Biju Viswanath1, Sam P Jose2, Alessio Squassina3, Jagadisha Thirthalli4, Meera Purushottam4, Odity Mukherjee5, Vladimir Vladimirov6, George P Patrinos7, Maria Del Zompo8, Sanjeev Jain9. 1. Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India; Centre for Brain Development and Repair, Institute of Stem Cell Biology and Regenerative Medicine, Bangalore, India. 2. Department of Psychiatry, Elite Mission Hospital, Koorkanchery, Thrissur, Kerala, India. 3. Laboratory of Pharmacogenomics, Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy. 4. Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India. 5. National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India. 6. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA. 7. University of Patras, School of Health Sciences, Department of Pharmacy, Patras, Greece. 8. Laboratory of Pharmacogenomics, Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy; Unit of Clinical Pharmacology, Teaching Hospital, Cagliari, Italy. 9. Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India. Electronic address: sjain.nimhans@gmail.com.
Abstract
BACKGROUND: There is an emerging interest in the use of cellular models to study psychiatric disorders. We have systematically reviewed the application of cellular models to understand the biological basis of bipolar disorder (BD). METHOD: Published scientific literature in MEDLINE, PsychINFO and SCOPUS databases were identified with the following search strategy: [(Lymphoblastoid OR Lymphoblast OR Fibroblast OR Pluripotent OR Olfactory epithelium OR Olfactory mucosa) AND (Bipolar disorder OR Lithium OR Valproate OR Mania)]. Studies were included if they had used cell cultures derived from BD patients. RESULTS: There were 65 articles on lymphoblastoid cell lines, 14 articles on fibroblasts, 4 articles on olfactory neuronal epithelium (ONE) and 2 articles on neurons reprogrammed from induced pluripotent stem cell lines (IPSC). Several parameters have been studied, and the most replicated findings are abnormalities in calcium signaling, endoplasmic reticulum (ER) stress response, mitochondrial oxidative pathway, membrane ion channels, circadian system and apoptosis related genes. These, although present in basal state, seem to be accentuated in the presence of cellular stressors (e.g. oxidative stress--rotenone; ER stress--thapsigargin), and are often reversed with in-vitro lithium. CONCLUSION: Cellular modeling has proven useful in BD, and potential pathways, especially in cellular resilience related mechanisms have been identified. These findings show consistency with other study designs (genome-wide association, brain-imaging, and post-mortem brain expression). ONE cells and IPSC reprogrammed neurons represent the next generation of cell models in BD. Future studies should focus on family-based study designs and combine cell models with deep sequencing and genetic manipulations.
BACKGROUND: There is an emerging interest in the use of cellular models to study psychiatric disorders. We have systematically reviewed the application of cellular models to understand the biological basis of bipolar disorder (BD). METHOD: Published scientific literature in MEDLINE, PsychINFO and SCOPUS databases were identified with the following search strategy: [(Lymphoblastoid OR Lymphoblast OR Fibroblast OR Pluripotent OR Olfactory epithelium OR Olfactory mucosa) AND (Bipolar disorder OR Lithium OR Valproate OR Mania)]. Studies were included if they had used cell cultures derived from BD patients. RESULTS: There were 65 articles on lymphoblastoid cell lines, 14 articles on fibroblasts, 4 articles on olfactory neuronal epithelium (ONE) and 2 articles on neurons reprogrammed from induced pluripotent stem cell lines (IPSC). Several parameters have been studied, and the most replicated findings are abnormalities in calcium signaling, endoplasmic reticulum (ER) stress response, mitochondrial oxidative pathway, membrane ion channels, circadian system and apoptosis related genes. These, although present in basal state, seem to be accentuated in the presence of cellular stressors (e.g. oxidative stress--rotenone; ER stress--thapsigargin), and are often reversed with in-vitro lithium. CONCLUSION: Cellular modeling has proven useful in BD, and potential pathways, especially in cellular resilience related mechanisms have been identified. These findings show consistency with other study designs (genome-wide association, brain-imaging, and post-mortem brain expression). ONE cells and IPSC reprogrammed neurons represent the next generation of cell models in BD. Future studies should focus on family-based study designs and combine cell models with deep sequencing and genetic manipulations.
Authors: Miroslava Vosahlikova; Lenka Roubalova; Hana Ujcikova; Martina Hlouskova; Stanislav Musil; Martin Alda; Petr Svoboda Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2019-02-21 Impact factor: 3.000
Authors: Brandi L Rollins; Ling Morgan; Brooke E Hjelm; Adolfo Sequeira; Alan F Schatzberg; Jack D Barchas; Francis S Lee; Rick M Myers; Stanley J Watson; Huda Akil; Steven G Potkin; William E Bunney; Marquis P Vawter Journal: Mol Neuropsychiatry Date: 2017-11-30
Authors: Claudia Pisanu; Donatella Congiu; Marta Costa; Caterina Chillotti; Raffaella Ardau; Giovanni Severino; Andrea Angius; Urs Heilbronner; Liping Hou; Francis J McMahon; Thomas G Schulze; Maria Del Zompo; Alessio Squassina Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2018-10-14 Impact factor: 3.568
Authors: Joanne H Huang; Shaunna S Berkovitch; Jonathan Iaconelli; Bradley Watmuff; Hyoungjun Park; Shrikanta Chattopadhyay; Donna McPhie; Dost Öngür; Bruce M Cohen; Clary B Clish; Rakesh Karmacharya Journal: Mol Neuropsychiatry Date: 2016-06-24
Authors: Ana P Marques; Rosa Resende; Diana F Silva; Mariana Batista; Daniela Pereira; Brigite Wildenberg; Sofia Morais; António Macedo; Cláudia Pais; Joana B Melo; Nuno Madeira; Cláudia F Pereira Journal: Biomedicines Date: 2021-05-07
Authors: Paul J Harrison; Andrea Cipriani; Catherine J Harmer; Anna C Nobre; Kate Saunders; Guy M Goodwin; John R Geddes Journal: Ann N Y Acad Sci Date: 2016-02 Impact factor: 5.691