A Study of Hematological Biomarkers in Depressed Postmenopausal Females
Received Date: Dec 01, 2016 / Accepted Date: Dec 21, 2016 / Published Date: Dec 28, 2016
Context: Due to the heterogeneity in the occurrence of depression in postmenopausal women and a lack of adequate data on correlation of severity of depression with the co-occurrence of thyroid, lipid and vitamin metabolism derangements in these women, this study was planned to examine the prevalence of these derangements and its correlation with severity of depression in depressed postmenopausal women.
Aims: The aim of the study was to find out the prevalence and correlation of TSH, Lipid Profile, Folate and Vitamin B12 derangements with the severity of depression in postmenopausal women.
Settings and design: A cross-sectional study was carried out at the Department of Psychiatry and Department of Obstetrics and Gynaecology, SMS Medical College, Jaipur. After screening 150 consecutive depressed postmenopausal females (age group of 45-60 years), 40 females and 40 healthy female controls, matched sociodemographic profile were included in the study.
Materials and methods: After taking written informed consent, all subjects were assessed using Hamilton rating scale for depression, Menopausal rating scale and blood levels of TSH, lipid profile, folate and vitamin B12 was assessed.
Statistical analysis used: Group comparisons were done with chi-square test, T-test and Pearson’s correlation, with help of SPSS, ver. 21.0.
Results: There is significantly more prevalence and correlation of TSH and lipid profile derangements in depressed post-menopausal women, and the derangement in TSH levels worsens with the severity of depression. The folate levels are also significantly worse in the depressed group, but not Vitamin B12. Both did not correlate with severity of depression in the current study.
Conclusion: Management of thyroid and lipid derangements can help manage depression in post-menopausal women more holistically. The role of folate and vitamin B12 replenishment can also be considered when judging treatment response in these patients.
Keywords: Depressed; Postmenopausal women; Blood biomarkers; TSH; Lipid Profile; Folate; Vitamin B12.
Depression is a common and costly disorder  which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality . It is one of the most important causes of disability worldwide . Epidemiological studies worldwide report the prevalence of major depressive disorder about twice as high in women compared to those in men, especially during the childbearing years and may increase during menopause [4,5]. Depression may be debilitating, decreases quality of life and many patients may not respond to antidepressant treatment or may discontinue drug therapy due to side effects . Neurobiological studies demonstrate that Estrogen regulates numerous aspects of Noradrenergic, Serotonergic, GABAergic and Dopaminergic transmission and may substantiate mood and depressive states .
Relationship between menopause and depression has not been clearly defined. However, clinical studies report altered mood and reduced libido in women during menopause [8,9]. It is reported that women are most likely to develop mood symptoms (i.e., depressed mood, apathy) during the mid to late-luteal phase of their menstrual cycle, a period during which Progesterone levels are peaking while Estrogen levels are declining . Many of these women who experience physical and neuropsychiatric symptoms of menopause have a diminished quality of life  and decreased functionality .
There is increased occurrence of thyroid dysfunction in menopausal women and may affect 10–15% of postmenopausal women . A study  suggested that natural menopause affects lipid metabolism adversely, particularly Plasma lipoproteins and cholesterol levels . Total Cholesterol, LDL (Low density Lipoproteins) levels and Triglyceride levels are increased, while, the HDL (High density Lipoproteins) levels are decreased in postmenopausal women, more than premenopausal women of same age and BMI (Body Mass Index) . Recent epidemiological and clinical studies investigating the relationship between serum cholesterol levels and depressive symptoms have yielded equivocal results [17,18]. It has been reported that disturbances in folate-dependent one-carbon metabolism may contribute to neurodegenerative diseases, including depression . Folate, a naturally occurring B vitamin, is necessary for the synthesis of the trimonoamine neurotransmitters implicated in depression and may enhance the effects of a traditional antidepressant . The Rotterdam study of older men and women found that hyperhomocysteinemia, vitamin B12 deficiency and folate deficiency were related to depressive disorders . Another study also suggested an inverse relationship between serum folate and depressive symptoms . An improved response to antidepressants is reported in postmenopausal women when administered in combination with folic acid and vitamin B supplements; thus, folate and vitamin B status might be related to depression .
