The continuing evolution of a cancer prevention, screening, and survivorship ECHO: A second year of implementation.

INTRODUCTION: An estimated 39,010 Indiana residents were diagnosed with cancer in 2021. To address the cancer burden, Project ECHO (Extension Community Healthcare Outcomes) was launched in 2019 in Indiana to build specialty healthcare capacity among non-specialists. Due to positive outcomes from the pilot year, the Cancer Prevention, Screening, and Survivorship ECHO was implemented for a second year. The purpose of this study was to measure the participation and regional impact of this ECHO. METHODS: ECHO sessions occurred twice monthly from October 2020 to October 2021. Changes were implemented in response to feedback from the pilot year, including making the curriculum more practical for learners and adding accreditation opportunities. Participant information and feedback was extracted from electronic surveys for review. RESULTS: There were 24 ECHO sessions with 213 unique participants, increased from 140 unique participants in the pilot year. An average of 23.5 individuals attended each session, increased from 15.5 individuals per session. Enrolled participants served in a diverse set of roles and represented 247 zip codes, 30 Indiana counties, and 32 states across the United States, each of which increased from the pilot year. DISCUSSION: In this second year, this ECHO expanded to reach more participants with increased attendance and a more diverse distribution of roles within healthcare, which may be attributed to feedback-driven curriculum design. Cancer care is multi-disciplinary, with health educators, nurses, and administrators, each acting within the cancer care continuum. As a result, this ECHO has been adapted to serve an increasingly broad distribution of professionals. CONCLUSION: The second year of the Cancer Prevention, Screening, and Survivorship ECHO displayed increased overall enrollment and participation, greater diversity among participant roles, and a wider reach across Indiana and the United States.

Development and Pretesting of Prescription Opioid Misuse Prevention Messages: Results and Implications for Practice.

Well-designed health communication campaigns can contribute to the uptake of preventive behaviors, but there has been a lack of attention on using communication research to develop opioid misuse prevention messages. We report the results of two studies designed to inform the development of prescription opioid misuse prevention messages for adults ages 30-59. In Study 1, 16 adults across 4 counties participated in semi-structured interviews to provide input on message concepts addressing six key prescription opioid misuse prevention behaviors. In Study 2, 1,335 adults completed an online, survey-based between-subjects experiment in which participants were randomized to a no message control condition or a message condition that aligned with a prevention behavior. The survey examined Reasoned Action Approach (RAA) predictors of intention in no message control participants and examined differences in intention to perform prevention behaviors among experimental conditions. The qualitative interviews yielded insights about message preferences and perceived facilitators and barriers related to the prevention behaviors. The online survey demonstrated that attitude and descriptive norms are important determinants of preventive behaviors and potential targets for communication interventions. Message testing results demonstrated that the draft messages were effective in changing intentions to safely store, securely dispose of, and monitor the use of prescription opioids, but they were not effective in increasing intentions to talk to healthcare providers, older adults, or children about proper opioid use. A communication campaign addressing attitudes and perceived descriptive norms may be successful in increasing intentions to engage in opioid misuse prevention behaviors.

The effectiveness of trauma-focused psychotherapy for complex post-traumatic stress disorder: A retrospective study.

OBJECTIVE: We retrospectively evaluated the effectiveness of trauma-focused psychotherapy (TF-P) versus stabilization and waiting in a civilian cohort of patients with an 11th version of the international classification of disease (ICD-11) diagnosis of complex post-traumatic stress disorder (CPTSD). METHODS: We identified patients with CPTSD treated at a specialist trauma service over a 3-year period by triangulating evidence from self-report questionnaires, file review, and expert-clinician opinion. Patients completed a phase-based treatment: stabilization consisting of symptom management and establishing safety, followed by waiting for treatment (phase 1); individual TF-P in the form of trauma-focused cognitive behavioral therapy (TF-CBT), or eye movement desensitization and reprocessing (EMDR) or TF-CBT plus EMDR (phase 2). Our primary outcome was PTSD symptoms during phase 2 versus phase 1. Secondary outcomes included depressive symptoms, functional impairment, and a proxy CPTSD measure. Exploratory analysis compared outcomes between treatments. Adverse outcomes were recorded. RESULTS: Fifty-nine patients were included. Compared to receiving only phase 1, patients completing TF-P showed statistically significant reductions in PTSD [t(58) = -3.99, p < 0.001], depressive symptoms [t(58) = -4.41, p < 0.001], functional impairment [t(58) = -2.26, p = 0.028], and proxy scores for CPTSD [t(58) = 4.69, p < 0.001]. There were no significant differences in outcomes between different treatments offered during phase 2. Baseline depressive symptoms were associated with higher PTSD symptoms and functional impairment. CONCLUSIONS: This study suggests that TF-P effectively improves symptoms of CPTSD. However, prospective research with validated measurements is necessary to evaluate current and new treatments and identify personal markers of treatment effectiveness for CPTSD.

