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Highlights
• A panel of 20 biomarkers was identified capable of differentiating BD patients from controls.
• Excellent discrimination between established BD patients and controls.
• Good to excellent discrimination between misdiagnosed BD patients and first onset MDD patients.
• Fair to good discrimination between pre-diagnostic BD patients and controls.
• Study demonstrates the potential utility of a protein biomarker panel as a diagnostic test for BD.
Abstract
Background: Bipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD.
Methods and findings: We performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies.
We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC) ⩾ 0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel.
Conclusions: An early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.
Lexical access speed and the development of phonological recoding during immediate serial recall
(2022)
A recent Registered Replication Report (RRR) of the development of verbal rehearsal during serial recall revealed that children verbalized at younger ages than previously thought, but did not identify sources of individual differences. Here, we use mediation analysis to reanalyze data from the 934 children ranging from 5 to 10 years old from the RRR for that purpose. From ages 5 to 7, the time taken for a child to label pictures (i.e. isolated naming speed) predicted the child’s spontaneous use of labels during a visually presented serial reconstruction task, despite no need for spoken responses. For 6- and 7-year-olds, isolated naming speed also predicted recall. The degree to which verbalization mediated the relation between isolated naming speed and recall changed across development. All relations dissipated by age 10. The same general pattern was observed in an exploratory analysis of delayed recall for which greater demands are placed on rehearsal for item maintenance. Overall, our findings suggest that spontaneous phonological recoding during a standard short-term memory task emerges around age 5, increases in efficiency during the early elementary school years, and is sufficiently automatic by age 10 to support immediate serial recall in most children. Moreover, the findings highlight the need to distinguish between phonological recoding and rehearsal in developmental studies of short-term memory.