5-HT1A receptor, 5-HT2A receptor and serotonin transporter binding in the human auditory cortex in depression

Abstract

Background: Serotonergic system abnormalities are implicated in many psychiatric disorders, including major depression. The temporal lobe receives a high density of serotonergic afferent projections, and responses in the primary auditory cortex to sound are modulated by serotonergic tone. However, the associations between changes in serotonergic tone, disease state and changes in auditory cortical function remain to be clarified.

Methods: We quantified serotonin 1A (5-HT1A) receptor binding, serotonin 2A (5-HT2A) receptor binding, and serotonin transporter (SERT) binding in Brodmann areas (BA) 41/42, 22, 9 and 4 from postmortem brain sections of 40 psychiatrically healthy controls and 39 individuals who had a history of a major depressive episode (MDE).

Results: There was 33% lower 5-HT2A receptor binding in BA 41/42 in individuals who had an MDE than in controls (p = 0.0069). Neither 5-HT1A nor SERT binding in BA 41/42 differed between individuals who had an MDE and controls. We also found 14% higher 5-HT1A receptor binding (p = 0.045) and 21% lower SERT binding in BA 9 of individuals who had an MDE (p = 0.045).

Limitations: The study was limited by the small number of postmortem brain samples including BA 41/42 available for binding assays and the large overlap between suicide and depression in the MDE sample.

Conclusion: Depression may be associated with altered serotonergic function in the auditory cortex involving the 5-HT2A receptor and is part of a wider view of the pathophysiology of mood disorders extending beyond psychopathology.

Fig. 1

[³H]Ketanserin binding across Brodmann area (BA) 4, BA 9, BA 22, and BA 41/42 in healthy controls (HC) and individuals with a history of major depressive episodes (MDE). [³H]Ketanserin binding was 33% lower in BA41/42 of the MDE compared with the control group (MDE mean 20.59 ± 6.5 fmol/mg, HC mean 30.78 ± 7.8 fmol/mg; t = −3.05, p = 0.0069). There were no significant differences in BA 4 (MDE mean 24.81 ± 8.35 fmol/mg, HC mean 22.32 ± 6.84 fmol/mg), BA 9 (MDE mean 34.44 ± 12.64 fmol/mg, HC mean 30.4 ± 9.57 fmol/mg), and BA 22 (MDE mean 25.86 ± 10.65 fmol/mg, HC mean 24.76 ± 8.75 fmol/mg).

Fig. 2

[³H]8-OH-DPAT binding across Brodmann area (BA) 4, BA 9, BA 22, and BA 41/42 in healthy controls (HC) and individuals with a history of major depressive episodes (MDE). [³H]8-OH-DPAT binding was 14% higher in BA 9 of the MDE group compared with the control group (MDE mean 16.07 ± 3.92 fmol/mg, HC mean 13.98 + 3.99 fmol/mg, t = 2.05, p = 0.045). However, after accounting for the effects of age and sex, this finding became a trend-level observation (t = 1.79, p = 0.079). There was no significant difference between the MDE group and the control group in BA 4 (MDE mean 12.17 ± 5.45 fmol/mg, HC mean 10.56 ± 4.15 fmol/mg), BA 22 (MDE mean 16.13 ± 6.44 fmol/mg, HC 14.07 ± 5.38 fmol/mg), and BA 41/42 (MDE mean 12.84 ± 3.42 fmol/mg, HC mean 9.47 ± 1.94 fmol/mg).

Fig. 3

[³H]Cyanoimipramine binding across Brodmann area (BA) 4, BA 9, BA 22, and BA 41/42 in healthy controls (HC) and individuals with a history of major depressive episodes (MDE). [³H]Cyanoimipramine binding was 21% lower in BA 9 in the MDE group compared with the control group in sulcus data (MDE mean 5.65 ± 2.4 fmol/mg, HC mean 7.09 ± 3.14 fmol/mg, t = −2.04, p = 0.045). There was no significant difference between the MDE group and the control group in BA 4 (MDE mean 8.04 ± 6.93 fmol/mg, HC mean 6.61 ± 3.4 fmol/mg), BA 22 (MDE mean 6.89 ± 4.53 fmol/mg, HC mean 7.45 ± 4.25 fmol/mg), and BA 41/42 (MDE mean 8.26 ± 5.04 fmol/mg, HC mean 5.05 ± 1.69 fmol/mg).