In vivo serotonin transporter and 1A receptor binding potential and ecological momentary assessment (EMA) of stress in major depression and suicidal behavior.

We examined relationships between the serotonin system and stress in major depression and suicidal behavior. Twenty-five medication-free depressed participants (13 suicide attempters) underwent same-day [C]DASB and [C]CUMI-101 positron emission tomography (PET) imaging. Binding potential (BP) to the serotonin transporter (5-HTT) and serotonin 1A (5-HT) receptor, respectively, was quantified using the NRU 5-HT atlas, reflecting distinct spatial distributions of multiple serotonin targets. Ecological momentary assessment (EMA) measured current stress over one week proximal to imaging. EMA stress did not differ between attempters and non-attempters. In all depressed participants, 5-HTT and 5-HT BP were unrelated to EMA stress. There were region-specific effects of 5-HTT (p=0.002) and 5-HT BP (p=0.03) in attempters vs. nonattempters. In attempters, region-specific associations between 5-HTT (p=0.03) and 5-HT (p=0.005) BP and EMA stress emerged. While no post-hoc 5-HTT BP correlations were significant, 5-HT BP correlated positively with EMA stress in attempters in 9/10 regions (p-values<0.007), including the entire cortex except the largely occipital region 5. Brodmann-based regional analyses found diminished effects for 5-HTT and subcortically localized positive corrrelations between 5-HT and EMA stress, in attempters only. Given comparable depression severity and childhood and current stress between attempters and nonattempters, lower 5-HTT binding in attempters vs. nonattempters may suggest a biological risk marker. Localized lower 5-HTT and widespread higher 5-HT binding with stress among attempters specifically may suggest that a serotonergic phenotype might be a key determinant of risk or resiliency for suicidal behavior.