UNLOCKING THE BRAIN'S CHOLESTEROL SECRETS: MEDICATION EFFECTS ON LIVER HEALTH IN PSYCHIATRIC PATIENTS

Abstract Background Cholesterol is necessary for the proper functioning of the brain. The brain, although it makes up about 2% of the total body weight, contains approximately 25% of cholesterol and its derivatives. Following critical observations, over the course of several years, we have confirmed that aripiprazole, trazodone, cariprazine, and haloperidol are strong inhibitors of sterol biosynthesis, each with profound biochemical effects on the developing brain. These are drugs believed to lead to the accumulation of 7DHC oxysterols, an important marker of oxidative stress. Oxidative stress has detrimental effects on most cellular structures; an excess of hydroxyl radicals and peroxynitrite will cause lipid peroxidation, resulting in damage to cell membranes and lipoproteins. In clinical practice, liver activity is monitored by measuring the concentrations of liver enzymes in blood serum. Gamma-glutamyl transferase is the one of most sensitive indicators of liver damage, particularly if the damage is caused by toxic substances (e.g., alcohol, drugs). Methods We conducted a study to assess the levels of cholesterol intermediates in blood samples from a population of psychiatric patients, which we further examined through a biochemical analysis of their blood serum. Participants were recruited for the study over a 6-month period from hospitalized patients at the Psychiatry Clinic in Osijek. Patients underwent a comprehensive clinical psychiatric examination, accompanied by a questionnaire designed specifically for this research. Blood samples were collected from the patients into serum tubes, and these samples were analyzed by LC-MS/MS, followed by biochemical processing. Results From the collected results through the implementation of the χ2 test and Fisher's exact test, elevated AST levels were identified in 15.1% of patients; elevated GGT levels in 25.4%, and reduced Che levels in 72.2% (N=205). Among patients with elevated oxysterols (7DHC), elevated AST levels were identified in 13.6% of patients, elevated GGT levels in 22.7%, and Che values were reduced in 75% of patients, with a statistically almost significant change primarily in the GGT concentration, which is the most sensitive indicator of liver damage. Conclusion In clinical practice, it is well-known that many drugs have hepatotoxic effects due to their metabolism. Considering that the liver is the primary organ responsible for storing exogenous cholesterol, among other functions, it is expected that the use of drugs that indirectly increase the concentration of 7DHC will lead to more significant damage. However, our research did not demonstrate statistical significance in the greater impact of the selected drugs compared to other psychopharmacotherapeutic medications.