No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

Circulating cell-free mitochondrial DNA (cf-mtDNA) is an emerging biomarker of psychobiological stress and disease which predicts mortality and is associated with various disease states. First, I present a systematic review of the literature that shows cf-mtDNA levels respond to common real-world stressors. The review discusses current knowledge on the mechanisms of cf-mtDNA release, its molecular forms of transport, potential physiological functions, cellular and neuroendocrine triggers, and factors that may contribute to cf-mtDNA removal from the circulation. Second, to evaluate the contribution of cf-mtDNA to health and disease states, standardized high-throughput procedures are needed to quantify cf-mtDNA in relevant biofluids. I describe the development of MitoQuicLy: Mitochondrial DNA Quantification in cell-free samples by Lysis. I demonstrate high agreement between MitoQuicLy and a commonly used column-based method, although MitoQuicLy is faster, cheaper, and requires a smaller input sample volume. I find that cf-mtDNA levels between concurrently collected plasma, serum, and saliva from the same individual differ on average by up to two orders of magnitude and are poorly correlated with one another, pointing to different cf-mtDNA biology or regulation between commonly used biofluids in clinical and research settings. Finally, I deploy MitoQuicLy in a highly phenotyped cohort of participants with mitochondrial disease and healthy controls to quantify the impact of a brief psychological stressor on cf-mtDNA levels in three biofluids and evaluate how cf-mtDNA release varies between individuals, biofluids, and mitochondrial disease status. These studies set the stage for a research agenda identifying novel links between psychological stress and physiological response, which may improve our understanding of how stressful experiences increase disease risk. In the future, cf-mtDNA release or its downstream effects may be targeted to modulate the impact of psychological stress on human health.

BACKGROUND: Major depression is a pervasive condition that affects every aspect of a patient’s life, and many patients are unable to find symptom alleviation with the current available medications. Ketamine has recently shown promise as a rapid-acting antidepressant, yet its mechanisms are not yet well-understood. OBJECTIVE: We sought to understand the change in depression symptom interrelationships, with particular interest in sleep, in the context of ketamine treatment in depression by completing a network analysis. METHODS: 97 patients with treatment-resistant depression were given ketamine over six treatments, and symptoms were examined via the Quick Inventory of Depressive Symptomology (QIDS-SR-16). Two networks were constructed: one prior to the first treatment, and one prior to the sixth treatment. Each symptom of the inventory formed a node, and partial correlations were used to construct the edges of the network. Centrality indices and network structure was then evaluated and compared. RESULTS: Centrality indices measured were unstable, limiting assertions to node strength, but global network structure was revealed to be changed between the networks. CONCLUSION: The data suggests that ketamine may affect the interrelationships between depressive symptoms, by impacting some symptoms more than others.