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Children's Facial Muscular Movements and Risk for Early Psychopathology: Assessing Clinical Utility.

ABSTRACT: Standardized developmentally based assessment systems have transformed the capacity to identify transdiagnostic behavioral markers of mental disorder risk in early childhood, notably, clinically significant irritability and externalizing behaviors. However, behavior-based instruments that both differentiate risk for persistent psychopathology from normative misbehavior, and are feasible for community clinicians to implement, are in nascent phases of development. Young children's facial expressions during frustration challenges may form the basis for novel assessments tools that are flexible, quick, and easy to implement as markers of psychopathology to complement validated questionnaires. However, the accuracy of facial expressions to correctly classify young children falling above and below clinical cut-offs is unknown. Our goal was to test how facial expressions during frustration, defined by different facial muscular movements, related to individual differences in irritability and externalizing behaviors and discriminated children with clinically significant levels from peers. Participants were 79 children (ages 3-7) who completed a short, moderately frustrating computer task while facial expressions were recorded. Only negative facial expressions that included eye constriction related to irritability and externalizing behaviors and were clinically discriminating. Moreover, these expressions significantly discriminated children with and without clinically significant irritability and externalizing symptoms with high Area Under the Curve (AUC) values (> .75) indicating good clinical utility. In contrast, expressions without eye constriction showed no clinical utility. The presence of negative expressions with eye constriction in response to a short frustration prompt may serve as an indicator of early psychopathology, raising the potential for novel assessment tools that may enhance precision of early identification.

SUBMITTER: Grabell AS

PROVIDER: S-EPMC7476425 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Children's Facial Muscular Movements and Risk for Early Psychopathology: Assessing Clinical Utility.

Grabell Adam S AS Jones Hannah M HM Wilett Aimee E AE Bemis Lisa M LM Wakschlag Lauren S LS Perlman Susan B SB

Behavior therapy 20190817 2

Standardized developmentally based assessment systems have transformed the capacity to identify transdiagnostic behavioral markers of mental disorder risk in early childhood, notably, clinically significant irritability and externalizing behaviors. However, behavior-based instruments that both differentiate risk for persistent psychopathology from normative misbehavior, and are feasible for community clinicians to implement, are in nascent phases of development. Young children's facial expressio ...[more]

PMID: 32138936

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Project description:BackgroundGenome-wide association studies have identified thousands of disease-associated single nucleotide polymorphisms (SNPs). A subset of these SNPs may be additively combined to generate genetic risk scores (GRSs) that confer risk for a specific disease. Although the clinical validity of GRSs to predict risk of specific diseases has been well established, there is still a great need to determine their clinical utility by applying GRSs in primary care for cancer risk assessment and targeted intervention.MethodsThis clinical study involved 281 primary care patients without a personal history of breast, prostate or colorectal cancer who were 40-70 years old. DNA was obtained from a pre-existing biobank at NorthShore University HealthSystem. GRSs for colorectal cancer and breast or prostate cancer were calculated and shared with participants through their primary care provider. Additional data was gathered using questionnaires as well as electronic medical record information. A t-test or Chi-square test was applied for comparison of demographic and key clinical variables among different groups.ResultsThe median age of the 281 participants was 58 years and the majority were female (66.6%). One hundred one (36.9%) participants received 2 low risk scores, 99 (35.2%) received 1 low risk and 1 average risk score, 37 (13.2%) received 1 low risk and 1 high risk score, 23 (8.2%) received 2 average risk scores, 21 (7.5%) received 1 average risk and 1 high risk score, and no one received 2 high risk scores. Before receiving GRSs, younger patients and women reported significantly more worry about risk of developing cancer. After receiving GRSs, those who received at least one high GRS reported significantly more worry about developing cancer. There were no significant differences found between gender, age, or GRS with regards to participants' reported optimism about their future health neither before nor after receiving GRS results.ConclusionsGenetic risk scores that quantify an individual's risk of developing breast, prostate and colorectal cancers as compared with a race-defined population average risk have potential clinical utility as a tool for risk stratification and to guide cancer screening in a primary care setting.

