Longitudinal Impact of Stressors in Adults With Tourette Syndrome (LISA-TS)

The Investigators propose a two-year, longitudinal pilot study of TS adults (>18) to determine impact of lifetime environmental stress exposure on tic severity, psychiatric comorbidity severity, and health-related quality of life (HRQOL).

Study Overview

• Status: Recruiting
• Conditions: Tourette Syndrome
• Intervention / Treatment: Other: None - observational study

Detailed Description

Tourette syndrome (TS) is a widely prevalent neurodevelopmental disorder with limited treatment options,(1,2) substantial impact on quality of life in children(3-7) and adults,(4,8-10) and two-fold increased risk of premature death.(11,12) Tics are the defining feature of TS, and as a result, TS is often narrowly perceived in terms of tics alone. Tics themselves tend to wane in late adolescence, with distressing tics persisting in only one-third of TS patients.(13) Because tics generally diminish with age, the plight of adults with TS is often neglected. Over half of TS adults suffer from anxiety and depression,(10,14) and a similar percentage experience symptoms of attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), findings recently corroborated in our own clinical population.(10) Many TS adults struggle to form meaningful relationships with peers, and one-third feel inadequately supported by their families.(13) The burden of TS in adulthood extends beyond mental and social health. In a national registry cohort study, individuals with TS had a mortality rate ratio of 1.8 relative to healthy controls, even after controlling for comorbid psychiatric diagnoses.(11) The causes of more frequent premature death in TS populations are unclear, with many mechanisms implicated, including suicide,(15) traumatic accidents,(12) substance abuse,(16) metabolic disorders,(12,17) and complications from pharmacotherapy.(18,19)

Environmental stressors are also postulated to impact the course of TS.(20) An environmental stressor is any external condition or event that poses a threat to an individual's well-being.(21) Such stressors are known to alter brain development(22-24) and increase risk of adulthood psychopathology.(25,26) A single study has explored the role of environmental stressors in TS, finding that selected stressors predicted two-year tic and psychiatric symptom severity in a pediatric cohort (n=37 patients).(27) No similar investigations have been undertaken in TS adults. The Investigators hypothesize that environmental stressors are risk factors for more severe adult TS phenotype. The Investigators propose a two-year, longitudinal pilot study of TS adults (>18) to determine impact of lifetime environmental stress exposure on tic severity, psychiatric comorbidity severity, and health-related quality of life (HRQOL).

Aim 1. Determine influence of lifetime environmental stressors on tic severity in TS adults. Hypothesis: Number of lifetime stressors at baseline assessment is associated with greater tic severity at two year follow-up. Seventy adults with TS will be recruited from the Vanderbilt TS Clinic to complete a baseline assessment, consisting of validated clinical rating scales for tic severity (Yale Global Tic Severity Scale), common psychiatric comorbidities, and lifetime environmental stressors (Stress and Adversity Inventory for Adults, STRAIN). Because acute and chronic stressors exert differential physiologic and clinical-level effects,(28-31) the STRAIN assesses these separately. The Investigators will use multivariable linear regression to examine the influence of acute and chronic lifetime stressor count at baseline on tic severity at two years, controlling for baseline tic severity and psychiatric comorbidities, as well as anti-tic medications at follow-up. Results will clarify the impact of environmental stressors on tic severity in TS adults.

Aim 2. Determine influence of lifetime environmental stressors on depression in TS adults.

Hypothesis: Number of lifetime stressors at baseline assessment is associated with more depressive symptoms at two-year follow-up. Depression is the psychiatric symptom that most impacts adult functioning and QOL.(10) As part of baseline and follow-up assessments, Aim 1 participants will complete standardized, semi-structured psychiatric interviews (Mini International Neuropsychiatric Interview, MINI) and validated self-report depression scales (NeuroQOL-Depression). The statistical approach from Aim 1 will be adopted to examine the influence of acute and chronic lifetime stressor count at baseline on depression symptom severity at two years, again controlling for select confounds. Findings will delineate the effects of acute and chronic environmental stressors on depression in adults with TS.

