Kathryn J Lester

• King's College London

Anxiety disorders are are chronic, pervasive, and debilitating; characterised by a persistent or exaggerated response to distal or abstract threats. Impaired threat discrimination (distinguishing safe from threatening stimuli) and impaired threat extinction (learning a once threatening stimulus is now safe), are known risk factors in the developmen...

Background The identification of predictors of treatment response is crucial for improving treatment outcome for children with anxiety disorders. Machine learning methods provide opportunities to identify combinations of factors that contribute to risk prediction models. Methods A machine learning approach was applied to predict anxiety disorder r...

The aftermath of the Covid-19 pandemic has seen an increase in persistent school absenteeism and Emotionally-Based School Avoidance (EBSA). However, suitable evidence-based psychological interventions are often unavailable. We aimed to assess the feasibility and acceptability of a new parent-focused online program, Intervention for School Anxiety a...

Background Children whose parents have anxiety problems are at increased risk of developing anxiety themselves. Parenting behaviors are a contributing factor to intergenerational transmission. Interventions which seek to limit anxiogenic parenting behaviors have shown potential in reducing anxiety in offspring but are not widely accessible. This pr...

Background Studies indicate that the children of mothers who have eating disorders are at an increased risk of developing eating disorders themselves. The aim of this qualitative study was to broaden and extend current understandings of the experiences of mothers with eating disorders. The present report focuses on maternal perspectives, experience...

Background Children and adolescents demonstrate diverse patterns of symptom change and disorder remission following cognitive behavioural therapy (CBT) for anxiety disorders. To better understand children who respond sub‐optimally to CBT, this study investigated youths (N = 1,483) who continued to meet criteria for one or more clinical anxiety diag...

The aftermath of the Covid-19 pandemic has seen an increase in persistent school absenteeism and Emotionally-Based School Avoidance (EBSA). However, suitable evidence-based psychological interventions are often unavailable. We aimed to assess the feasibility, acceptability and potential impacts of a new parent-focused online program, Intervention f...

The COVID-19 pandemic has shown that all emergencies, major incidents and disease outbreaks can have substantial mental health consequences, and it has demonstrated the proven need for additional care for populations in the wake of disasters. This book brings together practice and recent developments in pre-hospital emergency care, emergency medici...

Background The use of a second informant (co-respondent) is a common method of identifying potential bias in outcome data (e.g., parent-report child outcomes). There is, however, limited evidence regarding methods of increasing response rates from co-respondents. The use of financial incentives is associated with higher levels of engagement and fol...

Although primary schools in the UK were required to provide access to remote learning for pupils during Covid‐19 mandated school closures, there was less clarity for teachers and school leaders about expectations and priorities relating to the provision of social and emotional well‐being support for children at home during this period. Using an exi...

Background Covid-19 related school closures radically disrupted children’s access to social and educational opportunities and changed daily life for millions of families across the world. Emerging evidence indicates that, overall, closures were associated with a decline in children’s mental health and well-being, although individual experiences var...

Background: Parent-report questionnaires are a common method of generating data on child outcomes in mental health studies. A second report from another person who knows the child (co-respondent) is implemented to reduce bias and increase objectivity. The success of this approach is dependent on the engagement of co-respondents, which can be diffi...

Over the last 20 years, opportunities for young children to engage in self-directed free play with peers outdoors or during the school day has dramatically declined. Consequently, it is likely that play dates, defined as pre-arranged social contact at home, have become increasingly significant play environments for children. Preliminary research su...

p>Background: Anxiety is the most common childhood mental health condition and is associated with impaired child outcomes, including increased risk of mental health difficulties in adulthood. Anxiety runs in families: when a parent has anxiety, their child has a 50% higher chance of developing it themselves. Environmental factors are predominant in...

Background Anxiety is the most common childhood mental health condition and is associated with impaired child outcomes, including increased risk of mental health difficulties in adulthood. Anxiety runs in families: when a parent has anxiety, their child has a 50% higher chance of developing it themselves. Environmental factors are predominant in th...

Background: Anxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditio...

Objectives We aimed to examine differences in fear conditioning between anxious and nonanxious participants in a single large sample. Materials and methods We employed a remote fear conditioning task (FLARe) to collect data from participants from the Twins Early Development Study (n = 1,146; 41% anxious vs. 59% nonanxious). Differences between gro...

Background and objectives Fear conditioning paradigms use various measures to assess learned fear, including autonomic arousal responses like skin conductance, and self-reports of both associative (US-expectancies) and evaluative (affective ratings) learning. The present study uses a dimensional approach to examine associations among fear indices d...

