Lower Choline-Containing Metabolites/Creatine (Cr) Rise and Failure to Sustain NAA/Cr Levels in the Dorsolateral Prefrontal Cortex Are Associated with Depressive Episode Recurrence under Maintenance Therapy: A Proton Magnetic Resonance Spectroscopy Retrospective Cohort Study

Henigsberg, Neven; Šarac, Helena; Radoš, Marko; Ozretić, David; Foro, Tamara; Turk, Viktorija Erdeljić; Hrabač, Pero; Janović, Maja Bajs; Rak, Benedict; Kalember, Petra

doi:10.3389/fpsyt.2017.00277

Cited by 32 publications

(6 citation statements)

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“…The observed ratio changes may be the consequence of phosphorylcholine-to-glycerophosphorylcholine mediated synthesis-to-breakdown overbalance, a finding that would be congruent to functional connectivity changes observed in neuroimaging studies of the DLPFC ( 35 , 36 ). Consistent with our previous study ( 28 ), we demonstrated that metabolic changes in the brain suggesting an increase in neuronal integrity and membrane turnover continue beyond the acute treatment and remission phases, for at least 6 months after the initiation of maintenance antidepressant therapy. We do not know for how long these changes persist, but this finding certainly warrants the initiation of MRS studies of a considerably longer duration than is our current scientific practice.…”

Section: Discussionsupporting

confidence: 92%

“…Our research group already reported an increase in Cho/Cr ratio in the DLPFC during antidepressant treatment in early to intermediate responders after 3-6 weeks of SSRI treatment in recurrent depression comorbid to posttraumatic stress disorder ( 34 ). Our previous report on the same sample of patients showed that decreased Cho/Cr ratio at the onset of recovery phase predicted depression recurrence in patients on maintenance therapy, and that these patients also exhibited decreased NAA/Cr ratio ( 28 ). Our present study focused on all the patients who had depression recurrence whether during maintenance therapy or after the antidepressant withdrawal.…”

Section: Discussionmentioning

confidence: 89%

“…This retrospective cohort study was performed in patients with recurrent depression who participated in past or ongoing research on identification of predictors of therapeutic response ( 28 ). The patients were diagnosed according to International Classification of Diseases (ICD)-10, and the diagnosis was confirmed by Mini International Neuropsychiatric Interview (MINI) 5.0 ( 29 ).…”

Section: Participants and Methodsmentioning

confidence: 99%

“…Our previous 1H-MRS study on the same cohort of patients evaluated the risk of depressive symptoms recurrence in patients on a stable dose of antidepressant in maintenance therapy. Patients who experienced recurrence during maintenance treatment were compared with those who entered the discontinuation of antidepressants phase ( 28 ). Decreased Cho/Cr and NAA/Cr ratios after recovery were related to an elevated risk for recurrence during maintenance therapy, and decreased Cho/Cr was associated with a 2.7-fold increase in the risk of depression recurrence ( 28 ).…”

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confidence: 99%

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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 retrospective cohort study

et al. 2018

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AimTo 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.MethodsThis 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.ResultsNAA 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.ConclusionPatients 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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 89%

Section: Participants and Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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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 retrospective cohort study

et al. 2018

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“…Patients in our study generally had severe depressive conditions and were receiving antidepressants before admission. A drug-induced effect regrading MRS has not been clearly shown, but it may be responsible for the findings in patients with MDD 24) , although previous studies 5) 7) showed similar patient conditions. We also could not detect any correlations between symptom severity and concentration of Glx, consistent with previous MRS studies 5)8) .…”

Section: Discussionmentioning

confidence: 52%

Physiologic and Characteristic Distributions of Glutamate/Glutamine in Patients with Major Depressive Disorder

Sakamoto

Nakamura

Sasaki

et al. 2018

J St. Marianna Univ

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Purpose Glutamate is the most abundant neurotransmitter in the brain, and proton magnetic resonance spectroscopy (MRS) allows quantification of glutamate-related metabolites (glutamate/glutamine complex; Glx). In previous findings, Glx has been lower in several brain regions of patients with major depressive disorder than in those of healthy controls. However, the physiologic and characteristic distribution of Glx in the same individual remains unclear. We attempted to clarify which brain regions reflect changes associated with depression. Material and method We measured Glx in 12 patients with depression and 12 healthy controls matched for age and sex in three brain regions (left amygdala, left anterior cingulate cortex, and left dorsolateral prefrontal cortex), and then compared the physiologic and characteristic distribution of Glx between the two groups. Results In comparisons of the distributions, Glx was significantly higher in the amygdala than in other regions. Glx tended to be lower among the patients than the controls, although no significant differences were present between the groups. We could not detect the changes expected from major depressive disorder (reduced Glx) in the amygdala, which regulates emotions and shows higher concentrations of Glx than other regions. Conclusion Previous studies have suggested that the concentration of Glx decreases with age, and this might have influenced our results regarding changes with major depressive disorder. In addition, we could not clarify whether medications affected the patient condition, because treatment for depression increased Glx in previous studies. Further MRS studies are needed to clarify Glx distributions in the specific diagnosis of depression.

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Choline elevation in amygdala region at recovery indicates longer survival without depressive episode: a magnetic resonance spectroscopy study

et al. 2019

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Rationale Depression, with variable longitudinal patterns, recurs in one third of patients. We lack useful predictors of its course/ outcome, and proton magnetic resonance spectroscopy (1H-MRS) of brain metabolites is an underused research modality in finding outcome correlates. Objectives To determine if brain metabolite levels/changes in the amygdala region observed early in the recovery phase indicate depression recurrence risk in patients receiving maintenance therapy. Methods Forty-eight patients on stable-dose antidepressant (AD) maintenance therapy were analyzed from recovery onset until (i) recurrence of depression or (ii) start of AD discontinuation. Two 1H-MRS scans (6 months apart) were performed with a focus on amygdala at the beginning of recovery. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and Glx (glutamine/ glutamate and GABA) were evaluated with regard to time without recurrence, and risks were assessed by Cox proportional hazard modeling. Results Twenty patients had depression recurrence, and 23 patients reached AD discontinuation. General linear model repeated measures analysis displayed three-way interaction of measurement time, metabolite level, and recurrence on maintenance therapy, in a multivariate test, Wilks' lambda = 0.857, F(2,40) = 3.348, p = 0.045. Cho levels at the beginning of recovery and subsequent changes convey the highest risk for earlier recurrence. Patients experiencing higher amygdala Cho after recovery are at a significantly lower risk for depression recurrence (hazard ratio = 0.32; 95% confidence interval 0.13-0.77). Conclusion Cho levels/changes in the amygdala early in the recovery phase correlate with clinical outcome. In the absence of major NAA fluctuations, changes in Cho and Glx may suggest a shift towards reduction in (previously increased) glutamatergic neurotransmission. Investigation of a larger sample with greater sampling frequency is needed to confirm the possible predictive role of metabolite changes in the amygdala region early in the recovery phase.

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Lower Choline-Containing Metabolites/Creatine (Cr) Rise and Failure to Sustain NAA/Cr Levels in the Dorsolateral Prefrontal Cortex Are Associated with Depressive Episode Recurrence under Maintenance Therapy: A Proton Magnetic Resonance Spectroscopy Retrospective Cohort Study

Cited by 32 publications

References 26 publications

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 retrospective cohort study

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 retrospective cohort study

Physiologic and Characteristic Distributions of Glutamate/Glutamine in Patients with Major Depressive Disorder

Choline elevation in amygdala region at recovery indicates longer survival without depressive episode: a magnetic resonance spectroscopy study

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