DESIGN AND PROCEDURES

This study includes 2 parts. Part I is a comprehensive clinical research assessment that will provide publishable data on parental and child cognitive and mental health functioning and will also determine eligibility for Part II, which is the completion of Time-01

psychobiological assessments (24-hour urine collections, morning and evening salivary cortisol levels, sleep/wake activity measures, and MRI procedures) and the after 1-year Time-02 follow-up. 280 subjects referred for maltreatment and 140 controls will undergo Part I Clinical assessment, 140 subjects with histories of maltreatment (70 with PTSD, 70 without PTSD) and 70 controls will undergo the Part II psychobiological assessments and the after 1-year Time-02 follow-up.

Thus, this protocol will consist of: a) initial telephone screening to determine eligibility for Part I clinical assessment, b) Part I completion of Time-01 clinical assessment screening to determine presence of PTSD, psychiatric and neuropsychological assessments and Part II scheduling and completion of biological collections and MRI scans, if subject does not meet exclusion criteria, c) completion of Time-02, after one-year follow-up of all subjects who undergo Part II.

Time-01 Part I Clinical assessment will consist of a one-day visit to the Healthy Childhood Brain Development Program. Clinical research interviews and questionnaires of the parent and child will be conducted to determine the child’s mental health status, absence or presence of PTSD, family history of mental disorders, and cognitive function. Clinical research interviews and questionnaires of the parent will be conducted to determine the non-abusing parent’s mental health status, absence or presence of PTSD, family history of mental disorders, and health and cognitive function. Blood and salivary levels and vagal tone for determination of biological stress measures and markers of biological mediators of stress and brain development (i.e., cortisol, catecholamines) will be taken on the interview morning of the child. A brief physical exam of the child in the parent’s presence will determine cranial size, heart rate and sitting and standing blood pressure. Subjects may refuse these measures and still be eligible to complete the remaining protocol. Audiotaping of the interviews will be done to insure good reliability for the interviews. Dr. De Bellis and the clinical interviewer will review the tapes. If subjects choose not to have their interviews recorded, they may still participate in the study. It is estimated that the evaluations can be completed in 6 hours. We are planning on scheduling each child and legal guardian (caregiver) for one day consisting of 8 hours to allow for breaks. Lunches will be purchased by the study.

Part II: After Part I clinical assessments are completed, subjects who meet the eligibility inclusionary criteria and do not meet the exclusion criteria will be asked to undergo the following Part II procedures.

Since maltreated subjects usually do not disclose abuse after the first occurrence, especially when this abuse is incest (Putnam and Trickett 1993), it is important to ascertain if neglect on the part of the non-abusing caregiver is related to the delay in disclosure. It is important to measure emotional neglect as this may have its own contributions to adverse brain development. We also collect data on neglect as part of the interview process.

Biological Sample Collection: 24-hour urinary cortisol and catecholamine measures and morning and evening salivary cortisol measures will be collected as a reflection of biological stress system function. Subjects and their caregiver/s will be given detailed instructions. Subjects will follow a low monoamine diet and keep a daily log of diet and activities for two days prior to and on the days of collection. 24-hour urine collections will be performed over a non-school day in which the subjects are not engaged in stressful activities such as athletic competitions or studying for important exams. We also will ask our subjects to wear an actograph. This device measures levels of physical activity and sleep-wake cycle. We have found that subjects in this age group are compliant with the diet, daily log, complete

collections, and actigraphy measures. Urine collections will be done at the subject's home and brought in by subjects or picked up by our staff. Subjects can chose to do all, some, or none of these procedures. All subjects will also be asked to undertake a salivary alcohol test and urine drug screen prior to clinical assessment, MRI scans, and neuropsychological testing to assess recent substance use. Female subjects who started their periods, must undergo a urine pregnancy test before the MRI scan. Any positive results will be shared with the subjects and their parent.

MR brain scans (anatomical MRI, functional MRI and MR Spectroscopy): MRI technology is a safe and novel approach to measure brain structure and chemistry in living children. This technology does not use ionizing radiation. To date, we have successfully scanned over 200 children and adolescents (age range: 3 to 19 years) at Duke for anatomical MRI measures without sedation using the desensitization procedure described below. Subjects listened to relaxing music during the CAMROD scan and may watch videos during the BIAC scans. Showing movies for the children, using a projector and video screen during the actual scan, has not only greatly enhanced our success, but it has made scanning an enjoyable experience for the children. Subjects aged 6 to 7 are only asked to do one scan at the CAMROD scanner for anatomy, MRS and DTI. Subjects 8 years and older are asked to do 2 scans, the scan at CAMROD and an fMRI scan at BIAC. The MRI CAMROD

procedures take a total time of about 1.5 hours. The MRI BAIC procedures take a total time of about 2.5 hours. This includes an extra half hour to undergo the simulation scanner. We noted that less than 2% of children had difficulty completing a successful scan (due to movement artifact or claustrophobia). An experienced person will monitor the subject for anxiety by observation and by self report and physiological measurements of pulse, blood pressure and respiration. No sedation will be used during the actual scanning procedure. The caregiver is welcome to stay in the control room during the scan, where the child can be viewed via a video camera and talk through a two-way audio system. Prior to entering the MR scanner, subjects will be trained in our simulation scanner which reproduces the sights and sounds of the scanning environment. MRI measures will be performed at the

Department of Radiology, DUMC. Subjects may choose to do one, two or none of the MRI scans and still participate in other Part II procedures.

Completion of Time-02, after one-year follow-up will include repeat parent and child’s diagnostic clinical interview for presence of PTSD and other mental disorders, an assessment of interventions, repeat Biological Sample Collection, repeat neuropsychological testing, and may include another series of MRI scans.