Lack of association between PCK1 polymorphisms and obesity, physical activity, and fitness in European Youth Heart Study (EYHS)

Phosphoenolpyruvate carboxykinase-1 (PCK1) is the rate-limiting enzyme in the hepatic gluconeogenic pathway. Studies have shown that overexpression of Pck1 in mice results in obesity-related traits and higher levels of physical activity (PA). Therefore, our aims were to investigate whether common genetic variation in the PCK1 gene influences obesity-related traits, PA, and fitness, and to examine whether PA and fitness attenuate the influence of the PCK1 polymorphisms on obesity in children. Analyses were undertaken on data from Danish and Estonian children (958 boys and 1,104 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of children (mean ± s.d. age: 9.6 ± 0.4 years) and adolescents (15.5 ± 0.5 years). We genotyped eight polymorphisms that captured the common genetic variations in the PCK1 gene. The association between the PCK1 polymorphisms and BMI, waist circumference (WC), sum of four skinfolds, PA, and fitness was tested using an additive model adjusted for age, age-group, gender, maturity, and country. Interactions were tested by including interaction terms in the model. None of the polymorphisms were significantly associated with BMI, WC, sum of four skinfolds, PA, and fitness, and also with the risk of being overweight or obese (P > 0.05). The interactions between the polymorphisms and age-group, gender, PA, and fitness were not statistically significant. This is the first study to comprehensively examine the association of PCK1 polymorphisms with obesity, PA, and fitness. Despite strong evidence from animal studies, our study in the EYHS cohort failed to identify an association of PCK1 polymorphisms with obesity, PA, and fitness.

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.

Children and adolescents referred for treatment of anxiety disorders: differences in clinical characteristics

Background: Reports of the clinical characteristics of children and adolescents with anxiety disorders are typically based on community populations or from clinical samples with exclusion criterion applied. Little is known about the clinical characteristics of children and adolescents routinely referred for treatment for anxiety disorders. Furthermore, children and adolescents are typically treated as one homogeneous group although they may differ in ways that are clinically meaningful. Methods: A consecutive series of children (n = 100, aged 6-12 years) and adolescents (n = 100, aged 13-18 years), referred to a routine clinical service, were assessed for anxiety and comorbid disorders, school refusal and parental symptoms of psychopathology. Results: Children were significantly more likely to be diagnosed with separation anxiety disorder than adolescents. Adolescents with a primary anxiety disorder had significantly higher self and clinician rated anxiety symptoms and had more frequent primary diagnoses of social anxiety disorder, diagnoses and symptoms of mood disorders, and irregular school attendance. Limitations: Childhood and adolescence were considered categorically as distinct, developmental periods; in reality changes would be unlikely to occur in such a discrete manner. Conclusions: The finding that children and adolescents with anxiety disorders have distinct clinical characteristics has clear implications for treatment. Simply adapting treatments designed for children to make the materials more ‘adolescent-friendly’ is unlikely to sufficiently meet the needs of adolescents.

A low glycaemic load breakfast can attenuate cognitive impairments observed in middle aged obese females with impaired glucose tolerance.

Increased central adiposity and abnormalities in glucose tolerance preceding type 2 diabetes can have demonstrable negative effects on cognitive function, even in ostensibly healthy, middle-aged females. The potential for GL manipulations to modulate glycaemic response and cognitive function in type 2 diabetes and obesity merits further investigation..

Observing interactions between children and adolescents and their parents: the effects of anxiety disorder and age

Parental behaviors, most notably overcontrol, lack of warmth and expressed anxiety, have been implicated in models of the development and maintenance of anxiety disorders in children and young people. Theories of normative development have proposed that different parental responses are required to support emotional development in childhood and adolescence, yet age has not typically been taken into account in studies of parenting and anxiety disorders. In order to identify whether associations between anxiety disorder status and parenting differ in children and adolescents, we compared observed behaviors of parents of children (7–10 years) and adolescents (13–16 years) with and without anxiety disorders (n=120), while they undertook a series of mildly anxiety-provoking tasks. Parents of adolescents showed significantly lower levels of expressed anxiety, intrusiveness and warm engagement than parents of children. Furthermore, offspring age moderated the association between anxiety disorder status and parenting behaviors. Specifically, parents of adolescents with anxiety disorders showed higher intrusiveness and lower warm engagement than parents of non-anxious adolescents. A similar relationship between these parenting behaviors and anxiety disorder status was not observed among parents of children. The findings suggest that theoretical accounts of the role of parental behaviors in anxiety disorders in children and adolescents should distinguish between these different developmental periods. Further experimental research to establish causality, however, would be required before committing additional resources to targeting parenting factors within treatment.

