Symptom persistence and memory performance in posttraumatic stress disorder: a gene x environment pilot stud.

The FKBP5 gene, a glucocorticoid receptor (GR)-regulating co-chaperone of stress proteins, is of special interest because of its role in hypothalamic-pituitary-adrenal (HPA)-axis regulation. However, studies finding a genetic relationship between posttraumatic stress disorder (PTSD) and the FKBP5 gene have failed to distinguish between the development and persistence of PTSD, thereby limiting the prognostic usefulness of such a finding. The present study sought to longitudinally explore this question by examining the association between four single-nucleotide polymorphisms (SNPs) in the FKBP5 gene (rs3800373, rs9470080, rs1360780, and rs9296158), the persistence of PTSD (severity and diagnostic status), and memory performance among twenty-two treatment-seekers diagnosed with acute PTSD. Results showed that the four SNPs significantly interacted with improvement in PTSD symptoms as well as PTSD diagnostic status. Individuals homozygous for the dominant allele and having experienced higher levels of peritraumatic responses subsequently showed more memory dysfunction. The results of this study suggest that SNPs in the FKBP5 gene are associated with symptom persistence and memory dysfunction in acute PTSD.

Neural correlates of recovery from post-traumatic stress disorder: a longitudinal fMRI investigation of memory encoding.

Post-traumatic stress disorder (PTSD) is characterized by a failure of psychological recovery from a traumatic experience. At a neural level, it is associated with abnormalities of the areas of the neural system that process threatening information, including the amygdala and medial-prefrontal cortex, as well as of that involved in episodic memory, including the hippocampus. However, little is known about how the function of these regions may change as one recovers from the disorder. In this investigation, PTSD patients underwent two functional magnetic resonance imaging (fMRI) scans, 6-9 months apart, while viewing fearful and neutral faces in preparation for a memory test (administered outside the scanner). At Time 2, 65% of patients were in remission. Current symptom levels correlated positively with memory-related fMRI activity in the amygdala and ventral-medial prefrontal cortex (vmPFC). In addition, the change in activity within the hippocampus and the subgenual anterior cingulate cortex (sgACC) was associated with the degree of symptom improvement (n=18). These results suggest differential involvement of structures within the fear network in symptom manifestation and in recovery from PTSD: whereas activity within the amygdala and vmPFC appeared to be a marker of current symptom severity, functional changes in the hippocampus and sgACC reflected recovery. These results underscore the importance of longitudinal investigations for the identification of the differential neural structures associated with the expression and remission of anxiety disorders.

Consistency of retrospective reports of peritraumatic responses and their relation to PTSD diagnostic status.

Few studies have examined whether trauma-exposed individuals are consistent in their retrospective reports of how they reacted at the time of trauma exposure, and whether this phenomenon has any implications at the diagnostic level. In a series of three longitudinal studies (N = 113) with different timeframes, the authors prospectively investigated the consistency of peritraumatic response scores as a function of posttraumatic stress disorder (PTSD) diagnostic status. Across the three studies, consistency of scores was better among individuals who either did not develop PTSD or who remitted from it than among those whose PTSD did not remit. These results are consistent with the literature suggesting that compromised memory processes are related to sustained PTSD.

An fMRI investigation of memory encoding in PTSD: influence of symptom severity.

Previous studies have shown memory deficits in Post-Traumatic Stress Disorder (PTSD) patients, as well as abnormal patterns of brain activity, especially when retrieving trauma-related information. This study extended previous findings by investigating the neural correlates of successful memory encoding of trauma-unrelated stimuli and their relationship with PTSD symptom severity. We used the subsequent memory paradigm, in the context of event-related functional magnetic resonance imaging, in 27 PTSD patients to identify the brain regions involved in the encoding of fearful and neutral faces. Symptom severity was assessed by the Clinically Administered PTSD Scale (CAPS) scores. It was found that memory performance was negatively correlated with CAPS scores. Furthermore, a negative correlation was observed between CAPS scores and ventral medial prefrontal cortex (vmPFC) activity elicited by the subsequently forgotten faces. Finally, symptom severity predicted the contribution of the amygdala to the successful encoding of fearful faces. These results confirm the roles of the vmPFC and the amygdala in PTSD and highlight the importance of taking into account individual differences when assessing the behavioural and neural correlates of the disorder.

Cognitive estimation impairment in Alzheimer disease and mild cognitive impairment.

Intact executive functioning is believed to be required for performance on tasks requiring cognitive estimations. This study used a revised version of a cognitive estimations test (CET) to investigate whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with normal elderly controls (NECs). Neuropsychological tests were administered to determine the relationship between CET performance and other cognitive domains. AD patients displayed impaired CET performance when compared with NECs but MCI patients did not. Negative correlations between tests of working memory (WM) and semantic memory and the CET were found in NECs and AD patients, indicating that these cognitive domains were important for CET performance. Regression analysis suggests that AD patients were unable to maintain semantic information in WM to perform the task. The authors conclude that AD patients display deficits in working memory, semantic memory, and executive function, which are required for adequate CET performance.