Depression is a complex mental disorder with diverse symptoms and a heterogeneous etiology. It is characterized by symptoms such as depressed mood, anhedonia, irritability, and neurovegetative symptoms like changes in appetite and sleep. Depression is associated with significant health risks, including increased mortality from suicide, coronary artery disease, and type 2 diabetes. Despite its prevalence, the pathophysiology of depression remains poorly understood compared to other chronic diseases. The brain's complex nature makes it challenging to study, and current techniques for examining brain function are limited. Animal models have provided insights into the neural circuits involved in depression, but their interpretation is challenging. Recent studies have shown that depression results from maladaptive stress-induced neuroplastic changes in specific neural circuits. Understanding resilience to stress is crucial for developing new antidepressant treatments. The neurobiology of depression involves several brain regions, including the prefrontal cortex, hippocampus, amygdala, and subgenual cingulate cortex. Functional imaging has shown that increased activity in these regions is correlated with dysphoric emotions. Deep brain stimulation has shown promise in treating treatment-resistant depression. Monoamine-based antidepressants, such as SSRIs and MAOIs, are widely used but have limitations, including delayed onset and low remission rates. Recent research has focused on the role of neurotrophins, particularly BDNF, in depression. BDNF is involved in neuroplasticity and has been shown to mediate antidepressant effects. However, the BDNF hypothesis is complex and region-specific. Epigenetic mechanisms, such as DNA methylation and histone acetylation, also play a role in depression and antidepressant action. Neuroendocrine and neuroimmune interactions are important in depression, with glucocorticoids and cytokines playing significant roles. Epigenetic modifications, such as DNA methylation and histone acetylation, are involved in the pathophysiology of depression and can be influenced by environmental factors. Resilience to stress involves complex neurobiological mechanisms, including the role of the mesolimbic dopamine pathway and the regulation of BDNF. New insights into depression include the rapid antidepressant effects of ketamine and the role of MCH and other peptides in mood regulation. The field of depression research is evolving, incorporating gene-environment interactions, epigenetic mechanisms, and neuroplasticity. A multidisciplinary approach is needed to understand the neurobiology of depression and develop effective treatments.Depression is a complex mental disorder with diverse symptoms and a heterogeneous etiology. It is characterized by symptoms such as depressed mood, anhedonia, irritability, and neurovegetative symptoms like changes in appetite and sleep. Depression is associated with significant health risks, including increased mortality from suicide, coronary artery disease, and type 2 diabetes. Despite its prevalence, the pathophysiology of depression remains poorly understood compared to other chronic diseases. The brain's complex nature makes it challenging to study, and current techniques for examining brain function are limited. Animal models have provided insights into the neural circuits involved in depression, but their interpretation is challenging. Recent studies have shown that depression results from maladaptive stress-induced neuroplastic changes in specific neural circuits. Understanding resilience to stress is crucial for developing new antidepressant treatments. The neurobiology of depression involves several brain regions, including the prefrontal cortex, hippocampus, amygdala, and subgenual cingulate cortex. Functional imaging has shown that increased activity in these regions is correlated with dysphoric emotions. Deep brain stimulation has shown promise in treating treatment-resistant depression. Monoamine-based antidepressants, such as SSRIs and MAOIs, are widely used but have limitations, including delayed onset and low remission rates. Recent research has focused on the role of neurotrophins, particularly BDNF, in depression. BDNF is involved in neuroplasticity and has been shown to mediate antidepressant effects. However, the BDNF hypothesis is complex and region-specific. Epigenetic mechanisms, such as DNA methylation and histone acetylation, also play a role in depression and antidepressant action. Neuroendocrine and neuroimmune interactions are important in depression, with glucocorticoids and cytokines playing significant roles. Epigenetic modifications, such as DNA methylation and histone acetylation, are involved in the pathophysiology of depression and can be influenced by environmental factors. Resilience to stress involves complex neurobiological mechanisms, including the role of the mesolimbic dopamine pathway and the regulation of BDNF. New insights into depression include the rapid antidepressant effects of ketamine and the role of MCH and other peptides in mood regulation. The field of depression research is evolving, incorporating gene-environment interactions, epigenetic mechanisms, and neuroplasticity. A multidisciplinary approach is needed to understand the neurobiology of depression and develop effective treatments.