Mood disorders (major depressive disorders [MDDs] and bipolar disorders [BDs]) are common psychiatric conditions and major causes of morbidity and mortality worldwide. Their neurobiology is extensively studied, and major advances have been made in understanding the neuroanatomic, neurochemical, synaptic plasticity, and genetic correlates. In this review, we discuss the major neuroanatomic regions in the brain affected in mood disorders and brain structural and functional alterations, the main hypotheses for the neurobiology, the major neurotransmitters and neuromodulators implicated, the synaptic plasticity changes, the role of stress and the hypothalamic-pituitary-adrenal axis, the importance of circadian rhythms, and the role of genetics. We discuss differences in the neurobiology between MDDs and BDs and connect the knowledge of neurobiology to therapeutics. We discuss the main classes of medications, such as antidepressants for treatment of MDD and mood-stabilizing drugs for treatment of BD, and neuromodulation therapies such as transcranial magnetic stimulation. We point to unanswered questions and future directions, such as elucidation of the role of atypical neurotransmitter
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