Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder

Massardo T.Quintana J.C.b· Risco L.c· Corral S.c· Spuler J.a· Vicentini D.b· Castro-Muñoz G.a· Riedel B.a· Villa C.d· Pereira J.I.e

Author affiliations

aDepartment of Medicine, Nuclear Medicine Section Hospital Clínico de la Universidad de Chile, Santiago, Chile
bDepartment of Radiology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
cClínica Psiquiátrica Universitaria, Hospital Clínico de la Universidad de Chile, University of Chile, Santiago, Chile
dInstituto Psiquiátrico Dr. José Horwitz Barak, Santiago, Chile
eDepartment of Hematology-Oncology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

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Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: August 18, 2021
Accepted: November 18, 2021
Published online: January 28, 2022

Number of Print Pages: 15
Number of Figures: 6
Number of Tables: 4

ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)

For additional information: https://www.karger.com/NPS

Abstract

Introduction: Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD. Methods: We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck’s Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies. Results: Clinical scores decreased in both groups (p = 0.0001); Beck’s presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (p < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks. Conclusion: Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder.

© 2022 S. Karger AG, Basel

References Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annu Rev Public Health. 2013;34:119–38. Nemeroff CB, Goldschmidt-Clermont PJ. Heartache and heartbreak: the link between depression and cardiovascular disease. Nat Rev Cardiol. 2012;9(9):526–39. Baune BT, Stuart M, Gilmour A, Wersching H, Arolt V, Berger K. Moderators of the relationship between depression and cardiovascular disorders: a systematic review. Gen Hosp Psychiatry. 2012;34(5):478–92. Baune BT, Stuart M, Gilmour A, Wersching H, Heindel W, Arolt V, et al. The relationship between subtypes of depression and cardiovascular disease: a systematic review of biological models. Transl Psychiatry. 2012;2:e92. Gasse C, Laursen TM, Baune BT. Major depression and first-time hospitalization with ischemic heart disease, cardiac procedures and mortality in the general population: a retrospective Danish population-based cohort study. Eur J Prev Cardiol. 2014;21(5):532–40. Hare DL, Toukhsati SR, Johansson P, Jaarsma T. Depression and cardiovascular disease: a clinical review. Eur Heart J. 2014;35(21):1365–72. Li CT, Bai YM, Tu PC, Lee YC, Huang YL, Chen TJ, et al. Major depressive disorder and stroke risks: a 9-year follow-up population-based, matched cohort study. PLoS One. 2012;7(10):e46818. Andreone BJ, Lacoste B, Gu C. Neuronal and vascular interactions. Annu Rev Neurosci. 2015;38:25–46. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci. 2004;5(5):347–60. Clark L, Chamberlain SR, Sahakian BJ. Neurocognitive mechanisms in depression: implications for treatment. Annu Rev Neurosci. 2009;32:57–74. Dalili MN, Penton-Voak IS, Harmer CJ, Munafò MR. Meta-analysis of emotion recognition deficits in major depressive disorder. Psychol Med. 2015;45(6):1135–44. Snyder HR. Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review. Psychol Bull. 2013;139(1):81–132. Chen Q, Liu W, Li H, Zhang H, Tian M. Molecular imaging in patients with mood disorders: a review of PET findings. Eur J Nucl Med Mol Imaging. 2011;38(7):1367–80. Bora E, Fornito A, Pantelis C, Yücel M. Gray matter abnormalities in major depressive disorder: a meta-analysis of voxel based morphometry studies. J Affect Disord. 2012;138(1–2):9–18. Wise T, Cleare AJ, Herane A, Young AH, Arnone D. Diagnostic and therapeutic utility of neuroimaging in depression: an overview. Neuropsychiatr Dis Treat. 