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In tic disorders (TD), tic expression varies across the lifespan and as a function of contextual factors. This study explored connections between tic expression and contextual triggers across life periods in 74 adults (Mage = 23.2) with TDs. The Tic History and Coping Strategies form assessed retrospective self-reports of contextual antecedents, consequences, and tic severity during four life periods (middle school; 9th/10th grade; 11th/12th grade; college/work) and past month. Tics reportedly worsened during and after school in school-aged years and worsened in the evening during college/work years. Stress and anxiety were reported to consistently trigger tics across time. The impact of activities, places, and emotions did not differ across life periods. Attention-based consequences, most prevalent during middle school, were more common than escape- or avoidance-related consequences across all periods. Findings illuminate how contextual factors may influence tics across life periods and underscore the consistent impact of tic-triggering emotions and attention-related consequences.
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The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a "cold tumour," a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and in vivo EOC models. Noradrenaline (NA), an adrenergic agonist, did not directly regulate PD-L1 expression but PD-L1 was significantly upregulated by IFN-γ in EOC cell lines. IFN-γ also increased PD-L1 on extracellular vesicles (EVs) released by ID8 cells. PRO significantly decreased IFN-γ levels in primary immune cells activated ex vivo and showed increased viability of the CD8+ cell population in an EV-immune cell co-incubation. In addition, PRO reverted PD-L1 upregulation and significantly decreased IL-10 levels in an immune-cancer cell co-culture. Chronic behavioural stress increased metastasis in mice while PRO monotherapy and the combo of PRO and PD-(L)1 inhibitor significantly decreased stress-induced metastasis. The combined therapy also reduced tumour weight compared to the cancer control group and induced anti-tumour T-cell responses with significant CD8 expression in tumour tissues. In conclusion, PRO showed a modulation of the cancer immune response by decreasing IFN-γ production and, in turn, IFN-γ-mediated PD-L1 overexpression. The combined therapy of PRO and PD-(L)1 inhibitor decreased metastasis and improved anti-tumour immunity offering a promising new therapy.
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Antígeno B7-H1 , Neoplasias Ováricas , Propranolol , Animales , Femenino , Humanos , Ratones , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos , Terapia de Inmunosupresión , Interferón gamma/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/metabolismo , Propranolol/farmacologíaRESUMEN
INTRODUCTION: Deep brain stimulation (DBS) has emerged as a safe and effective therapy for refractory Tourette syndrome (TS). Recent studies have identified several neural targets as effective in reducing TS symptoms with DBS, but, to our knowledge, none has compared the effectiveness of DBS with conservative therapy. METHODS: A literature review was performed to identify studies investigating adult patient outcomes reported as Yale Global Tic Severity Scale (YGTSS) scores after DBS surgery, pharmacotherapy, and psychotherapy. Data were pooled using a random-effects model of inverse variance-weighted meta-analysis (n = 168 for DBS, n = 131 for medications, and n = 154 for behavioral therapy). RESULTS: DBS resulted in a significantly greater reduction in YGTSS total score (49.9 ± 17.5%) than pharmacotherapy (22.5 ± 15.2%, p = 0.001) or psychotherapy (20.0 ± 11.3%, p < 0.001), with a complication (adverse effect) rate of 0.15/case, 1.13/case, and 0.60/case, respectively. CONCLUSION: Our data suggest that adult patients with refractory TS undergoing DBS experience greater symptomatic improvement with surprisingly low morbidity than can be obtained with pharmacotherapy or psychotherapy.