In this conceptual article, we draw upon the literature regarding cognitive and behavioural factors that underpin childhood anxiety to outline how a range of these risk markers might be targeted through adventurous play. When children play in an adventurous way, climbing trees, riding their bikes fast downhill and jumping from rocks, they experienc...

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety...

Background Anxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditioni...

This study tested the theory that anxious fathers pose a quantitatively different environmental influence on childhood anxiety than anxious mothers. The analysed sample contained 502 linked adoption units from the Early Growth and Development Study (EGDS), a longitudinal multisite study that follows 561 adopted children (57.2% boys) and their adopt...

We introduce the Parent Play Questionnaire (PPQ), a parent‐report measure designed to assess frequency of parent‐infant play, parents’ attitudes towards play with their infant, and infants’ use of digital media. We describe measure development and empirical data across three samples of parent‐infant dyads (total N = 414, offspring aged 0.3 – 2.5 ye...

The Parent Play Questionnaire (PPQ) assesses frequency of parent-infant play, parents’ attitudes towards play with their infant, and infants’ use of digital media. The PPQ is tested here across three samples of parent-infant dyads (N = 414, offspring aged 0.3 – 2.5 years). Three latent factors explain the PPQ, corresponding with the theoretically d...

The Children of the Twins Early Development Study (CoTEDS) is a new prospective children-of-twins study in the UK, designed to investigate intergenerational associations across child developmental stages. CoTEDS will enable research on genetic and environmental factors that underpin parent–child associations, with a focus on mental health and cogni...

Fear conditioning models key processes related to the development, maintenance and treatment of anxiety disorders and is associated with group differences in anxiety. However, laboratory administration of tasks is time and cost intensive, precluding assessment in large samplesnecessary for the analysis of individual differences. This study introduc...

The Children of the Twins Early Development Study (CoTEDS) is a new prospective children-of-twins study in the UK, designed to investigate intergenerational associations across child developmental stages. CoTEDS will enable research on genetic and environmental factors that underpin parent-child associations, with a focus on mental-health and cogni...

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outc...

Questionnaire measures offer a time and cost-effective alternative to full diagnostic assessments for identifying and differentiating between potential anxiety disorders and are commonly used in clinical practice. Little is known, however, about the capacity of questionnaire measures to detect specific anxiety disorders in clinically anxious preado...

Therapygenetics refers to the prediction of psychological therapy outcomes from genetic markers. The rationale for this research derives from the gene–environment interaction literature, which has shown that individual differences in susceptibility to the environment are at least partly due to genetic variation for a wide range of phenotypes. While...

The transition from primary to secondary school is often associated with a period of heightened anxiety and worry. For most children, any feelings of anxiety subside relatively quickly but for a small minority, emotional difficulties can continue into the first year of secondary school and beyond. This study recruited 109 children and measured thei...

Fear conditioning models key processes related to the development, maintenance and treatment of anxiety disorders and is associated with group differences in anxiety. However, laboratory administration of tasks is time and cost intensive, precluding assessment in large samples, necessary for analysis of individual differences. This study introduces...

Background In order to retrieve episodic past events, the missing information needs to be reconstructed using information stored in semantic memory. Failures in these reconstructive processes are expressed as false memories. KIBRA single nucleotide polymorphism (rs17070145) has been linked to episodic memory performance as well as an increased risk...

Differential DNA methylation of the hypothalamic‐pituitary‐adrenal axis related gene FKBP5 has recently been shown to be associated with varying response to environmental influences and may play a role in how well people respond to psychological treatments. Participants (n = 111) received exposure‐based cognitive behavioural therapy (CBT) for agora...

Appendix S1. References to individual trials and a description of methods. Table S1. Percentage of cases per site for treatment formats within diagnostic categories. Table S2. Results of linear and logistic mixed models examining the relationship between primary diagnosis and treatment format in the full sample using all follow‐up points. Table S...

Dopamine D2 receptors (DRD2) have been strongly implicated in reward processing of natural stimuli and drugs. Using the approach-avoidance task (AAT), we recently demonstrated that smokers show an increased approach-bias toward smoking-related cues but not toward naturally rewarding stimuli. Here, we examined the contribution of the DRD2 Taq1B poly...

Table S1. Distributional statistics for the phenotypes in the study, including measurements of internal consistency of the basic summed scores resulting from the DANVA. Table S2. Associations between unbiased hit rates of emotion recognition for each emotion and covariates. Positive betas indicate more accurate emotion recognition. Table S3. Locu...

Exposure-based psychological treatments for anxiety have high efficacy. However, a substantial proportion of patients do not respond to therapy. Research examining the potential biological underpinnings of therapy response is still in its infancy, and most studies have focussed on candidate genes. To our knowledge, this study represents the first i...

