Testing for neuronal antibodies in first-episode psychosis – Asking the relevant questions

Where do we start?

Autoimmune encephalitis (AE) remains an essential differential diagnosis of first-episode psychosis (FEP) (Guasp et al., 2021). Patients with AE have pathogenic antibodies against neuronal proteins which interfere with their functions (Dalmau et al., 2008). While studies have emphasized a wide array of neuronal antibodies against both surface and intracellular antigens (Pollak et al., 2020), most have focused on the antibodies against the N-methyl-D-aspartate receptor (NMDAR), given the strong

Autoimmune encephalitis or autoimmune psychosis? (Graus and Dalmau, 2021)

The term AP was originally designated for patients with psychosis of suspected autoimmune origin who had serum neuronal antibodies (Graus and Dalmau, 2021). On the other hand, a definitive AE diagnosis requires the presence of neuronal antibodies in the CSF (Graus et al., 2016). While studies on antibodies in psychotic patients have mainly been restricted to serum samples (Pollak et al., 2020), the clinical significance of serum neuronal antibodies is unlikely relevant, since 1–5% of healthy

Where do we go from here?

Addressing these concerns, as well as common limitations of the real-world practice, Guasp et al. (2021) propose a new diagnostic algorithm in FEP:

• (1)

  patients with FEP and accompanying neurological symptoms should have CSF testing, antibodies included;

• (2)

  patients with FEP and absent neurological symptoms should have serum antibody testing (anti-NDMDAR antibodies first, as other antibodies are extremely rare in FEP with isolated psychiatric symptoms), along with brain MRI and EEG, and if any is

Financial disclosure

No funding or research grants were received in the course of study, research or assembly of the manuscript.

Funding source

None.

CRediT authorship contribution statement

D.P. drafted the manuscript and conceived the theoretical framework. N.G. assisted in conceiving the theoretical framework and worked on the manuscript. O.O.C. and I.V.M. supervised the project, provided feedback, and worked on the manuscript. All authors approved the final version of the manuscript.

Declarations of interest

None.

Acknowledgement

None.