Maggie Chow (firstname.lastname@example.org)
Graduate Program: Neurosciences
Lab PI: Eric Courchesne
Undergraduate Institution: UC Berkeley
Med-into-Grad clinical training area: (Pediatric) Neurology and Genetics
Main clinical mentors:
Dr Doris Trauner (email@example.com)
Dr Marilyn Jones (firstname.lastname@example.org)
Quotes: “The most important insight I gained through my clinical training was that doctors and scientists both agree that the diagnostic criteria is the biggest problem for autism now. Unlike scientists, however, clinicians are in the position to determine the clusters of symptoms that occur and the physical phenotypes that predict those clusters. Further, it seems that the effect of neuroleptics and anticonvulsants that are prescribed to patients with seizures and neurodevelopmental abnormalities on neurodevelopment is not well investigated, despite the obvious necessity of these studies. Lastly, for some of the genetic disorders that I encountered, there seemed to be very obvious methods of therapy that no one had yet tried.”
Rational for Med-into-Grad training: Currently, I am in my second year of the doctoral program in Neurosciences here at UCSD in the laboratory of Eric Courchesne. My goal is to be able to bridge my interests in molecular neuroscience with cognitive neuroscience through an examination of the genetic etiology and cortical development of patients with Autistic Disorder. I am currently studying postmortem gene expression differences and their SNP variations in autistic samples using whole genome microarray analyses and in situ hybridization. In the near future, I hope to also investigate the genetic correlates of cortical folding using structural magnetic resonance imaging (MRI) and whole genome single nucleotide polymorphisms in blood DNA in live autistic subjects.
I have always been interested in clinical phenotypes of the neuropsychiatric disorders that I study. On a more scientific level, however, disorders such as autism and schizophrenia are important to observe because the clinical diagnosis criteria are ambiguous. I was certain that being able to observe patients would help me gain insight into the specific clusters of symptoms that occur within patients and physical or physiological characteristics that would help me determine them. The ability to distinguish between autism subsets, for example, is a foremost issue in the field to date, and any research of biological pathways of the disorder will be affected by diagnosis. Thus, I knew that Med into Grad training would be invaluable, and indeed it has been.
Medical training and identification of medically-relevant research issues: Neurology Clinic: Here I learned a great deal about the features of a variety of seizure disorders and neurodevelopmental disorders (including autism). I learned the scheme of history-taking and the general neurological exam, as well as the different developmental skills that are regularly tested in pediatrics to ensure that children are growing normally cognitively.
Genetics Clinic: I learned about many of the malformations that can occur in people, and it was striking how attuned even the scientist’s eye is to any sort of abnormality. I learned the physical review of the 10 systems and many of the services and support groups that doctors must be familiar with to be able to serve their patients well.
Fellows seminars and Neurology Grand Rounds: Here I learned about aspects of research specifically directed at clinical populations and surveys done on diagnoses. The most important insight I gained through my clinical training was that doctors and scientists both agree that the diagnostic criteria is the biggest problem for autism now. Unlike scientists, however, clinicians are in the position to determine the clusters of symptoms that occur and the physical phenotypes that predict those clusters. Further, it seems that the effect of neuroleptics and anticonvulsants that are prescribed to patients with seizures and neurodevelopmental abnormalities on neurodevelopment is not well investigated, despite the obvious necessity of these studies. Lastly, for some of the genetic disorders that I encountered, there seemed to be very obvious methods of therapy that no one had yet tried upon literature searches. Thus, I concluded that much of medicine is still unknown and leaves room for scientists to investigate.
In the field of autism, genetic, and neuropsychiatric disorders, there are many open questions on the mechanisms of the disease or disorder, diagnostic tests, and therapeutics. Particularly in symptomologically-defined disorders like autism, since the diagnostic criteria were not created based on underlying etiology or molecular mechanisms, many scientific investigations lack the power or specificity to isolate mechanisms that may govern the process of a subset of patients. Furthermore, the effect of medications and therapies on neurodevelopmental and genetic disorders are not well documented since these studies are very difficult to do and involve many ethical issues.
Thus, my mentor and I discussed several possible investigations that may be performed with patients in conjunction with my PI’s lab. Firstly, we could hypothesize that certain physical characteristics vary with clusters of autistic symptoms and test whether or not these clusters actually exist. Secondly, we could investigate the effect of medications often given to child patients on the development of the brain and the pharmacogenetics of the therapeutic response.
