Presence and acquired origin of reduced recall for fear extinction in PTSD: results of a twin study.

Recall of fear extinction, which is thought to aid in recovery from a psychologically traumatic event, is hypothesized to be deficient in post-traumatic stress disorder (PTSD), but this has not yet been demonstrated in the laboratory, nor has its origin been investigated. To address these two issues, 14 pairs of monozygotic twins discordant for combat exposure, in 7 of which the combat-exposed twin had PTSD, underwent a two-day fear conditioning and extinction procedure. On Day 1, subjects viewed colored light conditioned stimuli, some of which were paired with mild electric shock, followed by extinction of the conditioned responses. On Day 2, recall of Day 1 extinction learning (i.e., extinction retention) was assessed. Skin conductance response (SCR) was the dependent measure. There were no group differences during acquisition or extinction learning. However, a significant PTSD Diagnosis (in the exposed twin) x combat Exposure interaction emerged during extinction recall, with the PTSD combat veterans having larger SCRs than their own co-twins, and than the non-PTSD combat veterans and their co-twins. These results indicate that retention of extinction of conditioned fear is deficient in PTSD. Furthermore, they support the conclusion that this deficit is acquired as a result of combat trauma leading to PTSD, rather than being a predisposing factor to developing PTSD upon the stress of combat.

[1]  Joseph E LeDoux,et al.  Emotional perseveration: an update on prefrontal-amygdala interactions in fear extinction. , 2004, Learning & memory.

[2]  J. Lanzetta,et al.  Facial expressions of emotion as conditioned stimuli for human autonomic responses. , 1980, Journal of personality and social psychology.

[3]  Psychophysiological assessment of posttraumatic stress disorder imagery in World War II and Korean combat veterans. , 1993 .

[4]  Michael Davis,et al.  Applying Learning Principles to the Treatment of Post‐Trauma Reactions , 2003, Annals of the New York Academy of Sciences.

[5]  Joseph E LeDoux,et al.  Extinction Learning in Humans Role of the Amygdala and vmPFC , 2004, Neuron.

[6]  S. Rauch,et al.  Context modulation of memory for fear extinction in humans. , 2005, Psychophysiology.

[7]  D. Charney,et al.  The development of a Clinician-Administered PTSD Scale , 1995, Journal of traumatic stress.

[8]  Test of the conditioning model of neurosis: Differential aversive conditioning of angry and neutral facial expressions in anxiety disorder patients. , 1986 .

[9]  Israel Liberzon,et al.  Corticolimbic blood flow during nontraumatic emotional processing in posttraumatic stress disorder. , 2006, Archives of general psychiatry.

[10]  F. Hu,et al.  Physiologic responses to sudden, loud tones in monozygotic twins discordant for combat exposure: association with posttraumatic stress disorder. , 2003, Archives of general psychiatry.

[11]  S. Rauch,et al.  Recall of Fear Extinction in Humans Activates the Ventromedial Prefrontal Cortex and Hippocampus in Concert , 2007, Biological Psychiatry.

[12]  J. Goldberg,et al.  Reliability and validity of a combat exposure index for vietnam era verterans , 1991 .

[13]  Rachel A. Millstein,et al.  Impaired Stress-Coping and Fear Extinction and Abnormal Corticolimbic Morphology in Serotonin Transporter Knock-Out Mice , 2007, The Journal of Neuroscience.

[14]  R. Bryant,et al.  Extinction Learning Before Trauma and Subsequent Posttraumatic Stress , 2006, Psychosomatic medicine.

[15]  Lisa M. Shin,et al.  Neurocircuitry Models of Posttraumatic Stress Disorder and Extinction: Human Neuroimaging Research—Past, Present, and Future , 2006, Biological Psychiatry.

[16]  Christian Grillon,et al.  Positron emission tomographic imaging of neural correlates of a fear acquisition and extinction paradigm in women with childhood sexual-abuse-related post-traumatic stress disorder , 2004, Psychological Medicine.

[17]  Nikolaus Weiskopf,et al.  Context-Dependent Human Extinction Memory Is Mediated by a Ventromedial Prefrontal and Hippocampal Network , 2006, The Journal of Neuroscience.

[18]  S. Orr,et al.  Effects of beta blockade, PTSD diagnosis, and explicit threat on the extinction and retention of an aversively conditioned response , 2006, Biological Psychology.

[19]  Gershon Ben-Shakhar,et al.  Psychophysiologic assessment of aversive conditioning in posttraumatic stress disorder , 2000, Biological Psychiatry.

[20]  S. Rauch,et al.  An fMRI study of anterior cingulate function in posttraumatic stress disorder , 2001, Biological Psychiatry.

[21]  Rick Richardson,et al.  Effects of D-Cycloserine on Extinction: Translation From Preclinical to Clinical Work , 2006, Biological Psychiatry.

[22]  G. Quirk,et al.  Neuronal signalling of fear memory , 2004, Nature Reviews Neuroscience.

[23]  Bruce Fischl,et al.  Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Darin D Dougherty,et al.  Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. , 2004, Archives of general psychiatry.

[25]  S. Rauch,et al.  Fear conditioning and extinction: influence of sex and menstrual cycle in healthy humans. , 2006, Behavioral neuroscience.

[26]  S. Rauch,et al.  Evidence for Acquired Pregenual Anterior Cingulate Gray Matter Loss from a Twin Study of Combat-Related Posttraumatic Stress Disorder , 2008, Biological Psychiatry.

[27]  Bruce Fischl,et al.  Orbitofrontal thickness, retention of fear extinction, and extraversion , 2005, Neuroreport.

[28]  S. Orr,et al.  De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder. , 2000, Journal of abnormal psychology.

[29]  S. Taylor,et al.  Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery , 2005, Biological Psychiatry.

[30]  I. Liberzon,et al.  Neural Correlates of Traumatic Recall in Posttraumatic Stress Disorder , 2003, Stress.

[31]  Frank H Wilhelm,et al.  Fear conditioning in posttraumatic stress disorder: evidence for delayed extinction of autonomic, experiential, and behavioural responses. , 2007, Behaviour research and therapy.

[32]  J. Davidson,et al.  Clinician‐administered PTSD scale: A review of the first ten years of research , 2001, Depression and anxiety.

[33]  S. Rauch,et al.  Fear extinction in rats: Implications for human brain imaging and anxiety disorders , 2006, Biological Psychology.

[34]  M. Shenton,et al.  Clarifying the Origin of Biological Abnormalities in PTSD Through the Study of Identical Twins Discordant for Combat Exposure , 2006, Annals of the New York Academy of Sciences.