Lab Tests for Psychosis

Psychosis is a neurological symptom that can develop when the brain is processing information inefficiently. Over 50 different medical conditions can affect brain functioning in ways that can produce psychosis. This article will list the medical tests that should be performed to look for the medical diseases that can potentially cause psychosis. Click here if you’d like to skip to the list of tests.

Psychosis is a symptom — it can have many causes

Psychosis is a lot like fever. It’s a symptom — not a diagnosis on its own. Psychosis can be a side effect of more than 100 different medications or drugs. Psychosis can be a symptom of more than 50 different medical diseases. Psychosis is also a symptom of about 6 different psychiatric conditions. But no one should jump to the conclusion that psychosis is part of a mental illness unless there’s been a thorough search for a medical or pharmacological cause. If someone is experiencing psychosis, the immediate and most important question is: “What’s the cause?”

How often is medical illness the cause of psychosis?

A landmark study in 1968 showed that 1 in every 8 patients admitted to a psychiatric hospital ward turned out to have a medical illness that either caused the psychiatric symptoms that led to hospitalization, or that made the symptoms worse. What’s even more alarming is that 80% of the time, these psychiatrically-relevant medical disorders (these important medical conditions) were missed at the initial assessment (Johnson, 1968) Richard Hall and collaborators from the University of Texas Medical School set up a study in which 100 patients that would have otherwise been sent to a state psychiatric hospital for long-term care were instead admitted to a specialized medical research unit, were each patient underwent a battery of relatively simple medical tests. Nearly 60% of the patients with psychosis in the study turned out to have a medical condition that either caused or significantly worsened their psychosis. Alarmingly, these medical conditions had not been detected prior to referral to the research unit. Subsequently, a team led by Philip Henneman at the Harbor-UCLA Medical Center used a relatively simple set of set of standard laboratory tests to screen for medical illness is 100 consecutively-admitted patients with new-onset psychiatric symptoms. They found that first-episode psychiatric symptoms were caused by underlying medical conditions over 60% of the time. A 1987 survey of 268 people with a first-episode of psychosis found medical causes in 1 of every 18 cases (Johnstone et al., 1987). Richards and Gurr estimate that 20% of patients admitted to the emergency department for psychosis have a medical disease that either caused the psychosis or intensified it. Meanwhile, Yousef Etlouba and colleagues found medical disease as a cause of psychosis in 55% of the 159 cases they identified in a Johannesburg emergency department. Many of those cases were attributed to HIV infection. However, removing HIV infection from the analysis, medical cause was the cause of psychosis in one third of cases. There has never been a large-scale, systematic study to figure out precisely how often medical diseases are the cause. However, as we can see from these smaller studies, medical causes of psychosis are common enough that they should be screened for routinely.

What are the medical diseases that can cause psychosis?

Psychosis may arise as the first symptom, only symptom, or most prominent symptom of more than 50 different medical conditions. Here is a list of them.

Some of the diseases that can cause psychosis

Addison’s disease	Adrenomyeloneuropathy	Celiac disease	Cerebral cysts and abscesses
Cerebral malaria	Cerebrovascular lesions	Chromosomal disorders	Cranial trauma
Cushing’s disease	Encephalitis and its sequelae	Fabry’s disease	Familial basal ganglia calcification
GM2 gangliosidosis	Hartnup disease	Hashimoto’s encephalopathy	HIV
Homocystinuria (MTHFR reductase deficiency)	Huntington’s disease	Hydrocephalus	Hyperparathyroidism
Hyperthyroidism	Hypoparathyroidism	Hypopituitarism	Hypothyroidism
Kartagener’s syndrome	Klinefelter’s syndrome	Metachromatic leukodystrophy	Narcolepsy
Neurosyphilis	NMDA receptor antibody encephalitis	Occult hydrocephalus	Oculocutaneous albinism
Pellagra	Pernicious anemia	Pick’s disease	Porphyrias
Prenatal static encephalopathy	Rheumatic chorea	Schilder’s cerebral sclerosis	Sheehan’s syndrome
Subarachnoid hemorrhage	Systemic lupus erythematosus	Tourette syndrome	Toxicity (drugs, medications, heavy metals)
Tuberous sclerosis	Tumors of the brain	Velocardiofacial syndrome	Vitamin A deficiency
Vitamin B12 deficiency	Vitamin D deficiency	Wilson’s disease	Zinc deficiency

Lab tests are important

Lab testing has an important role in the evaluation of psychosis. For many of the diseases listed above, psychosis might be the first symptom or the only obvious symptom. In other words, in some cases, there might not be any other physical signs of illness. In these cases, lab testing might be the only way to detect a medical disease that might be causing psychosis. In other cases, physical signs might be present but overlooked. It is possible to miss physical signs of disease if the psychosis is a very obvious symptom and physical signs are subtle. Psychosis might overshadow other symptoms. Laboratory testing can help avoid this problem. Lab testing for someone with psychosis might also address the situation where a person affected by psychosis is not able to talk about their non-psychiatric, physical symptoms in a way that makes sense to the clinician. This is another way that psychosis can overshadow physical signs of medical illness and again illustrates the importance of lab tests as part of a complete medical workup for psychosis.

