Adverse Adolescent Pathways to Substance Use

BEHAVIORAL

Trier Social Stress Test

Psychosocial stress procedure; 5 minutes of public speaking (preceded by 5 minutes of preparation) and 5 minutes of mental arithmetic.

Reaction time during the functional magnetic resonance imaging (FMRI) Stop Signal Task

Time frame: baseline, 12-months, 24-months

The Stop Signal Task is a measure of inhibitory control. Participants are presented with a right or left arrow and instructed to press one of two buttons corresponding with each arrow after it is presented. However, on certain trials, there is an up facing arrow immediately following the presentation of a left or right arrow, and participants are instructed to not press any buttons if they see an up arrow. The task measures the mean go reaction time to evaluate the participant's ability to inhibit when the up arrow is presented, with faster reaction times (measured in milliseconds) meaning lower inhibition.

Percent signal change during the FMRI Stop Signal Task

Time frame: baseline, 12-months, 24-months

Neural activation during the Stop Signal Task is measured through determining the percent signal change from baseline FMRI resting state to neural activation during the Stop Signal Task, particularly in the front-striatal-thalamic regions. Higher percent signal change would indicate higher levels of activation during the task. Percent signal change ranges between 1% to 5%.

Percent signal change activation during the No-stimuli, Predictable-stimuli, and Unpredictable-stimuli (NPU) task

Time frame: baseline, 12-months, 24-months

In the NPU task, participants are presented with fearful and neutral faces, with the fearful face presentation being sometimes cued with another associated visual stimuli immediately beforehand, and sometimes uncued and therefore unpredicted. This task measures cued anticipation of threat. The regions of interest are the intra-limbic regions, bed nucleus of the stria terminalis (BNST), and the amygdala. Higher percent signal change in these regions would indicate higher levels of activation during the task. Percent signal change ranges between 1% to 5%.

Percent signal change during the Attentional Load Paradigm (ALP) task

Time frame: baseline, 12-months, 24-months

In the ALP task, participants complete a letter search task while being presented with peripheral distractor letters on top of both fearful and neutral faces to evaluate the impact of perceptual load on the neural response to fearful vs neutral face distractors. The percent signal change will be specifically analyzed in the parietal and frontal cortices. Higher percent signal change in these regions would indicate higher levels of activation during the task. In addition, the ability to shift from affective-limbic to cognitive-pre-frontal cortex to complete the task will be evaluated as a key indicator of neural maturity. Percent signal change ranges between 1% to 5%.

Percent signal change during Emotional Face N-Back (EFNBack)

Time frame: baseline, 12-months, 24-months

In the EFNBack task, participants are shown images of emotionally salient (happy and fearful) and neutral faces as well as images of neutral places. Participants are instructed to determine whether each picture presented is a "Match" or a "No match". In the 0-back, low load condition, the "match" occurs when the picture presented is the same as a fixed target picture presented at the beginning. In the 2-back, high load condition, the "match" occurs when the picture presented is the same as the one shown two pictures ago. This task evaluates working memory and emotional regulation, as well as the percent signal change of the prefrontal cortex (PFC), amygdala, and anterior cingulate cortex (ACC), with higher percent signal change in these regions indicating higher levels of activation during the task. Percent signal change ranges between 1% to 5%.

Sympathetic and Parasympathetic nervous system ECG activation or heart rate variability (HRV) during a psychosocial stressful task (Trier Social Stress Test - TSST)

Time frame: at baseline, 12-month and 24-month

The Trier Social Stress Test for Children (TSST-C) -- a social stressor involving story telling in front of two neutral judges, preparation time and a cognitive stressor involving mental arithmetic-counting backward from 1023 by 13s -- is used to elicit physiological stress responses. The combination of stressors offers high levels of social-evaluative threat. The TSST-C will be administered in 4 parts: an anticipatory stress phase (5 min to prepare the speech); the speech task (5 min), the arithmetic task (5 min), and the recovery phase (up through 40 min post-task). For a five minute baseline period, and for the duration of the task, heart rate is measured to determine baseline resting state and HRV. HRV is the difference in the milliseconds between each heart beat. The higher the HRV, the more the nervous system is activated during the task. The level of HRV indicates the participant's nervous system response to stress.

Endocrine (cortisol) measures during a psychosocial stressful task (Trier Social Stress Test - TSST)

Time frame: at baseline, 12-month and 24-month

The Trier Social Stress Test for Children (TSST-C) -- a social stressor involving story telling in front of two neutral judges, preparation time and a cognitive stressor involving mental arithmetic-counting backward from 1023 by 13s-- is used to elicit physiological stress responses. The combination of these stressors offers elements of uncontrollability and high levels of social-evaluative threat. The TSST-C will be administered in 4 parts: an anticipatory stress phase (5 min to prepare the speech); the speech task (5 min), the arithmetic task (5 min), and the recovery phase (up through 40 min post-task). At rest, cortisol is collected through a saliva sample of passive drool. Then cortisol will be collected in 15 minute intervals for the duration of the task and recovery time. The higher the cortisol is found to be, the higher the stress response to the task.

Assessment of Liability and Exposure to Substance Use and Antisocial Behavior, Revised (ALEXSA-R)

Time frame: at baseline, 12-month and 24-month

The Assessment of Liability and Exposure to Substance use and Antisocial behavior, Revised (ALEXSA-R) is a system of youth-report measures of risks, resiliencies, risky health behavior. The youth-report Youth Risk Index (YRI) which is part of the ALEXSA-R will be used to screen for participants who are at high and low risk for early- to mid-adolescent problematic substance use. The YRI screening tool is designed for well-child visits to identify at-risk youths and refer them for prevention. The higher the YRI score (range 0-3) the higher the youth risk level.

Neurocognitive testing and executive functioning through NIH Toolbox

Time frame: at baseline, 12-month and 24-month

Neurodevelopmental maturity and cognitive functioning will be evaluated with NIH Cognitive Toolbox - Child Computerized performance tasks. These tasks test decision making, impulsivity, working memory, and attention. There is a memory task involving remembering the sequence of words, there is an inhibitory task involving pressing only certain buttons, and an attention task involving determining which pictures match and which do not. Each task produces a t score, with higher scores indicating higher performance on each task.

Multidimensional Anxiety Scale for Children 2 (MASC2)

Time frame: at baseline, 12-month and 24-month

The MASC2 is a comprehensive assessment of anxiety. It is a self-report scale for youth ages 8-19 with 50 items. It measures symptom severity, as well as range of symptoms across possible anxiety disorders and produces a t score which represents anxiety severity. This score can range from less than 40 (a low score) to above 70 (a high score).

State-Trait Anxiety Inventory for Children (STAI-C)

Time frame: at baseline, 12-month and 24-month

The STAI-C is a measure with two sub-surveys, with each one having 20 items each. The State measure assesses current anxiety at the moment of assessment, with a higher score meaning higher current anxiety. The Trait measure assesses level of anxiety severity in general as a trait of the participant, with a higher score meaning higher overall anxiety. The range in scores is between 20-80 for each sub-survey.

Tobacco Alcohol and Drug Use Survey

Time frame: 12-month and 24-month

Self-report survey to assess the frequency of use of multiple drugs: e.g., tobacco, alcohol, marijuana, cocaine, methamphetamine, opioids, etc. as the primary initial tool to assess what substances have been used by participants. This measure produces the number of days in the past year that the participant has used a substance as well as how recently the participant has used a substance.

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

Is it safe to participate?

Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

Will I be compensated?

Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.