2. Prof. Hani Hamed Dessoki, M.D.Psychiatry
Prof. Psychiatry
Chairman of Psychiatry Department
Beni Suef University
Supervisor of Psychiatry Department
El-Fayoum University
APA member

3. WINDOWS TO THE BRAIN | March 01, 2013
Oxytocin and Behavior: Evidence for Effects in
the Brain
Francis L. Stevens, Ph.D.; Omri Wiesman, Ph.D.;
Ruth Feldman, Ph.D.; Robin A. Hurley, M.D.;
Katherine H. Taber, Ph.D.
The Journal of Neuropsychiatry and Clinical
Neurosciences 2013;25:96-102.

4. Agenda
 Introduction
 Biological Correlates
 Clinical Perspectives
 Could Oxytocin Be Useful in Treating
Psychiatric Disorders?
 A Cautionary Note On Oxytocin as a
Treatment for Psychiatric Disorders
 Take home message

5. INTRODUCTION
 OT is a nine amino acid peptide, synthesized primarily in
the supraoptic and paraventricular nuclei (SON and
PVN) of the hypothalamus.
 Neurons in both the SON and PVN project to the posterior
pituitary gland, where OT is released into the bloodstream
in response to specific physiological events (e.g., sexual
stimulation, nursing, stress) and exerts multiple peripheral
effects.

6. The posterior pituitary gland hormones
 Posterior pituitary gland releases 2
hormones:
1. Antidiuretic hormone (ADH), or
arginine vasopressin (AVP).
2. Oxytocin
 Both hormones are produced in
hypothalamic nuclei:
- Supraoptic nucleus
(ADH + 1/6
oxytocin)
- Paraventricular nucleus
(Oxytocin + 1/6 ADH)

7. Action of oxytocin
1. Contraction of smooth muscles of the uterus
enhance labor.
2. Contraction of mammary gland myoepithelial cells of
the alveoli & the ducts
Ejection of milk as a reflex in
lactating women.
3. In men
ejaculation.
Remember: Oxytocin is concerned with releasing or
ejection of milk, while prolactin is concerned with
synthesis & production of milk.

8. INTRODUCTION
 The few available studies of OT fiber staining in human
brain suggest a generally similar pattern to the receptor
mapping, with fibers present in the basal forebrain (e.g.,
septal nucleus, diagonal band of Broca, bed nucleus
of the stria terminalis) and brainstem, but not in
amygdala or hippocampus.

9. INTRODUCTION
 Knowledge about the oxytocin (OT) system in the brain
has increased greatly over the past decade.
 Although this neuropeptide is best known for its peripheral
effects, direct modulation of central nervous system (CNS)
areas has also been implicated in OT’s actions, which
include a major role in a wide range of affiliative
behaviors.
 Often referred to as the “social bonding” hormone,
speculations are being made as to its applications and
potential uses in enhancing human relationships.

10. INTRODUCTION
 Alterations in the OT system have been implicated in
several neuropsychiatric disorders.
 Multiple types of psychopathology manifest in deficits in
social functioning, including inability to maintain
interpersonal relationships and engage in socially
appropriate behavior.
 The OT system may influence the efficacy of
psychotherapy, as research has repeatedly shown that the
therapeutic relationship is one of the largest predictors of
therapeutic change.
 OT may also have value as a therapeutic intervention.

11. Introduction
 Understanding how the brain processes social information
and regulates social behavior helps us understand
psychiatric disorders specifically affecting social behavior.
 Animal models provide an opportunity for experimental
manipulations that are not possible in human patients.

