Psychiatric patient stratification using biosignatures based on cerebrospinal fluid protein expression clusters

J Psychiatr Res. 2013 Nov;47(11):1572-80. doi: 10.1016/j.jpsychires.2013.07.021. Epub 2013 Aug 17.


Psychiatric disorders are caused by perturbed molecular pathways that affect brain circuitries. The identification of specific biosignatures that are the result of altered pathway activities in major depression, bipolar disorder and schizophrenia can contribute to a better understanding of disease etiology and aid in the implementation of diagnostic assays. In the present study we identified disease-specific protein biosignatures in cerebrospinal fluid of depressed (n: 36), bipolar (n: 27) and schizophrenic (n: 35) patients using the Reverse Phase Protein Microarray technology. These biosignatures were able to stratify patient groups in an objective manner according to cerebrospinal fluid protein expression patterns. Correct classification rates were over 90%. At the same time several protein sets that play a role in neuronal growth, proliferation and differentiation (NEGR1, NPDC1), neurotransmission (SEZ6) and protection from oxidative damage (GPX3) were able to distinguish diseased from healthy individuals (n: 35) indicating a molecular signature overlap for the different psychiatric phenotypes. Our study is a first step toward implementing a psychiatric patient stratification system based on molecular biosignatures. Protein signatures may eventually be of use as specific and sensitive biomarkers in clinical trials not only for patient diagnostic and subgroup stratification but also to follow treatment response.

Keywords: Biosignatures; Cerebrospinal fluid; Multiplex analysis; Protein clusters; Protein levels; Psychiatric patient group stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / cerebrospinal fluid*
  • Cell Adhesion Molecules, Neuronal / cerebrospinal fluid
  • Cluster Analysis
  • Female
  • GPI-Linked Proteins / cerebrospinal fluid
  • Glutathione Peroxidase / cerebrospinal fluid
  • Humans
  • Male
  • Membrane Proteins / cerebrospinal fluid
  • Mental Disorders / cerebrospinal fluid*
  • Middle Aged
  • Nerve Tissue Proteins / cerebrospinal fluid
  • Protein Array Analysis
  • Young Adult


  • Biomarkers
  • Cell Adhesion Molecules, Neuronal
  • GPI-Linked Proteins
  • Membrane Proteins
  • NEGR1 protein, human
  • NPDC1 protein, human
  • Nerve Tissue Proteins
  • SEZ6L protein, human
  • GPX3 protein, human
  • Glutathione Peroxidase