Neural Correlates of Suicidal Behavior in Youth

Neural Correlates of Suicidal Behavior in Youth: a Pre and Post CAMS Therapy Neuroimaging Study

This study, titled "Neural Correlates of Suicidal Behavior in Youth: a Pre and Post CAMS Therapy Neuroimaging Study," aims to better understand the brain mechanisms underlying suicidal thoughts and behaviors in adolescents and young adults (ages 14-24). Suicide is a leading cause of death in this population, and current clinical approaches often fail to accurately predict or prevent suicidal behavior. This study seeks to identify objective neurobiological markers associated with suicide risk and treatment response.

Participants will be divided into three groups: (1) high-risk individuals recently hospitalized following a suicide attempt, (2) medium-risk individuals with chronic suicidal ideation but no attempts, and (3) low-risk healthy controls. All participants will undergo advanced neuroimaging, including magnetoencephalography (MEG) and magnetic resonance imaging (MRI), along with comprehensive psychiatric assessments.

The study focuses on brain regions and networks implicated in suicidality, including the anterior cingulate cortex and salience network, as well as neurochemical markers such as glutamate. It also examines electrophysiological activity and functional connectivity patterns associated with suicidal thoughts and behaviors.

High-risk participants will receive an evidence-based psychotherapy called the Collaborative Assessment and Management of Suicidality (CAMS). This therapeutic approach emphasizes collaboration between patient and clinician to identify and address the underlying drivers of suicidal thoughts, with a focus on increasing hope and reducing psychological distress. Neuroimaging and clinical assessments will be repeated after completion of CAMS to evaluate treatment-related changes.

The study's primary goals are to:

• Identify neural and electrophysiological correlates of suicide risk.
• Distinguish biological differences between individuals with suicidal ideation and those who have attempted suicide.
• Determine how CAMS therapy affects brain function and neurochemistry.

By integrating clinical and neurobiological data, this research aims to improve understanding of suicidality, enhance risk prediction, and inform more effective, personalized interventions for at-risk youth.

Study Overview

• Status: Not yet recruiting
• Conditions: Suicidal Ideation; Suicidal Behavior; Hopelessness; Suicide Attempt; Depression / Major Depressive Disorder; Neurobiological
• Intervention / Treatment: Behavioral: CAMS

Detailed Description

This research study, titled "Neural Correlates of Suicidal Behavior in Youth: a Pre and Post CAMS Therapy Neuroimaging Study," is designed to advance understanding of the neurobiological and clinical mechanisms underlying suicidal thoughts and behaviors in adolescents and young adults aged 14-24 years. Suicide is one of the leading causes of death in this age group, and current clinical tools are often insufficient for accurately predicting risk or preventing future suicide attempts. A major limitation in the field is the lack of objective biological markers that can identify individuals at highest risk and guide targeted treatment.

The overarching goal of this study is to investigate how brain structure, function, and neurochemistry differ across varying levels of suicide risk, and how these features change following an evidence-based suicide-specific psychotherapy. The study combines advanced neuroimaging techniques with detailed clinical assessments to provide a comprehensive, multimodal understanding of suicidality.

Participants will be divided into three groups (n=60 total, 20 per group):

• High Risk (HR): Individuals recently hospitalized following a suicide attempt and with a history of multiple attempts.
• Medium Risk (MedR): Individuals with chronic suicidal ideation lasting at least one year but no history of attempts.
• Minimal Risk (MinR): Healthy controls with no history of suicidal ideation or behavior and no psychiatric treatment.

All participants will complete baseline assessments including structured psychiatric interviews and validated rating scales measuring depression, hopelessness, suicidal ideation, and overall functioning. Neuroimaging will include magnetoencephalography (MEG) to measure real-time brain activity and MRI-based techniques such as resting-state functional MRI (rsfMRI), magnetic resonance spectroscopy (MRS), and task-based imaging focused on episodic future thinking.

The study specifically targets brain regions and networks implicated in suicide risk, including the anterior cingulate cortex (ACC), anterior insula (AI), salience network, and default mode network. These regions are associated with emotional regulation, self-referential thinking, and processing of future-oriented thoughts. Prior research suggests that abnormalities in these systems-such as altered connectivity, metabolic imbalances (e.g., glutamate levels), and disrupted electrophysiological patterns-may contribute to suicidal ideation and behavior.

A key component of the study is the examination of hopelessness, which is considered a central psychological factor in suicidality and a potential proxy for suicide risk. The study will explore how neural markers correlate with levels of hopelessness and how these relationships differ across risk groups.

Following baseline assessments, participants in the high-risk group will receive the Collaborative Assessment and Management of Suicidality (CAMS) intervention. CAMS is a structured, evidence-based psychotherapy that emphasizes collaboration between the patient and clinician to identify the personal drivers of suicidal thoughts. It uses the Suicide Status Form (SSF) to guide assessment, treatment planning, and ongoing monitoring. Core principles of CAMS include empathy, collaboration, honesty, and a direct focus on suicidality. Treatment typically involves weekly sessions and continues until the patient demonstrates reduced suicide risk and improved coping.

After completing CAMS therapy (typically 3-12 sessions), high-risk participants will undergo repeat neuroimaging and clinical assessments. This pre-post design allows researchers to evaluate how psychotherapy influences brain function, connectivity, and neurochemical markers, as well as clinical symptoms such as hopelessness and suicidal ideation.