Increasing Uptake of Prescription Drug Take-Back Boxes: Eliciting Preferences and Applying the Theory of Planned Behavior to Predict Use.

This study assesses adults' perceptions of and predictors of intention to use prescription drug take-back boxes. This mixed methods study utilized focus groups and an online survey to examine factors related to intention to use a prescription drug take-back box. This study was conducted in [State] during the spring and summer of 2018. Themes identified in focus group data included the importance of take-back box location, benefits of take-back box use (such as reducing opportunities for medication misuse), and barriers to take-back box use (such as lack of awareness, stigma associated with law enforcement). Survey results indicate that pharmacies are the most preferred take-back box location and that attitudes, subjective norms, and perceived behavioral control are statistically significant predictors of intention to use a take-back box. Results suggest that individuals are open to using take-back boxes in secure, convenient locations, but many are unaware of take-back boxes as an option for safe disposal. These findings have implications for health communication and policy efforts designed to increase the use of take-back boxes for prescription drug disposal.

Effectiveness of psychosocial interventions in mitigating adverse mental health outcomes among disaster-exposed health care workers: A systematic review.

Health care workers worldwide are at an increased risk of a range of adverse mental health outcomes, including posttraumatic stress disorder (PTSD), following the unprecedented demand placed upon them during the COVID-19 pandemic. Psychosocial interventions offered to mitigate these risks should be based on the best available evidence; however, limited information regarding the comparative effectiveness of interventions is available. We undertook a systematic review of psychosocial interventions delivered to health care workers before, during, and after disasters. Eight databases were searched, including the Cochrane Central Register of Controlled Trials, PubMed/MEDLINE, EMBASE, and PsycINFO. Our primary outcomes were changes in symptoms of PTSD, anxiety, depression, and sleep. We calculated effect sizes, where unreported, and reliable change indices to appraise intervention effectiveness. The study was registered with PROSPERO (CRD42020182774). In total, 12,198 papers were screened, 14 of which were included in the present review. Interventions based on evidence-based protocols, including individual and group-based cognitive behavioral therapy (CBT) for PTSD, anxiety, and depression were found to lead to reliable changes in PTSD and anxiety symptoms. Single-session debriefing and psychological first aid workshops showed limited efficacy. There is limited evidence on psychosocial interventions for health care workers faced with disasters, with the strongest evidence base for CBT-based approaches. Future research should include controlled evaluations of interventions and aim to target identified risk factors.

Anticipating PTSD in severe COVID survivors: the case for screen-and-treat.

Based on research from previous pandemics, studies of critical care survivors, and emerging COVID-19 data, we estimate that up to 30% of survivors of severe COVID will develop PTSD. PTSD is frequently undetected across primary and secondary care settings and the psychological needs of survivors may be overshadowed by a focus on physical recovery. Delayed PTSD diagnosis is associated with poor outcomes. There is a clear case for survivors of severe COVID to be systematically screened for PTSD, and those that develop PTSD should receive timely access to evidence-based treatment for PTSD and other mental health problems by multidisciplinary teams.

Basados en la investigación de pandemias previas, los estudios de los sobrevivientes a cuidados críticos, y los datos emergentes de COVID-19, estimamos que hasta un 30% de los sobrevivientes del COVID grave desarrollarán TEPT. El TEPT es frecuentemente subdetectado en los servicios de salud primarios y secundarios y las necesidades psicológicas de los sobrevivientes puede verse eclipsadas por un enfoque en la recuperación física. El diagnóstico tardío de TEPT se asocia con pobres resultados. Existe un caso claro para que los sobrevivientes del COVID grave sean evaluados sistemáticamente para detectar el TEPT, y aquellos que desarrollan un TEPT deben tener acceso oportuno a tratamientos basados en la evidencia para el TEPT y para otros problemas de salud mental por equipos multidisciplinarios.

"While You're Down There": The Unexplored Role of Estheticians in the Health of Their Clients.

