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Day # 9: Workup for First Psychotic Episode

Welcome back to our current theme of psychotic spectrum disorders. Today we will round out some additional clinical pearls to include what additional medical work-up should be pursued in a patient with new psychotic symptoms.

Today's Content Level: Intermediate; Advanced

Introduction to First Episode Workup

•Whenever a patient presents for the first time with symptoms of psychosis (hallucinations, delusions, disorganized speech/behavior), before making a diagnosis of schizophrenia or other psychotic disorder, it is very important to determine if these symptoms are caused primarily by another medical or neurological condition or induced by medications or other substances. Also, keep in mind that first episode psychosis is typically preceded by subtle premorbid signs in childhood and prodromal symptoms.

•Although schizophrenia can occur at any age, the average age of onset tends to be in the late teens to the early 20's for men, and the late 20's to early 30's for women. It is uncommon for schizophrenia to be diagnosed in a person younger than 12 or older than 40. If psychotic symptoms present younger than 12 or older than 40 a thorough medical workup is critical.

•Review the vital signs. If they are normal they don't tell you much, but, if abnormal, this can be the first clue that something other than purely psychiatric is going on. For example, if the patient is febrile then consider infections, malignancy, or drug reactions. If the patient is hypertensive and tachycardic then consider alcohol withdrawal, intoxication (cocaine, amphetamines, etc.), or drug reactions.

•Perform a complete physical and neurological exam. Don't underestimate this step. This is an area that I need to continue to work on as well. Many conditions masquerading as schizophrenia have positive findings on physical exam. You may see cranial nerve abnormalities or focal weakness (brain tumors or space occupying lesions), yellowing of the eyes (scleral icterus in liver failure), or palpate an enlarged thyroid gland (thyroiditis), and much more.

Common Labs and Imaging

•Most hospitals and emergency departments tend to have a routine protocol or a "standard psych order set." These orders often include a CBC, CMP, LFTs, TSH, BAL, U tox, beta hCG, FTA-ABS, and HIV. This topic can be very complex, but for now let's briefly discuss why these are commonly included, so we can understand what we are looking for.

•CBC (complete blood count): rule out infectious causes. If patient is febrile also obtain blood cultures and rule out common infections such as a urinary tract infection (urinalysis), pneumonia (chest x ray), abdominal infection (abdominal exam), and head CT +/- lumbar puncture if focal neurological signs.

•CMP (complete metabolic panel): rule out electrolyte disturbances (pay attention to sodium and calcium in particular), glucose (hypoglycemia or diabetic ketoacidosis), creatinine, and BUN (renal failure).

•LFTs (liver function test): this is commonly included in the CMP. Liver failure from alcohol, fatty liver, or viral hepatitis can causes psychosis at its extreme. If elevated LFTs in the absence of drinking history consider screening for viral hepatitis.

•TSH (thyroid stimulating hormone): hyper (thyroid storm) or hypothyroid (myxedema) can cause psychosis.

•BAL and U tox (blood alcohol level and urine toxicology screen): screen for substance use to include alcohol, cocaine, amphetamines, PCP, marijuana, and opiates. Be aware that not all substances will show up including bath salts, inhalants, hallucinogens, synthetic forms of cannabis, etc.

•Beta hCG (pregnancy test): influences treatment decisions! This will be discussed in later lessons in detail.

•FTA-ABS (fluorescent treponemal antibody absorption): testing for syphilis. If not treated, 30% of patients may develop tertiary syphilis, where neurosyphilis is included. Neurosyphilis can present with a variety of psychiatric symptoms including mania, depression, psychosis, and dementia.

•HIV: the classic gold standard test used to be an ELISA and confirmed with western blot (beyond the scope of this article). Now commonly diagnosed with an HIV viral load. Three technologies measure HIV viral load in the blood: reverse transcription polymerase chain reaction (RT-PCR), branched DNA (bDNA) and nucleic acid sequence-based amplification assay (NASBA). New-onset psychosis is thought generally to occur in AIDS or in later stages of HIV disease.

