This study is closed to enrollment.
To view the final Progress Report, Click Here.
PURPOSE OF THE STUDY
The long term goal of our research program is to contribute to an empirically grounded picture of preschool psychiatric symptoms and disorders that can be translated into effective diagnostic, screening and treatment approaches to help young children and their families. In this study, we propose to determine the prevalence of apparent DSM-IV anxiety disorders in a pediatric primary care sample of preschoolers, and to examine their patterns of comorbidity, psychosocial disability (impairment), specialty service use, family functioning, parental psychopathology, and temperamental characteristics.
The specific aims of this proposal are as follows:
Aim 1. To establish prevalence rates for individual preschool anxiety disorders in pediatric primary care settings according to the DSM-IV criteria, by age, sex and ethnicity (African American vs. White). In particular we will focus on (1) SAD, (2) GAD, (3) social phobia, and (4) specific phobias.
Aim 2. To establish rates of comorbidity among the anxiety disorders (homotypic comorbidity).
Aim 3. To establish rates of comorbidity between the anxiety disorders and other disorders (heterotypic comorbidity). We will specifically address comorbidity with ADHD, ODD, CD, and depressive disorders (major and minor depression and dysthymia).
Aim 4. To establish clinical cutpoints for identifying abnormal levels of anxiety-related behavior for symptoms that may be particularly common in preschoolers who are not otherwise disordered.
Aim 5. To evaluate the match between service need and service use (including medication).
We are interested in identifying characteristics that are associated with specialty mental health service use (as a means of identifying starting points for clinician education), and particularly with medication prescription.
Aim 6. To establish the concurrent validity of parent-report preschool anxiety disorders.
Aim 7. To determine the relationships between DSM-IV anxiety diagnoses and the broad temperament constructs of negative affectivity and effortful control (including capacities for attention shifting and response inhibition). In particular, we are interested in the degree to which DSM-IV “anxiety disorders” and these anxiety-related temperament constructs are different names (derived from different research traditions) for the same things.
Aim 8. To use statistical methods, such as latent class analysis, to identify “natural classes” of individuals with particular patterns of anxiety-related symptomatology. This is another means of validating (or otherwise) the DSM-IV disorders, since the emergence of “natural classes” of individuals with symptom patterns resembling those specified by the DSM-IV criteria for particular disorders, would reinforce the utility of the disorders so defined.
BACKGROUND & SIGNIFICANCE
Anxiety is among the most common and disabling psychiatric problems of the preschool years. Effective psychopharmacological and psychotherapeutic treatments for older children have been developed and younger children too could potentially be helped, if they show similar patterns of symptoms, impairment, and prognosis. At present we know almost nothing about the prevalence and burden of preschool anxiety as it relates to the standard DSM or ICD taxonomies.
DESIGN & PROCEDURES
First, we will screen 4,410 parents of preschoolers attending a primary care pediatric clinic. Second, from this screened sample we will select a screen-stratified sample of 929 families with children ages 2-5 years old. We will conduct an in-home assessment with the primary parent (parent who consented to participate in the screening) about the child’s psychiatric symptoms and temperament, as well as the parent’s own personality traits, symptoms of anxiety and depression, and distress in the parent-child relationship. Third, we will recruit 500 of the 929 families to participate in a nested case-control study (250 children who meet criteria for an anxiety disorder and 250 children who do not meet criteria for an anxiety disorder). The primary parent and child will participate in an intensive laboratory assessment using multi-modal, multi-informant assessments of the child’s and parent’s anxiety, temperament, and psychopathology and interactions with each other. We will also collect teacher/childcare provider data on the nested cohort. We will offer teachers/caregivers the option of filling out the questionnaires by hand then returning them by mail or fill out the questionnaires at a secure website. The package sent to the teacher/caregiver will contain the consent forms from the parent for the teacher/caregiver to fill out the questionnaire, the questionnaires (Caregiver-Teacher Report Form and Social Skills Rating System), and the secure website URL and a password to access the form. If the teacher/caregiver decides to fill out the questionnaires by hand, they will sign the consent form and return the consent and questionnaires in the provided self-addressed, stamped envelope. If the teacher/caregiver opts to fill out the questionnaires online, they will electronically consent. The teacher/caregiver will only be able to access that particular subject. The password will expire upon the completion of the questionnaire or 30 days after the teacher/caregiver accesses the questionnaire (if the teacher/caregiver does not complete it on their first attempt). See Data Storage and Confidentiality Section below.
