Cathy Creswell

Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function

Turners syndrome is a sporadic disorder of human females in which all or part of one X chromosome is deleted. Intelligence is usually normal but social adjustment problems are common. Here we report a study of 80 females with Turners syndrome and a single X chromosome, in 55 of which the X was maternally derived (45,Xm) and in 25 it was of paternal origin (45,Xp). Members of the 45,Xp group were significantly better adjusted, with superior verbal and higher-order executive function skills, which mediate social interactions. Our observations suggest that there is a genetic locus for social cognition, which is imprinted and is not expressed from the maternally derived X chromosome. Neuropsychological and molecular investigations of eight females with partial deletions of the short arm of the X chromosome indicate that the putative imprinted locus escapes X-inactivation, and probably lies on Xq or close to the centromere on Xp. If expressed only from the X chromosome of paternal origin, the existence of this locus could explain why 46,XY males (whose single X chromosome is maternal) are more vulnerable to developmental disorders of language and social cognition, such as autism, than are 46,XX females.

The development of anxiety disorders in childhood: an integrative review.

We present an integrative review of the development of child anxiety, drawing on a number of strands of research. Family aggregation and genetic studies indicate raised vulnerability to anxiety in offspring of adults with the disorder (e.g. the temperamental style of behavioural inhibition, or information processing biases). Environmental factors are also important; these include adverse life events and exposure to negative information or modelling. Parents are likely to be key, although not unique, sources of such influences, particularly if they are anxious themselves. Some parenting behaviours associated with child anxiety, such as overprotection, may be elicited by child characteristics, especially in the context of parental anxiety, and these may serve to maintain child disorder. Emerging evidence emphasizes the importance of taking the nature of child and parental anxiety into account, of constructing assessments and interventions that are both disorder specific, and of considering bidirectional influences.

Therapygenetics: the 5HTTLPR and response to psychological therapy

Whilst pharmacogenetic research thrives 1 , genetic determinants of response to purely psychotherapeutic treatments remain unexplored. In a sample of children undergoing Cognitive Behavior Therapy (CBT) for an anxiety disorder, we tested whether treatment response is associated with the serotonin transporter gene promoter region (5HTTLPR), previously shown to moderate environmental influences on depression. Children with the short-short genotype were significantly more likely to respond to CBT than those carrying a long allele.

Individual Differences in Cognitive Planning on the Tower of Hanoi Task: Neuropsychological Maturity or Measurement Error?

The Tower of Hanoi (ToH) task was given to 238 children aged from 7 to 15 years, and 20 adults. Individual variation within an age band was substantial. ToH score did not correlate significantly with Verbal IQ, nor with ability to inhibit a prepotent response. We readministered the ToH to 45 children after 30 to 40 days. The test-retest correlation of .5 is low in relation to accepted psychometric standards, though at least as high as reliability of the related Tower of London (ToL) in adults. The reasons for low reliability remain unclear: task novelty did not seem to be involved, as children did not improve on retest. We conclude that it is not safe to use this test to index integrity or maturation of underlying neurological systems in children. We compared our results with three published studies using the ToL with children, and found similar levels of performance on problems involving the same number of moves. Another study using automated ToL obtained much poorer scores, suggesting that computerised presentation may impair childrens performance.

A Longitudinal Investigation of Maternal and Child 'Anxious Cognitions'

Overestimation of threat and underestimation of coping have been frequently reported amongst anxious adults and children. The current study examines the longitudinal relationship between mothers’ anxious cognitions and expectations about their child, and childrens anxious cognitions. 54 children (aged 10–11 years) and their mothers reported on their interpretation of ambiguous scenarios at two time points. Mothers also reported on their expectations about their childs reaction to ambiguous situations. Significant cross-sectional associations were found between mother and child anticipation of distress. Associations were most consistent between mothers’ expectations and childrens cognitions. Furthermore, based on regression analyses, mothers’ expectations predicted change in childrens anxious cognitions over time. Evidence for a reciprocal relationship, that child cognitions predict change in mothers’ expectations, was found for girls. The results provide empirical support for potential influences on the development of childrens ‘anxious cognitive style,’ and suggest targets for preventing and reducing maladaptive cognitions in children.

