biostudies-literatureNamkung HNational Alliance for Research on Schizophrenia and DepressionNIMH NIH HHSBrain and Behavior Research FoundationNational Institute of Mental Health220-235.e9https://www.ebi.ac.uk/biostudies/studies/S-EPMC10183200biostudies-literatureUnknown111(2)Schizophrenia (SZ) and bipolar disorder (BP) are highly heritable major psychiatric disorders that share a substantial portion of genetic risk as well as their clinical manifestations. This raises a fundamental question of whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. This study shows the miR-124-3p-AMPAR pathway as a key common neurobiological mediator that connects polygenic risks with behavioral changes shared between these two psychotic disorders. We discovered the upregulation of miR-124-3p in neuronal cells and the postmortem prefrontal cortex from both SZ and BP patients. Intriguingly, the upregulation is associated with the polygenic risks shared between these two disorders. Seeking mechanistic dissectiNeuronThe miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorder.PMC10183200MH-107730R01 MH092443MH-105660P50 MH094268R01 MH105660MH-092443MH-094268R01 MH107730RUSK/S-RJaaro-Peled HTian MFukudome DChatterjee NNamkung HZandi PSawa ANiwa MSharma KIshizuka KLee BJSrivastava RKannan SUrsini GLam SSaito AYukitake HHuganir RLfalseThe miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorder.Schizophrenia (SZ) and bipolar disorder (BP) are highly heritable major psychiatric disorders that share a substantial portion of genetic risk as well as their clinical manifestations. This raises a fundamental question of whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. This study shows the miR-124-3p-AMPAR pathway as a key common neurobiological mediator that connects polygenic risks with behavioral changes shared between these two psychotic disorders. We discovered the upregulation of miR-124-3p in neuronal cells and the postmortem prefrontal cortex from both SZ and BP patients. Intriguingly, the upregulation is associated with the polygenic risks shared between these two disorders. Seeking mechanistic dissecti2023-01-01T00:00:00Z2023 Jan2026-05-28T21:53:23.863Z2024-11-14T18:04:41.835ZS-EPMC101832003637921410.1016/j.neuron.2022.10.031