On the threshold of adulthood: a new approach for the use of maturation indicators to assess puberty in adolescents from medieval England

Objectives: This study provides the first large scale analysis of the age at which adolescents in medieval England entered and completed the pubertal growth spurt. This new method has implications for expanding our knowledge of adolescent maturation across different time periods and regions. Methods: In total, 994 adolescent skeletons (10-25 years) from four urban sites in medieval England (AD 900-1550) were analysed for evidence of pubertal stage using new osteological techniques developed from the clinical literature (i.e. hamate hook development, CVM, canine mineralisation, iliac crest ossification, radial fusion). Results: Adolescents began puberty at a similar age to modern children at around 10-12 years, but the onset of menarche in girls was delayed by up to 3 years, occurring around 15 for most in the study sample and 17 years for females living in London. Modern European males usually complete their maturation by 16-18 years; medieval males took longer with the deceleration stage of the growth spurt extending as late as 21 years. Conclusions: This research provides the first attempt to directly assess the age of pubertal development in adolescents during the tenth to seventeenth centuries. Poor diet, infections, and physical exertion may have contributed to delayed development in the medieval adolescents, particularly for those living in the city of London. This study sheds new light on the nature of adolescence in the medieval period, highlighting an extended period of physical and social transition.

Improving mood with psychoanalytic and cognitive therapies (IMPACT): a pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial

Background Up to 70% of adolescents with moderate to severe unipolar major depression respond to psychological treatment plus Fluoxetine (20-50 mg) with symptom reduction and improved social function reported by 24 weeks after beginning treatment. Around 20% of non responders appear treatment resistant and 30% of responders relapse within 2 years. The specific efficacy of different psychological therapies and the moderators and mediators that influence risk for relapse are unclear. The cost-effectiveness and safety of psychological treatments remain poorly evaluated. Methods/Design Improving Mood with Psychoanalytic and Cognitive Therapies, the IMPACT Study, will determine whether Cognitive Behavioural Therapy or Short Term Psychoanalytic Therapy is superior in reducing relapse compared with Specialist Clinical Care. The study is a multicentre pragmatic effectiveness superiority randomised clinical trial: Cognitive Behavioural Therapy consists of 20 sessions over 30 weeks, Short Term Psychoanalytic Psychotherapy 30 sessions over 30 weeks and Specialist Clinical Care 12 sessions over 20 weeks. We will recruit 540 patients with 180 randomised to each arm. Patients will be reassessed at 6, 12, 36, 52 and 86 weeks. Methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, research assessors independent of treatment team and blind to randomization, analysis by intention to treat, data management using remote data entry, measures of quality assurance, advanced statistical analysis, manualised treatment protocols, checks of adherence and competence of therapists and assessment of cost-effectiveness. We will also determine whether time to recovery and/or relapse are moderated by variations in brain structure and function and selected genetic and hormone biomarkers taken at entry. Discussion The objective of this clinical trial is to determine whether there are specific effects of specialist psychotherapy that reduce relapse in unipolar major depression in adolescents and thereby costs of treatment to society. We also anticipate being able to utilise psychotherapy experience, neuroimaging, genetic and hormone measures to reveal what techniques and their protocols may work best for which patients.

Interpretation of ambiguity: differences between children and adolescents with and without an anxiety disorder

Background: Theory and treatment of anxiety disorders in young people are commonly based on the premise that interpretation biases found in anxious adults are also found in children and adolescents. Although there is some evidence that this may be the case, studies have not typically taken age into account, which is surprising given the normative changes in cognition that occur throughout childhood. The aim of the current study was to identify whether associations between anxiety disorder status and interpretation biases differed in children and adolescents. Methods: The responses of children (7-10 years) and adolescents (13-16 years) with and without anxiety disorders (n = 120) were compared on an ambiguous scenarios task. Results: Children and adolescents with an anxiety disorder showed significantly higher levels of threat interpretation and avoidant strategies than non-anxious children and adolescents. However, age significantly moderated the effect of anxiety disorder status on interpretation of ambiguity, in that adolescents with anxiety disorders showed significantly higher levels of threat interpretation and associated negative emotion than non-anxious adolescents, but a similar relationship was not observed among children. Conclusions: The findings suggest that theoretical accounts of interpretation biases in anxiety disorders in children and adolescents should distinguish between different developmental periods. For both ages, treatment that targets behavioral avoidance appears warranted. However, while adolescents are likely to benefit from treatment that addresses interpretation biases, there may be limited benefit for children under the age of ten.

