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The etiology of bipolar disorder (BD) is unknown and the neurobiological underpinnings are not fully understood. Both genetic and environmental factors contribute to the risk of BD, which may be linked through epigenetic mechanisms, including those regulated by histone deacetylase (HDAC) enzymes. This study measures in vivo HDAC expression in individuals with BD for the first time using the HDAC-specific radiotracer [11C]Martinostat. Eleven participants with BD and 11 age- and sex-matched control participants (CON) completed a simultaneous magnetic resonance – positron emission tomography (MR-PET) scan with [11C]Martinostat. Lower [11C]Martinostat uptake was found in the right amygdala of BD compared to CON. We assessed uptake in the dorsolateral prefrontal cortex (DLPFC) to compare previous findings of lower uptake in the DLPFC in schizophrenia and found no group differences in BD. Exploratory whole-brain voxelwise analysis showed lower [11C]Martinostat uptake in the bilateral thalamus, orbitofrontal cortex, right hippocampus, and right amygdala in BD compared to CON. Furthermore, regional [11C]Martinostat uptake was associated with emotion regulation in BD in fronto-limbic areas, which aligns with findings from previous structural, functional, and molecular neuroimaging studies in BD. Regional [11C]Martinostat uptake was associated with attention in BD in fronto-parietal and temporal regions. These findings indicate a potential role of HDACs in BD pathophysiology. In particular, HDAC expression levels may modulate attention and emotion regulation, which represent two core clinical features of BD.

Neurofibrillary tangle (NFT) imaging methods at the distinct scales of atomic and whole-brain resolutions have coevolved rapidly. Linking these two areas of research provides insight into how and why certain tau radiotracers, using positron emission tomography (PET), bind selectively to certain morphological forms of the NFT fibril. In this Review, a brief history and background for each research area is presented leading to a summary of the current state of knowledge, with a synopsis of PET NFT radiotracers and an outlook for near-term research efforts. The continued integration of information provided at the level of each of these scales of resolution will catalyze the next generation of clinical imaging technique development and enhance our interpretations of them.

The number of chemicals identified as endocrine disruptors continues to rise, and, yet, many assays intended to prioritize them for further action cannot gauge their impact on cells. Stossi and colleagues present new high-throughput screening methods that inform estrogen receptor biology, leading to questions about "safe alternatives" for one compound, bisphenol A.