Biomarkers as Predictors of Suicidal Risk in Adolescents
Condition: Suicide, Attempted; Suicidal Ideation; Suicidal Intention; Suicide
MeSH terms: Suicide; Suicidal Ideation; Suicide, Attempted
Study type: Observational

Summary: 
      Suicide is one of the most devastating events in society at all levels. The primary goal of
      this study is to predict suicide in adolescents at risk. We will utilize blood biomarker
      measurement and clinical risk factor scales to develop a tool to identify adolescents at risk
      for suicide earlier, which will allow clinicians to prescribe timely treatment and prevent
      suicide.
    

Detailed description: 
      Suicide, the second leading cause of death in adolescents (15-24 year olds), is the most
      tragic complication of a psychiatric condition in this age group. Every year, approximately
      157,000 youth receive medical care for suicide related injuries at emergency departments
      throughout the U.S. Despite some progress, suicide prevention continues to be a daunting
      task. In adolescents, the risk of a second suicide attempt is approximately 30% after
      discharge from an inpatient psychiatric unit. Up to 80% of suicidal patients who subsequently
      died by suicide deny suicidal ideation in their last communication with a health care
      provider. Therefore, there is an urgent need for the development of biomarkers that can
      objectively identify which youth are most likely to engage in subsequent suicide attempts.

      Several lines of evidence (postmortem studies, genetic studies, biomarker studies) as well as
      preliminary studies conducted by our group have pointed to neuroinflammation as one of the
      neurobiological findings observed in suicidal behavior. In particular, the principal
      investigator and co- investigators have identified S100B - an astrocytic protein, which is a
      marker of blood brain barrier (BBB) impairment, as a novel biomarker associated with
      suicidality in adolescents. We are now also investigating three additional and important
      markers Kynurenic Acid (KYNA), Quinolinic Acid (QUIN), and Picolinic Acid (PIC) identified by
      Dr. Lena Brundin (Van Andel Institute) to be altered in patients after a suicide attempt.
      Other studies have reported several other peripheral inflammatory markers (PlMs) including
      interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) as
      associated with suicidality. Hence, PlMs either on their own or along with clinical markers
      may be particularly useful in predicting future suicide attempts. This study will investigate
      whether PIM levels, with or without clinical predictors, can be useful at the time of
      discharge from an inpatient psychiatric unit to predict suicidality in adolescent patients in
      the subsequent 12 months. The first aim of this study is to determine whether plasma levels
      of S100B, IL-1ß, IL-6, TNF-α, KYNA, QUIN, and PIC correlate with suicidal behavior (SB).
      Secondly, this study will investigate if any of the PlMs can predict suicidal attempts.
      Finally, we will test which combination of clinical risk factors and PlMs is able to most
      efficiently predict SB post-discharge from the inpatient unit.

      Innovative aspects of this study include: 1) The first study to longitudinally investigate
      levels of PlMs at the time of admission and their change at the time of discharge in
      adolescent patients being admitted for SB. 2) The first study to investigate whether level of
      PIMS (alone or in combination with clinical risk factors) at the time of discharge can
      predict readmissions for SB in the next 12 months. 3) Beside the well-studied PIMs in adult
      samples, specifically investigate novel biomarkers of inflammation- S100B and 3 markers of
      the Kynurenine pathway (KYNA, QUIN and PIC).
    

Intervention name(s): Clinical assessments and blood samples; follow-up for 12 mos; Clinical assessments and blood samples; no 12mo follow-up
Intervention type(s): Other; Other
Intervention description(s): Kiddie-Sads Present and Lifetime Version Diagnostic Interview, Columbia-Suicide Severity Rating Scale, Suicidal Ideation Questionnaire, Children's Depression Rating Scale-Revised, Multidimensional Anxiety Scale for Children (2nd Ed), Adverse Childhood Experiences Questionnaire, Life Events Checklist-5, Pubertal Development Scale. All assessments administered at baseline, and a smaller subset of assessments administered at discharge and other time points throughout 12 months follow-up. Blood samples taken at baseline (admission to unit) and day of discharge.; Kiddie-Sads Present and Lifetime Version Diagnostic Interview, Columbia-Suicide Severity Rating Scale, Suicidal Ideation Questionnaire, Children's Depression Rating Scale-Revised, Multidimensional Anxiety Scale for Children (2nd Ed), Adverse Childhood Experiences Questionnaire, Life Events Checklist-5, Pubertal Development Scale. All assessments administered at baseline, and a smaller subset of assessments administered at discharge time point (5-7 days after baseline). Blood samples taken at baseline and discharge time points (5-7 days after baseline).
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The suicide attempt study group will be recruited from all patients (ages 12-18 years)
        admitted to the Cleveland Clinic inpatient child and adolescent psychiatry unit after a
        suicide attempt. Healthy adolescent control group (ages 12-18 years) will be recruited
        through the Cleveland Clinic pediatric outpatient offices.
      
Biospecimen description: 
      Plasma and serum
    
Keywords: Adolescent; Biological Markers; Biomarkers; Biomarkers for suicidality; Blood brain barrier; Clinical predictors; Cytokine; Feeling suicidal; Inflammation; Inflammatory marker; Inpatient discharge; Interleukin-1 beta; IL-1ß; Interleukin-6; IL-6; Kynurenic acid; Kynurenine pathway; Neuroinflammation; Novel marker; Peripheral blood biomarkers; Picolinic acid; Plasma biomarker; Psychiatric inpatient; S100B; Serum biomarker; Stress; Suicide; Suicidal behavior; Suicidal risk; Tumor necrosis factor alpha; TNF-α