Paul Satz - US grants

The proposed objectives have the following aims: (1) to determine whether a shift in the distribution of handedness exists in an unselected sample of autistic children and adults; (2) if so, to determine its underlying constructs; (3) to determine whether the constructs are specific to autism or whether they relate more generally to overall mental retardation irrespective of autistic symptomatology and (4) to determine whether these phenotypes provide potential neurobiological markers of different etiological subgroups within or between disorders. Subjects will consist of two unselected autistic samples as follows: (a) UCLA Sample (n=50) which comprises a younger and higher functioning outpatient group; (b) Camarillo Sample (n=80) which comprises an older and lower functioning inpatient group. Two lower and higher functioning MR non-autistic samples will be selected from UCLA and Camarillo State Hospital as comparison matches for the two target samples. The research design involves a rigorous one week test-retest assessment of handedness using multiple items normed for developmentally retarded Ss. These measures will be used to investigate Aims 1-3 which essentially involve the identification of various handedness phenotypes. A unique feature of this project, including the assessment of handedness, concerns an extension of the PLH model (Satz, 1972) to deal with multiple handedness phenotypes. This revised model provides a conceptual and quantitative framework for dealing with potential etiological subgroups of autistic and/or MR subjects. The subtypes will first be validated against external behavioral criteria to determine whether they correlate with different neurobehavioral outcomes (e.g., adaptive behavior, intelligence, familial handedness, trophic changes in extremities). If group differences occur, as preliminary results suggest, then a random subset of each phenotype will be given high resolution computerized tomography to determine whether these phenotypes confer any significance as biological markers of etiological subtypes in infantile autism. The proposal seeks to explain some of the known heterogeneity that has long plagued research in this disorder(s).

The purpose of this 3-year cross-sectional study is to investigate the neurobehavioral effects of HIV-1 infection in black males at risk for AIDS. The primary high-risk categories to be studied are HIV-1 serostatus, drug use, and homosexual/bisexual orientation (H/B) and related risk behaviors. The study seeks to achieve the following five aims: 1. to standardize the neuropsychological (NP) and brain imaging (BI) parameters in seronegative (SN) black non-drug users (D-); 2. to estimate the possible effects of sexual orientation and behavior on NP and BI outcomes in SN black D-; 3. To estimate the possible independent and interaction effects of HIV-1 serostatus, drug use and IQ on NP & BI outcomes in H/B blacks who are asymptomatic (ASP) for AIDS; 4. to estimate the possible effects of AIDS-related symptoms on NP & BI outcomes in H/B seropositive (SSP) black D-; and, 5. to determine whether any of the effects noted above are mediated by psychosocial (PS) factors Two cohorts of black males (18-50 yrs) will be recruited. Cohort 1 (Parent cohort) will comprise a sample of 750 black males that will be classified by HIV-1 serostatus, drug use and sexual orientation into six groups: 100 gay/bisexual ASP/D+, 100 gay/bisexual SN/D+, 100 gay/bisexual ASP/D-, 50 gay/bisexual SSP, 200 gay/bisexual SN/D- (gay comparison), and 200 heterosexual SN/D- (heterosexual comparison). The parent cohort will be tested with a comprehensive battery of NP and PS measures, and basic demographic, history of drug use and sexual practices information will be obtained. The sample of 400 comparison SB will serve as the standardization sample to establish appropriate Np & BI norms (Aim 1), and to test for the effects of sexual orientation and behavior on NP & BI outcomes (Aim 2) The psychosocial hypotheses will be tested on the entire sample. Cohort 2 (Nested cohort) will be a random sample of 250 H/B subjects from the parent cohort and will be tested with comprehensive neuroimaging measures including MRI and SPECT, and used to test for NP, PS and BI differences between the 5 gay/bisexual groups (Aims 3, 4 & 5). It is expected that the results of this study should provide a strong empirical foundation for future research on the neurobehavioral consequences of HIV-1 infection in black men.

DESCRIPTION (Provided by applicant): This submission is a competing continuation of our on-going "Neuropsychology of HIV/AIDS Fellowship" at UCLA that, for the past 10 years, has provided training support for postdoctoral Fellows specializing in HIV research. We propose to continue training three post-doctoral Fellows per year with each Fellow receiving two years of funding. Emphasis will be on training Fellows in clinical research in the Neuropsychology of HIV/AIDS. Fellows will be engaged in a primary research project and one or more secondary research projects, working with Dr. Paul Satz (P.I.), Dr. Charles Hinkin (Co-PI), and Dr. Eric Miller (Co-PI), as well as, with other primary faculty. This HIV research Fellowship is embedded in the UCLA Neuropsychology Postdoctoral Training Program in Neuropsychology, headed by Dr. Satz since 1981, that annually trains 8-10 fellows in clinical and research Neuropsychology. The HIV training faculty, hold multiple NIH and private research grants, thus affording Fellows the opportunity to participate on a wide-array of research projects. Fellows also have the opportunity to collaborate with multiple supervisors, exposing them to a breadth of experience and supervisory styles. Fellows will also encounter a heavy clinical exposure to HIV-1 infected individuals and will provide clinical neuropsychological assessments on at least one HIV-1 infected patient per week. Additional clinical experience will be available at community-based AIDS service organization (AIDS Project Los Angeles). A rich didactic base, including coursework from 8-5 every Thursday, rounds out the training experience. We are committed to continue recruitment and training of women and members of traditionally underrepresented groups in our Fellowship, who together represented 64 percent of the Fellows supported by this training grant. Over the past ten years we successfully recruited and trained 8 Fellows who were members of underrepresented groups (40 percent of our total Fellows enrolled). The successful career trajectories of our graduated? Fellows demonstrates the success of our program. We are eager to continue our training efforts in this important area of clinical research of another five years.