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    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Acknowledgment
    References
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 Table of Contents    
ORIGINAL ARTICLE  
Year : 2013  |  Volume : 55  |  Issue : 7  |  Page : 397-399
Low serum brain derived neurotrophic factor in non-suicidal out-patients with depression: Relation to depression scores


1 Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
2 Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India

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Date of Web Publication8-Aug-2013
 

   Abstract 

Context: Low brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression. The relation between BDNF and severity of depression has been investigated.
Aims: In this study, we aimed to measured serum BDNF levels in never-treated non-suicidal out-patients with depression and relate this to the severity of depression.
Settings and Design: This study was conducted in an out-patient setting in a tertiary care psychiatric hospital on consenting depressed patients.
Materials and Methods: Forty three (19 females) antidepressant-naive out-patients with depression, aged between 18 and 55 years and 24 (13 females) age-matched healthy volunteers gave consent for the study. Serum BDNF levels were assayed by using the sandwich enzyme-linked immunosorbent assay method on morning serum samples before starting treatment. These were compared between patients and controls using independent sample t-test. Pearson's correlation coefficient was used to assess the association between baseline BDNF and Hamilton depression rating scale (HDRS).
Results: Serum BDNF was significantly lower in patients with depression (mean±standard deviation (SD)=18.59±4.9 ng/ml) than in healthy volunteers (mean±SD=23.6±5.6 ng/ml; P=0.001). There was a significant negative correlation between the HDRS total scores and BDNF levels ( P=0.04), indicating that more severely depressed patients had lower BDNF scores.
Conclusions: Serum BDNF level is lower in non-suicidal out-patients with depression. The inverse correlation between ratings of depression and BDNF levels suggests possible relationship between depression, (role of illness on) BDNF levels and neuroplasticity thereof.

Keywords: Brain derived neurotrophic factor, depression, hamilton depression rating scale

How to cite this article:
Varambally S, Naveen G H, Rao M G, Thirthalli J, Sharma R, Christopher R, Gangadhar B N. Low serum brain derived neurotrophic factor in non-suicidal out-patients with depression: Relation to depression scores. Indian J Psychiatry 2013;55, Suppl S3:397-9

How to cite this URL:
Varambally S, Naveen G H, Rao M G, Thirthalli J, Sharma R, Christopher R, Gangadhar B N. Low serum brain derived neurotrophic factor in non-suicidal out-patients with depression: Relation to depression scores. Indian J Psychiatry [serial online] 2013 [cited 2019 Sep 15];55, Suppl S3:397-9. Available from: http://www.indianjpsychiatry.org/text.asp?2013/55/7/397/116311



   Introduction Top


Decreased neuroplasticity in hippocampus is pathophysiologically linked to depression. [1] This can help us understand the link between stress and depression. [2] Brain derived neurotrophic factor (BDNF) is a modulator of neuroplasticity in the brain (neuronal survival, synaptic signaling and synaptic consolidation) and is implicated in the pathophysiology of depression, [3],[4] through the stress pathway. [5]

Decreased serum BDNF levels in drug free patients with depression in comparison with healthy controls has been reported. [6] BDNF levels have been shown to increase with antidepressant treatment. [7],[8],[9] Some studies have shown an association between the severity of depression and low BDNF levels. [10] Given this relationship, it is understandable that non-suicidal (perhaps milder) depressive patients did not have as low BDNF levels as their suicidal counterparts. [11] In this study, we investigated if serum BDNF in never-treated non-suicidal patients with depressive disorder is lower than matched healthy comparison controls, and the relation of serum BDNF to depression scores.


