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IN THIS ISSUE:
November 2010

SAMe for Depression?
The first placebo-controlled trial of SAMe as an adjunct to antidepressants in patients with treatment-resistant depression has yielded positive results.

IV Ketamine for Bipolar Depression
In a randomized, add-on trial, one infusion of IV ketamine improved depressive symptoms in patients with treatment-resistant bipolar depression.

Receptor-Binding Profiles of New Antipsychotics
The new antipsychotics paliperidone (Invega), iloperidone (Fanapt), and asenapine (Saphris) have different receptor-binding properties.

Sex Steroids for Schizophrenia?
In a double-blind trial, low-dose pregnenolone but not dehydroepiandrosterone (DHEA) improved outcomes in patients with schizophrenia when used to augment antipsychotic treatment.

In Brief
FDA Advisory Committee Votes Against Approval of Weight-Loss Drug Lorcaserin; Neonatal Levels of Vitamin D Associated with Increased Schizophrenia Risk; Warning Issued that Anticonvulsant Drug Lamotrigine (Lamictal) Can Cause Aseptic Meningitis

ADHD Symptoms, Food Additives, and Genetic Variations
Genetic variations may underlie differences in how artificial food dyes affect attention-deficit/hyperactivity disorder (ADHD) symptoms in children.

ADHD Symptoms, Food Additives, and Genetic Variations

November 2010

The syndromes psychiatrists and other practitioners treat consist of self-reported symptoms and behavioral observations. Presumably, most or all of these syndromes comprise many biologically distinct subtypes, which makes it difficult to establish the efficacy of treatments. A clue to understanding the heterogeneity of psychiatric disorders and a possible small step toward personalized medicine in psychiatry comes from a recent study in England.1

Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention, impulsivity, and overactivity. Children fall along a spectrum in the extent to which they manifest these symptoms, and a diagnosis of ADHD is made based on severity of symptoms and functional impairment.

A common theory links artificial food additives with ADHD symptoms in children with ADHD and in broader community samples. Many studies in preschool- and school-aged children suggest that artificial food colors and dyes may, in fact, aggravate problems of attention, impulse control, and overactivity, but some results have conflicted. Biological heterogeneity might account for differences in responses to provocative agents, much as it does for differences in responses to treatments.

Kaplan observes that food additives trigger histamine release, and some subtypes of histamine receptors are present in mammalian brain.2 Although histamine has been a relatively neglected neurotransmitter in ADHD genetic studies, Stevenson and colleagues included genetic polymorphisms from this system in their double-blind, placebo-controlled crossover trial with a two-food-color additive challenge.1 Genetic polymorphisms from the dopaminergic and adrenergic neurotransmitter systems, which have previously been implicated in ADHD, were also studied.

Investigators enrolled a general community sample of 153 three-year-old children and 144 eight- and nine-year-old children. The color-additive challenge involved two artificial dyes and a sodium benzoate preservative mixed in a fruit drink. The "placebo" was fruit juice alone. Association of adverse response to the color additives with gene polymorphisms yielded most interesting and provocative findings. The adverse effect of the two food additives on ADHD symptoms was moderated by two histamine-degradation gene polymorphisms in both age groups. In the eight- and nine-year-old children, a variant in a dopamine-related neurotransmission polymorphism also was related to ADHD symptoms.

One implication of these findings is that brain histamine may mediate the effects of at least some food additives on ADHD symptoms. Another is that variations in genes that influence the action of histamine (and possibly dopamine) may explain inconsistent findings regarding food additives and behavioral symptoms that have emerged from previous studies. We hope this study helps map a path to a better understanding of the interplay between individuals' unique genetic endowment and environmental influences, including what we eat and drink.

1Stevenson J, Sonuga-Barke E, McCann D, Grimshaw K, Parker KM, Rose-Zerilli MJ, Holloway JW, Warner JO: The role of histamine degradation gene polymorphisms in moderating the effects of food additives on children's ADHD symptoms. Am J Psychiatry 2010;167:1108-1115.

2Kaplan BJ: Food additives and behavior: First genetic insights. Am J Psychiatry 2010;167:1023-1025.