Young women (18-25 years) are more likely to engage in pubic hair removal and experience higher rates of negative sexual health outcomes (e.g., sexually transmitted infections [STIs]). Hair removal salons may serve as novel environments for health interventions. The Sexual Health and Esthetician (SHE) Study aimed to better understand the pubic hair removal profession, explore the esthetician-client relationship, and assess potential for esthetician offices/salons serving as health promotion/sexual health promotion intervention settings. Using an exploratory qualitative design, in-depth interviews (N = 28) were conducted with licensed estheticians who provided pubic waxing services. In a large urban area in Southern California, the catchment area of salons included five unique neighborhoods, each with high reported STI rates. Data were analyzed using a social constructivist perspective and emergent themes from interviews. Synthesis of data showed estheticians provide a variety of waxing services for young women; during appointments, sex-related discussions occur, creating "sexy spaces" where otherwise taboo conversations happen with ease; they notice clients' possible health concerns, including STIs, but have no protocols/procedures for handling these occurrences; and interactions with clients often result in the development of an intimate bond. Results indicate estheticians may be effective conveyors of sexual health promotion and risk reduction interventions.

Rural adults' perceived role of family members in prescription opioid misuse prevention: Implications for family-based approaches.

PURPOSE: This study explored and documented rural adults' perceptions of family roles in prescription opioid misuse prevention and the predisposing, reinforcing, and enabling factors that influence family members from taking those roles. METHODS: Nine focus groups with rural adults (n = 55) were conducted to evoke discussion about family roles in prescription opioid misuse prevention. Transcripts were coded based on common ideas that arose during the focus groups, previous literature, and the PRECEDE-PROCEED program planning model. FINDINGS: Findings suggest that rural adults perceive the opioid epidemic as partially a family problem. Additionally, rural adults perceive themselves as having a critical role in preventing prescription opioid misuse among family members. Participants identified specific predisposing, reinforcing, and enabling factors that influence whether or not family members take responsibility in preventing prescription opioid misuse within their families. Rural adults also perceive that family-based education is important in preventing prescription opioid misuse. CONCLUSIONS: These results suggest that there is an interest in family-based approaches that enable or foster the skills and resources necessary to engage in prescription opioid misuse prevention behaviors. Specifically, family-based prevention programming should include efforts to shape knowledge and attitudes about prescription opioid misuse, increase resources to facilitate prevention behaviors, and build skills related to prevention.

Cancer prevention, screening, and survivorship ECHO: A pilot experience with an educational telehealth program.

INTRODUCTION: The American Cancer Society, Inc. (ACS) estimates that 37,940 Indiana residents were diagnosed with cancer in 2020, which remains the leading cause of death in the state. Across the cancer continuum, national goals have been established targeting recommended benchmarks for states in prevention, screening, treatment, and survivorship. Indiana consistently falls below most goals for each of these targeted categories. METHODS: To address these disparities, we implemented Project ECHO (Extension for Community Healthcare Outcomes) as a virtual telehealth educational platform targeted at local healthcare providers. ECHO programs utilize a novel tele-mentoring approach to the education of clinicians in a hub/spoke design. Sessions occurred twice monthly from September 2019 to September 2020 and consisted of a traditional didactic lecture and a case-based discussion led by participating providers. RESULTS: During the pilot year there were a total of 22 ECHO sessions with 140 different participants. On average, 15.5 spokes attended each session with increasing participation at the end of the year. Post-session surveys suggested generally favorable perception with 72% of respondents finding the quality "excellent." DISCUSSION: Given the increasing rate of recurrent participation toward the end of the pilot year in conjunction with the favorable survey responses following each session, it was felt that the program was overall successful and warranted continued implementation. CONCLUSION: The Project ECHO platform is a validated telehealth education platform that has the potential to impact cancer care at multiple points along the cancer continuum at the regional level.

A Randomized, Double-Blind, Multicenter, Noninferiority Study Comparing Paliperidone Palmitate 6-Month Versus the 3-Month Long-Acting Injectable in Patients With Schizophrenia.

