Chapter 68: Schizophrenia Spectrum and Other Psychotic Disorders

Psychotic disorders involve fundamental disturbances in thought content and processing that reflect a loss of contact with reality, with schizophrenia affecting approximately 20 million individuals globally and representing one of the most disabling conditions contributing to disease burden worldwide. The onset typically occurs during adolescence or early adulthood, though females often experience first episodes in their late twenties to mid-thirties, with prognosis varying considerably among patients—roughly one-third achieve recovery, one-third experience fluctuating symptoms, and one-third follow a chronic degenerative course. The pathophysiology results from complex interactions between genetic vulnerability and environmental triggers, supported by twin study data showing 50 percent concordance in monozygotic twins, alongside structural brain differences including reduced prefrontal cortex and hippocampal volumes and dysregulation of dopaminergic, glutamatergic, GABAergic, and cholinergic systems. Clinical presentation comprises four major symptom domains: positive symptoms including delusions and auditory hallucinations that reflect pathological additions to normal experience; negative symptoms representing diminished emotional expression and motivation; cognitive deficits affecting memory and executive function that strongly predict functional outcomes; and affective disturbances including depression and anxiety that substantially elevate suicide risk. Diagnosis according to DSM-5-TR criteria requires at least two symptoms persisting for one month with six months of overall disturbance, while the broader spectrum includes schizoaffective disorder combining psychosis with mood episodes, schizophreniform disorder with shorter symptom duration, and brief psychotic disorder. Critical differential diagnosis involves ruling out substance-induced psychosis from cannabis or stimulants, medication effects, medical conditions including infections and metabolic derangements, and delirium. Management emphasizes multidisciplinary treatment combining antipsychotic pharmacotherapy—first-generation agents controlling positive symptoms but causing motor side effects, second-generation agents offering improved tolerability but metabolic risks, and clozapine for treatment-resistant cases—with psychosocial interventions including cognitive behavioral therapy for psychosis and assertive community treatment providing intensive support. Additional considerations address developmental and geriatric populations, the substantial lifespan reduction resulting from suicide and medical comorbidities, and the deleterious effects of stigma on treatment engagement and adherence, with recovery models emphasizing peer support and therapeutic alliance.