SUBJECT ENCOUNTER DATA
Subjects consented to a medical records review at the time of initial screening. A review of the medical record encounter data for each subject will provide information regarding the type and severity of medical conditions of the subjects in this study. The encounter data will include diagnosis codes (ICD-9 Codes), procedure codes, encounter type, and charges (CPT Codes), allowing for us to identify the medical conditions of subjects, including important exclusions for this study such as autism or other developmental disorders, as well as allowing us to identify children with asthma or other medical conditions severe enough to lead to hospitalization or ED (emergency department) utilization or other high utilization of the clinic or cost, indicating severity. As part of the encounter data, details regarding procedures and inpatient hospitalization will be collected, again to assist in understanding severity of medical conditions that could affect development of anxiety in our subjects. Vital signs, including height and weight are gathered as part of routine encounters and will also be collected as part of assessing the health status of participants (underweight again being a sign of poor health). Finally, routine laboratory studies associated with pediatric encounters including CBC, lead, and rapid strep will be collected as part of assessing the health of subjects, as anemia, lead toxicity, and strep have been found to be linked to anxiety and other psychiatric conditions.
JUSTIFICATION FOR ENCOUNTER DATA
(1) To exclude data from individuals who have pervasive developmental disorders (which we would identify from chart review). In the funded proposal we planned achieve this exclusion as follows: “Parents of children younger than 3 years of age will be asked to complete the Modified Checklist for Autism in Toddlers (M-CHAT)277, while parents of children 3 years of age and older will be asked to complete the Social Communication Questionnaire (SCQ).278 Any positive questionnaire would be followed up with a phone interview that used items from the Autism Diagnostic Interview (ADI) to determine whether the behavior is really atypical or not. Exclusion for autism or other PDD will be based on the results of the screen and telephone follow-up.” In practice, it turned out that the proposed screens identified an unreasonably large number of children (around 30%), so the ADI telephone follow-up was impractical. In the light of that we decided that review of the medical records would be a much more practical alternative.
2) Anxiety has been associated with atopic disorders in older children and adults, and we want to know whether this is also true in preschoolers. As far as we know no-one has looked at this question in children this young. We described this aim as follows in the grant: “To date there has never been a detailed study of a broad range of anxiety symptoms in relation to atopy in children as young as those who will participate in the proposed study. We now propose to search each participant’s medical record for evidence of atopic symptomatology and diagnoses, and treatment for such disorders. We will then determine whether the association between atopy and anxiety observed in older children is already present during the preschool years. Atopic disorders have been added to our list of “putative risk factors” in the body of the proposal.”
(3) Aim 5 of the grant is to “evaluate the match between service need and service use (including medication). We can already be sure that referral for specialist service use will be uncommon, but we are interested in identifying characteristics that are associated with specialty mental health service use (as a means of identifying starting points for clinician education), and particularly with medication prescription.” While we gather some data on service referral and medications with our current assessments, a medical records review will enable us to obtain more detailed data on mental health diagnoses, referrals, and treatments including medications. We also did obtain permission in our consent form to review the medical records of the children who participated in our other preschool study. The main aim of that study is also to understand early childhood anxiety and depression. Thus, the need to be able to account for medical disorders, such as allergy, asthma, and other atopic disorders, as well as diagnosis of mental health disorders and treatment with medications is the same as for the preschool anxiety study. More over, we also include autism and other pervasive developmental disorders as an exclusion criterion and have relied upon parent report for this designation.
