Brain Imaging of Intranasal Oxytocin Treatment in Autism

We hypothesize that intranasal oxytocin treatment (OT) of individuals with an autism
spectrum disorder (ASD) will:

Hypothesis 1a. will produce greater increases in Ventral Tegmental Area (VTA) and Nucleus
Accumbens (NAc) activation during social reward anticipation compared to placebo, providing
evidence that OT increases activation in brain regions critical for social motivation.
(NICHD funding for this section/aim- Dr. Joe Piven -U54 HD079124-01)

Hypothesis 1b. will spend proportionally more time attending to the social image on a screen
vs. the non-social image compared to placebo.

Hypothesis 2a. will produce differential effects in VTA and NAc activation during social
reward anticipation compared with the oxytocin 8 IU vs. oxytocin 40 IU dose, providing
evidence that OT dose-dependently increases activation in brain regions critical for social
motivation.

Hypothesis 2b. will differentially attend to the social image on a screen vs. the non-social
image compared in the oxytocin 8 IU vs. oxytocin 40 IU dose, providing evidence that OT
dose-dependently changes the value of social stimuli.

Inclusion Criteria:

- Between 6 and 18 years of age, inclusive

- Have a clinical diagnosis of an autism spectrum disorder confirmed according to the
Autism Diagnostic Observation Scale (ADOS, Lord et al., 1989). Diagnosis may also be
confirmed using the Autism Diagnostic Interview-Revised (ADI-R).

- Male or female of any race or ethnicity

- Ambulatory status (outpatient) at time of assent/consent

- Estimated IQ greater than or equal to 70 and capable of making an informed decision
based on assessment of their understanding and judgment

Exclusion Criteria:

- History of neurological injury: head trauma, poorly-controlled seizure disorder (i.e.
seizure within the preceding six month period), stroke, prior neurosurgery, or under
the care of a neurologist or neurosurgeon as determined by interview

- History of claustrophobia

- Implanted medical devices, implanted metal debris, shrapnel, certain tattoos, or
permanent makeup that is contraindicated for MRI. Participants fill out a detailed
questionnaire on the day of scanning to identify potential MRI risks

- Subjects with a medical condition that might interfere with the conduct of the study,
confound interpretation of the study results, or endanger their own well-being. This
includes, but is not limited to: Rett Syndrome, impairment of renal function,
evidence or history of malignancy or any significant hematological, endocrine,
cardiovascular (including any rhythm disorder or uncontrolled hypertension),
respiratory, hepatic, or gastrointestinal disease

- Marked sensory impairment such as deafness or blindness that would interfere with the
conduct of the study

- Pregnant or nursing because of the unknown effects of oxytocin to unborn babies
and/or nursing infants. All females of child-bearing potential will be administered a
serum pregnancy test at screening and at any point during the study at physician
discretion. Refusal to undergo a pregnancy test will result in exclusion from the
study. We will share results of a pregnancy test with the subject's legal guardian.

- Refusal to do pregnancy testing with understanding that guardian will be informed of
positive test results

- Inability or refusal of sexually active female subjects (who have begun menses) to
utilize two medically accepted barrier forms of birth control

- Use of hormonal birth control

- Subjects who have a history of an anaphylactic reaction from prior treatment with
oxytocin (nasal spray)

- Inability of caretakers to speak English

- Absence of a consistent caretaker to report on symptoms

- Subjects who, in the Investigator's opinion, might not be suitable for the study