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Review
. 2002 Oct 15;99(21):13365-7.
doi: 10.1073/pnas.222532599. Epub 2002 Oct 8.

The discovery of susceptibility genes for mental disorders

C Robert Cloninger  1
Affiliations
Review

The discovery of susceptibility genes for mental disorders

C Robert Cloninger. Proc Natl Acad Sci U S A. .
No abstract available

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Figures

Fig 1.
Fig 1.
Chromosomal locations of four susceptibility genes for schizophrenia.
Fig 2.
Fig 2.
The NMDA receptor hypofunction model of schizophrenia is based on the disinhibition of certain limbic brain regions and neocortical regions, such as the retrosplenial cortical (RSC) neurons. The disinhibition circuitry of this model is depicted here. Glutamate acts through NMDA receptors on GABAergic, serotonergic, and noradrenergic neurons to maintain tonic inhibitory control over two major excitatory pathways that convergently innervate RSC neurons. Systemic administration of an NMDA antagonist blocks NMDA receptors in multiple brain regions, thereby abolishing inhibitory control over both of the excitatory inputs to the RSC neuron. The disinhibited excitatory pathways then simultaneously hyperactivate the RSC neuron. Abnormal functioning of the hyperactivated RSC neuron would produce derangements in neuronal and neurotransmitter function downstrean from the hyperactivated RSC neuron. This circuit diagram focuses exclusively on RSC neurons. A similar disinhibition mechanism and similar, but not necessarily identical, neural circuits and receptor mechanisms probably exist in other corticolimbic brain regions. +, Excitatory input; −, inhibitory input; ACh, acetylcholine; NE, norepinephrine; 5HT, serotonin; α2, α2 subtype of adrenergic receptor; GA, GABA type A subtype of GABA receptor; m3, m3 subtype of muscarinic cholinergic receptor; AMPA/KA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainic acid subtype of Glu receptor; NMDA, NMDA subtype of Glu receptor; σ, sigma site; 5HT2A, 5HT2A subtype of serotonin receptor. Asterisks indicate the postulated sites where dopamine inputs may presynaptically regulate Glu release. This diagram was provided by John W. Olney, John W. Newcomer, and Nuri B. Farber, Washington University School of Medicine.
See this image and copyright information in PMC

Comment on

  • Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia.
    Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H, Bougueleret L, Barry C, Tanaka H, La Rosa P, Puech A, Tahri N, Cohen-Akenine A, Delabrosse S, Lissarrague S, Picard FP, Maurice K, Essioux L, Millasseau P, Grel P, Debailleul V, Simon AM, Caterina D, Dufaure I, Malekzadeh K, Belova M, Luan JJ, Bouillot M, Sambucy JL, Primas G, Saumier M, Boubkiri N, Martin-Saumier S, Nasroune M, Peixoto H, Delaye A, Pinchot V, Bastucci M, Guillou S, Chevillon M, Sainz-Fuertes R, Meguenni S, Aurich-Costa J, Cherif D, Gimalac A, Van Duijn C, Gauvreau D, Ouellette G, Fortier I, Raelson J, Sherbatich T, Riazanskaia N, Rogaev E, Raeymaekers P, Aerssens J, Konings F, Luyten W, Macciardi F, Sham PC, Straub RE, Weinberger DR, Cohen N, Cohen D. Chumakov I, et al. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13675-80. doi: 10.1073/pnas.182412499. Epub 2002 Oct 3. Proc Natl Acad Sci U S A. 2002. PMID: 12364586 Free PMC article.

References

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