Neuroscience Research 149 (2019) 1–13 Contents lists available at ScienceDirect Neuroscience Research jo ur nal homepage: www.elsevier.com/locate/neures Review article Insulin growth factor 2 (IGF2) as an emergent target in psychiatric and neurological disorders. Review M. Pardo a,∗ , Y. Cheng b , Y.H. Sitbon c , J.A. Lowell d , S.F. Grieco e , R.J. Worthen d , S. Desse d , A. Barreda-Diaz a a University of Miami Miller School of Medicine, Department of Neurology, Miami, FL, USA b University of California Los Angeles, Neurology Department, Los Angeles, CA, USA c University of Miami Miller School of Medicine, Department of Molecular and Cellular Pharmacology, Miami, FL, USA d University of Miami, Department of Psychiatry & Behavioral Sciences, Miami, FL, USA e University of California, Department of Anatomy and Neurobiology, Irvine, CA, USA a r t i c l e i n f o Article history: Received 2 August 2018 Received in revised form 5 October 2018 Accepted 29 October 2018 Available online 31 October 2018 Keywords: Insulin growth factor 2 Memory Cognitive disabilities PTSD Schizophrenia Alzheimer a b s t r a c t Insulin-like growth factor 2 (IGF2) is abundantly expressed in the central nervous system (CNS). Recent evidence highlights the role of IGF2 in the brain, sustained by data showing its alterations as a common feature across a variety of psychiatric and neurological disorders. Previous studies emphasize the poten- tial role of IGF2 in psychiatric and neurological conditions as well as in memory impairments, targeting IGF2 as a pro-cognitive agent. New research on animal models supports that upcoming investigations should explore IGF2 ′ s strong promising role as a memory enhancer. The lack of effective treatments for cognitive disturbances as a result of psychiatric diseases lead to further explore IGF2 as a promising tar- get for the development of new pharmacology for the treatment of memory dysfunctions. In this review, we aim at gathering all recent relevant studies and findings on the role of IGF2 in the development of psychiatric diseases that occur with cognitive problems. Published by Elsevier B.V. Contents 1. Insulin-like growth factor 2 (IGF2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 2. IGF2 in psychiatric diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2.1. IGF2 and post-traumatic stress disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2.2. IGF2 and schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.3. Bipolar disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.4. Fragile X syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.5. Alcohol-related disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5 2.6. IGF2 and Alzheimer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2.7. Memory impairments as a main symptom in psychiatric and neurological disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 3. IGF2 in memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 4. Mechanisms underlying IGF2 effects and clinical relevance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 ∗ Corresponding author at: Department of Neurology, Miller School of Medicine, University of Miami, 1951 NW 7th Ave, Suite 2216, Miami, FL, 33136, USA. E-mail addresses: mpardodoc@med.miami.edu (M. Pardo), YCheng@mednet.ucla.edu (Y. Cheng), yxs454@miami.edu (Y.H. Sitbon), jefflowell12@med.miami.edu (J.A. Lowell), sgrieco@uci.edu (S.F. Grieco), rjw102@miami.edu (R.J. Worthen), sachidesse@msn.com (S. Desse), axb1748@miami.edu (A. Barreda-Diaz). https://doi.org/10.1016/j.neures.2018.10.012 0168-0102/Published by Elsevier B.V.