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Posttraumatic stress disorder (PTSD) is accompanied by marked alterations in cognition and behavior, particularly when negative, high-value information is present (Aupperle, Melrose, Stein, & Paulus, 2012; Hayes, Vanelzakker, & Shin, 2012) . However, the underlying processes are unclear; such alterations could result from differences in how this high value information is updated or in its effects on processing future information. To untangle the effects of different aspects of behavior, we used a computational psychiatry approach to disambiguate the roles of increased learning from previously surprising outcomes (i.e. associability; Li, Schiller, Schoenbaum, Phelps, & Daw, 2011) and from large value differences (i.e. prediction error; Montague, 1996; Schultz, Dayan, & Montague, 1997) in PTSD. Combat-deployed military veterans with varying levels of PTSD symptoms completed a learning task while undergoing fMRI; behavioral choices and neural activation were modeled using reinforcement learning. We found that associability-based loss learning at a neural and behavioral level increased with PTSD severity, particularly with hyperarousal symptoms, and that the interaction of PTSD severity and neural markers of associability based learning predicted behavior. In contrast, PTSD severity did not modulate prediction error neural signal or behavioral learning rate. These results suggest that increased associability-based learning underlies neurobehavioral alterations in PTSD. / Master of Science

The present study aimed to investigate sleep disturbances and negative emotions as predictors of posttraumatic stress disorder (PTSD) symptom trajectories in a publicly available longitudinal dataset of patients (N = 1127; mean age = 36.53; SD = 13.29; 65.5% women) who presented to a U.S. emergency department (ED) in the early aftermath of a trauma exposure. Latent growth curve models were fitted iteratively to characterize PTSD symptom trajectories over 1-year. Models then examined the simultaneous influence of sleep disturbances (i.e., insomnia symptoms, nightmares, and sleep duration) and negative emotions (i.e., feelings of anxiety and depression) on PTSD symptom trajectories, as well as whether negative emotions mediate the link between sleep disturbances and PTSD symptom trajectories. Results indicated that (a) PTSD symptom trajectories reflected a quadratic trend across time, although there was variability between individuals, (b) both sleep disturbances and negative emotions were uniquely associated with PTSD symptom trajectories, and (c) negative emotions partially explained associations between sleep disturbances and PTSD symptom trajectories. The results from this study can potentially aid detection of modifiable risk factors during the early course of PTSD and inform cognitive-behavioral intervention efforts.

This study began testing the Sewell and Williams (in press) model that differing trauma types yield differing presentations in social versus event processing domains. Other hypotheses explored trauma type with levels of guilt, and shame-proneness with anxiety. Volunteers were 44 male combat veterans being treated for PTSD. Data analyses determined whether trauma type related to guilt and perceived social support and whether shame-proneness related to levels of anxiety. High shame persons may process anxiety and social support differently than low shame persons. Results can assist professionals understand how a person's functioning is affected by certain types of trauma. Future research should focus on increasing social support for persons who have experienced trauma.

This study examined police officers' perceptions of self, occupational role and their relation to perceived stress and posttraumatic stress symptomology. Self-report measures for the study variables were completed by 101 police officers. Hypotheses predicted that perception of self and role would be associated with perception of stress and that perception of the stress would mediate PTSD symptomology. Neuroticism, job quality and general job satisfaction were the main predictors of stress. Stress levels mediated between 1) job quality and the symptoms of anxious arousal and impaired self-reference; 2) general job satisfaction and the symptoms of defensive avoidance and dissociation; and 3) neuroticism and the symptom of defensive avoidance. This implies that police officers' job quality, their feelings of general job satisfaction, and low levels of neuroticism are important in alleviating stress and subsequent psychological sequela.

Three recent studies attempted to substantiate Sewell and Cromwell's (1990) theory of Posttraumatic Stress Disorder (PTSD; American Psychiatric Association, 1994) based on personal construct theory (Kelly, 1955). One crucial aspect of the model that was tested in each of the studies is "elaboration," which is the process of bringing more of a person's repertoire of understanding (constructions) to a certain experience to give it meaning. Elaboration is representative of whether or not the individual is using an integrated set of constructs to deal with a traumatic event. A two-part study (1) reanalyzed existing data to assist in understanding discrepancies in past findings, and (2) content analyzed constructs given by subjects in all three studies. Findings concerning elaboration remained somewhat discrepant but suggested possible differences when investigating the emergent versus submerged poles of constructs.