DESIGN & PROCEDURES
This is a continuation of a Duke Preschool Anxiety Study of normal and abnormal development that began in January 2007 and will continue through July 2011. At this point, interviews have been completed with 482 families (51.9% of recruitment sample). It is estimated that an additional 447 families will be enrolled by July 2011.
|Proposed Mail Collection Protocol:
· Initial phone call to invite subject’s family to participate in the saliva collection
· Send out mail packet within 3-5 days: letter further describing saliva collection, consent form, saliva collection kit, instructions
· Send out mail reminder postcard within 3-5 days
· Place reminder call one week later to subject’s family about saliva kit; respond to questions / concerns; convert refusals; inquire about need to send second saliva kit; inquire about need for face-to-face collection
In the case of new families (approximately 447), subjects will be recruited as part of the in-home or office-based interviews to provide Orgene saliva samples. Saliva collection is minimally invasive, well-tolerated, low risk and cost effective. Oragene is a particular good alternative to venipuncture for large-scale epidemiology studies as research has demonstrated it produces high quality DNA that may be used for Taqman genotyping. Parents will be provided consent form that describe the saliva collection and genotyping procedures. A trained data technician will procure the saliva samples.
This leaves the approximately 500 families that have already completed interviews. We propose a hybrid approach to collecting samples, in order to strike the best balance between maximizing the sample and minimizing the costs. Investigators for the Wisconsin Longitudinal Study piloted experimental groups to determine how to maximize response rates for mail collection of saliva. Response rates varied based upon the number of total contacts, and timing of contact. Our proposed protocol (see text box) will replicate their optimal condition which achieved a high response rate. All families would be contacted by phone to have the study described. Packets would be sent to the families with consent forms, saliva collection kits, instructions, and a return envelope. Contact information of study personnel will be provided to parents.
Some families may not return mailed collection kits. In these cases, the data technician will follow up with these families by phone to schedule face-to-face collection. A data technician would then travel to the families’ homes, review consent forms with the parents, and collect saliva samples.
Table 1 below details the schedule of assessments to be used in this study.
|Table 1. Schedule of Assessments|
|Screening||4,410||1° Parent||CBCL 1½-5; M-CHAT (< 3 years old); SCQ ( > 3 years old)||15 mins|
|In-home assessment for whole cohort||929||1° Parent||PAPA, ECBQ/CBQ, BDI, BAI, NEO-FFS, PSI-SF||2 hrs|
|Laboratory assessment for nested cohort||500||1° Parent and child||DB-DOS/ P-COS Behavioral inhibition/disinhibition protocol, Effortful control tasks of attention shifting and inhibitory control, Eye Tracking Protocol, Doll House Protocol PPVT, CTS parent-child and CTS2, CIDI, SSRS||2 to 3 hrs|
|Teacher/child-care provider assessment||400||Teacher/ childcare provider||C-TRF, SSRS||25 mins|
Costs to participants are their time and effort. There are no expenses associated with this study. The risks of the study are those associated with discussing personal issues with a trained interviewer: possible embarrassment and distress. Interviewers are trained to ameliorate these effects and procedures are in place for referring seriously distressed subjects for psychiatric evaluation and treatment (see below). Compensation for subjects is described below. Direct benefits to the parents are the compensation provided (see below) and the opportunity to help in a study that will greatly increase public knowledge about anxiety disorders in very young children and the need for treatment and prevention of preschool mental illness.
The following procedures were added for the 2009 amendment.
The risks of the study are those associated with spitting into a small receptacle and are considered minimal. The benefits of the study are the chance to contribute to our understanding of genetic contributions to the development of anxiety and depressive disorders.
Children or parents are occasionally identified who appear to be at serious risk of suicidal or homicidal actions, or who are subject to physical, sexual, or emotional abuse or neglect. When an interviewer believes that such a possibility exists, s/he will at once consult with the project coordinator. She will determine if the case meets the criteria laid down in the guidelines specified by the study’s clinical faculty (Angold and Egger) and will consult with one of them. Drs. Angold and Egger are both child psychiatrists. If it is determined by the clinician that intervention is mandated, the interviewer will call and explain to the parent the reasons why it was deemed necessary to obtain a clinical consultation, and will offer referral to the appropriate agency or, in the case of suspected abuse, file the necessary Child Protective Services Law report. All parents will be given information about the mental health services available at Duke Primary Care pediatric clinic and through the child psychiatry department at Duke University Medical Center. All written reports will be made each time an emergency plan is implemented.
