This week in Morning Report, one of our residents discussed the case of an older adult referred for symptoms of new-onset psychosis. Psychosis is of course a big reason for referral to psychiatrists, but also to internists and family doctors — which is why it’s key to have a solid diagnostic approach to this topic.

Let’s discuss our learning points from this case!

1. Understanding the definition of psychosis

Psychosis is generally defined as a loss of contact with reality. This can encompass:

• Delusions, or fixed false beliefs: These can be of many types, including delusions of grandeur, persecutory delusions, delusions of reference, delusions of control, etc.
• Hallucinations, or sensory experiences that are not real: These can be auditory, visual, or somatic/tactile.
• Disorganization of thought: Inability to organize speech, thoughts, or behaviour to the point of impairment of function

Remember that psychosis may also be associated with so-called ‘negative symptoms’ such as reduced facial expressions, paucity of speech, amotivation, and loss of cognition, to name a few.

2. Remember three main etiologies for psychosis, and their distinguishing features

I think of psychosis in the following 3 big buckets shown in the figure below (internists usually get involved in the latter 2 scenarios). Substance-induced psychosis is usually easy to identify based on history, concurrent clinical symptoms, and investigations. To differentiate between primary psychiatric disease vs. psychosis due to a medical condition, it is crucial to elicit the age of onset of symptoms and the timecourse of symptoms on history (summarized below).

Remember also that psychosis may be a feature of psychiatric diseases that are not primarily classified as psychotic disorders (e.g., Major Depressive Disorder with psychotic symptoms).

3. Psychosis can be caused by numerous medical conditions

The differential diagnosis for psychosis due to medical conditions is large, and can range from common (endocrinopathies, delirium) to rare (autoimmune encephalitis).

To help conceptualize and organize our differential diagnosis, let’s go system-by-system, summarized in the table below.

A few pearls we discussed:

• Remember that diagnosis = localization x timecourse; in other words, your investigations will be carefully guided by any positive findings on review of systems, physical, and bloodwork
• Autoimmune encephalitis is an important diagnosis to consider in acute onset psychosis that may progress in severity to include other neurologic manifestations (impaired memory, cognition, followed by agitation, seizures, and/or depressed level of consciousness). These rare encephalitidies are often paraneoplastic in nature and can behave as ‘canaries in the coalmine’ for malignancies such as lung cancer, testicular cancers, and thymomas, to name a few.
• Occupational/exposure histories are key to obtain if you’re at the ‘zebra’ end of the diagnosis spectrum — e.g., looking for any signs/symptoms of heavy metal poisoning (e.g., lead), arsenic exposure, toluene exposure, etc.

As an initial starting point, my workup for a medical cause of psychosis would likely include (at minimum) CBC, lytes, extended lytes, Cr, liver enzymes, TSH, B12, HIV, VDLR, urine drug screen, +/- rheum panel/LP/EEG/imaging as guided by my history and physical examination above.

Overall, new-onset psychosis is not an uncommon reason for referral to primary care or the ED — I hope this approach was useful to your learning!