Clinical Predictors of Response to Cognitive-Behavioral Therapy in Pediatric Anxiety Disorders: The Genes for Treatment (GxT) Study

Objective The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined demographic and clinical predictors of response to CBT. We hypothesized that the child’s gender, type of anxiety disorder, initial severity and comorbidity, and parents’ psychopathology would significantly predict outcome. Method A sample of 1,519 children 5 to 18 years of age with a primary anxiety diagnosis received CBT across 11 sites. Outcome was defined as response (change in diagnostic severity) and remission (absence of the primary diagnosis) at each time point (posttreatment, 3-, 6-, and/or 12-month follow-up) and analyzed using linear and logistic mixed models. Separate analyses were conducted using data from posttreatment and follow-up assessments to explore the relative importance of predictors at these time points. Results Individuals with social anxiety disorder (SoAD) had significantly poorer outcomes (poorer response and lower rates of remission) than those with generalized anxiety disorder (GAD). Although individuals with specific phobia (SP) also had poorer outcomes than those with GAD at posttreatment, these differences were not maintained at follow-up. Both comorbid mood and externalizing disorders significantly predicted poorer outcomes at posttreatment and follow-up, whereas self-reported parental psychopathology had little effect on posttreatment outcomes but significantly predicted response (although not remission) at follow-up. Conclusion SoAD, nonanxiety comorbidity, and parental psychopathology were associated with poorer outcomes after CBT. The results highlight the need for enhanced treatments for children at risk for poorer outcomes.

Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35–45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT.

Treatment of child anxiety: an exploratory study of the role of maternal anxiety and behaviours in treatment outcome

Anxiety disorders are common among parents of anxious children and have been found to impede child treatment outcomes, yet it is unclear whether it is parental anxiety that needs to be targeted in therapy or associated parental behaviours. Twenty-two children (6-12 years) with a current anxiety disorder and their mothers received cognitive-behavioural treatment (CBT) for child anxiety. In addition, of the 12 mothers who met criteria for a current anxiety disorder, 6 received CBT for their own disorder. Assessments were made of the mother-child interaction. The main findings were: (1) children did less well from treatment where their mothers had a current anxiety disorder; (2) treatment of maternal anxiety disorder did not improve child treatment outcome; and (3) maternal overinvolvement and expression of fear was associated with child treatment outcome. The results suggest that in the context of maternal anxiety disorder, child treatment outcome may be improved by specifically targeting parenting behaviours.

Defensive coping styles in chronic fatigue syndrome

OBJECTIVE The cognitive-behavioral model of chronic fatigue syndrome (CFS) proposes that rigidly held beliefs act to defend individuals against low self-esteem. This study is the first to investigate the prevalence of a potential mechanism, the Defensive High Anxious coping style, among individuals with CFS. METHODS The study comprised 68 participants (24 CFS; 24 healthy volunteers; 20 chronic illness volunteers). Participants completed the Bendig short form of the Taylor Manifest Anxiety Scale (B-MAS) and the Marlowe-Crowne Social Desirability Scale (MC) in order to ascertain the distribution of participants in each group within the four coping styles defined by Weinberger et al. [J. Abnorm. Psychol. 88 (1979) 369]. RESULTS A greater number of participants in the CFS group (46%) were classified as Defensive High Anxious compared to the two comparison groups [chi(2)(2)=8.84, P=.012]. CONCLUSION This study provides support for the existence of defensive coping mechanisms as described by the cognitive-behavioral model of CFS. Furthermore, it has been suggested that this particular coping style may impinge directly on physical well being through similar mechanisms as identified in CFS, and further research linking these areas of research is warranted.

Assessment and management of anxiety disorders in children and adolescents

Anxiety disorders in childhood and adolescence are extremely common and are often associated with lifelong psychiatric disturbance. Consistent with DSM-5 and the extant literature, this review concerns the assessment and treatment of specific phobias, separation anxiety disorder, generalised anxiety disorder, social anxiety disorder, panic disorder and agoraphobia. Evidence-based psychological treatments (cognitive behaviour therapy; CBT) for these disorders have been developed and investigated, and in recent years promising low-intensity versions of CBT interventions have been proposed that offer a means to increase access to evidence-based treatments. There is some evidence of effectiveness of pharmacological treatments for anxiety disorders in children and young people, however, routine prescription is not recommended due to concerns about potential harm.