Adriana Foster

Prevention of oxidative stress-mediated neuropathology and improved clinical outcome by adjunctive use of a combination of antioxidants and omega-3 fatty acids in schizophrenia

Summary Schizophrenia is associated with a broad range of neurodevelopmental, structural and behavioral abnormalities that often progress with or without treatment. Evidence indicates that such neurodevelopmental abnormalities may result from defective genes and/or non-genetic factors such as pre-natal and neonatal infections, birth complications, famines, maternal malnutrition, drug and alcohol abuse, season of birth, sex, birth order and life style. Experimentally, these factors have been found to cause the cellular metabolic stress that often results in oxidative stress, such as increased cellular levels of reactive oxygen species (ROS) over the antioxidant capacity. This can trigger the oxidative cell damage (i.e., DNA breaks, protein inactivation, altered gene expression, loss of membrane lipid-bound essential polyunsaturated fatty acids [EPUFAs] and often apoptosis) contributing to abnormal neural growth and differentiation. The brain is preferentially susceptible to oxidative damage since it is under very high oxygen tension and highly enriched in ROS susceptible proteins, lipids and poor DNA repair. Evidence is increasing for increased oxidative stress and cell damage in schizophrenia. Furthermore, treatments with some anti-psychotics together with the lifestyle and dietary patterns, that are pro-oxidant, can exacerbate the oxidative cell damage and trigger progression of neuropathology. Therefore, adjunctive use of dietary antioxidants and EPUFAs, which are known to regulate the growth factors and neuroplasticity, can effectively improve the clinical outcome. The dietary supplementation of either antioxidants or EPUFAs, particularly omega-3 has already been found to improve some psychopathologies. However, a combination of antioxidants and omega-3 EPUFAs, particularly in the early stages of illness, when brain has high degree of neuroplasticity, potentially may be even more effective for long-term improved clinical outcome of schizophrenia.

Complicated Pain Management in a CYP450 2D6 Poor Metabolizer

▪ Abstract:  We describe the case of a patient with significant adverse effects from posttraumatic analgesic therapy with opioid analgesics who was found by microarray analysis to have a CYP2D6 genotype predictive of a poor metabolizer phenotype. In addition to her poor tolerance and limited response to opioid analgesics, she developed further discomfort when the antiemetic promethazine was administered to treat her gastrointestinal adverse effects. In our discussion we review the literature about the clinical impact of CYP450 2D6 polymorphisms in treatment with the commonly used opioid analgesics codeine, oxycodone, hydrocodone, hydromorphone, and morphine, as well as the antiemetic promethazine. The case we present, as well as the literature we review, demonstrates the clinical utility of CYP2D6 genotyping in patients with adverse effects from analgesia therapy. ▪

Homelessness in schizophrenia.

The impact of mental illness, comorbid substance abuse, and medication nonadherence, coupled with disjointed psychiatric and social services, conspires to a disproportionately high rate of psychiatric disorders among people who are homeless in the United States. This article reviews the prevalence of homeless among the mentally ill as well as the prevalence of mental illness among the homeless and details barriers in access to care and the solutions that have been attempted. The need and solutions to introduce a new generation of physicians and allied health care workers to the unique health care needs of the homeless population are highlighted.

Pharmacogenetics and Schizophrenia

Emergent pharmacogenetic studies indicate that the efficacy of antipsychotic medications in schizophrenia may be predicted through genetic analysis. There also is evidence that the side-effect profiles of second-generation antipsychotic medications and their propensity to cause weight gain, glucose and lipid abnormalities, and tardive dyskinesia may be predicted by pharmacogenetic analysis in this patient population. In the future, this targeted approach with the choice of antipsychotic medication based on the likelihood of clinical response and development of side effects in light of a particular patients genetic status may gain hold as new treatments are developed with even fewer side effects.

