Major Depressive Disorder

Major depressive disorder (MDD) is a mood disorder characterized by persistent depressed mood or loss of interest/pleasure (anhedonia) lasting at least 2 weeks, accompanied by functional impairment. The pathophysiology involves multiple interconnected mechanisms. The monoamine hypothesis proposes that depression results from deficiency of serotonin (5-HT), norepinephrine (NE), and/or dopamine (DA) in synaptic clefts of the limbic system and prefrontal cortex. Serotonin regulates mood, sleep, appetite, and impulse control; norepinephrine regulates energy, alertness, and motivation; dopamine regulates pleasure, reward, and psychomotor activity. Beyond simple neurotransmitter deficiency, current understanding includes neuroplasticity dysfunction: chronic stress elevates cortisol (HPA axis hyperactivation), which damages hippocampal neurons, reduces brain-derived neurotrophic factor (BDNF), and impairs neurogenesis. This leads to hippocampal volume reduction (seen on MRI in chronic depression) and disrupted neural circuits between the prefrontal cortex (executive function), amygdala (emotional processing), and hippocampus (memory and context). Inflammatory mechanisms also contribute: elevated pro-inflammatory cytokines (IL-6, TNF-alpha, CRP) are found in depressed patients and can drive sickness behavior resembling depression. The practical nurse assesses mood, monitors safety, administers medications, and provides therapeutic communication.