|Year : 2015 | Volume
| Issue : 2 | Page : 59-61
Serum cholesterol and depression: A puzzle never finished
Satish Kumar Budania1, Monika Rathi2, Shalini Singh3, Suresh Yadav4
1 Department of Psychiatry, Lala Lajpat Rai Memorial Medical College, Meerut, Uttar Pradesh, India
2 Department of Pathology, Lala Lajpat Rai Memorial Medical College, Meerut, Uttar Pradesh, India
3 Department of Psychiatry, Lady Hardinge Medical College, New Delhi, India
4 Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India
|Date of Web Publication||14-May-2015|
228/16, Saket Colony, North Civil Lines,Muzaffar Nagar - 251 001, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Depression is a state of sadness, hopelessness, and discouragement. Various studies have been conducted to uncover the etiological factors involved in depression. Serum folic acid is one such factor. Many researchers have reported an inverse association between serum folic acid and depression. We did an extensive computerized database searches on PubMed, Medline, and EBSCO and found that low serum folic acid are associated with depression, not only in adults, but also in elderly and diabetic patients. Further augmentation of folic acid with antidepressant treatment also improves the treatment outcome in depressed patients. Hence, considering the high benefits to the adverse effects ratio of serum folic acid, its supplementation should be done in "at risk" population whenever possible.
Keywords: Depression, pregnancy, serum folic acid
|How to cite this article:|
Budania SK, Rathi M, Singh S, Yadav S. Serum cholesterol and depression: A puzzle never finished. J Sci Soc 2015;42:59-61
| Introduction|| |
Depression is a common and treatable psychiatric illness. Various studies have been done to establish a relationship between serum folic acid and depression. Majority of them have reported an association between the two.
Folic acid plays an important role in the synthesis of neurotransmitters, purine, thymidine, nucleotide, DNA, structural components of neurons, by regulating the genomic and nongenomic methylation reactions. , The mechanism involved behind this is that folic acid and Vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups in many reactions, including methylation of membrane phospholipids, thereby affecting the membrane properties crucial for neurological functions. , Further, SAM also has anti-depressant actions, and it acts by raising brain 5-hydroxytryptamine.  Thus, deficiency of folate leads to depression.
Regarding causes of low folate levels, it is also hypothesized that low dietary intake of folate, polymorphism of the genes involved in folate metabolism are responsible for folate deficiency.  Interestingly, it is seen that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate) have very low lifetime rates of major depression.  Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is overrepresented among depressive subjects.
Increased plasma homocysteine levels act as a marker of both folate and Vitamin B12 deficiency. Hence, a common decrease in serum/red blood cell folate, serum Vitamin B12 and an increase in plasma homocysteine has often been reported in depression. 
Folic acid deficiency and Vitamin B12 deficiency have overlapping neuropsychiatric manifestations, which range from cognitive impairment, dementia, depression to the less common manifestations like peripheral neuropathy and combined degeneration of the spinal cord.  Studies have also shown that deficiency of folic acid and Vitamin B12 have negative consequences on the brain development in the infants, which leads to a greater risk of depression in adulthood. 
| Materials and methods|| |
We reviewed the literature on computerized databases like PubMed, Medline, and EBSCO, using folic acid, depression, psychiatry as keywords from 2003 to 2014. We also searched the reference lists of the relevant articles in order to include as many relevant studies as possible. We also consulted the experts in this field to take their guidance.
Studies approving association between low serum folate levels and depression
It has been proved that low serum folate levels were found to be associated with fluoxetine resistant major depressive disease.  Studies have also proved that low folate level are associated with relapse during the continuation phase of treatment with fluoxetine. 
Various other studies have also shown the association between low folate levels and depression. ,,,,,,,, Yaremco et al. did a study on 24 pregnant women with a history of mood disorders. They found that red blood cell folate of these women had an inclination towards low normal range despite the daily use of folic acid supplements.  Miyaki et al. also reported a low incidence of depression in patients with normal serum folate levels. 
Loria-Kohen et al. did a prospective, clinical trial on the depressive status of 24 patients of eating disorders. They supplemented these patients with 10 mg/day of folic acid. They found a significant improvement in the depressive status of these patients after folate supplementation. 
Permoda-Osip et al. treated 20 patients with bipolar depression with ketamine infusion. They found that that the patients whose responded more than 50% on Hamilton depression rating scale had significantly higher levels of Vitamin B12. However, they found no difference with regard to serum folic acid levels and homocysteine levels. 
Venkatasubramanian et al. treated 42 depressive female outpatients with 20 mg fluoxetine. They augmented 23 patients with 1.5 mg folic acid/day and 19 patients with 5 mg folic acid/day. They found that augmentation with 5 mg/day folic acid was more beneficial in depressive patients. 
Studies disapproving association between low serum folate levels and depression
Aishwarya et al. did a postpartum study on 103 women. They found significant elevations in homocysteine levels in women with postpartum depression, both at 24-48 h as well as 6 weeks after delivery. However, they found no associations between folate and B12 levels. 
Walker et al. did a randomized control trial on 909 depressed older adults (60-74 years). They found that neither folic acid plus B12 nor physical activity were effective in reducing depressive symptoms. Instead, mental health literacy had a transient effect on decreasing depressive symptoms.  Lukose et al. found that antenatal depressive symptoms in early pregnancy are not associated with folate deficiency.  Similar findings were reported in pregnant women by Bodnar et al. ,
Mazeh et al. also denied the association between folic acid deficiency and psychiatric illness in elderly. 
Studies approving the association between low serum folate and depression on special populations
Gosney et al. did a study on older people in nursing homes and residential homes and found that depression was significantly associated with selenium levels in older people, but not with folic acid. 
Researchers have reported low folate levels in elderly people of age. ,,,, Few studies have reported the association between depressive symptoms in pregnancy and folate levels. ,
Nanri did a study on type 2 diabetic patients and found an inverse association between folic acid levels and depression. 
| Discussion|| |
We conclude that not only majority of the studies have proved an association between low serum folate levels and depression, few studies have also suggested that antidepressants augmented with folic acid have better results on treatment outcome. Considering low costs and lesser side-effects of folic acid, folic acid supplements should be given to the depressed patients whenever possible.
| Acknowledgments|| |
We acknowledge Randy A. Sansone, Domenico De Berardis, Stefano Marini, Monica Piersanti, Marilde Cavuto, Giampaolo Perna, Alessandro Valchera, Monica Mazza, Michele Fornaro, Felice Iasevoli, Giovanni Martinotti, and Massimo Di Giannantonio for their guidance. We also acknowledge Engineer Ayush for his technical help.
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