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Comprehensive Behavioral Intervention for Tics (CBIT) is recommended as a first-line treatment for Tourette syndrome in children and adults. While there is strong evidence proving its efficacy, the mechanisms of reduction in tic severity during CBIT are still poorly understood. In a recent study, our group identified a functional brain network involved in tic suppression in children with TS. We reasoned that voluntary tic suppression and CBIT may share some mechanisms and thus we wanted to assess whether functional connectivity during tic suppression was associated with CBIT outcome.
Thirty-two children with TS, aged 8 to 13 years old, participated in a randomized controlled trial of CBIT v. a treatment-as-usual control condition. EEG was recorded during tic suppression in all participants at baseline and endpoint. We used a source-reconstructed EEG connectivity pipeline to assess functional connectivity during tic suppression.
Functional connectivity during tic suppression did not change from baseline to endpoint. However, baseline tic suppression-related functional connectivity specifically predicted the decrease in vocal tic severity from baseline to endpoint in the CBIT group. Supplementary analyses revealed that the functional connectivity between the right superior frontal gyrus and the right angular gyrus was mainly driving this effect.
This study revealed that functional connectivity during tic suppression at baseline predicted reduction in vocal tic severity. These results suggest probable overlap between the mechanisms of voluntary tic suppression and those of behavior therapy for tics.
The symptoms of obsessive−compulsive disorder (OCD) are highly heterogeneous and it is unclear what is the optimal way to conceptualize this heterogeneity. This study aimed to establish a comprehensive symptom structure model of OCD across the lifespan using factor and network analytic techniques.
A large multinational cohort of well-characterized children, adolescents, and adults diagnosed with OCD (N = 1366) participated in the study. All completed the Dimensional Yale-Brown Obsessive−Compulsive Scale, which contains an expanded checklist of 87 distinct OCD symptoms. Exploratory and confirmatory factor analysis were used to outline empirically supported symptom dimensions, and interconnections among the resulting dimensions were established using network analysis. Associations between dimensions and sociodemographic and clinical variables were explored using structural equation modeling (SEM).
Thirteen first-order symptom dimensions emerged that could be parsimoniously reduced to eight broad dimensions, which were valid across the lifespan: Disturbing Thoughts, Incompleteness, Contamination, Hoarding, Transformation, Body Focus, Superstition, and Loss/Separation. A general OCD factor could be included in the final factor model without a significant decline in model fit according to most fit indices. Network analysis showed that Incompleteness and Disturbing Thoughts were most central (i.e. had most unique interconnections with other dimensions). SEM showed that the eight broad dimensions were differentially related to sociodemographic and clinical variables.
Future research will need to establish if this expanded hierarchical and multidimensional model can help improve our understanding of the etiology, neurobiology and treatment of OCD.
This article provides an overview of selected ongoing international efforts that have been inspired by Edward Zigler's vision to improve programs and policies for young children and families in the United States. The efforts presented are in close alignment with three strategies articulated by Edward Zigler: (a) conduct research that will inform policy advocacy; (b) design, implement, and revise quality early childhood development (ECD) programs; and (c) invest in building the next generation of scholars and advocates in child development. The intergenerational legacy left by Edward Zigler has had an impact on young children not only in the United States, but also across the globe. More needs to be done. We need to work together with a full commitment to ensure the optimal development of each child.
This study integrated an experimental medicine approach and a randomized cross-over clinical trial design following CONSORT recommendations to evaluate a cognitive training (CT) intervention for attention deficit hyperactivity disorder (ADHD). The experimental medicine approach was adopted because of documented pathophysiological heterogeneity within the diagnosis of ADHD. The cross-over design was adopted to provide the intervention for all participants and make maximum use of data.
Children (n = 93, mean age 7.3 +/− 1.1 years) with or sub-threshold for ADHD were randomly assigned to CT exercises over 15 weeks, before or after 15 weeks of treatment-as-usual (TAU). Fifteen dropped out of the CT/TAU group and 12 out of the TAU/CT group, leaving 66 for cross-over analysis. Seven in the CT/TAU group completed CT before dropping out making 73 available for experimental medicine analyses. Attention, response inhibition, and working memory were assessed before and after CT and TAU.
Children were more likely to improve with CT than TAU (27/66 v. 13/66, McNemar p = 0.02). Consistent with the experimental medicine hypotheses, responders improved on all tests of executive function (p = 0.009–0.01) while non-responders improved on none (p = 0.27–0.81). The degree of clinical improvement was predicted by baseline and change scores in focused attention and working memory (p = 0.008). The response rate was higher in inattentive and combined subtypes than hyperactive-impulsive subtype (p = 0.003).
Targeting cognitive dysfunction decreases clinical symptoms in proportion to improvement in cognition. Inattentive and combined subtypes were more likely to respond, consistent with targeted pathology and clinically relevant heterogeneity within ADHD.
