This document summarizes research on the role of oxytocin in autism and social phobia. It discusses how oxytocin is involved in regulating social behaviors and emotional responses. For individuals with autism and social phobia, abnormalities in oxytocin levels and receptor activity in the amygdala and hypothalamic-pituitary-adrenal axis may contribute to social deficits by improperly regulating stress and fear responses during social situations. Studies examining intranasal oxytocin administration provide initial evidence that oxytocin could be an effective treatment for core symptoms in autism and social anxiety by reducing amygdala activation and stress hormone levels.

1. Role of Oxytocin in
Autism and Social Phobia
PSYC 342
Dr JC Pruessner
Karen Falcicchio, Chelsey Lam,Yoojung Lee,
Candice Lee Kit, Emma Vallance

2. Oxytocin (OT)
• Neuropeptide hormone
synthesized in hypothalamic
nuclei & secreted by posterior
pituitary
• Peripheral (hormonal) actions,
and actions in brain mediated
by specific, high affinity oxytocin
receptors

3. Oxytocin
• Established role lactation, labour
and birth
• Animal models support the
involvement of oxytocin in maternal
affiliative behaviors (i.e., licking and
grooming)
• Role in human maternal affiliative
behaviors, trust and attachment
• Oxytocin may have an important
role in the regulation of social
behaviors, emotional reactivity and
repetitive behaviors

4. Oxytocin, Autism &
Social Phobia?
• Given that oxytocin is involved in the regulation of
repetitive and affiliative behaviours, and that these are
key features of autism, it is believed that oxytocin may
play a role in autism and that oxytocin may be an
effective treatment for these two core symptom
domains
• Studies of individuals with social phobia/ social anxiety
disorder suggest a possible role for oxytocin as a
facilitator of social behavior, an effect which may not be
fully utilized in individuals with severe social anxiety

5. What is Social Phobia?

6. Feelings & Symptoms
• Blushing • Clammy Hands
• Difficulty Talking • Nausea
• Stomach • Weeping
Discomfort
• Profuse Sweating
• Tantrums
• Palpitations
• Shaking
• Trembling

7. Common Characteristics
• Fear of social or performance situations in which
the person is exposed to unfamiliar people or to
possible scrutiny by others
• Exposure to the feared social situation provokes
anxiety
• The person recognizes that the fear is excessive or
unreasonable.
• The situations are avoided or else are endured
with intense anxiety or distress

8. Everyday fear or
something more serious?

9. The Extra Step Faced by
Social Phobics
• Heightened anxiety levels to the point of avoidance
• Advance worry of the social situation days to
weeks before
• Interpretation of natural fear response cues as
dangerous
• Avoid forming/maintaining close relationships
• Turn down chances to advance their careers
• Selective Mutism
• Housebound

10. Why Do Some People
Develop Social Phobia?
• A person's biological/cognitive makeup
• No one gene implicated, but genetic and hormonal
disposition predisposes an individual to specified
characteristics
• Heriditary: Pedigree shows that first-degree relatives of
probands with social phobia are 3 times more likely to
develop than controls [Bernstein et al.]
• Behaviors learned from role models
• Overprotective parent
• Shy parent
• Life events and experiences
• Born with a cautious/inhibited nature due to stressful
experience in early life
• Teased or bullied

11. Cognitive/
Neurobiology Aspect
• Increased activation of amygdala
• Sensitization of the HPA axis stress response
• Studies by Bernstein et al. show that very low
weight (600-1250 g) babies may be at higher risk
due to abnormalities in the uncinate fasciculus,
(white matter tract connecting the frontal
cortex to the amygdala, and other limbic
temporal regions)

12. Prevalence
• THIRD largest psychological
disorder in United States
• Prevalence rates vary widely
because of its vague diagnostic
criteria and its overlapping
symptoms with other disorders
• Onset of social phobia typically
occurs between 11 and 19 years of
age
• Male : Female ratio being 2:3 in
general population, but clinical ratio
is higher for men than women

