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Major depressive disorder (MDD) is associated with deficits in representing reward prediction errors (RPEs), which are the difference between experienced and predicted reward. Reward prediction errors underlie learning of values in reinforcement learning models, are represented by phasic dopamine release, and are known to affect momentary mood.To combine functional neuroimaging, computational modeling, and smartphone-based large-scale data collection to test, in the absence of learning-related concerns, the hypothesis that depression attenuates the impact of RPEs.Functional magnetic resonance imaging (fMRI) data were collected on 32 individuals with moderate MDD and 20 control participants who performed a probabilistic reward task. A risky decision task with repeated happiness ratings as a measure of momentary mood was also tested in the laboratory in 74 participants and with a smartphone-based platform in 1833 participants. The study was conducted from November 20, 2012, to February 17, 2015.Blood oxygen level-dependent activity was measured in ventral striatum, a dopamine target area known to represent RPEs. Momentary mood was measured during risky decision making.Of the 52 fMRI participants (mean [SD] age, 34.0 [9.1] years), 30 (58%) were women and 32 had MDD. Of the 74 participants in the laboratory risky decision task (mean age, 34.2 [10.3] years), 44 (59%) were women and 54 had MDD. Of the smartphone group, 543 (30%) had a depression history and 1290 (70%) had no depression history; 918 (50%) were women, and 593 (32%) were younger than 30 years. Contrary to previous results in reinforcement learning tasks, individuals with moderate depression showed intact RPE signals in ventral striatum (z = 3.16; P = .002) that did not differ significantly from controls (z = 0.91; P = .36). Symptom severity correlated with baseline mood parameters in laboratory (ρ = -0.54; P 1 × 10-6) and smartphone (ρ = -0.30; P 1 × 10-39) data. However, participants with depression showed an intact association between RPEs and happiness in a computational model of momentary mood dynamics (z = 4.55; P .001) that was not attenuated compared with controls (z = -0.42; P = .67).The neural and emotional impact of RPEs is intact in major depression. These results suggest that depression does not affect the expression of dopaminergic RPEs and that attenuated RPEs in previous reports may reflect downstream effects more closely related to aberrant behavior. The correlation between symptom severity and baseline mood parameters supports an association between depression and momentary mood fluctuations during cognitive tasks. These results demonstrate a potential for smartphones in large-scale computational phenotyping, which is a goal for computational psychiatry.

Introduction Finding an accurate and convenient biomarker for cancer progression in Barrett9s (BE) is of high clinical importance. DNA ploidy abnormalities (DNA-PA) are a reliable predictor of cancer risk in BE, but measurement is expensive and scarcely available. We have shown polo-like kinase-1 (PLK1) may act as a surrogate marker of DNA-PA in oesophageal adenocarcinoma (OA) resection specimens. This study aimed to examine the potential of PLK1 in predicting DNA-PA in the metaplasia-dysplasia-OA sequence. Methods 36 paraffin embedded oesophageal tissue specimens were selected from patients with non-dysplastic BE (NDBE, n=5), low grade dysplasia (LGD, n=5), high grade dysplasia (HGD, n=12), intramucosal cancer (IMC, n=5) and invasive OA (IOA, n=9). Sections were mounted and immunostained with 2 PLK-1 antibodies PLK1-M and PLK1-L using an automated system (BOND-MAX, Leica) for consistency. Results were reported by two independent expert pathologists blinded to patient status with the Allred scoring system, a composite of the percentage and intensity of staining. Results Aneuploidy was present in LGD (20%), HGD (75%), IMC (20%) and IOA (56%) samples. Using linear regression analysis, Pearson coefficient was calculated for the correlation between DNA-PA and mean Allred expression scores for each PLK1 antibody. PLK1-M had a higher degree of correlation (r 2 =0.26, p=0.001) then PLK1-L (r 2 =0.22, p=0.004). Inter-observer analysis with linear κ scores confirmed good correlation of PLK1-M (κ=0.72, 95% CI 0.60 to 0.83) and PLK1-L (κ=0.53, 95% CI 0.38 to 0.68), but a Bland–Altman plot found pathologist 2 had a trend to score PLK-L more highly. However, intra-observer analysis confirmed both PLK1-L scores correlated with ploidy status (r 2 =0.14, p=0.023 and r 2 =0.27, p=0.0016). Pathologists took 90.3 s/slide (mean) to review and score with the Allred method. Using a mean Allred cut off score of 3.5, the sensitivity and specificity for the detection of aneuploidy were 81.3% and 75% for PLK1-M, 93.8% and 45% for PLK1-L. Conclusion This pilot study demonstrated a significant correlation between Allred reporting of PLK1 staining and DNA-PA. PLK1-L appears more sensitive and PLK1-M more specific. PLK1 immunostaining is relatively inexpensive, less work intensive and is more available than current methods to predict DNA-PA. Scoring staining with Allred is rapid and reproducible. In future, PLK1 staining may provide the basis of a more durable biomarker panel to predict DNA ploidy. Competing interests None declared.