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Tratamiento Conservador/métodos , Estimulación Encefálica Profunda/métodos , Síndrome de Tourette/diagnóstico por imagen , Síndrome de Tourette/terapia , Ensayos Clínicos como Asunto/métodos , Tratamiento Conservador/tendencias , Estimulación Encefálica Profunda/tendencias , Humanos , Resultado del TratamientoRESUMEN
The recent identification of profilin1 mutations in 25 familial ALS cases has linked altered function of this cytoskeleton-regulating protein to the pathogenesis of motor neuron disease. To investigate the pathological role of mutant profilin1 in motor neuron disease, we generated transgenic lines of mice expressing human profilin1 with a mutation at position 118 (hPFN1G118V). One of the mouse lines expressing high levels of mutant human PFN1 protein in the brain and spinal cord exhibited many key clinical and pathological features consistent with human ALS disease. These include loss of lower (ventral horn) and upper motor neurons (corticospinal motor neurons in layer V), mutant profilin1 aggregation, abnormally ubiquitinated proteins, reduced choline acetyltransferase (ChAT) enzyme expression, fragmented mitochondria, glial cell activation, muscle atrophy, weight loss, and reduced survival. Our investigations of actin dynamics and axonal integrity suggest that mutant PFN1 protein is associated with an abnormally low filamentous/globular (F/G)-actin ratio that may be the underlying cause of severe damage to ventral root axons resulting in a Wallerian-like degeneration. These observations indicate that our novel profilin1 mutant mouse line may provide a new ALS model with the opportunity to gain unique perspectives into mechanisms of neurodegeneration that contribute to ALS pathogenesis.
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Esclerosis Amiotrófica Lateral/metabolismo , Encéfalo/metabolismo , Mutación Missense , Profilinas/biosíntesis , Médula Espinal/metabolismo , Sustitución de Aminoácidos , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología , Animales , Encéfalo/patología , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Transgénicos , Profilinas/genética , Médula Espinal/patologíaRESUMEN
Hypertension is not consistently associated with postoperative cardiovascular morbidity and is therefore not considered a major peri-operative risk factor. However, hypertension may predispose to peri-operative haemodynamic changes known to be associated with peri-operative morbidity and mortality, such as intra-operative hypotension and tachycardia. The objective of this study was to determine whether pre-operative hypertension was independently associated with haemodynamic changes known to be associated with adverse peri-operative outcomes. We performed a five-day multicentre, prospective, observational cohort study which included all adult inpatients undergoing elective, non-cardiac, non-obstetric surgery. We recruited 343 patients of whom 164 (47.8%) were hypertensive. An intra-operative mean arterial pressure of < 55 mmHg occurred in 59 (18.2%) patients, of which 25 (42.4%) were hypertensive. Intra-operative tachycardia (heart rate> 100 beats.min-1 ) occurred in 126 (38.9%) patients, of whom 61 (48.4%) were hypertensive. Multivariable logistic regression did not show an independent association between the stage of hypertension and either clinically significant hypotension or tachycardia, when controlled for ASA physical status, functional status, major surgery, duration of surgery or blood transfusion. There was no association between pre-operative hypertension and peri-operative haemodynamic changes known to be associated with major morbidity and mortality. These data, therefore, support the recommendation of the Joint Guidelines of the Association of Anaesthetists of Great Britain and Ireland (AAGBI) and the British Hypertension Society to proceed with elective surgery if a patient's blood pressure is < 180/110 mmHg.
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Hemodinámica , Hipertensión/complicaciones , Hipertensión/epidemiología , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Presión Arterial , Determinación de la Presión Sanguínea , Estudios de Cohortes , Femenino , Humanos , Hipertensión/fisiopatología , Complicaciones Intraoperatorias/epidemiología , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Estudios Prospectivos , Taquicardia/fisiopatologíaRESUMEN
Role of zooplankton in the organic matter flux was studied in the Kara and Laptev seas using sediment traps in the course of voyage 63 of the Academician Mstislav Keldysh research vessel in August-October 2015. The values of the total flux and that of organic matter were at least an order of magnitude higher than those obtained before the 2000s. A hypothesis is proposed on an increasing influence of the river runoff on the Kara Sea area under climatic changes. Zooplankton contribution into Corg flux varied broadly, averaging 50%. The highest flux values and contribution of zooplankton in them (up to 96%) were recorded in the frontal (gradient) zones.
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Agua de Mar/química , Zooplancton/fisiología , Animales , Regiones Árticas , SiberiaRESUMEN
BACKGROUND: The mechanisms by which stress hormones impact triple-negative breast cancer (TNBC) etiology and treatment are unclear. We have previously shown that stress hormones, cortisol, and catecholamines induce rapid DNA damage and impact DNA repair in NIH 3T3 fibroblasts. This study investigates whether stress hormones increase DNA damage in breast cancer cells and if this impacts drug efficacy. METHODS: We first screened a panel of 39 breast cancer cell lines for expression of adrenergic and glucocorticoid receptors and examined if stress hormones induce DNA damage and alter cell cycle regulation in vitro. A TNBC xenograft model was used to assess the impact of restraint stress on tumour growth and chemosensitivity to paclitaxel. RESULTS: We found that stress hormones induced DNA damage, phosphorylation of ATR, which was accompanied by an up-regulation of the G1 cell kinase inhibitor p21 and a cell cycle halt of TNBCs in the G1 phase. p21 knockdown abrogated G1 arrest by stress hormones. We also demonstrated that stress significantly decreased efficacy of paclitaxel. CONCLUSION: We describe a novel mechanism through which stress hormones can induce drug resistance to paclitaxel, which may have profound implications for treating drug resistance in patients with TNBC.
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Antineoplásicos Fitogénicos/farmacología , Catecolaminas/farmacología , Daño del ADN/efectos de los fármacos , Hidrocortisona/farmacología , Paclitaxel/farmacología , Estrés Fisiológico/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/patología , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Femenino , Citometría de Flujo , Humanos , Ratones , Ratones Desnudos , Receptores de Estrógenos/metabolismo , Transducción de Señal , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
With infertility challenges posing an obstacle to many couples, the extension of variables to assess male fertility is an important line of research. At the Reproductive Biology Unit where the study was undertaken, a considerable proportion of male patient's seeking fertility assessment presented with hyperviscous semen samples and elevated concentrations of leucocytes. Despite viscosity being included as part of a routine spermiogram, it raises a considerable amount of concern as it is assessed semiquantitatively. The study was undertaken to evaluate the quantification of semen viscosity in centipoise (cP) and to investigate whether a correlation exists between hyperviscosity and leucocytospermia. A total of 200 semen samples were assessed from a sample cohort of two population groups: 162 male patients undergoing fertility assessment and 38 volunteer donors. Semen viscosity was determined by measuring the filling time of a capillary-loaded Leja chamber and quantifying the viscosity in cP. Leucocytes were identified histochemically with a leucocyte peroxidase test. The viscosity when quantified in cP was significantly higher in the peroxidase positive sample group (9.01 ± 0.49 vs. 7.39 ± 0.23 cP; P < 0.005). The introduction of a more accurate method of quantifying viscosity may possibly help to identify, diagnose and treat patients suffering from leucocytospermia to ultimately enhance their fertility potential.
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Leucocitosis/diagnóstico , Análisis de Semen , Semen/inmunología , Estudios de Cohortes , Humanos , Masculino , ViscosidadRESUMEN
Tic severity is composed of several dimensions. Tic frequency and intensity are two such dimensions, but little empirical data exist regarding their relative contributions to functional impairment in those with chronic tic disorders (CTD). The present study examined the relative contributions of these dimensions in predicting tic-related impairment across several psychosocial domains. Using data collected from parents of youth with CTD, multivariate regression analyses revealed that both tic frequency and intensity predicted tic-related impairment in several areas; including family and peer relationships, school interference, and social endeavors, even when controlling for the presence of comorbid anxiety symptoms and Attention Deficit Hyperactivity Disorder diagnostic status. Results showed that tic intensity predicted more variance across more domains than tic frequency.
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Padres , Calidad de Vida/psicología , Trastornos de Tic/psicología , Tics/psicología , Adolescente , Niño , Femenino , Humanos , Masculino , Grupo Paritario , Percepción , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Evaluación de Síntomas , Trastornos de Tic/diagnóstico , Tics/diagnósticoRESUMEN
BACKGROUND: Interest in the effectiveness of mindfulness-based interventions such as yoga in primary schools has grown. Evidence shows promise, as youth who engage in yoga to promote mindfulness show improved coping skills, increased socio-emotional competence and prosocial skills, academic performance, attention span, and ability to deal with stress. OBJECTIVE: This study reports the results of a program evaluation of a universal health and wellness curriculum, Pure Power, designed to teach youth yoga techniques, mindfulness, and emotion regulation. METHODS: A non-randomized comparison design examined outcomes among participants from schools that completed the intervention with highest fidelity of implementation (n = 461) and from students in matched comparison schools (n = 420). Standard measures of coping, emotion regulation and emotion dysregulation, spelling, and math achievement were collected. RESULTS: Analyses suggest the youth in the intervention schools demonstrated relative improvement on measures of emotion regulation, spelling, and math. CONCLUSIONS: Challenges in implementation in real-life settings are vital to identify. The data provide some real-world evidence for the effectiveness of a universal health and wellness curriculum on emotion regulation and positive academic outcomes. Training school staff to deliver the intervention may foster implementation. Future research should test the effectiveness of who delivers the intervention; for example, teacher-delivered groups vs. other wellness personnel.
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Atención Plena , Yoga , Adolescente , Humanos , Yoga/psicología , Salud Mental , Atención Plena/métodos , Evaluación de Programas y Proyectos de Salud , Instituciones Académicas , CurriculumRESUMEN
Behavior therapy is a well-established and empirically supported treatment for tic disorders (TDs). However, concerns have been expressed about the negative effects of behavioral interventions, such as tic worsening, tic substitution, and excessive effort. This study explored perceived negative effects of tic management strategies in adults with TDs and predictors of these experiences. Participants (N = 72) completed semi-structured interviews 11 years after receiving behavior therapy or supportive therapy in a randomized clinical trial. We examined responses to interview questions about managing tics and predictors of reported negative effects. Most participants did not experience tic worsening (84%) or tic substitution (75%) from tic management strategies. The majority felt they could manage tics while participating in their environment (87%) and did not report life interference from tic management (77%). About half (45%) felt less present when managing tics. Treatment non-responders in the original trial were more likely to report negative effects of tic management strategies. No differences in reported negative consequences were found between those who received behavior therapy versus supportive therapy, suggesting that behavior therapy specifically does not lead to such adverse effects. These findings could reduce misconceptions about behavior therapy for TDs and enhance its acceptability and utilization.
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Terapia Conductista , Trastornos de Tic , Humanos , Trastornos de Tic/terapia , Trastornos de Tic/psicología , Masculino , Femenino , Adulto , Terapia Conductista/métodos , Persona de Mediana Edad , Adulto JovenRESUMEN
Treatment-resistant obsessive-compulsive disorder (OCD) occurs in approximately one-third of OCD patients. Obsessions may fluctuate over time but often occur or worsen in the presence of internal (emotional state and thoughts) and external (visual and tactile) triggering stimuli. Obsessive thoughts and related compulsive urges fluctuate (are episodic) and so may respond well to a time-locked brain stimulation strategy sensitive and responsive to these symptom fluctuations. Early evidence suggests that neural activity can be captured from ventral striatal regions implicated in OCD to guide such a closed-loop approach. Here, we report on a first-in-human application of responsive deep brain stimulation (rDBS) of the ventral striatum for a treatment-refractory OCD individual who also had comorbid epilepsy. Self-reported obsessive symptoms and provoked OCD-related distress correlated with ventral striatal electrophysiology. rDBS detected the time-domain area-based feature from invasive electroencephalography low-frequency oscillatory power fluctuations that triggered bursts of stimulation to ameliorate OCD symptoms in a closed-loop fashion. rDBS provided rapid, robust, and durable improvement in obsessions and compulsions. These results provide proof of concept for a personalized, physiologically guided DBS strategy for OCD.
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Estimulación Encefálica Profunda , Trastorno Obsesivo Compulsivo , Estriado Ventral , Humanos , Estimulación Encefálica Profunda/métodos , Resultado del Tratamiento , Trastorno Obsesivo Compulsivo/terapia , Conducta ObsesivaRESUMEN
To determine the humane use of slaughter methods we examined the clinical signs of life in 61 American alligators harvested on-farm using one of three methods: (i) captive bolt and spinal cord severance; (ii) electrostunning, spinal cord severance and pithing; and (iii) spinal cord severance and pithing. Loss of consciousness and the six clinical signs of life that can be used on-farm were assessed for evidence of irreversible unconsciousness and death at Time 0, 0.5, 1, 2, 5, 10, 20, and 30 min post slaughter. The brains of alligators from each slaughter method were removed to assess brain tissue disruption. A combination of loss of blink reflex, pupillary light response, jaw tone and respiration are a reliable on-farm tool for determining death. Heartbeat and withdrawal reflex persisted. Captive bolt and electrostunning methods were effective in immediately producing loss of response consistent with irreversible unconsciousness, subsequent death and destruction of neural tissue integrity in the mid and hind brain. They are therefore humane forms of slaughter in American alligators.
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Background: Although rarely framed as enacted stigma, adults with Tourette syndrome (ATS) have long suffered from discrimination associated with their tic symptoms. Given the high stress levels of enacted stigma that ATS experience, it is expected that their tic symptoms are profoundly impacted. However, the evidence linking enacted stigma to ATS's tic symptoms remains limited. Methods: This study used a secondary data-analysis approach to reanalyze the data from the follow-up phase of a multi-centered, randomized controlled trial in which a behavioral intervention was tested for its efficacy in managing tic symptoms. This study first conducted psychometric testing on a list of 16 enacted stigma events across five life stages and identified the underlying factor structure. The Yale Global Tic Severity Scale (YGTSS) was used to assess severity and impairment of current tic symptoms, whereas the Clinical Global Impression of Severity scale (CGI) was used to obtain the gestalt of clinical judgment on tic severity. A series of multivariate linear models were then fitted to test the relationships between different types of lifetime enacted stigma and current tic symptoms. Results: The analytic sample included 73 young ATS (average age of 23.2 [standard deviation = 2.5] years). The factor analysis identified three types of enacted stigmas: "traumatic events," "confrontations," and "subtle mistreatments." In multivariate models, traumatic events significantly associated with YGTSS-severity, whereas subtle mistreatments provided additional explanations for CGI. Conclusions: Enacted stigma may play important roles in shaping ATS's current tics symptom severity and, therefore, should be carefully considered in future intervention development.
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INTRODUCTION: Comprehensive behavioral intervention for tics (CBIT) is an efficacious, first-line treatment for Tourette syndrome (TS) and other chronic or persistent tic disorders. However, CBIT's public health impact has been limited by suboptimal treatment access. Preliminary research has shown that providing CBIT over videoconference (teleCBIT) is a promising delivery method for patients who cannot access in-person care. However, extant studies have been small efficacy trials focused only on pediatric patients. Replication of these studies is needed in additional treatment settings and across a wider age range of patients, especially in light of advances in telehealth technology and increasing telehealth adoption among practitioners. METHODS: We conducted a single-arm trial to evaluate the feasibility, acceptability, and effectiveness of teleCBIT embedded in comprehensive, medical tic specialty clinics. From October 2016 to September 2018, patients were offered teleCBIT at their usual care appointments. Those who were interested and met inclusion/exclusion criteria received 8 sessions of CBIT guided by a manualized protocol. An independent evaluator, masked to treatment progress, administered assessments at baseline, post-treatment, and 3 and 6 months after treatment. RESULTS: Twenty-five percent of patients who were offered treatment initiated teleCBIT through the study, and all treatment initiators completed treatment. From pre- to post-treatment, decreases in Yale Global Tic Severity Scale (YGTSS) total tic severity scores showed a large effect size among pediatric patients (n = 19; t = 5.72, P < 0.001, d = 1.31) and a medium-to-large effect size for adult patients (n = 10, t = 1.41, P = 0.096, d = 0.664). Thirteen of 19 pediatric patients (68%) and 6 of 10 adult patients (60%) had a positive global treatment response at post-treatment. Patients rated the treatment as highly satisfactory. Ninety-three percent of sessions were free of substantial technical problems. DISCUSSION: Within the context of medical tic specialty clinics, teleCBIT demonstrated strong evidence of feasibility, acceptability, and preliminary effectiveness comparable to in-person treatment for both pediatric and adult patients. TeleCBIT warrants study in future research on enhancing care systems for patients with TS. TRIAL REGISTRY: https://clinicaltrials.gov/ct2/keydates/NCT04007913.
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BACKGROUND: Identifying neural activation patterns that predict youths' treatment response may aid in the development of imaging-based assessment of emotion dysregulation following trauma and foster tailored intervention. Changes in cortical hemodynamic activity measured with functional near-infrared spectroscopy (fNIRS) may provide a time and cost-effective option for such work. We examined youths' PTSD symptom change following treatment and tested if previously identified activation patterns would predict treatment response. METHODS: Youth (N = 73, mean age = 12.97, SD = 3.09 years) were randomly assigned to trauma-focused cognitive behavioral therapy (TF-CBT), cue-centered therapy (CCT), or treatment as usual (TAU). Parents and youth reported on youth's PTSD symptoms at pre-intervention, post-intervention, and follow-up. Neuroimaging data (N = 31) assessed at pre-intervention were obtained while youth engaged in an emotion expression task. Treatment response slopes were calculated for youth's PTSD symptoms. RESULTS: Overall, PTSD symptoms decreased from pre-intervention through follow-up across conditions, with some evidence of relative benefit of TF-CBT and CCT over TAU but significant individual variation in treatment response. Cortical activation patterns were correlated with PTSD symptom improvement slopes (r = 0.53). In particular, cortical responses to fearful and neutral facial stimuli in six fNIRS channels in the bilateral dlPFC were important predictors of PTSD symptom improvement. CONCLUSIONS: The use of fNIRS provides a method of monitoring and assessing cortical activation patterns in a relatively inexpensive and portable manner. Associations between functional activation and youths' PTSD symptoms improvement may be a promising avenue for understanding emotion dysregulation in clinical populations.
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Terapia Cognitivo-Conductual , Padres , Humanos , Adolescente , NiñoRESUMEN
Background: Individuals with Tourette Syndrome and Persistent Tic Disorders (collectively TS) often experience premonitory urges-aversive physical sensations that precede tics and are temporarily relieved by tic expression. The relationship between tics and premonitory urges plays a key role in the neurobehavioral treatment model of TS, which underlies first-line treatments such as the Comprehensive Behavioral Intervention for Tics (CBIT). Despite the efficacy of CBIT and related behavioral therapies, less than 40% of adults with TS respond to these treatments. Further examination of the relationship between premonitory urges, tic severity, and tic impairment can provide new insights into therapeutic targets to optimize behavioral treatment outcomes. This study examined whether urge intolerance-difficulty tolerating premonitory urges-predicted tic severity and tic-related impairment among adults with TS. Methods: Participants were 80 adults with TS. Assessments characterized premonitory urge, distress tolerance, tic severity, and tic impairment. We used structural equation modeling (SEM) to examine the construct of urge intolerance-comprised of premonitory urge ratings and distress tolerance ratings. We first evaluated a measurement model of urge intolerance through bifactor modeling, including tests of the incremental value of subfactors that reflect premonitory urge severity and distress tolerance within the model. We then evaluated a structural model where we predicted clinician-rated tic severity and tic impairment by the latent variable of urge intolerance established in our measurement model. Results: Analyses supported a bifactor measurement model of urge intolerance among adults with TS. Consistent with theoretical models, higher levels of urge intolerance predicted greater levels of clinician-rated tic severity and tic impairment. Conclusion: This investigation supports the construct of urge intolerance among adults with TS and distinguishes it from subcomponents of urge severity and distress tolerance. Given its predictive relationship with tic severity and tic impairment, urge intolerance represents a promising treatment target to improve therapeutic outcomes in adults with TS.
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OBJECTIVE: To determine the long-term durability of behavior therapy for tics among youth with Tourette disorder and persistent (chronic) motor or vocal tic disorders. METHOD: Of the 126 youth who participated in a randomized controlled trial of behavior therapy 11 years prior, 80 were recruited for this longitudinal follow-up. Consenting participants were interviewed in person or remotely (Web-based video) by trained evaluators to determine the course of tics, current tic severity, and tic-related impairment. Recruitment and data collection occurred between 2014 and 2019, with an average follow-up duration of 11.2 years. RESULTS: Treatment responders to both conditions in the original trial achieved partial, but not full, tic remission. Tic severity also decreased significantly across the sample, with 40% reporting partial remission. Behavior therapy responders (n = 21) in the original trial were more likely (67%) to achieve remission at follow-up (Total Tic Score = 12.52, SD = 10.75) compared to psychoeducation/supportive therapy responders (n = 6, 0%) at follow-up (Total Tic Score = 20.67, SD = 6.92) on the Yale Global Tic Severity Scale. Tic-related impairment decreased across the sample, with no significant differences between treatment groups or responders. CONCLUSION: Despite limitations of unmeasured variables and veracity of self-report at follow-up, this study supports guidelines recommending behavior therapy as the first-line intervention for tics. Further investigation of behavior therapy as an early preventive intervention also merits attention.
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Trastornos de Tic , Tics , Síndrome de Tourette , Adolescente , Terapia Conductista , Humanos , Índice de Severidad de la Enfermedad , Trastornos de Tic/terapia , Tics/terapia , Síndrome de Tourette/terapiaRESUMEN
Tics peak in late childhood and decline during adolescence. Yet, for some with Tourette's disorder, tics persist into adulthood. We evaluated childhood predictors of adult tic severity and tic impairment, and change over time. Eighty adolescents/adults were evaluated 11 years following a randomized-controlled trial of behavior therapy. An independent evaluator rated tic severity and tic impairment at baseline, posttreatment, and long-term follow-up. At baseline, parents completed demographics/medical history, and youth tic, internalizing, and externalizing symptom ratings. Youth rated premonitory urge severity and family functioning. After controlling for prior tic treatment effects, female sex and higher tic severity predicted higher tic severity in adulthood; and female sex, no stimulant medication use, higher tic severity, and poorer family functioning predicted higher tic impairment. Higher tic severity and premonitory urge severity predicted smaller reductions in tic severity, whereas higher externalizing symptoms predicted greater reduction in tic severity. Female sex predicted smaller reduction in tic impairment, and externalizing symptoms predicted greater reduction in tic impairment. Female sex and childhood tic severity are important predictors of tic severity and tic impairment in adulthood. Family functioning, premonitory urge severity, and tic severity are important modifiable targets for early or targeted intervention to improve long-term outcomes.
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Trastornos de Tic , Tics , Síndrome de Tourette , Adolescente , Adulto , Terapia Conductista , Niño , Femenino , Humanos , Índice de Severidad de la Enfermedad , Trastornos de Tic/complicaciones , Trastornos de Tic/terapia , Tics/terapia , Síndrome de Tourette/complicaciones , Síndrome de Tourette/terapiaRESUMEN
Given the limited treatment options for trichotillomania (TTM), or Hair Pulling Disorder, this large randomized clinical trial evaluated the efficacy of acceptance-enhanced behavior therapy for TTM (AEBT-TTM) in reducing TTM severity relative to psychoeducation and supportive therapy (PST). Eighty-five adults (78 women) with TTM received 10 sessions (over 12 weeks) of either AEBT-TTM or PST. Independent evaluators masked to treatment assignment assessed participants at baseline (week 0), midpoint (week 6), and endpoint (week 12). Consistent with a priori hypotheses, 64% of the adults treated with AEBT-TTM were classified as clinical responders at post-treatment relative to 38% treated with PST. Clinical responders were identified by a score of 1 or 2 on the Clinical Global Impressions-Improvement (CGI-I) scale. Relative to the PST group, the AEBT-TTM group demonstrated significantly greater pre-to post-treatment reductions on the self-report Massachusetts General Hospital-Hairpulling Scale (MGH-HS) and the evaluator-rated National Institute of Mental Health Trichotillomania Severity Scale (NIMH-TSS). There were no significant post-treatment group differences on the Clinical Global Impressions-Severity (CGI-S) scale, or rate of TTM diagnoses. Results suggest AEBT-TTM provides greater treatment benefit than PST. Future research should continue to investigate AEBT-TTM along with mediators and moderators of its efficacy.