2014;10:1509–22. Palmer SM, Crewther SG, Carey LM, Team SP. A meta-analysis of changes in brain activity in clinical depression. Front Hum Neurosci. 2014;8:1045. Drevets WC, Bogers W, Raichle ME. Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism. Eur Neuropsychopharmacol. 2002;12(6):527–44. Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, et al. Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry. 2000;48(8):830–43. Smith DJ, Cavanagh JT. The use of single photon emission computed tomography in depressive disorders. Nucl Med Commun. 2005;26(3):197–203. Videbech P. PET measurements of brain glucose metabolism and blood flow in major depressive disorder: a critical review. Acta Psychiatr Scand. 2000;101(1):11–20. Graff-Guerrero A, González-Olvera J, Mendoza-Espinosa Y, Vaugier V, García-Reyna JC. Correlation between cerebral blood flow and items of the Hamilton rating scale for depression in antidepressant-naive patients. J Affect Disord. 2004;80(1):55–63. Galynker II, Cai J, Ongseng F, Finestone H, Dutta E, Serseni D. Hypofrontality and negative symptoms in major depressive disorder. J Nucl Med. 1998;39(4):608–12. Kohn Y, Freedman N, Lester H, Krausz Y, Chisin R, Lerer B, et al. 99mTc-HMPAO SPECT study of cerebral perfusion after treatment with medication and electroconvulsive therapy in major depression. J Nucl Med. 2007;48(8):1273–8. Richieri R, Boyer L, Farisse J, Colavolpe C, Mundler O, Lancon C, et al. Predictive value of brain perfusion SPECT for rTMS response in pharmacoresistant depression. Eur J Nucl Med Mol Imaging. 2011;38(9):1715–22. Carey PD, Warwick J, Niehaus DJ, van der Linden G, van Heerden BB, Harvey BH, et al. Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram. BMC Psychiatry. 2004;4:30. Ota M, Noda T, Sato N, Hattori K, Teraishi T, Hori H, et al. Characteristic distributions of regional cerebral blood flow changes in major depressive disorder patients: a pseudo-continuous arterial spin labeling (pCASL) study. J Affect Disord. 2014;165:59–63. Kohn Y, Freedman N, Lester H, Krausz Y, Chisin R, Lerer B, et al. Cerebral perfusion after a 2-year remission in major depression. Int J Neuropsychopharmacol. 2008;11(6):837–43. Ruhe HG, Booij J, Veltman DJ, Michel MC, Schene AH. Successful pharmacologic treatment of major depressive disorder attenuates amygdala activation to negative facial expressions: a functional magnetic resonance imaging study. J Clin Psychiatry. 2012;73(4):451–9. Kennedy SH, Konarski JZ, Segal ZV, Lau MA, Bieling PJ, McIntyre RS, et al. Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial. Am J Psychiatry. 2007;164(5):778–88. Vlassenko A, Sheline YI, Fischer K, Mintun MA. Cerebral perfusion response to successful treatment of depression with different serotoninergic agents. J Neuropsychiatry Clin Neurosci. 2004;16(3):360–3. Willeumier K, Taylor DV, Amen DG. Decreased cerebral blood flow in the limbic and prefrontal cortex using SPECT imaging in a cohort of completed suicides. Transl Psychiatry. 2011;1:e28. Hayley S. Toward an anti-inflammatory strategy for depression. Front Behav Neurosci. 2011;5:19. Rattan S. 3-Hydroxymethyl coenzyme A reductase inhibition attenuates spontaneous smooth muscle tone via RhoA/ROCK pathway regulated by RhoA prenylation. Am J Physiol Gastrointest Liver Physiol. 2010;298(6):G962–9. Loas G, Dalleau E, Lecointe H, Yon V. Relationships between anhedonia, alexithymia, impulsivity, suicidal ideation, recent suicide attempt, C-reactive protein and serum lipid levels among 122 inpatients with mood or anxious disorders. Psychiatry Res. 2016;246:296–302. Shrivastava A, Johnston M, Campbell R, De Sousa A, Shah N. Serum cholesterol and suicide in first episode psychosis: a preliminary study. Indian J Psychiatry. 2017;59(4):478–82. De Berardis D, Conti CM, Serroni N, Moschetta FS, Carano A, Salerno RM, et al. The role of cholesterol levels in mood disorders and suicide. J Biol Regul Homeost Agents. 