Medical Conditions Associated with Psychosis

CONDITION	EXAMPLES
Delirium	​Sleep deprivation, Serum electrolyte abnormalities, Sepsis
Seizure Disorders	Particularly temporal lobe
​Central Nervous System Lesions	Brain tumors, Head trauma, Congenital malformations
Infections	Encephalitis, Meningitis
​Metabolic Disorders	B1, B3, or B12 deficiency, Hypocalcemia, Hypomagnesemia
​Endocrine Disorders	Cushing Disease, Diabetes mellitus, Thyroid disease
​Genetic Syndromes	Wilson’s, Huntington’s
Autoimmune Disorders	Lupus, Multiple sclerosis, Anti-NMDA receptor or other encephalitis
Toxic Exposures	Carbon monoxide, Organophosphates, Heavy metals
Pharmacologic	​Stimulants, Cannabis, Dextromethorphan, Lysergic acid, Diethylamide, Hallucinogenic mushrooms, Psilocybin, Peyote, Solvents & inhalants, Serotonin syndrome
Nutritional	​Hypoglycemia, Uremia, Acute intermittent porphyria

Many medical conditions can lead to psychotic symptoms, too many to include a detailed review here. A consultation with MCPAP or other psychiatric service provider is recommended to consider which tests or assessments may be indicated. See also the list of resources at the end of this page.
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Importantly, medical conditions or drugs may not only directly lead to the onset of psychotic-spectrum symptoms but can also trigger the onset of symptoms in individuals already vulnerable to psychosis (e.g., genetics, early central nervous symptom [CNS] insults, etc.). CNS insults associated with higher risk for psychosis include obstetrical complications, in utero toxic exposures, and traumatic brain injury.

Recommended Medical Workup for First Presentation of Symptoms

1

CAREFUL HISTORY

• Temporal pattern of onset of psychiatric symptoms
• Recent drug ingestion, infectious disease, head injury, or seizure
• New or worsening headaches
• Family history of psychiatric disorders (Review of specific symptoms and treatment may be needed to identify history of psychosis; see Asking about Family History)
• Collateral history from family to clarify behavioral changes and timeline
• Suicidal or violent thoughts and actions

2

PHYSICAL EXAMINATION

• Mental status, including cognitive functioning
• Neurological examination; note emergence of new signs or symptoms, subtle involuntary movements
• Signs of fever, endocrinopathies, metabolic illness
• Tachyccardia or severe hypertension

3

LABORATORY STUDIES

• CBC with differential to consider possible infectious illness
• Urine toxicology
• Imaging and EEG are not indicated in the absence of specific indicators (new, severe, unremitting headache, focal neurological deficits, or history of recent head trauma)
• Further assessment if initial observations and studies suggest pathology

​Comprehensive metabolic panel, including:
– Electrolytes: Na, K, CO2, Chloride
– Glucose
– BUN
– Creatinine
– Albumin, Total Protein
– Ca, Mg
– Alkaline phosphatase (ALP)
– Alanine amino transaminase (ALT or SGOT)
– Aspartate amino transaminase (AST or SGOT)
– Bilirubin
– Parathyroid hormone
– Vitamin B12, Folate, Niacin

BASELINE STUDIES PRIOR TO INITIATING ANTIPSYCHOTIC MEDICATIONS

• Lipid profile, fasting
• Glucose, fasting
• Height, weight, body mass index, waist circumference
• Comprehensive metabolic panel

Tips for Differential Diagnosis

1. Symptoms due to intoxication typically have an abrupt onset in the context of substance use and resolve within days to weeks of drug discontinuation.
2. Isolated symptoms (e.g., hearing voices) in the absence of depression, anxiety, decline in function, or of familial psychiatric illness are less likely to inidicate a serious illness.
3. Visual hallucinations in conjunction with neurologic signs, headache or seizures are more consistent with a neurologic disorder.
4. Consciousness and awareness are usually, if not always, intact in major psychotic disorders such as schizophrenia, bipolar disorder, schizoaffective disorder, etc.
5. Consider the pattern of onset: 
   1. Acute onset (days or weeks) may be more likely to be associated with drug effects, infection, or other specific medical states. It may also be associated with psychiatric states resulting from discrete stressors. More rapid onset is also more typical of major depressive disorder or bipolar disorder (vs. schizophrenia), particularly as mood symptoms intensify.
   2. Subacute onset (less than 12 weeks) may also be associated with neurological or medical illnesses (e.g., autoimmune encephalitis, which is uncommon but requires immediate assessment and treatment).
   3. Insidious or more gradual onset is more frequently seen in schizophrenia and more characteristic of child or adolescent onset. This is considered one of the reasons that accurate diagnosis is often delayed years in this age group, with unfortunate long-term consequences.

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Resources

1. Recognition and Differential Diagnosis of Psychosis in Primary Care, Griswold KS, et.al., , Am Fam Physician. 2015 Jun 15;91(12): 856-863. https://www.aafp.org/afp/2015/0615/p856.html
2. Diagnosis and Evaluation of Hallucinations and Other Psychotic Symptoms in Children and Adolescents, Sikith, L, Child and Adolescent Psychiatric Clinics of North America, 22(4), 655-673.
3. Psychotic Disorders in Children and Adolescents: A Primer on Contemporary Evaluation and Management, Stevens, J.R. et al., Prim Care Companion CNS Disord. 2014;16(2):PCC. 13f01514 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116281/#
4. Pediatric Autoimmune Encephalitis, Barbagallo M, et.al., J Pediatr Neurosci. 2017 Apr-Jun; 12(2): 130–134.
5. A clinical approach to diagnosis of autoimmune encephalitis, Graus F, et.al., Lancet Neurology, 2016; 15:391-404.
6. Practice Parameter for the Assessment and Treatment of Children and Adolescents With Schizophrenia, McClellan, J. et al. Journal of the American Academy of Child & Adolescent Psychiatry, Volume 52, Issue 9, 976 – 990 https://www.jaacap.org/article/S0890-8567%2813%2900112-3/fulltext#sec8.1
7. Patterns of health services use prior to a first diagnosis of psychosis: the importance of primary care, Anderson KK, Fuhrer R, Wynant W, Abrahamowicz M, Buckeridge DL, Malla A. Soc Psychiatry Psychiatr Epidemiol. 2013;(48):1389-1398.
8. The prevalence and correlates of nonaffective psychosis in the National Comorbidity Survey Replication (NCS-R), Kessler RC, Birnbaum H, Demler O, et al. Biol Psychiatry. 2005;58(8):668–676. doi:10.1016/j. biopsych.2005.04.034