Research review: Cholinergic mechanisms, early brain development, and risk for schizophrenia.
The onset of diagnostic symptomology for neuropsychiatric diseases is often the end result of a decades-long process of aberrant brain development. Identification of novel treatment strategies aimed at normalizing early brain development and preventing mental illness should be a major therapeutic goal. However, there are few models for how this goal might be achieved. This review uses the development of a psychophysiological correlate of attentional deficits in schizophrenia to propose a developmental model with translational primary prevention implications. Review of genetic and neurobiological studies suggests that an early interaction between alpha7 nicotinic receptor density and choline availability may contribute to the development of schizophrenia-associated attentional deficits. Therapeutic implications, including perinatal dietary choline supplementation, are discussed.
Ross
Randal G
RG
Department of Psychiatry, University of Colorado Denver, Aurora, CO, USA.
Stevens
Karen E
KE
Proctor
William R
WR
Leonard
Sherry
S
Kisley
Michael A
MA
Hunter
Sharon K
SK
Freedman
Robert
R
Adams
Catherine E
CE
D000818:Animals; D001921:Brain / Q000254:growth & development*; D002794:Choline / Q000502:physiology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005072:Evoked Potentials, Auditory / Q000502:physiology; D005190:Family; D006801:Humans; D051379:Mice; D011950:Receptors, Cholinergic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology; D012307:Risk Factors; D012559:Schizophrenia / Q000209:etiology* / Q000517:prevention & control; D055139:Sensory Gating / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002794:Choline