Due to the heterogeneity in the occurrence of depression in postmenopausal women and a lack of adequate data on correlation of severity of depression with the co-occurrence of thyroid, lipid, folate and vitamin B12 derangements in these women, this study was planned to examine the prevalence of thyroid, lipid, folate and vitamin B12 level derangements and its correlation with severity of depression in depressed postmenopausal women.
The aim of the study was to find out the prevalence and correlation of TSH (Thyroid Stimulating Hormone), Lipid, folate and vitamin B12 derangements with the severity of depression in postmenopausal women.
A cross-sectional study was carried out at the Department of Psychiatry and Department of Obstetrics and Gynaecology, SMS Medical College, Jaipur. After screening 150 consecutive depressed postmenopausal females (age group of 45-60 years) , 40 females were included in the study as per the inclusion and exclusion criteria that were set. An equal number of controls were recruited which were matched to the cases on sociodemographic profile.
Inclusion criteria for cases (depressed postmenopausal females)
1. Females who met the ICD-10 criteria for Major depression, diagnosis being confirmed by a senior psychiatrist.
2. Those who were in the age group of post-menopause, i.e., 45-60 years.
3. Those whose menopause had set in >/=12 months back .
4. Those who were drug naive, both psychiatric and hormonal drugs included.
5. Those who could understand the nature of the study and willing to give informed consent for participation.
Exclusion criteria for cases
1. Those who could not communicate well, either by virtue of intellectual impairment or any physical impairment.
2. Those with significant physical or neurological illness.
3. Any evidence of co-morbid psychiatric disorder other than depression.
4. Those having a prior history of psychiatric illness or of having received any hormonal or psychiatric treatment.
5. Those who were not willing to give informed consent.
Inclusion criteria for controls (non-depressed postmenopausal females)
1. Those who were in the age group of post-menopause, i.e., 45-60 years.
2. Those whose menopause had set in >/=12 months back .
3. Those who were drug naive, both psychiatric and hormonal drugs included.
4. Those who could understand the nature of the study and willing to give informed consent for participation.
5. Those who scored <7 on Hamilton rating scale for depression (<7=No depression)
Exclusion criteria for controls
1. Those who could not communicate well, either by virtue of intellectual impairment or any physical impairment.
2. Those with significant psychiatric, physical or neurological illness.
3. Those having a prior history of psychiatric illness or of having received any hormonal or psychiatric treatment.
4. Those who were not willing to give informed consent.
Tools of Study
1. Sociodemographic form: This was a semi-structured investigator filled form which contained the details of sociodemographic profile of the patient. The socioeconomic status was recorded as per the modified Kuppuswami Index .
2. Hamilton’s Rating Scale for Depression (HAM-D) : It is the most widely used clinician administered depression assessment scale. It contains 17 items pertaining to symptoms of depression experienced over the past week and is used to assess the severity of depressive symptoms. It takes 20- 30 minutes to administer. A score < or = 7 is considered normal, 7-13 (mild depression), 14-24 (moderate to severe depression), >24 (severe depression).
3. Menopause rating scale : It is a 11-item clinician administered scale to assess the various menopausal symptoms and assess its severity on a likert scale from 0 (no symptoms) to 4 (very severe symptoms). It takes about 10 min to administer. In this study, we have used it as a reference for listing presence or absence of menopausal symptoms only, as assessment of severity was not in the scope of this study.
4. Blood investigations: Blood samples of all subjects were collected for testing TSH, lipid, folate and vitamin B12 levels in the morning after an overnight fasting of 10-12 h. 5 ml of venous blood was drawn and assessed in laboratory. Serum lipid profile and TSH were assessed using the auto-analyser (Selectre-E and Micro lab-300) and Automated- immunoassay analyser (Immulite 1000) by using commercially available reagents and kits. Serum folate and serum vitamin B12 levels were assessed on automated machines by Chemiluminicent Immunoassay (C.L.I.A).
