Neuroinflammation, Stress-Related Suicidal Ideation, and Negative Mood in Depression
Authors: Sarah Herzog, Elizabeth A. Bartlett, Francesca Zanderigo, Hanga C. Galfalvy, Ainsley Burke, Akiva Mintz, Mike Schmidt, Eric Hauser, Yung-yu Huang, Nadine Melhem, M. Elizabeth Sublette, Jeffrey M. Miller, J. John Mann
Journal: JAMA Psychiatry (2024)

Importance Brain translocator protein 18k Da (TSPO) binding, a putative marker of neuroinflammatory processes (eg, gliosis), is associated with stress and elevated in depressed and suicidal populations. However, it is unclear whether neuroinflammation moderates the impact of daily life stress on suicidal ideation and negative affect, thereby increasing risk for suicidal behavior. Objective To examine the association of TSPO binding in participants with depression with real-world daily experiences of acute stress-related suicidal ideation and negative affect, as well as history of suicidal behavior and clinician-rated suicidal ideation. Design, Setting, and Participants Data for this cross-sectional study were collected from June 2019 through July 2023. Procedures were conducted at a hospital-based research center in New York, New York. Participants were recruited via clinical referrals, the Columbia University research subject web portal, and from responses to internet advertisements. Of 148 participants who signed informed consent for study protocols, 53 adults aged 18 to 60 years who met DSM-5 diagnostic criteria for current major depressive disorder completed procedures with approved data and were enrolled. Participants were free of schizophrenia spectrum disorders, active physical illness, cognitive impairment, and substance intoxication or withdrawal at the time of scan. Exposures All participants underwent positron emission tomography imaging of TSPO binding with 11 C-ER176 and concurrent arterial blood sampling. Main Outcome and Measures A weighted average of 11 C-ER176 total distribution volume (V T ) was computed across 11 a priori brain regions and made up the primary outcome measure. Clinician-rated suicidal ideation was measured via the Beck Scale for Suicidal Ideation (BSS). A subset of participants (n = 21) completed 7 days of ecological momentary assessment (EMA), reporting daily on suicidal ideation, negative affect, and stressors. Results In the overall sample of 53 participants (mean [SD] age, 29.5 [9.8] years; 37 [69.8%] female and 16 [30.2%] male), 11 C-ER176 V T was associated at trend levels with clinician-rated suicidal ideation severity (β, 0.19; 95% CI, −0.03 to 0.39; P = .09) and did not differ by suicide attempt history (n = 15; β, 0.18; 95% CI, −0.04 to 0.37; P = .11). Exploratory analyses indicated that presence of suicidal ideation (on BSS or EMA) was associated with higher 11 C-ER176 V T (β, 0.21; 95% CI, 0.01 to 0.98; P = .045). In 21 participants who completed EMA, 11 C-ER176 V T was associated with greater suicidal ideation and negative affect during EMA periods with stressors compared with nonstress periods (β, 0.12; SE, 0.06; 95% CI, 0.01 to 0.23; P = .03 and β, 0.19; SE, 0.06; 95% CI, 0.08 to 0.30; P &amp;amp;lt; .001, respectively). Conclusion and Relevance TSPO binding in individuals with depression may be a marker of vulnerability to acute stress-related increases in suicidal ideation and negative affect. Continued study is needed to determine the causal direction of TSPO binding and stress-related suicidal ideation or negative affect and whether targeting neuroinflammation may improve resilience to life stress in patients with depression.