Elsevier

Biological Psychiatry

Volume 66, Issue 3, 1 August 2009, Pages 223-230
Biological Psychiatry

Archival Report
Positron Emission Tomography Quantification of Serotonin-1A Receptor Binding in Medication-Free Bipolar Depression

https://doi.org/10.1016/j.biopsych.2009.01.028Get rights and content

Background

Little is known about the serotonin-1A receptor (5-HT1A) in bipolar depression despite altered 5-HT1A binding in major depressive disorder. Utilizing positron emission tomography (PET) and the radioligand N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide ([Carbonyl-C-11]WAY-100635), 5-HT1A binding was compared between depressed bipolar disorder (BD) and controls.

Methods

Brain 5-HT1A binding potential (BPF = Bmax/KD, where Bmax = total available receptors, and 1/KD = ligand affinity) was measured in 32 currently depressed, medication-free BD subjects and 47 controls. Participants were genotyped for the 5-HT1A promoter polymorphism C(-1019)G.

Results

The bipolar depressed group demonstrated higher 5-HT1A BPF across all regions of interest (ROIs; p = .022). Post hoc analyses indicated that male BD patients had higher 5-HT1A BPF than male controls (p = .025), with higher 5-HT1A BPF found in every region (by 102% in raphe nuclei and 29% to 50% in the forebrain ROIs); whereas, female subgroups did not differ in 5-HT1A BPF (p = .32). Serotonin-1A BPF did not correlate with depression severity. The GG genotype was overrepresented at trend level in the BD group (p = .057). Number of G-allele copies was associated with higher 5-HT1A BPF in raphe (p = .0050), amygdala (p = .022), and hippocampus (p = .041).

Conclusions

Higher 5-HT1A BPF in bipolar depressed males suggests higher raphe autoreceptor binding, potentially causing less serotonin release and compensatory upregulation of forebrain postsynaptic 5-HT1A receptors. The raphe effect may be partly genetic. No difference in 5-HT1A BPF between BD and control females may reflect greater effect of prior antidepressant exposure in BD females.

Section snippets

Participants

Thirty-two patients who presented in a MDE and met DSM-IV criteria for bipolar I or bipolar II disorder on Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition (SCID-I/P) (12), psychiatric interview, and chart review were enrolled. Forty-seven healthy volunteer control participants were also enrolled if free of Axis I diagnosis by Structured Clinical Interview for DSM-IV Axis I Disorders Non-Patient Edition SCID-I/NP (12) and without history of mood or psychotic disorder or

Results

The healthy volunteer and bipolar disorder groups were of comparable age (t = −.14; p = .89) and sex distribution (X2, p = .87). Table 1 provides sociodemographic and clinical data for the two groups. The ROI analysis of the [Carbonyl-C-11]WAY-100635 PET data revealed expected differences in the binding to 5-HT1A, expressed as BPF, across brain regions [F(12,900) = 976.1, p < .0001].

Discussion

To our knowledge, this is the first published report employing PET to assess 5-HT1A binding in vivo in a homogeneous, nonmedicated, patient sample with bipolar depression. Using the 5-HT1A antagonist radioligand [Carbonyl-C-11]WAY-100635, we identified in bipolar depression higher 5-HT1A BPF, in particular in the raphe autoreceptors and to a lesser degree across all terminal field ROIs. Post hoc analyses indicated the higher 5-HT1A BPF was specific to male bipolar depressed patients compared

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