Psychosis is not a single illness but a symptom cluster involving a break from reality, such as hallucinations (hearing voices or seeing things that aren't there), delusions (fixed false beliefs), disorganized thinking, or paranoia. It appears in conditions like schizophrenia, bipolar disorder, severe depression, or substance-induced states. Importantly, there is no single "main" cause psychosis arises from a complex interplay of factors, often described by the stress-vulnerability model. This framework posits that individuals have an underlying biological vulnerability, which interacts with environmental stressors to trigger episodes.

Biological factors form the foundation of vulnerability:

• Genetics: Twin studies show heritability of 70–80% for schizophrenia-spectrum disorders. Specific genes (e.g., those affecting dopamine regulation like COMT or DISC1) increase risk, but no single gene causes psychosis.
• Neurochemistry: Excess dopamine activity in the mesolimbic pathway is strongly implicated (supported by antipsychotic drugs blocking D2 receptors). Glutamate dysfunction (NMDA receptor hypofunction) is another key mechanism, evidenced by ketamine models inducing psychosis-like states.
• Brain structure: MRI studies reveal reduced gray matter in prefrontal cortex and hippocampus, plus enlarged ventricles, often present before symptom onset.

Environmental triggers activate vulnerability:

• Stress: Childhood trauma (abuse, neglect) raises risk 3–5-fold via HPA-axis dysregulation and epigenetic changes.
• Substances: Cannabis (especially high-THC strains in adolescence), amphetamines, or cocaine can precipitate psychosis in vulnerable individuals; ~50% of first-episode cases involve drug use.
• Medical factors: Infections, autoimmune disorders (e.g., anti-NMDA encephalitis), or sleep deprivation lower the threshold.

In summary, psychosis emerges when genetic/neurobiological predisposition meets stressors, not from one cause. Early intervention targeting both biology (medication) and environment (therapy, social support) yields best outcomes