   Materials and Methods Top


Subjects

Consecutive never treated patients with depression were recruited (n=43, females=19) from the out-patient psychiatry clinic of a research and clinical care hospital. They were aged between 18 and 55 years and had a score of 11 or more on the 17 item Hamilton depression rating scale (HDRS). [12] Diagnosis of major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders-IV, [13] was confirmed by a psychiatrist using Mini International Neuropsychiatric Interview. [14] Only patients who had a score of≤2 on the suicide item of Hamilton rating scale for depression (HDRS) were included. This status too was confirmed by the psychiatrist who made a diagnosis of depression. Patients with mental retardation, substance abuse disorders (except nicotine and caffeine), organic disorders such as dementia, epilepsy or cerebrovascular accidents, history suggestive of psychosis or bipolar disorder or catatonia were excluded. Age and education-matched healthy consenting volunteers were recruited (n=24, 13 females). The same exclusion criteria were used as for the patients. Consent was obtained from all subjects. The Institutional Ethics Committee of the National Institute of Mental Health and Neurosciences approved the study.

Assessment of BDNF

A total volume of 5 ml venous blood was collected from patients (before starting any medication) and healthy controls in anticoagulant-free tubes between 9 and 11 am and serum was separated after 30 min by centrifugation (2900 rpm for 15 min). Coded serum sample was stored at −80°C. Serum BDNF levels were measured by using the enzyme-linked immuno sorbent assay by using commercial reagents (Aquin Technologies Private Limited) according to the manufacturer's instructions. The laboratory staff was unaware of clinical details. The intra- and inter-assay coefficient of variations was 1.34% and 4.34%, respectively.

Statistical analysis

Independent sample t-test was used to compare patients and healthy volunteers in terms of age, education and baseline serum BDNF levels. Pearson's correlation coefficient was computed between baseline BDNF and HDRS scores as well as duration of illness.


   Results Top


There was no difference between patients with depression and healthy controls with regards to age, sex and education [Table 1]. Mean age of onset of illness was 32.2 years (SD: 8.9), mean duration of illness was 11.7 months (SD: 14.6) and mean HDRS score was 18.5 (SD: 4.6). Serum BDNF was significantly lower in patients with depression in comparison with healthy volunteers and the effect size of the difference was 1.0 [Table 1]. There was significant negative correlation between serum BDNF levels and depression scores on the 17-item HDRS (Spearman's r=−0.32, P=0.040). Serum BDNF levels did not correlate with duration of illness. Serum BDNF was not different between sexes either within patients or controls.
Table 1: Demographic and clinical details of the subjects

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   Discussion Top


The present study shows that serum BDNF levels were lower in never-treated, non-suicidal patients with depression in comparison with the healthy controls. This is consistent with previous reports. Serum BDNF values were in a range comparable to previous studies. Brunoni et al. (2008), [15] reviewing 20 studies on 1504 patients found a value of 19.59 ng/ml for patients and 25.78 ng/ml for controls with an effect size of 0.91. Bocchio-Chiavetto et al. [16] in a meta-analysis of 15 studies found an average value of 20 ng/ml in patients compared with 32 ng/ml in controls. This consistent finding indicates that decreased BDNF levels may be an important factor in the pathophysiology of depression.

Severity of depression was negatively correlated with BDNF level in our study. This was despite most patients (75%) having a HDRS score<22 (perhaps as only non-suicidal patients were included). This is similar to previous studies that have showed a negative correlation between severity of depression and BDNF levels. [17],[18],[19],[20] The effect size found in this study was 1.0, similar to that reported in earlier studies. [15] BDNF is present in both the central and peripheral nervous system. [21] Pan et al. [22] have reported that BDNF crosses the blood brain barrier, so that serum BDNF concentrations may reliably reflect BDNF brain concentrations.

In summary, out-patients with major depression have low levels of serum BDNF. The BDNF levels were negatively correlated with depression scores suggesting a pathophysiological role in the illness.


   Acknowledgment Top


We would like to thank Dr. R. Nagaratna, Dean, Life Sciences, SVYASA, Bangalore for her support, encouragement and guidance.

