Wink, LK; Adams, R; Pedapati, EV; Dominick, KC; Fox, E; Buck, C; Erickson, CA. Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder. Journal of Autism and Developmental Disorders. 2017; 47(7):2290-2294.
Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of antipsychotic-induced weight gain in youth with ASD. In this report we assess the long-term impact of metformin on antipsychotic-associated weight gain in a naturalistic sample of 53 youth with ASD. Results indicate that treatment with metformin stabilized BMI z-score over a nearly two year mean treatment period. Determining the safety and efficacy of metformin treatment in youth with ASD shows the need for further work, as well as predictors of response as a treatment for antipsychotic-induced weight gain.
Hong, MP; Guilfoyle, JL; Mooney, LN; Wink, LK; Pedapati, EV; Shaffer, RC; Sweeney, JA; Erickson, CA. Eye gaze and pupillary response in Angelman syndrome. Research in Developmental Disabilities. 2017; 68:88-94.
This manuscript describes the use of acamprosate, a drug FDA approved for the treatment of alcoholism, to correct brain deficits in the fragile X syndrome knockout mouse model. The drug reduced anxiety and locomotor deficits in the mouse model. Acamprosate use also corrected abnormally elevated brain levels of activated extracellular signal related kinase and increased cortical brain hyperexcitability as measured in brain slices. This work has supported ongoing efforts by the authors to study this drug in human drug trials in fragile X syndrome.
Schaefer, TL; Davenport, MH; Grainger, LM; Robinson, CK; Earnheart, AT; Stegman, MS; Lang, AL; Ashworth, AA; Molinaro, G; Huber, KM; Erickson, CA. Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety. Journal of Neurodevelopmental Disorders. 2017; 9(1).
Angelman syndrome (AS) is a rare neurological disorder characterized by severe developmental disability, communication impairment, elevated seizure risk, and motor system abnormalities. The aims of this study were to determine the feasibility of social scene eye tracking and pupillometry measures in individuals with AS and to compare the performance of AS participants to individuals with idiopathic autism spectrum disorder (ASD) and typically developing controls (TDC). Forty-seven percent of recruited AS participants completed the eye tracking paradigm. Compared to TDC, AS subjects demonstrated significantly less preference for social scenes than geometric shapes. Additionally, AS subjects did not show increased pupil dilation, compared to TDC, when viewing social scenes versus geometric shapes. There was no significant difference found between AS and ASD subjects in either social eye tracking or pupillometry. The use of eye tracking and pupillometry may represent an innovative measure for quantifying AS-associated impairments in social salience.
Tan, WH; Bird, LM; Sadhwani, A; Barbieri-Welge, RL; Skinner, SA; Horowitz, LT; Bacino, CA; Noll, LM; Fu, C; Hundley, RJ; Wink, LK; Erickson, CA; Barnes, GN; Slavotinek, A; Jeremy, R; Rotenberg, A; Kothare, SV; Olson, HE; Poduri, A; Nespeca, MP; Chu, HC; Willen, JM; Haas, KF; Weeber, EJ; Rufo, PA. A randomized controlled trial of levodopa in patients with Angelman syndrome. American Journal of Medical Genetics, Part A. 2018; 176(5):1099-1107.
Training child psychiatrists integrates the psychiatric, behavioral, and medical care of people with developmental disabilities. For many child psychiatrists, there remains a critical knowledge gap in understanding the rationale for molecular genetic testing and whether there is an indication for further testing. Dr. Ernest Pedapati, under the charge of the American Association of Child and Adolescent Psychiatry Autism and Intellectual Disability Committee, co-chaired a committee of expert child psychiatrists from several major academic centers to summarized the guidelines for diagnostic genetic testing in people with developmental disabilities. The Journal of American Child and Adolescent Psychiatry, a highly credible and widely accessible platform to aid child psychiatrists in their clinical practice, accepted this work for publication .
Muhle, RA; Reed, HE; Vo, LC; Mehta, S; McGuire, K; Veenstra-VanderWeele, J; Pedapati, E. Clinical Diagnostic Genetic Testing for Individuals With Developmental Disorders. Journal of the American Academy of Child and Adolescent Psychiatry. 2017; 56(11):910-913.
Treatment for Angelman Syndrome (AS) is currently limited to symptomatic interventions. We conducted a multi‐center double‐blind randomized placebo‐controlled 1‐year trial of levodopa / carbidopa with either 10 or 15 mg/kg/day of levodopa in children with AS. The outcome of this intervention assessing using either the Bayley Scales of Infant Development or the Mullen Scales of Early Learning, as well as the Vineland Adaptive Behavior Scales, and the Aberrant Behavior Checklist. Of the 78 participants enrolled, 67 participants received study medication (33 on levodopa, 34 on placebo), and 55 participants (29 on levodopa, 26 on placebo) completed the one‐year study. There were no clinically or statistically significant changes in any of the outcome measures over a one‐year period comparing the levodopa and placebo groups. The number of adverse events reported, including the more serious adverse events, was similar in both groups, but none relate to treatment with levodopa. Our data demonstrate that levodopa is well‐tolerated by children with AS. However, in the doses used in this study, it failed to improve their neurodevelopment or behavioral outcome.