This study examined the relation between level of rape acknowledgement and levels of PTSD symptoms reported in female college students. Subjects were administered the Sexual Experiences Survey (SES), the PTSD Interview, and a demographics questionnaire. Subjects were then grouped into the following categories based on their responses to the SES: reported rape victims, acknowledged rape victims, unacknowledged rape victims, and a control group of non-rape subjects. Small sample analyses did not reveal the expected linear relation between the two variables. Only the acknowledged group showed greater PTSD symptoms. The unacknowledged and control groups did not significantly differ on overall PTSD symptom severity, or on any cluster of PTSD symptoms. Naturalistic selection factors are discussed that could have affected the outcome of the study.

Measurement is the foundation of epidemiologic thought and practice. The appropriate measurement of exposures and outcomes of interest is the underlying assumption to all causal investigations. Poor quality measurement, be it through inappropriate data collection methods or changing diagnostic criteria, which can result in erroneous estimates, has a deleterious impact on scientists, policy makers, and the public. Mental health disorders particularly suffer from a lack of diagnostic clarity as diagnosis is often based on self-report of overlapping symptoms with no clear measureable biomarkers. The release of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) in May of 2013 is the most recent attempt to codify existing diagnostic criteria for psychiatric disorders. Posttraumatic stress disorder (PTSD) diagnostic criteria shifted from a three-cluster approach of avoidance, hyper-arousal, and re- experiencing to a four-cluster approach of avoidance, arousal, negative cognitions and mood, and re- experiencing. The very existence of multiple diagnostic frameworks for the same psychiatric disorder is proof that accurate diagnosis is a complex and unresolved issue that warrants investigation. This complexity in posttraumatic stress disorder (PTSD) symptom presentation, limits our ability to develop appropriate responses. In this dissertation I conducted four independent but related studies to explore the construct validity of PTSD. In Chapter 1 I systematically reviewed the extant empiric literature from PubMed and PsychINFO on PTSD symptom structure to identify a universal PTSD factor structure. I found 40 (3%) of 1,302 citations published between 1980-2014 provided empiric PTSD factor structure estimates forming the basis of my review. While consensus exists with respect to the general multifactorial make-up of PTSD, a universal understanding of the specific operationalization of this structure, supported by the empiric literature, is absent. In Chapter 2, I used population-based, cross-sectional data from adult survivors of the 2010 earthquake in Haiti, to assesses model fit of six theoretical factor structures of PTSD: one-factor Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV; three-factor DSM-IV-TR (arousal, avoidance, and intrusion); three-main factor (arousal, avoidance, and intrusion) and one-hierarchical factor DSM-IV-TR; four-factor King 1998 (avoidance, hypervigilance, emotional numbing, re-experiencing); four-factor Simms 2002 (avoidance, dysphoria, hyperarousal, intrusion); and four-factor DSM-5 (arousal, avoidance, intrusion, negative mood and cognition) models through confirmatory factor analyses (CFA). While all models adequately fit the data, the three-factor DSM-IV-TR (arousal, avoidance, and intrusion) model best fit the sample (χ2=593.257, 116 degrees of freedom; RMSEA=0.056; CFI=0.927; TLI=0.915, WRMR=1.769; AIC=24,760.459; and BIC=24,952.178). Again drawing on the cross-sectional, population data from Haitian earthquake survivors, in Chapter 3 I used multiple linear regressions to model pre-, peri-, and post-earthquake factor associations with mean PTSD symptom cluster (arousal, intrusion, and avoidance, validated in Chapter 2) endorsement. I found that mean PTSD symptom factor endorsement is heterogeneously associated with pre-, peri-, and post- earthquake factors, consistent with dimensional theoretical foundations: arousal endorsement more likely to be associated with pre-earthquake factors, intrusion endorsement more likely to be associated with factors across the temporal field, and avoidance endorsement more likely to be associated with post- earthquake factors. In Chapter 4, I used exploratory factor analysis (EFA) to assess the factor stability of the DSM-IV-TR (arousal, intrusion, avoidance) defined PTSD structure when major depressive disorder (MDD) items are introduced, in the same Haitian post-earthquake population-based study. A six-factor, 25-item model was estimated and fit the data (χ2=253.427, 165 degrees of freedom, p<0.001; RMSEA=0.021, 90% CI:0.016, 0.026; CFI=0.987; TLI=0.976) better than the PTSD-only model specified in Chapter 2. PTSD-specific items did not load on the original PTSD factors or with the original factor items (new factors included items from 0-3 different original PTSD factors), in the presence of MDD items. PTSD dimensionality was not stable in the presence of MDD items, thus challenging the discriminant validity of PTSD. This exploration into PTSD construct validity found that while consensus exists with respect to the general multifactorial make-up of PTSD, a universal understanding of the specific operationalization of this structure, supported by the empiric literature, is absent. The tight range in model fit statistics documented in the CFA provides additional evidence of this, suggesting that empirical-based model selection is insufficient to universally characterize PTSD. Given the overall consensus of general factors, the significant and heterogeneous pre-, peri-, and post-earthquake factor associations with the unique PTSD symptom clusters provides additional evidence of the multidimensional theoretical mechanisms behind PTSD psychopathology. PTSD model stability, an indication of discriminant validity, failed to hold when challenged by MDD items, further challenging PTSD construct validity. There are several important implications of this work. First, based on the systematic review and CFA findings, adjudication of PTSD model selection based on empiric findings is insufficient and should be theoretically driven. Future investigations should always include the most commonly supported models as they develop and refine additional models, thus enabling rigorous cross-context, cross-potentially traumatic event, and cross-study comparisons that are currently not possible. Second, the multidimensional modeling of PTSD factors provided valuable insight into the psychopathology of PTSD without additional data collection burden and should be widely adopted. Researchers should look to model PTSD both as a dichotomous variable and on a continuous scale, both as a complete construct and by each dimensional component. Third, while the exploration into discriminant validity builds on another study that found PTSD factor structure unstable in the presence of MDD item challenges, more research is needed here to understand the theoretic and empiric utility of the specified six-factor model across settings and diagnostic criteria. Fourth, while endeavoring to explore construct validity, exploratory qualitative methods with populations beyond the highly studied U.S. military populations are needed to propose additional items that could, provide valuable missing empiric evidence for PTSD factor dimensionality.

