Lower brain FAAH levels were linked to more severe psychotic symptoms in untreated patients | Research

The takeaway

The first PET imaging study of brain FAAH in psychosis found that while overall FAAH levels did not differ between patients and controls, lower FAAH predicted more severe positive psychotic symptoms with a large effect size.

Psychiatrists and neuroscientists studying psychosis biology, PET imaging researchers, and those investigating the endocannabinoid system in mental illness.

Lower FAAH predicted worse positive symptoms (Cohen's f=0.42)

What the researchers found

FAAH did not differ significantly between 27 patients with psychotic disorders and 36 healthy controls. However, within patients, lower FAAH predicted greater positive symptom severity (p=0.002, Cohen's f=0.42). Shorter illness duration and shorter duration of untreated psychosis also predicted lower FAAH. Results were independent of past cannabis exposure.

Why it matters

FAAH controls brain levels of anandamide, which is elevated in psychosis. This study suggests FAAH may be a biomarker for active psychotic symptom severity and a potential therapeutic target, independent of cannabis use history.

The numbers in context

27 patients, 36 controls. No group difference in FAAH (p=0.49). Lower FAAH predicted positive symptoms (p=0.002, Cohen's f=0.42, large effect). Shorter illness duration predicted lower FAAH (p=0.001). FAAH higher in females (p=0.002). Marked regional brain differences (p<10^-56).

How the study worked

PET imaging study using [11C]CURB radioligand in 27 patients with schizophrenia spectrum disorders and 36 healthy controls. Structural MRI for anatomical reference. Irreversible 2-tissue compartment model with arterial input function for quantification.

What this study cannot tell us

Cross-sectional design cannot determine causation. Small patient sample. Some patients were taking antipsychotics though this did not explain findings. PET imaging is expensive and not practical for routine clinical use.

How to read the evidence

Novel PET imaging study with robust analytical methods, but small cross-sectional sample and expensive methodology.

When this study was published

2020 study. First-ever in vivo measurement of brain FAAH in psychotic disorders.

The bigger picture

If FAAH serves as a biomarker for psychotic symptom state, it could help guide treatment decisions. The relationship between low FAAH, high anandamide, and active symptoms suggests the endocannabinoid system may play a compensatory role early in psychosis.

Questions still open

Does FAAH change with treatment response? Could FAAH levels predict which patients will respond to specific therapies? Would FAAH inhibitors worsen or improve psychotic symptoms? Does the sex difference in FAAH contribute to sex differences in psychosis?

Common questions

What is FAAH?

Fatty acid amide hydrolase (FAAH) is the enzyme that breaks down anandamide, one of the brain's main endocannabinoids. Lower FAAH means higher anandamide levels.

Is this related to cannabis use?

The findings were independent of past cannabis exposure. While cannabis targets the same endocannabinoid system, this study suggests FAAH changes in psychosis are part of the disease process rather than a consequence of cannabis use.

Read the original research

Imaging Brain Fatty Acid Amide Hydrolase in Untreated Patients With Psychosis.

Biological psychiatry, 88(9), 727-735

View on PubMed ↗Publisher’s paper ↗

Citation

Watts, Jeremy J; Jacobson, Maya R; Lalang, Nittha; Boileau, Isabelle; Tyndale, Rachel F; Kiang, Michael; Ross, Ruth A; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo; Mizrahi, Romina. (2020). Imaging Brain Fatty Acid Amide Hydrolase in Untreated Patients With Psychosis.. Biological psychiatry, 88(9), 727-735. https://doi.org/10.1016/j.biopsych.2020.03.003