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Background Several biological abnormalities in major depressive disorder (MDD) persist during episode remission, including altered serotonin neurotransmission, and may reflect underlying pathophysiology. We previously described elevated brain serotonin 1A (5-HT1A) receptor binding in antidepressant-naïve subjects with MDD within a major depressive episode (MDE) compared to healthy controls using positron emission tomography (PET). In the current study, we measured 5-HT1A receptor binding in unmedicated subjects with MDD during sustained remission, hypothesizing higher binding compared with healthy controls, and binding comparable to currently depressed antidepressant-naïve subjects, indicative of a biologic trait. Methods We compared 5-HT1A binding potential (BPF) assessed through PET scanning with [11C]WAY-100635 in 15 subjects with recurrent MDD in remission for ≥12 months and off antidepressant medication for ≥ six months, 51 healthy controls, and 13 antidepressant-naïve MDD subjects in a current MDE. Metabolite-corrected arterial input functions were acquired for estimation of BPF. Results Remitted depressed subjects had higher 5-HT1A BPF than healthy controls; this group difference did not vary significantly in magnitude across brain regions. 5-HT1A BPF was comparable in remitted and currently depressed subjects. Conclusions Elevated 5-HT1A BPF among subjects with remitted MDD appears to be a trait abnormality in MDD, which may underlie recurrent major depressive episodes. Future studies should evaluate the role of genetic and environmental factors in producing elevated 5-HT1A BPF and MDD, and examine whether 5-HT1A BPF is a vulnerability factor to MDEs that could have a role in screening high-risk populations for MDD.

Purpose Metabotropic glutamate receptor subtype 5 (mGluR5) dysfunction has been implicated in several disorders. [11C]ABP688, a Positron Emission Tomography (PET) ligand targeting mGluR5, could be a valuable tool in the development of novel therapeutics for these disorders by establishing in vivo drug occupancy. Due to safety concerns in humans, these studies may be performed in nonhuman primates. Therefore, in vivo characterization of [11C]ABP688 in nonhuman primates is essential. Methods Test/retest studies were performed in Papio anubis to compare modeling approaches and determine the optimal reference region. The mGluR5-specific antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) was then used in test/block studies, in which ligand binding was measured before and after MTEP administration. Test/block data were analyzed both by calculating changes in binding and using a graphical approach, which allowed estimation of both MTEP occupancy and nonspecific binding. Results Test/retest results, which have not been previously reported for [11C]ABP688, indicated that [11C]ABP688 variability is low using an unconstrained two-tissue compartment model. The most appropriate, though not ideal, reference region was found to be the grey matter of the cerebellum. Using these optimal modeling techniques on the test/block data, ~90% occupancy was estimated by the graphical approach. Conclusions These studies are the first to demonstrate the specificity of [11C]ABP688 for mGluR5 with in vivo PET in nonhuman primates. The results indicate that, in baboons, occupancy of mGluR5 is detectable by in vivo PET, a useful finding for proceeding to human studies, or performing further baboon studies, quantifying the in vivo occupancy of novel therapeutics targeting mGluR5.

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To become full and active participants in today's technologically saturated society, young people need to become creators (and not just consumers) of interactive media. Developing the requisite abilities and capacities is not a wholly individual process; it is important for young people to have access to communities where they can collaborate and share ideas. This article uses the Scratch online community for exploring how different forms of participation and collaboration can support and shape the ways in which young people develop as creators of interactive media. We describe participation in this community in terms of a spectrum ranging from socializing to creating and present examples of three forms of collaboration within the community. We argue that the most exciting interactive media creation and valuable learning experiences are taking place in the middle space, where participants draw on the best of socializing and creating practices.

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While the hype around Massive Open Online Courses (MOOCs) has subsided in the past few years, such environments provide a rich opportunity to explore ongoing questions at the intersection of teaching, learning, and technology. This paper explores how a set of facilitation teams described enacting their learner-centered pedagogical aspirations through MOOC platforms. Drawing on in-depth interviews, we present a set of six facilitator actions: “giving up control,” “distributing facilitation,” “being live,” “amplifying,” “modeling,” and “being explicit.” We discuss these actions as emerging from the negotiation between existing pedagogical aspirations and the realities of a new medium, highlighting how they involve facilitators both stepping back (making space for and foregrounding learner expertise and perspectives) and stepping in (intervening and directing as a facilitator). This research contributes to the ongoing work of articulating the substance and specificity of teaching in learner-centered pedagogy and the persistent challenges of enacting that pedagogy in massive, online spaces.

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