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Higher serotonin 1A binding in a second major depression cohort: modeling and reference region considerations.

ABSTRACT: Serotonin 1A receptors (5-HT(1A)) are implicated in major depressive disorder (MDD). We previously reported higher 5-HT(1A) binding potential (BP(F)) in antidepressant naive MDD subjects compared with control subjects, while other studies report lower BP(ND). Discrepancies can be related to differences in study population or methodology. We sought to replicate our findings in a novel cohort and determine whether choice of reference region and outcome measure could explain discrepancies.Nine new control subjects and 22 new not recently medicated (NRM) MDD subjects underwent positron emission tomography. BP(F) and BP(ND) were determined using a metabolite and free fraction corrected arterial input function. BP(ND) was also determined using cerebellar gray matter (CGM) and cerebellar white matter (CWM) reference regions as input functions.BP(F) was higher in the new NRM cohort (p = .037) compared with new control subjects, comparable to the previous cohort (p = .04). Cohorts were combined to examine the reference region and outcome measure. BP(F) was higher in the NRM compared with control subjects (p = .0001). Neither BP(ND) using CWM (p = .86) nor volume of distribution (V(T)) (p = .374) differed between groups. When CGM was used, the NRM group had lower 5-HT(1A) BP(ND) compared with control subjects (p = .03); CGM V(T) was higher in NRM compared with control subjects (p = .007).Choice of reference region and outcome measure can produce different 5-HT(1A) findings. Higher 5-HT(1A) BP(F) in MDD was found with the method with fewest assumptions about nonspecific binding and a reference region without receptors.

SUBMITTER: Parsey RV

PROVIDER: S-EPMC2900398 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Higher serotonin 1A binding in a second major depression cohort: modeling and reference region considerations.

Parsey Ramin V RV Ogden R Todd RT Miller Jeffrey M JM Tin Adrienne A Hesselgrave Natalie N Goldstein Ellen E Mikhno Arthur A Milak Matthew M Zanderigo Francesca F Sullivan Gregory M GM Oquendo Maria A MA Mann J John JJ

Biological psychiatry 20100523 2

<h4>Background</h4>Serotonin 1A receptors (5-HT(1A)) are implicated in major depressive disorder (MDD). We previously reported higher 5-HT(1A) binding potential (BP(F)) in antidepressant naive MDD subjects compared with control subjects, while other studies report lower BP(ND). Discrepancies can be related to differences in study population or methodology. We sought to replicate our findings in a novel cohort and determine whether choice of reference region and outcome measure could explain disc ...[more]

PMID: 20497898

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Project description:BackgroundWe previously reported higher serotonin 1A receptor (5-HT1A) binding in subjects with major depressive disorder (MDD) during a major depressive episode using positron emission tomography imaging with [(11)C]WAY-100635. 5-HT1A receptor binding is also associated with treatment outcome after nonstandardized antidepressant treatment. We examined whether pretreatment 5-HT1A binding is associated with treatment outcome following standardized escitalopram treatment in MDD. We also compared 5-HT1A binding between all MDD subjects in this cohort and a sample of healthy control subjects.MethodsTwenty-four MDD subjects in a current major depressive episode and 51 previously studied healthy control subjects underwent positron emission tomography scanning with [(11)C]WAY-100635, acquiring a metabolite-corrected arterial input function and free-fraction measurement to estimate 5-HT1A binding potential (BPF = Bmax/KD, where Bmax = available receptors and KD = dissociation constant). Major depressive disorder subjects then received 8 weeks of treatment with escitalopram; remission was defined as a posttreatment 24-item Hamilton Depression Rating Scale <10 and ≥ 50% reduction in Hamilton Depression Rating Scale.ResultsRemitters to escitalopram had 33% higher baseline 5-HT1A binding in the raphe nuclei than nonremitters (p = .047). Across 12 cortical and subcortical regions, 5-HT1A binding did not differ between remitters and nonremitters (p = .86). Serotonin 1A receptor binding was higher in MDD than control subjects across all regions (p = .0003). Remitters did not differ from nonremitters in several relevant clinical measures.ConclusionsElevated 5-HT1A binding in raphe nuclei is associated with subsequent remission with the selective serotonin reuptake inhibitor escitalopram; this is consistent with data from a separate cohort receiving naturalistic antidepressant treatment. We confirmed our previous findings of higher 5-HT1A binding in current MDD compared with control subjects.

Dataset Information

Higher serotonin 1A binding in a second major depression cohort: modeling and reference region considerations.

Publications

Higher serotonin 1A binding in a second major depression cohort: modeling and reference region considerations.

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