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Dysregulation of adult hippocampal neuroplasticity in major depression: pathogenesis and therapeutic implications

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Abstract

Major depressive disorder (MDD) was previously hypothesized to be a disease of monoamine deficiency in which low levels of monoamines in the synaptic cleft were believed to underlie depressive symptoms. More recently, however, there has been a paradigm shift toward a neuroplasticity hypothesis of depression in which downstream effects of antidepressants, such as increased neurogenesis, contribute to improvements in cognition and mood. This review takes a top-down approach to assess how changes in behavior and hippocampal-dependent circuits may be attributed to abnormalities at the molecular, structural, and synaptic level. We conclude with a discussion of how antidepressant treatments share a common effect in modulating neuroplasticity and consider outstanding questions and future perspectives.

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Fig. 1: Hippocampus anatomy.
Fig. 2: Mechanisms of synaptic plasticity.
Fig. 3: Molecular regulators of neuroplasticity.
Fig. 4: Before and after treatment.

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Conception: AT and MB. Original draft—AT, MM, and MB. Clinical insights—JJM and MB. Editing: JJM and RH. All authors revised the literature, reviewed, edited, and approved the final version.

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Tartt, A.N., Mariani, M.B., Hen, R. et al. Dysregulation of adult hippocampal neuroplasticity in major depression: pathogenesis and therapeutic implications. Mol Psychiatry 27, 2689–2699 (2022). https://doi.org/10.1038/s41380-022-01520-y

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