Elsevier

Biological Psychiatry

Volume 68, Issue 2, 15 July 2010, Pages 170-178
Biological Psychiatry

Archival Report
Higher Serotonin 1A Binding in a Second Major Depression Cohort: Modeling and Reference Region Considerations

https://doi.org/10.1016/j.biopsych.2010.03.023Get rights and content

Background

Serotonin 1A receptors (5-HT1A) are implicated in major depressive disorder (MDD). We previously reported higher 5-HT1A binding potential (BPF) in antidepressant naive MDD subjects compared with control subjects, while other studies report lower BPND. 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.

Methods

Nine new control subjects and 22 new not recently medicated (NRM) MDD subjects underwent positron emission tomography. BPF and BPND were determined using a metabolite and free fraction corrected arterial input function. BPND was also determined using cerebellar gray matter (CGM) and cerebellar white matter (CWM) reference regions as input functions.

Results

BPF 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. BPF was higher in the NRM compared with control subjects (p = .0001). Neither BPND using CWM (p = .86) nor volume of distribution (VT) (p = .374) differed between groups. When CGM was used, the NRM group had lower 5-HT1A BPND compared with control subjects (p = .03); CGM VT was higher in NRM compared with control subjects (p = .007).

Conclusions

Choice of reference region and outcome measure can produce different 5-HT1A findings. Higher 5-HT1A BPF in MDD was found with the method with fewest assumptions about nonspecific binding and a reference region without receptors.

Section snippets

Subjects

Thirty subjects who met DSM-IV (17) criteria for a current major depressive episode and 51 control subjects were included. Inclusion criteria were assessed through history, chart review, Structured Clinical Interview for DSM-IV Axis I Disorders (18), review of systems, physical examination, routine blood tests, pregnancy test, urine toxicology, and electrocardiogram. The Beck Depression Inventory (19), Hamilton Depression Rating Scale (20), and Global Assessment Scale (21) assessed subjective

Replication

The previous cohort NRM have higher [11C]WAY-100635 BPF compared with previous control subjects (df = 1,48; F = 4.621; p = .037). The new cohort NRM have higher [11C]WAY-100635 BPF compared with the new control subjects (df = 1,29; F = 4.606; p = .04; Figure 1). Combining the previous and new cohort NRM and control subjects, the NRM have higher BPF than control subjects (df = 1,79; F = 17.77; p = .0001; Figure 2). As mentioned above, groups differed in ID and IM. When IM is added to the model,

Replication

We sought to replicate our findings and to reconcile our data with previous publications. In the previous cohort, new cohort, and the combined cohort of 51 control subjects and 30 NRM MDD subjects, NRM have higher 5-HT1A BPF compared with control subjects (Figure 1). This was the case even though the second cohort included only nine healthy control subjects. Strikingly, the magnitude of difference between control and NRM MDD subjects is nearly identical to that observed in the previous cohort

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