Neurodevelopment, GABA System Dysfunction, and Schizophrenia

Abstract

The origins of schizophrenia have eluded clinicians and researchers since Kraepelin and Bleuler began documenting their findings. However, large clinical research efforts in recent decades have identified numerous genetic and environmental risk factors for schizophrenia. The combined data strongly support the neurodevelopmental hypothesis of schizophrenia and underscore the importance of the common converging effects of diverse insults. In this review, we discuss the evidence that genetic and environmental risk factors that predispose to schizophrenia disrupt the development and normal functioning of the GABAergic system.

Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: Potential roles in GABAergic interneuron pathology

“…In keeping with previous literature, the 2D-DIGE method identified reductions in the expression of hippocampal of parvalbumin (PVALB) in both diagnostic groups, (Konradi et al, 2011a;Konradi et al, 2011b;Schmidt and Mirnics, 2014).…”

Neurodevelopment and the Origins of Brain Disorders

“…The discussion highlights the many challenges to understanding heterogeneous findings in the context of individual differences between children, as well as the technical caveats of current neuroimaging and analytical methodologies. Schmidt and Mirnics (2015) provide a practical evaluation of the evidence supporting the neurodevelopmental hypothesis of schizophrenia. The review integrates genetic risk factors that point, in part, to the development of interneurons, with a perspective on excitatory-inhibitory balance in the context of schizophrenia risk and pathophysiology.…”

Different Paths to Core Pathology: The Equifinal Model of the Schizophrenia Syndrome

“…Maternal immune activation and adolescent cannabis use represent just 2 examples, selected from a pool of schizophrenia syndrome risk factors, which can interact with other genetic, environmental, and developmental risk factors to create a schizophrenia etiology [102][103][104] ( figure 1). Throughout their lifetimes, individuals are invariably exposed to a wide range of schizophrenia-related risk factors.…”