Posttraumatic Stress Disorder (PTSD) is a psychiatric condition that can develop following exposure to a traumatic event involving actual or threatened death or serious injury. Responses include intense fear, helplessness or horror. Symptoms are characterised into clusters, described as re-experiencing, avoidance, and arousal. These symptoms, which are also evident in other conditions, have been associated with dysfunctions in the central acetylcholinergic system. Benefits from administering acetylcholinesterase inhibitors (AChEI) to people suffering these symptoms have been demonstrated. Donepezil hydrochloride, a reversible inhibitor of the enzyme acetylcholinesterase, is used in the treatment of conditions with difficulties in cognitive function, but has not been used in PTSD. The aim of this thesis was to determine (1) whether there was a difference in the ACh system in people with PTSD and (2) whether administration of an AChEI would change the symtomatology. IDEX (I¹ ² ³ iododexetimide) has been useful in imaging muscarinic-ACh receptors using Single Photon Emission Computerised Tomography (SPECT) and was utilised to investigate whether cholinergic activity in PTSD is altered. One hundred and sixty eight potential subjects were screened and eleven PTSD subjects were enrolled in the IDEX SPECT study. Three healthy non-PTSD control subjects also completed the study. Due to technical complications only the data obtained from eight PTSD and two control subjects was available for analysis. Imaging data for 2 further healthy non-PTSD control subjects were obtained from another study. Sixteen subjects were enrolled in the donepezil open label study (assessed at baseline, Week 2, 6 and 10). Nine PTSD subjects completed the 10-week trial and seven withdrew prematurely (at or after Week 2) due to side effects or a worsening of PTSD symptoms. For the IDEX SPECT study, a voxel-by-voxel statistical analysis of the PTSD subject group versus the control group showed both areas of reduced and increased IDEX uptake. Significant clusters in the PTSD group with a reduced IDEX uptake centred around the bilateral hippocampus, left insula and right precuneus, while increased IDEX uptake appeared in the caudate head. For the donepezil study, in the per-protocol analysis (including only the 9 subjects that completed the protocol), all psychological assessments revealed a difference between the totals obtained at the Week 10 visit compared to those at the Baseline visit and the improvement was in the order of 51%. The intention-to-treat analysis (including all 16 subjects), a repeated measures Analysis of Variance (ANOVA) with a mixed models approach showed that all psychological measures demonstrated statistically significant benefits of the treatment. All subjects who completed the protocol recounted considerable improvement in their overall PTSD symptom profile, which covered symptoms in each of the three clusters. The results of the IDEX SPECT study suggest that alterations in ACh binding in PTSD are evident and may begin to explain a part of the altered cognitive symptomatology apparent in this condition. The pilot open label donepezil trial provided some preliminary evidence that treatment with an AChEI can lessen the intrusions and distress associated with traumatic memories in people with PTSD. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1374974 / Thesis (M.Med.Sc.) -- University of Adelaide, School of Medicine, 2009