Aim 3. Determine influence of positive childhood experiences on health-related quality of life (HRQOL) in TS adults. Hypothesis: Greater number of positive childhood experiences is associated with better HRQOL in TS adults at two-year follow-up. Positive childhood experiences partially mitigate the negative effects of adverse childhood experiences.(32) At baseline and follow-up visits, Aim 1 participants will report number and type of positive childhood experiences. They will also complete a validated HRQOL measure specific to TS: the Gilles de la Tourette-Quality of Life Scale (GTS-QOL). The Investigators will use multivariable regression modeling to examine the influence of positive childhood experiences on future HRQOL, controlling for environmental stressors and baseline HRQOL. Results will elucidate the potentially moderating role of positive childhood experiences on HRQOL in TS adults.

• Study Type: Observational
• Enrollment (Estimated): 140

Contacts and Locations

• Study Contact: Name: Michelle Eckland, BS; Phone Number: 615-875-7394; Email: michelle.r.eckland.1@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232-5400
      • Recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: David Isaacs, MD, MPH
      • Contact: Michelle Eckland, BS; Phone Number: 6159362025; Email: michelle.r.eckland.1@vumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

adults (>18 years of age) with Tourette syndrome or other chronic tic disorder

Description

Inclusion Criteria:

• adults (>18) meeting Diagnostic and Statistics Manual, 5th edition (DSM-V) criteria for Tourette syndrome, chronic motor tic disorder, or chronic vocal tic disorder
• ability to provide informed consent
• English proficiency

Exclusion Criteria:

- significant medical, neurologic, or psychiatric diagnoses (e.g. uncontrolled epilepsy, chronic heart failure, schizophrenia) besides TS and its commonly co-occurring psychiatric diagnoses

