(185) Long-term Transcriptomic Changes in Patients with Suicidal Ideation

Background: Suicide is a multifactorial event with biological and psychosocial factors. Identifying the molecular basis of suicidal ideation (SI) may provide targets for the development of novel treatment strategies and identify patients at risk of suicide.1-2 We aimed to longitudinally characterize the transcriptomic dynamics of peripheral blood mononuclear cells (PBMCs) in hospitalized patients with mood disorders admitted due to acute SI. 

Methods: We recruited forty-two patients with mood disorders, ages 18 or older, hospitalized with SI (Beck Scale for Suicidal Ideation (BSS) >4). All subjects provided blood samples upon admission (T1) and immediately before discharge (T2). Bulk and single-cell RNA sequencing was performed at the two time points in N=15 and N=3 patients with significant improvement of SI ( >50% of reduction in BSS scores between T1 and T2), respectively, using Illumina 2x150bp sequencing and 10X Genomics ChromiumTM3’ system. Paired analysis compared gene expression between T1 and T2 with correction for multiple comparisons. 

Results: Twenty-six patients showed significant improvement of SI during hospitalization (mean(SD) BSS scores were 17.8(8.31) at T1 and 1.0(4.75) at T2). Three genes were differentially expressed between T1 and T2 (FDR=0.10) in patients that showed SI improvement, including ZNF704 (logFC=1.70), STMN1 (logFC=0.49), and DDIT4 (logFC=0.67). Changes in BSS significantly correlated with changes in ZNF704 expression (r=0.597,p=0.019). The levels of B-cells and monocytes were significantly down-regulated at T2 compared to T1, while the levels of natural killer (NK) and T-cells were up-regulated (p< 0.05). 

Discussion: This study investigated the longitudinal transcriptomic profile of PBMCs in mood disorder patients hospitalized for acute SI. Our findings provide preliminary evidence for the potential of peripheral blood gene expression as a biomarker for monitoring SI and treatment response. Three genes were identified to be associated with significant SI improvement. Notably, changes in ZNF704 expression significantly correlated with BSS score changes, suggesting a potential role in targeting SI severity. We observed significant changes in blood cell composition following SI improvement. This suggests a potential link between immune system activity and SI resolution. 

Conclusions: SI symptom improvement could not be predicted by demographic and clinical variables at baseline, however was associated with significant blood transcriptomic changes. Symptom improvement was associated with major blood cell changes and specific changes in monocyte subtypes.   

References:  

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   Johnston JN, Campbell D, Caruncho HJ, Henter ID, Ballard ED, Zarate CA. Suicide Biomarkers to Predict Risk, Classify Diagnostic Subtypes, and Identify Novel Therapeutic Targets: 5 Years of Promising Research. Int J Neuropsychopharmacol. 2022 Mar 17;25(3):197-214.