This is an excerpt from the proposal I wrote with my mentor’s approval: “We are proposing to investigate the genetic variants of children with autism that respond behaviorally and cognitively to risperidone, and the neurodevelopmental effects of this treatment. We also ask whether changes in the volume of certain brain regions and fiber tracts correlate with improvement or decrement in behavior and cognition, and whether SNP variants can predict the neurodevelopmental response to risperidone. We propose to assess genetic variants using whole genome array single nucleotide polymorphisms (SNPs). We hypothesize that the integrity of the frontal-striatal white matter pathways in autistic children and the volume of the frontal lobe after treatment will be different from those with placebo, without treatment, and controls. Finally, we predict that these changes in brain structure due to risperidone will correlate with improvement in behavioral and cognitive symptoms, and that some SNP variants or combinations of variants may predict these changes in structure.” This proposed study would be an imaging, genetic, and behavioral study in child autistics in the pediatric neurology clinic with my PI’s lab.
Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs: I do feel as though I received a thorough understanding of diagnostic and therapeutic tests often used in pediatric neurology and genetics. For each of these clinics there are standard arrays of tests that the doctors use to figure out what disorder or disease the patient’s symptoms are most consistent with, but often these tests are not decisive, and doctors sometimes choose not to do them in case the ambiguous results return to cause the patient’s family anxiety.
As stated before in autism, the diagnostic criteria were not created based on underlying etiology or molecular mechanisms, many scientific investigations lack the power or specificity to isolate mechanisms that may govern the process of a subset of patients. As a result, therapeutics are nonspecific and thus may present many unnecessary side effects.
Diagnostic & Therapeutic collaborations: Diagnostic tests for autism would require large multisite studies that are currently being performed around the world due to the increasing prevalence of the disorder. My clinical mentor and I would not be able to perform these studies by ourselves, since the power required for significance and the elucidation of subsets is great. However, a priori hypotheses of the defining phenotypes of these subsets may help increase power. Once these studies are completed, the development of diagnostics will be more efficient and fruitful. Thus, therapeutics currently are dependent on the ability of scientists to discover ways of subtyping patients. Currently, I do not have any plans to collaborate with physicians in their development apart from the possible study that my clinical mentor and I proposed.
Long term impact: Before this experience, I had heard of in theory but not observed firsthand the heterogeneity of autism. It was invaluable to be able to experience these patients because I will now be more able to form hypotheses on the mechanisms of the disorder, and I will be better able to judge whether studies and ideas from others are viable. In the long term, this experience has made me a stronger clinical observer and more knowledgeable on the medical process and needs of the field. Since I am a neuroscience grad, it is not surprising that I perseverate on all things brain-related. However, neuropsychiatric disorders like autism have many more manifestations than just neurologically-related, and without this experience I would not have learned of them to get a more complete picture of the disorder.
Student-specific experiences: My time in the genetics and dysmorphology clinic has made a deep impression on me despite not being well associated with my field of research. There are terrible medical abnormalities that can arise from mutations in the genome that are sometimes immediately fatal or cause serious challenges to a patient throughout life. Unfortunately, many of these genetic disorders cannot be treated, but I certainly have found some that need to be studied because clear molecular pathways have been implicated and thus lend themselves to scientific investigation. It is encouraging and motivating to meet these patients and their hopeful parents since they would be the ones that would benefit from scientific study of these disorders.
Advice for new trainees--Autumn preparatory quarter: The coursework and readings were lined up well to set up the basis for our clinical rotations, and I recommend enjoying learning this material and observing the variety of patients that will come through the “science meets the patient” course. Outside of the coursework, I recommend the brain cutting seminar (especially for non-neuroscience disciplines) and neurology grand rounds. What you get out of this program will really depend on your motivation and what you want to put in.
Advice for new trainees—Winter clinical training quarter: Bring a flexible and open mind, because day to day medicine is so much different than day to day science. I personally did not experience any ‘jump’ from autumn to winter quarters but to be fair I have spent a considerable amount of time in neurology clinics for other programs I have participated in, in the past. I hear that this is a big issue with other students and my advice would be just to enjoy the observations and learning whether it is a slow day when patients fail to show up or it is a hectic day with multiple challenging patients. Always dress and act professionally, adhere to HIPAA rules, and respect everyone that you meet in the clinic. Doctors enjoy questions so be as proactive as possible in asking them, and it helps to read about the disorders that you see afterward to show you how the doctors came to the diagnosis that they did.
Take home perspective on Med-into-Grad at UCSD: I would highly recommend the Med into Grad program for all students who have interest in pursuing clinically-related research. This program is motivating and the experience is invaluable because the opportunity to just take time away from research and just observe the other side is rare. This experience will undoubtedly help me in my future research and allow me to write stronger grants because I have a more gestalt view of the disorder that I am studying. It has been an outstanding experience working with Drs Trauner and Jones, and I would highly recommend working with them if their clinic matches the student’s interests.