DKK1 levels elevated in psychosis patients with comorbid drug abuse
MedWire News: Results from an Italian study show that drug abuse is associated with increased serum levels of the protein Dickkopf-1 (DKK1) in patients with psychosis.
Daniele Serata (Sapienza University, Rome) and team explain that DKK1 "is an inhibitor of the canonical Wnt pathway, which is known to be impaired in both psychotic and neurodegenerative disorders."
They add: "Interestingly, 3,4-methylendioxymethamphetamine (MDMA or ecstasy), one of the most widely abused drugs worldwide, causes DKK1 induction… thus establishing a potential link between suppression of the canonical Wnt pathway and neurodegeneration induced by drugs of abuse."
For the current study, Serata and team investigated DKK1 levels, as an indicator of neurodegeneration, among 44 inpatients (mean age 33.2 years) with psychosis, of whom 22 had a history of drug abuse. For comparison, DKK1 levels were also assessed in 16 age- and gender-matched mentally healthy individuals (controls).
Blood samples were collected from all of the participants and assessed for serum DKK1 concentrations using enzyme-linked immunosorbent assay.
Participants with psychosis were also assessed for psychopathology using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) severity scale, and the Global Assessment of Functioning (GAF) scale. The Simpson-Angus Neurological Rating Scale (NRS) was used to evaluate extrapyramidal motor symptoms.
The researchers found that psychosis patients with a history of drug abuse had significantly higher median DKK1 levels than those without, at 2.48 versus 1.76 ng/mL. And median DKK1 levels in both groups of psychosis patients were significantly higher than in controls, at 0.71 ng/mL.
Psychosis patients with a history of drug abuse had a significantly earlier age at illness onset (22.1 vs 24.4 years), a longer duration of psychosis (10.7 vs 6.6 years), and higher mean NRS scores for extrapyramidal motor symptoms (5.9 vs 4.3) than those without.
However, there were no significant correlations between DKK1 levels and scores on the PANSS, the CGI scale, or the GAF scale, the researchers note.
Serata and team conclude in Progress in Neuro-Psychopharmacology and Biological Psychiatry: "Psychosis led to elevated serum DKK1 levels, and substance abuse led to a further increase."
They add: "Knowing that there is a correlation between brain and blood levels of DKK1, we speculate that the observed increase in DKK1 levels reflects drug-induced neurotoxicity in our patients."
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By Mark Cowen