No Evidence for the Association between a Polymorphism in the PCLO Depression Candidate Gene with Memory Bias in Remitted Depressed Patients and Healthy Individuals

Abstract

The PCLO rs2522833 candidate polymorphism for depression has been associated to monoaminergic neurotransmission. In healthy and currently depressed individuals, the polymorphism has been found to affect activation of brain areas during memory processing, but no direct association of PCLO with memory bias was found. We hypothesized that the absence of this association might have been obscured by current depressive symptoms or genetically driven individual differences in reactivity to stressful events. Experiencing stressful childhood events fosters dysfunctional assumptions that are related to cognitive biases, and may modulate the predisposition for depression via epigenetic effects. The association between PCLO and memory bias, as well as interaction between PCLO and childhood events was studied in patients remitted from depression (N = 299), as well as a sample of healthy individuals (N = 157). The participants performed an emotional verbal memory task after a sad mood induction. Childhood trauma and adversity were measured with a questionnaire. The Genotype main effect, and Genotype by Childhood Events interaction were analyzed for memory bias in both samples. PCLO risk allele carrying remitted depressed patients did not show more negatively biased memory than non-risk allele carriers, not even patients with stressful childhood events. A similar pattern of results was found in healthy individuals. Memory bias may not be strongly associated with the PCLO rs2522833 polymorphism. We did not find any support for the PCLO-childhood events interaction, but the power of our study was insufficient to exclude this possibility.

Automatic approach-avoidance tendencies as a candidate intermediate phenotype for depression: Associations with childhood trauma and the 5-HTTLPR transporter polymorphism

“…This study is part of the ‘Info in Genes’ study, which involves a total of 337 remitted depressed patients. In the ‘Info in Genes’ study, the role of cognitive biases and genetic susceptibility to depression is investigated by assessing biased processing in several domains in remitted depressed patients [ 20 , 21 , 22 ]. Included were those who met DSM-IV-TR criteria [ 1 ] for at least one previous Major Depressive episode (primary diagnosis).…”

“…Using an adapted version of the 21-item Life Events Questionnaire, which has good psychometric properties [ 53 ], participants were asked to indicate whether they had experienced a set of concrete life events before the age of 16 years, after the age of 16 and/or within the last year. In line with Vrijsen and colleagues [ 20 , 21 ], a childhood trauma variable was calculated including the following four interpersonal trauma items: physical/verbal aggression within the family, physical/verbal aggression outside the family, sexual abuse within the family and sexual abuse outside the family. This variable was coded ‘1’ when participants had experienced one of these events before the age of 16 years, and ‘0’ if they had not experienced these events before the age of 16.…”

“…Importantly, genetic risk alleles and childhood trauma have been associated with biased processing as an intermediate phenotype for depression [ 11 , 14 , 15 ]. Most intermediate phenotype studies were conducted in healthy / community samples [ 10 , 16 , 17 , 18 , 19 ], and only some focused on clinical samples [ 20 , 21 , 22 ]. These studies typically point out that risk-allele carriers who experienced childhood trauma show most negative and least positive biased information processing.…”

Developmental Stage Epigenetic Modifications and Clinical Symptoms Associated with the Trauma and Stress of Enslavement and Institutionalized Racism

“…However, the picture would also have to include significance evidence of resilience and adaptive survival mechanisms emerging that ameliorated many of the disadvantageous consequences of a sub-optimal environment [84]. The evidence for resilience mechanisms to partially Depressed mood/ sadness, mood swings Van der Does [25] Hasler et al [26] Perkovic et al [27] Alterations in expression of PCLO rs2522833 candidate polymorphisms [28] Histone acetylation, as well as DNA methylation/hydroxymethylation, in the mammalian CNS [29] Leukocyte mRNA levels in glucocorticoid receptor, neurotrophic factors, cell adhesion molecules, SR protein splicing factors, transcription factors, epigenetic factors (histone deacetylase, sirtuin, DNA methyltransferase) suggests use of state and trait markers in combination improves differential diagnoses [30] Alterations in brain derived neurotrophic factor (BDNF) controlled neuroplasticity [31] Lower methylation in glucocorticoid receptor regulator FK506 binding protein S [32] Loss of interest or pleasure Fried et al [ [46] Difficulty concentrating…”