The study has three primary aims:

1. To identify electrophysiological markers of suicidality using MEG, including oscillatory dynamics and network connectivity patterns.
2. To examine neuroimaging correlates of suicide risk, including functional connectivity, brain activation during future thinking tasks, and metabolic measures obtained through MRS.
3. To assess the effects of CAMS therapy on brain function and neurochemistry in high-risk individuals.

In addition to the main study, qualitative focus groups will be conducted with adolescents participating in an intensive outpatient program. These groups aim to gather patient perspectives on barriers to research participation and treatment engagement, helping to improve study design and clinical care approaches.

Data analysis will include comparisons across risk groups using statistical models such as ANOVA and regression analyses, as well as correlation analyses to examine relationships between clinical measures and neurobiological variables. Longitudinal analyses will evaluate changes following CAMS therapy.

The potential impact of this study is significant. By identifying objective neural markers associated with suicide risk and treatment response, the research could improve early detection of high-risk individuals and guide personalized interventions. Understanding how CAMS therapy produces changes in the brain may also help refine and optimize treatment strategies for suicidal youth.

Ultimately, this study aims to bridge the gap between clinical psychiatry and neuroscience, contributing to more effective, biologically informed approaches to suicide prevention in young people.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tatiana Falcone, M.D.; Phone Number: (216) 444-7459; Email: falcont1@ccf.org
• Study Contact Backup: Name: Christina A Deisz, LISW-S; Phone Number: (440) 225-6193; Email: deiszc@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
      • Contact: Tatiana Falcone, M.D.; Phone Number: (216) 444-7459; Email: falcont1@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects must be 14-24 years old

• Subjects must be:

  • High Risk Subjects: Psychiatrically admitted due to a suicide attempt or history of 2 previous suicide attempts
  • Medium Risk Subjects: Suicide ideation for the past year with no suicide attempt
  • Minimal Risk Subjects: No previous history of suicidal ideation or behavior, not taking any psychiatric history or medication, and no family history of suicide
• Subjects must have the ability to understand and the willingness to sign a written informed consent/assent document
• Subjects must be English speaking

Exclusion Criteria:

• Subjects with known history of Autism Spectrum Disorder; non-verbal patients
• Subjects with moderate or severe intellectual disability (IQ less than 70 and those patients in special education classes full time)
• Subjects with Schizophrenia or history of any type of psychosis including mood related psychosis and brief reactive psychosis
• Within 6 months before initial screening, urine toxicology positive for phencyclidine, cocaine or amphetamines (subjects prescribed amphetamines for the management of ADHD will not be excluded)
• Subjects with a history of moderate or severe substance or alcohol use per DSM-5 criteria in the past 6 months
• Subjects who are currently pregnant or breastfeeding
• Subjects in custody of Children's Services
• Subjects with recent bone, tendon, spine or joint surgery
• Subjects with recent metallic dental implants
• Subjects weighing less than 30 kg or more than 200 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High risk (HR); patients discharged within 1 week from the hospital for a SA and with a history of 2 previous SAs	Behavioral: CAMS; CAMS weekly sessions will be started immediately as an inpatient at the start of the study for the high risk participants. CAMS will be continued weekly after the patient is discharged and followed up as an outpatient. Weekly CAMS sessions will be terminated after the subject, as an outpatient, has three consecutive outpatient CAMS sessions with an overall risk < 2 (# 6 on the SSF Core Assessment) along with a positive response regarding their thoughts/feelings and clinician indicating behavioral stability (suicidal behavior).
No Intervention: Medium risk (MedR); patients with 1 year history of SI with no attempts
No Intervention: Minimal risk (MinR); age-matched controls with no prior history of SI or behavior, not taking any psychotropic medication and no family history of suicide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MEG and suicidality	Measure the difference on the connectivity within the salience network. This will be quantified using phase-locking values (PLV) across different frequency bands in 10-second intervals. The average PLV-based connectivity will serve as an electrophysiological biomarker for correlation with SI. To test hypothesis 1, salience network connectivity will be compared between groups using ANOVA.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Suicidality & network connectivity	To study the relationship of suicidality with network connectivity, activation during an episodic future thinking task, and MRS measures. To test this, activation strength of the ventral medial prefrontal cortex will be tested using a between-group ANOVA. Using the MRS voxel locations as a guide, functional connectivity between the pregenual anterior cingula cortex and anterior insula will be calculated. Glutamine and myo-inositol levels and rsfMRI strength will be compared using between-group ANOVAs.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAMS on MEG and MRS metabolites	To investigate the the changes of Baseline SSF scoring before and after CAMS on MEG and MRS metabolites in the HR group. MRS measures of Glutamine and myo-inositol and MEG salience network measures will be tested using a repeated measures ANOVA. To test this, the change in Glutamine and myo-inositol levels will be calculated and correlated with measures of hopelessness and SI using the Beck Hopelessness Scale and Optimism and Hope scale along with the Beck SSI.	5 years

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: MQ Mental Health Research
• Investigators: Principal Investigator: Tatiana Falcone, M.D., The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Estimated): April 13, 2026
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): October 1, 2031

Study Registration Dates

• First Submitted: April 10, 2026
• First Submitted That Met QC Criteria: April 29, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Suicidal behavior; Neuroimaging; Suicidal ideation; Hopelessness; Suicide attempt; Youth suicide; CAMS therapy
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Self-Injurious Behavior; Mood Disorders; Suicide; Depressive Disorder; Behavior; Suicidal Ideation; Depression; Depressive Disorder, Major; Suicide, Attempted
• Other Study ID Numbers: IRB 25-894

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No