Olfactory and gustatory dysfunction in depression: Could it be a marker of folate deficiency?

To the Editor

Olfaction has a close association with emotional and behavioral processing in specific brain regions, particularly Habenular nuclei and their connections (Oral et al., 2013). Dysfunction of this area may lead to depression and impairment of social, sexual as well as psychomotor functioning (Oral et al., 2013). There is a negative correlation with the neuronal density of Habenula and depressive symptoms (Oral et al., 2013).

A 50-year-old, non-diabetic, non-hypertensive male with history of smoking since last 12 years had presented with low mood, anxiety, decreased interest in interaction and work, difficulty in concentration and reduced libido for 11 months. He also had progressive loss of smell leading to anosmia within 1 month of onset of depressive symptoms along with decreased taste perception.

There was no past or family history of psychiatric illness. Obvious psychosocial stressors were absent. Mental status examination had revealed depressed affect, pessimistic views about future and death wishes.

He was diagnosed with major depressive disorder and was prescribed Escitalopram 10 mg/day, which was later increased to 20 mg/day along with clonazepam 0.25 mg as and when required. Opinion was taken from oto-rhinologist and neurologist for anosmia and possible organic causes were ruled out.

His routine hemogram, liver and renal function tests and thyroid profile were within normal limits. As there was no improvement in depression after adequate trial of >3 months, the patient was switched to Bupropion (300 mg/day). Serum folic acid and Vitamin-B12 level was estimated due to persistent poor response. Folic acid level was found to be significantly low for which folate supplementation (7.5 mg/day, alpha-metyl-folate) had been started. Within 2 weeks, his depressive symptoms, olfaction, gestation as well as libido had improved significantly with reduction of Hamilton Depression Rating Scale (HAM-D) score from 17 to 7.

There is over-lapping between the brain areas related to depression and olfactory processing which might be responsible for occurrence of olfactory dysfunction in depression and could be considered a potential early marker (Marine and Boriana, 2014). Taste perception is dependent on olfactory perception; olfactory deficits are likely to influence taste perception. As neuroplasticity (prominently seen in the olfactory bulbs) is dependent on several nutritional elements like folate, its deficiency is likely to produce impairment of synthesis of neurotransmitters responsible for depression (i.e. serotonin, norepinephrine, dopamine) (Fava and Mischoulon, 2009). Olfactory dysfunction can be a possible phenotypic marker of folate deficiency in treatment resistant depression.