Mentor:  Blythe A. Corbett, Ph.D.
Duration:  Short or long-term
Description:  Autism is a severe neurodevelopmental disorder characterized by impairment in communication, social interaction, repetitive behaviors and difficulty adapting to novel experiences. The Hypothalamic-Pituitary-Adrenocortical (HPA) system responds consistently to perceived novel or unfamiliar situations and can serve as an important biomarker of the response to a variety of different stimuli. Circadian rhythms of salivary cortisol were estimated in a recent study from our lab indicating that children with autism, but not typical children, show a more variable circadian rhythm as well as statistically significant elevations in cortisol following exposure to a novel, nonsocial stimulus. The results suggest that children with autism process and respond idiosyncratically to novel and threatening events resulting in an exaggerated cortisol response. Currently, we have a series of studies evaluating the circadian rhythms and response to stress in children with autism, Tourette syndrome and typically developing children. Trainees will get direct experience of patient interaction along with the opportunity to learn about and get involved with data collection and analysis.

Background reading

• Corbett, B.A., Mendoza, S., Abdullah, M., Wegelin, J.A., & Levine, S. (2006). Cortisol circadian rhythms and response to stress in children with autism. Psychoneuroendocrinology. 2006 Jan;31(1):59-68. Epub 2005 Jul 7.
• Amaral, D.G., & Corbett, B.A. (2003). The amygdala, autism and anxiety (pp. 177-197). In Symposium on Novartis Foundation Symposium, 251, Autism: Neural basis and treatment possibilities. 177-197.

Mentor:  Blythe A. Corbett, Ph.D.
Duration:  Short or long-term
Description:  Autism is a severe neurodevelopmental disorder characterized by qualitative impairment before the age of three in verbal and nonverbal communication, reciprocal social interaction, and a markedly restricted repertoire of activities and interests. In addition to these features, recent findings in our lab suggest that attentional abnormalities, impulsive responding and hyperactive behavior consistent with attention deficit hyperactivity disorder (ADHD) are present in many children with ASD. Trainees will get direct experience of patient interaction along with the opportunity to learn about and get involved with data collection and analysis using the methods of neuropsychology and neuroimaging.

Background reading

• Corbett, B.A., & Constantine, L. (2006) Autism and attention deficit hyperactivity disorder: Assessing attention and response control with the Integrated Visual and Auditory continuous performance test. Child Neuropsychology, 12, 1-14.
• Corbett, B., & Glidden, H. (2000). Processing affective stimuli in children with attention-deficit hyperactivity disorder. Child Neuropsychology, 6, (2), 144-155.

Mentor(s):  Robert Hendren, D.O.
Duration:  Short or long-term
Description:  Trainees can observe and assist with clinical assessments, administering rating scales, and doing physical exams. Trainees will gain experience and appreciate the special consents, assents, and ethical considerations in working with children and people with developmental disabilities. Highly motivated trainees can help write review papers on topics in child and adolescent psychiatry. Trainees may also have the opportunity to help manage interesting cases that can be written into a brief report for publication.

Mentor:  Karl D. Murray, Ph.D.
Duration:  Short-term
Description:  The most consistent observation in prefrontal cortex of postmortem schizophrenic brains is a decrease in the molecular phenotype associated with a specific class of inhibitory interneurons that express the calcium binding protein parvalbumin. Decreased expression of GAD67, the rate limiting enzyme for GABA production, GAT-1, a GABA transporter and parvalbumin suggest that inhibitory neurotransmission is compromised in schizophrenic cortex. How these changes affect cellular circuitry in cortex is unknown. This project will utilize a new technology, laser capture microscopy (LCM), to analyze the molecular changes that occur in defined neuronal populations in schizophrenic and non-diseased brain. The trainee will collaborate with lab members in developing analyses of neuronal classes by combining histology and LCM with microarray technology. By identifying molecular changes in a cell-specific manner it is hope that we will gain insight into the alterations in neural circuitry underlying the expression of schizophrenia.

Background reading

• Blatow, M., Caputi, A., & Monyer, H. (2005). Molecular diversity of neocortical GABAergic interneurones. J Physiol 562:99-105.
• Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005). Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6:312-324.
• Mirnics, K., Levitt, P., & Lewis, D. A. (2004). DNA microarray analysis of postmortem brain tissue. Int Rev Neurobiol 60:153-181.