13. Comorbidity
• Schizophrenia
• Acute Stress Disorder
• Suicidal/ Homicidal Ideation
• Substance Abuse
• Panic Disorder
• Generalized Anxiety Disorder (GAD)
• Depression
• Autism Spectrum Disorder

14. What is Autism?

15. What is Autism?

16. Autism Spectrum Disorder
From the DSM-IV TR
• Social and Communication Deficits
• Fixated Interests and Repetitive Behaviors
• Symptoms must be present in early
childhood

17. Prevalence
• 1 in 166; 68/day; 3/hour
• Present cross-culturally and
cross-nationally
• Found at all income levels
• 4:1 male to female ratio
• 10:1 male to female ratio in “high
functioning” ASD (Autism
Spectrum Disorder)

18. Characteristics I
• Impairments in Social Interaction
• Expressive non-verbal behavior
• Joint Attention
• Social “mind” and reciprocity
• Communication: speech and language
• Echolalia and other repetitions
• Poor pragmatic use of language

19. Characteristics II
• Behavioral Symptoms
• Repetitive patterns of interests
• Self stimulation
• Restricted interest
• Preoccupation with parts of objects
• Cognitive Aspects
• Deficit in abstraction
• Lack of “Theory of Mind”

20. Biological Aspects
• Lower levels of serum oxytocin compared to
controls
• Higher levels of oxytocin precursor levels
• Autism has been associated with specific variants
of the oxytocin receptor genes (Petrovic et al.,
2008)
• Heightened amygdala activation (faces with a direct
gaze)

21. Feelings
• A common myth: Do autistics feel emotion
at all?
• Missing emotions:
• Romantic love
• Grief
• Expressing emotions:
• Through writing
• Improves with age

22. The Autism Spectrum
• The Autism Spectrum
• Characterized by widespread abnormalities
of social interactions and communication, as
well as severely restricted interests and
highly repetitive behavior
• Evidence for dimensional spectrum:
• Severity of symptoms vary
• Any level of IQ possible
• Presence of traits in close relatives

23. The Autism Spectrum
• Autism
• Asperger’s Syndrome
• Similar to Autism but no significant delay
in language development
• PDD-NOS (Pervasive Developmental
Disorder Not Otherwise Specified)
• “Atypical Autism” - most common and
somewhat milder than Autism

24. What could the mechanism be
by which variations in Oxytocin
could have an effect on autism
and social phobia?

25. Quick Review: Social Stress
• HPA axis is highly
responsive to
psychosocial stress
• Main hormones
involved: CRF, ACTH,
Cortisol, Epinephrine
• Regulates fight or flight
response and increases
alertness to cope with
stress

26. Quick Review: Social Fear
1. a) Sensory information is
process in the thalamus
b) Pre-frontal cortex
2. Amygdala is activated and
projects to brainstem
3. Fear response (similar to
stress response)
• Research using fearful faces as a cue for social fear can
activate the amygdala (seen in fMRI)

27. Role of Oxytocin in
Stress & Fear
A) Oxytocin in CNS
• Oxytocin has receptors in the limbic
system (amygdala)
• has an inhibitory effect
Evidence:
• Intranasal oxytocin + social stimulus
(emotional faces, measured by fMRI)
showed decreased amygdala activation
(Kirsch et al., 2005)

28. Role of Oxytocin in
Stress & Fear
• Activation of amygdala and brain stem connection also
significantly decreased (Kirsch et al., 2005)
Text
• Conclusion: Increased oxytocin inhibited the social fear
response

29. Role of Oxytocin in
Stress & Fear
B) Peripheral Oxytocin:
• During social stress, oxytocin was
found to inhibit secretion of
ACTH, cortisol & catecholamines
(ex. epinephrine)
• Protective factor because it
facilitates approach behavior and
inhibits overactivation of HPA
axis
• Oxytocin increases the ability to
interact socially