Descriptive data was analysed in frequencies, mean and standard deviations. Comparison and correlations among groups was established using chi-square tests, independent T-tests and Pearson’s correlation. The results were considered significant at p<0.05. All tests were applied using the software, SPSS, ver. 21, IBM Corp.
The depressed and non-depressed postmenopausal females groups did not differ significantly from each other in the sociodemographic profile. Most of the females belonged to Hindu religion (30 and 33, respectively) and lower socioeconomic status (30 and 28, respectively). Nuclear family was the predominant family type (27 and 22, respectively) and majority of females were housewives (30 and 35, respectively) (Table 1).
The depressed and non-depressed postmenopausal female groups differed significantly from each other on parameters of heart discomfort (p=0.023), physical and mental exhaustion (p=0.010), sexual dysfunction (p=0.045), bladder dysfunction (p=0.050), depressive mood (p=0.000), irritability (p=0.000), anxiety (p=0.000) and joint and muscle aches (p=0.000) (Table 2).
The depressed and non-depressed postmenopausal female groups differed significantly in serum levels of cholesterol (p=0.023), triglycerides (p=0.020) and HDL (p=0.000), TSH (p=0.042), Folate (p=0.036), Vit B12 (p=0.002). There was no significant difference in levels of LDL and VLDL (Table 3).
The depressed and non-depressed postmenopausal females differed significantly in serum levels of TSH and folate. There was no difference in vitamin B12 levels (Table 4).
The HAM-D scores of depressed postmenopausal females correlated significantly with serum levels of TSH (p=0.000), cholesterol (p=0.000), triglycerides (p=0.000), HDL (p=0.000) and LDL levels (p=0.000) (Table 5).
Women in the menopausal transition and the postmenopausal period are affected with vasomotor symptoms, urogenital atrophy, sexual dysfunction, somatic symptoms, cognitive difficulty, sleep disturbance and psychological problems . The psychological symptoms such as depression, loneliness and despair tend to persist longer than physiological symptoms [26-29]. 19% post-menopausal women in the community report depressive symptoms and around the same number report thyroid and lipid profile derangements . It has been suggested that folate and vitamin B12 have a role in depression, but the results of epidemiologic studies on this issue have been inconsistent. It is hypothesized that the deficiencies in folate and vitamin B12 can lead to elevated homocysteine concentrations, which have been associated with depression [30-33]. Hence we decided to study the prevalence and correlation of these factors in this study.
The depressed postmenopausal females group had significantly higher climecteric symptomatology than the non-depressed group, particularly on parameters of heart discomfort, physical and mental exhaustion, sexual dysfunction, bladder dysfunction, depressive mood, irritability, anxiety and joint and muscle aches. No differences were found in prevalence of hot flushes, sleep disturbances and dryness of genital tract. These symptoms are more attributed to estrogen and progesterone level fluctuations , rather than the thyroid, lipid and vitamin derangements that this study focused on.
The depressed and non-depressed postmenopausal female groups differed significantly in serum levels of TSH, cholesterol, triglycerides and HDL. There was no significant difference in levels of LDL and VLDL. The HAM-D scores of depressed postmenopausal females correlated significantly, positively with serum levels of TSH, cholesterol, triglycerides, LDL and negatively with HDL levels. This meant that depressed group had greater derangement in the TSH levels and lipid profile than the non-depressed group. Also, as the severity of depression increased, the serum levels of TSH, cholesterol, triglycerides and LDL increased, while those of HDL decreased. Another study also found similar results  but there is also a study  that had findings contrary to our study, where they didnot find significant correlation between severity of depression and deranged lipid profile. Even mild thyroid failure, as seen by raised TSH levels, can have a number of clinical effects such as depression, memory loss, cognitive impairment and a variety of neuromuscular complaints in post-menopausal women  and hence the need to study its contributory role in postmenopausal depression. There are studies that report TSH derangements of the same tune as our study .
|Sociodemographic profile||Groups||X2* (d.f.)||Signi † (2-tailed)|
|Depressed pm females||Non-Depressed Pm Females|
|Age group||<=48 years||15||15||0.720 (2)||0.698|
|Socioeconomic status||Lower||30||28||1.736 (2)||0.420|
|Family type||Nuclear||27||22||1.317 (1)||0.251|
*Chi Square test value, †Significance
Table 1: Sociodemographic profile.
