Somatodendritic 5-hydroxytryptamine1A (5-HT1A) autoreceptor function in major depression as assessed using the shift in electroencephalographic frequency spectrum with buspirone

Psychol Med. 2014 Mar;44(4):767-77. doi: 10.1017/S0033291713001475. Epub 2013 Jul 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / pharmacology*
  • Autoreceptors / genetics
  • Autoreceptors / physiology*
  • Buspirone / administration & dosage
  • Buspirone / pharmacology*
  • Cohort Studies
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / physiopathology*
  • Electroencephalography* / drug effects
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / physiopathology
  • Receptor, Serotonin, 5-HT1A / biosynthesis*
  • Receptor, Serotonin, 5-HT1A / genetics
  • Synapses / drug effects
  • Synapses / genetics*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Young Adult


  • Anti-Anxiety Agents
  • Autoreceptors
  • Receptor, Serotonin, 5-HT1A
  • Buspirone