medwireNews: Researchers have found subtle lipid disturbances in the prefrontal cortex of patients with schizophrenia, which may play a role in the pathology of the disease.
These disturbances were primarily in esterified fatty acid absolute concentrations in the cholesteryl ester lipid pool and in esterified palmitate, pamitoleic acid, linoleic acid (LA), γ-linolenic acid, and n-3 docosapentaenoic acid (DPA) within total lipids, triglycerides, or total or individual phospholipids.
"Although cholestryl ester is a minor lipid pool in the brain, it is a precursor to oxidized cholesterol products that can cause neuronal death," the researchers note in the Journal of Psychiatric Research.
"Thus an increase in cholesteryl ester fatty acid concentration and possibly turnover in SCZ [schizophrenia] may reflect the excitotoxicity and neuronal loss reported in SCZ patients," they explain.
The team, led by Ameer Taha, from the National Institutes of Health in Bethesda, Maryland, USA, extracted lipids from the post mortem prefrontal cortex of 10 patients with schizophrenia and 10 mentally healthy controls matched for age.
The researchers quantified absolute concentrations (nmol/g wet weight) and fractional concentrations, based on the percentage of total fatty acids.
The average concentrations of total lipid, phospholipid, individual phospholipids, plamalogen, triglyceride, and cholesteryl ester did not differ between the two groups.
By contrast, schizophrenia patients, compared with controls, had significantly higher cholesteryl ester concentrations of LA (4.0-fold), arachidonic acid (AA; 3.8-fold), docosahexanoic acid (DHA; 2.5-fold), n-6 DPA (3.0-fold), and n-3 DPA (4.3-fold).
Significantly higher levels, of between 21% and 95%, were also seen in schizophrenia patients for palmitate absolute concentration within individual phospholipids, and esterified fatty acids including palmitoleic acid, LA, γ-linolenic acid, and n-3 DPA showed significant differences in total lipids, triglycerides, and total or individual phospholipids between patients and controls.
These changes suggest disturbed fatty acid metabolism and phospholipid remodelling in patients with schizophrenia, say the researchers. Such disturbances support previous findings of hypoglutamatergic and hyperdopaminergic neurotransmitter signaling in the brains of schizophrenia patients, which are associated with neuronal loss and disease worsening over time, they add.
The researchers note that, while there were no significant differences in absolute concentrations of major polyunsaturated fatty acids, such as AA and DHA, in phospholipids between the two groups, concentrations were significantly lower in schizophrenia patients within total lipids and total and individual phospholipids when expressed as fractional concentrations.
They suggest the use of "PET [positron emission tomography] imaging of SCZ and control patients with radiotracers... to determine whether regional disturbances in AA or DHA metabolism exist, in relation to disease severity, progression, and clinical management with antipsychotics."
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