What are the recommended lab tests for psychosis?

Considering how common psychosis is – and how often it can arise as a symptom of medical illness – there is not a single, consensus-accepted medical test panel to screen for medical causes of psychosis. Considering how common algorithm-driven practice has become in the field of medicine, the lack of widely-publicized medical test panels for psychosis is surprising. Nonetheless, there have been several prior attempts to define the necessary medical workup for psychosis. I will list them chronologically:

Coleman & Gillberg, 1997

In 1996, Drs. Mary Coleman and Christopher Gillberg published a book called The Schizophrenias: A Biological Approach to the Schizophrenia Spectrum Disorders, in which they surveyed the medical illnesses that can produce schizophrenia-like psychosis and proposed batteries of medical tests to screen for them. They published a summary of the proposed medical tests in a 1997 paper, which appeared in the Journal of Neuropsychiatry and Clinical Neuroscience. The recommended tests are: Blood tests

• Complete blood count (CBC)
• Tests of immune function (not specified)
• Electrolytes
• Blood urea nitrogen (BUN)
• Glucose
• Calcium
• Phosphorous
• Thyroid stimulating hormone (TSH), with additional tests (t3, T4, and thyroid-reducing hormone (TRH) test to be ordered if the TSH level is abnormal.
• Liver function tests
• Syphilis screen
• Antinuclear antibodies
• Vitamin A (serum)
• Vitamin B12 (serum)
• 1,25-dihydroxy vitamin D (serum)
• Copper (serum)
• Ceruloplasmin
• Methionine
• Phenlyalanine
• Zinc
• Porphobilinogen deaminase measured in mature red blood cells
• Levels of saturated very long chain fatty acids (males only)
• Alpha-galactosidase A level in lymphoblasts (males only)

Urine tests

• Drug screen
• 24-hour urine levels of
  • Copper
  • amino acids
  • vitamin B3 end products
  • adrenal steroids

Imaging

• Chest X-ray
• Brain CT or Brain MRI

Other tests

• EEG

Freudenreich et al., 2009

Oliver Freudenreich and colleagues in a 2009 paper surveyed the medical test recommendations that had been published by the Royal Australian and New Zealand College of Psychiatrists (2003), the American Psychiatric Association (2004), and the Canadian Psychiatric Association (2005). Synthesizing this information and adding their own perspectives, the authors produced the following list of recommended tests: Blood:

• Complete blood count
• Electrolytes
• Calcium
• Renal function tests (i.e., BUN and creatinine)
• Liver function tests
• Erythrocyte sedimentation rate
• Antinuclear antibody
• Fasting glucose
• Lipid profile
• Consider prolactin level
• Consider hepatitis C (if risk factors)
• Pregnancy test (in women of childbearing age)
• TSH (thyroid stimulating hormone)
• Syphilis screen (specifically, the FTA (fluorescent treponemal antibody) method)
• HIV test
• Ceruloplasmin
• Vitamin B12

Urine

• Urine drug screen

Imaging

• MRI (preferred over CT)

Additional tests, if indicated, could include: chest X-ray, lumbar puncture, karyotype, or heavy metals testing. Electrocardiogram (ECG, EKG) is recommended for anyone thought to have cardiac risk factors.

Galletley et al., 2016 (RANZCP Guidelines)

The Royal Australian and New Zealand College of Psychiatrists in 2016 updated their Clinical Practice Guidelines for the Management of Schizophrenia and Related Disorders. Professor Cherrie Galletly was the report’s first author. These are the medical tests recommended in the 2016 RANZCP guidelines Blood

• Full blood count
• Erythrocyte sedimentation rate
• Electrolytes
• Liver function tests
• Hepatitis screen (if indicated)
• “Other blood-borne diseases, for example HIV” (if indicated)
• Screening for sexually-transmitted diseases, if indicated
• Anti-NMDA receptor antibodies
• Anti-voltage-gated potassium channel antibodies
• Anti-glutamic acid decarboxylase antibodies

