Background: The DSM-5 mixed features specifier for mood disorders encourages renewed interest in mixed states and led us to pool research findings regarding prevalence of mixed features in episodes of major depressive (MDD) and bipolar disorders (BD).
Methods: We systematically searched to July 2017 for reports on mixed symptoms in depressive episodes of MDD and in depression and mania or hypomania in types I and II BD. For primary mood-states and diagnostic groups we compared rates of the presence of mixed symptoms: as defined by DSM-5 (≥3 features opposite to the dominant mood-polarity but not overlapping those of the primary disorder) or as having any ≥3 features of opposite polarity.
Results: We identified 17 reports, from 13 world regions involving 19,198 participants meeting standard diagnostic criteria for an index major depressive or [hypo]manic episode. Prevalence of cases with ≥3 features of opposite polarity averaged 27.8% [CI: 27.2-28.5] overall, and differed significantly between BD and MDD disorders, ranking: BD-depressed (35.2% [33.8-36.5]) = BD-[hypo]manic (35.1% [32.9-37.3]) > MDD-depressed (23.8% [23.0-24.5]).
Limitations: Available findings were limited to mood disorders with mixed features by particular criteria, with few comparisons to other criteria or to their prognostic or therapeutic implications.
Conclusions: Prevalence of ≥3 features of opposite polarity ranked: depressive = [hypo]manic episodes of BD > depression in MDD.
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http://dx.doi.org/10.1016/j.jad.2017.09.006 | DOI Listing |
Curr Biol
October 2021
Department of Biochemistry and Molecular Biology, the Uniformed Services University of the Health Sciences- F. Edward Hébert School of Medicine, Bethesda, MD 20814, USA. Electronic address:
Cytoplasmic dynein is activated by the dynactin complex, cargo adapters and LIS1 (Lissencephaly 1). How this process is regulated in vivo remains unclear. The dynein motor ring contains six AAA+ (ATPases associated with diverse cellular activities) domains.
View Article and Find Full Text PDFCell Chem Biol
October 2021
Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY 10065, USA. Electronic address:
Cytoplasmic dyneins are AAA (ATPase associated with diverse cellular activities) motor proteins responsible for microtubule minus-end-directed intracellular transport. Dynein's unusually large size, four distinct nucleotide-binding sites, and conformational dynamics pose challenges for the design of potent and selective chemical inhibitors. Here we use structural approaches to develop a model for the inhibition of a well-characterized S.
View Article and Find Full Text PDFNat Commun
November 2020
Department of Anatomy and Structural Biology and Gruss Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Cytoplasmic dynein is the primary motor for microtubule minus-end-directed transport and is indispensable to eukaryotic cells. Although each motor domain of dynein contains three active AAA+ ATPases (AAA1, 3, and 4), only the functions of AAA1 and 3 are known. Here, we use single-molecule fluorescence and optical tweezers studies to elucidate the role of AAA4 in dynein's mechanochemical cycle.
View Article and Find Full Text PDFStructure
December 2018
Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA. Electronic address:
Cytoplasmic dynein, whose motor domain belongs to the AAA+ family, walks on microtubules toward the minus end. Using the available structures in different nucleotide states, we performed simulations of a coarse-grained model to elucidate the dynamics of allosteric transitions. Binding of ATP closes the cleft between the AAA1 and AAA2 domains, triggering conformational changes in the rest of the motor domain, thus forming the pre-power stroke state.
View Article and Find Full Text PDFCell
September 2017
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address:
Regulation is central to the functional versatility of cytoplasmic dynein, a motor involved in intracellular transport, cell division, and neurodevelopment. Previous work established that Lis1, a conserved regulator of dynein, binds to its motor domain and induces a tight microtubule-binding state in dynein. The work we present here-a combination of biochemistry, single-molecule assays, and cryoelectron microscopy-led to the surprising discovery that Lis1 has two opposing modes of regulating dynein, being capable of inducing both low and high affinity for the microtubule.
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