Psychosis is a mental state where a person loses touch with reality, experiencing hallucinations (false perceptions like hearing voices) or delusions (fixed false beliefs). Brain imaging and neuroscience reveal key disruptions in neural circuits, chemistry, and structure.

Neurochemical Imbalance: The dominant theory is excess dopamine in the mesolimbic pathway, a reward circuit linking the ventral tegmental area (VTA) to the nucleus accumbens. This hyperactivity amplifies "salience" making irrelevant stimuli seem profoundly meaningful, fueling delusions. Antipsychotic drugs block D2 dopamine receptors, reducing symptoms in ~70% of cases (per meta-analyses in The Lancet Psychiatry). Low dopamine in the prefrontal cortex impairs executive function, worsening disorganized thinking.

Circuit Dysconnectivity: fMRI studies show weakened connectivity between the prefrontal cortex (PFC, for reasoning) and subcortical areas like the striatum and thalamus. This "dysconnectivity hypothesis" (Friston, 1998) leads to poor filtering of sensory input, causing hallucinations. The default mode network (DMN), active during self-reflection, becomes hyperactive and poorly regulated, blurring internal thoughts with external reality.

Structural Changes: MRI reveals reduced gray matter in the PFC, hippocampus, and temporal lobes, especially in chronic schizophrenia (a common psychosis cause). Enlarged ventricles indicate neuron loss. Glutamate dysfunction via NMDA receptor hypofunction triggers excitotoxicity, amplifying dopamine release and oxidative stress.

Inflammatory & Genetic Factors: Elevated cytokines (e.g., IL-6) suggest neuroinflammation disrupts blood-brain barrier integrity. Genetic risks (e.g., COMT gene variants) alter dopamine metabolism.

In acute psychosis, these changes create a "perfect storm": overactive subcortical signals overwhelm rational PFC control. Early intervention with antipsychotics and therapy can restore balance, but prolonged episodes risk permanent alterations.