Neurotransmitters and Learning, Memory and Developmental Disorders

By Margaret Lahey and Shari Rosen
BAMFORD-LAHEY CHILDREN'S FOUNDATION

DIETARY INFLUENCES
Most neurotransmitters are synthesized within the brain; however, dietary precursors can influence both rate and function of some neurotransmitters even when no deficiency exists (Anderson & Johnston, 1983; Young, 1996). The manufacture and release of these neurotransmitters depends in large part on the concentration of the particular precursor in the blood (Lamb, 1983). Although factors within the brain also control synthesis and function of neurotransmitters, ingestion of particular foods can give rise to changes in the neural activity in the brain with resultant changes in physiological functioning and behavior; changes may be subtle in the healthy individual but for those with particular diseases or problems (e.g., depression) they could be significant (Maher, 2000; Young, 1996). To have any effect on behavior, the neurotransmitter must be released from the neurons and act on the receptors of postsynaptic neurons and this may be influenced by factors other than the level of the neurotransmitter (Young, 1996).

Amino acids, which are the building blocks of proteins and present in food proteins, are precursors for a number of neurotransmitters. In fact, some amino acids, such as tryptophan, are available only from dietary sources (Groff & Gropper, 1999). The effect of food is most obvious for the amino acids tryptophan, tyrosine, phenylalanine and these amino acids serve as the biosynthetic precursors for the neurotransmitters serotonin, dopamine, and norepinephrine. Single meals can influence the brain's uptake of these amino acids and modify their conversion to neurotransmitters (e.g., Fernstrom, 1994; Groff & Gropper, 1999; Wurtman, 1988). The transport of amino acids into the brain and thus their conversion into neurotransmitters is determined by the ratio of plasma levels of large molecule neutral amino acids to one another; for example, the plasma tryptophan ratio to other plasma amino acids affects brain levels of tryptophan (e.g., Liberman, Caballero, & Finer, 1986; Maher, 2000; Yokogoshi & Wurtman, 1986). Large neutral amino acids such as tryptophan and tyrosine compete with one another for transport into the brain and there is less tryptophan in most proteins than other amino acids like tyrosine. Plasma and brain levels of tryptophan and the synthesis of serotonin are increased in animals and humans following a carbohydrate meal but are blocked if protein is eaten first or is included with the carbohydrates (e.g., Fernstrom, 1988; Fernstrom & Fernstrom, 1995; Spring, 1984). Although carbohydrates lack the amino acid tryptophan, the carbohydrate meal affects tryptophan plasma levels by increasing the levels of insulin, which in turn stimulates the uptake of competing amino acids (but not tryptophan) into muscle tissue (e.g., Groff & Gropper, 1999; Spring, 1984). By contrast, ingestion of protein increases the levels of competing amino acids thus decreasing the likelihood that tryptophan will be transported across the blood-brain barrier (e.g., Spring, 1984). Most of the research on dietary precursors to neurotransmitters has been done on tryptophan.
The amino acids tyrosine and phenylalanine are precursors to dopamine; norephrine is synthesized from dopamine and epinephrine is synthesized from norephrine. As noted above, the level of these precursors in the blood influences the amount of tryptophan that crosses the blood brain barrier (Fernstrom, 1994). However, increased levels of tyrosine in the brain do not directly correlate with an increase in the neurotransmitter dopamine and the behavioral effects of loading with tyrosine are controversial (Groff & Gropper, 1999). The effect of increased dietary sources of tyrosine on levels of tyrosine in the brain appears to vary with region of the brain and the effect of increased levels in the brain on neural activity is influenced by the firing rate of the neuron (McTavish, Cowen, & Sharp, 1999: Groff & Gropper, 1999). When firing rate is markedly increased as in Parkinson's disease or dopamine-depleting lesions, tyrosine can increase levels of dopamine (Groff & Gropper, 1999). The amino acids glutamate and aspartate are neurotransmitters but their level in the brain seems not to be influenced by diet.

Choline is the precursor for the neurotransmitter acetylcholine and is found in the form of phosphatidylcholine, or lecithin, in many foods (e.g., eggs, liver, soybeans, peanuts) but the richest source used by the brain is endogenous. However, taken in large quantities, dietary lecithin does increase plasma and brain levels of choline. The effect of dietary precursors on acetycholine release in animals is influenced by a number of factors including environmental conditions such as novel surroundings (Kopf, Buchholzer, Hilgert, et al., 2001). Dietary deficiency of choline impairs the release of acetylcholine in the hippocampus and impairs memory in animals (Nakamura, Suzuki, Umegaki, et al., 2001). As with tyrosine, it appears that synthesis of acetycholine in response to dietary choline restriction may vary with the region of the brain (Nakamura et al., 2001). Cholergenic antagonists can produce memory deficits, and choline supplementation has been found to produce memory improvement in animals, human adults with choline deficiency, and in young normal humans (Gozes, Bardea, Reshef, et al., 1996; Groff & Gropper, 1999; Ladd, Sommer, LaBerge, & Toscano, 1993; Holmes, Yang, Liu, et al., 2002; Buchman, Sobel, Brown, et al., 2001). The availability of a dietary source of choline is particularly important for brain development related to memory and attention in the fetus and infant of animals and humans (Meck, & Williams, 1999; Yang, Liu, Cermak, et al., 2000; Yen, Mar, Meeker, et al., 2001; Zeisel, 2000).

The effect of diet on the function and levels of the neurotransmitters that are important for learning and behavior is another way that diet can affect learning and behavior as noted in Hypothesis A above. Given this possible effect, it is important to consider whether there is any dysfunction of neurotransmitters in developmental disorders and whether diet is associated with such dysfunction.