Posttraumatic Stress Disorder (PTSD) is a psychiatric condition that can develop following exposure to a traumatic event involving actual or threatened death or serious injury. Responses include intense fear, helplessness or horror. Symptoms are characterised into clusters, described as re-experiencing, avoidance, and arousal. These symptoms, which are also evident in other conditions, have been associated with dysfunctions in the central acetylcholinergic system. Benefits from administering acetylcholinesterase inhibitors (AChEI) to people suffering these symptoms have been demonstrated. Donepezil hydrochloride, a reversible inhibitor of the enzyme acetylcholinesterase, is used in the treatment of conditions with difficulties in cognitive function, but has not been used in PTSD. The aim of this thesis was to determine (1) whether there was a difference in the ACh system in people with PTSD and (2) whether administration of an AChEI would change the symtomatology. IDEX (I¹ ² ³ iododexetimide) has been useful in imaging muscarinic-ACh receptors using Single Photon Emission Computerised Tomography (SPECT) and was utilised to investigate whether cholinergic activity in PTSD is altered. One hundred and sixty eight potential subjects were screened and eleven PTSD subjects were enrolled in the IDEX SPECT study. Three healthy non-PTSD control subjects also completed the study. Due to technical complications only the data obtained from eight PTSD and two control subjects was available for analysis. Imaging data for 2 further healthy non-PTSD control subjects were obtained from another study. Sixteen subjects were enrolled in the donepezil open label study (assessed at baseline, Week 2, 6 and 10). Nine PTSD subjects completed the 10-week trial and seven withdrew prematurely (at or after Week 2) due to side effects or a worsening of PTSD symptoms. For the IDEX SPECT study, a voxel-by-voxel statistical analysis of the PTSD subject group versus the control group showed both areas of reduced and increased IDEX uptake. Significant clusters in the PTSD group with a reduced IDEX uptake centred around the bilateral hippocampus, left insula and right precuneus, while increased IDEX uptake appeared in the caudate head. For the donepezil study, in the per-protocol analysis (including only the 9 subjects that completed the protocol), all psychological assessments revealed a difference between the totals obtained at the Week 10 visit compared to those at the Baseline visit and the improvement was in the order of 51%. The intention-to-treat analysis (including all 16 subjects), a repeated measures Analysis of Variance (ANOVA) with a mixed models approach showed that all psychological measures demonstrated statistically significant benefits of the treatment. All subjects who completed the protocol recounted considerable improvement in their overall PTSD symptom profile, which covered symptoms in each of the three clusters. The results of the IDEX SPECT study suggest that alterations in ACh binding in PTSD are evident and may begin to explain a part of the altered cognitive symptomatology apparent in this condition. The pilot open label donepezil trial provided some preliminary evidence that treatment with an AChEI can lessen the intrusions and distress associated with traumatic memories in people with PTSD. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1374974 / Thesis (M.Med.Sc.) -- University of Adelaide, School of Medicine, 2009