Urine

• Urine drug screening

Imaging

• MRI scan of the brain

Other studies

• Psychometric testing, if possible

Keepers et al., 2020 (American Psychiatric Association Guidelines)

In 2020, the American Psychiatric Association updated its Practice Guideline for the Treatment of Patients with Schizophrenia. Here are the lab tests recommended in that report Blood

• Complete blood count, including absolute neutrophil count
• Electrolytes
• Renal function tests
• Liver function tests
• Thyroid stimulating hormone level (TSH)
• Pregnancy test for women of childbearing potential
• Lipid panel
• Fasting blood glucose
• Prolactin level, if indicated on the basis of clinical history

Urine

• Drug toxicology screen, if clinically indicated

Other studies

• Brain imaging (CT or MRI, with MRI being preferred), if indicated on the basis of neurological examination or history
• Chromosomal testing, if indicated on the basis of physical examination or history, including developmental history
• Electrocardiogram (ECG, EKG) before treatment with chlorpromazine, droperidol, iloperidone, pimozide, thioridazine, or ziprasidone or in the presence of cardiac risk factors

My recommendations

Several of the recommended lab tests are obvious. Things like complete blood count, electrolytes, or kidney function tests appear on all of the above recommended panels. Other things that seem obvious, like screening for inflammatory disease – a rapid and very inexpensive screening test for a family of diseases well-known for their ability to cause or worsen psychosis — are not universally recommended across all guidelines. My suggestion for a basic screening panel is based on tests that have been identified in a majority of prior recommendations, or that are relatively inexpensive one-time tests that can sensitively screen for treatable medical disorders that can cause psychosis. Using these criteria, here is the list of sensible lab tests for psychosis: Blood

• Complete blood count with differential
• Electrolytes
• Calcium level
• Renal function tests (BUN, Creatinine)
• Liver function tests (AST, ALT, Bilirubin)
• Lipid panel
• Fasting blood glucose
• Hemoglobin A1c
• Uric acid
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP)
• TSH (thyroid stimulating hormone)
• Thyroid peroxidase antibody
• Gliadin antibody
• Tissue transglutaminase antibody
• Syphilis screen by FTA method
• HIV antibody screen
• Autoimmune encephalitis panel
  • NMDA receptor antibody
  • Voltage-gated potassium channel antibody
  • Glutamic acid decarboxylase antibody
• Hepatitis screen
• Prolactin level
• Ceruloplasmin
• Vitamin B12
• Pregnancy screen in women of childbearing age
• Urine drug screen
• Urinalysis

Imaging

• Brain imaging (MRI preferred over CT)
• Chest X-ray

Other tests

• Electrocardiogram (ECG, EKG)

References

Coleman, M. & Gillberg, C. The schizophrenias: a biological approach to the schizophrenia spectrum disorders. (Springer Publishing Company, 1996). Coleman, M. & Gillberg, C. A biological approach to the schizophrenia spectrum disorders. J. Neuropsychiatry Clin. Neurosci. 9, 601–605 (1997) Etlouba, Y., Laher, A., Motara, F., Moolla, M. & Ariefdien, N. First Presentation with Psychotic Symptoms to the Emergency Department. J. Emerg. Med. 55, 78–86 (2018) Freudenreich, O., Schulz, S. C. & Goff, D. C. Initial medical work-up of first-episode psychosis: a conceptual review. Early Interv. Psychiatry 3, 10–18 (2009) Galletly, C. et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Aust. N. Z. J. Psychiatry 50, 410–472 (2016) Johnson, D. A. The evaluation of routine physical examination in psychiatric cases. Practitioner 200, 686–691 (1968) Johnstone, E. C., Macmillan, J. F. & Crow, T. J. The occurrence of organic disease of possible or probable aetiological significance in a population of 268 cases of first episode schizophrenia. Psychol. Med. 17, 371–379 (1987) Keepers, G. A. et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. AJP 177, 868–872 (2020) Hall, R. C., Gardner, E. R., Stickney, S. K., LeCann, A. F. & Popkin, M. K. Physical illness manifesting as psychiatric disease. II. Analysis of a state hospital inpatient population. Arch. Gen. Psychiatry 37, 989–995 (1980) Henneman, P. L., Mendoza, R. & Lewis, R. J. Prospective evaluation of emergency department medical clearance. Ann. Emerg. Med. 24, 672–677 (1994) Richards, C. F. & Gurr, D. E. Psychosis. Emerg. Med. Clin. North Am. 18, 253–62, ix (2000)