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| BRIEF REPORT |
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| Year : 2022 | Volume
: 7
| Issue : 2 | Page : 95-97 |
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Elevated homocysteine and depression outcomes in patients with comorbid medical conditions in rural primary care
Krishnamachari Srinivasan1, Luke Joshua Salazar2, Elsa Heylen3, Maria L Ekstrand4
1 Department of Psychiatry, St. John's Medical College; Division of Mental Health and Neurosciences, St. John's Research Institute, Bengaluru, Karnataka, India
2 Department of Psychiatry, St. John's Medical College, Bengaluru, Karnataka, India
3 Department of Medicine, Division of Prevention Sciences, University of California, San Francisco, California, USA
4 Division of Mental Health and Neurosciences, St. John's Research Institute, Bengaluru, Karnataka, India; Department of Medicine, Division of Prevention Sciences, University of California, San Francisco, California, USA
| Date of Submission | 02-Mar-2022 |
| Date of Acceptance | 18-Mar-2022 |
| Date of Web Publication | 22-Jul-2022 |
Correspondence Address:
Dr. Krishnamachari Srinivasan
Department of Psychiatry, St. John's Medical College Hospital, Sarjapur Road, Bengaluru - 560 034, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jncd.jncd_18_22
We examined the association of elevated concentration of total homocysteine (tHcy) with the severity of depression in patients diagnosed with depression and comorbid chronic medical conditions in rural primary care settings in Karnataka. Participants were included from the control arm of a cluster-randomized controlled trial designed to evaluate the effects of using a collaborative care model to integrate screening and treatment of primary health center patients. tHcy was assayed at baseline, and depression severity scores were assessed using the Patient Health Questionnaire (PHQ-9) 6 months later. There was no difference in the mean PHQ-9 score between those with (mean PHQ = 7.4) and without (mean PHQ = 7.6) elevated tHcy levels (P = 0.67).
Keywords: Depression, homocysteine, primary health care
How to cite this article:
Srinivasan K, Salazar LJ, Heylen E, Ekstrand ML. Elevated homocysteine and depression outcomes in patients with comorbid medical conditions in rural primary care. Int J Non-Commun Dis 2022;7:95-7 |
How to cite this URL:
Srinivasan K, Salazar LJ, Heylen E, Ekstrand ML. Elevated homocysteine and depression outcomes in patients with comorbid medical conditions in rural primary care. Int J Non-Commun Dis [serial online] 2022 [cited 2022 Aug 14];7:95-7. Available from: https://www.ijncd.org/text.asp?2022/7/2/95/351744 |
| Introduction | |  |
An elevated concentration of total homocysteine (tHcy) has been shown to be associated with an increased risk for several neuropsychiatric conditions including depression.[1] A recent meta-analysis of 46 observational studies that included population-based and clinic-based studies found that subjects diagnosed with depression had a significantly elevated concentration of homocysteine compared to healthy controls (weighted mean difference = 2.53 μmol/L, 95% confidence interval [CI]: 1.77, 3.30), and individuals with elevated concentration of homocysteine had a significantly higher risk of developing depression (pooled risk = 1.34, 95% CI: 1.19, 1.52).[2]
A few community-based studies have reported an association between tHcy concentrations and severity and course of depressive symptoms.[3],[4],[5],[6] A study from Australia noted that individuals in the lowest quartile of tHcy reported fewer depressive symptoms adjusted for several confounders,[3] but others failed to find a significant association between serum tHcy concentrations and depressive symptoms,[4] while another study reported an association only among older subjects (≥50 years).[5] A longitudinal study among men and women aged 65 years or older did not find any associations between baseline tHcy concentrations and either change in depression score over 16 years or incident depression.[6]
To our knowledge, elevated concentration of tHcy as a predictor of the severity of depression in patients diagnosed with depression and comorbid chronic medical conditions has not been studied. The aim of the present study was to address this gap in the literature.
| Methods | | |
Setting and participants
The present study was a part of a cluster-randomized controlled trial (cRCT) designed to evaluate the effects of using a collaborative care model to integrate screening and treatment of primary health center (PHC) patients with depression who were also diagnosed with chronic medical conditions, in rural Karnataka.[7] The study was conducted in 49 PHCs in the rural Ramnagara district of Karnataka state in southern India. PHCs were randomly selected and were randomized 1:1 into the collaborative care and “enhanced” standard care arms. Intervention (collaborative care) arm PHC staff were trained in mental health diagnosis, treatment, and the collaborative care model. All staff in the PHCs that were randomized to the control (enhanced standard care) arm received a full day of basic training in established clinical protocols for the management of depression. The present analysis included 205 participants from the “enhanced” standard care arm with Patient Health Questionnaire (PHQ-9) scores of at least 10 and with 6-month follow-up data available. Participants were adults (≥30 years) with depression and comorbid medical conditions that included either hypertension, diabetes, or ischemic heart disease.
Measures
We collected demographic details of the participants including age, gender, marital status, educational status, and household income. The Generalized Anxiety Disorder Scale and the PHQ-9 Depression Scale were used to assess the severity of anxiety and depression, respectively, at baseline and 6-month follow-up.[8],[9] We had collected 10 ml of venous blood at baseline as part of the parent study to perform laboratory diagnostic tests and blood was stored at −80°C.