SUBJECT IDENTIFICATION, RECRUITMENT, AND COMPENSATION
Please see the Design and Procedures section for details about the subject identification and recruitment. Subjects will be compensated for participating in this study. The primary parents will be given $75 for completion of the in-home assessment and $100 for completion of the lab assessment. The “other” parent(s) will be given $50 for completion of the CIDI and NEO-FF. Parental reimbursement is intended to pay for travel, parking, and childcare for siblings, and to reimburse participants for their time and effort. We will provide cab or bus fare for subjects who do not have transportation or if they cannot afford the cost of cab or bus fare. This will be in addition to subject payment; cab or bus fare will not be deducted from subject payment. The index child will be given a small gift (stuffed animal, drawing pad, and crayons) after the lab session. A healthy snack will also be provided to the child during the laboratory assessment. Teachers/childcare providers who fill out the measures will be given a $10.00 gift certificate. There is no additional proposed compensation for providing saliva.
We will not include parents who are not competent to provide consent. If the child objects to participating in any part of the protocol or becomes distressed, we will stop the assessment.
Inclusion/exclusion criteria for the screened sample (n=4,410)
Screening inclusion criteria will be (1) a child who is between 24 and 71 months old, (2) the presence of a parent/legal guardian at the clinic visit who speaks English well enough to consent to participate in the screening, (3) the child’s attendance at the Duke pediatric clinic during a screening period. Exclusion criteria will be (1) lack of a parent with adequate fluency in English to complete the interview, and (2) the index child being known to have mental retardation (IQ < 70), autism, or other pervasive developmental disorders. Parents of children younger than 3 years of age will be asked to complete the Modified Checklist for Autism in Toddlers (M-CHAT), while parents of children 3 years of age and older will be asked to complete the Social Communication Questionnaire (SCQ). Any positive questionnaire would be followed up with a phone interview that used items from the Autism Diagnostic Interview (ADI) to determine whether the behavior is truly atypical. Exclusion for autism or other PDD will be based on the results of the screen and telephone follow-up; (3) sibling already enrolled in the study. If the parent brings more than one child between the ages of 24-71 months old to see the pediatrician, the recruiter will consult pre-computed random selection tables to select which child to enroll in the study.
Inclusion criteria for screen-stratified in-home interviewed sample (n=929)
Children who score 4 or more on the narrow band anxious/depressed syndrome scale of the CBCL1 ½ -5 will be recruited to participate in the study (N=706). We will randomly select 7.9% of children who score less than 4 on the anxious/depressed scale (N=223).
Inclusion criteria for nested case-control sample (n=500)
We will run the diagnostic algorithms on data from the in-home assessment to determine whether the child meets diagnostic criteria for any DSM-IV anxiety disorder (SAD, GAD, simple phobia, social phobia, PTSD, and/or selective mutism), and attempt to recruit all children with an anxiety disorder. We expect to recruit 250 children who meet these criteria, 240 from the screen positive group and 10 from the screen negative group. We will also randomly select 7.9% of children who do not have an anxiety disorder (N=37 from the screen highs, and 223 from the screen lows). We will ask the parent who completed the in-home assessment to complete the laboratory assessment with his/her child.
COSTS TO THE SUBJECT
Subjects will incur no costs as result of participating in this study.
DATA ANALYSIS & MONITORING
Statistical methods for data analysis will include exploratory data analysis, factor analysis, and logistic regression for testing hypotheses and model building. Our statistical expert Alaattin Erkanli, PhD. will be closely involved in all phases of the data analyses. No data monitoring committee will be used. Data on eye position will be analyzed using both multivariate and spatial statistics.
DATA STORAGE & CONFIDENTIALITY
Data will be collected in the form of electronic interview schedules, digital voice recordings (MP3 files) of the interviews, and video recordings. Ensuring the integrity and confidentiality of the data is an essential part of safeguarding the rights of subjects. The Center for Developmental Epidemiology, from whose offices the study will be conducted, has instituted a series of checks at several levels of data handling, to maintain its quality and confidentiality. (1) Interviewers, many of whom have years of experience in survey work, will be given extra training in the importance of confidentiality in psychiatric interviewing. Like all study personnel, they will promise in writing to maintain that confidentiality. (2) After data are entered, the protocol (in both its physical (paper and pencil) and electronic (entered data forms) will be identified by number only. From this point it will not be possible to trace it back to an individual except by linking with a separate computer file that includes both the identification number and the individual’s identity. This file is password protected, and kept in a special computer volume to which only our (a) network administrator and (b) senior data manager have access rights. (3) Protocols and tapes will be kept in locked file cabinets in a locked storage room in a research facility that is locked at night. (4) Written reports and papers will not identify subjects or make identification possible, without the written consent of the person concerned. Our data storage plans have been developed to be fully compliant with HIPPA safeguards.