Emotion recognition is disrupted in many mental health disorders, which may reflect shared genetic aetiology between this trait and these disorders. We explored genetic influences on emotion recognition and the relationship between these influences and mental health phenotypes. Eight-year-old participants (n = 4,097) from the Avon Longitudinal Stud...

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have...

Supporting Information.

Background The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candida...

Objectives: Exposure-based cognitive behavioural therapy (eCBT) is an effective treatment for anxiety disorders. Response varies between individuals. Gene expression integrates genetic and environmental influences. We analysed the effect of gene expression and genetic markers separately and together on treatment response. Methods: Adult participant...

Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re-emerge. Given the role of the endocann...

Background: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candi...

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety diso...

Supporting Material

Attentional control theory (ACT) proposes that anxiety is associated with executive functioning deficits. The theory has been widely investigated in adults. The current study tested whether symptoms of childhood anxiety and depression were associated with experimentally measured attentional control in the context of non-emotional and emotional stim...

Diurnal preference is an individual's preference for daily activities and sleep timing and is strongly correlated with the underlying circadian clock and the sleep-wake cycle validating its use as an indirect circadian measure in humans. Recent research has implicated DNA methylation as a mechanism involved in the regulation of the circadian clock...

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT).Methods Children with a...

Background We previously reported an association between 5HTTLPR genotype and outcome following cognitive-behavioural therapy (CBT) in child anxiety (Cohort 1). Children homozygous for the low-expression short-allele showed more positive outcomes. Other similar studies have produced mixed results, with most reporting no association between genotype...

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 hypothesiz...

This study examined the effects of verbal information and approach-avoidance training on fear-related cognitive and behavioural responses about novel animals. One hundred and sixty children (7-11 years) were randomly allocated to receive: a) positive verbal information about one novel animal and threat information about a second novel animal (verba...

Background Adolescent depression is a common neuropsychiatric disorder that often continues into adulthood and is associated with a wide range of poor outcomes including suicide. Whilst there have been a number of studies of genetic markers associated with depression, the role of epigenetic variation remains relatively unexplored. We selected monoz...

Background: Childhood anxiety and depression frequently co-occur. Exploring specificity in cognitive processes for anxiety and depression in childhood can provide insight into cognitive vulnerabilities contributing to the development of anxiety and depressive disorders and inform targeted psychological interventions. Anxiety sensitivity and rumina...

Depression frequently co-occurs with paediatric obsessive-compulsive disorder (OCD), yet the clinical correlates and impact of depression on CBT outcomes remain unclear. The prevalence and clinical correlates of depression were examined in a paediatric specialist OCD-clinic sample (N = 295; Mean = 15 [7 – 18] years, 42 % female), using both dimensi...

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. Rece...

Sleep and circadian rhythms are intrinsically linked, with several sleep traits, including sleep timing and duration, influenced by both sleep homeostasis and the circadian phase. Genetic variation in several circadian genes has been associated with diurnal preference (preference in timing of sleep), although there has been limited research on whet...

Sleep is a critical behavior shared by most higher animals. Sleep disturbances are comorbid with numerous psychiatric disorders, most notably symptoms of depression. Twin studies have suggested that genetic influences partially underlie the variation seen for numerous sleep-related traits across individuals. Recently, two Genome-Wide Association St...

Background: Within a therapeutic gene by environment (G × E) framework, we recently demonstrated that variation in the Serotonin Transporter Promoter Polymorphism; 5HTTLPR and marker rs6330 in Nerve Growth Factor gene; NGF is associated with poorer outcomes following cognitive behaviour therapy (CBT) for child anxiety disorders. The aim of this st...

Considerable variation is evident in response to psychological therapies for mood and anxiety disorders. Genetic factors alongside environmental variables and gene-environment interactions are implicated in the etiology of these disorders and it is plausible that these same factors may also be important in predicting individual differences in respo...

Theoretical frameworks highlight the importance of threat-related information-processing biases for understanding the emergence of anxiety in childhood. The psychometric properties of several tasks measuring these biases and their associations with anxiety were examined in an unselected sample of 9-year-old children (N = 155). In each task, threat...

Background: Twin studies in children reveal that familial aggregation of anxiety disorders is due to both genetic and environmental factors. Cognitive biases for threat information are considered a robust characteristic of childhood anxiety. However, little is known regarding the underlying aetiology of such biases and their role in anxiety disorde...

Attentional biases are most often framed in a threat relevance framework. Alternatively, it could be that not only threat-related stimuli draw attention but also that preferential attention is drawn to all stimuli that have relevance for an individual. We investigated this stimulus relevance theory in primary school-age children by means of a visua...