2009;23(3):133–40. Mayberg HS. Limbic-cortical dysregulation: a proposed model of depression. J Neuropsychiatry Clin Neurosci. 1997;9(3):471–81. Mayberg HS, Brannan SK, Mahurin RK, Jerabek PA, Brickman JS, Tekell JL, et al. Cingulate function in depression: a potential predictor of treatment response. Neuroreport. 1997;8(4):1057–61. Manji HK, Drevets WC, Charney DS. The cellular neurobiology of depression. Nat Med. 2001;7(5):541–7. Manji HK, Duman RS. Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics. Psychopharmacol Bull. 2001;35(2):5–49. Duman RS, Nakagawa S, Malberg J. Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmacology. 2001;25(6):836–44. Vaidya VA, Duman RS. Depresssion: emerging insights from neurobiology. Br Med Bull. 2001;57:61–79. Nemeroff CB, Owens MJ. Treatment of mood disorders. Nat Neurosci. 2002;5 Suppl:1068–70. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron. 2002;34(1):13–25. Ramirez-Mahaluf JP, Medel V, Tepper A, Alliende LM, Sato JR, Ossandon T, et al. Transitions between human functional brain networks reveal complex, cost-efficient and behaviorally-relevant temporal paths. Neuroimage. 2020;219:117027. Ramirez-Mahaluf JP, Perramon J, Otal B, Villoslada P, Compte A. Author correction: subgenual anterior cingulate cortex controls sadness-induced modulations of cognitive and emotional network hubs. Sci Rep. 2018;8(1):11237. Ramirez-Mahaluf JP, Perramon J, Otal B, Villoslada P, Compte A. Subgenual anterior cingulate cortex controls sadness-induced modulations of cognitive and emotional network hubs. Sci Rep. 2018;8(1):8566. Hamilton JP, Chen MC, Gotlib IH. Neural systems approaches to understanding major depressive disorder: an intrinsic functional organization perspective. Neurobiol Dis. 2013;52:4–11. Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005;45(5):651–60. Rock PL, Roiser JP, Riedel WJ, Blackwell AD. Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med. 2014;44(10):2029–40. Bora E, Harrison BJ, Yücel M, Pantelis C. Cognitive impairment in euthymic major depressive disorder: a meta-analysis. Psychol Med. 2013;43(10):2017–26. Hasselbalch BJ, Knorr U, Kessing LV. Cognitive impairment in the remitted state of unipolar depressive disorder: a systematic review. J Affect Disord. 2011;134(1–3):20–31. Thakkar I, Massardo T, Pereira J, Quintana JC, Risco L, Saez CG, et al. Identification of Statin’s action in a small cohort of patients with major depression. Appl Sci. 2021;11(6):2827. Williams LJ, Pasco JA, Mohebbi M, Jacka FN, Stuart AL, Venugopal K, et al. Statin and aspirin use and the risk of mood disorders among men. Int J Neuropsychopharmacol. 2016;19(6):pyw008. Kim SW, Kang HJ, Jhon M, Kim JW, Lee JY, Walker AJ, et al. Statins and inflammation: new therapeutic opportunities in psychiatry. Front Psychiatry. 2019;10:103. Majd M, Saunders EFH, Engeland CG. Inflammation and the dimensions of depression: a review. Front Neuroendocrinol. 2020;56:100800. Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res. 2017;120(1):229–43. McFarland AJ, Anoopkumar-Dukie S, Arora DS, Grant GD, McDermott CM, Perkins AV, et al. Molecular mechanisms underlying the effects of statins in the central nervous system. Int J Mol Sci. 2014;15(11):20607–37. Schultz BG, Patten DK, Berlau DJ. The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms. Transl Neurodegener. 2018;7:5. White CM. A review of the pharmacologic and pharmacokinetic aspects of Rosuvastatin. J Clin Pharmacol. 2002;42(9):963–70. Redlich C, Berk M, Williams LJ, Sundquist J, Sundquist K, Li X. Statin use and risk of depression: a Swedish national cohort study. BMC Psychiatry. 2014;14:348. O’Neil A, Sanna L, Redlich C, Sanderson K, Jacka F, Williams LJ, et al. The impact of statins on psychological wellbeing: a systematic review and meta-analysis. BMC Med. 2012;10:154. Samaras K, Makkar SR, Crawford JD, Kochan NA, Slavin MJ, Wen W, et al. Effects of statins on memory, cognition, and brain volume in the elderly. J Am Coll Cardiol. 