Neurobiology of Mood Disorders

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 neurotransmitters in mood disorders, the need for better understanding of the genetics and interactions between the immune and central nervous systems, and the development of biomarkers and personalized therapeutics based on the neurobiology. Notably, there are discrepancies in the current scientific knowledge and many unanswered questions in the neurobiology due to the different ages of patients, disease stage, presence of medications, and other comorbidities. It is notable, however, that mood disorders have a clearly established biological basis with alterations in the immune and central nervous systems that affect synaptic plasticity, neural circuits, and larger-scale brain networks and communicate with the autonomic nervous system. This review contains 5 figures, 4 tables and 62 references Key words: antidepressant, bipolar disorder, epigenetics, hypothalamic-pituitary-adrenal axis, immune system, limbic system, major depressive disorder, mood stabilizer, neurotransmitter, synaptic plasticity, transcranial magnetic stimulation