A 28-year-old man presents with a 3-month history of hearing voices commenting on his actions, belief that his thoughts are being broadcast to others, and social withdrawal. He has no prior psychiatric history. Which investigation is most appropriate to exclude organic causes before confirming a diagnosis of schizophrenia?

## Investigation Strategy in First-Episode Psychosis **Key Point:** Before diagnosing schizophrenia, organic causes of psychosis must be excluded. **MRI brain** is the most appropriate single investigation to rule out structural organic pathology (tumours, demyelinating disease, encephalitis, vascular lesions) in a first-episode psychosis presentation. ### Rationale for Correct Answer MRI brain is the **investigation of choice to exclude organic causes** in first-episode psychosis because: 1. **Structural lesions** — brain tumours (especially frontal/temporal), demyelinating plaques (MS), limbic encephalitis, and vascular lesions can all present with hallucinations, thought disorder, and social withdrawal indistinguishable from schizophrenia. 2. **Superior sensitivity** — MRI provides far greater anatomical detail than CT, detecting subtle cortical, subcortical, and white-matter pathology that would be missed on plain imaging. 3. **Guideline-recommended** — NICE (CG178), RANZCP, and most international first-episode psychosis protocols recommend neuroimaging (preferably MRI) as part of the organic exclusion workup, particularly when the diagnosis is being made for the first time. 4. **Irreversible consequences of missing organic disease** — a missed brain tumour or autoimmune encephalitis treated as schizophrenia carries serious morbidity; MRI is the safest screen. **High-Yield:** The standard workup for first-episode psychosis includes: - **MRI brain** (to exclude structural/organic pathology) ← most appropriate single investigation - Full blood count, U&Es, LFTs, fasting glucose, lipid profile - Thyroid function tests (TFTs) and prolactin (baseline endocrine screen) - Urine drug screen (to exclude substance-induced psychosis) - EEG only if seizure disorder or catatonia is suspected ### Why Serum Prolactin + TFTs Are Not the Best Answer Here Prolactin and TFTs are **important baseline metabolic/endocrine investigations** but they do not exclude the most dangerous organic mimics of schizophrenia (structural brain disease, autoimmune encephalitis). The question specifically asks for the investigation "most appropriate to **exclude organic causes**" — this points to neuroimaging, not endocrine screening. **Clinical Pearl:** Thyroid dysfunction and hyperprolactinaemia are relatively uncommon causes of a full schizophrenia-like syndrome; structural and autoimmune CNS disease is the primary concern when excluding organic psychosis. MRI brain addresses this most directly. (Harrison's Principles of Internal Medicine, 21st ed.; NICE CG178 Psychosis and Schizophrenia in Adults, 2014) ### Investigation Hierarchy in Psychosis | Investigation | Indication | Timing | |---|---|---| | **MRI brain** | **Exclude structural organic causes — all first-episode psychosis** | **First-line** | | Prolactin, TFTs, FBC, U&Es, LFTs, glucose | Metabolic/endocrine baseline | Baseline (before antipsychotic) | | Urine drug screen | Suspected substance use | Baseline | | EEG | Suspected seizure disorder, catatonia | If indicated | | PET scan | Research only; not diagnostic | Not routine | [cite: NICE CG178 Psychosis and Schizophrenia in Adults; Harrison's Principles of Internal Medicine, 21st ed., Chapter on Schizophrenia]