No abstract

In 18 boys with ADHD (ages 6-12) in a balanced crossover design, parent and teacher hyperactivity rating differences between one month of dextroamphetamine and one month of placebo correlated significantly (p less than .05, 2 tailed) on Pearson's r with baseline hair zinc levels and nonsignificantly with 24-hour urinary zinc excretion. The signs of the correlations were such that a higher baseline zinc predicted a better placebo-controlled response to amphetamine. Patient baseline urinary zinc was significantly (p less than .02) lower than 7 normal controls. These findings are compatible with the possibility that some ADHD children may be mildly deficient in zinc and constitute poorer stimulant responders. Correlations of zinc levels with 24-hour urinary MHPG were in the expected direction but nonsignificantly by 2-tailed test.

Essential fatty acids are structural components of all biological membranes and form the environment for membrane receptors, ion channels, and enzymes. Dietary linoleic acid is metabolized by delta-6-desaturase to gamma-Iinolenic acid (GLA). Through several further metabolic steps, GLA is eventually converted to series-1 prostaglandins, thromboxanes, and other molecules involved in regulating the moment-to-moment function of various physiological processes. For example, prostaglandins interact with dopamine neurotransmission. The biochemistry and physiology of essential fatty acids are reviewed, with attention to possible implications for behavior. Delta-6-desaturase deficiency has been hypothesized to be one cause of attention-deficit hyperactivity disorder (ADHD). To explore this possibility, we examined the correlations of serum lipids and behavior in a double-blind crossover comparison of GLA, d-amphetamine, and placebo in 16 boys (ages 6-12) with ADHD. Looking at the fatty-acid components of serum triglycerides across treatment conditions, we found that higher scores for behavior problems correlated with lower levels of GLA (for each of four behavioral ratings, p < 0.015) but not with its precursor, linoleic acid. This is compatible with a metabolic bottleneck at delta-6-desaturase being related to some ADHD symptoms. These preliminary findings are consistent with the possibility that fatty-acid intake or metabolism may influence behavior, at least in children with ADHD, and could conceivably modulate the effects of psychopharmacological treatment. This study must be considered exploratory and heuristic, and more definitive studies are needed to examine the possible relevance of fatty-acid metabolism to psychiatric disorders.Several possible mechanisms may link essential fatty-acid metabolism to behavior. These potential connections include not only the effects of general body metabolism on brain function, but also the structural need for polyunsaturated fatty acids in neuronal membranes and the influence of these fatty acids and their metabolic products on neurotransmitter production, release, and effects. This article will review the biochemistry and physiology of essential fatty acids, consider some suggestive animal behavior findings, focus more specifically on possible implications of gamma-linolenic acid (GLA) for attention-deficit hyperactivity disorder (ADHD), and finally present some relevant pilot data.