Immunopathogenetic link between depression and folate deficiency
EDITOR, - EH Reynolds discusses a role of folate deficiency in the
pathogenesis of depression and dementia.1 There is no doubt about the
crucial importance of folic acid for the functioning of the central
nervous system, and indeed folate deficiency can cause several neurologic
and psychiatric symptoms especially in the elderly.
However, the article
of EH Reynolds does not provide a rationale for the development of folate
deficiency in such patients, and it appears that besides side effects of
drugs, primarily insufficient dietary intake of the vitamin is considered
to underlie central nervous disturbances. Still the question remains
whether folate deficiency is primary or whether other causes may
contribute to it. Actually immune activation and oxidative stress could
play a role. On the one hand, immune activation is associated with
tryptophan degradation which interferes with the biosynthesis of
neurotransmitter serotonin.2 On the other hand, it might be an important
source for the overwhelming production of oxidizing compounds and thereby
contribute to the depletion of antioxidants.3 Consequently the demand of
vitamins especially of those sensitive to oxidation like vitamins C and E
is increasing. Also the 5,6,7,8-tetrahydro-derivatives of folate, which
are the active cofactors required for C1 group metabolism and for
remethylation of homocysteine, are very susceptible to oxidation.
Importantly immune activation and oxidative stress could contribute to
folate deficiency even in the case when dietary intake is sufficient.
Chronic immune activation is found in patients with depression and
dementia,3-5 and it might provide an explanation why supplementation with
antioxidant vitamins but also treatment with anti-inflammatory drugs has
some capacity to slow-down progression of symptoms in patients.
Katharina Schroecksnadel, research assistant, Barbara Frick, research
assistant,
Dietmar Fuchs, professor of medical chemistry, Institute of Medical
Chemistry and Biochemistry, Leopold Franzens University, A-6020 Innsbuck,
Austria,
2 Widner B, Ledochowski M, Fuchs D. Interferon-gamma-induced tryptophan
degradation: neuropsychiatry and immunological consequences. Curr Drug
Metabol 2000; 1: 193-204.
5 van West D, Maes M. Activation of the inflammatory response system: A
new look at the etiopathogenesis of major depression. Neuroendocrinol Lett
1999; 20:11-7.
Competing interests:
4 Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression.J Neurol Neurosurg Psychiatry 2000; 69: 228-32.
Rapid Response:
Immunopathogenetic link between depression and folate deficiency
EDITOR, - EH Reynolds discusses a role of folate deficiency in the
pathogenesis of depression and dementia.1 There is no doubt about the
crucial importance of folic acid for the functioning of the central
nervous system, and indeed folate deficiency can cause several neurologic
and psychiatric symptoms especially in the elderly.
However, the article
of EH Reynolds does not provide a rationale for the development of folate
deficiency in such patients, and it appears that besides side effects of
drugs, primarily insufficient dietary intake of the vitamin is considered
to underlie central nervous disturbances. Still the question remains
whether folate deficiency is primary or whether other causes may
contribute to it. Actually immune activation and oxidative stress could
play a role. On the one hand, immune activation is associated with
tryptophan degradation which interferes with the biosynthesis of
neurotransmitter serotonin.2 On the other hand, it might be an important
source for the overwhelming production of oxidizing compounds and thereby
contribute to the depletion of antioxidants.3 Consequently the demand of
vitamins especially of those sensitive to oxidation like vitamins C and E
is increasing. Also the 5,6,7,8-tetrahydro-derivatives of folate, which
are the active cofactors required for C1 group metabolism and for
remethylation of homocysteine, are very susceptible to oxidation.
Importantly immune activation and oxidative stress could contribute to
folate deficiency even in the case when dietary intake is sufficient.
Chronic immune activation is found in patients with depression and
dementia,3-5 and it might provide an explanation why supplementation with
antioxidant vitamins but also treatment with anti-inflammatory drugs has
some capacity to slow-down progression of symptoms in patients.
Katharina Schroecksnadel, research assistant, Barbara Frick, research
assistant,
Dietmar Fuchs, professor of medical chemistry, Institute of Medical
Chemistry and Biochemistry, Leopold Franzens University, A-6020 Innsbuck,
Austria,
dietmar.fuchs@uibk.ac.at
1 Reynolds Eh. Folic acid, ageing, depression, and dementia. BMJ
2002; 324:1512-5.
2 Widner B, Ledochowski M, Fuchs D. Interferon-gamma-induced tryptophan
degradation: neuropsychiatry and immunological consequences. Curr Drug
Metabol 2000; 1: 193-204.
5 van West D, Maes M. Activation of the inflammatory response system: A
new look at the etiopathogenesis of major depression. Neuroendocrinol Lett
1999; 20:11-7.
Competing interests: 4 Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression.J Neurol Neurosurg Psychiatry 2000; 69: 228-32.