78 research outputs found
Forty Years of Clathrin-coated vesicles
The purification of coated vesicles and the discovery of clathrin by Barbara Pearse in 1975 was a landmark in cell biology. Over the past 40 years, work from many labs has uncoveredthe molecular details of clathrin and its associated proteins, including how they assemble into a coated vesicle and how they select cargo. Unexpected connections have been found with signalling, development, neuronal transmission, infection, immunity, and genetic disorders. But there are still a number of unanswered questions, including how clathrin-mediated trafficking is regulated and how the machinery evolved.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/tra.1233
Parental internalizing symptoms as predictors of anxiety symptoms in clinic-referred children
Background:
Mothersâ and fathersâ internalizing symptoms may influence childrenâs anxiety symptoms differently.
Objective:
To explore the relationship between parental internalizing symptoms and childrenâs anxiety symptoms in a clinical sample of children with anxiety disorders.
Method:
The sample was recruited through community mental health clinics for a randomized controlled anxiety treatment trial. At pre-intervention, children (n = 182), mothers (n = 165), and fathers (n = 72) reported childrenâs anxiety symptoms. Mothers and fathers also reported their own internalizing symptoms. The children were aged 8 to 15 years (Mage = 11.5 years, SD = 2.1, 52.2% girls) and all had a diagnosis of separation anxiety, social phobia, and/or generalized anxiety disorder. We examined parental internalizing symptoms as predictors of child anxiety symptoms in multiple regression models.
Results:
Both mother and father rated internalizing symptoms predicted childrenâs self-rated anxiety levels (adj. R2 = 22.0%). Mother-rated internalizing symptoms predicted mother-rated anxiety symptoms in children (adj. R2 = 7.0%). Father-rated internalizing symptoms did not predict father-rated anxiety in children.
Conclusions:
Clinicians should incorporate parental level of internalizing symptoms in their case conceptualizations
Adherence, Competence, and Alliance as Predictors of Long-term Outcomes of Cognitive Behavioral Therapy for Youth Anxiety Disorders
The present study investigated therapist adherence, therapist competence, and patient-therapist alliance as predictors of long-term outcomes of cognitive behavioral therapy (CBT) for anxiety disorders in youth. Potential differential effects for group versus individual CBT, for therapists with or without formal CBT training, and based on youth symptom severity were examined. Videotapes (nâ=â181) from treatment sessions in a randomized controlled effectiveness trial comprising youth (Nâ=â170, M ageâ=â11.6 years, SDâ=â2.1) with anxiety disorders were assessed for therapist adherence and competence. Alliance was rated by therapists and youth. Participants completed a diagnostic interview and an anxiety symptom measure at pre-treatment, post-treatment, one-year follow-up, and long-term follow-up (Mâ=â3.9 years post-treatment, SDâ=â0.8, rangeâ=â2.2â5.9 years). The change in anxiety symptoms or diagnostic status from pre-treatment to long-term follow-up was not significantly related to any predictor variables. However, several interaction effects were found. For loss of principal diagnosis, therapist competence predicted positive outcome when therapist adherence also was high. Adherence was found to predict positive outcome if CBT was provided individually. Therapist-rated alliance was related to both loss of principal diagnosis and loss of all diagnoses when CBT was provided in groups. Interaction effects suggested that therapists displaying both high adherence and high competence produced better long-term outcomes. Further, the alliance may be particularly important for outcomes in group CBT, whereas adherence may be particularly important for outcomes in individual CBT.publishedVersio
A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to psychological treatments for child anxiety Disorders
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 candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to cognitive behavioural therapy (CBT) in children with anxiety disorders.
Methods: We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1,026 monozygotic twin pairs was examined as a function of the pairs' genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders.
Results: The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9, 55.5 and 41.6%, respectively).
Conclusions: Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments but also benefit more from the most intensive types of treatment
Agreement on Web-based Diagnoses and Severity of Mental Health Problems in Norwegian Child and Adolescent Mental Health Services
Objective: This study examined the agreement between diagnoses and severity ratings assigned by clinicians using a structured web-based interview within a child and adolescent mental health outpatient setting. Method: Information on 100 youths was obtained from multiple informants through a web-based Development and Well-Being Assessment (DAWBA). Based on this information, four experienced clinicians independently diagnosed (according to the International Classification of Diseases Revision 10) and rated the severity of mental health problems according to the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) and the Childrenâs Global Assessment Scale (C-GAS). Results: Agreement for diagnosis was Îș=0.69-0.82. Intra-class correlation for single measures was 0.78 for HoNOSCA and 0.74 for C-GAS, and 0.93 and 0.92, respectively for average measures. Conclusions: Agreement was good to excellent for all diagnostic categories. Agreement for severity was moderate, but improved to substantial when the average of the ratings given by all clinicians was considered. Therefore, we conclude that experienced clinicians can assign reliable diagnoses and assess severity based on DAWBA data collected online
Patterns of subâoptimal change following CBT for childhood anxiety
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 subâoptimally to CBT, this study investigated youths (N = 1,483) who continued to meet criteria for one or more clinical anxiety diagnosis immediately following treatment or at any point during the 12 months following treatment. Methods: Data were collected from 10 clinical sites with assessments at preâand postâtreatment and at least once more at 3, 6 or 12âmonth followâup. Participants were assigned to one of three groups based on diagnostic status for youths who: (a) retained an anxiety diagnosis from post to end point (minimal responders); (b) remitted anxiety diagnoses at post but relapsed by end point (relapsed responders); and (c) retained a diagnosis at post but remitted to be diagnosis free at end point (delayed responders). Growth curve models assessed patterns of change over time for the three groups and examined predictors associated with these patterns including demographic, clinical and parental factors, as well as treatment factors. Results: Higher primary disorder severity, being older, having a greater number of anxiety disorders, having social anxiety disorder, as well as higher maternal psychopathology differentiated the minimal responders from the delayed and relapsed responders at the baseline. Results from the growth curve models showed that severity of the primary disorder and treatment modality differentiated patterns of linear change only. Higher severity was associated with significantly less improvement over time for the minimal and relapsed response groups, as was receiving group CBT, when compared to the delayed response group. Conclusions: Subâoptimal response patterns can be partially differentiated using variables assessed at preâtreatment. Increased understanding of different patterns of change following treatment may provide direction for clinical decisionâmaking and for tailoring treatments to specific groups of clinically anxious youth. Future research may benefit from assessing progress during treatment to detect emerging response patterns earlier
The utility of the SCAS-C/P to detect specific anxiety disorders among clinically anxious children
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 preadolescent children. This study aimed to establish the ability of the Spence Childrenâs Anxiety Scale (SCAS) subscales to identify children with specific anxiety disorders in a large clinic-referred sample (N = 1,438) of children aged 7 to 12 years. We examined the capacity of the Separation Anxiety, Social Phobia, Generalized Anxiety, and Physical Injury Fears (phobias) subscales to discriminate between children with and without the target disorder. We also identified optimal cutoff scores on subscales for accurate identification of children with the corresponding disorder, and examined the contribution of child, mother, and father reports. The Separation Anxiety subscale was able to accurately identify children with separation anxiety disorder, and this was replicated across all 3 reporters. Mother- and father-reported Social Phobia subscales also accurately identified children with social anxiety disorder, although child report was only able to accurately detect social anxiety disorder in girls. Using 2 or more reporters improved the sensitivity of the Separation Anxiety and Social Phobia subscales but reduced specificity. The Generalized Anxiety and Physical Injury Fears subscales failed to accurately identify children with the corresponding disorders. These findings have implications for the potential use of mother-, father-, and child-report SCAS subscales to detect specific disorders in preadolescent children in clinical settings
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
Genome-wide association study of response to cognitive-behavioural therapy in children with anxiety disorders
Background
Anxiety disorders are common, and cognitiveâbehavioural 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 disorders (n = 980).
Method
Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.
Results
No variants passed a genome-wide significance threshold (P = 5Ă10â8) in either analysis. Four variants met criteria for suggestive significance (P<5Ă10â6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.
Conclusions
This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts
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