12. Social Recognition and the Neural
Processing of Social Stimuli
 Several studies suggest that the brain has specific neural
circuits involved in processing social information rather
than nonsocial stimuli.
 Human brain imaging studies have demonstrated that the
brain processes social visual stimuli differently from
nonsocial stimuli.
 For example, the lateral fusiform gyrus is activated to a
greater degree when subjects view faces than when
viewing nonface objects

13. Pathways of Emotional Expression
Attitudes
Feelings
Behaviors
Trauma
Triangle
Anger
Depression
©2009 B. Bryan Post

14. Critical areas of the brain for love
and attachment
Hypothalamus
(Oxytocin
Response)
Hippocampus
(Short-term
Memory)
Orbitofrontal Cortex
(Social/Emotional Control
Center)
Pituitary Gland
Amygdala
(Fight, Flight, or
Freeze)
Neural Circuitry
Adrenal Glands
Brain Stem
(Lower
Limbic/Reptilian)
Spinal Cord
14

15. Peripheral Oxytocin
 Numerous studies in humans have reported correlations between
peripheral levels of OT (i.e., in blood, saliva, or urine) and sociallyrelevant behaviors.
 Plasma OT levels of pregnant women in the first trimester predict
the amount of postpartum maternal–infant bonding behavior, and
the increase in OT from the first to third trimester predicts thirdtrimester strength of maternal bonding.
 Mothers at higher risk for postpartum depression, based on selfreported symptoms pre- and postpartum, had lower plasma OT
during pregnancy.

16. Postpartum “blues”: biological
attachment hypothesis
 Neurobiological systems foster attachment between
mammalian mothers & infants.
 Oxytocin activates limbic structures (e.g. the ACG) that
mediate the interface between attention & emotion.
 Postpartum reactivity may stem from this.
 With stressors, depression may result.

17. Clinical Perspectives

18. Social stress and anxiety
 Recent neuroimaging studies suggest a modulatory role of OT on
amygdala responsiveness to unconditioned and conditioned
socially relevant stimuli.
 The attenuating effect on amygdala activity in response to both
positive and negative stimuli might reflect reduced uncertainty about
the predictive value of a social stimulus and thereby facilitate social
approach behavior.

19. Social cognition and social approach
 To summarize, there is accumulating evidence that in humans, OT
modulates social perception, social cognition, and social
behavior, thereby promoting social approach and affiliation.
 Besides the stress-reducing and anxiolytic effects, OT modulates
social cognitive functions such as trust, emotion recognition and
social memory.

20. Autism Spectrum Disorder
 There is increasing evidence that both OT gene might be
involved in the development of ASD.
 Furthermore, a number of studies show that the availability
of OT is associated with socio-cognitive functioning in
ASD.
 Finally, two studies suggest that systemic infusions of OT
reduce repetitive behavior and improve emotion
recognition in ASD (however, better intranasal).

21. Social Anxiety Disorder
 Intranasal oxytocin was found to suppress fear-related
activation of the amygdala in healthy subjects.
 As oxytocin in humans was also associated with both an
enhanced ability to interact socially and a better central
nervous control of stress and anxiety in social
interactions.
 Patients administered with oxytocin showed improved selfevaluations of appearance and speech performance.
 Future research is needed.

22. Early Trauma and Associated
Disorders
 Borderline personality disorder (BPD) is associated with a
remarkably high prevalence of severe childhood trauma and neglect
and by a pervasive pattern of instability in affect and interpersonal
relationships, (auto-) aggressive behaviors as well as unresolved,
preoccupied, and fearful types of attachment.
 In particular, BPD has been associated with excessive socioaffective vigilance and enhanced reactivity to emotional and
social stimuli.
 Thus, neuropeptides might play a significant role in the development
of the insecure attachment and the fundamental distrust in others
that many BPD patients report.

23. Obsessive-Compulsive Disorder
 Although an initial case study reported symptomatic
improvement in OCD patients treated with intranasal OT,
subsequent controlled studies were not able to confirm
therapeutic effects of systemic or intranasal
administration of OT in OCD.

24. Depression
 To date, only a small number of studies have
investigated the role of OT in the development of affective
disorders, in particular in unipolar depression.
 It might also be the case that some characteristics in
depression (e.g., social withdrawal) are associated with
blunted OT, but this hypothesis clearly needs further
investigation.

25. Schizophrenia
 The empirical evidence of OTfunctioning in schizophrenia
is limited and controversial, although recent studies in
humans and animals suggest impairments of OT
metabolism in schizophrenia that might be related to
impaired social cognitive functioning.