Interactive Virtual-Patient Scenarios: An Evolving Tool in Psychiatric Education

Standardized patients (SPs) are routinely used to teach medical students communication and physical diagnosis skills (1–5). Standardization and decreased risk of possible harm being committed by training students (6) are only a few of the advantages provided by SPs. SPs can provide a detailed history, can answer directly to the students, and give feedback for improvement (1, 6, 7). However, SP interactions are limited by the availability of the actors, time constraints, and costs (8). An alternative to SPs is use of computer simulation. Virtual-patient (VP) systems are computer programs that simulate real-life clinical scenarios in which the learner can complete a patient interview and physical exam, while making diagnostic and therapeutic decisions (9). VP systems allow standardized instruction, immediate and objective performance feedback, and unlimited opportunity for repetitive practice (10). VPs and computer simulations are already used in various branches of medicine to teach communication, counseling, crisis management, procedures, leadership, teamwork, and medical decision-making skills (11). Virtual reality is already used as exposure therapy to treat panic disorders, posttraumatic stress disorder, (12) social phobias, and specific phobias (13, 14). In 1966, ELIZA (15) became the first virtual psychiatric tool by engaging the user in a text-based psychotherapy session. It was never used as an actual treatment protocol, but it did set the stage for using computer simulation as a tool in diagnosing and treating mental illnesses (13). However, even with the foundation laid, there are only a few published applications of a psychiatric VP scenario used as a training modality in medical student education (8, 16). We present the preliminary evaluation of a web-based VP scenario that assesses students’ ability to elicit symptoms of major depression. The study was performed using the online application called Virtual People Factory (VPF; http://www. virtualpeoplefactory.com), (17) developed by the University of Florida’s Virtual Experiences Research Group. Currently, many VP systems entail the learners’ going through an evolving scenario where they sequentially answer multiple-choice questions about history, diagnosis, and management of patients. VPF is a web-based, instantmessaging application that elicits a VP’s medical history, based on the questions a user asks, therefore allowing students to make their own assessments of the most appropriate next step in the interview, rather than passively choosing from a list of possible answers. The process of creating a VPF interaction entails the following steps: Initially, an editor creates a script of the medical scenario, including what can be potentially said to the VP (questions/statements) and what the VP will respond back (speeches). Next, the scenario is sent out to users. Users log in to the system, are presented with a brief introduction of the patient similar to the introduction given to students before they enter the room to interview an SP, and then ushered into the chat interface. Once inside the interface, the user can engage the patient in conversation to obtain a full medical history. Every user’s input will yield a speech response. If there is not a speech response affiliated with a question or if the speech response is incorrect for a given question, the event is logged for the editor, to either create a new speech response or connect it correctly with the right question. Numerous user interactions will therefore allow for a robust database of the various questions and speech responses to be built for any medical scenario. Received June 17, 2010; revised November 22, 2010; accepted January 29, 2011. From Georgia Health Sciences University (HS, DL, SDL, AF), University of Florida (BR, BL), and Drexel University College of Medicine (SDL). Send correspondence to Dr. Foster; afoster@ georgiahealth.edu (e-mail). Copyright

Pharmacogenetics and schizophrenia.

The wide interindividual variability in clinical response and tolerability of antipsychotic medications has led investigators to postulate that these variabilities may be under genetic control. Although not always consistent, there are promising indications from emergent pharmacogenetic studies that efficacy of antipsychotic medications for the various symptom domains of psychopathology in schizophrenia may be genetically regulated. This is an encouraging approach. Moreover, there are also suggestive findings that the side-effect profiles of second-generation antipsychotic medications and their propensity to cause weight gain and glucose and lipid abnormalities as well as tardive dyskinesia may be related to pharmacogenetic factors in this patient population. Ultimately, such approaches could drive choices of antipsychotic medication based on the likelihood of clinical response and development of side effects in light of a particular patients genetic profile. In the future, this targeted approach (personalized medicine) may become informative for clinicians choosing an antipsychotic medication for an individual patient with schizophrenia.

The Use of Simulation to Teach Suicide Risk Assessment to Health Profession Trainees—Rationale, Methodology, and a Proof of Concept Demonstration with a Virtual Patient

