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Psychol Med ; 44(4): 767-77, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23809646

RESUMO

BACKGROUND: Positron emission tomography and post-mortem studies of the number of somatodendritic 5-hydroxytryptamine(1A) (5-HT(1A)) autoreceptors in raphé nuclei have found both increases and decreases in depression. However, recent genetic studies suggest they may be increased in number and/or function. The current study examined the effect of buspirone on the electroencephalographic (EEG) centroid frequency, a putative index of somatodendritic 5-HT(1A) receptor functional status, in a cohort of medication-free depressed patients and controls. METHOD: A total of 15 depressed patients (nine male) and intelligence quotient (IQ)-, gender- and age-matched healthy controls had resting EEG recorded from 29 scalp electrodes prior to and 30, 60 and 90 min after oral buspirone (30 mg) administration. The effect of buspirone on somatodendritic 5-HT(1A) receptors was assessed by calculating the EEG centroid frequency between 6 and 10.5 Hz. The effect of buspirone on postsynaptic 5-HT(1A) receptors was assessed by measuring plasma growth hormone, prolactin and cortisol concentrations. RESULTS: Analysis of variance revealed a significantly greater effect of buspirone on the EEG centroid frequency in patients compared with controls (F1,28 = 6.55, p = 0.016). There was no significant difference in the neuroendocrine responses between the two groups. CONCLUSIONS: These findings are consistent with an increase in the functional status of somatodendritic, but not postsynaptic, 5-HT1A autoreceptors, in medication-free depressed patients in line with hypotheses based on genetic data. This increase in functional status would be hypothesized to lead to an increase in serotonergic negative feedback, and hence decreased release of 5-HT at raphé projection sites, in depressed patients.


Assuntos
Ansiolíticos/farmacologia , Autorreceptores/fisiologia , Buspirona/farmacologia , Transtorno Depressivo Maior/fisiopatologia , Eletroencefalografia , Receptor 5-HT1A de Serotonina/biossíntese , Sinapses/genética , Adulto , Ansiolíticos/administração & dosagem , Autorreceptores/genética , Buspirona/administração & dosagem , Estudos de Coortes , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Eletroencefalografia/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Núcleos da Rafe/efeitos dos fármacos , Núcleos da Rafe/fisiopatologia , Receptor 5-HT1A de Serotonina/genética , Sinapses/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Adulto Jovem
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