26. Could Oxytocin Be Useful in Treating
Psychiatric Disorders?
 Oxytocin could be a useful treatment for certain mental
health diagnoses -- particularly those involving impaired
social functioning.
 Oxytocin's involvement in "social decision making,
evaluating and responding to social stimuli, mediating
social interactions, and forming social memories" in
humans.
Harvard Review of Psychiatry. 2013

27. Could Oxytocin Be Useful in Treating
Psychiatric Disorders?
 Possible Treatment Benefits in Autism and Schizophrenia Based on
initial trials, oxytocin may one day "be a useful treatment agent for
improving some aspects of social cognition and for reducing
repetitive behaviors" in patients with autism spectrum disorders,
although studies are only in the early stages to fully evaluate clinical
effectiveness.
Harvard Review of Psychiatry. 2013

28. Could Oxytocin Be Useful in Treating
Psychiatric Disorders?
 Studies of oxytocin's relationship to schizophrenia have yielded
conflicting results -- associations with oxytocin-related genes
don't appear as strong as for autism.
 Because oxytocin is involved in responses to stress, studies have
also looked at its potential role in mood disorders and anxiety
disorders.
Harvard Review of Psychiatry. 2013

29. Could Oxytocin Be Useful in Treating
Psychiatric Disorders?
 For example, there's evidence that oxytocin may be involved in
beneficial responses to electroconvulsive therapy for severe
depression.
 But so far, there's little evidence that oxytocin is a useful treatment
for anxiety and depression.
 The same is true for early studies of oxytocin for treatment of
obsessive-compulsive disorder and borderline personality
disorder.
Harvard Review of Psychiatry. 2013

30. Method of Adminstration
 Thus despite some promising results, it's much too early to conclude
that oxytocin is a helpful treatment for autism, schizophrenia, or any
other psychiatric disorder.
 Even if the evidence were stronger, there's currently no reliable way of
giving oxytocin treatment so that it gets to the brain in a predictable
way.
 Nasal administration seems to be the most promising alternative, but
larger studies are needed to understand how it gets to the brain
receptors necessary for its effects.
Harvard Review of Psychiatry. 2013

31. Could Oxytocin Be Useful in Treating
Psychiatric Disorders?
 “Proper clinical trials are only recently being undertaken," which
"should provide a better understanding of the extent and limitations of
the clinical effects of externally delivered oxytocin."
Harvard Review of Psychiatry. 2013

32. A Cautionary Note On Oxytocin as a
Treatment for Psychiatric Disorders
 A new study now published in Biological Psychiatry indicates that
the promising short-term effects often observed after a single
dose of oxytocin may not translate to positive effects after longterm administration.
Science News ,2013

33. A Cautionary Note On Oxytocin as a
Treatment for Psychiatric Disorders
 The fact that long term treatment with oxytocin had the opposite
impact of initial doses with the same substance suggests that special
strategies will be needed if oxytocin is ever to become a long-term
treatment for autism or schizophrenia,"
Science News ,2013

34. Take Home Massage
 OT is associated with the regulation of the behavioral and
endocrine stress response, i.e., OT is released in response to
socially relevant challenges and attenuates endocrine and
autonomic responses to stress.
 OT is released in response to positive social interactions, such
as social support or social proximity, thus possibly representing a
mediator for the well-known stress-protective effects of social
support.
 The neural substrate for the anxiolytic effects of OT has been
suspected in limbic areas, in particular in the amygdala
(attenuate amygdala reactivity ).

35. Take Home Massage
 Finally, there is initial evidence that the central OT system is
altered in several mental disorders that are characterized by
severe social disturbances, such as ASD, OCD, personality
disorders, and following early trauma.
 Although still in the early stages of development as a treatment,
OT’s ability to increase trust and enhance emotional empathy
suggests considerable potential in neuropsychiatry, either as an
addition to other medications or in combination with
psychotherapy.
 Despite a general consensus that oxytocin (OT) has prosocial
effects, there is no clear agreement on how these effects are
achieved.