In the absence of definitive etiological markers of vulnerability or a unitary profile of pathophysiology for obsessive-compulsive disorder (OCD), obsessive-compulsive (OC) symptom dimensions seem to offer a fruitful point of orientation.The complex clinical presentation of OCD can be summarized using a few consistent and temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping features that are likely to be continuous with “normal” worries and extend beyond the traditional nosological boundaries of OCD. Although the understanding of the dimensional structure of obsessive-compulsive symptoms (OCS) is still imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. Preliminary data suggest that these dimensional phenotypes may be useful in studies of the natural history, genetics, neurobiology, and treatment outcome of OCD. A dimensional approach is not mutually exclusive of other methods to parse the larger spectrum of disorders related to OCD. Thus far, age-of-onset of OCS and the individual's “tic-related” status seem to be particularly useful categorical distinctions. Finally, existing assessment methods are inadequate and new dimensional scales are needed to take full advantage of a dimensional approach in clinical and population-based studies.
Introduction: Selective serotonin reuptake inhibitors are considered the most effective and well-established pharmacotherapy for the treatment of obsessive-compulsive disorder (OCD), a chronic and disabling condition. However, ~40% of patients do not have a significant improvement, suggesting that new medications are needed. This study was designed to investigate the treatment response to escitalopram in OCD patients.
Methods: This open-label study involved 11 adult OCD outpatients diagnosed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders. Data were collected and the treatment response was assessed by an experienced psychiatrist by using the Yale-Brown Obsessive-Compulsive Scale. Subjects received escitalopram 30 mg/day for 12 weeks starting at 10 mg/day. Dosage adjustments were made within 2 weeks, depending on the tolerability of the patient.
Results: Six of the 11 patients (54.5%) presented a reduction of at least 40% in the baseline total Yale-Brown Obsessive-Compulsive Scale scores.
Conclusion: Despite the small sample size and the open-label nature of this trial, these data suggest that escitalopram may be a useful option for patients with OCD.
This chapter focuses on alcohol dependence (alcoholism), because the diagnosis is more reliable and because most of the genetic data focus on dependence. The earliest genetic association studies in alcoholism were candidate gene studies targeting coding variations in the genes that metabolize alcohol. Certain variations in alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH) genes have very strong effects on the risk for alcoholism. Variations in other genes appear to have a much smaller effect on risk. Linkage studies and their follow-up, along with candidate gene studies and genome-wide association studies (GWAS), are beginning to fill the gaps. Initial findings must be confirmed in independent studies, and much work remains to elucidate the mechanisms involved. The future will involve studies of epigenetic factors, copy number variants, and gene expression, as well as tests for rare variants of large effect in specific families.
Children with Tourette syndrome generally experience improvement of tics by age 18 years, but psychosocial and comorbidity outcomes at this age are unclear.
To compare psychosocial outcomes and lifetime comorbidity rates in older adolescents with Tourette syndrome and controls. We hypothesised a priori that individuals with Tourette syndrome would have lower Children's Global Assessment Scale (CGAS) scores.
A total of 65 individuals with Tourette syndrome, identified in childhood, and 65 matched community controls without tic or obsessive–compulsive disorder (OCD) symptoms were assessed around 18 years of age regarding psychosocial functioning and lifetime psychiatric disorders.
Compared with controls, individuals with Tourette syndrome had substantially lower CGAS scores (P=10−8) and higher rates of attention-deficit hyperactivity disorder (ADHD), major depression, learning disorder and conduct disorder (P⩽0.01). In the participants with Tourette syndrome, poorer psychosocial outcomes were associated with greater ADHD, OCD and tic severity.
Clinically ascertained children with Tourette syndrome typically have impaired psychosocial functioning and high comorbidity rates in late adolescence.
in addition to endogenously produced opiates, which are part of normal affiliative neurocircuitry and attachment formation, exogenous opiates – such as drugs of addiction and abuse – may affect affiliation. we consider possible modulatory effects of such exogenous opiates on the development of early parent–infant attachment from both parents' and infants' perspectives.
In addition to the infant cry being a signal for attention, it may also be a critical component of the early formation of attachments with caregivers. We consider the complex development of that attachment, which involves reciprocal interactive signaling and a host of evolutionarily conserved caregiver factors.
This study examined social-emotional functioning in children with Gilles de la Tourette's
syndrome (TS) alone and children with TS and Attention Deficit Hyperactivity Disorder
(ADHD). In addition, the contribution of family functioning to social competence was
examined. Children with a clinical diagnosis of TS were recruited from the Yale Child Study
Center TS specialty clinic. Unaffected control children were recruited through newspaper
advertisements and announcements within the university and at area schools. The final
sample consisted of 72 children (45 boys and 27 girls) between the ages of 8 and 14. Sixteen
children met DMS-III-R criteria for TS, 33 children met criteria for TS and ADHD, and 23
children had no psychiatric diagnoses. Children with TS and ADHD evidenced more
externalizing and internalizing behavior problems and poorer social adaptation than
children with TS only or unaffected controls. Children with TS only were not significantly
different from unaffected controls on most measures of externalizing behaviors and social
adaptation but did exhibit more internalizing symptoms. Tic symptom severity was not
associated with social, behavioral, or emotional functioning among children with TS, even
after stratifying by medication status. However, ADHD diagnosis, obsessional symptom
severity, and family functioning were significantly associated with social and emotional
adjustment among TS children. Moreover, family functioning was associated with social and
emotional adjustment even after controlling for TS and ADHD diagnostic status. These
findings demonstrate that much of the social and behavioral dysfunction in children with TS
is ADHD-specific and children with TS alone have a very different social-emotional profile
than do those with TS plus ADHD. Finally, social-emotional adjustment in children with TS
is best understood within the family context.