The depressed and non-depressed postmenopausal females differed significantly in serum levels of folate but there was no difference in vitamin B12 levels. Neither level correlated with severity of depression in postmenopausal females. Likewise, other studies [32,37] also found no statistically significant relationship between depressive symptoms and either folate or vitamin B12 level in postmenopausal women in our study. Although theoretically, the consumption of folate and vitamin B complexes, through diet or supplementation, decreases the total plasma concentration of homocysteine and may enhance responses to standard antidepressant treatment. Treatment with vitamin B complexes can reduce the long-term prevalence of depression in at-risk people, such as stroke survivors .
|Menopausal rating scale parameters||Group||X2* (d.f.)||Signi† (2-tailed)|
|Depressed pm females||Non-depressed pm females|
|Hot flushes||Absent||10||16||2.051 (1)||0.152|
|Heart discomfort||Absent||2||9||5.165 (1)||0.023|
|Sleep disturbances||Absent||7||11||1.147 (1)||0.284|
|Physical and mental exhaustion||Absent||3||12||6.646 (1)||0.010|
|Sexual dysfunction||Absent||4||11||4.021 (1)||0.045|
|Bladder dysfunction||Absent||8||16||3.810 (1)||0.050|
|Dryness of genital tract||Absent||6||11||1.867 (1)||0.172|
|Depressive mood||Absent||9||27||16.364 (1)||0.000|
|Joint and muscle aches||Absent||6||21||12.579 (1)||0.000|
*Chi Square test value, †Significance.
Table 2: Menopausal rating scale.
|Lipid Profile Parameters (mg/ml)||Group||Mean (s.d.)||t-Value* (d.f.)||Signi† (2-tailed)|
|Cholesterol||Depressed PM Females||160.08 (18.868)||2.314 (78)||0.023|
|Non-Depressed PM Females||151.43 (14.241)|
|Triglycerides||Depressed PM Females||92.83 (24.516)||2.368 (78)||0.020|
|Non-Depressed PM Females||80.83 (20.651)|
|HDL||Depressed PM Females||44.40 (5.647)||-4.622 (78)||0.000|
|Non-Depressed PM Females||51.25 (7.482)|
|LDL||Depressed PM Females||98.55 (19.155)||1.795 (78)||0.077|
|Non-Depressed PM Females||92.38 (10.317)|
|VLDL||Depressed PM Females||19.13 (3.653)||1.524 (78)||0.132|
|Non-Depressed PM Females||17.90 (3.536)|
|TSH||Depressed PM Females||6.23
|Non-Depressed PM Females||3.74
|Folate||Depressed PM Females||5.110
|Non-Depressed PM Females||6.634
|Vit B12||Depressed PM Females||150.40
|Non-Depressed PM Females||176.35
*Independent t-test value, †Significance
Table 3: Blood biomarkers mean values.
|Serum levels||Group||X2* (d.f.)||Signi† (2-tailed)|
|Depressed pm females||Non-depressed pm females|
|TSH (mcg/mL)||<4.00||22||31||4.528 (1)||0.033|
|Folate (ng/mL)||<=5.5||18||8||5.698 (1)||0.017|
|Vitamin B12 (pg/mL)||<=211||37||36||0.157 (1)||0.692|
*Chi square test value, †Significance
Table 4: TSH, B12, Folate levels.
Table 5: Correlations.
