This document summarizes a presentation by Dr. Paul Arnold on the roots of anxiety. It discusses how anxiety disorders are commonly treated with SSRIs or CBT. Genetic factors play a role, as anxiety runs in families and certain genetic variants may increase risk. However, genes interact with the environment - those with risk variants may be more susceptible to environmental stressors. Understanding the biological and environmental roots of anxiety can help advance prevention and more targeted treatment approaches.

1. The Roots of Anxiety
Dr. Paul Arnold, MD, PhD, FRCPC
Professor, Cumming School of Medicine
Director, Mathison Centre for Mental Health Research &
Education
November 1, 2018

2. • Professor, Cumming School of
Medicine
• Director, Mathison Centre for
Mental Health Research and
Education
• Member, Hotchkiss Brain Institute
• Alberta Innovates Health Solutions
Translational Health Chair in Child
and Youth Mental Health
• Research areas include obsessive-
compulsive disorder (OCD), anxiety
disorders, child and adolescent
mental health, genetics and
neurobiology
Dr. Paul Arnold, MD, PhD
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3. Summary of presentation
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• What are Anxiety Disorders and how are they
treated?
• Roots of anxiety: genetic and environmental risk
factors
• Orchids and dandelions: how genes and the
environment interact

4. What is anxiety and when is it a concern?
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• Anxiety: Normal human response that alerts a person to
danger or threat
• Clinical anxiety: Anxiety that is persistent, associated with
distress or impairment and excessive for context
• Anxiety traits: Continuous manifestation of anxiety as
more/less severe
• Anxiety disorders: Categorical manifestation of anxiety with
specific features

5. Anxiety disorders: Tip
of the iceberg

6. Anxiety disorders
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• Three broad categories:
• Obsessive-compulsive disorder (OCD)
• Post-traumatic Stress Disorder (PTSD)
• Anxiety Disorders
• Social Anxiety Disorder
• Generalized Anxiety Disorder (GAD)
• Separation Anxiety Disorder
• Panic Disorder
• Phobias

7. Anxiety symptoms
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• Emotional
• Feeling nervous, restless, or tense
• Sense of impending doom
• Cognitive
• Trouble concentrating
• Difficulty controlling worries
• Physiological
• Increased heart rate, hyperventilation, sweating, etc.
• Behavioural - avoidance

8. Anxiety disorders …
• Are common (between 20 – 30% of people develop anxiety
disorders in their lifetime)
• Typically begin early (50% before age 11), BUT can begin later
in life
• Affect women about twice as often as men
• Persist over time, and can increase risk for other mental
health disorders (particularly Depression)

9. Are more people becoming anxious?
• More people reporting anxious symptoms on questionnaires
• More people seeking treatment for anxiety disorders
• Unclear if more people are developing anxiety disorders, or if
we are just more likely to self-identify as having anxiety
(Bandelow et al., 2015)

10. Treatments
• Two good, evidence-based treatments
• Selective serotonin reuptake inhibitors (SSRIs)
(Locher et al., JAMA Psychiatry, 2017)
• Cognitive behavioural therapy (CBT)
(Walkup et al., NEJM 2008)

11. Anxiety: Nature or nurture
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• Anxiety runs in families: Parents of people with
anxiety disorders - 5X increased risk of anxiety
(Hettema et al., 2001)
• Children of parents with anxiety disorders –
characterized by behavioural inhibition in childhood,
increased risk of anxiety disorders in adulthood
• However, genetic risk is not destiny, environment
equally important (Pine & Fox, 2015)

12. Lessons from twins
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• ~30% of risk for anxiety disorders and anxiety traits
due to genetic factors
• Most of environmental risk is “non-shared” between
siblings
• Risk for different anxiety disorder is shared, and
genetic risk overlaps with depression and trait
anxiety (Gottschalk et al., 2015)

13. Early risk factors
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• Behavioural inhibition – temperamental style first
seen in early childhood
• Consistent tendency to show marked behavioural restraint
or fearfulness with unfamiliar people, situations, or events
• Parental mental health disorders (nature or nurture?)
• Parenting stress
(Pahl et al., 2010)

14. Roots of Anxiety: Genes,
brains and neurochemistry
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15. Serotonin Transporter
• A protein that removes
serotonin from the synapse
(space between neurons
• The site of action of SSRI
medications
• A genetic variant with “long”
(l) and “short” (s) versions
has been associated with
anxiety disorders and traits

16. Functional Neuroimaging – Fearful Faces and the Serotonin
Transporter Gene (Van Den Bulk, 2014)
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17. Gene by environment interaction
Similar findings for other environmental risks, e.g.
childhood maltreatment

18. • “Orchids” (s allele) are at
particular risk in adverse
environments, may
flourish in good
environments
• “Dandelions” (l allele) do
well in most
environments
(Boyce, Ellis, Belsky)
Gene by environment interaction
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19. Epigenetics: How environments influence
expression of our genes

20. Translating genetic discoveries
into clinical care
• By implicating novel biological pathways, genetic studies
should advance our ability to prevent, detect and treat
anxiety disorders
• Understanding how individual differences in risk and
resilience are influenced by genetic and epigenetic factors will
inform a precision medicine approach to anxiety disorder
• The aim of precision medicine is to be able to target
treatments to the right person at the right time in the course
of their development and thereby improve their outcomes

21. Take-home messages
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• Anxiety is a common and impairing disorder that
often begins early in life
• Anxiety is treatable
• Both “Nature” (Genes) and “Nurture” (the
environment) interact to produce anxiety

22. Some relevant current research at the
Mathison Centre, University of Calgary
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• Genetics of childhood anxiety disorders and OCD (Arnold)
• Genes interacting with early trauma
• Genetics of neuroimaging and EEG traits underlying childhood mental
health disorders
• Long-term study of adolescents with a parent with anxiety or depressive
disorder (Kopala-Sibley)
• Canadian Psychiatric Risk and Outcome Study (PROCAN, Addington,
MacQueen)
• School-based mental health study (Arnold, Dimitropoulos, Bulloch &
Patten)

23. Recommended resources
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• Anxiety Canada (formerly Anxiety BC)
https://www.anxietycanada.com
• Anxiety and Depression Association of America
(ADAA) (www.adaa.org)

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Acknowledgments