January 2013

Metabolic profile of clinical depression

Fig. 4 from October 2012 Zheng et al Paper in Press in the journal Molecular & Cellular Proteomics: summary of the urinary metabolites involved in disturbance of energy metabolism 

Clinical depression, also known as major depressive disorder, robs its victims of interest and pleasure, sleep, appetite and concentration. Clinically depressed people also suffer from excessive fatigue and dark thoughts. The illness is a major cause of disability, suicide and physical problems. However, a diagnosis for the illness is based on psychiatric reviews, which can be subjective. In a paper in Molecular & Cellular Proteomics, Chinese researchers described a test that could objectively diagnose the illness.

Depression is a complex mental disorder that involves multiple factors. The disease diagnosis is subjective because it can present a number of different symptoms and the exact causes of it are not understood. “Despite overwhelming efforts to identify the biomarkers for MDD, there were still no empirical laboratory tests available to diagnose MDD,” says Peng Xie of Chongqing Medical University, who was the senior author on the MCP paper, adding that the current subjective diagnosis process has a considerable error rate.

The researchers decided to analyze urine, a sample that can be collected easily, for metabolites that could act as markers for depression. By using nuclear magnetic resonance spectroscopy, they were able to identify five molecules in urine that together seemed to sort out people who suffered from depression from those who didn’t. The molecules were malonate, formate, N-methylnicotinamide, m-hydroxyphenylacetate and alanine. Malonate and formate are primarily involved in energy metabolism, m-hydroxyphenylacetate has a role in gut microbial metabolism, and N-methylnicotinamide affects tryptophan-nicotinic acid metabolism. Alanine is one of the 20 amino acids used to make proteins. Xie says, “Based on the previous clinical and basic studies, we suggest that disturbances of these metabolic pathyways are implicated in the development of MDD.”

Xie says the researchers zoomed in on a few metabolites as markers because, in clinical practice, it is not convenient or economically feasible to measure simultaneously a large number of metabolites for diagnosis. The current work is a proof-of-concept and opens up more avenues of investigation. Xie says, for one, the researchers would like to collect urine samples from depression patients and healthy controls from more ethnically diverse populations to validate further the diagnostic performance of the five metabolites. They also would like to dig deeper into the underlying metabolic pathways of these five molecules to see if they can uncover how these biochemical pathways play into the disease.

  1. 1. Zheng, Peng, et al. Mol. Cell. Proteomics doi: 10.1074/mcp.M112.021816

Raj_MukhopadhyayRajendrani Mukhopadhyay (rmukhopadhyay@asbmb.org) is the senior science writer for ASBMB Today and the technical editor for The Journal of Biological Chemistry. Follow her on Twitter (www.twitter.com/rajmukhop), and read her ASBMB Today blog, Wild Types.

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