In this study, the aim was to study the occurrence and correlation of thyroid, lipid, folate and vitamin B12 derangements in depressed and non-depressed postmenopausal females. This was intended to give an insight into the hematological parameters that could serve as biomarkers for depressed state in post-menopausal women. While we did have significant derangements of TSH, lipids and folate levels, vitamin B12 did not differ much. This could be attributed to the fact that non-vegetarian diets and consumption of over-the-counter multivitamins could have confounded these findings in our study population. Nevertheless, the correlation of depression severity and derangement of these hematological parameters (TSH, cholesterol, triglycerides, LDL and HDL) were established. Though, we did not find significant correlation between severity of depression and levels of folate and vitamin B12, it would still be interesting to see the effect of replenishment of these vitamins and their effect on depression and its response to treatment, as suggested by multiple theoretical studies. The management of these non-psychiatric causes of morbidity will enhance the achievement of healthy life for patients of postmenopausal depression. The small sample size and cross-sectional study design have limited our study from being generalized but it definitely serves as a stimulus for future studies which can give us large evidence base in the field of management of postmenopausal depression.
- Kessler RC, Berglund P, Demler O, Jin R, Koretz D, at al. (2003) The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R). JAMA 289: 3095-3105.
- Angst F, Stassen HH, Clayton PJ, Angst J (2002) Mortality of patients with mood disorders: Follow-up over 34-38 years. J Affect Disord 68: 167-181.
- Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ (2006) Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. Lancet 367: 1747-1757.
- Schmidt PJ, Roca CA, Bloch M, Rubinow DR (1997) The perimenopause and affective disorders. Semin Reprod Endocrinol 15: 91-100.
- Archer JS (1999) NAMS/Solvay resident essay award. Relationship between estrogen, serotonin and depression. Menopause 6: 71-78.
- Leung BM, Kaplan BJ (2009) Perinatal depression prevalence, risks and the nutrition link-a review of the literature. J Am Diet Assoc 109: 1566-1575.
- Huttner RP, Shepherd JE (2003) Gonadal steroids, Selective serotonin reuptake inhibitors and mood disorders in women. Med Clin NorthAm 87: 1065-1076.
- Halbreich U (1997) Role of estrogen in postmenopausal depression. Neurology 48: S16-19.
- Genazzani AR, Monteleone P, Gambacciani M (2002) Hormonal influence on the central nervous system. Maturitas 43 Suppl 1: S11-17.
- Martel M, Klump K, Nigg JT, Breedlove SM, Sisk CL (2009) Potential hormonal mechanisms of attention-deficit/hyperactive disorder and major depressive disorder: A new perspective. Horm Behav 55: 465-478.
- Anderson E, Hamburger S, Liu JH, Rebar RW (1987) Characteristics of menopausal women seeking assistance. Am J Obstet Gynecol 156: 428-433.
- Alexopoulas GS, Kalz IR, Reynolds CF III, Carpenter D, Doherthy JP (2001) The expert consensus guideline series: Pharmacotherapy of depressive disorders in older patients. Post Graduate Medicine Special Report, pp: 1-86.
- Bagchi N, Brown TR, Parish RF (1990) Thyroid dysfunction in adults over age 55 years. A study in an urban US community. Arch Intern Med 150: 785-787.
- Terzic MM, Dotlic J, Maricic S, Mihailovic T, Tosic-Race B (2009) Influence of red clover-derived isoflavones on serum lipid profile in postmenopausal women. J Obstet Gynaecol Res 35: 1091-1095.
- de Kleijn MJ, van der Schouw YT, Banga JD, van der Graaf Y (1996) The effect of menopause on risk factors for ischemic diseases. Ned Tijdschr Geneeskd 140: 478-482.
- Glueck CJ, Tieger M, Kunkel R, Hamer T, Tracy T, et al. (1994) Hypocholesterolemia and affective disorders. Am J Med Sci 308: 218-225.
- Nakao M, Yano E (2004) Relationship between major depression and high serum cholesterol in Japanese men. Tohoku J Exp Med 204: 273-287.
- Herrmann W, Obeid R (2007) Biomarkers of folate and vitamin B(12) status in cerebrospinal fluid. Clin Chem Lab Med 45: 1614-1620.
- Fava M, Mischoulon D (2010) Evidence for folate in combination with antidepressants at initiation of therapy. J Clin Psychiatry 71: e31.