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Individuals with Tourette syndrome (TS); Individuals previously diagnosed with Tourette syndrome (TS). Participants must be 18 years of age or older.	Other: None - observational study; None - observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Tic Score from Yale Global Tic Severity Scale (YGTSS)	Semi-structured, clinician-administered interview to assess tic severity. Total tic scores are a composite of motor tic scores (0-25) and phonic tic scores (0-25) based on 5 dimensions of tic severity: number, frequency, intensity, complexity, and interference. Total tic scores range from 0-50. Higher scores indicate great tic severity. The YGTSS is the gold-standard clinical rating scale for tic severity.	2 years post-baseline assessment
NeuroQOL-Depression Score	NeuroQOL-Depression is a validated, 8-item self-report scale assessing symptoms of depression. Raw total scores range from 8-40; raw scores are converted to T-scores based on normative samples. Higher scores indicate more depressive symptoms. NeuroQOL-Depression is part of the Neuro-QOL (Quality of Life in Neurological Disorders) measurement system. The scale is designed to be completed with one minute.	2 years post-baseline assessment
Gilles de la Tourette Quality of Life Scale (GTS-QOL) Score	The GTS-QOL is a 27-item self-report scale. Respondents rate each item on a Likert scale ranging from 0 ("no problem") to 4 ("extreme problem"). The scale is composed of four sub-scales: Psychological (11 items), Physical/Activities of Daily Living (Physical/ADL) (7 items), Obsessive-Compulsive (OC) (5 items), and Cognitive (4 items) (39). Item scores within each subscale are summed and then normalized to 100 to generate the subscale score. The four subscale scores are then summed and normalized to 100 to yield the total score. Higher scores indicate worse health-related quality of life.	2 years post-baseline assessment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NeuroQOL-Anxiety Score	NeuroQOL-Depression is a validated, 8-item self-report scale assessing symptoms of anxiety. Raw total scores range from 8-40; raw scores are converted to T-scores based on normative samples. Higher scores indicate more anxiety symptoms. NeuroQOL-Anxiety is part of the Neuro-QOL (Quality of Life in Neurological Disorders) measurement system. The scale is designed to be completed with one minute.	2 years post-baseline assessment
Adult ADHD Self-Report Screening Scale for DSM-V (ASRS-V) Score	ASRS-V is a 6-question scale screening for symptoms of inattention and hyperactivity. Each item is rated 0 ("never") to 4 ("very often"). Total score is the sum of individual item scores. Higher score indicates more ADHD symptoms. In clinical populations, ASRS-V total score cutoff ≥ 14 is 81% sensitive and 70% specific for detecting ADHD.	2 years post-baseline assessment
Dimensional Obsessive-Compulsive Scale (DOCS) Score	DOCS is a 20-item, validated self-report scale assessing for severity of obsessive-compulsive symptoms. Total score ranges from 0-80, with higher scores indicating more OCD symptoms. In clinical populations, DOCS total score cutoff ≥ 21 is 70% sensitive and 70% specific in distinguishing OCD from other anxiety disorders.	2 years post-baseline assessment
Mini International Neuropsychiatric Interview (MINI)	The Mini-International Neuropsychiatric Interview (M.I.N.I.) is a brief structured diagnostic interview for common DSM-V psychiatric disorders. Scale administration is typically 15-20 minutes. Scale output is presence/absence of psychiatric diagnoses currently and/or in the past.	2 years post-baseline assessment
Lifetime Adult STRAIN	The STRAIN (https://www.uclastresslab.org/projects/strain-stress-and-adversity-inventory/) is a NIMH/RDoC-recommended online stress assessment system that measures individuals' lifetime exposure to different types of acute and chronic stress that have implications for health. STRAIN questions automatically adapt based on a user's responses. The STRAIN generates multiple stressor scores, including total stressor count and severity, childhood and adulthood stressor counts and severities, and domain-specific stressor counts and severities.	2 years post-baseline assessment
Multifactoral Assessment of Perceived Social Support (MAPSS)	The MAPSS is an 8-item, unidimensional, validated, clinically relevant, self-report measure of social support.	2 years post-baseline assessment
Sensory Gating Inventory (SGI)	The SGI is a 36-item, validated instrument assessing hyper- or hypo-sensitivity to sensory stimuli (primarily sight and sound). Each scale item is a statement to which participants must rate their agreement on a 6-point Likert scale (1 = "never true"; 6 = "always true"). The minimum score on the scale is 36; the maximum score is 216. Higher scores indicate more abnormal sensory experiences.	2 years post-baseline assessment
Body Perception Questionnaire-Short Form (BPQ-SF)	The BPQ-SF is a self-report questionnaire that assesses the frequency of specific body stress reactions in organs that are innervated by the autonomic nervous system. Combined scores from organs throughout the body provide a measure of autonomic stress response patterns. The questionnaire has been used in a range of international neural, behavioral, and clinical studies and translated into several languages.	2 years post-baseline assessment
Emotion Regulation Questionnaire	The Emotion Regulation Questionnaire is a 10-item, self-report questionnaire designed to assess individual differences in the habitual use of two emotion regulation strategies: cognitive reappraisal and expressive suppression. Participants rate each statement about emotion regulation on a 7-point Likert scale (1 = "strongly disagree"; 7 = "strongly agree").	2 years post-baseline assessment
Response to Stress Questionnaire-Interpersonal Stress (RSQ)	The RSQ measures coping and involuntary stress responses. It begins with a checklist of stressors that pertain to interpersonal stress, which the participant rates in terms of how often each stressor has occurred in the recent past. The questionnaire then asks the participant to keep those specific stressors in mind when responding to the items that comprise the stress responses. Participants rate how often they use each coping method or experience each type of involuntary stress response on a scale of 1 (Not at all) to 4 (A lot). Some items require participants to select an answer on the 1 to 4 scale and write in additional information to describe specifically how they employed that particular coping strategy. The RSQ contains items to measure three types of coping and two types of involuntary stress responses. The measure thus yields five factors: primary control coping, secondary control coping, disengagement coping, involuntary engagement, and involuntary disengagement.	2 years post-baseline assessment

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: University of California, Los Angeles
• Investigators: Principal Investigator: David A Isaacs, MD, MPH, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Stress; Psychosocial stress; Environmental stress
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Genetic Diseases, Inborn; Neurodegenerative Diseases; Neurodevelopmental Disorders; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Tic Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Tourette Syndrome
• Other Study ID Numbers: U12134

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
• product manufactured in and exported from the U.S.: No