2019;74(21):2554–68. Iadecola C, Parikh NS. Statins and cognitive impairment: not a culprit, protective in some? J Am Coll Cardiol. 2019;74(21):2569–71. Parsaik AK, Singh B, Murad MH, Singh K, Mascarenhas SS, Williams MD, et al. Statins use and risk of depression: a systematic review and meta-analysis. J Affect Disord. 2014;160:62–7. Lee MC, Peng TR, Lee CH, Wang JY, Lee JA, Chen SM, et al. Statin use and depression risk: a systematic review and meta-analysis. J Affect Disord. 2021;282:308–15. Salagre E, Fernandes BS, Dodd S, Brownstein DJ, Berk M. Statins for the treatment of depression: a meta-analysis of randomized, double-blind, placebo-controlled trials. J Affect Disord. 2016;200:235–42. Yatham MS, Yatham KS, Ravindran AV, Sullivan F. Do statins have an effect on depressive symptoms? A systematic review and meta-analysis. J Affect Disord. 2019;257:55–63. Husain MI, Strawbridge R, Stokes PR, Young AH. Anti-inflammatory treatments for mood disorders: systematic review and meta-analysis. J Psychopharmacol. 2017;31(9):1137–48. Husain MI, Chaudhry IB, Khoso AB, Husain MO, Rahman RR, Hamirani MM, et al. Adjunctive simvastatin for treatment-resistant depression: study protocol of a 12-week randomised controlled trial. BJPsych Open. 2019;5(1):e13. De Giorgi R, De Crescenzo F, Rizzo Pesci N, Martens M, Howard W, Cowen PJ, et al. Statins for major depressive disorder: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2021;16(3):e0249409. Nenna A, Nappi F, Lusini M, Satriano UM, Schiliro D, Spadaccio C, et al. Effect of statins on platelet activation and function: from molecular pathways to clinical effects. Biomed Res Int. 2021;2021:6661847. Szczeklik A, Undas A, Musial J, Gajewski P, Swadzba J, Jankowski M. Antithrombotic actions of statins. Med Sci Monit. 2001;7(6):1381–5. Undas A, Brummel-Ziedins KE, Mann KG. Anticoagulant effects of statins and their clinical implications. Thromb Haemost. 2014;111(3):392–400. Gialluisi A, Izzi B, Di Castelnuovo A, Cerletti C, Donati MB, de Gaetano G, et al. Revisiting the link between platelets and depression through genetic epidemiology: new insights from platelet distribution width. Haematologica. 2020;105(5):e246–8. Izzi B, Tirozzi A, Cerletti C, Donati MB, de Gaetano G, Hoylaerts MF, et al. Beyond haemostasis and thrombosis: platelets in depression and its co-morbidities. Int J Mol Sci. 2020;21(22):8817. Morel-Kopp MC, McLean L, Chen Q, Tofler GH, Tennant C, Maddison V, et al. The association of depression with platelet activation: evidence for a treatment effect. J Thromb Haemost. 2009;7(4):573–81. Mendelson SD. The current status of the platelet 5-HT(2A) receptor in depression. J Affect Disord. 2000;57(1–3):13–24. Mendelson SD. Platelet function and sertraline. Am J Psychiatry. 2001;158(5):823–4. Massardo T, Quintana JC, Jaimovich R, Saez CG, Risco L, Liberman C, et al. Regional brain perfusion is associated with endothelial dysfunction markers in major depressive disorder. Neuropsychobiology. 2021;80(3):214–24. Massardo T, Quintana J, Pereira J, Saez C, Risco L, Olivares N, et al. Effect of statins on brain perfusion in major depression as an addition to standard therapy. SPM analysis of inflammation, platelet activation, endothelial dysfunction and neurocognitive parameters. Eur J Nucl Med Mol Imaging. 2020;47(Suppl 1):S446–7; abstract EPS169. Le-Niculescu H, Roseberry K, Gill SS, Levey DF, Phalen PL, Mullen J, et al. Precision medicine for mood disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs. Mol Psychiatry. 2021;26(7):2776–804. Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: August 18, 2021
Accepted: November 18, 2021
Published online: January 28, 2022

Number of Print Pages: 15
Number of Figures: 6
Number of Tables: 4

ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)

For additional information: https://www.karger.com/NPS

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