Choline and N-acetyl Aspartate Levels in the Dorsolateral Prefrontal Cortex at the Beginning of the Recovery Phase As Markers of Increased Risk for Depressive Episode Recurrence Under Different Duration of Maintenance Therapy and After It: A...

Overview

Journal Croat Med J

Specialty General Medicine

Date 2018 Nov 6

PMID 30394016

Citations 1

Authors

Neven Henigsberg

Aleksandar Savic

Marko Rados

Helena Sarac

Milan Rados

David Ozretic

Maja Bajs Janovic

Viktorija Erdeljic Turk

Ana Secic

Petra Kalember

Pero Hrabac

Affiliations

Soon will be listed here.

Abstract

Aim: To evaluate the relationship between the dynamics of proton magnetic resonance spectroscopy (1H-MRS) brain metabolite levels at the beginning of the recovery phase of the index depressive episode and the time to the recurrence of depression.

Methods: This retrospective cohort study analyzed the changes in N-acetyl aspartate (NAA), choline (Cho), and glutamate-glutamine in 48 patients with recurrent depression treated with maintenance antidepressant monotherapy at a stable dose. 1H-MRS was performed at the start of the recovery phase and 6 months later. 1H-MRS parameters, index episode descriptors, and depressive disorder course were analyzed by Cox proportional hazards model.

Results: NAA and Cho decrease six months after the beginning of the recovery period were time-independent risk factors for depressive episode recurrence. Hazard ratio associated with NAA decrease was 2.02 (95% confidence interval 1.06-3.84) and that associated with Cho decrease was 2.06 (95% confidence interval 1.02-4.17). These changes were not related to symptoms severity, as Montgomery-Asberg Depression Scale score remained generally unchanged (mean -0.01; standard deviation 1.6) over the first 6 months of recovery.

Conclusion: Patients receiving maintenance antidepressant therapy after recovery who experience a decrease in NAA or Cho levels early in the recovery phase have a double risk of depressive episode recurrence. Sustained NAA and Cho levels at the beginning of the recovery phase may indicate increased brain resilience conferred by antidepressant therapy, while NAA and Cho decrease may indicate only the trait-related temporal effect of therapy in another stratum of patients.

Citing Articles

Neurochemical and microstructural alterations in bipolar and depressive disorders: A multimodal magnetic resonance imaging study.

Kong L, Li H, Lin F, Zheng W, Zhang H, Wu R Front Neurol. 2023; 14:1089067.

PMID: 36937532 PMC: 10014904. DOI: 10.3389/fneur.2023.1089067.

References

Steingard R, Yurgelun-Todd D, Hennen J, Moore J, Moore C, Vakili K . Increased orbitofrontal cortex levels of choline in depressed adolescents as detected by in vivo proton magnetic resonance spectroscopy. Biol Psychiatry. 2000; 48(11):1053-61. DOI: 10.1016/s0006-3223(00)00942-2. View

Ten Doesschate M, Bockting C, Koeter M, Schene A . Prediction of recurrence in recurrent depression: a 5.5-year prospective study. J Clin Psychiatry. 2010; 71(8):984-91. DOI: 10.4088/JCP.08m04858blu. View

Mayberg H, Brannan S, Tekell J, Silva J, Mahurin R, McGinnis S . Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry. 2000; 48(8):830-43. DOI: 10.1016/s0006-3223(00)01036-2. View

Borges S, Chen Y, Laughren T, Temple R, Patel H, David P . Review of maintenance trials for major depressive disorder: a 25-year perspective from the US Food and Drug Administration. J Clin Psychiatry. 2014; 75(3):205-14. DOI: 10.4088/JCP.13r08722. View

Arnone D, Mumuni A, Jauhar S, Condon B, Cavanagh J . Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: meta-analysis of absolute prefrontal neuro-metabolic concentrations. Eur Neuropsychopharmacol. 2015; 25(8):1109-17. DOI: 10.1016/j.euroneuro.2015.04.016. View

Solomon D, Keller M, Leon A, Mueller T, Lavori P, Shea M . Multiple recurrences of major depressive disorder. Am J Psychiatry. 2000; 157(2):229-33. DOI: 10.1176/appi.ajp.157.2.229. View

