Neurodevelopment, GABA System Dysfunction, and Schizophrenia

Overview

Journal Neuropsychopharmacology

Date 2014 Apr 25

PMID 24759129

Citations 97

Authors

Martin J Schmidt

Karoly Mirnics

Affiliations

Soon will be listed here.

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.

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References

Akbarian S, Kim J, Potkin S, Hetrick W, Bunney Jr W, Jones E . Maldistribution of interstitial neurons in prefrontal white matter of the brains of schizophrenic patients. Arch Gen Psychiatry. 1996; 53(5):425-36. DOI: 10.1001/archpsyc.1996.01830050061010. View

Mei L, Xiong W . Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci. 2008; 9(6):437-52. PMC: 2682371. DOI: 10.1038/nrn2392. View

Mata I, Perez-Iglesias R, Roiz-Santianez R, Tordesillas-Gutierrez D, Gonzalez-Mandly A, Berja A . Additive effect of NRG1 and DISC1 genes on lateral ventricle enlargement in first episode schizophrenia. Neuroimage. 2009; 53(3):1016-22. DOI: 10.1016/j.neuroimage.2009.11.010. View

. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature. 2008; 455(7210):237-41. PMC: 3912847. DOI: 10.1038/nature07239. View

Giovanoli S, Engler H, Engler A, Richetto J, Voget M, Willi R . Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice. Science. 2013; 339(6123):1095-9. DOI: 10.1126/science.1228261. View

Kreczmanski P, Heinsen H, Mantua V, Woltersdorf F, Masson T, Ulfig N . Volume, neuron density and total neuron number in five subcortical regions in schizophrenia. Brain. 2007; 130(Pt 3):678-92. DOI: 10.1093/brain/awl386. View

Adam D . Mental health: On the spectrum. Nature. 2013; 496(7446):416-8. DOI: 10.1038/496416a. View

Harrison P, Law A . Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biol Psychiatry. 2006; 60(2):132-40. DOI: 10.1016/j.biopsych.2005.11.002. View

St Clair D, Blackwood D, Muir W, Carothers A, Walker M, Spowart G . Association within a family of a balanced autosomal translocation with major mental illness. Lancet. 1990; 336(8706):13-6. DOI: 10.1016/0140-6736(90)91520-k. View

10.

Nadarajah B, Parnavelas J . Modes of neuronal migration in the developing cerebral cortex. Nat Rev Neurosci. 2002; 3(6):423-32. DOI: 10.1038/nrn845. View

11.

Costa E, Davis J, Dong E, Grayson D, Guidotti A, Tremolizzo L . A GABAergic cortical deficit dominates schizophrenia pathophysiology. Crit Rev Neurobiol. 2004; 16(1-2):1-23. DOI: 10.1615/critrevneurobiol.v16.i12.10. View

12.

Berninger B, Marty S, Zafra F, Da Penha Berzaghi M, Thoenen H, Lindholm D . GABAergic stimulation switches from enhancing to repressing BDNF expression in rat hippocampal neurons during maturation in vitro. Development. 1995; 121(8):2327-35. DOI: 10.1242/dev.121.8.2327. View

13.

Cardno A, Gottesman I . Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am J Med Genet. 2000; 97(1):12-7. View

14.

Aberg K, Liu Y, Bukszar J, McClay J, Khachane A, Andreassen O . A comprehensive family-based replication study of schizophrenia genes. JAMA Psychiatry. 2013; 70(6):573-81. PMC: 5297889. DOI: 10.1001/jamapsychiatry.2013.288. View

15.

Chen C, Cheng L, Grennan K, Pibiri F, Zhang C, Badner J . Two gene co-expression modules differentiate psychotics and controls. Mol Psychiatry. 2012; 18(12):1308-14. PMC: 4018461. DOI: 10.1038/mp.2012.146. View

16.

Wang D, Kriegstein A . GABA regulates excitatory synapse formation in the neocortex via NMDA receptor activation. J Neurosci. 2008; 28(21):5547-58. PMC: 2684685. DOI: 10.1523/JNEUROSCI.5599-07.2008. View

17.

Losonczy A, Biro A, Nusser Z . Persistently active cannabinoid receptors mute a subpopulation of hippocampal interneurons. Proc Natl Acad Sci U S A. 2004; 101(5):1362-7. PMC: 337058. DOI: 10.1073/pnas.0304752101. View

18.

Bitanihirwe B, Peleg-Raibstein D, Mouttet F, Feldon J, Meyer U . Late prenatal immune activation in mice leads to behavioral and neurochemical abnormalities relevant to the negative symptoms of schizophrenia. Neuropsychopharmacology. 2010; 35(12):2462-78. PMC: 3055332. DOI: 10.1038/npp.2010.129. View

19.

Arion D, Lewis D . Altered expression of regulators of the cortical chloride transporters NKCC1 and KCC2 in schizophrenia. Arch Gen Psychiatry. 2010; 68(1):21-31. PMC: 3015012. DOI: 10.1001/archgenpsychiatry.2010.114. View

20.

Iritani S, Kuroki N, Niizato K, Ikeda K . Morphological changes in neuropeptide Y-positive fiber in the hippocampal formation of schizophrenics. Prog Neuropsychopharmacol Biol Psychiatry. 2000; 24(2):241-9. DOI: 10.1016/s0278-5846(99)00102-5. View