Potential of Pretreatment Neural Activity in the Visual Cortex During Emotional Processing to Predict Treatment Response to Scopolamine in Major Depressive Disorder

Background Repetitive Transcranial Magnetic Stimulation [rTMS] is increasingly being used to treat Major Depressive Disorder [MDD]. Given that not all patients respond to rTMS, it would be clinically useful to have reliable biomarkers that predict treatment response. Oxidized phosphatidylcholine [OxPC] and some oxylipins are important plasma biomarkers of oxidative stress and inflammation. Not only is depression associated with oxidative stress, but rTMS has been shown to have anti-oxidative effects. Objectives To investigate whether plasma oxolipidomics profiles could predict treatment response in patients with treatment resistant MDD. Methods Fourty-eight patients undergoing rTMS treatment for MDD were recruited along with nine healthy control subjects. Plasma OxPCs and oxylipins were extracted and analyzed through high performance liquid chromatography coupled with mass spectrometry. Patients with a Hamilton Depression Rating Scale score [Ham-D] ≤7 post-treatment were defined as having entered remission. Results Fifty-seven OxPC and 32 oxylipin species were identified in our subjects. MDD patients who entered remission following rTMS had significantly higher pre-rTMS levels of total and fragmented OxPCs compared to non-remitters and controls [one-way ANOVA, p<0.05]. However, no significant changes in OxPC levels were found as a result of rTMS, regardless of treatment response [p>0.05]. No differences in plasma oxylipins were found between remitters and non-remitters at baseline. Conclusion Certain categories of OxPCs may be useful predictive biomarkers for response to rTMS treatment in MDD. Given that elevated oxidized lipids may indicate higher levels of oxidative stress and inflammation in the brain, patients with this phenotype of depression may be more receptive to rTMS treatment.

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Using biomarkers to predict treatment response in major depressive disorder: evidence from past and present studies

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2014.16.4/mthase ◽

2014 ◽

Vol 16 (4) ◽

pp. 539-544 ◽

Cited By ~ 11

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Treatment Response ◽

Cortical Activation ◽

Variable Response ◽

Major Depressive ◽

Distant Future ◽

Wide Range ◽

Research Findings ◽

Predict Treatment Response

Major depressive disorder (MDD) is a heterogeneous condition with a variable response to a wide range of treatments. Despite intensive efforts, no biomarker has been identified to date that can reliably predict response or non-response to any form of treatment, nor has one been identified that can be used to identify those at high risk of developing treatment-resistant depression (ie, non-response to a sequence of treatments delivered for adequate duration and intensity). This manuscript reviews some past areas of research that have proved informative, such as studies using indexes of hypercortisolism or sleep disturbance, and more recent research findings using measures of inflammation and different indicators of regional cortical activation to predict treatment response. It is concluded that, although no method has yet been demonstrated to be sufficiently accurate to be applied in clinical practice, progress has been made. It thus seems likely that--at some point in the not-too-distant future--it will be possible to prospectively identify, at least for some MDD patients, the likelihood of response or non-response to cognitive therapy or various antidepressant medications.

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