be back to accident and emergency so often and we would be sending you less ‘urgent’ referrals’.
Learning Objective 2:
Outline how evolutionary perspectives can be utilized in conceptualizing anxiety disorders.
Adopting evolutionary perspectives is likely to greatly enhance the understanding of anxiety disorders for patients and healthcare workers. The process of applying evolutionary principles begins with reverting to the key principles outlined previously:
Beginning with the last of those principles (Viewing Diseases as Adaptations or VDAA) it is important to outline from the beginning that anxiety disorders in themselves are unlikely to serve adaptive functions. However, anxiety disorders can be conceptualised as exaggerated and aberrant manifestations of normal evolved safety responses and behaviours that have evolved over countless millennia and served to keep us from harm. In other words, anxiety itself can be useful in certain contexts (i.e. as a ‘threat detection system’, to prevent loss) and anxiety disorders represent states which have ‘overshot the mark’ (Nesse, 2022).
Below are some of the key evolutionary principles that lead us to be vulnerable to anxiety disorders (Nesse, 2022):
1) Stochasticity – forms the main explanation which leaves us vulnerable to anxiety disorders. In the context of anxiety disorders, stochasticity means that some people might randomly end up with higher or lower levels of anxiety, simply due to natural variation in how their bodies and brains function, even if there’s no clear reason for it. In this regard, individuals will inevitably fall outside of the distribution and present with excessive or deficient levels of anxiety.
2) Path dependence – suggests that our anxiety responses are "stuck" on a path set by our evolutionary history, even though the original reasons for these responses might no longer be relevant. This concept helps explain why anxiety disorders persist, as our bodies are still responding to threats in ways that were useful long ago, but may now cause distress rather than protection e.g. a flight or fight response when giving a public speech.
3) Mismatch – A key evolutionary principle explains perhaps why we have skewed towards excessive anxiety and the sometimes obsolete retention of fears such as snakes and spiders. Much of our normal background levels of anxiety are set for optimal functioning and survival in the much more hostile and dangerous pre-agricultural environment of our ancestors, in comparison to the generally safe modern environments that we currently occupy. For example, a certain degree of generalized anxiety and even agoraphobia would have been important and protective in pre-agricultural settings whereby predation by animals and attack from other humans was a much more pressing concern than now.
4) Trade-offs – More anxiety may aid better survival but lower reproductive success and other risks that bring benefits, whereas less anxiety may bring regular danger to survival but more propitiousness to risks. In other words, high levels of anxiety are associated with higher levels of safety behaviours, thus leading to improved survival chances but perhaps reduced opportunity for mating and other important activities. Likewise, abnormally low levels of anxiety (hypophobia) may increase opportunities but also increase the chances of harm or even premature death due to misadventure.
5) Traits that benefit genes at the expense of the individual - The next principle relates to how natural selection maximizes reproduction but not necessarily health, happiness or even longevity of individuals. In the case of Mary Dunne and her family, her mother’s terror during thunder storms and insistence that her daughters hide under a bed was clearly distressing and excessive but, in the infinitesimally small chance that the house would be struck by lightning, her extreme safety behaviour may have saved the family. Indeed the utility of the panic response can be described well by the smoke detector principle. If a false alarm costs 100 calories, but a failure to express the panic response is 100,000 calories (i.e. death), then the system that produces 999 false alarm panic episodes out of a 100,000, can be said to be operating optimally (Nesse, 2022). In this way it is generally better to have a background level of anxiety and a high number of false alarms than a ‘faulty’ anxiety system whereby threats are missed, thus impacting negatively on our survival chances and reproductive potential (In the case of Mary, her panic response may be guided by considering at least 300,000 calories!)
‘I’m also very interested in how evolutionary perspectives can enhance standard approaches’.
The following Monday morning Dr Kelly meets with the new Clinical Psychologist and Clinical Nurse Specialist who have just joined her to form the beginnings of a truly multidisciplinary psychiatric consultation-liaison team for the City Hospital.
Dr Kelly gives her new colleagues a summary of clinical activity data for the past year and a breakdown of the main clinical problems that she encounters. When she comes to the topic of anxiety disorders, the case of Mrs Dunne is still fresh in her mind from the previous Friday. She outlines how the evolutionary perspective on anxiety and panic seemed to strike a chord with Mrs Dunne, her sister and the referring doctor.
