Irritability rather than depression during interferon treatment is linked to increased tryptophan catabolism.
OBJECTIVE
Treatment with recombinant interferon is associated with high rates of psychiatric comorbidity. We investigated the relation between catabolism of the essential amino acid tryptophan, being rate-limiting of peripheral and cerebral serotonin formation, and psychiatric symptoms in patients undergoing combination treatment with interferon-alpha and ribavirin.


METHODS
Eighteen patients with viral hepatitis C who received interferon were included. A psychiatrist screened patients before and while on interferon-alpha treatment for 2 months, using a structured diagnostic interview. Fasting plasma tryptophan and platelet serotonin levels were measured at each visit.


RESULTS
At baseline no evident psychopathology was observed. After 2 months of interferon treatment, 10 patients experienced increased irritability. No other structural psychopathology was observed. Decreased plasma tryptophan level correlated with the presence of irritability (p = .047). Platelet serotonin levels were found to be decreased during treatment (p = .002).


CONCLUSIONS
Aggressive impulse dysregulation is highly prevalent in patients receiving interferon treatment. This is associated with decreased plasma tryptophan levels which may lead to attenuated peripheral and central serotonergic neurotransmission.
Russo
Sascha
S
Department of Biological Psychiatry, University Hospital Groningen, Groningen, The Netherlands. s.r.russo@acggn.azg.nl
Kema
Ido P
IP
Haagsma
Elizabeth B
EB
Boon
Jim C
JC
Willemse
Pax H B
PH
den Boer
Johan A
JA
de Vries
Elisabeth G E
EG
Korf
Jakob
J
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001792:Blood Platelets / Q000737:chemistry; D003866:Depressive Disorder / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D004359:Drug Therapy, Combination; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015994:Incidence; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D007372:Interferons / Q000009:adverse effects* / Q000627:therapeutic use; D007508:Irritable Mood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D012701:Serotonin / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D014364:Tryptophan / Q000097:blood / Q000187:drug effects / Q000378:metabolism*
D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012701:Serotonin; D012254:Ribavirin; D014364:Tryptophan; D007372:Interferons