Biochemistry assessments
Homocysteine (μmol/L)
tHcy was analyzed by enzymatic method on Cobas Integra chemistry autoanalyzer with dedicated reagent from Roche Diagnostics (Switzerland). Two levels of tHcy control were used. Within-day imprecision was <5% and between-day imprecision was 4.02% and 4.0% for Level 1 (12.85 ± 0.52) and Level 2 (40.03 ± 1.60), respectively.
Folate (ng/mL) and Vitamin B12 (pg/mL)
Folate and Vitamin B12 were analyzed by electrochemiluminescence on Cobas e411 immunoassay analyzer with dedicated reagents from Roche Diagnostics (Switzerland). Within-day imprecision for folate was <10% and between-day imprecision was 10.84%, 14.23%, and 15.92% for Level 1 (mean 2.65 ± 0.29), Level 2 (mean 7.55 ± 1.07), and Level 3 (mean: 15.85 ± 2.52), respectively. For Vitamin B12, within-day imprecision was 10% and between-day imprecision was 5.84%, 5.30%, and 4.90% for Level 1 (mean: 391.73 ± 22.89), Level 2 (mean: 548.51 ± 29.07), and Level 3 (mean: 701.51 ± 34.35), respectively.
Statistical analysis
Descriptive statistics used were mean with standard deviation for continuous variables, and frequencies and percentages for categorical variables. Independent sample's t-test and linear regression were used to examine the association between elevated baseline tHcy concentrations and PHQ-9 scores at 6 months, overall, and with age as a moderator. All analyses were performed using IBM SPSS Statistics for Windows, Version 25.0. (Armonk, NY: IBM Corp).
Ethical considerations
Ethics approval was obtained from the Institutional Ethical Review Board at St. John's Medical College and Hospital, and the Committee on Human Research, University of California, San Francisco. All participants provided written informed consent.
| Results | | |
The baseline characteristics of the study participants are shown in [Table 1].
There was no difference in the mean PHQ-9 score between those with (mean: PHQ = 7.4) and without (mean: PHQ = 7.6) elevated tHcy levels (P = 0.67). There was no significant interaction between age and elevated tHcy on depression severity (P = 0.44). Among those aged ≥65 years with elevated tHcy (n = 38), PHQ scores tended to be higher compared to those with normal tHcy concentrations (n = 32) (8.2 ± 3.2 vs. 7.8 ± 2.9, P = 0.65).
| Discussion | | |
In our sample of patients with clinical depression, elevated tHcy did not predict the severity of depression 6 months later. Similar findings were reported in another study, in which no significant associations were found between tHcy concentrations and change in depression scores over 16 years, as captured by the Center for Epidemiologic Studies Depression Scale[6] In addition, a meta-analysis reported that tools used to measure depression severity can be a source of heterogeneity, with studies that used PHQ-9 as a measure of depressive symptoms failing to find associations between tHcy concentrations and depression.[2]
Although, in the present study, age was not found to have a significant influence on the relationship between elevated tHcy and the severity of depression, others have reported a significant and positive association between tHcy concentrations and elevated depressive symptoms only among the elderly.[5]
While our study is limited by the relatively small sample size, it is worthwhile exploring the association between elevated tHcy concentrations and severity of depression, particularly among elderly subjects in future studies.
Acknowledgment
We gratefully acknowledge Dr. Anitha Devanath from the Department of Biochemistry, St. John's Medical College, who did the biochemical assessments and provided expertise on the same.
Financial support and sponsorship
This research was supported by the US National Institute of Mental Health (R01 MH100311).
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Pana A. Homocysteine and neuropsychiatric disease. Psychiatr Ann 2015;45:463-8.  |
| 2. | Moradi F, Lotfi K, Armin M, Clark CC, Askari G, Rouhani MH. The association between serum homocysteine and depression: A systematic review and meta-analysis of observational studies. Eur J Clin Invest 2021;51:e13486. |
| 3. | Sachdev PS, Parslow RA, Lux O, Salonikas C, Wen W, Naidoo D, et al. Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Psychol Med 2005;35:529-38. |
| 4. | Nanri A, Mizoue T, Matsushita Y, Sasaki S, Ohta M, Sato M, et al. Serum folate and homocysteine and depressive symptoms among Japanese men and women. Eur J Clin Nutr 2010;64:289-96. |
| 5. | Beydoun MA, Shroff MR, Beydoun HA, Zonderman AB. Serum folate, Vitamin B-12, and homocysteine and their association with depressive symptoms among U.S. adults. Psychosom Med 2010;72:862-73. |
| 6. | Elstgeest LE, Brouwer IA, Penninx BW, van Schoor NM, Visser M. Vitamin B 12, homocysteine and depressive symptoms: A longitudinal study among older adults. Eur J Clin Nutr 2017;71:468-75. |
| 7. | Srinivasan K, Mazur A, Mony PK, Whooley M, Ekstrand ML. Improving mental health through integration with primary care in rural Karnataka: Study protocol of a cluster randomized control trial. BMC Fam Pract 2018;19:158. |
| 8. | Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Intern Med 2006;166:1092-7. |
| 9. | Kroenke K, Spitzer RL, Williams JB. The PHQ-9: Validity of a brief depression severity measure. J Gen Intern Med 2001;16:606-13. |
[Table 1]
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