Human pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is trisomy of chromosome 12. Here we dissect the cellular and molecular implications of this trisomy in hPSCs. Global gene expression analyses reveal that trisomy 12 profoundly affects the gene expression profile of hPSCs, inducing a transcriptional programme similar to that of germ cell tumours. Comparison of proliferation, differentiation and apoptosis between diploid and aneuploid hPSCs shows that trisomy 12 significantly increases the proliferation rate of hPSCs, mainly as a consequence of increased replication. Furthermore, trisomy 12 increases the tumorigenicity of hPSCs in vivo, inducing transcriptionally distinct teratomas from which pluripotent cells can be recovered. Last, a chemical screen of 89 anticancer drugs discovers that trisomy 12 raises the sensitivity of hPSCs to several replication inhibitors. Together, these findings demonstrate the extensive effect of trisomy 12 and highlight its perils for successful hPSC applications.

Background The COVID-19 pandemic has led to extensive social distancing measures. For those suffering from social anxiety, social distancing coincides with a tendency to avoid social interactions. We used this natural experiment imposed by a COVID-19 lockdown to examine how mandated low social exposure influenced socially anxious university students, and compared their anxiety to that of socially anxious students in preceding academic years with no social distancing. Methods Ninety-nine socially anxious students were assessed for social anxiety symptoms at the beginning of the fall and spring semesters. Students from the 2019-2020 academic year (which included a lockdown followed by social distancing measures at the end of the fall semester) were compared to students from preceding years (2016-2019) on social anxiety levels. Results Whereas social anxiety decreased in socially anxious students from the fall to the spring semester in the years preceding the pandemic, during the 2019-2020 academic year social anxiety levels remained high and unchanged. These results held when controlling for depressive symptoms and when analyzing social anxiety items that cannot be confounded with COVID-19-related anxiety. Conclusions The current results suggest that reduced exposure to social situations may play a role in the maintenance of social anxiety. Alternative explanations are discussed.

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Background Attention bias modification (ABM) therapy aims to modify threat‐related attention patterns via computerized tasks. Despite showing medium clinical effect sizes for anxiety disorders, underlying neural‐cognitive mechanisms of change remain unclear. We used visual mismatch negativity (vMMN), an event‐related potential sensitive to violations of learned statistical contingencies, to assess therapy‐related contingency extraction processes in healthy participants and in patients with social anxiety disorder (SAD). We then assessed whether vMMN amplitude predicts ABM treatment outcome. Methods A modified version of the dot‐probe task was used to elicit vMMN, in which 80% of trials were standard and 20% were deviant. In study 1, 30 healthy adults were randomly assigned to one of two ABM conditions: one in which threat‐congruent targets were deviant trials and threat‐incongruent targets were standard trials, and another in which the contingency was reversed. Electroencephalography (EEG) was continuously measured and vMMN analyzed. In study 2, 38 patients with SAD underwent six sessions of ABM therapy. We tested whether rule extraction in the ABM task, indicated by vMMN amplitude, predicts treatment outcome. Results vMMN clearly emerged over prespecified scalp locations indicating contingency extraction during ABM (study 1). vMMN amplitude predicted clinical improvement after ABM therapy, uniquely accounting for 7% and 14.4% of the variance in clinician‐rated and self‐reported posttreatment SAD symptoms, respectively. Conclusions vMMN emerges as a neural marker for contingency learning in ABM, suggesting a significant role for contingency extraction processes in the clinical efficacy of this therapy.

Understanding psychopathology in the context of a developmental cognitive neuroscience approach entails the notion that specific individual differences in information processing can serve as both etiologic and maintaining factors in the development of specific disorders. It is posited that such mechanistic understanding of neurocognitive aberrations during development can then serve focused translational efforts in the form of cognitive bias modification treatments. In the review by Lau and Waters (this issue), an astute developmental model is suggested regarding the role of potential neurocognitive mechanisms in depression and anxiety in youth. A framework is offered in which information-processing mechanisms, such as threatrelated attention bias or threat-safety cue discrimination, may serve as proximal mediators of more distal risk factors, such as parental environment, temperament, and genetics, together contributing to the development and manifestation of depression and anxiety throughout the course of development. It is further implied that different combinations of distal risk factors and proximal information-processing mechanisms could eventually account for commonalities and differential aspects of anxiety and depression. The proposed model challenges the traditional divide between the diagnostic entities of anxiety and depression, laying preliminary grounds for a more mechanistic research and diagnostic approach. In this model, emphasis is redirected from symptom clusters to their underlying mechanisms and interconnections (Cuthbert, 2014;Insel et al., 2010).The role of four rudimentary information-processing mechanisms is reviewed in relation to anxiety and depression: threat-related attention bias, threatsafety cue discrimination (related to fear conditioning and extinction), memory, and stimulus appraisal (related to interpretation of ambiguous internal and external information). Arguably, these bundles of core information-processing mechanisms reflect a wide range of neurocognitive computations that together support adaptive or maladaptive mental and behavioral adjustment. While considerable research indicates quite stable anxiety-depression commonalities and distinctions in relation to specific informationprocessing biases, only preliminary and rather scattered support is observed for mediation of associations between distal factors and these disorders by specific cognitive biases. It quickly becomes evident from the review that lack of methodological consistency between studies and lack of integrated effort to produce a critical mass of consistent and reliable findings pose a major obstacle for advancement in mechanism elucidation and treatment development. Clearly lacking are single studies integrating across cognitive mechanisms and clinical populations. Accordingly, when interrogating their model in relation to the extant literature, Lau and Waters are often forced to conclude that currently the field is understudied to afford decisive inferences about their model. For instance, memory biases ...