ObjectiveThere is increasing use of educational technologies in medical and surgical specialties. Described herein is the development and application of an interactive virtual patient (VP) to teach suicide risk assessment to health profession trainees. We studied the effect of the following: (1) an interaction with a bipolar VP who attempts suicide or (2) completion of a video-teaching module on interviewing a bipolar patient, on medical students’ proficiency in assessing suicide risk in standardized patients. We hypothesized that students who interact with a bipolar VP will be at least as likely to assess suicide risk, as their peers who completed a video module.MethodsIn a randomized, controlled study, we compared the frequency with which second-year students at the Medical College of Georgia asked suicide risk and bipolar symptoms questions by VP/video group.ResultsWe recruited 67 students. The VP group inquired more frequently than the video group in 4 of 5 suicide risk areas and 11 of 14 other bipolar symptomatology areas. There were minimal to small effect sizes in favor of the VP technology. The students preferred the video over the VP as an educational tool (p = 0.007).ConclusionsOur study provides proof of concept that both VP and video module approaches are feasible for teaching students to assess suicide risk, and we present evidence about the role of active learning to improve communication skills. Depending on the learning context, interviewing a VP or observation of a videotaped interview can enhance the students’ suicide risk assessment proficiency in an interview with a standardized patient. An interactive VP is a plausible modality to deliver basic concepts of suicide risk assessment to medical students, can facilitate individual preferences by providing easy access and portability, and has potential generalizability to other aspects of psychiatric training.

Pharmacogenetics of antipsychotic adverse effects: Case studies and a literature review for clinicians

There is a growing body of literature supporting the contribution of genetic variability to the mechanisms responsible for the adverse effects of antipsychotic medications particularly movement disorders and weight gain. Despite the current gap between research studies and the practical tools available to the clinician to identify such risks, it is hoped that in the foreseeable future, pharmacogenetics will become a critical aid to guide the development of personalized therapeutic regimes with fewer adverse effects. We provide a summary of two cases that are examples of using cytochrome P450 pharmacogenetics in an attempt to guide treatment in the context of recent literature concerning the role of pharmacogenetics in the manifestation of adverse effects of antipsychotic therapies. These examples and the review of recent literature on pharmacogenetics of antipsychotic adverse effects illustrate the potential for applying the principles of predictive, preventive, and personalized medicine to the therapy of psychotic disorders.

Using Virtual Patients to Teach Empathy: A Randomized Controlled Study to Enhance Medical Students' Empathic Communication.

Introduction Physician empathy is a complex phenomenon known to improve illness outcomes; however, few tools are available for deliberate practice of empathy. We used a virtual patient (VP) to teach empathic communication to first-year medical students. We then evaluated students’ verbal empathy in a standardized patient (SP) interaction. Methods Seventy medical students, randomly assigned to 3 separate study groups, interacted with (1) a control VP portraying depression, (2) a VP with a backstory simulating patient shadowing, or (3) a VP able to give immediate feedback about empathic communication (empathy-feedback VP). Subsequently, the students interviewed an SP portraying a scenario that included opportunities to express empathy. All SP interviews were recorded and transcribed. The study outcomes were (1) the students’ verbal response to the empathic opportunities presented by the SP, as coded by reliable assessors using the Empathic Communication Coding System, and (2) the students’ responses as coded by the SPs, using a communication checklist. Results There were no significant differences in student demographics between groups. The students who interacted with the empathy-feedback VP showed higher empathy in the SP interview than did the students in the backstory VP and the control VP groups [mean (SD) empathy scores coded on a 0–6 scale were 2.91 (0.16) vs. 2.20 (0.22) and 2.27 (0.21), respectively). The difference in scores was significant only for the empathy-feedback VP versus the backstory VP group (P = 0.027). The SPs rated the empathy-feedback and the backstory VP groups significantly higher than the control VP group on offering empathic statements (P < 0.0001), appearing warm and caring (P = 0.015), and forming rapport (P = 0.004). Conclusions Feedback on empathy in a VP interaction increased students’ empathy in encounters with SPs, as rated by trained assessors, whereas a simulation of patient shadowing did not. Both VP interventions increased students’ empathy as rated by SPs, compared with the control VP group.

Building Virtual Humans with Back Stories: Training Interpersonal Communication Skills in Medical Students

We conducted a study which investigated if we could overcome challenges associated with interpersonal communication skills training by building a virtual human with back story. Eighteen students interacted with a virtual human who provided back story, and seventeen students interacted with the same virtual human who did not provide back story. Back story was achieved through the use of cutscenes which played throughout the virtual human interaction. Cutscenes were created with The Sims 3 and depicted short moments that occurred in the virtual human’s life. We found medical students who interacted with a virtual human with a back story, when interacting with a standardized patient, were perceived by the standardized patient as more empathetic compared to the students who interacted with the virtual human without a back story. The results have practical implications for building virtual human experiences to train interpersonal skills. Providing back story appears to be an effective method to overcome challenges associated with training interpersonal skills with virtual humans.