Tuesday, January 28, 2014

Autism Spectrum Disorders: Tales from the Mouse

On Friday, January 24, I attended "Autism Spectrum Disorders: Tales from the Mouse," Dr. “Manny” DiCicco-Bloom’s keynote presentation to the Neuroscience, Behavior and Health Research Forum offered by the Vermont Chapter of the Society for Neuroscience. As a clinician I hoped to learn more about Autism Spectrum Disorders (ASD), as a researcher-in-training I wanted to hear about mouse models, and as a translational science student I wanted to get ideas for presenting research on a clinical condition to a mixed audience.

You will find some detailed notes on content below, but here is my take-away list:

  1. “Everybody who has autism has a different type of autism” so there’s no hope of finding a single common cause or single effective treatment. Researchers have to make each kind of model and look for the pathways that can be fixed. [This is directly analogous to my work in Auditory Processing Dysfunction.]
  2. Mouse models allow researchers to identify specific molecular pathway abnormalities that may underlie specific disease symptoms, determine whether altering pathway activities can overcome specific abnormalities, and develop new therapies for human conditions.
  3. There is increasing support for an integrated neurobiological approach to studying complex conditions like autism. NIMH launched Research Domain Criteria project (RDoC) to define basic dimensions of functioning that can be studied across domains (genes, neural circuits, behaviors).
  4. TimRoberts at CHOP is doing mouse research on auditory pathways in autism!
  5. Interactions among researchers, clinicians, government funding agencies, private funding organizations, families, and patients are important, interesting, and complex.

Here are some content notes:

Nationwide prevalence of Autism Spectrum Disorders (ASD) is approximately 1:88 nationwide, similar to mental retardation and cerebral palsy. After acknowledging the challenge of talking about ASD as the DSM-(diagnostic and statistical manual) 4R gives way to new criteria in the DSM-5, Dr. DiCicco-Bloom shared clinical features of autism (social interactions, communications, restricted repetitive behaviors and interests), different historical labels on the spectrum (Autism, Aspergers, pervasive developmental disorder not otherwise specified), and associated conditions (mental retardation, seizures, problem behaviors, anxiety/mood disorders). Children who later develop autism may have detectable developmental differences in motor skills at 6-12 months and eye gaze as early as two months. It’s not always clear who is best to see and treat these patients.

The challenge for basic scientists presented by Dr. DiCicco-Bloom is that the clinical construct of Autism is based on a menu behavior descriptions that don't directly map to specific underlying causes that likely vary among children. How does one go about making a model of a construct that does not have a single definition? “So researchers talk about the nervous system, or the gut, or whatever” they can model. As such, basic scientists are never working on a “mouse model of Autism,” but rather they’re working on a feature of Autism that they can model.

After a brief reorientation to brain anatomy and physiology, Dr. DiCicco-Bloom talked about some developmental brain abnormalities that are seen in children with in autism although they are not absolute features and cannot be used for diagnosis. He outlined different ways genes can be associated with risk (single genes, common variants, copy-number variants) in a way that was exceptionally clear and helpful for me. He shared examples of environmental factors increasing the brain’s vulnerability to damage including peripheral immune system activation (e.g., Sydenham’s chorea, maternal Lupus, schizophrenia) and environmental toxins (e.g., lead, mercury). He mentioned fMRI research that was done partly for the "translational" component of having a familiar clinical measure to discuss with clinicians. Finally, he shared the example of Fragile X syndrome (FXS, the most common inherited form of autism and caused by the silencing of a single gene) as a success story in which a mouse model enabled the discovery of a pharmacological treatment effective to repair neurological and behavioral symptoms in human adults with dendritic spine defect.

Friday, January 10, 2014

Kessler to speak in Oregon

Rodger Kessler, PhD, Assistant Professor of Family Medicine, will give Grand Rounds at Oregon Health and Science University in Portland on February 12, 2014.  Congratulations!

Tuesday, January 7, 2014

Clinical Research Oriented Workshop (CROW) Meeting: December 19, 2013

Present:  Marianne Burke, Kat Cheung, Abby Crocker, Kairn Kelley, Amanda Kennedy, Rodger Kessler, Ben Littenberg, Connie van Eeghen

Start Up: The financing intricacies of academics – used to be a maze; now getting easier to trace. 

1.                  Discussion: CROW’s schedule for Spring Semester is set for every Thursday.  We’ll gather at 11:30, topic discussion from 11:45 – 12:45. Starting: Jan 9

2.                  Discussion:  Ben’s planned grant application to identify depression “valences” in the twitter-sphere
a.       Ben summarized the definition of social modeling (the focus of the grant) in terms of mood of twitter correspondents.  Research questions include whether tweets can be given a “depression” valence, whether valence can be affected by response tweets within a social network, and whether valence can be affected by deliberately placed tweets.  Interventions were discussed, along with ethical issues and feasibility, e.g. post-partum mothers who may be experiencing onset of depression.  Further research questions could include tweets from hospital patients, and the ability to assist them on discharge.

3.                  Next Workshop Meeting(s): NEW MEETING TIME on Thursdays, 11:30 a.m. – 12:45 p.m., at Given Courtyard South Level 4.   Remember: the first 15 minutes are for checking in with each other.
a.       January 9: TBA

Recorder: Connie van Eeghen

Job opportunity for Research Specialist - data analysis, programming and modeling

The UVM Transportation Research Center (TRC) has an opening for a Research Specialist with credentials and experience in data analysis, programming and modeling. The Research Specialist position accomplishes this on research project teams that design data collection including travel surveys, tabulate data including through use of programming languages, conduct statistical analysis of data including modeling and run simulations.  The position contributes to the writing of reports, proposals and journal papers including graphical communication of tables, figures, maps and equations.  Generation of new knowledge and dissemination are key outcomes of the TRC’s research work.   TRC’s research spans traditional disciplines and incorporates both qualitative and quantitative analysis.  

More info at http://www.uvm.edu/~transctr/?Page=facstaff%2Fresearch_position_1_7_2013.html