Neural Correlates of Suicidal Behavior in Youth

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:

• To identify electrophysiological markers of suicidality using MEG, including oscillatory dynamics and network connectivity patterns.
• To examine neuroimaging correlates of suicide risk, including functional connectivity, brain activation during future thinking tasks, and metabolic measures obtained through MRS.
• 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.

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