Mentor:  Sally Ozonoff, Ph.D.
Duration:  Long-term
Description:  Autism begins in the first three years of life, with two distinct onset patterns evident. The early onset phenotype presents early in life, with parents reporting developmental abnormalities before the first birthday. The regression phenotype includes a period of typical or mostly typical development (18-24 months), followed by a loss of previously acquired skills and onset of symptoms of autism. The etiologies of these phenotypes, and whether they differ, are unknown. In multiplex families (those with more than one child with autism), it is unknown if both children demonstrate the same onset type or if this can differ within a family and similar genetic background. Trainees will conduct brief phone interviews with mothers of multiple children with autism regarding symptom onset. They will then analyze data and assist in publication write-up.

Background reading

• Lainhart, J.E., Ozonoff, S., Coon, H., Krasny, L., & McMahon, W. (2002). Autism, regression and genetics. American Journal of Medical Genetics, 113, 231-237.
• Werner, E., & Dawson, G. (2005). Validation of the phenomenon of autistic regression using home videotapes. Archives of General Psychiatry, 62, 889-895.

Mentor:  Tony J. Simon, Ph.D.
Duration:  Long-term
Description :  Chromosome 22q11.2 deletion syndrome (22q) is a very common yet ill-understood neurogenetic disorder that produces characteristic cognitive impairments and elevated risk for psychological/psychiatric disorders (including ADHD, OCD & Schizophrenia). Our lab carries our translational research using cognitive processing, neuroimaging and genetics tools as well as psychological, behavioral and psychiatric assessments. Trainees will get direct experience of patient interaction along with the opportunity to learn about and get involved with data collection and analysis using the methods of cognitive neuroscience as well as preparing results for publication.

Background reading

• Simon, T.J., Ding, L., Bish, J.P., McDonald-McGinn, D., Zackai, E.H., & Gee, J. (2005) Volumetric, connective and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: An integrative study. NeuroImage , 25: 169-180.
• Simon, T.J., Bish, J.P., Bearden, C.E., Ferrante, S., Ding, L., Nguyen, V., Gee, J., McDonald-McGinn, D., Zackai, E.H., & Emanuel, B. (2005) A multi-level analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children. Development and Psychopathology , 17, 753-784.

Mentor:  Peter Yellowlees, M.D.
Duration:  Long-term
Description :  To further develop, and validate, a novel machine learning computerized screening tool analyzing visual or auditory material for depression, anxiety and substance abuse, and potentially other medical conditions, which is ideally suited for use in primary care., especially in rural regions. Ex-Ray is a new application of machine learning technology developed by PY that uses samples of a few minutes of a patient's objective behavior, including recorded voice, transcribed language, and visual images, to screen for and monitor common mental health or other conditions. It can be operated by a medical assistant or layperson with minimal training, and can maintain the confidentiality of the results and the nature of the screening. It can be configured to screen for or monitor a wide range of disorders using a single session's sample, and can be used repeatedly with long or short inter-test intervals to monitor change in a chronic condition. It has been piloted on a small sample of clinically confirmed patients and has shown better than 85% accuracy for distinguishing patients from controls. Trainees will develop hypotheses about specific groups of patients, collect data using audio or video interviews, and analyse the data using the Ex-Ray data mining technology before writing up their results.

Background reading

• Diederich, J., & Yellowlees, P. (2002). Ex-ray: Text classification and the assessment of mental health. Proceedings of the Australasian Document Computing Symposium , Sydney, Australia.

Mentor:  Jong H. Yoon, M.D.
Duration:  Short-term
Description :  fMRI presents an unprecedented opportunity to examine the neural underpinnings of schizophrenia. However, a fundamental methodological issue in the application of fMRI analysis to the study of this illness remain unresolved-- the verification that no difference in the fMRI marker of neural activity, the blood oxygen dependent level (BOLD) signal, is unaltered in schizophrenia. The presence of a difference between subjects with schizophrenia and controls would have significant impact on how we should conduct fMRI analysis of any study comparing activations between groups. With this study, trainees will be exposed to general experimental methods, statistics, and fMRI analysis pertinent to conducting studies comparing neural function in healthy controls and subjects with schizophrenia. The trainee will then apply this knowledge to analyze fMRI data, which have already been gathered. The trainees will also assist in generating a manuscript for publication.

Mentor:  Jong H. Yoon, M.D.
Duration:  Short-term
Description :  This study is related to the above experiment in its examination of the BOLD signal in schizophrenia. This study's main aim is, however, on determining the effect of psychiatric medication on the BOLD signal. The trainee will analyze fMRI data that has already been generated, which are derived from patients with schizophrenia who have undergone fMRI scanning pre- and post-medication treatment. This unique data set provides a within subject design capable of evaluating whether psychiatric medications alter the BOLD response.