Abstract
Background
The development of depressive symptomatology is a recognised complication of treatment with the cytokine, interferon-α, and has been seen as supporting inflammatory theories of the pathophysiology of major depression. Major depression has been associated with changes in glutamatergic activity and recent formulations of interferon-induced depression have implicated neurotoxic influences which could also lead to changes in glutamate function. The present study used magnetic resonance spectroscopy (MRS) to measure both glutamate and its major metabolite, glutamine in patients with hepatitis C who received treatment with pegylated-interferon-α and ribavirin.
Methods
MRS measurements of glutamate and glutamine were taken from a 25x20x20mm voxel including pregenual anterior cingulate cortex in 12 patients before and after 4-6 weeks treatment with interferon.
Results
Interferon treatment led to an increase in cortical levels of glutamine (p= 0.02) and a significant elevation in the ratio of glutamine to glutamate (p<.01). Further, changes in glutamine level correlated significantly with ratings of depression and anxiety at the time of the second scan.
Conclusions
We conclude that treatment with interferon-α is associated with MRS-visible
changes in glutamatergic metabolism. However, the changes seen differ from those reported in major depression which suggests that the pathophysiology of interferon-induced depression may be distinct from that of major depression more generally.
The development of depressive symptomatology is a recognised complication of treatment with the cytokine, interferon-α, and has been seen as supporting inflammatory theories of the pathophysiology of major depression. Major depression has been associated with changes in glutamatergic activity and recent formulations of interferon-induced depression have implicated neurotoxic influences which could also lead to changes in glutamate function. The present study used magnetic resonance spectroscopy (MRS) to measure both glutamate and its major metabolite, glutamine in patients with hepatitis C who received treatment with pegylated-interferon-α and ribavirin.
Methods
MRS measurements of glutamate and glutamine were taken from a 25x20x20mm voxel including pregenual anterior cingulate cortex in 12 patients before and after 4-6 weeks treatment with interferon.
Results
Interferon treatment led to an increase in cortical levels of glutamine (p= 0.02) and a significant elevation in the ratio of glutamine to glutamate (p<.01). Further, changes in glutamine level correlated significantly with ratings of depression and anxiety at the time of the second scan.
Conclusions
We conclude that treatment with interferon-α is associated with MRS-visible
changes in glutamatergic metabolism. However, the changes seen differ from those reported in major depression which suggests that the pathophysiology of interferon-induced depression may be distinct from that of major depression more generally.
| Original language | English |
|---|---|
| Article number | N/A |
| Pages (from-to) | 789-795 |
| Number of pages | 7 |
| Journal | Psychological Medicine |
| Volume | 44 |
| Issue number | 4 |
| Early online date | 10 May 2013 |
| DOIs | |
| Publication status | Published - Mar 2014 |