BACKGROUND: This double-blind (DB), randomized, parallel-group study was designed to evaluate efficacy and safety of paliperidone palmitate 6-month (PP6M) formulation relative to paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia. METHODS: Following screening, patients entered an open-label (OL) maintenance phase and received 1 injection cycle of paliperidone palmitate 1-month (PP1M; 100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). Clinically stable patients were randomized (2:1) to receive PP6M (700 or 1000 mg eq., gluteal injections) or PP3M (350 or 525 mg eq.) in a 12-month DB phase; 2 doses of PP6M (corresponding to doses of PP1M and PP3M) were chosen. RESULTS: Overall, 1036 patients were screened, 838 entered the OL phase, and 702 (mean age: 40.8 years) were randomized (PP6M: 478; PP3M: 224); 618 (88.0%) patients completed the DB phase (PP6M: 416 [87.0%]; PP3M: 202 [90.2%]). Relapse rates were PP6M, 7.5% (n = 36) and PP3M, 4.9% (n = 11). The Kaplan-Meier estimate of the difference (95% CI) between treatment groups (PP6M - PP3M) in the percentages of patients who remained relapse free was -2.9% (-6.8%, 1.1%), thus meeting noninferiority criteria (95% CI lower bound is larger than the pre-specified noninferiority margin of -10%). Secondary efficacy endpoints corroborated the primary analysis. Incidences of treatment-emergent adverse events were similar between PP6M (62.1%) and PP3M (58.5%). No new safety concerns emerged. CONCLUSIONS: The efficacy of a twice-yearly dosing regimen of PP6M was noninferior to that of PP3M in preventing relapse in patients with schizophrenia adequately treated with PP1M or PP3M. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT03345342.

Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree.

Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder with complex patterns of genetic inheritance. Recent genetic findings in TS have highlighted both numerous common variants with small effects and a few rare variants with moderate or large effects. Here we searched for genetic causes of TS in a large, densely-affected British pedigree using a systematic genomic approach. This pedigree spans six generations and includes 122 members, 85 of whom were individually interviewed, and 53 of whom were diagnosed as "cases" (consisting of 28 with definite or probable TS, 20 with chronic multiple tics [CMT], and five with obsessive-compulsive behaviors [OCB]). A total of 66 DNA samples were available (25 TS, 15 CMT, 4 OCB cases, and 22 unaffecteds) and all were genotyped using a dense single nucleotide polymorphism (SNP) array to identify shared segments, copy number variants (CNVs), and to calculate genetic risk scores. Eight cases were also whole genome sequenced to test whether any rare variants were shared identical by descent. While we did not identify any notable CNVs, single nucleotide variants, indels or repeat expansions of near-Mendelian effect, the most distinctive feature of this family proved to be an unusually high load of common risk alleles for TS. We found that cases within this family carried a higher load of TS common variant risk similar to that previously found in unrelated TS cases. Thus far, the strongest evidence from genetic data for contribution to TS risk in this family comes from multiple common risk variants rather than one or a few variants of strong effect.

Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

BACKGROUND: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation. OBJECTIVE: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT. METHODS: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature. RESULTS: Rates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates. CONCLUSIONS: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Mental health first aid training for Extension agents in rural communities.

OBJECTIVE: The goal of the current study is to evaluate the effectiveness of Mental Health First Aid (MHFA) in broadening the network of gatekeepers in rural communities. METHOD: Extension agents in Mississippi who completed MHFA training were recruited via email to participate in a 22-item, web-based, quantitative and qualitative, six-month follow-up survey that measured demographic characteristics, which MHFA skills agents used post-training, barriers to skill use, and confidence in ability to use those skills (n = 80). RESULTS: Over 60% of the agents reported using the skills learned from the MHFA training, and nearly 15% of agents reported having an encounter with someone in crisis since completing the MHFA training. Agent participants reported using the skills learned from the training with farmers, 4-H youth, volunteers, and parents, family members, colleagues, and friends. One agent commented that the training, "has been very helpful in speaking with various people and has increased confidence when encountering someone with mental health challenges." CONCLUSION: MHFA trainings appear to increase the confidence and competence of Extension agents as community gatekeepers and may greatly enhance the reach of the mental health network of rural areas by increasing identification and referral of those requiring mental health services.

Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

The addition of spices and herbs to vegetables in the National School Lunch Program increased vegetable intake at an urban, economically-underserved, and predominantly African-American high school.

