title: Further evidence for plasma progranulin as a biomarker in bipolar disorder.
abstract: BACKGROUND
  A recent study suggested that progranulin (encoded by the fronto-temporal dementia risk gene GRN) plasma levels are decreased in bipolar disorder (BD). Replication of this finding is however lacking.
  
  
  METHODS
  Progranulin plasma levels of bipolar patients (n=104) and healthy controls (n=80) were measured by enzyme-linked immunosorbent assay (ELISA). Participants were also genotyped for three single nucleotide polymorphisms (SNPs) in the GRN gene (rs2879096, rs4792938 and rs5848), and the effect of genetic variation on progranulin levels was examined.
  
  
  RESULTS
  Plasma progranulin levels were decreased in BD (ANCOVA, p=0.001). Furthermore, age was significantly and positively correlated with plasma progranulin (Pearson׳s correlation, r=0.269, p<0.001). Also, lithium treatment but no other medication had a significant effect on progranulin plasma levels (ANCOVA, p=0.007). Specifically in BD, the GRN SNP rs5848 was associated with progranulin plasma levels (Kruskal-Wallis test, p<0.005).
  
  
  CONCLUSIONS
  Subgroup analysis regarding bipolar I vs. bipolar II subtype and polarity of the episode at sampling (manic vs. depressed vs. mixed vs. rapid cycling vs. euthymic) could only be performed with limited validity due to the relatively small sample size. The suitability of peripheral progranulin as a biomarker for BD is limited due to the overlap between patients and controls.
  
  
  CONCLUSIONS
  The findings strengthen the evidence for progranulin being involved in pathomechanisms of bipolar disorder, and suggest a genetic determinant of progranulin concentrations that is relevant specifically in bipolar patients.
authors.affiliation: Bipolar Disorder Program, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Germany. Electronic address: Kittel_S@klinik.uni-wuerzburg.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kittel-Schneider
authors.affiliation: Bipolar Disorder Program, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Weigl
authors.affiliation: Bipolar Disorder Program, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Volkert
authors.affiliation: Bipolar Disorder Program, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Geßner
authors.affiliation: Bipolar Disorder Program, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schmidt
authors.affiliation: Bipolar Disorder Program, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hempel
authors.affiliation: Bipolar Disorder Program, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Kiel
authors.affiliation: Department of Neurology, University of Erlangen, Germany.
authors.forename: David G
authors.initials: DG
authors.lastname: Olmes
authors.affiliation: Neurobiochemistry Laboratory, University Clinic for Child and Adolescent Psychiatry, University of Zurich, Switzerland.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Bartl
authors.affiliation: IZKF Microarray Core Unit, University of Würzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Weber
authors.affiliation: Bipolar Disorder Program, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Kopf
authors.affiliation: Bipolar Disorder Program, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000077153:Progranulins
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D008094:Lithium
keywords: Biomarker; Bipolar disorder; Genetic variants; Inflammation; Neurodegeneration; Progranulin