| 1 | Pharmacogenomics 2011 Feb 12: 171-84 |
|---|---|
| PMID | 21332311 |
| Title | Genome-wide expression profiling of human lymphoblastoid cell lines identifies CHL1 as a putative SSRI antidepressant response biomarker. |
| Abstract | Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressants for treating major depression. However, approximately 30% of patients do not respond sufficiently to first-line antidepressant drug treatment and require alternative therapeutics. Genome-wide studies searching for SSRI response DNA biomarkers or studies of candidate serotonin-related genes so far have given inconclusive or contradictory results. Here, we present an alternative transcriptome-based genome-wide approach for searching antidepressant drug-response biomarkers by using drug-effect phenotypes in human lymphoblastoid cell lines (LCLs). We screened 80 LCLs from healthy adult female individuals for growth inhibition by paroxetine. A total of 14 LCLs with reproducible high and low sensitivities to paroxetine (seven from each phenotypic group) were chosen for genome-wide expression profiling with commercial microarrays. The most notable genome-wide transcriptome difference between LCLs displaying high versus low paroxetine sensitivities was a 6.3-fold lower (p = 0.0000256) basal expression of CHL1, a gene coding for a neuronal cell adhesion protein implicated in correct thalamocortical circuitry, schizophrenia and autism. The microarray findings were confirmed by real-time PCR (36-fold lower CHL1 expression levels in the high paroxetine sensitivity group). Several additional genes implicated in synaptogenesis or in psychiatric disorders, including ARRB1, CCL5, DDX60, DDX60L, ENDOD1, ENPP2, FLT1, GABRA4, GAP43, MCTP2 and SPRY2, also differed by more than 1.5-fold and a p-value of less than 0.005 between the two paroxetine sensitivity groups, as confirmed by real-time PCR experiments. Genome-wide transcriptional profiling of in vitro phenotyped LCLs identified CHL1 and additional genes implicated in synaptogenesis and brain circuitry as putative SSRI response biomarkers. This method might be used as a preliminary tool for searching for potential depression treatment biomarkers. |
| SCZ Keywords | schizophrenia |
| 2 | Neurosci Biobehav Rev 2014 May 42: 93-115 |
| PMID | 24513303 |
| Title | Chemokines and chemokine receptors in mood disorders, schizophrenia, and cognitive impairment: a systematic review of biomarker studies. |
| Abstract | The search for immune biomarkers in psychiatric disorders has primarily focused on pro-inflammatory cytokines. Other immune proteins including chemokines have been relatively neglected in such studies. Recent evidence has implicated chemokines in many neurobiological processes potentially relevant to psychiatric disorders, beyond their classical chemotactic functions. These may include neuromodulator effects, neurotransmitter-like effects, and direct/indirect regulation of neurogenesis. This systematic review presents the existing early evidence which supports an association of many chemokines with the psychiatric disorders: depression, bipolar disorder, schizophrenia, mild cognitive impairment and Alzheimer's disease. The non-specific association of chemokines including CXCL8 (IL-8), CCL2 (MCP-1), CCL3 (MIP-1?) and CCL5 (RANTES) with these disorders across diagnostic categories implies a generalised involvement of many chemokine systemic with psychiatric disease. Additional chemokines with great mechanistic relevance including CXCL12 (SDF-1) and CX3CL1 (fractalkine) have been rarely reported in the existing human literature and should be included in future clinical studies. The potential utility of these proteins as pathologically relevant biomarkers or therapeutic targets should be considered by future clinical and translational research. |
| SCZ Keywords | schizophrenia |