Vegetable intake is far below recommendations among African-American adolescents living in economically-underserved urban areas. While the National School Lunch Program (NSLP) helps overcome access barriers, vegetable intake remains challenging and novel interventions are required. A two-year, multi-phase, school-based intervention was conducted at an urban, economically-underserved, and predominantly African-American high school in Baltimore, Maryland to determine whether stakeholder-informed addition of spices and herbs to NSLP vegetables would increase intake. The stakeholder engagement phase included assessment of NSLP vegetable attitudes/preferences among 43 school stakeholders and subsequent student sensory testing. The second phase was conducted in the school cafeteria and consisted of eight weeks comparing student intake of typical vegetable recipes versus otherwise-identical recipes with spices and herbs. 4,570 student lunch plates were included in the vegetable intake comparison. Vegetable intake was measured by lunch tray plate waste. Willingness to try vegetables was assessed by the difference between plate waste and estimated mean vegetable served weight. Intake of typical vegetable recipes and vegetable recipes with spices and herbs was compared with student's t-test. Chi-square test was used to compare willingness to try vegetables. Total vegetable intake was 18.2% higher (8.22 grams per meal, p<0.0001) with spices and herbs than with typical recipes. There were no differences in trying vegetables with spices and herbs, although student-led advocacy was associated with increased trying vegetables with spices and herbs (78.8% with advocacy, 67.5% without advocacy, p<0.0001). The addition of spices and herbs to vegetables in the NSLP was feasible and associated with small increases in vegetable intake at an urban, economically-underserved, and predominantly African-American high school.

Gilles de la Tourette Syndrome: advice in the times of COVID-19.

The novel coronavirus disease (COVID-19) was identified as the cause of an outbreak of respiratory disease in China at the end of 2019. It then spread with enormous rapidity and by mid-March 2020 was declared a world pandemic. Gilles de la Tourette Syndrome (GTS) is a childhood-onset neurodevelopmental disorder with a worldwide prevalence of about 1% of the population. The clinical symptoms include multiple motor and one or more phonic (vocal) tics. Germane to this communication is that 85% of patients with GTS have associated psychiatric co-morbidities, many of which are being exacerbated in the current global health crisis. In addition, several symptoms of GTS may mimic COVID-19, such as a dry cough and sniffing (phonic tics), while other symptoms such as spitting, inappropriate touching of others and "non-obscene socially inappropriate symptoms" can potentially get patients with GTS into trouble with the law. We suggest that a clear explanation of the COVID-19 illness and GTS is important to enable colleagues of various specialities who tend to patients with GTS. It is important to acknowledge at the outset that the information available on the COVID-19 pandemic changes daily, including cases infected, deaths reported, and how various national health systems are planning and or coping or not. It is fair to say that having read the current medical and lay press we conclude that it is not easy to reassure our patients with absolute certainty. However, notwithstanding that, we hope our documentation is of some assistance.

An Onsite Fitness Facility and Integrative Wellness Program Positively Impacted Health-Related Outcomes Among Teachers and Staff at an Urban Elementary/Middle School.

BACKGROUND: Given the large number of obesity-focused studies conducted in schools, there is a surprising lack of data regarding teacher workplace health behaviors in the United States. OBJECTIVE: To determine the feasibility and effectiveness of an onsite fitness facility with a structured integrative wellness program to improve health-related outcomes among teachers and staff at an urban elementary/middle school. METHODS: A 2-year mixed-methods analysis using Patient-Reported Outcomes Measurement Information System (PROMIS) measures and qualitative interviews included 39 teachers and staff employed at an urban elementary/middle school in Baltimore, Maryland. The fitness facility was dedicated exclusively to teachers and staff and the integrative wellness program included group exercise classes, yoga, mindfulness, and nutrition competitions. T tests were used to compare quantitative outcomes at baseline, the end of year 1, and the end of year 2. RESULTS: Compared to baseline, at year 1, there was a significant improvement in the PROMIS Sleep Disturbance score. From baseline to end of year 2, there were significant increases in the PROMIS Global Physical Health as well as significant decreases in Sleep Disturbances, Fatigue, and Social Isolation. Qualitative interviews conducted at the end of year 1 indicated that teachers who used the facility felt that it improved their mood, increased their energy, motivated them to eat healthily, and gave them opportunities to socialize with their colleagues in new ways. This impact was further enhanced in year 2. CONCLUSIONS: An onsite fitness facility with an integrative wellness program may improve health-related outcomes among urban elementary school teachers and staff, with the greatest benefits seen after 2 years of implementation.

Interrogating the Genetic Determinants of Tourette's Syndrome and Other Tic Disorders Through Genome-Wide Association Studies.

OBJECTIVE: Tourette's syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette's syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette's syndrome polygenic risk to test whether Tourette's and related tic disorders have an underlying shared genetic etiology and whether Tourette's polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity. METHODS: GWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette's syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette's polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined. RESULTS: GWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette's syndrome heritability. Tourette's-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette's PRS significantly predicted both Tourette's syndrome and tic spectrum disorders status in the population-based sample. Tourette's PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects. CONCLUSIONS: Modulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette's syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette's syndrome and other tic disorders in future diagnostic schemata. Tourette's PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity.