Abstract
Normative brain development is contingent on the complex interplay between genes and environment. Schizophrenia (SCZ) is considered a highly polygenic, neurodevelopmental disorder associated with impaired neural circuit development, neurocognitive function and variations in neurotransmitter signaling systems, including dopamine. Significant evidence, accumulated over the last 30 years indicates a role for the in utero environment in SCZ pathophysiology. Emerging data suggests that changes in placental programming and function may mediate the link between genetic risk, early life complications (ELC) and adverse neurodevelopmental outcomes, with risk highlighted in key developmental drivers that converge on AKT/mTOR signaling. In this article we overview select risk genes identified through recent genome-wide association studies of SCZ including AKT3, miR-137, DRD2, and AKT1 itself. We propose that through convergence on AKT/mTOR signaling, these genes are critical factors directing both placentation and neurodevelopment, influencing risk for SCZ through dysregulation of placental function, metabolism and early brain development. We discuss association of risk genes in the context of their known roles in neurodevelopment, placental expression and their possible mechanistic links to SCZ in the broad context of the ‘developmental origins of adult disease’ construct. Understanding how common genetic variation impacts early fetal programming may advance our knowledge of disease etiology and identify early critical developmental windows for prevention and intervention.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.