Serotonin-1A autoreceptor binding in the dorsal raphe nucleus of depressed suicides

Abstract

Serotonergic dysfunction is present in mood disorders and suicide. Brainstem 5-HT1A somatodendritic autoreceptors regulate serotonin neuron firing but studies of autoreceptor binding in the dorsal raphe nucleus (DRN) in depressed suicides report conflicting results. We sought to determine: (1) the anatomical distribution of 5-HT1A receptor binding in the DRN in depressed suicides and psychiatrically normal controls; and (2) whether sex differences in 5-HT1A binding in the DRN contribute to differences between depressed suicides and controls. Previously collected quantitative receptor autoradiograms of [3H]8-hydroxy-2-(di-n-propyl)aminotetralin (3H-8-OH-DPAT) in postmortem tissue sections containing the DRN from drug-free suicide victims (n=10) and matched controls (n=10) were analyzed. Less total receptor binding (fmol/mg tissuexmm3) was observed in the entire DRN in depressed suicides compared with controls (p<0.05). Group differences along the rostrocaudal extent of the DRN were observed for cross-sectional 5-HT(1A) binding (fmol/mg tissue) and receptor binding (fmol/mgxmm3, p<0.05). Cross-sectional 5-HT1A DRN binding in depressed suicides compared with controls was higher rostrally and lower caudally. The differences between depressed suicides and controls were present in males and females, although females had more binding than males. Less autoreceptor binding in the DRN of depressed suicides may represent a homeostatic response to less serotonin release, increasing serotonin neuron firing. More autoreceptor binding in rostral DRN might contribute to deficient serotonin release in ventromedial prefrontal cortex by lower neuronal firing.

Fig. 1

A series of immunoautoradiograms illustrating the rostrocaudal distribution of 5-HT_1A receptor binding in a representative brain. The largest part of the dorsal raphe nucleus is indicated as the origin (0 mm) and the other five levels are measured as actual distance (in mm) rostral and caudal to the origin.

Fig. 2

5-HT_1A receptor ([³H]-8-OH DPAT) binding density in controls and depressed suicides in total sample (a), in females (b) and in males (c) at each dorsal raphe nucleus rostrocaudal level. Binding density is higher in the rostral raphe and lower in the caudal raphe in depressed suicides compared to controls. In controls, 5-HT_1A receptor binding is higher in females than in males. In suicides, 5-HT_1A binding is lower in females than in males.

Fig. 3

5-HT_1A receptor ([³H]-8-OH0DPAT) binding distribution area in controls and depressed suicides in total sample (a), in females (b) and in males (c) at each dorsal raphe nucleus rostrocaudal level. Binding distribution area is lower in depressed suicides than in controls. In females, Area is lower in depressed suicides at most rostrocaudal levels compared to controls. In males, Area is lower only at the most rostral level in suicides versus controls. Distribution area is not affected by sex in controls. Female suicides have lower distribution area than male suicides.

Fig. 4

5-HT_1A receptor [³H]-8-OH DPAT binding capacity in controls and depressed suicides in total sample (a), in females (b) and in males (c) at each dorsal raphe nucleus rostrocaudal level. Binding capacity is lower in depressed suicides than in controls, and this is true at all levels in females, and more selectively in males. In controls, binding capacity is higher in females than in males, but in suicides, binding capacity is lower in females than in males.