Many psychiatric illnesses, including bipolar disorder, schizophrenia, autism, attention deficit hyperactivity disorder (ADHD), and anxiety disorders may stem from abnormalities in brain development that begin before birth. Researchers are trying to determine whether dietary supplements taken by pregnant mothers or infants can reduce the risk of such illnesses. At a recent scientific meeting, researcher Randal Ross and colleagues reported that compared to placebo, choline supplements reduced problems with a brain process called sensory gating in one-month-old infants and also improved the children’s attention span and social skills at age 3.
Sensory gating is the process by which the brain filters out unimportant information, to avoid flooding higher cortical centers with irrelevant stimuli. Deficits in the way the brain inhibits response to this type of irrelevant information are associated with mental illnesses such as schizophrenia.
In Ross’s study, healthy pregnant mothers received either a placebo or 6300 mg of choline, a nutrient found in liver, egg yolks, and meat. After delivery, the infants also received 700 mg of supplemental choline per day. In children who carried CHRNA7, a risk gene for schizophrenia discovered by Ross’s colleague Robert Freedman, choline reversed the associated risk of sensory gating problems and normalized their behavior at age 3.
In the past there has been some concern that selective serotonin reuptake inhibitor (SSRI) antidepressants taken during pregnancy could increase an infant’s risk of cardiac problems. There was particular concern that the SSRI paroxetine could lead to right ventricular outflow tract obstruction, and sertraline could lead to ventricular septal defects. A 2014 study by KF Huybrechts et al. in the New England Journal of Medicine analyzed data from 949,504 women in a Medicaid system from three months before pregnancy until one month after delivery during the years 2000-2007.
Infants born to mothers who had taken antidepressants during their first trimester were compared to infants whose mothers had not taken antidepressants. In total, 6.8% or 64,389 women had used antidepressants in their first trimester.
While the rate of cardiac defects in newborns was greater among those mothers who had taken antidepressants (90.1 infants per 10,000 infants who had been exposed to antidepressants versus 72.3 infants per 10,000 infants who had not been exposed to antidepressants), this relationship diminished as confounding variables were removed. The relative risk of any cardiac defect after taking SSRIs was 1.25, but this decreased to 1.12 when restricted to only those mothers who were diagnosed with depression, and to 1.06 when the researchers controlled for things like depression severity. (All relative risk numbers were calculated with a 95% confidence interval.)
The researchers concluded that there is no substantial risk of increased cardiac defects in children born to mothers who took antidepressants during their first trimester.
Choline Treatment For Pregnant Mothers And Newborns Improves Babies’ Cognition and Normalizes a Risk Factor for Schizophrenia
Deficiencies in GABA inhibition have been linked to the risk of schizophrenia (and perhaps bipolar disorder). GABA receptors are initially excitatory but switch to being inhibitory early in life. Choline derived from phosphatidylcholine or from eggs and meat in the diet is important in increasing GABA receptor development and maturity.
Ross et al. reported this year in the American Journal of Psychiatry that in a placebo-controlled study in which mothers took phosphatidylcholine in the last 2 trimesters of pregnancy (at doses of 3,600mg in the morning plus 2,700mg in the evening) and infants took 100mg/day for 12 weeks, the infants who received choline showed better neuronal inhibition than infants who did not receive choline on a P50 test of auditory evoked potential, in which the brain’s response to a series of beeps is recorded. An overactive P50 response is a sign of deficiencies in GABA inhibition.
In infants with a common gene variant in the alpha 7 nicotinic receptor that makes it function less well (which also may be a risk factor for the development of schizophrenia), the choline regimen normalized the P50 test, while placebo had no effect. However, in a recent study by Cabranes et al. published in Psychiatry Research, there was no association of the alpha 7 gene variant and schizophrenia or bipolar disorder, although patients with bipolar disorder and patients with schizophrenia did perform differently on the P50 evoked potential test than controls did.
Editor’s Note: In an editorial by Judy Rapoport that accompanied the Ross et al. study, the difficulty of using the findings in clinical practice are discussed. Meck et al. showed in 1999 that choline supplementation enhanced spatial memory, and in several cases nutritional supplements can have beneficial effects on the brain. Rapoport notes the success of perinatal folate in preventing neural tube defects and the likelihood that Vitamin D supplementation can prevent some cases of schizophrenia.
However, extrapolating the choline findings of Ross et al. to clinical practice, especially given the lack of association of the alpha 7 gene variation to psychiatric illness in the study by Cabranes et al., might be premature. Instead, Rapoport recommends a good diet and prevention of infection as first steps for treatment. Choline supplementation would be roughly equivalent to three eggs a day.