Michelle M. Martel - US grants

[unreadable] DESCRIPTION (provided by applicant): Attention-Deficit/Hyperactivity Disorder (ADHD) has a male-to-female ratio ranging from 2:1 to 9:1, a ratio that suggests that boys and girls may follow different pathways or have differential vulnerability for the disorder. The proposed study would examine sex differences in neuropsychological and cognitive functioning, temperament traits, and sex hormone levels as they relate to ADHD symptom expression. Child participants between ages eight and thirteen will be recruited through public advertisements and outreach and will undergo a multistage screening process consisting of parent and teacher behavior rating scales and parent clinical interviews. Children will complete a battery of neuropsychological and cognitive tests to assess executive functions, delay aversion, intelligence, and achievement. Parents and children will complete temperament ratings to assess effortful and reactive control. Venipuncture blood draws will be obtained to assess estradiol and testosterone. Sample size will range from 150 to 585 with approximately thirty percent of the sample female. A key question addressed by regression analyses will be whether sex differences exist in the temperament and neuropsychological correlates of ADHD. Temperament and neuropsychological executive function will also be explored as potential mediators of the relationship between hormones levels and ADHD symptoms. These studies are novel and will provide new knowledge in a much theorized area. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): This proposal represents a first step in a program of work designed to develop a screening measure to improve early identification of children at risk for severe, persistent or increasing disruptive behavior or attention problems or both (i.e., symptoms of Attention-Deficit/Hyperactivity Disorder [ADHD] and/or Oppositional- Defiant Disorder [ODD]). The primary aim tested is that temperamental traits and cognitive control will differentiate children at risk for severe, persistent or increasing symptoms of disruptive behavior and/or attention problems over one year. Subsidiary aims include: 1) examination of whether temperament trait and cognitive control profiles vary as a function of diagnostic status and 2) evaluation of whether individual differences in temperament traits and cognitive control predict the one-year course of severe preschool disruptive behaviors over and above initial symptom levels. Distinct temperamental and cognitive factors are expected to be associated with each diagnosis and changes in their symptom levels. Children with severe, persistent or increasing attention problems (ADHD) will be characterized by low levels of trait and cognitive control, while children with severe, persistent or increasing oppositional-defiance and hyperactivity-impulsivity (ODD or ADHD+ODD) will be characterized by high levels of negative emotionality and approach. Using a one- year short-term longitudinal design, a sample of 120 children between the ages of three and six will be recruited via newspaper, radio, and posted advertisements until a target of at least 30 children per diagnostic group (i.e., ADHD, ODD, ADHD+ODD, and non-ADHD/ODD) is reached. During the initial in-person assessment, parents will complete a semi-structured diagnostic interview to evaluate children's diagnostic status. Temperament will be measured using the Laboratory Temperament Assessment Battery (observational ratings), the California Q-Sort (examiner ratings), and the Child Behavior Questionnaire (parent ratings). Cognitive control will be measured by having the children complete four tasks: Shape School and Snack Delay will measure response inhibition, Digit Span will measure working memory, and Trails-P will measure set- shifting. At six months and one year following the initial assessment, the diagnostic interview will be conducted with parents again, over the telephone. Analyses will evaluate the utility of incorporating temperament and cognitive control measures with standard diagnostic screening measures to improve prediction of the one-year course of severe preschool disruptive behaviors. This is the first study to comprehensively evaluate whether the short-term course of preschool disruptive behaviors can be predicted by initial status on temperament traits and cognitive control. The current study will evaluate whether the incorporation of temperament and cognitive control assessment into standard diagnostic batteries will enable better prediction of the course of severe disruptive behavior problems, thereby improving the ability to identify children who would benefit most from early intervention. PUBLIC HEALTH RELEVANCE: The current proposal seeks to evaluate temperament and cognitive control as mechanisms of preschool disruptive behaviors (inattention, hyperactivity-impulsivity, and oppositional-defiance;Attention- Deficit/Hyperactivity Disorder and/or Oppositional-Defiant Disorder). The integration of temperament and cognitive mechanisms of preschool disruptive behavior disorders with standard diagnostic assessment procedures may allow for more accurate prediction of the one-year course of disruptive behavior problems and thus more accurately identify those children who would benefit most from early intervention.

Females with Attention-Deficit/Hyperactivity Disorder (ADHD) remain dramatically understudied, even though they exhibit increased impairment beginning around puberty. Estrogen rises rapidly at puberty and exerts important effects on dopamine and cognition in both humans and animals. Both animal and human work suggest that cognition and ADHD symptoms may be sensitive to hormonal effects, particularly in highly impulsive females. Yet, the effect of estrogen on ADHD symptoms in young adult women remains virtually unstudied. Our pilot data in 33 naturally-cycling young women suggest that among women with greater ADHD symptoms, within-person declines in estrogen, particularly in the context of rising levels of progesterone, just post-ovulation, are associated with clinically significant increases in ADHD symptoms. Yet, no published empirical work has directly examined the role of circulating estrogen in relation to ADHD symptoms and cognitive mechanisms in women with ADHD. The current study would pioneer a new stage of work by being the first to utilize a rigorous quasi-experimental design that involves intensive longitudinal measurement across the menstrual cycle in order to examine within-person estrogen effects on ADHD and cognitive mechanisms in young women with ADHD. A sample of 120 young women ages 18 to 25 with inattention, overactivity, or impulsivity problems will be recruited from the university health center and local ADHD clinic, psychology department, and through social media. Participants will be comprehensively assessed for ADHD and exclusion criteria (e.g., use of hormone-based medication or hormonal conditions). Female participants will complete well-established assessment measures of ADHD and other psychopathological symptoms and diagnoses and cognition and provide saliva samples of hormones in the laboratory during a baseline laboratory visit within the first few days of the start of their menstrual cycle (i.e., during the mid-follicular phase, characterized by stable low estrogen). Then, they will provide daily saliva samples for hormone assay each morning and complete short daily assessments of ADHD and cognition every evening for up to 2 full menstrual cycles. They will also complete laboratory cognitive testing of inhibition and working memory targeted to key cycle phases characterized by declining estrogen (post-ovulatory, perimenstrual) and a cycle phase characterized by stable high estrogen levels (midluteal), based on menses onset and ovulation test results. Multi-level modeling will evaluate the clinical significance of within-person estrogen associations with ADHD and cognition with consideration of progesterone as an interactive factor. Effects of comorbid disorders and affect will also be explored. Study results have the potential to shift our understanding of ADHD in women by consideration of dynamic hormone influences. In addition, results will change clinical practice by indicating the need to account for cycle phase in ADHD evaluations in women, as well as suggest personalized approaches to treatment targeted to cycle phase or hormone levels.