Project description:PAPER 1:"Identification of novel subgroups of high-risk pediatric precursor B acute lymphoblastic leukemia (B-ALL) by unsupervised microarray analysis: clinical correlates and therapeutic implications. A Children's Oncology Group (COG) study." ABSTRACT We examined gene expression profiles of pre-treatment specimens from 207 patients from the COG P9906 study to identify signatures of children with high risk B-precursor acute lymphoblastic leukemia (ALL) and to determine whether the resulting clusters are associated with either specific clinical features or treatment response characteristics. Four unsupervised clustering methods were utilized to classify patients into similar groups. The different clustering algorithms showed significant overlap in cluster membership. Two clusters contained all cases with either t(1;19)(q23;p13) translocations or MLL rearrangements. The other six clusters were novel and had no recurring chromosomal abnormalities or distinctive clinical features. Members of two of these novel clusters had significant survival differences when compared to the overall 4-year relapse-free survival (RFS) of 61%. These included clusters of patients with either significantly better (94.7%) or worse (21.0%) RFS at 4 years. Children of Hispanic/Latino ethnicity were disproportionately present in the poor outcome cluster. The poor outcome cluster represents a novel biologically distinctive subset of B-precursor ALL that may occur at least as frequently as BCR/ABL. Further molecular characterization of this cluster may lead to the discovery of genomic abnormalities that can be targeted to improve the currently dismal outcome for children with this gene signature. The Sample data have also been used in another study: PAPER 2: "Gene expression classifiers for minimal residual disease and relapse free survival improve outcome prediction and risk classification in children with high risk acute lymphoblastic leukemia. A Children's Oncology Group study". ABSTRACT Background. Nearly 25% of children with B-precursor ALL present with "high-risk" disease (HR-ALL) that is resistant to current therapies. Gene expression profiling may yield molecular classifiers for outcome prediction that can be used to improve risk classification and therapeutic targeting. Methods. Expression profiles were obtained in pre-treatment leukemic samples from 207 uniformly treated children with HR-ALL. Relapse free survival (RFS) was 61% at 4 years and flow cytometric measures of minimal residual disease (MRD) at the end of induction (day 29) were predictive of outcome (P<0.001). Molecular classifiers predictive of RFS and MRD were developed using extensive cross-validation procedures. Results. A 38 gene molecular risk classifier predictive of RFS (MRC-RFS) distinguished two groups in HR-ALL with different relapse risks: low (4 yr RFS: 81%, n=109) vs. high (4 yr RFS: 50%, n=98) (P<0.0001). In multivariate analysis, the best predictor combined MRC-RFS and day 29 flow MRD data, classifying children into low (87% RFS), intermediate (62% RFS), or high risk (29% RFS) groups (P<0.0001). A 21 gene molecular classifier predictive of MRD could effectively substitute for day 29 flow MRD, yielding a combined classifier that similarly distinguished three risk groups at pre-treatment (low: 82% RFS; intermediate: 63% RFS; and high risk: 45% RFS) (P<0.0001). This combined molecular classifier was further validated on an independent cohort of 84 children with HR-ALL (P = 0.006). Conclusions. Molecular classifiers predictive of RFS and MRD can be used to distinguish distinct prognostic groups within HR-ALL, significantly improving risk classification schemes and the ability to prospectively identify children at diagnosis who will respond to or fail current treatment regimens. NOTE: Due to Children's Oncology Group (COG) restrictions, outcome and MRD data cannot be provided as part of the covariate data for this dataset at the present time. If you would like to arrange individual access to this data, please contact COG or the PI of this study, Dr. Cheryl Willman, at the University of New Mexico Cancer Center (cwillman@unm.edu) to arrange a collaboration.

Dataset Information

Children's Facial Muscular Movements and Risk for Early Psychopathology: Assessing Clinical Utility.

Publications

Children's Facial Muscular Movements and Risk for Early Psychopathology: Assessing Clinical Utility.

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