Cognitive biases are known to play an important role in anxiety. In this study we investigate whether maternal anxiety is associated with biases in interpretation, attention, and catastrophic processing about self-referent stimuli that may signal potential threat in the mother's own environment. We also investigate whether maternal anxiety is assoc...

Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment

Therapygenetics, the study of genetic determinants of response to psychological therapies, is in its infancy. Here, we investigate whether single-nucleotide polymorphisms in nerve growth factor (NGF) (rs6330) and brain-derived neutrotrophic factor (BDNF) (rs6265) genes predict the response to cognitive behaviour therapy (CBT). Neurotrophic genes re...

This study investigated the effects of experimentally modifying interpretation biases for children's cognitions, avoidance behavior, anxiety vulnerability, and physiological responding. Sixty-seven children (6-11 years) were randomly assigned to receive a positive or negative interpretation bias modification procedure to induce interpretation biase...

Cognitive Bias Modification (CBM) procedures have been used to train individuals to interpret ambiguous information in a negative or benign direction and have provided evidence that negative biases causally contribute to emotional vulnerability. Here we present the development and validation of a new form of CBM designed to manipulate the cognitive...

If there is a spider in the room, then the spider phobic in your group is most likely to point it out to you. This phenomenon is believed to arise because our attentional systems are hardwired to attend to threat in our environment, and, to a spider phobic, spiders are threatening. However, an alternative explanation is simply that attention is qui...

We examined the effects of training to approach or avoid novel animals on fear-related responses in children. Ninety-nine primary school children (9-12 years old) were instructed to repeatedly move a manikin toward or away from pictures of novel animals. The training produced more positive self-reported attitudes for the animal that was repeatedly...

Using an experimental bias modification task, an interpretation bias towards or away from threat was induced about animal or social situations in a sample of 103 children split into a young (7-10 years) and old age group (11-15 years). Children rapidly learned to select outcomes of ambiguous situations which were congruent with their assigned modif...

This study investigated the effect of filmed peer modeling on fear beliefs and approach-avoidance behaviors towards animals in 8- to 10-year-old typically developing children. Ninety-seven children randomly received either a positive or negative modeling film in which they saw peers interact with a novel animal. Before and after this film, children...

Clinical and experimental theories assume that processing biases in attention and interpretation are a causal mechanism through which anxiety develops. Despite growing evidence that these processing biases are present in children and, therefore, develop long before adulthood, these theories ignore the potential role of child development. This revie...

The intergenerational transmission of anxious cognitions and behaviors may be a possible mechanism underlying concordance between maternal and child anxieties. By disambiguating ambiguous situations for their child in a threatening manner, anxious mothers may 'train' their children towards a general tendency to also interpret ambiguity in a threate...

We conducted a follow up over 23 years of depressed patients originally presenting to general practice in 1981 and studied in detail at that time. Aims were to assess the long term course and outcome of depression in primary care. Patterns of recovery and recurrence of major depressive episodes, together with other aspects of course, treatment and...

Anxiety disorders are known to run in families [Turner, S. M., Beidel, D. C., & Costello, A. (1987). Psychopathology in the offspring of anxiety disorder patients. Journal of Consulting and Clinical Psychology, 55(2), 229-235] and environmental factors may largely account for the concordance between parental and child anxieties. Cognitive psycholog...

Anxiety is associated with threat-related biases in information processing such as heightened attentional vigilance to potential threat. Such biases are an important focus of psychological treatments for anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of a range of anxiety disorders. The aim of this...

Although research into evaluative conditioning (EC) has progressed considerably over the past 30 years, there have been some doubts about the strength and reliability of conditioning effects – especially when visual stimuli are used. Partly this has been due to well-documented methodological debates and empirical evidence of alternative causes of a...

To determine whether writing clinical guideline recommendations in behaviourally specified "plain English" language increases the likelihood of their implementation by service users (patients). Randomised controlled trial in which participants received either the original text of the National Institute for Clinical Excellence (NICE) public guidelin...

This study investigates risk communication within genetic counselling. Transcripts of 115 U.K. genetic consultations were reliably coded into form of risk expression used, whether the patient responded with understanding and agreement or showed signs of misunderstanding or disagreement, or did not respond at all, and whether clinicians assessed pat...

Appearance related distress in both clinical and general populations is associated with the increasing identification of surgery as a solution, leading to referrals for cosmetic surgery and pressure on NHS resources. Cosmetic surgery guidelines are designed to control this growing demand, but lack a sound evidence base. Where exceptions are provide...