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Schizophrenia has long been considered a neurodevelopmental disorder in which onset of diagnostic symptoms in late adolescence or adulthood is the end result of a decades-long interaction between genes and environment that begins in the womb.
Choline is an essential nutrient similar to vitamins and is found in foods such as liver, muscle meats, fish, nuts, and eggs. Findings from a recent study suggest that when it is given as a dietary supplement in the last 2 trimesters of pregnancy and in early infancy, there is a lower rate of physiological schizophrenia risk factors in infants 33 days old.1 The study breaks new ground both in its potentially therapeutic findings and in its use of a surrogate indicator as a target for psychiatric illness prevention.
Schizophrenia has long been considered a neurodevelopmental disorder in which onset of diagnostic symptoms in late adolescence or adulthood is the end result of a decades-long interaction between genes and environment that begins in the womb. Most recent versions of this theory postulate 2 particularly critical windows during development: one in the perinatal period in which vulnerability develops, and one in adolescence when the vulnerability is converted into the full illness.
Under way are a number of efforts that focus on the adolescent and young adult period and are attempting to decrease conversion from vulnerability into the full disorder. However, one of the less discussed issues is that even if the conversion to full illness never occurs, vulnerability itself is associated with lifelong difficulties in attention and with increased risk of other forms of psychiatric illness, such as anxiety and depression. Increased focus on the first critical window may have lifelong benefits with a broad range of impact.
The recent study at the University of Colorado School of Medicine used a dietary supplement, phosphatidylcholine, which converts into choline in vivo, during pregnancy, and in the young infant.1 Mothers received 6300 mg/d of phosphatidylcholine (equivalent to the amount of choline in 3 large eggs) from the fourth month of pregnancy through delivery; then infants received 700 mg/d (equivalent to about 100 mg of choline) .
Normally, the brain responds fully to an initial clicking sound but inhibits its response to a second click that follows immediately. In patients with schizophrenia, deficient inhibition is common and is related to poor sensory filtering and familial transmission of schizophrenia risk. Since schizophrenia does not usually appear until adolescence, this trait-measurable in infancy-was chosen to represent the illness.
Findings from the study indicate that 76% of the infants who received the prenatal and postnatal choline supplementation showed intact P50 sensory gating, compared with only 43% of infants who received placebo. A separate group of infants was followed into toddlerhood: the infants with more intact sensory gating had fewer behavioral problems at 3½ years of age. Work in a mouse model suggests that the effect of choline supplementation was mediated by stimulation of the alpha7 nicotinic cholinergic receptor during early development.
Robert Freedman, MD, Professor and Chair of the University of Colorado Department of Psychiatry and one of the study’s authors and Editor of The American Journal of Psychiatry, points out, “Genes associated with schizophrenia are common, so prevention has to be applied to the entire population, and it has to be safe. Basic research indicates that choline supplementation during pregnancy facilitates cognitive functioning in offspring. Our finding that it ameliorates some of the pathophysiology associated with risk for schizophrenia now requires longer-term follow-up to assess whether it decreases risk for the later development of illness as well.” If the study can be successfully replicated and if long-term follow-up finds that improvement in early brain physiology is predictive of lower rates and/or severity of psychotic illness, then this study may lead to the first use of a dietary supplementation strategy to decrease long-term risk of illness.
Dr Ross is Professor, departments of psychiatry and pediatrics, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora. He receives support from the Institute for Children’s Mental Disorders, the Anschutz Family Foundation, and NIH grants P50MH086383 and R01MH056539.
1. Ross RG, Hunter SK, McCarthy L, et al. Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. Am J Psychiatry. 2013 Jan 15. doi:10.1176/appi.ajp.2012.12070940. [Epub ahead of print]