Psychiatry
Research Training Opportunities in the
Department of Psychiatry & Behavioral Sciences
letter to interested students ... April 27, 2006
Sleep disorders in children with autism

Mentors: Thomas F. Anders (tfanders@ucdavis.edu), M.D.,
Beth Goodlin-Jones (blgoodlin@ucdavis.edu), Ph.D.

Duration: Short or long-term

Description: Children with autism are reported to have more sleep problems than children with other developmental disabilities and children who are typically developing. However, the kind of sleep problems, their severity and their duration are largely unstudied. Using actigraphy and videosomnography, this study is examining sleep-wake state organization and sleep disorders in 180 children (60 children with autism, 60 children with developmental delay without autism and 60 typically developing children). We are also studying daytime attention, activity and memory to see whether sleep loss is associated with daytime functioning. The trainee would be involved in all aspects of the project from data collection to data analysis and publishing results. Working effectively with parents and children is a necessary prerequisite.

Background reading:
  • Honomichl, R.D., Goodlin-Jones, B.L., Burnham, M., Gaylor, E., & Anders, T.F. (2002). Sleep patterns of children with pervasive developmental disorders. Journal of Autism and Developmental Disorders, 32, 553-561.
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    Functions of RGS proteins at synapses

    Mentor: Marie Burns (meburns@ucdavis.edu), Ph.D.

    Duration: Long term

    Description: G protein cascades are a common mechanism used by all cells to transduce extracellular stimuli into cellular responses. Families of proteins that regulate G protein activity (Regulators of G protein Signaling, or RGS), are expressed throughout the nervous system in a cell-specific fashion, suggesting that RGSs may serve as a synapse-specific control point for modulating neurotransmission. RGS proteins can be upregulated or downregulated following long-term changes in synaptic strength, long-term dopamine depletion, and in psychiatric illnesses like schizophrenia. Perhaps not surprisingly, drugs of addiction, including morphine and cocaine, also alter RGS expression levels. This project will examine how changing RGS activity or expression ultimately alters neuronal function. Trainees will learn how to dissect brain tissue, maintain primary neuronal cultures, perform imaging or single cell electrophysiology experiments, analyze data and assist in writing up the results. Previous wet lab experience is required.

    Background reading:
  • Neubig RR, Siderovski DP (2002) Regulators of G protein signaling as new central nervous system drug targets. Nat Rev Drug Discov 1:187-197.
  • Burns ME, Wensel TG (2003) From molecules to behavior: new clues for RGS function in the striatum. Neuron 38:853-856
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    Feasibility of imaging methods for testing new drug targets in primary neuronal cultures
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    Mentor: Marie Burns (meburns@ucdavis.edu), Ph.D.

    Duration: Short term

    Description: Selective serotonin reuptake inhibitors (SSRIs) initiate long-term changes in gene expression by first increasing the levels of serotonin in the synaptic cleft. However, the non-specific nature of this effect results in many common undesirable side effects, including weight gain and sexual dysfunction. Targeting intracellular signaling processing that occurs downstream of serotonin receptors, like RGS proteins, is highly desirable for developing more specific psychotropic drugs. This project will determine the feasibilitiy of the latest intracellular imaging techniques for manipulating signal transduction mechanisms at serotonergic synapses. Trainees will perform literature searches and work with senior lab members to develop novel drug targets and experimental approaches.

    Background reading:
  • Neubig, R. R., Siderovski, D. P. (2002). Regulators of G protein signaling as new central nervous system drug targets. Nat Rev Drug Discov 1:187-197.
  • Willard, F. S., Kimple, R. J., Kimple, A. J., Johnston, C. A. &, Siderovski, D. P. (2004). Fluorescence-based assays for RGS box function. Methods Enzymol 389:56-71.
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    The role of stress in children with autism spectrum disorders

    Mentor: Blythe A. Corbett (blythe.corbett@ucdmc.ucdavis.edu), 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.
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    Autism spectrum disorders and attention-deficit hyperactivity disorder

    Mentor: Blythe A. Corbett (blythe.corbett@ucdmc.ucdavis.edu), 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. (in press) Autism and attention deficit hyperactivity disorder: Assessing attention and response control with the Integrated Visual and Auditory continuous performance test. Child Neuropsychology.
  • Corbett, B., & Glidden, H. (2000). Processing affective stimuli in children with attention-deficit hyperactivity disorder. Child Neuropsychology, 6, (2), 144-155.
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    MR imaging of children with autism, bipolar disorder, schizophrenia, fragile X, psychosis, and affective instability.

    Mentors: Robert Hendren (robert.hendren@ucdmc.ucdavis.edu ), D.O.;
    Sufen Chiub (sufen.chiu@ucdmc.ucdavis.edu), M.D., Ph.D.

    Duration: Short or long- term

    Description: Depending on interest and time, trainees can observe and assist with clinical assessments, administer rating scales, learn to acquire MR structural and spectroscopy images, and analyze imaging data. 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.