- Tiemeier H, van Tuijl HR, Hofman A, Meijer J, Kiliaan AJ, et al. (2002) Vitamin B12, folate and homocysteine in depression: The Rotterdam study. Am J Psychiatry 159: 2099-2101.
- Nanri A (2013) Nutritional epidemiology of type 2 diabetes and depressive symptoms. J Epidemiol 23: 243-250.
- Kravitz HM, Ganz PA, Bromberger J, Powell LH, Sutton-Tyrrell K, et al. (2003) Sleep difficulty in women at midlife: A community survey of sleep and the menopausal transition. Menopause 10: 19-28.
- Kuppuswamy B (1981) Manual of Socioeconomic Status (Urban) 1st ed. Delhi: Manasayan 66-72.
- Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56-62.
- Heinemann LA, Potthoff P, Schneider HP (2003) International versions of the menopause rating scale (MRS). Health Qual Life Outcomes 1: 28.
- Kwon SH, Kim YJ, Moon KN, Kim IS, Park KJ, et al. (1995) The climacteric symptoms and recurrent depressive disorder in middle-aged women. Korean J Women Health Nurs 2: 235-243.
- Beydoun MA, Kuczmarski MT, Beydoun HA, Shroff MR, Mason MA, et al. (2009) The sex-specific role of plasma folate in mediating the association of dietary quality with depression symptoms. J Nutr 140: 338-347.
- Bottiglieri T (2005) Homocysteine and folate metabolism in depression. Prog Neuropsychopharmacol Biol Psychiatry 29: 1103-1112.
- D'Anci KE, Rosenberg IH (2004) Folate and brain function in the elderly. Curr Opin Clin Nutr Metab Care 7: 659-664.
- Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, et al. (2000) Homocysteine, folate, methylation and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 69: 228-232.
- Bell IR, Edman JS, Morrow FD, Marby DW, Mirages S, et al. (1991) B complex vitamin patterns in geriatric and young adult inpatients with major depression. J Am Geriatr Soc 39: 252-257.
- Sengül O, Uygur D, Güleç M, Dilbaz B, Simsek EM, et al. (2014) The comparison of folate and vitamin B12 levels between depressive and non-depressive postmenopausal women. Turk J Med Sci 44: 611-615.
- Carels RA, Darby LA, Cacciapaglia HM, Douglass OM (2004) Reducing cardiovascular risk factors in postmenopausal women through a lifestyle change intervention. J Womens Health (Larchmt) 13: 412-426.
- Chen CC, Huang TL (2006) Association of serum lipid profiles with depressive and anxiety disorders in menopausal women. Chang Gung Med J 29: 325-330.
- Schindler AE (2003) Thyroid function and post-menopause. Gynecol Endocrinol 17: 79-85.
- Walker JG, Mackinnon AJ, Batterham P, Jorm AF, Hickie I, et al. (2010) Mental health literacy, folic acid and vitamin B 12 and physical activity for the prevention of depression in older adults: Randomised controlled trial. Br J Psychiatry 197: 45-54.
- Almeida OP, Marsh K, Alfonso H, Flicker L, Davis TM, et al. (2010) B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial. Ann Neurol 68: 503-510.
Citation: Solanki RK, Malhotra S, Borade PB, Ranawat A (2016) A Study of Hematological Biomarkers in Depressed Postmenopausal Females. Bipolar Disord 2: 111. Doi: 10.4172/2472-1077.1000111
Copyright: ©2016 Solanki RK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Select your language of interest to view the total content in your interested language
Share This Article
International Conference on Bipolar Disorder: Psychiatry and Mental Health
September 24-25, 2018 Dubai, UAE
28th World Summit on Neurology, Neuroscience and Neuropharmacology
September 26-27, 2018 Montreal, Canada
27th International Conference on Neurology and Cognitive Neuroscience
October 18-19, 2018 Warsaw, Poland
- Total views: 948
- [From(publication date): 0-2016 - Jul 18, 2018]
- Breakdown by view type
- HTML page views: 855
- PDF downloads: 93