Psychiatry

Biogenic Amines and ADHD

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Science  29 Sep 2000:
Vol. 289, Issue 5488, pp. 2241-2243
DOI: 10.1126/science.289.5488.2241e

The widespread treatment of children who show signs of attention deficit hyperactivity disorder (ADHD) with Ritalin (methylphenidate) has contributed to arguments about overmedication. The controversy surrounding ADHD treatment contrasts with its standing as a psychiatric disorder whose genetic basis is understood better than that of many psychiatric diseases.

The efficacious treatment of ADHD patients with methylphenidate, a drug that inhibits dopamine uptake, is satisfyingly consistent with multiple reports of the association of ADHD with an allele of the dopamine D4 receptor gene. This allele, characterized by a 48-base pair repeat in exon 3 that likely affects the function of the receptor, is shown to be significantly increased in ADHD patients and their parents by Holmes et al., although a previously demonstrated association between ADHD and the DAT1 dopamine transporter is not replicated. But as this part of the story solidifies, McCracken et al. find an association of ADHD with a different allele of the dopamine D4 receptor that has a repeat element in the 5' transcription initiation site, Quist et al. find that the serotonin 2A receptor allele Tyr452 is preferentially transmitted to children with ADHD, and Barr et al. find no link between ADHD and the dopamine D5 receptor. Sorting out the true associations may require functional assessment of the candidate alleles and application of imaging methods such as single photon emission computed tomography (SPECT), as pursued by Dahlstrom et al., which can determine the availability of neurotransmitter receptors in the living brain — KK

Mol. Psychiatry5, 523; 531; 537; 546; 514 (2000)

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