•Brain CT or MRI (computed tomography or magnetic resonance imaging): this is controversial as the % of patients with abnormal or treatment altering imaging findings is low. Still, some clinicians advocate for imaging at least once given the potential to dramatically influence disease course and prognosis. Evaluate for space-occupying lesions (tumors, arteriovenous malformations, abscess, etc.), demyelinating disorders, stroke, or hemorrhage.1

•Fun fact: in 6200 psychiatric patients with MRI, 1.6% had treatment altering MRI findings; multiple sclerosis and hemorrhage being the most common. 2

Extra Testing

•Other diagnostic tests that are less commonly included in standard order sets, but should still be considered in certain patients. These include vit B12, folate, ESR, ANA, heavy metal screen, copper/ceruloplasmin screen, prolactin level, genetic testing, EEG, LP, and neuropsychiatric testing.

•Vitamin B12 (cobalamin) and Vitamin B9 (folate): The exact role of vitamins B12 and folic acid in the pathogenesis and treatment of psychotic disorders is not fully understood, however, there is significant evidence to suggest there is an association. A study by Silver (2000) on 644 bedridden psychotics reported that 78.3% of schizophrenic patients had vitamin B12 deficiency. 3 Some studies have clearly indicated the contribution of folic acid, vitamin B12, and homocysteine to altered single-carbon metabolism and its role in the psychopathophysiology of schizophrenia.

•Vitamin B1 (thiamine): Thiamine deficiency over time can lead to something called Wernicke–Korsakoff syndrome. This commonly occurs secondary to alcoholism or malabsorption. You WILL see someone with this condition at some point in your career. This is commonly missed. It is generally agreed that Wernicke encephalopathy results from severe acute deficiency of thiamine (vitamin B1), whilst Korsakoff's psychosis is a chronic neurologic sequela of Wernicke encephalopathy.

•ESR (erythrocyte sedimentation rate): ESR is a marker of inflammation. In later lessons we will explore the relationship of inflammation and mental disorders, however, for now, know that high ESR is associated with increased risk for schizophrenia and can also be used to screen for vasculitis for specific patients, a known rare cause of psychosis.

•ANA (antinuclear antibody): several large-scale epidemiologic studies have found positive associations between autoimmune diseases and psychosis. Particularly, autoimmune diseases such as multiple sclerosis and lupus are known to have higher frequencies of neuropsychiatric symptoms, including psychosis, compared to healthy controls. 4

•Serum cortisol: adrenal insufficiency has been shown to display a wealth of possible psychiatric presentations including psychosis, depression, anxiety, mania, and cognitive impairment, alongside the known vague physical symptoms. Also, mildly high cortisol levels are seen in schizophrenia. 5

•Heavy metal screen: the heavy metals most commonly associated with poisoning of humans are lead, mercury, arsenic and cadmium. Heavy metal poisoning may occur as a result of industrial exposure, air or water pollution, foods, medicines, improperly coated food containers, or the ingestion of lead-based paints.

•Copper/ceruloplasmin: Wilson's disease (disorder of copper metabolism) is very rare, however it can have neuropsychiatric manifestations to include psychosis.

•Anti-N-methyl-D-aspartate receptor (NR1) immunoglobulin antibodies: autoimmune encephalitis affecting predominantly young females. It is characterized with neuropsychiatric symptoms, including personality changes, psychosis, autonomic dysfunction, seizures and movement disorders.

•Genetic testing: there are a number of studies looking at testable genes to predict the risk of schizophrenia and other psychotic disorders. To date, most experts haven't found consistent results to be clinically useful at this point, but this may become a significant part of our future clinical work.

•EEG (electroencephalogram): to rule out seizure disorder if there is a history consistent with possible seizure activity.

•LP (lumbar puncture): a lumbar puncture is indicated to rule out meningitis or other evidence of infection if there is evidence of delirium, fever, leukocytosis, or change in level of consciousness.

•Neuropsychiatric testing: you may opt to send the patient for thorough neuropsychiatric testing to gain a more in-depth understanding of their cognition and personality.


Today was hopefully a very practical lesson on how to diagnostically approach a patient who is first experiencing psychotic symptoms. It is important to balance being thorough in your workup, considering risk factors specific to the patient in front of you, and also being conscientious of the cost associated with extensive workups. Tomorrow will be another practical discussion focused on the nonpharmacologic treatment considerations in psychotic disorders. After that will come a few days of discussion regarding the pharmacology of antipsychotic medications.

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