Aberrant brain responses to emotionally valent words is normalised after cognitive behavioural therapy in female depressed adolescents

AbstractBackground Depression in adolescence is debilitating with high recurrence in adulthood, yet its pathophysiological mechanism remains enigmatic. To examine the interaction between emotion, cognition and treatment, functional brain responses to sad and happy distractors in an affective go/no-go task were explored before and after Cognitive Behavioural Therapy (CBT) in depressed female adolescents, and healthy participants. Methods Eighty-two Depressed and 24 healthy female adolescents, aged 12 to 17 years, performed a functional magnetic resonance imaging (fMRI) affective go/no-go task at baseline. Participants were instructed to withhold their responses upon seeing happy or sad words. Among these participants, 13 patients had CBT over approximately 30 weeks. These participants and 20 matched controls then repeated the task. Results At baseline, increased activation in response to happy relative to neutral distractors was observed in the orbitofrontal cortex in depressed patients which was normalized after CBT. No significant group differences were found behaviourally or in brain activation in response to sad distractors. Improvements in symptoms (mean: 9.31, 95% CI: 5.35-13.27) were related at trend-level to activation changes in orbitofrontal cortex. Limitations In the follow-up section, a limited number of post-CBT patients were recruited. Conclusions To our knowledge, this is the first fMRI study addressing the effect of CBT in adolescent depression. Although a bias toward negative information is widely accepted as a hallmark of depression, aberrant brain hyperactivity to positive distractors was found and normalised after CBT. Research, assessment and treatment focused on positive stimuli could be a future consideration. Moreover, a pathophysiological mechanism distinct from adult depression may be suggested and awaits further exploration.

Is cognitive bias modification training truly beneficial for adolescents?

Background Cognitive Bias Modification (CBM) has been shown to change interpretation biases commonly associated with anxiety and depression and may help ameliorate symptoms of these disorders. However, its evidence base for adolescents is scarce. Previous results have been hard to interpret because of methodological issues. In particular, many studies have used negative bias training as the control condition. This would tend to inflate any apparent benefits of CBM compared to a neutral control. Most studies also only examined the effects of a single training session and lacked follow-up assessment or ecologically valid outcome measures. Method Seventy-four adolescents, aged 16–18 years, were randomised to two sessions of CBM training or neutral control. Interpretation bias and mood were assessed three times: at baseline, immediately post-training and 1 week post-training. A controlled experimental stressor was also used, and responses to everyday stressors were recorded for 1 week after training to assess responses to psychological challenges. Feedback for the training programme was collected. Results The CBM group reported a greater reduction in negative affect than control participants. However, other hypothesised advantages of CBM were not demonstrated. Regardless of training group, participants reported increased positive interpretations, decreased negative interpretations, reduced depressive symptoms and no change in trait anxiety. The two groups did not differ in their stress reactivity. After controlling for group differences in training performance, all the mood effects disappeared. Conclusions When tested under stringent experimental conditions the effects of CBM in healthy adolescents appear to be minimal. Future studies should concentrate on participants with elevated cognitive biases and/or mood symptoms who may be more sensitive to CBM.

‘It Was All My Fault’: negative interpretation bias in depressed adolescents

The extent to which cognitive models of development and maintenance of depression apply to adolescents is largely untested, despite the widespread application of Cognitive Behavior Therapy (CBT) for depressed adolescents. Cognitive models suggest that negative cognitions, including interpretation bias, play a role in etiology and maintenance of depression. Given that cognitive development is incomplete by the teenage years and that CBT is not superior to non-cognitive treatments in the treatment of adolescent depression, it is important to test the underlying model. The primary aim of this study was to test the hypothesis that interpretation biases are exhibited by depressed adolescents. Four groups of adolescents were recruited: clinically-referred depressed (n = 27), clinically-referred non-depressed (n = 24), community with elevated depression symptoms (n = 42) and healthy community (n = 150). Participants completed a 20 item ambiguous scenarios questionnaire. Clinically-referred depressed adolescents made significantly more negative interpretations and rated scenarios as less pleasant than all other groups. The results suggest that this element of the cognitive model of depression is applicable to adolescents. Other aspects of the model should be tested so that cognitive treatment can be modified or adapted if necessary.