‘I know you’re both experienced in psychiatric consultation-liaison work so you will be very familiar with standard medication and psychotherapy approaches to managing anxiety and panic related problems. But I’m also very interested in how evolutionary perspectives can enhance standard approaches’. Her new colleagues look puzzled.
Learning Objective 3:
Outline how therapy for anxiety disorders can be enhanced by adopting an evolutionary perspective.
The principles discussed earlier, such as VDAA, mismatch, trade-offs, maximizing reproduction over well-being, and anxiety symptoms as defensive responses, can be effectively integrated into individual and group psychotherapy for managing anxiety disorders. Evolutionary explanations offer patients an empowering perspective by reframing anxiety and panic not as mere psychopathology, but as systems that can malfunction and exceed their adaptive capacities. For example, understanding the origins of the need to flee can enhance patient engagement in therapy and help prevent misattribution of anxiety's physical symptoms to neurological or cardiac issues (Nesse, 2022).
Everyone exists on a spectrum between two global motivational states: promotion and prevention (Higgins and Spiegel, 2007), which allows for a wider understanding of the context in which the anxiety arises:
Promotion State: This is a motivation focused on achieving positive outcomes, growth, and aspirations. People in a promotion state are driven by the desire to gain rewards, advance, and accomplish goals. They are more likely to take risks and pursue opportunities that might lead to success. When applied to anxiety, individuals with a promotion focus might experience anxiety related to missing out on positive outcomes or not reaching their potential.
Prevention State: This is a motivation focused on avoiding negative outcomes, safety, and security. People in a prevention state are driven by the desire to avoid losses, mistakes, and dangers. They are more cautious, focused on fulfilling responsibilities, and ensuring that they don’t fail or experience harm. In the context of anxiety, those with a prevention focus might be more prone to anxiety because they are constantly vigilant about potential threats or failures, which can lead to a heightened state of worry or fear.
In the context of Generalized Anxiety Disorder (GAD), individuals tend to lean more towards a prevention state, where their focus on avoiding negative outcomes can lead to chronic worry and anxiety. Understanding whether a person is in a promotion or prevention state can help tailor therapeutic approaches to better address their specific motivations and anxieties. Additionally, acknowledging that due to stochasticity, some individuals will naturally fall outside the normal distribution range and be more predisposed to anxiety disorders is crucial (Nesse, 2022).
The 'smoke detector' principle is particularly effective as it explains how panic and anxiety can be perceived as false alarms, with both psychological and physical dimensions. These false alarms are part of essential, adaptive systems that, while usually functional, can sometimes misfire.
Understanding the evolutionary basis for anxiety and panic symptoms also deepens the appreciation of pharmacotherapy. SSRIs, although slow to take effect, work by reducing the sensitivity of these systems, potentially maintaining benefits even after discontinuation. The primary benefits of SSRIs during treatment include reducing the frequency and intensity of symptoms, allowing patients to achieve some emotional and physical distance from their anxiety, which in turn decreases associated distress and safety behaviors. SSRIs disrupt the self-perpetuating cycles of anxiety and avoidance, much like how anti-inflammatory medications address damaging inflammatory processes. Conversely, evolutionary explanations might help reframe the short-term relief provided by alcohol and benzodiazepines, highlighting that, while these substances offer temporary comfort, they are unlikely to lead to lasting improvement.
This emotional distancing further facilitates patient engagement in cognitive behavioral therapy (CBT). When CBT is grounded in evolutionary principles, it becomes a more persuasive and effective approach, offering additional benefits over the application of CBT techniques in isolation (Abrams, 2021). Evolution-informed CBT emphasizes that anxiety symptoms are often useless and meaningless, yet distressing and damaging, aligning with the 'smoke detector principle' and moving away from psychotherapy approaches that seek underlying 'reasons' for symptoms.
In Mrs. Dunne’s case, while several factors, such as genetic predispositions and early childhood experiences, may have contributed to her condition, they are largely irrelevant to her current therapy. The initial focus should be on 'turning down' her overactive smoke detector. This will allow her to be more receptive and engage better in her therapy including the cognitive explanations for her anxiety.
Work is underway at testing these theories in practice. We are currently involved in a multi-site study assessing the benefits of evolutionary explanations for anxiety disorders. Eventually this will pave the way for further research to be funded and conducted, including double-blinded randomised controlled trials. We are optimistic, with the mounting evidence, evolutionary explanations for anxiety disorders will be commonplace in mental health services.
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This sound a lot like evolutionary function analysis and the drive and threat systems in Compassion Focused Therapy.