Psychosis is a syndrome associated with dysregulation of the neurotransmitters dopamine and serotonin, and abnormal functioning of key brain circuits, particularly involving frontal, temporal, and mesostriatal brain regions.[1]McCutcheon RA, Reis Marques T, Howes OD. Schizophrenia-an overview. JAMA Psychiatry. 2020 Feb 1;77(2):201-10.
http://www.ncbi.nlm.nih.gov/pubmed/31664453?tool=bestpractice.com
People with psychosis typically experience hallucinations (e.g., auditory, visual, tactile), delusions, and disorganized thoughts and actions.
Psychosis can be due to primary ('non-organic') psychiatric disorders or can be secondary to substance use or specific medical ('organic') etiologies.[2]American Psychiatric Association. Diagnostic and statistical manual of mental disorders, fifth edition, text revision (DSM-5-TR). Washington, DC: American Psychiatric Association; 2022. Primary psychotic disorders include schizophrenia, delusional disorder, schizoaffective disorder, schizophreniform disorder, and brief psychotic disorder. A psychotic syndrome may also accompany other psychiatric conditions such as major depressive disorder and bipolar disorder.[3]Carvalho AF, Firth J, Vieta E. Bipolar disorder. N Engl J Med. 2020 Jul 2;383(1):58-66.
http://www.ncbi.nlm.nih.gov/pubmed/32609982?tool=bestpractice.com
Patients with psychosis associated with psychiatric disorders present with a combination of hallucinations (mostly auditory), delusions, and disorganized thought process, but are usually oriented and have minimal overt cognitive deficits. With the exception of acute agitation, patients with psychosis (who are otherwise healthy) tend to have normal vital signs. Patients with psychosis secondary to drug use or medical causes often present with altered vital signs, visual hallucinations, and severe cognitive impairment, including confusion or disorientation.
The evaluation of psychosis includes a physical exam, a complete psychiatric and medical history, and a laboratory work-up. The physical exam should include a detailed neurologic exam and a complete mental status exam, with the following areas of focus: mood and affect, thought process and content (including an evaluation of delusions, abnormal perceptions, suicidal and homicidal ideation, and insight), and a cognitive exam.
The medical history should include a review of head injury, seizures, cerebrovascular disease, sexually transmitted infections, and new or worsening headaches. Collateral history from relatives is recommended to chart the onset and course of the psychosis.
Recommended initial laboratory work-up includes a complete blood count, comprehensive metabolic profile, thyroid function tests, urine toxicology, and measurement of parathyroid hormone, calcium, vitamin B12, folate, and niacin.[4]The American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, third edition. Washington, DC: American Psychiatric Association Publishing; 2021.
https://psychiatryonline.org/doi/book/10.1176/appi.books.9780890424841
[5]Freudenreich O, Schulz SC, Goff DC. Initial medical work-up of first-episode psychosis: a conceptual review. Early Interv Psychiatry. 2009 Feb;3(1):10-8.
http://www.ncbi.nlm.nih.gov/pubmed/21352170?tool=bestpractice.com
Based on clinical suspicion, testing for HIV infection and hepatitis C, as well as brain neuroimaging (e.g., CT or MRI), should be considered as part of the initial work-up.[4]The American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia, third edition. Washington, DC: American Psychiatric Association Publishing; 2021.
https://psychiatryonline.org/doi/book/10.1176/appi.books.9780890424841
[5]Freudenreich O, Schulz SC, Goff DC. Initial medical work-up of first-episode psychosis: a conceptual review. Early Interv Psychiatry. 2009 Feb;3(1):10-8.
http://www.ncbi.nlm.nih.gov/pubmed/21352170?tool=bestpractice.com
[6]American College of Radiology. ACR appropriateness criteria; altered mental status, coma, delirium, and psychosis. 2024 [internet publication].
https://www.acr.org/Clinical-Resources/ACR-Appropriateness-Criteria
Epidemiology
The lifetime prevalence of psychosis in the general population is about 3%, with 0.21% of cases attributable to medical conditions.[7]Perälä J, Suvisaari J, Saarni SI, et al. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry. 2007 Jan;64(1):19-28.
https://www.doi.org/10.1001/archpsyc.64.1.19
http://www.ncbi.nlm.nih.gov/pubmed/17199051?tool=bestpractice.com
Most commonly, psychotic symptoms are associated with other mental disorders. The lifetime prevalence of schizophrenia is approximately 0.3% to 0.7%.[8]McGrath J, Saha S, Chant D, et al. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev. 2008 May 14;30:67-76.
https://www.doi.org/10.1093/epirev/mxn001
http://www.ncbi.nlm.nih.gov/pubmed/18480098?tool=bestpractice.com
In one urban primary care population study, 20.9% of adult patients reported 1 or more psychotic symptoms; psychosis co-occurred with depressive, anxiety, and panic disorders, and substance use disorders.[9]Olfson M, Lewis-Fernández R, Weissman MM, et al. Psychotic symptoms in an urban general medicine practice. Am J Psychiatry. 2002 Aug;159(8):1412-9.
https://www.doi.org/10.1176/appi.ajp.159.8.1412
http://www.ncbi.nlm.nih.gov/pubmed/12153836?tool=bestpractice.com
One cross-sectional study found that the rates of positive symptoms of psychosis occurring during acute mood episodes of bipolar disorder (BD) (mania, depression, and mixed states) is similar to the rates observed in schizophrenia.[10]Pini S, de Queiroz V, Dell'Osso L, et al. Cross-sectional similarities and differences between schizophrenia, schizoaffective disorder and mania or mixed mania with mood-incongruent psychotic features. Eur Psychiatry. 2004 Feb;19(1):8-14.
http://www.ncbi.nlm.nih.gov/pubmed/14969775?tool=bestpractice.com
[11]van Bergen AH, Verkooijen S, Vreeker A, et al. The characteristics of psychotic features in bipolar disorder. Psychol Med. 2019 Sep;49(12):2036-48.
http://www.ncbi.nlm.nih.gov/pubmed/30303059?tool=bestpractice.com
The rate of peripartum psychosis, which is a type of brief psychotic disorder, is 1 to 2 per 1000 childbirths; risk factors include a history of depression, bipolar disorder, or past peripartum psychosis or mood disorder.[5]Freudenreich O, Schulz SC, Goff DC. Initial medical work-up of first-episode psychosis: a conceptual review. Early Interv Psychiatry. 2009 Feb;3(1):10-8.
http://www.ncbi.nlm.nih.gov/pubmed/21352170?tool=bestpractice.com