Rapid and Accurate Behavioral Health Diagnostic Screening: Initial Validation Study of a Web-Based, Self-Report Tool (the SAGE-SR).

BACKGROUND: The Structured Clinical Interview for DSM (SCID) is considered the gold standard assessment for accurate, reliable psychiatric diagnoses; however, because of its length, complexity, and training required, the SCID is rarely used outside of research. OBJECTIVE: This paper aims to describe the development and initial validation of a Web-based, self-report screening instrument (the Screening Assessment for Guiding Evaluation-Self-Report, SAGE-SR) based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the SCID-5-Clinician Version (CV) intended to make accurate, broad-based behavioral health diagnostic screening more accessible within clinical care. METHODS: First, study staff drafted approximately 1200 self-report items representing individual granular symptoms in the diagnostic criteria for the 8 primary SCID-CV modules. An expert panel iteratively reviewed, critiqued, and revised items. The resulting items were iteratively administered and revised through 3 rounds of cognitive interviewing with community mental health center participants. In the first 2 rounds, the SCID was also administered to participants to directly compare their Likert self-report and SCID responses. A second expert panel evaluated the final pool of items from cognitive interviewing and criteria in the DSM-5 to construct the SAGE-SR, a computerized adaptive instrument that uses branching logic from a screener section to administer appropriate follow-up questions to refine the differential diagnoses. The SAGE-SR was administered to healthy controls and outpatient mental health clinic clients to assess test duration and test-retest reliability. Cutoff scores for screening into follow-up diagnostic sections and criteria for inclusion of diagnoses in the differential diagnosis were evaluated. RESULTS: The expert panel reduced the initial 1200 test items to 664 items that panel members agreed collectively represented the SCID items from the 8 targeted modules and DSM criteria for the covered diagnoses. These 664 items were iteratively submitted to 3 rounds of cognitive interviewing with 50 community mental health center participants; the expert panel reviewed session summaries and agreed on a final set of 661 clear and concise self-report items representing the desired criteria in the DSM-5. The SAGE-SR constructed from this item pool took an average of 14 min to complete in a nonclinical sample versus 24 min in a clinical sample. Responses to individual items can be combined to generate DSM criteria endorsements and differential diagnoses, as well as provide indices of individual symptom severity. Preliminary measures of test-retest reliability in a small, nonclinical sample were promising, with good to excellent reliability for screener items in 11 of 13 diagnostic screening modules (intraclass correlation coefficient [ICC] or kappa coefficients ranging from .60 to .90), with mania achieving fair test-retest reliability (ICC=.50) and other substance use endorsed too infrequently for analysis. CONCLUSIONS: The SAGE-SR is a computerized adaptive self-report instrument designed to provide rigorous differential diagnostic information to clinicians.

The Role of Pharmacogenetic Testing in the Amelioration of Antidepressant-Related Motor Disturbances in 2 Young Adult Men With Major Depressive Disorder.

This report describes the cases of 2 young adult men with depressive symptoms who experienced severe and disruptive motor disturbances while taking serotonin reuptake inhibitors. Both patients had a long history of medication failures and complex presentations. Genetic testing was utilized to guide effective treatment plans and to provide insight into previous medication failures. Most notably, testing in these patients revealed variations in the serotonin transporter protein and cytochrome P450 2D6 and 2C19 enzymes. These cases demonstrate the utility of genetic testing in clinical practice to help identify effective treatment plans in psychiatric patients.

Receptor specificity of influenza A H3N2 viruses isolated in mammalian cells and embryonated chicken eggs.

Isolation of human subtype H3N2 influenza viruses in embryonated chicken eggs yields viruses with amino acid substitutions in the hemagglutinin (HA) that often affect binding to sialic acid receptors. We used a glycan array approach to analyze the repertoire of sialylated glycans recognized by viruses from the same clinical specimen isolated in eggs or cell cultures. The binding profiles of whole virions to 85 sialoglycans on the microarray allowed the categorization of cell isolates into two groups. Group 1 cell isolates displayed binding to a restricted set of alpha2-6 and alpha2-3 sialoglycans, whereas group 2 cell isolates revealed receptor specificity broader than that of their egg counterparts. Egg isolates from group 1 showed binding specificities similar to those of cell isolates, whereas group 2 egg isolates showed a significantly reduced binding to alpha2-6- and alpha2-3-type receptors but retained substantial binding to specific O- and N-linked alpha2-3 glycans, including alpha2-3GalNAc and fucosylated alpha2-3 glycans (including sialyl Lewis x), both of which may be important receptors for H3N2 virus replication in eggs. These results revealed an unexpected diversity in receptor binding specificities among recent H3N2 viruses, with distinct patterns of amino acid substitution in the HA occurring upon isolation and/or propagation in eggs. These findings also suggest that clinical specimens containing viruses with group 1-like receptor binding profiles would be less prone to undergoing receptor binding or antigenic changes upon isolation in eggs. Screening cell isolates for appropriate receptor binding properties might help focus efforts to isolate the most suitable viruses in eggs for production of antigenically well-matched influenza vaccines.