Label-free, live optical imaging of reprogrammed bipolar disorder patient-derived cells reveals a functional correlate of lithium responsiveness

• Published in: Translational psychiatry Vol. 4; no. 8; p. e428
• Main Authors: Wang, J L, Shamah, S M, Sun, A X, Waldman, I D, Haggarty, S J, Perlis, R H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.08.2014; Nature Publishing Group
• Subjects: 631/378/87; 631/80/2373; 692/699/476/1333; Affect - drug effects; Behavioral Sciences; Biological Psychology; Bipolar Disorder - drug therapy; Bipolar Disorder - genetics; Bipolar Disorder - physiopathology; Cellular Reprogramming - drug effects; Cellular Reprogramming - physiology; Genome-Wide Association Study; Humans; Lithium Carbonate - pharmacology; Lithium Carbonate - therapeutic use; Medicine; Medicine & Public Health; Neurosciences; Optical Imaging; Original; original-article; Pharmacogenetics; Pharmacotherapy; Psychiatry; Sodium-Bicarbonate Symporters - genetics; Treatment Outcome
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/tp.2014.72

Development of novel treatments and diagnostic tools for psychiatric illness has been hindered by the absence of cellular models of disease. With the advent of cellular reprogramming, it may be possible to recapitulate the disease biology of psychiatric disorders using patient skin cells transdifferentiated to neurons. However, efficiently identifying and characterizing relevant neuronal phenotypes in the absence of well-defined pathophysiology remains a challenge. In this study, we collected fibroblast samples from patients with bipolar 1 disorder, characterized by their lithium response ( n =12), and healthy control subjects ( n =6). We identified a cellular phenotype in reprogrammed neurons using a label-free imaging assay based on a nanostructured photonic crystal biosensor and found that an optical measure of cell adhesion was associated with clinical response to lithium treatment. This cellular phenotype may represent a useful biomarker to evaluate drug response and screen for novel therapeutics.