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Neuropsychobiology. 2012;65(3):126-32. doi: 10.1159/000330585. Epub 2012 Feb 24.

Psychiatric side effects and fluctuations in serotonergic parameters in the treatment of chronic hepatitis C infection.

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Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.



Treatment of hepatitis C with peginterferon induces psychiatric side effects. These might include changes in serotonergic function.


Twenty-two hepatitis C patients were treated with peginterferon. At different time points, psychometric assessment was performed using the profile of mood states. Plasma samples were taken to study serotonergic parameters.


Anger and depression increased compared to baseline, starting with anger (from week 3 onwards), followed by depression (from week 7 onwards). Other scores did not show consistent changes. No consistent changes were observed in tryptophan, tryptophan/large neutral amino acids ratio, biopterin and 5-hydroxyindoleacetic acid. The tyrosine/large neutral amino acids ratio, neopterin, phenylalanine/tyrosine ratio, and prolactin concentrations increased compared to baseline. Prolactin levels were associated with the occurrence of depression and anger.


Particularly anger and depression increased during treatment. Neither a decrease in tryptophan and tryptophan availability was seen, nor a relationship between these parameters and the development of psychopathology. Therefore, other mechanisms in the induction of psychopathology should be considered. The observed increases in neopterin and phenylalanine/tyrosine ratio are indicative of changes in tetrahydrobiopterin, which is involved in the metabolism of serotonin, noradrenaline and dopamine, and possibly mediating the increase in prolactin. The increase in prolactin levels and its relationship with depression and anger needs further exploration.

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