PKCα is genetically linked to memory capacity in healthy subjects and to risk for posttraumatic stress disorder in genocide survivors

Strong memory of a traumatic event is thought to contribute to the development and symptoms of posttraumatic stress disorder (PTSD). Therefore, a genetic predisposition to build strong memories could lead to increased risk for PTSD after a traumatic event. Here we show that genetic variability of the gene encoding PKCα (PRKCA) was associated with memory capacity—including aversive memory—in nontraumatized subjects of European descent. This finding was replicated in an independent sample of nontraumatized subjects, who additionally underwent functional magnetic resonance imaging (fMRI). fMRI analysis revealed PRKCA genotype-dependent brain activation differences during successful encoding of aversive information. Further, the identified genetic variant was also related to traumatic memory and to the risk for PTSD in heavily traumatized survivors of the Rwandan genocide. Our results indicate a role for PKCα in memory and suggest a genetic link between memory and the risk for PTSD.

[1]  J. Sweatt,et al.  A role for the beta isoform of protein kinase C in fear conditioning. , 2000, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  Edna B. Foa,et al.  The Validation of a Self-Report Measure of Posttraumatic Stress Disorder , 1997 .

[3]  P. Lang,et al.  International Affective Picture System (IAPS): Instruction Manual and Affective Ratings (Tech. Rep. No. A-4) , 1999 .

[4]  T. Michael,et al.  Enhanced priming for trauma-related material in posttraumatic stress disorder. , 2005, Emotion.

[5]  Maureen Ritchey,et al.  fMRI studies of successful emotional memory encoding: A quantitative meta-analysis , 2010, Neuropsychologia.

[6]  Dick J Veltman,et al.  Increased anterior cingulate cortex and hippocampus activation in Complex PTSD during encoding of negative words. , 2013, Social cognitive and affective neuroscience.

[7]  T. Elbert,et al.  Burnt into memory. , 2002, Nature.

[8]  J. D. McGaugh.  Memory consolidation and the amygdala: a systems perspective , 2002, Trends in Neurosciences.

[9]  K. Roeder,et al.  Genomic Control for Association Studies , 1999, Biometrics.

[10]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[11]  R. Hu.  Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) , 2003 .

[12]  A. Gevins,et al.  Spatiotemporal dynamics of component processes in human working memory. , 1993, Electroencephalography and clinical neurophysiology.

[13]  Lars-Göran Öst,et al.  Attentional and memory bias for emotional information in crime victims with acute posttraumatic stress disorder (PTSD). , 2002, Journal of anxiety disorders.

[14]  G. Liao,et al.  Evidence for direct protein kinase-C mediated modulation of N-methyl-D-aspartate receptor current. , 2001, Molecular pharmacology.

[15]  P. Brennan,et al.  Protein kinase Cα mediates a novel form of plasticity in the accessory olfactory bulb , 2009, Neuroscience.

[16]  S. Southwick,et al.  Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. , 1999, The American journal of psychiatry.

[17]  Thomas Elbert,et al.  A deletion variant of the α2b-adrenoceptor is related to emotional memory in Europeans and Africans , 2007, Nature Neuroscience.

[18]  J. Grafman,et al.  Focal brain damage protects against post-traumatic stress disorder in combat veterans , 2008, Nature Neuroscience.

[19]  L. Covi,et al.  The Hopkins Symptom Checklist (HSCL): a self-report symptom inventory. , 1974, Behavioral science.

[20]  Joseph E LeDoux,et al.  Molecular Mechanisms Underlying Emotional Learning and Memory in the Lateral Amygdala , 2004, Neuron.

[21]  A. Anderson,et al.  Genetic differences in emotionally enhanced memory , 2011, Neuropsychologia.

[22]  T. Elbert,et al.  Psychological trauma: Burnt into memory , 2002, Nature.

[23]  R. Yehuda.  POST-TRAUMATIC STRESS DISORDER , 1985, The Lancet.

[24]  D. Reich,et al.  Principal components analysis corrects for stratification in genome-wide association studies , 2006, Nature Genetics.

[25]  T. Elbert,et al.  The Nakivale Camp Mental Health Project: building local competency for psychological assistance to traumatised refugees , 2004 .

[26]  J. D. McGaugh.  Memory--a century of consolidation. , 2000, Science.

[27]  T. Elbert,et al.  Treatment of posttraumatic stress disorder by trained lay counselors in an African refugee settlement: a randomized controlled trial. , 2008, Journal of consulting and clinical psychology.

[28]  Joseph E LeDoux,et al.  Contributions of the Amygdala to Emotion Processing: From Animal Models to Human Behavior , 2005, Neuron.

[29]  T. Dalgleish,et al.  Memory bias for emotional information in children and adolescents with posttraumatic stress disorder: a preliminary study. , 2000, Journal of anxiety disorders.

[30]  T. Elbert,et al.  Association study of trauma load and SLC6A4 promoter polymorphism in posttraumatic stress disorder: evidence from survivors of the Rwandan genocide. , 2010, The Journal of clinical psychiatry.

[31]  S. Southwick,et al.  Neural correlates of declarative memory for emotionally valenced words in women with posttraumatic stress disorder related to early childhood sexual abuse , 2003, Biological Psychiatry.

[32]  J L Lancaster,et al.  Automated Talairach Atlas labels for functional brain mapping , 2000, Human brain mapping.

[33]  P. Boesiger,et al.  SENSE: Sensitivity encoding for fast MRI , 1999, Magnetic resonance in medicine.

[34]  R. Pitman,et al.  Post-traumatic stress disorder, hormones, and memory , 1989, Biological Psychiatry.

[35]  Stephan Kolassa,et al.  The Risk of Posttraumatic Stress Disorder After Trauma Depends on Traumatic Load and the Catechol-O-Methyltransferase Val158Met Polymorphism , 2010, Biological Psychiatry.

[36]  Chris R Brewin,et al.  Psychological theories of posttraumatic stress disorder. , 2003, Clinical psychology review.

[37]  Thomas Elbert,et al.  Psychological trauma and evidence for enhanced vulnerability for posttraumatic stress disorder through previous trauma among West Nile refugees , 2004, BMC psychiatry.

[38]  Edwin J. Weeber,et al.  A Role for the β Isoform of Protein Kinase C in Fear Conditioning , 2000, The Journal of Neuroscience.

[39]  C. Ranganath.  A unified framework for the functional organization of the medial temporal lobes and the phenomenology of episodic memory , 2010, Hippocampus.