We thank Mr. Sushrutha and Mr. Bhagath of Swami Vivekananda Yoga Anusandhana Samsthana for their help with transliteration

 
   References Top

1.Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006;59:1116-27.  Back to cited text no. 1
    
2.Calabrese F, Molteni R, Racagni G, Riva MA. Neuronal plasticity: A link between stress and mood disorders. Psychoneuroendocrinology 2009;34 Suppl 1:S208-16.  Back to cited text no. 2
    
3.Lee BH, Kim YK. The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Psychiatry Investig 2010;7:231-5.  Back to cited text no. 3
    
4.Allen SJ, Dawbarn D. Clinical relevance of the neurotrophins and their receptors. Clin Sci (Lond) 2006;110:175-91.  Back to cited text no. 4
    
5.Andrade C, Rao NS. How antidepressant drugs act: A primer on neuroplasticity as the eventual mediator of antidepressant efficacy. Indian J Psychiatry 2010;52:378-86.  Back to cited text no. 5
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6.Aydemir O, Deveci A, Taskin OE, Taneli F, Esen-Danaci A. Serum brain-derived neurotrophic factor level in dysthymia: A comparative study with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:1023-6.  Back to cited text no. 6
    
7.Huang TL, Lee CT, Liu YL. Serum brain-derived neurotrophic factor levels in patients with major depression: Effects of antidepressants. J Psychiatr Res 2008;42:521-5.  Back to cited text no. 7
    
8.Matrisciano F, Bonaccorso S, Ricciardi A, Scaccianoce S, Panaccione I, Wang L, et al. Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine. J Psychiatr Res 2009;43:247-54.  Back to cited text no. 8
    
9.Molendijk ML, Bus BA, Spinhoven P, Penninx BW, Kenis G, Prickaerts J, et al. Serum levels of brain-derived neurotrophic factor in major depressive disorder: State-trait issues, clinical features and pharmacological treatment. Mol Psychiatry 2011;16:1088-95.  Back to cited text no. 9
    
10.Bus BA, Tendolkar I, Franke B, de Graaf J, Heijer MD, Buitelaar JK, et al. Serum brain-derived neurotrophic factor: Determinants and relationship with depressive symptoms in a community population of middle-aged and elderly people. World J Biol Psychiatry 2012;13:39-47.  Back to cited text no. 10
    
11.Kim YK, Lee HP, Won SD, Park EY, Lee HY, Lee BH, et al. Low plasma BDNF is associated with suicidal behavior in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:78-85.  Back to cited text no. 11
    
12.Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.  Back to cited text no. 12
    
13.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4 th ed. (Text Revision). Washington, DC: American Psychiatric Association; 2000.  Back to cited text no. 13
    
14.Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59 Suppl 20:22-33.  Back to cited text no. 14
    
15.Brunoni AR, Lopes M, Fregni F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: Implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol 2008;11:1169-80.  Back to cited text no. 15
    
16.Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, et al. Serum and plasma BDNF levels in major depression: A replication study and meta-analyses. World J Biol Psychiatry 2010;11:763-73.  Back to cited text no. 16
    
17.Gervasoni N, Aubry JM, Bondolfi G, Osiek C, Schwald M, Bertschy G, et al. Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode. Neuropsychobiology 2005;51:234-8.  Back to cited text no. 17
    
18.Gonul AS, Akdeniz F, Taneli F, Donat O, Eker C, Vahip S. Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients. Eur Arch Psychiatry Clin Neurosci 2005;255:381-6.  Back to cited text no. 18
    
19.Karege F, Bondolfi G, Gervasoni N, Schwald M, Aubry JM, Bertschy G. Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry 2005;57:1068-72.  Back to cited text no. 19
    
20.Yoshimura R, Mitoma M, Sugita A, Hori H, Okamoto T, Umene W, et al. Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:1034-7.  Back to cited text no. 20
    
21.Lindsay RM, Wiegand SJ, Altar CA, DiStefano PS. Neurotrophic factors: From molecule to man. Trends Neurosci 1994;17:182-90.  Back to cited text no. 21
    
22.Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 1998;37:1553-61.  Back to cited text no. 22
    

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Correspondence Address:
S Varambally
Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore - 560 029, Karnataka
India
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Source of Support: The research was done under the Advanced Centre for Yoga - Mental Health and Neurosciences, a collaborative centre of NIMHANS and the Morarji Desai Institute of Yoga, New Delhi, Conflict of Interest: None


DOI: 10.4103/0019-5545.116311

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