Alzheimer’s Protein Elevated in Youth With Early Psychosis

Liam Davenport

October 28, 2016

Young people with early-onset psychosis (EOP) have increased blood levels of a protein that is typically associated with neurodegeneration in Alzheimer's disease, the results of a new study indicate.

The findings, presented at the IEPA 10th International Conference on Early Intervention in Mental Health, in Milan, Italy, indicate that levels of the caspase cleaved tau protein (c-tau) were almost twice as high in EOP patients than in healthy control persons.

"This finding suggests that tau protein metabolism may be altered in EOP. The results may have implications for the understanding of the pathophysiology of EOP and for new treatment strategies," the investigators note. The study was led by Dr Mathias Lundberg, Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden.

Dr Lundberg told Medscape Medical News that any neurodegeneration occurring in EOP patients is more likely to be due to the loss of the connections between cells, rather than cell death itself.

However, he noted that, on the basis of available evidence, "it is not clear" whether the elevated protein levels seen in the current study reflects cell death or loss of connections.

"This protein has been shown to be increased in trauma and also in Alzheimer's disease, of course, but we need more data. I must say that this is preliminary data; we haven't published it, and other people need to confirm it before we can really be 100%," he added.

Dr Lundberg pointed out that for EOP patients, in addition to possible increases in neurodegeneration, there could be disturbances in neuroregeneration. "Maybe both these processes are disturbed in schizophrenia; it's complex," he added.

Previous studies have indicated that there is a severe loss of neurocognitive function at the start of EOP. It has been suggested that this indicates an underlying pathophysiology involving neurodegeneration.

Because the microtubule-binding tau protein and c-tau have been linked to neurodegenerative disorders, and because c-tau is neurotoxic, the researchers examined plasma levels of total tau protein (t-tau) and c-tau in EOP patients.

The investigators obtained plasma samples from 20 EOP patients who had been admitted to a child and adolescent psychosis unit and from 20 healthy matched control persons. Concentrations of t-tau and c-tau were determined using commercial sandwich enzyme-linked immunosorbent assays.

The mean age of the EOP patients was 17 years; the mean age of control persons was 16 years. Sixteen EOP patients and 10 control persons were female.

The researchers found that plasma levels of c-tau were significantly higher in EOP patients than in control persons, at a mean of 2150 pg/mL vs 1100 pg/mL (P < .018). There were no significant differences in t-tau concentrations between the two groups (P = .246).

Psychosis a Neurodegenerative Disorder

Commenting on the findings for Medscape Medical News, William R. McFarlane, MD, former director of the Center for Psychiatric Research at Maine Medical Center in Portland, said that study is "quite new, and it's very interesting.

"My thoughts are that this very much fits with what we've known now for quite a long time, and that is that, not just in early psychosis but even prior to the onset of psychosis, there's substantial losses in the entire range of higher neurocognitive functioning in young people...and that those neurocognitive changes tend to get worse as people progress from the prodromal into the actual psychotic phase," he added.

Dr McFarlane said that he has been "trying to advocate" for the view that, fundamentally, psychosis "looks like a neurodegenerative disorder."

"In my teaching, I always emphasize that the known predisposing factors for psychosis ― in particular, schizophrenia ― are the same as for many other neurological disorders."

He noted that the c-tau protein could "very well indicate something about the very fundamental process that's going on that leads to brain volume loss and neurocognitive loss, and then ultimately severe deterioration in social and role functioning. Now, what's causing that, of course, would be another $64,000 question, because we don't know really much of what causes it in Alzheimer's."

Dr McFarlane said he hopes the study findings don't generate pessimism and lead to the belief that EOP is an "inevitable" process that can't be stopped, because all the indications are that early intervention does stop the downstream results of these processes.

"The exciting news is we followed up young people who'd been treated in Portland, Maine, for anywhere up to 12 years and found that three quarters of them were in school or working, and that's not what would have been expected if they'd had a full episode."

Dr Lundberg and colleagues are planning a 2-year prospective study to assess possible changes in levels of the biomarkers in response to treatment as well as changes in symptoms and whether they could be used to determine treatment response.

He said that it also may be interesting to look at biomarker levels in plasma samples from schizophrenia patients who respond to treatment with clozapine, because previous studies have indicated that these patients can experience cortical thinning after taking the drug.

No funding for the study has been disclosed. The investigators have disclosed no relevant financial relationshps.

IEPA 10th International Conference on Early Intervention in Mental Health. Poster A72. Presented October 20, 2016.

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