Biomarkers as Predictors of Suicidal Risk in Adolescents

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).

Inclusion criteria

Suicide Attempt Study Group:

• 12-18 years of age
• admitted to the Cleveland Clinic inpatient child and adolescent psychiatry unit after suicidal ideations or a suicide attempt

Healthy Control Group:

• 12-18 years of age
• No history of suicide attempt

Exclusion criteria

Suicide Attempt Study Group:

• History of autism spectrum disorder
• Non-verbal
• Moderate or severe intellectual disability (IQ<70 and patients in special education full-time)
• Schizophrenia or schizoaffective disorder diagnosis
• Current diagnosis of anorexia or bulimia
• History of generalized tonic-clonic epileptic seizures in last 3 months (If patient does not have a history of seizures, and generalized tonic-clonic seizure was clinically determined to be caused by patient's recent overdose attempt, patient can still be recruited for study if 24 hours has passed since last seizure)
• History of traumatic brain injury, brain tumor, or any major neurological disorder
• Delirium or mood disorder secondary to general medical condition
• Current infection, fever, antibiotic use in the last 2 weeks
• History of autoimmune or immunodeficiency diseases
• Current untreated major endocrine disorder
• Current pregnancy or delivery within the last month
• Diagnosed malnutrition
• Positive urine toxicology for benzodiazepines or opiates on admission
• Current substance use disorder diagnosis and referral for CD assessment upon discharge
• Current diagnosis of morbid obesity or a current BMI greater than 40 kg/m2
• Abnormal complete blood count (CBC)

Healthy Control Group:

• History of any psychiatric diagnosis / treatment (behavioral diagnoses [ADD/ADHD/etc] are okay)
• History of suicidal ideation, behavior, or attempt
• Family history of suicide attempts
• Diagnosis of schizophrenia or bipolar disorder in parents or siblings
• History of autism spectrum disorder
• Moderate or severe intellectual disability (IQ<70 and patients in special education full-time)
• History of generalized tonic-clonic epileptic seizures in last 3 months
• History of headaches or migraines in the last month
• History of traumatic brain injury, brain tumor, or any major neurological disorder
• Delirium or mood disorder secondary to general medical condition
• Current infection, fever, antibiotic use in the last 2 weeks
• History of autoimmune or immunodeficiency diseases
• Current untreated major endocrine disorder
• Current pregnancy or delivery within the last month
• Diagnosed malnutrition
• Report of any substance use in week prior