Περίληψη:
Substantial evidence supports a role for dysfunction of brain
serotonergic (5-HT) systems in the pathogenesis of major affective
disorder, both unipolar (recurrent major depression) and bipolar.(1)
Modification of serotonergic neurotransmission is pivotally implicated
in the mechanism of action of antidepressant drugs(2) and also in the
action of mood stabilizing agents, particularly lithium carbonate.(3)
Accordingly, genes that code for the multiple subtypes of serotonin
receptors that have been cloned and are expressed in brain,(4) are
strong candidates for a role in the genetic etiology of affective
illness. We examined a structural variant of the serotonin 2C (5-HT2C)
receptor gene (HTR2C) that gives rise to a cysteine to serine
substitution in the N terminal extracellular domain of the receptor
protein (cys23ser),(5) in 513 patients with recurrent major depression
(MDD-R), 649 patients with bipolar (BP) affective disorder and 901
normal controls. The subjects were drawn from nine European countries
participating in the European Collaborative Project on Affective
Disorders. There was significant variation in the frequency of the HT2CR
ser23 allele among the 10 population groups included in the sample (from
24.6% in Greek control subjects to 9.2% in Scots, chi (2)=20.9, df 9,
P=0.01). Logistic regression analysis demonstrated that over and above
this interpopulation variability, there was a significant excess of
HT2CR ser23 allele carriers in patients compared to normal controls that
was demonstrable for both the MDD (chi (2) = 7.34, df 1, P = 0.006) and
BP (chi (2) = 5.45, df 1, P = 0.02) patients. These findings support a
possible role for genetically based structural variation in 5-HT2C
receptors in the pathogenesis of major affective disorder.
Συγγραφείς:
Lerer, B
Macciardi, F
Segman, RH
Adolfsson, R
Blackwood,
D
Blairy, S
Del Favero, J
Dikeos, DG
Kaneva, R and
Lilli, R
Massat, I
Milanova, V
Muir, W
Noethen, M and
Oruc, L
Petrova, T
Papadimitriou, GN
Rietschel, M and
Serretti, A
Souery, D
Van Gestel, S
Van Broeckhoven, C and
Mendlewicz, J
