title: Modulatory effects of the piccolo genotype on emotional memory in health and depression.
abstract: Major depressive disorder (MDD) has been associated with biased memory formation for mood-congruent information, which may be related to altered monoamine levels. The piccolo (PCLO) gene, involved in monoaminergic neurotransmission, has previously been linked to depression in a genome-wide association study. Here, we investigated the role of the PCLO risk allele on functional magnetic resonance imaging (MRI) correlates of emotional memory in a sample of 89 MDD patients (64 PCLO risk allele carriers) and 29 healthy controls (18 PCLO risk allele carriers). During negative word encoding, risk allele carriers showed significant lower activity relative to non-risk allele carriers in the insula, and trend-wise in the anterior cingulate cortex and inferior frontal gyrus. Moreover, depressed risk allele carriers showed significant lower activity relative to non-risk allele carriers in the striatum, an effect which was absent in healthy controls. Finally, amygdalar response during processing new positive words vs. known words was blunted in healthy PCLO+ carriers and in MDD patients irrespective of genotype, which may indicate that signalling of salient novel information does not occur to the same extent in PCLO+ carriers and MDD patients. The PCLO risk allele may increase vulnerability for MDD by modulating local brain function with regard to responsiveness to salient stimuli (i.e. insula) and processing novel negative information. Also, depression-specific effects of PCLO on dorsal striatal activation during negative word encoding and the absence of amygdalar salience signalling for novel positive information further suggest a role of PCLO in symptom maintenance in MDD.
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands. s.woudstra@vumc.nl
authors.forename: Saskia
authors.initials: S
authors.lastname: Woudstra
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: van Tol
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Bochdanovits
authors.forename: Nic J
authors.initials: NJ
authors.lastname: van der Wee
authors.forename: Frans G
authors.initials: FG
authors.lastname: Zitman
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.forename: Esther M
authors.initials: EM
authors.lastname: Opmeer
authors.forename: André
authors.initials: A
authors.lastname: Aleman
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Penninx
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.forename: Witte J
authors.initials: WJ
authors.lastname: Hoogendijk
mesh_terms: D000328:Adult; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D004644:Emotions / Q000187:drug effects; D005260:Female; D020022:Genetic Predisposition to Disease; D006179:Gyrus Cinguli / Q000473:pathology / Q000503:physiopathology; D006262:Health; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D017072:Neostriatum / Q000473:pathology / Q000503:physiopathology; D009479:Neuropeptides / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013647:Task Performance and Analysis
chemical_list: D003598:Cytoskeletal Proteins; D009479:Neuropeptides; D017367:Selective Serotonin Reuptake Inhibitors; C498630:PCLO protein, human