Neuroscience in Pictures: 4. Depression

Major depressive disorder represents a complex heterogeneous syndrome with significant public health impact. This pictorial review explores the multifaceted pathophysiology of depression through the case of an individual suffering from depression. Genetic vulnerability and environmental etiological factors, including early life adversity, and their interactions create a biological diathesis through alterations in stress response systems and neural circuitry. We review current evidence for several interconnected pathophysiological mechanisms underlying depression, including monoamine neurotransmission, hypothalamic-pituitary-adrenal axis dysfunction, chronic inflammation, and reduced neuroplasticity. Using the Research Domain Criteria framework, we connect these mechanisms across multiple levels of analysis—from genes, circuits to behavior. Neuroimaging findings highlight disruptions in key networks including the default mode, salience, and executive control circuits. The effectiveness of pharmacological, psychotherapeutic and other non-pharmacological interventions in depression underscores the importance of targeting multiple biological systems. This review emphasizes depression’s complex etiology involving dynamic interactions between genetic predisposition, environmental stressors, and neurobiological alterations, suggesting the need for personalized, multimodal therapeutic approaches.