Attachment has generally been examined from the infant's perspective. We focused on
mothers' post-partum thoughts and behaviors. Guided by an ethological approach, maternal
bonding was examined under conditions of proximity, separation, and potential loss.
Ninety-one mothers were interviewed: mothers of full-term infants who maintained
continuous proximity to the infant, mothers of healthy premature infants who were
separated from the infant, and mothers of very low birthweight infants who experienced
potential loss and prolonged separation. Mothers of term infants reported medium-to-high
levels of preoccupations with thoughts of infant safety and well-being. Preoccupations
increased with separation (Group 2) and significantly decreased with impending loss (Group
3). Attachment behaviors and representations were the highest among mothers of term
infants and declined linearly with the duration of mother–infant separation. Maternal trait
anxiety and depression were related respectively to higher levels of preoccupations and
reduced attachment behaviors and representations, independent of the infant medical
condition and mother–child separation. Discussion focused on the comparability of maternal
and infant attachment in relation to the neurobiological system underlying bond formation.
Obsessive–compulsive disorder (OCD) is heterogeneous, with some forms related to Gilles de la Tourette's syndrome (GTS). This is a phenomenological study designed to investigate the nature of these possible OCD subtypes and the relationship between OCD and GTS.
We evaluated 20 adult outpatients with OCD, 21 with GTS, and 20 with OCD plus GTS using a semi-structured interview designed to assess cognitive, sensory and autonomic phenomena preceding repetitive behaviours.
More cognitions and autonomic anxiety and fewer sensory phenomena were reported in OCD than in GTS. Like the GTS group, the OCD plus GTS group reported more sensory phenomena and fewer cognitions than the OCD group.
The presence or absence of cognitions, sensory phenomena, and autonomic anxiety distinguishes repetitive behaviours in patients with OCD from those with OCD plus GTS, and GTS. These subjective experiences may be useful in subtyping OCD and may represent valid predictors of prognosis and treatment response.
The phenomenological features of 35 obsessive–compulsive disorder (OCD) patients with a lifetime history of tics were compared to 35 age- and sex-matched OCD patients without tics. Seven categories of obsessions and nine categories of compulsions were determined using the symptom checklist of the Yale–Brown Obsessive–Compulsive Scale (YBOCS). Discriminant function analysis revealed that, compared to their counterparts without tics, OCD patients with tics had more touching, tapping, rubbing, blinking and staring rituals, and fewer cleaning rituals, but did not differ on obsessions. These preliminary findings suggest that the types of compulsions present may help to discriminate between two putative subgroups of OCD, i.e. those with and without tics.
Analyses were undertaken to examine whether a wide range of psychiatric disorders, including anxiety, affective, substance abuse and psychotic disorders, represent variant manifestations of Tourette's syndrome (TS). Previous studies have suggested that chronic tics (CT) and obsessive-compulsive disorder (OCD) are variant expressions of TS since both CT and OCD are elevated among relatives of TS probands. In the current study, no other psychiatric disorder was significantly elevated among the relatives who did not have TS, CT or OCD when compared with a control sample. These findings are not consistent with the hypothesis that a wide range of psychiatric and behavioural disorders are variant expressions of TS.
Family-genetic studies of child and adult psychiatric disorders have become increasingly fashionable over the past decade. The development of structured diagnostic interview schedules, the emergence of uniform diagnostic criteria such as DSM-III, and the use of refined design and analytic techniques from the field of chronic disease epidemiology have made substantial contributions to the methodology of such studies. Advances in molecular genetics, particularly our emerging capacity to perform chromosomal linkage studies throughout the human genome, have renewed hope that the constitutional underpinnings of some psychiatric disorders can be identified and that the pathophysiology of these disorders can be elucidated. Family-genetic techniques in child and adult psychiatry are discussed with a particular focus on their potential value in validating diagnostic categories spanning developmental epochs.
An analysis of recently published family history data on rapid eye movement (REM) narcolepsy was undertaken to determine the goodness-of-fit of a multifactorial (MF) model of inheritance. The analysis revealed that a two-threshold MF model can successfully account for the prevalence of REM narcolepsy and other disorders of excessive sleep (DES) observed in the first-degree relatives of the REM narcoleptic probands studied.
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