30. Oxytocin & Social Phobia
• One study found that when given intranasal oxytocin
normal individuals showed decreased levels of cortisol in
response to social stress vs. controls
• Oxytocin seems to promote social behavior by reducing
stress and anxiety when presented with social situations
• The regulation by oxytocin of the HPA axis may be
dysfunctional in individuals with social phobia
• May lead to the large increase in stress and anxiety in
social situations seen with people suffering from social
phobia

31. Oxytocin & Autism
• Hypothesis of autism =
increased social fear and
social deficits due to
increased regulation of fear
response by oxytocin

32. Autism Studies
• Several studies have linked specific characteristics
and behaviors of autism with oxytocin levels
1. Affective Mind Reading
2. Emotional significance to speech intonation
3. Repetitive behaviors (Heinrichs and Gaab)

33. Andari et al., 2010
• High functioning autism spectrum disorders were given oxytocin
intranasally
• Played a virtual game of ball toss with 3 virtual players
(social, neutral, antisocial)
• Visual face scanning task
• Results:
• Increased ability to process socially relevant cues
• Increased time gazing at the face, specifically the eyes, and
decreased number of saccades

34. What other hormones
are involved in Social
Phobia and Autism?

35. Cortisol
• Shy children and children with behavioral
inhibition typically have higher cortisol levels
(Stein, 1998)
• Many studies have shown that cortisol levels of
individuals with social phobia are normal
compared to controls’, whether measuring using
urinary free cortisol, plasma cortisol or
dexamethasone suppression tests (Bell, Malizia &
Nutt, 1999)
• Suggests that HPA activity is normal in people
with social phobia at the level of cortisol

36. Growth Hormone (GH)
• Stabler et al., reported a striking incidence of social phobia
(38%) in individuals with GH deficiency who were treated with
GH during childhood
• Trancer, Stein & Uhde (1996), discovered that people with
social phobia have blunted GH response
• Implies central non-adrenergic dysfunction → elevated
noradrenaline leads to down regulation of GH
• Hypothesis: People with social phobia have lower GH -
Two possible explanations:
• Presence of social phobia leads to GH
deficiency
• GH deficiency leads to increased risk of
developing social phobia

37. ACTH
• Buitelaar et al. (1992): Autistic children treated
with a synthetic analog for ACTH for 4 weeks.
• Increased amount and improved quality of
social interaction (more eye contact,
mutual smiling, and decrease in
stereotyped behaviours).
• Tordjman et al. (1997): Measured ACTH in
autistic adults and children compared to
controls.

38. ACTH
• Found higher plasma levels of ACTH in the
autistic group compared to controls.
• Could be due to chronic hyperarousal, or acute
hyperarousal in response to stress, or both
• Researchers believe the second to be true,
because many studies have reported normal
baseline functioning of the HPA axis.

39. Testosterone
• Extreme Male Brain Theory: Autism as an
extreme manifestation of some sexually
dimorphic traits
• Testosterone, 2D:4D & Autism
• Males have lower 2D:4D than females
• De Bruin (2006): Males with ASD have
lower 2D:4D than unaffected
individuals
• Manning (2001): Siblings and parents
of autistic individuals have lower 2D:
4D than unaffected males

40. Testosterone
• Knickmeyer et al. (2005): Analysed fetal testosterone
via amniocentesis of 58 children. When they were
age 4, their mothers completed a questionnaire
assessing language, quality of social relationships, and
restricted interests.
• Girls scored better on measures of social
relationships, and it was related to fetal testosterone
levels.
• Boys had more restricted interests, and it was related
to fetal testosterone levels.
• No differences in language, which could reflect a type
II error, or an age effect.

41. Conclusions
• Oxytocin is a neuropeptide hormone that plays an
important role in the regulation of social behaviors
• Autism and Social Phobia are disorders
characterized by poor social functioning
• Individuals with these disorders appear to have
abnormalities in oxytocin at the level of the
amygdala and HPA axis which may contribute to the
etiology of the symptoms
• Although oxytocin appears to play a central role,
there are several other hormones that may be
involved

43. Questions?

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