Objective 1: Recruitment and screening

Recruitment

1) A marketing agency identified potential participants based on a population - based sampling method.

2) An introductory letter describing the study, the personnel involved, and a forthcoming phone call from a study recruiter to answer questions about the study was sent to addresses provided by the marketing agency to each study site.

3) A brochure describing the study, a stamped, addressed post card, and an incentive (a fridge magnet with the title of the project) was sent along with this letter.

Screening

4) An initial recruiting telephone call was made to all families, except those who asked not to be contacted in the returned postcard.

5) During the call, the Brief Telephone Screening Interview was administered to ensure that the family had a child within the target age range, that English is the child’s primary language, that at least one parent is proficient in reading English, and that the potential child participant does not have a diagnosed chronic medical psychiatric condition, learning, or neurological disorder.

6) If the family was interested in participating, they then received a letter, a brief description of the study, and a telephone interview screening consent form with an addressed and stamped envelope. This form included a telephone number that parents could call if they had questions.

7) Included with the consent was the CBCL, a behavior rating scale to be completed by the parent and returned with the signed consent form. Also included was an outline of the Full Telephone Screening Interview. The family was informed that a telephone call would be made within 10 days to ascertain if they received the study documents and at this time a phone appointment would be made to conduct the Full Telephone Screening Interview.

8) A follow-up phone call took place (if documents had not been received) to inquire if the family had mailed the required forms (the parent CBCL is used for screening purposes and therefore is needed for the interaction with the family to proceed), and to offer assistance if needed.

9) At the time of the phone appointment for full telephone screening, any remaining questions the parents had about the interview or the consent form were answered. If the signed consent form had not been received, a verbal consent was obtained and documented, and the parents were asked to sign the consent form and mail it back to the investigators with the completed behavior rating forms.

10) The Full Telephone Screening Interview consists of the administration of a medical and developmental history questionnaire and a review of any missing information on the rating scale returned with the screening consent form. If the subject remained eligible, a structured psychiatric interview (The MRI Study of Normal Brain Development 27 Version: November 2006 Diagnostic Interview Schedule for Children [DISC] for subjects over 7 years of age), and the Family History Interview for Genetic Studies (FIGS) was administered to the parent. Adolescents over age 11 also completed the DISC Predictive Scales (DPS) interview. Following this phone call, and assuming all inclusion criteria have been reviewed and met, an appointment for an on-site evaluation and MRI was made with eligible families.

11) A telephone call to confirm the next-day hospital appointment was made.

Objective 1: On-site procedures

The on-site evaluation and MR scans may require up to two days.

Evaluation procedures

1) Consent forms describing the study and all evaluations were signed and witnessed; children aged 6-17 gave their written assent.

2) Portions of the evaluation that may determine the final screens for eligibility and exclusion were conducted prior to MR scanning, as were further clinical/ behavioral testing that is used for brain-behavior correlation.

3) A physician conducted a physical/neurological examination (including the Petersen Pubertal Development Scale, when appropriate).

4) Urine and saliva samples were collected. Two saliva samples were collected for the measurement of sex hormones as a more sensitive indicator of stage of maturation than chronological age. A urine sample was collected for endocrine measurements, to complement the Petersen staging and growth data. Adrenal and gonadal steroids were measured in the saliva and urine.

Additional screeners

5) The physical/neurological examination, served as an additional screen for eligibility and exclusionary criteria.

6) In adolescent girls of childbearing potential (who have begun menses) a urine test was taken to rule out pregnancy (using a stick test). A positive pregnancy test led to a laboratory test to rule out a false positive. A refusal for pregnancy testing resulted in exclusion from the study.

Clinical/behavioral battery

7) Following these initial on-site evaluations, a psychologist or trained research assistant conducted testing with a battery of neuropsychological tests. (The results of these tests will be used for purposes of brain-behavior correlations and also to determine continuance in the study; e.g., an IQ rating < 70, or scores on any achievement test greater than 2 SD below the mean would exclude the child.)

MRI scans

8) The MR scans will be conducted in addition to the clinical/behavioral evaluations described above, but possibly on another day depending upon the preference of the family, the temperament/fatigue of the child, the availability of scanning slots, and best practices of the site in terms of eliciting cooperation and motion-free scans.

9) For example, young children may be scanned late at night to encourage them to sleep in the scanner. Parents have the option to be with their child in the scanner room, if they desire, and if they have no contraindications for entering the MRI scanner room.

10) The actual scanning time for the anatomic MRI is approximately 30-40 minutes.

11) Those children participating in the additional MRS will have an extra 6-20 minutes of scanning time. The complete scan session will be approximately 35-60 minutes.

12) The entire procedure from arriving to the MR suite to leaving the suite upon completion of the MR studies takes approximately 1 to 1-1/2 hours.

13) For the youngest children and those children who express anxiety about the MR procedure, one or more 15–20 minute sessions with a mock scanner may have been scheduled. At one site selected subjects may be asked to return for a more prolonged (70 minute) MRS study scheduled at a different time.

14) Participants were asked to return two more times at two-year intervals.

15) The full telephone interview, behavior rating scales, on-site evaluations, and MR scans are repeated at each time point and participants sign, in full, new consents and assents at each follow-up visit.

16) Subjects were compensated for their time (in the order of $50-100 per day; final amounts to be decided by each PSC and made known to the other centers to maintain consistency, whilst keeping in mind regional factors dictating differences), and travel, parking, and meal expenses were covered.

For more information, please see the NIHPD protocol.