Evaluation of serotonin 1A receptor binding in diabetes and depression

Introduction

Research has shown a greater prevalence of depression in diabetes. It is estimated that 20% of diabetics will develop clinical depression during their lives, as compared to 5–10% of the general population. Animal models have shown hyperglycemia-induced alterations in the serotonin system, as well as structural and functional alterations in hippocampus. Positron emission tomography (PET) imaging studies have indicated altered serotonin-1A (5-HT1A) receptor binding in healthy depressed subjects relative to controls. The aim of the present study was to assess 5-HT1A receptor binding in Type 2 (NIDDM) diabetics, with and without depression. Methods. PET and [carbonyl-C-11]WAY 100635 were used to measure 5-HT1A receptor binding in non-depressed (NDD: n=15, 8 M, 56±10 yrs) and depressed (DD: n=8, 3 M, 63±11 yrs) Type 2 diabetics and medically healthy non-depressed controls (Cont: n=10, 3 M, 66±11 yrs). The depressed diabetics were free of anti-depressant medication at the time of the PET study. The Type 2 subjects were without major medical complications. PET and arterial blood data were acquired over 90 min (ECAT HR+, 15 mCi). The Logan graphical analysis (GLLS smoothing [1]) was used to determine regional binding potential (BP) measures that were based upon distribution volume (DV) ratios with the cerebellar DV as non-specific reference. Data were corrected for cerebral atrophy. Results. The dorsal raphe BP value was greatest for depressed diabetics (DRN BP: DD=5.0±0.7, NDD=4.1±1.4, Cont=3.8±0.7). Regression analysis, that controlled for body-mass index, indicated significantly greater DRN BP for depressed diabetics relative to non-depressed diabetics (p=0.01). The hippocampal BP was greatest for the non-depressed diabetics (HIP BP: NDD=11.3±3.6, DD=9.4±2.6, Cont=8.4±2.9) and different between NDD and control subjects (p<0.05). Trend level differences (p∼0.1) were observed, between the diabetic groups, in lateral orbital frontal cortex and occipital. No group differences were evident for the cerebellar DV values (DD: 0.77±0.31, NDD: 0.81±0.34, Cont: 0.89±0.43). Conclusion. These findings suggest that depression in diabetes is not associated with widespread decreases in 5-HT1A receptor binding, relative to non-depressed diabetics. The results further suggest that alterations in serotonergic neurotransmission in diabetes and depression are consistent with reduced hippocampal neurotransmission via both lower hippocampal and greater DRN 5-HT1A receptor binding.