Caverzasi E, Pichiecchio A, Poloni G, Calligaro A, Pasin M, Palesi F . Magnetic resonance spectroscopy in the evaluation of treatment efficacy in unipolar major depressive disorder: a review of the literature. Funct Neurol. 2012; 27(1):13-22. PMC: 3812759. View

Frank E, Prien R, Jarrett R, Keller M, Kupfer D, Lavori P . Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991; 48(9):851-5. DOI: 10.1001/archpsyc.1991.01810330075011. View

Rush A, Kraemer H, Sackeim H, Fava M, Trivedi M, Frank E . Report by the ACNP Task Force on response and remission in major depressive disorder. Neuropsychopharmacology. 2006; 31(9):1841-53. DOI: 10.1038/sj.npp.1301131. View

10.

Hardeveld F, Spijker J, de Graaf R, Nolen W, Beekman A . Prevalence and predictors of recurrence of major depressive disorder in the adult population. Acta Psychiatr Scand. 2009; 122(3):184-91. DOI: 10.1111/j.1600-0447.2009.01519.x. View

11.

Sheehan D, Lecrubier Y, Sheehan K, Amorim P, Janavs J, Weiller E . 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. 1999; 59 Suppl 20:22-33;quiz 34-57. View

12.

Zhang Y, Han Y, Wang Y, Zhang Y, Li L, Jin E . A MRS study of metabolic alterations in the frontal white matter of major depressive disorder patients with the treatment of SSRIs. BMC Psychiatry. 2015; 15:99. PMC: 4458012. DOI: 10.1186/s12888-015-0489-7. View

13.

Jang J, Kwon J, Jang D, Moon W, Lee J, Ha T . A proton MRSI study of brain N-acetylaspartate level after 12 weeks of citalopram treatment in drug-naive patients with obsessive-compulsive disorder. Am J Psychiatry. 2006; 163(7):1202-7. DOI: 10.1176/ajp.2006.163.7.1202. View

14.

Zimmerman M, McGlinchey J, Posternak M, Friedman M, Attiullah N, Boerescu D . How should remission from depression be defined? The depressed patient's perspective. Am J Psychiatry. 2006; 163(1):148-50. DOI: 10.1176/appi.ajp.163.1.148. View

15.

Hasler G, Neumeister A, van der Veen J, Tumonis T, Bain E, Shen J . Normal prefrontal gamma-aminobutyric acid levels in remitted depressed subjects determined by proton magnetic resonance spectroscopy. Biol Psychiatry. 2005; 58(12):969-73. DOI: 10.1016/j.biopsych.2005.05.017. View

16.

Tsai G, Coyle J . N-acetylaspartate in neuropsychiatric disorders. Prog Neurobiol. 1995; 46(5):531-40. DOI: 10.1016/0301-0082(95)00014-m. View

17.

Gonul A, Kitis O, Ozan E, Akdeniz F, Eker C, Eker O . The effect of antidepressant treatment on N-acetyl aspartate levels of medial frontal cortex in drug-free depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 30(1):120-5. DOI: 10.1016/j.pnpbp.2005.08.017. View

18.

Sager T, Topp S, Torup L, Hanson L, Egestad B, Moller A . Evaluation of CA1 damage using single-voxel 1H-MRS and un-biased stereology: Can non-invasive measures of N-acetyl-asparate following global ischemia be used as a reliable measure of neuronal damage?. Brain Res. 2001; 892(1):166-75. DOI: 10.1016/s0006-8993(00)03274-1. View

19.

Zaremba D, Dohm K, Redlich R, Grotegerd D, Strojny R, Meinert S . Association of Brain Cortical Changes With Relapse in Patients With Major Depressive Disorder. JAMA Psychiatry. 2018; 75(5):484-492. PMC: 5875383. DOI: 10.1001/jamapsychiatry.2018.0123. View

20.

Fales C, Barch D, Rundle M, Mintun M, Mathews J, Snyder A . Antidepressant treatment normalizes hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression. J Affect Disord. 2008; 112(1-3):206-11. PMC: 2825146. DOI: 10.1016/j.jad.2008.04.027. View