Potential MDD Biomarkers May Lead to Objective Diagnosis


A safe, noninvasive method for early detection of depression could be around the corner.

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What if expert use of biomarkers gleaned from laboratory examinations could catch an MDD diagnosis early? A small study by a team of Chinese researchers provides insight into that possibility.1

Accumulating research has demonstrated a neuroendocrinal basis for MDD that is measurable via salivary cortisol and α-amylase levels and also 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging. The neuroendocrinal axes involved are the hypothalamic-pituitary-adrenocortical (HPA) axis, responsible for cortisol production, and also the sympathetic adrenomedullary (SAM) system, for which salivary α-amylase acts as a biomarker for dysregulation.

In the first published study of its kind, the researchers compared salivary cortisol and α-amylase levels as well as glucose metabolism via 18F-FDG PET imaging of the brain in patients with MDD versus healthy controls.

The study population was recruited from a single center, the Division of PET Center, Department of Nuclear Medicine, Huashan Hospital, Fudan University in Shanghai, China. The stringent recruitment procedures (age 50 to 60 years; no comorbidities; and no use of antidepressants, antibiotics, or other drugs that could affect the SAM system or HPA axis for 4 weeks prior to the screening) resulted in a study analysis population of only 16 subjects: 8 patients with MDD and 8 matched controls.

The combination of salivary cortisol and α-amylase analysis and 18F-FDG PET imaging could potentially be a safe, noninvasive method of early diagnosis of MDD.

Salivary cortisol levels (14.2 ± 1.5 nmol/L vs 6.3 ± 8.8 nmol/L) and salivary α-amylase levels (200.3 ± 14.5 IU/mL vs 114.5 ± 12.4 IU/mL) were significantly higher in patients with MDD than in healthy controls (P < .01 for both measures). In alignment with results reported in previously published studies, 18F-FDG PET imaging demonstrated slower glucose metabolism in the frontal lobe, left superior frontal gyrus, left cingulate gyrus, left rectal gyrus, and right orbital gyrus in patients with MDD compared with healthy controls (P < .05).2

The researchers noted that although findings from each test could be used as a potential biomarker for MDD, regression analysis showed that the combination of salivary cortisol and α-amylase analysis and 18F-FDG PET imaging of glucose metabolism in the superior frontal gyrus and rectal gyrus was a more reliable predictor of an MDD diagnosis than any of the tests done individually (P < .001).

It was argued that the combination of salivary cortisol and α-amylase analysis and 18F-FDG PET imaging could be a safe, noninvasive method of early diagnosis of MDD. The study had a number of limitations, though, primarily its small, single-center size. The researchers also conceded that cortisol measures would be more accurate if tested at 1-hour intervals over a 24-hour period to catch circadian and ultradian fluctuations in cortisol secretion.

Furthermore, they noted that no changes to salivary cortisol or α-amylase levels or glucose metabolism were observed when depressive symptoms were relieved, but details regarding treatment type, length, and follow-up were not provided in the report of the study. In all, this research may spur further investigation of the relationships between glucose metabolism, SAM systems, HPA axis function, and MDD-perhaps leading to new, objective diagnostic methods and new pharmacologic treatments.


1. Wei K, Xue HL, Guan YH, et al. Analysis of glucose metabolism of 18F-FDG in major depression patients using PET imaging: correlation of salivary cortisol and α-amylase. Neurosci Lett. 2016;629:52-57.
2. Hosokawa T, Momose T, Kasai K. Brain glucose metabolism difference between bipolar and unipolar mood disorders in depressed and euthymic states. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:243-250.

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