ÌÇÐÄvlog

QuestionÌý Is elevated translocator protein (TSPO) binding, a putative measure of neuroinflammation, associated with increased risk of suicide under conditions of stress in individuals with depression?

FindingsÌý In this cross-sectional study of 53 adults with major depressive disorder, elevated TSPO binding, measured in vivo with ¹¹C-ER176 positron emission tomography total volume of distribution, was associated with more pronounced daily suicidal ideation and negative affect in the context of real-world stressors.

MeaningÌý The findings suggest that elevated brain TSPO binding in individuals with depression may be an indicator of vulnerability to acute stress-related increases in suicidal ideation and negative affect, thereby raising risk of suicide.

ImportanceÌý 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.

ObjectiveÌý 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 ParticipantsÌý 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.

ExposuresÌý All participants underwent positron emission tomography imaging of TSPO binding with ¹¹C-ER176 and concurrent arterial blood sampling.

Main Outcome and MeasuresÌý A weighted average of ¹¹C-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.

ResultsÌý In the overall sample of 53 participants (mean [SD] age, 29.5 [9.8] years; 37 [69.8%] female and 16 [30.2%] male), ¹¹C-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 ¹¹C-ER176 V_T (β, 0.21; 95% CI, 0.01 to 0.98; P = .045). In 21 participants who completed EMA, ¹¹C-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 < .001, respectively).

Conclusion and RelevanceÌý 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.