hani hamed dessoki oxytocin

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

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.

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

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.

INTRODUCTION

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)

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.

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.

INTRODUCTION

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.

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.

INTRODUCTION

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.

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

Pathways of Emotional Expression

Attitudes

Feelings

Behaviors

Anger Depression

Trauma

Triangle

©2009 B. Bryan Post

14

Critical areas of the brain for love and attachment

Orbitofrontal Cortex

Pituitary Gland

Amygdala

Hippocampus

Adrenal Glands Spinal Cord

Neural Circuitry

(Fight, Flight, or Freeze)

(Lower Limbic/Reptilian)

(Short-term Memory)

(Social/Emotional Control Center)

Brain Stem

Hypothalamus(Oxytocin Response)

Peripheral Oxytocin

Numerous studies in humans have reported correlations between peripheral levels of OT (i.e., in blood, saliva, or urine) and socially-relevant 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 third-trimester strength of maternal bonding.

Mothers at higher risk for postpartum depression, based on self-reported symptoms pre- and postpartum, had lower plasma OT during pregnancy.

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.

Clinical Perspectives

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.

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.

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).

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 self-evaluations of appearance and speech performance.

Future research is needed.

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 socio- affective 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.

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.

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.

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.


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

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.



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.



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.



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.

Method of Adminstration


“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."




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 long-term administration.

Science News ,2013


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

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 ).

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.

hani hamed dessoki oxytocin

Health & Medicine

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introduction ot

social behavior

action of oxytocin

peripheral levels of

social functioning

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