Common mechanisms of excitatory and inhibitory imbalance in schizophrenia and autism spectrum disorders.
Autism Spectrum Disorders (ASD) and Schizophrenia (SCZ) are cognitive disorders with complex genetic architectures but overlapping behavioral phenotypes, which suggests common pathway perturbations. Multiple lines of evidence implicate imbalances in excitatory and inhibitory activity (E/I imbalance) as a shared pathophysiological mechanism. Thus, understanding the molecular underpinnings of E/I imbalance may provide essential insight into the etiology of these disorders and may uncover novel targets for future drug discovery. Here, we review key genetic, physiological, neuropathological, functional, and pathway studies that suggest alterations to excitatory/inhibitory circuits are keys to ASD and SCZ pathogenesis.
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Department of Physiology, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60611, USA. p-penzes@northwestern.edu.
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D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology; D059330:GABAergic Neurons / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases