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Association of Small Life Events With Self Reports of Tic Severity in Pediatric and Adult Tic Disorder Patients
Abstract
Clinical experience suggests an association between stressful life events and fluctuations in symptom severity of tic disorder patients. The aim of the present study was to examine this possible relationship in a prospective longitudinal design.
Two groups of patients with tic disorder according to the research criteria of the Tourette Syndrome Classification Study Group were included in this study (Sept. 2001 through March 2002): a pediatric group aged from 7 through 16 years (N = 25) and an adult group aged 18 years and older (N = 32). During a 12-week period, participants were asked weekly to fill out questionnaires regarding the occurrence of small life events and self ratings of tic severity.
Twenty-four of 25 patients in the pediatric group completed the study, and 28 of 32 patients in the adult group completed the study and reported at least 1 life event. In the adult group as a whole, we found a weak but statistically significant correlation between negative small life events and tic severity during the same week (r = 0.268, p <.001). However, only a minority of individual pediatric (21%) and adult (18%) patients demonstrated significant relationships between the frequency of small life events and tic severity in the same week or 1 week later (p </=.05), with undesirable small life events positively associated with tic severity in some patients and negatively associated with tic severity in other patients.
Contrary to traditional views, in general, life events do not account for changes in tic severity. Only in a minority of tic disorder patients do fluctuations in symptom severity appear to be associated with possibly stressful small life events.
... Biomolecules 2020, 10, 848 2 of 23 syndrome [10,11]. Tourette's patients display enhanced frequency and intensity of stereotypic motor patterns (tics) under threatening situations [12,13], and children show increased SB in unfamiliar settings [1]. The variability among human Tourette patients precludes a thorough exploration of the underlying mechanism(s), underlining the need for animal models of this syndrome. ...
... The elevated stress signaling [100] and reduced inhibitory tone in executive brain regions of the emotional motor interface [101,102] in Tourette's syndrome parallel our observations in TgR mice. The frequency and intensity of tics (a stereotypic motor pattern) displayed by Tourette's patients increase under situations perceived as threatening [12,13]. In addition, striatal cholinergic activity is involved in both human SB and psychosis. ...
Stereotypic behavior (SB) is common in emotional stress-involved psychiatric disorders and is often attributed to glutamatergic impairments, but the underlying molecular mechanisms are unknown. Given the neuro-modulatory role of acetylcholine, we sought behavioral-transcriptomic links in SB using TgR transgenic mice with impaired cholinergic transmission due to over-expression of the stress-inducible soluble ‘readthrough’ acetylcholinesterase-R splice variant AChE-R. TgR mice showed impaired organization of behavior, performance errors in a serial maze test, escape-like locomotion, intensified reaction to pilocarpine and reduced rearing in unfamiliar situations. Small-RNA sequencing revealed 36 differentially expressed (DE) microRNAs in TgR mice hippocampi, 8 of which target more than 5 cholinergic transcripts. Moreover, compared to FVB/N mice, TgR prefrontal cortices displayed individually variable changes in over 400 DE mRNA transcripts, primarily acetylcholine and glutamate-related. Furthermore, TgR brains presented c-fos over-expression in motor behavior-regulating brain regions and immune-labeled AChE-R excess in the basal ganglia, limbic brain nuclei and the brain stem, indicating a link with the observed behavioral phenotypes. Our findings demonstrate association of stress-induced SB to previously unknown microRNA-mediated perturbations of cholinergic/glutamatergic networks and underscore new therapeutic strategies for correcting stereotypic behaviors.
... Furthermore, tic severity is correlated with self-report ratings of daily stress [12] and recent adverse events [13]. Tics can be exacerbated by specific stressors, such as hypostimulation and fatigue [14]; the contribution of acute psychosocial stress may be more complex [15]. ...
Ample evidence suggests that acute stress can worsen symptom severity in Tourette syndrome (TS); however, the neurobiological underpinnings of this phenomenon remain poorly understood. We previously showed that acute stress exacerbates tic-like and other TS-associated responses via the neurosteroid allopregnanolone (AP) in an animal model of repetitive behavioral pathology. To verify the relevance of this mechanism to tic pathophysiology, here we tested the effects of AP in a mouse model recapitulating the partial depletion of dorsolateral cholinergic interneurons (CINs) seen in post-mortem studies of TS. Mice underwent targeted depletion of striatal CINs during adolescence and were tested in young adulthood. Compared with controls, partially CIN-depleted male mice exhibited several TS-relevant abnormalities, including deficient prepulse inhibition (PPI) and increased grooming stereotypies after a 30-min session of spatial confinement - a mild acute stressor that increases AP levels in the prefrontal cortex (PFC). These effects were not seen in females. Systemic and intra-PFC AP administration dose-dependently worsened grooming stereotypies and PPI deficits in partially CIN-depleted males. Conversely, both AP synthesis inhibition and pharmacological antagonism reduced the effects of stress. These results further suggest that AP in the PFC mediates the adverse effects of stress on the severity of tics and other TS-related manifestations. Future studies will be necessary to confirm these mechanisms in patients and define the circuitry responsible for the effects of AP on tics.
... This relationship has been confirmed by longitudinal analyses, which have documented that cumulative psychosocial stress predicts future tic severity 11 . Furthermore, tic severity is correlated with self-report ratings of daily stress 12 and recent adverse events 13 . Tics can be exacerbated by specific stressors, such as hypostimulation and fatigue 14 ; the contribution of acute psychosocial stress may be more complex 15 . ...
Ample evidence suggests that acute stress can worsen symptom severity in Tourette syndrome (TS); however, the neurobiological underpinnings of this phenomenon remain poorly understood. We previously showed that acute stress exacerbates tic-like and other TS-associated responses via the neurosteroid allopregnanolone (AP) in an animal model of repetitive behavioral pathology. To verify the relevance of this mechanism to tic pathophysiology, here we tested the effects of AP in a mouse model recapitulating the partial depletion of cholinergic interneurons (CINs) in the striatum seen in postmortem studies of TS. Mice underwent targeted depletion of striatal CINs during adolescence and were tested in young adulthood. Compared with controls, CIN-depleted male mice exhibited several TS-relevant abnormalities, including deficient prepulse inhibition (PPI) and increased grooming stereotypies after a 30-min session of spatial confinement, a mild acute stressor that increases AP synthesis in the prefrontal cortex (PFC). These effects were not seen in females. Systemic and intra-PFC AP administration dose-dependently worsened grooming stereotypies and PPI deficits in CIN-depleted males. Conversely, both AP synthesis inhibition and pharmacological antagonism reduced the effects of stress. These results further suggest that AP in the PFC mediates the adverse effects of stress on the severity of tics and other TS manifestations. Future studies will be necessary to confirm these mechanisms in patients and define the circuitry responsible for the effects of AP on tics.
... Inflammation, microenvironmental change, and immune response are major contributors to asthma, allergic disease, and related neuropsychiatric disorders. Small life events aggravate tic behavior and increase the severity of TS [27]. Whether neuropsychiatric adverse drug reactions (ADRs) such as anxiety or aggravation are induced or further trigger tics or TS events with LTRA use remains unknown. ...
(1) Background: Cysteinyl leukotriene receptor antagonists (LTRAs), including montelukast and zafirlukast, are FDA-approved for treating pediatric asthma and allergic diseases. Tourette syndrome (TS), a common neuropsychiatric disorder in children, is associated with allergic diseases and asthma. In this study, we investigated the risk of TS following an LTRA prescription for pediatric allergic diseases. (2) Methods: Children younger than 18 years of age who were newly diagnosed with asthma, allergic rhinitis, or atopic dermatitis between 1 January 2005 and 31 December 2018 and who were registered in the Taiwan National Health Insurance Research Database, which comprises the medical records of nearly 23 million Taiwanese population, were enrolled. LTRA users were matched with randomly selected LTRA non-users by sex, age, asthma-diagnosis year, and urbanization level. In total, 26,984 participants with allergic disease and TS were enrolled and included in the Cox proportional hazards model analysis. (3) Results: Children with allergic disease and asthma treated with LTRAs had a higher risk for TS than LTRA non-users (adjusted hazard ratio 1.376 [95% CI: 1.232–1.536], p < 0.001). LTRA users had a significantly higher risk for TS than LTRA non-users with allergic disease. The cumulative incidence of TS was significantly higher in LTRA users than in non-users with allergic diseases and asthma (log-rank test, p < 0.0001). (4) Conclusion: A prescription of LTRAs, mainly montelukast, increased the risk of TS among children with asthma, allergic rhinitis, or atopic dermatitis. The mechanism underlying the neuropsychiatric effect of LTRAs needs further investigation.
... Other studies show similar results. In a prospective longitudinal study from 2004, there was a small but statistically significant correlation between negative minor life events and tic severity on the aggregate level [35]. However, when the same study looked at the association on the individual level, only a minority of participants demonstrated a significant relationship between the two. ...
Much of the research regarding Tourette’s syndrome (TS) has focused on why certain individuals develop tics while others do not. However, a separate line of research focuses on the momentary influences that cause tics to increase or decrease in patients who are already known to have TS or another chronic tic disorder (CTD). Environmental and internal variables such as fatigue, anxiety, and certain types of thoughts all have been shown to worsen tic severity and may even overcome the positive effects of treatment. Other influences such as stress, distraction, and being observed have had mixed effects in the various studies that have examined them. Still, other variables such as social media exposure and dietary habits have received only minimal research attention and would benefit from additional study. Understanding the impact of these environmental and internal influences provides an opportunity to improve behavioral treatments for TS/CTD and to improve the lives of those living with these conditions. This review will examine the current literature on how these moment-to-moment influences impact tic expression in those with TS/CTD.
... In contrast, tic suppressibility frequently occurs with concentration, participating in emotionally pleasing activities, or while asleep. 4 A premonitory urge/sensation occurs in up to 95% of people with tic disorders with most becoming aware of its presence by age 10. 5 Peak tic severity is greatest between 10-12 years of age with subsequent improvement thereafter in about 70% of affected individuals. 6,7 Chronic tic disorders (CTD) are more frequent in males, require the presence of tics for greater than one year, have an age of onset before age 18, a waxing and waning course, and the absence of either a substance-induced or general medical condition causation for the tics. ...
Background and Objectives
Since the onset of the COVID-19 pandemic, there has been a dramatic change in the presentation of patients with tics. The explosive presentation of atypical tics has been noted worldwide and thought to be the manifestation of a pandemic-associated functional neurological disorder following social media exposure to tics. Nevertheless, despite the frequent diagnosis of functional tics, there is no existing formal diagnostic criteria. The primary aim of this study was to create a patient-based diagnostic checklist for making the diagnosis of a functional tic disorder during the COVID-19 pandemic.
Methods
A retrospective chart review at a single institution during the pandemic was performed. Based on available literature, diagnostic criteria were created for typical tics, functional tics, and patients with dramatically evolving symptoms (i.e., ‘mixed’ with prior history of mild tics with later fulminant functional worsening). Patient demographics, comorbidities, and tic characteristics of these groups were then compared. Following initial assessments, new diagnostic criteria were established and statistically reanalyzed.
Results
198 patients underwent investigation. Significant differences in age, sex, psychological comorbidities, tic characteristics, and tic severity were found between patients with typical tics when compared to either of the two the functional groups. Only the presence of rostrocaudal progression and increased obsessive-compulsive behaviors were significantly different between patients with new onset functional tics and those with functional worsening of a previous tic disorder. Results also showed that age of tic onset was not a contributing factor for group differentiation. Many patients with functional tics were not exposed to videos depicting tics on social media.
Discussion
This study confirms the presence of a distinct presentation of atypical tics during the pandemic period. It further establishes the validity of specific criteria useful in dividing patients with tics into three formal diagnostic criteria: 1) primary tic disorders; 2) a strictly functional tic disorder; and 3) a mixed tic disorder consisting of patients with an initial history of a primary tic disorder and the later development of functional tics. Explicit diagnostic criteria should enable clinicians and researchers to make a definitive identification and assist patients and families become more knowledgeable and accepting of the diagnosis of functional tics.
... Several explanations may be possible for the significant magnitude-response relationship between maternal depressive/anxious symptoms and children's later tic frequency. First, maternal depressive/anxious symptoms may affect the occurrence, persistence, and exacerbation of children's tics as an environmental factor because environmental factors such as psychosocial stresses are known to exacerbate tics (55)(56)(57)(58)(59). In addition, several studies have shown that tic frequency can be influenced by antecedent environmental events and social consequences although they referred relatively immediate and short term reaction. ...
Background: Previous studies have revealed an association between maternal depressive/anxious symptoms and children's tics. However, the longitudinal relationships between these symptoms remain unclear. We examined the longitudinal relationships between maternal depressive/anxious symptoms and children's tic frequency in early adolescence with a population-based sample.
Methods: The participants consisted of 3,171 children and their mothers from the Tokyo Teen Cohort (TTC) study, a population-representative longitudinal study that was launched in Tokyo in 2012. Maternal depressive/anxious symptoms and children's tics were examined using self-report questionnaires at the ages of 10 (time 1, T1) and 12 (time 2, T2). A cross-lagged model was used to explore the relationships between maternal depressive/anxious symptoms and children's tic frequency.
Results: Higher levels of maternal depressive/anxious symptoms at T1 were related to an increased children's tic frequency at T2 (β = 0.06, p < 0.001). Furthermore, more frequent children's tics at T1 were positively related to maternal depressive/anxious symptoms at T2 (β = 0.06, p < 0.001).
Conclusions: These findings suggest a longitudinal bidirectional relationship between maternal depressive/anxious symptoms and children's tic frequency in early adolescence that may exacerbate each other over time and possibly create a vicious cycle. When an early adolescent has tics, it might be important to identify and treat related maternal depressive/anxious symptoms.
... Furthermore, other studies have shown that tic severity is correlated with self-report ratings of daily stress 94 and recent negative events 95 . While these studies support the conventional framework that acute or short-term stress has a detrimental impact on tic This article is protected by copyright. ...
The neurosteroid allopregnanolone (3α‐hydroxy‐5α‐pregnan‐20‐one; AP) elicits pleiotropic effects in the central nervous system, ranging from neuroprotective and anti‐inflammatory functions to the regulation of mood and emotional responses. Several lines of research show that the brain rapidly produces AP in response to acute stress to reduce the allostatic load and enhance coping. These effects are likely mediated by GABAA receptor activation but may also be contributed by other mechanisms, such as the stimulation of membrane progesterone receptors. In keeping with this evidence, AP has been shown to exert rapid, potent antidepressant properties and has been recently approved for the therapy of moderate‐to‐severe postpartum depression. In addition to depression, emerging evidence points to the potential of AP as a therapy for other neuropsychiatric disorders, including anxiety, seizures, PTSD, and cognitive problems. While this evidence has spurred interest in further therapeutic applications of AP, some investigations suggest that this neurosteroid may also be associated with adverse events in specific disorders. For example, our group has recently documented that AP increases tic‐like manifestations in several animal models of tic disorders; furthermore, our results indicate that inhibiting AP synthesis and signaling reduces the exacerbation of tic severity associated with acute stress. Although the specific mechanisms of these effects remain partially elusive, our findings point to the possibility that the GABAergic activation by AP may also lead to disinhibitory effects, which could interfere with the ability of patients to suppress their tics. Future studies will be necessary to verify whether these mechanisms may apply to other externalizing manifestations, such as impulse‐control problems and manic symptoms.
... Several explanations may be possible for the signi cant magnitude-response relationship between maternal depressive/anxious symptoms and children's later tics. First, maternal depressive/anxious symptoms may affect the occurrence, persistence, and exacerbation of children's tics as an environmental factor because environmental factors such as psychosocial stresses are known to exacerbate tics (44)(45)(46)(47)(48). There are no reports of an association between maternal psychiatric symptoms and the course of children's tics. ...
Background: Previous studies have revealed an association between maternal depressive/anxious symptoms and children’s tics. However, the longitudinal relationships between these symptoms remain unclear. We examined the longitudinal relationships between maternal depressive/anxious symptoms and children’s tics across early adolescence in a population-based sample.
Methods: The participants consisted of 3,171 children and their mothers from the Tokyo Teen Cohort (TTC) study, a population-representative longitudinal study that was launched in Tokyo in 2012. Maternal depressive/anxious symptoms and children’s tics were examined using self-report questionnaires at the ages of 10 (time 1, T1) and 12 (time 2, T2). A cross-lagged model was used to explore the relationships between maternal depressive/anxious symptoms and children’s tics.
Results: Higher levels of maternal depressive/anxious symptoms at T1 were related to an increased likelihood of children’s tics at T2 (β = .06, p = .001). Furthermore, the presence of children’s tics at T1 was positively related to maternal depressive/anxious symptoms at T2 (β = .06, p = .001).
Conclusions: These findings suggest a longitudinal bidirectional relationship between maternal depressive/anxious symptoms and children’s tics during early adolescence that may exacerbate each other over time and possibly create a vicious cycle. When an early adolescent has tics, it might be important to identify and treat related maternal depressive/anxious symptoms.
... 28 Yukardaki faktörlere ek olarak TS'li çocuklarla ilgili yapılan bir çalışmada; hastalığın doğal seyrini, günlük yaşam stresörlerinin önemli yaşam olaylarından daha çok etkilediği gösterilmiştir. 31 Ayrıca termal duyarlılığı olan bazı hastalarda artmış tik sıklığı ile vücut sıcaklığı ile ilişkili olabileceği savunulmuştur. 32 Yapılan prospektif uzunlamasına nörogörüntüleme çalışmalarından elde edilen veriler, çocukluk döneminde kaudat çekirdeğinin hacminin, tik ve OKB semptomlarının seyrinin erişkin döneme geçişini öngördürebileceği yönünde olmuştur. ...
In this chapter, we offer an exploration of Tourette's Syndrome (TS), tracing its historical and clinical understandings, from its early identification in nineteenth-century France to contemporary perspectives on its aetiology, symptomatology, and treatment. We delve into the development of definitions and labelled characteristics of TS, as well as its prevalence, clinical manifestations, and comorbidities such as Attention Deficit/Hyperactive Disorder (ADHD) and Obsessive-Compulsive Disorder (OCD). In so doing, we critically review previous theories that have linked TS to hysteria, psychosexual disturbance, and voluntary habit formation, highlighting the paradigm shift to a more nuanced neurobiological understanding of the condition. Finally, we critique dominant medicalised models of disability, arguing for a critical realist approach that recognises the often hidden role of stigmatising attitudes as well as discriminatory behaviours and structural barriers in the experience of TS. This highlights the importance of integrating the lived experiences of people with Tourette’s into the discourse, moving away from mainly pathological perspectives, and advocating for a more inclusive understanding of TS as part of a complex neurodevelopmental spectrum. Participants’ quotes throughout the text provide real-world insights into the experience of living with TS, illustrating its polymorphous nature. Our objective is to foster a critical dialogue on the biological, social, and psychological dimensions of TS, urging for medical and social reforms to improve the quality of life for people with Tourette’s that take into account the nuanced, intersectional, and diverse nature of the condition.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Tourette syndrome (TS) is now recognized as a common neurodevelopmental disorder affecting children and adults. It has gained increasingly public awareness and scientific interest worldwide. Knowledge of its clinical presentation and available treatment approaches has increased dramatically over the last two decades. Tourette Syndrome offers a unique, comprehensive, and up-to-date overview of TS. The volume highlights the latest findings regarding clinical presentation, underlying genetic, epigenetic, immunological, and neurobiological causal mechanisms, and state-of-the-art therapies. Importantly, in this digital world of ours and given the ongoing pandemic, this volume also provides a detailed review of the latest available multifaceted and multidisciplinary treatment options including psychoeducational and cognitive-behavioral interventions, many of which can now be accessed online. More than 50 leading scientists and expert clinicians from across the globe authored the chapters. Readers can also access videotaped presentations recorded by several of these scholars. Fortunately, several of these presentations include individuals with TS and related conditions who have graciously volunteered to discuss their life’s journey. This volume is a useful source for a wide audience of scholars and clinicians, all of whom will have access to what is known so far on TS and related conditions within their area of expertise. It provides readers an opportunity to expand and update their knowledge base in other areas of science and advocacy. Families and health professionals will also have access to updates from a broad range of advocacy associations and organizations all around the world that are dedicated to improving lives of individuals with TS.
Tourette syndrome (TS) is now recognized as a common neurodevelopmental disorder affecting children and adults. It has gained increasingly public awareness and scientific interest worldwide. Knowledge of its clinical presentation and available treatment approaches has increased dramatically over the last two decades. Tourette Syndrome offers a unique, comprehensive, and up-to-date overview of TS. The volume highlights the latest findings regarding clinical presentation, underlying genetic, epigenetic, immunological, and neurobiological causal mechanisms, and state-of-the-art therapies. Importantly, in this digital world of ours and given the ongoing pandemic, this volume also provides a detailed review of the latest available multifaceted and multidisciplinary treatment options including psychoeducational and cognitive-behavioral interventions, many of which can now be accessed online. More than 50 leading scientists and expert clinicians from across the globe authored the chapters. Readers can also access videotaped presentations recorded by several of these scholars. Fortunately, several of these presentations include individuals with TS and related conditions who have graciously volunteered to discuss their life’s journey. This volume is a useful source for a wide audience of scholars and clinicians, all of whom will have access to what is known so far on TS and related conditions within their area of expertise. It provides readers an opportunity to expand and update their knowledge base in other areas of science and advocacy. Families and health professionals will also have access to updates from a broad range of advocacy associations and organizations all around the world that are dedicated to improving lives of individuals with TS.
The complex neurobiology of motor and phonic tics remains under active investigation. The phenomenology of tics—their timing and varied expression over the course of a lifetime—provide a foundation for understanding the neurobiology of tic disorders. Their waxing and waning course, and the frequent presence of “premonitory” urges, experienced just prior to a tic, are core elements of the phenomenology of tics. Indeed, gaining control of premonitory urges are at the heart of proven behavioral interventions for tic disorders. A clearer understanding of the pathophysiology of tics will set the stage for novel treatments. However, each individual with tics is unique with regard to their genetic background, their physical and social environment during the course their development, as well as the frequent co-occurrence of other neuropsychiatric symptoms, including attentional difficulties, motoric hyperactivity, and obsessive-compulsive behaviors. There are also a number of individuals with tic disorders who are on the autism spectrum. A deeper understanding of the altered structural connectivity seen in many individuals with tics will be an important next step. However, for the clients and families that we serve, as well as for the next generation of clinicians, scholars, teachers, and peers, it is very important that they gain an understanding of the phenomenology of tic disorders and related conditions that may lead to better clinical social and academic outcomes.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Tourette syndrome (TS) is now recognized as a common neurodevelopmental disorder affecting children and adults. It has gained increasingly public awareness and scientific interest worldwide. Knowledge of its clinical presentation and available treatment approaches has increased dramatically over the last two decades. Tourette Syndrome offers a unique, comprehensive, and up-to-date overview of TS. The volume highlights the latest findings regarding clinical presentation, underlying genetic, epigenetic, immunological, and neurobiological causal mechanisms, and state-of-the-art therapies. Importantly, in this digital world of ours and given the ongoing pandemic, this volume also provides a detailed review of the latest available multifaceted and multidisciplinary treatment options including psychoeducational and cognitive-behavioral interventions, many of which can now be accessed online. More than 50 leading scientists and expert clinicians from across the globe authored the chapters. Readers can also access videotaped presentations recorded by several of these scholars. Fortunately, several of these presentations include individuals with TS and related conditions who have graciously volunteered to discuss their life’s journey. This volume is a useful source for a wide audience of scholars and clinicians, all of whom will have access to what is known so far on TS and related conditions within their area of expertise. It provides readers an opportunity to expand and update their knowledge base in other areas of science and advocacy. Families and health professionals will also have access to updates from a broad range of advocacy associations and organizations all around the world that are dedicated to improving lives of individuals with TS.
Tourette syndrome (TS) is now recognized as a common neurodevelopmental disorder affecting children and adults. It has gained increasingly public awareness and scientific interest worldwide. Knowledge of its clinical presentation and available treatment approaches has increased dramatically over the last two decades. Tourette Syndrome offers a unique, comprehensive, and up-to-date overview of TS. The volume highlights the latest findings regarding clinical presentation, underlying genetic, epigenetic, immunological, and neurobiological causal mechanisms, and state-of-the-art therapies. Importantly, in this digital world of ours and given the ongoing pandemic, this volume also provides a detailed review of the latest available multifaceted and multidisciplinary treatment options including psychoeducational and cognitive-behavioral interventions, many of which can now be accessed online. More than 50 leading scientists and expert clinicians from across the globe authored the chapters. Readers can also access videotaped presentations recorded by several of these scholars. Fortunately, several of these presentations include individuals with TS and related conditions who have graciously volunteered to discuss their life’s journey. This volume is a useful source for a wide audience of scholars and clinicians, all of whom will have access to what is known so far on TS and related conditions within their area of expertise. It provides readers an opportunity to expand and update their knowledge base in other areas of science and advocacy. Families and health professionals will also have access to updates from a broad range of advocacy associations and organizations all around the world that are dedicated to improving lives of individuals with TS.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Childhood adversity is associated with the development or expression of many neuropsychiatric disorders, including those with strong genetic underpinnings. Despite reported associations between perceived stress and tic severity, the relationship between potentially traumatic events in childhood and Tourette Syndrome (TS), a highly heritable neuropsychiatric disorder, is unknown. This study aimed to assess whether exposure to eight categories of adverse childhood experiences (ACEs) is associated with TS severity and impairment, and whether TS genetic risk modifies this association. Online survey data were collected from 351 adult males with TS who previously participated in genetic studies. Participants completed the ACE questionnaire and a lifetime version of the Yale Global Tic Severity Scale (YGTSS). Demographic and relevant health data were assessed; polygenic risk scores (PRS) measuring aggregated TS genetic risk were derived using genome-wide association data. Univariable and multivariable linear regressions examined the relationships between childhood adversity and retrospectively recalled worst-ever tic severity and impairment, adjusting for covariates. Potential gene-by-environment (GxE) interactions between ACE and PRS were estimated. After covariate adjustment, there was a significant graded dose-response relationship between ACE Scores and increases in lifetime worst-ever tic severity and impairment. There was some evidence that TS genetic risk moderated the relationship between ACE Score and tic impairment, but not tic severity, particularly for individuals with higher TS polygenic risk. We provide evidence that childhood adversity is associated with higher lifetime TS severity and impairment, although future longitudinal studies with genetically-sensitive designs are needed to determine whether these relationships are causal and/or directional.
Tourette syndrome (TS) is now recognized as a common neurodevelopmental disorder affecting children and adults. It has gained increasingly public awareness and scientific interest worldwide. Knowledge of its clinical presentation and available treatment approaches has increased dramatically over the last two decades. Tourette Syndrome offers a unique, comprehensive, and up-to-date overview of TS. The volume highlights the latest findings regarding clinical presentation, underlying genetic, epigenetic, immunological, and neurobiological causal mechanisms, and state-of-the-art therapies. Importantly, in this digital world of ours and given the ongoing pandemic, this volume also provides a detailed review of the latest available multifaceted and multidisciplinary treatment options including psychoeducational and cognitive-behavioral interventions, many of which can now be accessed online. More than 50 leading scientists and expert clinicians from across the globe authored the chapters. Readers can also access videotaped presentations recorded by several of these scholars. Fortunately, several of these presentations include individuals with TS and related conditions who have graciously volunteered to discuss their life’s journey. This volume is a useful source for a wide audience of scholars and clinicians, all of whom will have access to what is known so far on TS and related conditions within their area of expertise. It provides readers an opportunity to expand and update their knowledge base in other areas of science and advocacy. Families and health professionals will also have access to updates from a broad range of advocacy associations and organizations all around the world that are dedicated to improving lives of individuals with TS.
Tic disorders, exemplified by Tourette syndrome, are movement abnormalities manifested by brief movements or sounds that begin in childhood, are frequently associated with various comorbid problems, and often cause psychosocial difficulties, that may persist into adulthood. This chapter provides a practical approach for understanding, evaluating, and treating tic disorders. The specific etiologies and neuroanatomical locations remain under investigation. Behavioral, pharmacological, and surgical treatments usually improve the quality of lite of patients with tics.
Tics can be associated with neurological disorders and are thought to be the result of dysfunctional basal ganglia pathways. In Tourette Syndrome (TS), excess dopamine in the striatum is thought to excite the thalamocortical circuits, producing tics. When external stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, more dopamine is produced, furthering the excitation of tic-producing pathways. Emotional processing structures in the limbic are also activated during tics, providing further evidence of a possible emotional component in motor ticking behaviors.
Tics can be associated with neurological disorders and are thought to be the result of dysfunctional basal ganglia pathways. In Tourette Syndrome (TS), excess dopamine in the striatum is thought to excite the thalamo-cortical circuits, producing tics. When external stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, more dopamine is produced, furthering the excitation of tic-producing pathways. Emotional processing structures in the limbic are also activated during tics, providing further evidence of a possible emotional component in motor ticking behaviors. The purpose of this review is to better understand the relationship between emotional states and ticking behavior. We found support for the notion that premonitory sensory phenomena (PSP), sensory stimulation, and other environmental stressors that impact the HPA axis can influence tics through dopaminergic neurotransmission. Dopamine plays a vital role in cognition and motor control and is an important neurotransmitter in the pathophysiology of other disorders such as obsessive–compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD), which tend to be comorbid with ticking disorders and are thought to use similar pathways. It is concluded that there is an emotional component to ticking behaviors. Emotions primarily involving anxiety, tension, stress, and frustration have been associated with exacerbated tics, with PSP contributing to these feelings.
Tics can be associated with neurological disorders and are thought to be the result of dysfunctional basal ganglia pathways. In Tourette Syndrome (TS), excess dopamine in the striatum is thought to excite the thalamo-cortical circuits, producing tics. When external stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, more dopamine is produced, furthering the excitation of tic-producing pathways. Emotional processing structures in the limbic are also activated during tics, providing further evidence of a possible emotional component in motor ticking behaviors. The purpose of the review is to better understand the relationship between emotional states and ticking behavior. We found support for the notion that premonitory-sensory phenomena (PSP), sensory stimulation, and other environmental stressors that impact the HPA-axis can influence tics through dopaminergic neurotransmission. Dopamine plays a vital role in cognition and motor control, and is an important neurotransmitter in the pathophysiology of other disorders such as obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD), which tend to be comorbid with ticking disorders and are thought to use similar pathways. It is concluded that there is an emotional component to ticking behaviors. Emotions primarily involving anxiety, tension, stress, and frustration have been associated with exacerbated tics, with PSP contributing to these feelings.
Gilles de la Tourette syndrome (TS) is a common, childhood-onset psychiatric disorder characterized by persistent motor and vocal tics. It is a heterogeneous disorder in which the phenotypic expression may be affected by environmental factors, such as immune responses. Furthermore, several studies have shown that genetic factors play a vital role in the etiology of TS, as well as its comorbidity with other disorders, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, and autism spectrum disorder. TS has a complex inheritance pattern and, according to various genetic studies, several genes and loci have been correlated with TS. Genome-wide linkage studies have identified Slit and Trk-like 1 (SLITRK1) and histidine decarboxylase (HDC) genes, and candidate gene association studies have extensively investigated the dopamine and serotonin system genes, but there have been no consistent results. Moreover, genome-wide association studies have implicated several genetic loci; however, larger study cohorts are needed to confirm this. Copy number variations, which are polymorphisms in the number of gene copies due to chromosomal deletions or duplications, are considered another significant source of mutations in TS. In the last decade, whole genome/exome sequencing has identified several novel genetic mutations in patients with TS. In conclusion, more studies are needed to reveal the exact mechanisms of underlying TS, which may help to provide more information on the prognosis and therapeutic plans for TS.
Background: Previous studies have revealed an association between maternal depressive/anxious symptoms and children’s tics. However, the longitudinal relationships between these symptoms remain unclear. We examined the longitudinal relationships between maternal depressive/anxious symptoms and children’s tic frequency in early adolescence with a population-based sample.
Methods: The participants consisted of 3,171 children and their mothers from the Tokyo Teen Cohort (TTC) study, a population-representative longitudinal study that was launched in Tokyo in 2012. Maternal depressive/anxious symptoms and children’s tics were examined using self-report questionnaires at the ages of 10 (time 1, T1) and 12 (time 2, T2). A cross-lagged model was used to explore the relationships between maternal depressive/anxious symptoms and children’s tic frequency.
Results: Higher levels of maternal depressive/anxious symptoms at T1 were related to an increased children’s tic frequency at T2 (β = .06, p < .001). Furthermore, more frequent children’s tics at T1 were positively related to maternal depressive/anxious symptoms at T2 (β = .06, p < .001).
Conclusions: These findings suggest a longitudinal bidirectional relationship between maternal depressive/anxious symptoms and children’s tic frequency in early adolescence that may exacerbate each other over time and possibly create a vicious cycle. When an early adolescent has tics, it might be important to identify and treat related maternal depressive/anxious symptoms.
The development of an inventory to assess small events is described. In the construction of the inventory specific criteria were established and existing event inventories were screened for items and new items written to fit these criteria. The event had to denote an observable change in a person's everyday life, have a discrete beginning, be classifiable as either desirable or undesirable, and be scaled as having an average of 250 Life Change Units or less using B. S. Dohrenwend, Krasnoff, Askenasy, Dohrenwend's (1978) magnitude estimation parameters. The inventory was constructed to cover events in major areas of life concern: family, work, leisure, household, financial, health/illness, nonfamily relations, crime/criminal activity, education, religion, and transportation. Two studies are reported that test the utility of the inventory.
This study examined prospectively the effects of stressful events, depressive symptoms, social support, coping methods, and cortisol levels on progression of HIV-1 infection.
Eighty-two homosexual men with HIV type-1 infection without AIDS or symptoms at baseline were studied every 6 months for up to 7. 5 years. Men were recruited from rural and urban areas in North Carolina, and none was using antiretroviral medications at entry. Disease progression was defined as CD4(+) lymphocyte count <200/microl or the presence of an AIDS indicator condition.
Cox regression models with time-dependent covariates were used adjusting for race, baseline CD4(+) count and viral load, and cumulative average antiretroviral medications. Faster progression to AIDS was associated with higher cumulative average stressful life events, coping by means of denial, and higher serum cortisol as well as with lower cumulative average satisfaction with social support. Other background (e.g., age, education) and health habit variables (e.g., tobacco use, risky sexual behavior) did not significantly predict disease progression. The risk of AIDS was approximately doubled for every 1.5-unit decrease in cumulative average support satisfaction and for every cumulative average increase of one severe stressor, one unit of denial, and 5 mg/dl of cortisol.
Further research is needed to determine if treatments based on these findings might alter the clinical course of HIV-1 infection.
We provide a review of recent research findings which support the involvement of autoimmunity in childhood-onset tic disorders, in particular the presence of antineuronal autoantibodies, D8/17 B lymphocyte overexpression, a marker of chorea associated with streptococcal infection, and possible beneficial effects of immunomodulatory intervention. One of the most controversial areas in this field is the validity of the proposed PANDAS concept. Some researchers have delineated a putatively unique subgroup of patients, from the spectrum of illness encompassing Tourette's syndrome and obsessive-compulsive disorder (OCD), whose tics and obsessive-compulsive symptoms are shown to arise in response to beta-hemolytic streptococcal infections. They designated it by the term pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Herein we additionally present pros and cons concerning the concept of PANDAS. Finally, recommendations for future research directions are given.
: We review empirical evidence from two field studies for the role of stressful life events in disease flare-ups among patients with rheumatoid arthritis (RA). RA patients were expected to be more vulnerable psychologically, and physiologically, to stressful events in their everyday lives than other arthritis patients without an autoimmune disease. Findings from two studies are reviewed both for their substantive contribution, but also to provide guidance on measurement issues in future field research of this kind. One study included 41 patients with RA, who were interviewed weekly and called to a clinic for blood work and joint examinations when their levels of interpersonal stress increased significantly. A second study used a similar design but included comparison samples of patients with osteoarthritis (OA) and healthy controls of similar age and the same gender as the RA sample. The findings provided support for the proposition that interpersonal stressors are predictive of increases in disease activity. Not all RA patients, however, showed these relationships, and there was evidence that some participants with OA who were depressed also showed higher disease activity following interpersonal stressors. Significant individual differences in the stress-disease relationship were uncovered that deserve greater attention in future studies. Important improvements in the assessment of stressful events and refinements in panel study design are also presented as guides to research on the role of stress in disease processes.
The relationship of daily uplifts and hassles to adaptational outcomes has gained increasing attention in recent years. However, investigators have focused considerably more on hassles than uplifts. In an attempt to rectify this trend, the present study examines the relationship of uplifts and hassles to anxiety, depression, distress, self-restraint, perceived sup-port from friends, perceived social competence, and general self-worth in a sample of 23 sixth graders (141 girls). Results indicate that both hassles and uplifts are substantially related to these outcomes in the expected direction, with the exception of a modest positive association between uplift and anxiety for girls. Moreover, in most cases uplifts add significantly to the relationship between hassles and outcomes, thus high-lighting the importance of uplifts. Other findings idicate that uplifts/hassles patterns vary as a function of gender and the particular outcome being considered. Similarities to and differences from adult findings are discussed in regard to gender-role and general development.
This study investigated headache parameters (frequency and intensity) in relation to (the number and severity of) two types of psychosocial stress: major life events (as assessed by a revised Social Readjustment Rating Scale) and minor daily hassles (as assessed by a revised Hassles Scale). Subjects were 261 volunteers reporting headache. Results revealed that both headache frequency and intensity were significantly predicted by daily hassles, in particular, the average severity of these hassles, but there was a negligible relationship between headache parameters and any of the life event measures. Furthermore, a significant relationship emerged between life events and daily hassles themselves. This fits with recent findings that life events (while exerting little direct effect on headache) may trigger a succession of hassles which culminate in headaches. Also, it is not the number of hassles, but the perceived severity of these hassles that best predicts headache frequency and intensity. Finally, though significant as predictors, daily hassles explained a small portion of the variance in headache, thus pointing to the host of other possible biological and psychosocial contributions to headache.
Abstract— The purpose of this paper is to assess how 29 different environmental factors affected Tourette symptomatology in 14 children and adolescents (6.6–14.5 years; mean 10.3) who had never received any medication for their disorder. Assessment was based on patients' responses to the Tourette Syndrome (TS) Questionnaire. Eleven different factors were associated with a decrease in symptoms and included doctor visits, talking to friends, and reading for pleasure. The 10 factors reported to have no impact on Tourette symptomatology included various foods, weather, and living away from home. Seventeen factors associated with an increase in Tourette symptoms included events causing anxiety, emotional trauma, and social gatherings.
Objective: This study examined the effects of change in interpersonal stress on disease activity among 41 women with rheumatoid
arthritis (RA). Methods: Measures of everyday stressful events and perceived stress were collected weekly for twelve weeks
and related to disease activity in a series of pooled time-series regression analyses. Results: Increases in the number of
interpersonal stressors in the same week and one week prior were associated with increases in disease activity. Pain from
joint tenderness also was significantly related to a decrease in stressful events one week later. A subgroup of 20 patients
showed a significant increase in interpersonal stress from baseline during the course of the study. For this group, significant
elevations in DR+CD3 cells, sIL-2R, clinician's rating of disease, and self-reports of joint tenderness were found during
the week of increased interpersonal stress. Conclusions: Interpersonal stress appears to be associated with increases in disease
activity among RA patients
To investigate the relationship between changes in daily hassles and life events and biological (lipoproteins, blood pressure, body fat, and body fat distribution) and lifestyle (physical activity, smoking and alcohol consumption) risk factors for coronary heart disease (CHD) 166 subjects were measured twice, at 27 and 29 years of age. The results showed that changes in daily hassles were positively related to changes in lipoprotein levels, daily physical activity, and to smoking behavior. These relationships were more pronounced for subjects with a “rigid” coping style and subjects with type A behavior. Changes in life events were also positively related to lipoprotein levels, but only for subjects with a “rigid” coping style and only when the subjective appraisal of life events was taken into account. It was concluded that the relationships seemed to be mediated by different coping styles and type A behavior, that daily hassles were more important in these relationships than life events, and that the relationships with biological CHD risk factors were not influenced by lifestyle.
Despite the overt nature of most motor and phonic tic phenomena, the development of valid and reliable scales to rate tic severity has been an elusive goal. The Yale Global Tic Severity Scale (YGTSS) is a new clinical rating instrument that was designed for use in studies of Tourette's syndrome and other tic disorders. The YGTSS provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. Data from 105 subjects, aged 5 to 51 years, support the construct, convergent, and discriminant validity of the instrument. These results indicate that the YGTSS is a promising instrument for the assessment of tic severity in children, adolescents and adults.
The purpose of this paper is to assess how 29 different environmental factors affected Tourette symptomatology in 14 children and adolescents (6.6-14.5 years; mean 10.3) who had never received any medication for their disorder. Assessment was based on patients' responses to the Tourette Syndrome (TS) Questionnaire. Eleven different factors were associated with a decrease in symptoms and included doctor visits, talking to friends, and reading for pleasure. The 10 factors reported to have no impact on Tourette symptomatology included various foods, weather, and living away from home. Seventeen factors associated with an increase in Tourette symptoms included events causing anxiety, emotional trauma, and social gatherings.
Tourette's syndrome (TS) is a complex inherited neuropsychiatric disorder that is characterized by multiple motor and phonic tics. Stress-related fluctuations in symptom severity and medication responsiveness are common, and patients often report that tics are worsened by fatigue, emotional trauma, and anxiety. We examined the effects of lumbar puncture (LP) stress on plasma adrenocorticotropin (ACTH) and cortisol, urinary catecholamines, and self- and clinician ratings of anxiety in 13 medication-free TS patients and 10 normal controls, ages 17 to 41 years. The TS patients secreted significantly more ACTH than the normal controls in response to the stress of the lumbar puncture. Compared to the controls the TS patients had significantly greater postLP mean and postLP peak ACTH levels. The TS patients also excreted significantly more norepinephrine in the 20 hr preceding the lumbar puncture and reported higher levels of anxiety before and during the procedure than the controls. In addition, urinary norepinephrine excretion of the TS patients was significantly correlated with clinician ratings of tic severity. The results were not related to current levels of depression and anxiety. Taken together, these findings suggest that a subset of TS patients may be characterized by heightened reactivity of the hypothalamic-pituitary-adrenal axis and related noradrenergic sympathetic systems.
To assess the influence of life event stress and hassles, and the moderating effects of psychological coping style, social support, and family environment, on susceptibility to upper respiratory tract infectious illness.
One hundred seven adults aged 18 to 65 years took part in a 15-week study. Measures of life event stress were obtained for the 12 months preceding the study and for the study period itself, and social support, information seeking and avoidant coping styles, and family environment were assessed. Hassles and perceived stress were measured weekly, whereas dysphoric mood and changes in personal health practices (smoking, alcohol consumption, exercise, and sleep patterns) were assessed at three weekly intervals. Episodes of upper respiratory tract infectious illness were verified by clinical examination.
During the study period, 29 individuals experienced at least one clinically verified episode of upper respiratory tract illness. There were no differences in cigarette smoking, sleep habits, or exercise between those who did and did not become ill but alcohol consumption was lower among those who experienced verified episodes. Risk of infectious illness was greater in those who experienced high life event stress both before and during the study period, but the impact of life events was buffered by an avoidant coping style. Strict family organization was associated with illness risk. The three weeks preceding illness onset were characterised by high levels of perceived stress, but also by a decrease in the number of hassles reported.
Results suggest that under naturalistic conditions, the influence of stressful experience on risk of infectious illness is moderated by psychosocial resources. Variations in personal health practices do not seem to be responsible.
In a recent article, Erenberg and Fahn¹ presented reasons why they prefer the Tourette Syndrome Association classification of tic disorders² to that of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).³ Other authors4,5 have similarly expressed reservations about the DSM-IV criteria. We agree with the points raised by Erenberg and Fahn and now present additional concerns about the DSM-IV criteria and provide an alternative classification scheme that we believe is more consistent with current information and is more appropriate for application to genetic studies. Accurate phenotypic diagnosis is crucial to our current research efforts to localize the genetic defects of Tourette syndrome (TS). 1. Vocal tics are sounds produced by moving air through the nose, mouth, or throat.² The movement of air and the production of sounds are accomplished by the contraction of muscles of the mouth, tongue, pharynx, larynx, diaphragm, and
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) is a relatively new diagnostic construct applied to children or adolescents who develop, and have repeated exacerbations of, tic disorders and/or obsessive-compulsive disorder following group A beta-hemolytic streptococcal infections. The proposed pathophysiology is that the group A beta-hemolytic streptococcal bacteria trigger antibodies that cross-react with the basal ganglia of genetically susceptible hosts leading to obsessive-compulsive disorder and/or tics. This is similar to the etiologic mechanisms proposed for Sydenham's chorea, in which group A beta-hemolytic streptococcal antibodies cross-react with the basal ganglia and result in abnormal behavior and involuntary movements. When first proposed, there was much controversy about the idea that streptococcal infections were etiologically related to rheumatic fever. In a like manner, discussion has arisen about the concept of infection-triggered obsessive-compulsive disorder and tic disorders. We review the historical background to these controversies, give an update on the findings provided by research on PANDAS, and address areas of future study.
Fifty-five boys and 61 girls, aged 5-16 years, took part in a 15-week longitudinal study of stress and upper respiratory infectious illness. Life events, social support, and psychological coping were measured, and hassles and mood were assessed repeatedly throughout the study period. Upper respiratory symptoms were recorded daily, and episodes of upper respiratory infection were verified by clinical examination. Forty-eight verified episodes of infection were recorded from 41 participants (35.3% of the total sample). Life events and social support interacted in predicting the occurrence of infection, whereas hassles interacted with avoidant psychological coping, independently of age, gender, family composition, social class, negative affect, parental perceived stress, parental smoking, or alcohol consumption. The duration of symptomatic episodes was negatively associated with problem-focused coping, and positively related to avoidant coping. Hassle levels were elevated 3 weeks prior to symptom onset. These results indicate that the impact of life stress on vulnerability to infectious illness in children is moderated by psychological coping and social resources, and that different psychosocial factors influence the occurrence and duration of infections.
With the goal of evaluating the available literature on the course of Tourette's disorder, we conducted a systematic literature search through electronic databases for pertinent scientific articles in English with a minimum of 20 subjects. We also examined bibliographies of papers identified in this manner for additional sources. We found only 16 articles; most consisted of retrospective reports on treated samples. Overall, the available literature suggests that Tourette's disorder follows a remitting course in a sizeable number of individuals. Little has been published regarding predictors of remission or persistence. More work is needed using longitudinal prospective studies to better define the course and outcome of Tourette's disorder.
As our knowledge of Gilles de la Tourette's syndrome increases, so does our appreciation for the pathogenic complexity of this disorder and the challenges associated with its treatment. Advances in the neurosciences have led to new models of pathogenesis, whereas clinical studies have reinvigorated early hypotheses. The interdependent roles of genes and environment in disease formation have yet to be fully elucidated. Results of epidemiological studies have prompted debate on how best to characterise and diagnose this disorder. Absence of ideal anti-tic drugs, combined with knowledge that uncomplicated cases of childhood Tourette's syndrome frequently have a favourable outcome, has led to striking changes in care and treatment of patients. This seminar focuses on these changing views and offers a new perspective on our understanding of the pathogenesis of Tourette's syndrome and on principles for treatment of patients with this disorder.
The Yale Children's Global Stress Index (YCGSI) is a new clinical rating instrument designed to provide objective global clinician ratings of psychosocial stress in studies of children and adolescents. This study was designed to evaluate the psychometric properties of the YCGSI.
Independent ratings of clinical severity and psychosocial stress were obtained at two time points separated by 4 months from 33 subjects with Tourette's syndrome (TS) and/or early-onset obsessive-compulsive disorder (OCD), aged 7 to 17 years, and 25 age-matched control subjects. Parents and children were interviewed separately. Multiple measures of stress were obtained including the YCGSI and the Daily Life Stressors Scale (DLSS).
Data support the interrater reliability and convergent and divergent validity of the YCGSI. At both time points, children and adolescents with TS and OCD had, on average, experienced significantly more psychosocial stress than did the controls. Cross-sectional ratings of tic and obsessive-compulsive symptom severity did not correlate with the YCGSI, but did correlate with self-report ratings of stress on the DLSS. In contrast, ratings on the YCGSI were associated with clinician ratings of depression.
The YCGSI has acceptable psychometric properties. Children and adolescents with TS and OCD appear to be at increased risk of experiencing higher levels of psychosocial stress and adversities compared with their peers in the community. Future studies need to examine the possible differential contributions of distinctive forms of stress on the intramorbid course of these disorders.
Measuring small life events Uplifts, hassles, and adaptational outcomes in early adolescents
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PANDAS: The search for Environmental Triggers of Pediatric Neuropsychiatric Disorders. Lessons from Rheumatic Fever
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