Lessons From an MD PhD - From SLC13A5 to Neurology.

The journey towards becoming a physician scientist is a long, arduous, and uncertain journey. Few medical students pursue a career as a physician scientist. Even those that do, the path towards maintaining a robust research career and clinical training can be difficult given the personal and social pressures to focus solely on research or clinical work. Despite the long history of science and medicine, there is question concerning the role that physician scientist in modern medicine. As a recent physician scientist graduate, physician scientists are greatly needed in the medical profession. The ability to overlap science, medicine, and the humanities together is an essential part of the producing a well-rounded and effective physician for a rapidly changing profession and world. Through my journey as a physician scientist in training, the lessons I've learned through my training in both the basic science and clinical portions can be helpful for medical students traversing both sides of the divide.

Metformin, valproic acid, and starvation induce seizures in a patient with partial SLC13A5 deficiency: a case of pharmaco-synergistic heterozygosity.

SLC13A5/NaCT is a sodium-coupled citrate transporter expressed in the plasma membrane of the liver, testis, and brain. In these tissues, SLC13A5 has important functions in the synthesis of fatty acids, cholesterol, and neurotransmitters. In recent years, patients homozygous for recessive mutations in SLC13A5, known as SLC13A5 deficiency [early infantile epileptic encephalopathy-25 (EIEE-25)], exhibit severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting tooth development. Although the pathogenesis of SLC13A5 deficiency remains not clearly understood, cytoplasmic citrate deficits, decreased energy status in neurons, and citrate-zinc chelation are hypothesized to explain the neurological deficits. However, no study has examined the possibility of specific pharmacological drugs and/or lifestyle changes synergizing with heterozygosity of SLC13A5 deficiency to increase the risk of EIEE-25 clinical phenotype. Here, we report on a heterozygous SLC13A5-deficient patient who demonstrated evidence of pharmaco-synergistic heterozygosity upon administration of metformin, valproic acid, and starvation. The report illustrates the importance of careful consideration of the potential adverse effects of specific pharmacological treatments in patients with heterozygosity for disease-causing recessive mutations in SLC13A5.

Buprenorphine use for pain and suicidal ideation in severely suicidal patients.

OBJECTIVE: Chronic pain is frequently comorbid with opioid abuse and severe depression, a combination that greatly compounds suicide risk. In addition to the therapeutic value of buprenorphine in addiction and analgesia, growing evidence suggests potential use as an antidepressant. Data supporting buprenorphine antisuicidal properties are scarce. We aim to contribute to the discussion of buprenorphine antisuicidal potential in patients with significant psychiatric and medical comorbidity. METHODS: We performed a chart review of suicidal adult depressed patients with comorbid chronic pain and opioid use disorder who received off-label buprenorphine in outpatient and inpatient settings in a university hospital between 2013 and 2016. RESULTS: Four of the patients had an early positive response. However, only three continue to adhere to treatment for six months or longer. CONCLUSIONS: More severe opioid use disorder seems to more negatively influence clinical outcome, independently of cluster b personality traits. Identification of patients who could benefit from buprenorphine will require further studies.

Choreoathetoid movements associated with methamphetamine: A case report and review of literature.

BACKGROUND AND OBJECTIVES: Physicians and psychiatrists often encounter patients in the emergency department presenting after methamphetamine use. While physical and psychiatric manifestations associated with methamphetamine use are well known, movement disorders are relatively less common. The aim of this case report is to add to existing literature awareness about the possibility of movement disorders occurring after methamphetamine use, discuss the possible mechanism by which such use leads to dyskinesia, and describe possible management strategies. METHODS AND RESULTS: In this case report, we describe choreoathetoid movements occurring in a young female after relatively short-term methamphetamine use. DISCUSSION AND CONCLUSIONS: Evidence for treatment of methamphetamine induced choreoathetosis is limited. Expectant management of such symptoms is a viable option if there are no additional comorbidities that require therapy. SCIENTIFIC SIGNIFICANCE: Clinicians should be alert to the possibility of movement disorders in methamphetamine users and familiar with treatment options. (Am J Addict 2018;XX:1-4).

Response to unfairness across the suicide risk spectrum.

Suicidal behavior is frequently triggered by social crises, such as familial, romantic, social or work-related conflict. A variety of cognitive and social functioning impairments has been associated with suicidal thoughts and acts. One of the precipitating and perpetuating factors of social conflict is the desire for retribution after a perceived offense, even at one's own detriment. We utilized the Ultimatum Game-a behavioral economic task which examines the behavioral response to perceived unfairness-in order to characterize the response to unfairness across the acute suicide risk spectrum. We examined five groups of adult individuals of both genders (n = 204): High- and Low-Lethality recent Suicide Attempters, Suicidal Ideators, Non-Suicidal Depressed Patients; and Healthy Controls. We also measured demographic and clinical variables. Even though all depressed groups showed similar rejection rates in the Ultimatum Game, there was a higher likelihood of rejecting offers in the low stakes condition in all acutely suicidal groups compared with healthy controls. Stake size, offer, education, and gender of the proposer were significantly associated with rejection rates. Acutely suicidal patients may be more vulnerable to adverse interpersonal interactions. Further characterization of social behavior may provide targets for secondary and tertiary prevention for high-risk individuals.

Association between C-reactive protein and suicidal behavior in an adult inpatient population.

OBJECTIVES: To examine the relationship of inflammation and suicidal behavior in hospitalized adult psychiatric patients. METHOD: We retrospectively examined serum high sensitivity C-reactive protein (hsCRP) levels in inpatients at a tertiary-level university hospital (N = 184). The inpatients comprised three cohorts: 1) patients admitted following a suicide attempt, 2) patients with suicidal ideation, and 3) inpatient psychiatric controls. Additionally, we gathered demographic data, clinical data, smoking status, white blood cell count, and fasting lipid panel. RESULTS: As CRP level increased, the probability of patients belonging to the suicide attempt group increased as compared to both the probabilities of being in inpatient psychiatric control and or suicide ideation groups [OR = 2.09, CI = (1.29, 3.38) and OR = 1.75, CI = (1.15, 2.66) respectively]. We also observed a significant effect of depression in that depressed patients were more likely to have a suicide attempt when compared to patients with no depression or with mania [OR = 10.38, CI = (1.97, 54.70)]. CONCLUSIONS: There seems to be an inflammation gradient, measured by CRP levels, from recent suicide attempters, suicidal ideators and psychiatric controls. We replicated the association between a pro-inflammatory state and suicidal behavior in a sample of "real world" severely ill psychiatric inpatients.