Factors that influence the detection of psychological problems in adolescents attending general practices

Background Epidemiological studies indicate that the prevalence of psychological problems in patients attending primary care services may be as high as 25%. Aim To identify factors that influence the detection of psychological difficulties in adolescent patients receiving primary care in the UK. Design of study A prospective study of 13-16 year olds consecutively attending general practices. Setting General practices, Norfolk, UK. Method Information was obtained from adolescents and parents using the validated Strengths and Difficulties Questionnaire (SDQ) and from GF`s using the consultation assessment form. Results Ninety-eight adolescents were recruited by 13 GPs in Norfolk (mean age = 14.4 years, SD = 1.08; 38 males, 60 females). The study identified psychological difficulties in almost one-third of adolescents (31/98, 31.6%). Three factors significant to the detection of psychological disorders in adolescents were identified: adolescents' perceptions of difficulties according to the self-report SDQ, the severity of their problems as indicated by the self-report SDQ, and whether psychological issues were discussed in the consultation. GPs did not always explore psychological problems with adolescents, even if GPs perceived these to be present. Nineteen of 31 adolescents with psychological difficulties were identified by GPs (sensitivity = 61.2%, specificity = 85.1%). A management plan or follow-up was made for only seven of 19 adolescents identified, suggesting that ongoing psychological difficulties in many patients are not being addressed. Conclusions GPs are in a good position to identify psychological issues in adolescents, but GPs and adolescents seem reluctant to explore these openly. Open discussion of psychological issues in GP consultations was found to be the most important factor in determining whether psychological difficulties in adolescents are detected by GPs.

Examining Cognitive Models of Obsessive Compulsive Disorder in Adolescents

Abstract. Three influential theoretical models of OCD focus upon the cognitive factors of inflated responsibility (Salkovskis, 1985), thought-action fusion (Rachman, 1993) and meta-cognitive beliefs (Wells and Matthews, 1994). Little is known about the relevance of these models in adolescents or about the nature of any direct or mediating relationships between these variables and OCD symptoms. This was a cross-sectional correlational design with 223 non-clinical adolescents aged 13 to 16 years. All participants completed questionnaires measuring inflated responsibility, thought-action fusion, meta-cognitive beliefs and obsessive-compulsive symptoms. Inflated responsibility, thought-action fusion and metacognitive beliefs were significantly associated with higher levels of obsessive-compulsive symptoms. These variables accounted for 35% of the variance in obsessive-compulsive symptoms, with inflated responsibility and meta-cognitive beliefs both emerging as significant independent predictors. Inflated responsibility completely mediated the effect of thoughtaction fusion and partially mediated the effect of meta-cognitive beliefs. Support for the downward extension of cognitive models to understanding OCD in a younger population was shown. Findings suggest that inflated responsibility and meta-cognitive beliefs may be particularly important cognitive concepts in OCD. Methodological limitations must be borne in mind and future research is needed to replicate and extend findings in clinical samples. Keywords: Obsessive compulsive disorder, adolescents, cognitive models.

Do Cognitive Models of Obsessive Compulsive Disorder Apply to Children and Adolescents?

Cognitive models of obsessive compulsive disorder (OCD) have been influential in understanding and treating the disorder in adults. Cognitive models may also be applicable to children and adolescents and would have important implications for treatment. The aim of this systematic review was to evaluate research that examined the applicability of the cognitive model of OCD to children and adolescents. Inclusion criteria were set broadly but most studies identified included data regarding responsibility appraisals, thought-action fusion or meta-cognitive models of OCD in children or adolescents. Eleven studies were identified in a systematic literature search. Seven studies were with non clinical samples, and 10 studies were cross-sectional. Only one study did not support cognitive models of OCD in children and adolescents and this was with a clinical sample and was the only experimental study. Overall, the results strongly supported the applicability of cognitive models of OCD to children and young people. There were, however, clear gaps in the literature. Future research should include experimental studies, clinical groups, and should test which of the different models provide more explanatory power.