The web application that supports the teacher questionnaire uses strong encryption technology for all data transfers, secure passwords for user accounts and server infrastructure that is maintained to comply with Duke Health Enterprise Computer Security Standards. These Standards have been designed by the Duke Information Security Office (ISO) to ensure enterprise-wide compliance with applicable Federal and North Carolina law, such as HIPAA and the NC Identity Theft Protection Act. The ISO verifies compliance of covered systems by performing internal audits.
We have applied for a Certificate of Confidentiality. A Certificate of Confidentiality helps researchers protect the privacy of human research participants enrolled in biomedical, behavioral, clinical and other forms of sensitive research. Certificates protect against compulsory legal demands, such as court orders and subpoenas, for identifying information or identifying characteristics of a research participant.
In 2009, an amendment was added to study genomic contributions to the development of psychiatric disorders across various types of environmental adversity.
All saliva samples will be labeled with unique identification numbers (different from the study identification numbers) and processed by the Duke Center for Human Genetics DNA Bank. They are experienced with processing samples under unique IDs. A key file will be kept on a secure server for the purpose of linking the saliva samples with the study IDs. The merging of genotyping data with phenotypic and environmental data will be completed by a database manager at the Center for Developmental epidemiology.
The following procedures were added in 2012 amendment.
We will complete two (2) short, follow-up questionnaires: SPENCE Children Anxiety Scales (Parent Version) and a shortened version of the Mood and Feelings Questionnaire (Parent Report on Child). We will complete the questionnaires by phone, and it is anticipated to take less than five (5) minutes. We will only complete these questionnaires with subjects that completed the Lab assessment (N=503). All subjects that completed the lab consented to be contacted in the future for further research.
The following procedures were added in 2014 amendment.
PURPOSE OF AMENDMENT
We propose to re-contact parents of participants in the Preschool Anxiety Disorders in Primary Care Study (PAS) to see if they would be willing to share home videos during their child’s first year of life. All of these parents and children agreed to be re-contacted about new phases of research as part of their initial consent into the project.
The purpose of this portion of the study is to develop automated computerized methods for coding behaviors of infants from home videos taken during the first two years of life. The long range goal of this research is to develop efficient, cost-effective methods for detecting early signs of developmental or mental health disorders such as autism spectrum disorder (ASD).
We will send out an initial mailing letter with information about the new phase of study to all families who participated in the PAS who have all indicated they are willing to be re-contacted about future studies. We will then follow up with anyone who expresses interest in this portion of the study. After explaining and signing consent forms, participants will be given the following options for sharing their home videos: (1) dropping their videos off with approved study personnel at the Department of Developmental Epidemiology Offices during normal business hours; (2) having a staff member come pick up videos at their home; or (3) sending in their video using a self-addressed stamped padded envelope provided by our offices. We will provide blank DVDs or appropriate recording medium (e.g. data card) for those who only have a digitized copy of their videos.
Participant videos, which can be as short as a few minutes long, will be used to develop more sophisticated, automated, coding technologies to try to distinguish critical elements of behavior (e.g., head movements, visual gaze, facial expressions, gestures in response to various sensory and social stimuli etc.). This process will include developing programming techniques for automatic detection and recognition of facial landmarks and expressions that might be correlated with specific activities that are typical for children at this age (e.g., playing with toys, birthday party, etc.).
All videos will be labeled with a unique identification numbers and will be digitized and returned to participants along with $25.00 for their participation. All videos will be stored in locked cabinets per IRB instructions and/or transferred to a restricted access network on a secure Duke University server only accessible by approved study personnel. The videos will only be viewed by approved individuals for the purposes of the specific research. If parents agree, segments used for presentation/teaching purposes will be de-identified so they are not recognizable (e.g. faces blurred).