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Positron emission tomography quantification of serotonin-1A receptor binding in medication-free bipolar depression.

ABSTRACT: 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.Brain 5-HT1A binding potential (BP(F) = B(max)/K(D), where B(max) = total available receptors, and 1/K(D) = 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.The bipolar depressed group demonstrated higher 5-HT1A BP(F) across all regions of interest (ROIs; p = .022). Post hoc analyses indicated that male BD patients had higher 5-HT1A BP(F) than male controls (p = .025), with higher 5-HT1A BP(F) 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 BP(F) (p = .32). Serotonin-1A BP(F) 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 BP(F) in raphe (p = .0050), amygdala (p = .022), and hippocampus (p = .041).Higher 5-HT1A BP(F) 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 BP(F) between BD and control females may reflect greater effect of prior antidepressant exposure in BD females.

SUBMITTER: Sullivan GM

PROVIDER: S-EPMC2778225 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Positron emission tomography quantification of serotonin-1A receptor binding in medication-free bipolar depression.

Sullivan Gregory M GM Ogden R Todd RT Oquendo Maria A MA Kumar J S Dileep JS Simpson Norman N Huang Yung-yu YY Mann J John JJ Parsey Ramin V RV

Biological psychiatry 20090317 3

<h4>Background</h4>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.<h4>Methods</h4>Brain 5-HT1A binding potential (BP(F) = B(max)/K(D), where B(max) ...[more]

PMID: 19278673

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Project description:BackgroundThe pathophysiology of bipolar disorder (BD) remains largely unknown despite it causing significant disability and suicide risk. Serotonin signaling may play a role in the pathophysiology, but direct evidence for this is lacking. Treatment of the depressed phase of the disorder is limited. Previous studies have indicated that positron emission tomography (PET) imaging of the serotonin 1A receptor (5HT1AR) may predict antidepressant response.MethodsA total of 20 participants with BD in a current major depressive episode and 16 healthy volunteers had PET imaging with [11C]CUMI-101, employing a metabolite-corrected input function for quantification of binding potential to the 5HT1AR. Bipolar participants then received an open-labeled, 6-week clinical trial with a selective serotonin reuptake inhibitor (SSRI) in addition to their mood stabilizer. Clinical ratings were obtained at baseline and during SSRI treatment.ResultsPretreatment binding potential (BPF) of [11C]CUMI-101 was associated with a number of pretreatment clinical variables within BD participants. Within the raphe nucleus, it was inversely associated with the baseline Montgomery Åsberg Rating Scale (P = .026), the Beck Depression Inventory score (P = .0023), and the Buss Durkee Hostility Index (P = .0058), a measure of lifetime aggression. A secondary analysis found [11C]CUMI-101 BPF was higher in bipolar participants compared with healthy volunteers (P = .00275). [11C]CUMI-101 BPF did not differ between SSRI responders and non-responders (P = .907) to treatment and did not predict antidepressant response (P = .580). Voxel-wise analyses confirmed the results obtained in regions of interest analyses.ConclusionsA disturbance of serotonin system function is associated with both the diagnosis of BD and its severity of depression. Pretreatment 5HT1AR binding did not predict SSRI antidepressant outcome.The study was listed on clinicaltrials.gov with identifier NCT02473250.

Dataset Information

Positron emission tomography quantification of serotonin-1A receptor binding in medication-free bipolar depression.

Publications

Positron emission tomography quantification of serotonin-1A receptor binding in medication-free bipolar depression.

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