Original articleAltered Serotonin 1A Binding in Major Depression: A [carbonyl-C-11]WAY100635 Positron Emission Tomography Study
Section snippets
Subjects
Twenty eight subjects who met DSM-IV(American Psychiatric Association 1994) criteria for a current major depressive episode and 43 control subjects were included in this study. Inclusion criteria were assessed through history, chart review, Structured Clinical Interview for DSM IV (SCID I) (First et al 1995), review of systems, physical examination, routine blood tests, pregnancy test, urine toxicology and EKG. The Beck Depression Inventory (BDI) (Beck et al 1961), Hamilton Depression Rating
Comparison of Depressed Subjects with Controls
Across all regions there was no difference in BP between controls and MDD subjects using a test for mean within the mixed effects model (F = 1.028, df = 1, 68, p = .235; Figure 1).
Effects of Previous Exposure to Antidepressants
Dividing the MDD group into antidepressant naive (AN) and subjects with antidepressants exposure (AE), and including the controls, there is a significant group effect within the mixed effects model (F = 4.60, df = 2, 67, p = .013, Figure 2). Post-hoc analysis applying a one-way model to each region reveals a
Discussion
We report no differences in BP in MDD subjects compared to controls but significantly higher BP in never medicated MDD subjects during a MDE compared with controls and MDD subjects previously treated with antidepressants. We find a trend for the higher expressing GG (-1019) promoter genotype to be more common in MDD and to correlate with higher BP.
Limitations
While this is the largest sample size of MDD subjects (n = 28) and controls (n = 43) ever reported, when broken down in to AN (n = 13) and AE (n = 15), our sample sizes are still comparable to a publication with a mixed unipolar (n = 8) and bipolar population (n = 4, Drevets et al 1999) and a second with 15 unmedicated subjects (Sargent et al 2000). The subjects were treated naturalistically in the community with a variety of classes of antidepressants. Future prospective studies can be
Conclusions
We found increased 5-HT1A BP in all brain regions of antidepressant naive depressed subjects compared to controls and to previously treated depressed subjects. This may be due to greater gene expression. More autoreceptor binding may result in less serotonin neuron firing and hypofunction consistent with the indoleamine hypothesis of major depression. Reversal of that effect by antidepressant medications may exert an antidepressant effect in some subjects but perhaps not in treatment resistant
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