Relations between cortical thickness, serotonin 1A receptor binding, and structural connectivity: A multimodal imaging study

Serotonin 1A (5-HT_1A) receptors play a direct role in neuronal development, cell proliferation, and dendritic branching. We hypothesized that variability in 5-HT_1A binding can affect cortical thickness, and may account for a subtype of major depressive disorder (MDD) in which both are altered. To evaluate this, we measured cortical thickness from structural magnetic resonance imaging (MRI) and 5-HT_1A binding by positron emission tomography (PET) in an exploratory study. To examine a range of 5-HT_1A binding and cortical thickness values, we recruited 25 healthy controls and 19 patients with MDD. We hypothesized increased 5-HT_1A binding in the raphe nucleus (RN) would be negatively associated with cortical thickness due to reduced serotonergic transmission. Contrary to our hypothesis, raphe 5-HT_1A binding was positively correlated with cortical thickness in right posterior cingulate cortex (PCC), a region implicated in the default mode network. Cortical thickness was also positively correlated with 5-HT_1A in each cortical region. We further hypothesized that the strength of 5-HT_1A-cortical thickness correlation depends on the number of axons between the raphe nucleus and each region. To explore this we related 5-HT_1A–cortical thickness correlation coefficients to the number of tracts connecting that region and the raphe, as measured by diffusion tensor imaging (DTI) in an independent sample. The 5-HT_1A–cortical thickness association correlated significantly with the number of tracts to each region, supporting our hypothesis. We posit a defect in the raphe may affect the PCC within the default mode network in MDD through serotonergic fibers, resulting in increased ruminative processing.