Serotonergic system in children and adolescents affected by depressive disorders: Biological and genetic aspects

M. Nobile, B. Begni, A. Frigerio, R. Giorda, C. Marino, C. Ferrarese, M. Molteni

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Abstract

Abnormalities in serotonergic systems are largely implicated in adult depression. Many investigators reported a low density of platelet and brain serotonin transporter (5-HTT) sites in drug-free depressed patients and decreased maximal uptake rate (Vmax) value for 5-HT. Previous association studies of a variable number of tandem repeat (VNTR) polymorphisms in intron 2 and a functional insertion/deletion polymorphism in the promoter of the 5-HTT gene have produced conflicting results. We evaluated serotonergic function in nine drug-free children and adolescents affected by depressive disorders and seven controls, by analysis of both [3H]-5HT uptake and [3H]Paroxetine binding in platelets and we analyzed possible correlations between 5HT uptake, 5HTT binding, and the 5-HTT gene polymorphisms. A significantly lower maximum rate of 5HT uptake (P = 0.042) and of paroxetine binding density (P = 0.026) was observed in the depressed patients than in controls, indicating a possible serotonergic dysfunction also in young depressed patients. In the control group, the short variant of 5-HTTLPR (linked polymorphic region) was associated with a significantly lower Vmax value for 5HT (t = 5.12, P = 0.004, C.I. = 5.8-17.7). On the contrary, this association was not confirmed in depressed patients. No significant association of depressive disorders with VNTR (genotype 12-12 and allele 12) and 5-HTTLPR polymorphisms was found These findings suggest that in normal controls, 5-HTT expression and function are regulated by 5-HTTLPR while in young depressed patients they might be regulated by some other unknown factors.

Original languageEnglish
Pages (from-to)550
Number of pages1
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume81
Issue number6
Publication statusPublished - Nov 6 1998

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ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

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