    Background reading:

  • Brooks, W.M.J., Hodde-Vargas, J., Vargas, L.A., Yeo, R.A., Ford, C.C., & Hendren, R.L. Frontal lobe of children with schizophrenia spectrum disorders: A proton magnetic resonance spectroscopic study. Biological Psychiatry, 43, 663-269.
  • Grecius, M.D. (2003). Neuroimaging in developmental disorders. Current Opinions in Neurology, 16, 143-146.
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    Clinical drug trials for autism, post-traumatic stress disorder, major depressive disorder, schizophrenia, and bipolar disorder.

    Mentors: Robert Hendren (robert.hendren@ucdmc.ucdavis.edu), D.O.,
    Sufen Chiu (sufen.chiu@ucdmc.ucdavis.edu), M.D., Ph.D.

    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.
    Cell-type specific transcriptional mapping in schizophrenic and non-diseased brain.

    Mentor: Karl D. Murray (kdmurray@ucdavis.edu), 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.
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    Concordance of onset types in siblings with autism spectrum disorders

    Mentor: Sally Ozonoff (sjozonoff@ucdavis.edu), 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.
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    Parent concerns about development in the first year of life in younger siblings of children with autism.

     Mentor: Sally Ozonoff (sjozonoff@ucdavis.edu), Ph.D.

    Duration: Short term

    Description: Autism runs in families and genetic factors are strongly implicated in etiology. The recurrence risk after one child with autism is currently estimated to be 5 - 15%. In an ongoing study of recurrence risk, open-ended questions about parent concerns are collected at every visit (6, 12, 18, 24, and 36 months of age). This project examines these concerns and their validity in predicting developmental outcome. Trainees will develop a coding system to categorize the concerns raised by parents, analyze data, and assist in publication write-up.

    Background reading:
  • Wetherby, A. M., Woods, J., Allen, L., Cleary, J., Dickinson, H., & Lord, C. (2004). Early indicators of autism spectrum disorders in the second year of life. Journal of Autism and Developmental Disorders, 34, 473-493.
  • Zwaigenbaum, L., et al. (2005). Behavioral manifestations of autism in the first year of life. International Journal of Developmental Neuroscience, 23, 143-152.
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    Developmental milestone achievement in the first year of life in younger siblings of children with autism.

     Mentor: Sally Ozonoff (sjozonoff@ucdavis.edu), Ph.D.

    Duration: Short term

    Description: Younger siblings of children with autism are at heightened risk not only for autism, but also for other developmental delays. As part of an ongoing study of infant siblings, parents fill out calendars about developmental achievements on a regular basis. Age at achievement of several salient milestones will be examined and analyzed compared to infant siblings of children with typical development. Trainees will participate in data coding, analysis, and publication.

    Background reading:
  • Bailey, A., Palferman, S., Heavey, L., & LeCouteur, A. (1998). Autism: The phenotype in relatives. Journal of Autism and Developmental Disorders, 28, 369-392.
  • Zwaigenbaum, L., et al. (2005). Behavioral manifestations of autism in the first year of life. International Journal of Developmental Neuroscience, 23, 143-152.
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    Case report of a boy with Childhood Disintegrative Disorder using family home movies.

     Mentor: Sally Ozonoff (sjozonoff@ucdavis.edu), Ph.D.

    Duration: Short term

    Description: Childhood Disintegrative Disorder (CDD) is a very rare subtype of autism spectrum disorder in which onset is very late. After at least 2 and often 3-plus years of typical development, there is a severe regression that is more pervasive and catastrophic than seen in typical autism. Trainees will analyze videotape of a boy recorded by his parents since birth, who exhibits clear evidence of this late regression and drastic change in developmental skills on video. Using videotape already coded by a team blind to diagnostic status, this project will objectively document the rate of loss and deceleration of development in this child with CDD. Trainees will participate in analysis and writing for publication.

    Background reading:

  • Fombonne, E. (2002). Prevalence of childhood disintegrative disorder. Autism, 6, 149-157.
  • Volkmar, F. R., & Rutter, M. (1995). Childhood disintegrative disorder: results of the DSM-IV autism field trial. Journal of the American Academy of Child and Adolescent Psychiatry, 34, 1092-1095.
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    Neurocognitive foundations of intellectual impairments and psychiatric disorders in children with chromosome 22q11.2 deletion syndrome.

    Mentor: Tony J. Simon (tjsimon@ucdavis.edu), 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.
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    Developing screening and diagnostic tools using novel data mining techniques

    Mentor: Peter Yellowlees (peter.yellowlees@ucdmc.ucdavis.edu), 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.
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    Assessment of the BOLD signal in schizophrenia in three cortical regions

     Mentor: Jong H. Yoon (jhyyoon@ucdavis.edu), 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.
    The effect of neuroleptic medication on the BOLD signal and type II error in detecting activations using the general linear model

    Mentor: Jong H. Yoon (jhyyoon@ucdavis.edu), 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.