Journal of Traumatic Stress April 2015, 28, 102–109

The Neurocognitive Performance of Female Veterans With Posttraumatic Stress Disorder Nikki H. Stricker,1,2 Jenna E. Keller,3,4 Diane T. Castillo,4,5,6 and Kathleen Y. Haaland5,6,7 1

Psychology Service, VA Boston Healthcare System, Boston, Massachusetts, USA Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, USA 3 Biomedical Research Institute of New Mexico, Albuquerque, New Mexico, USA 4 Psychology Service, New Mexico VA Healthcare System, Albuquerque, New Mexico, USA 5 Research Service, New Mexico VA Healthcare System, Albuquerque, New Mexico, USA 6 Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA 7 Department of Neurology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA 2

Neurocognitive problems are common with posttraumatic stress disorder (PTSD) and are important to understand because of their association with the success of PTSD treatment and its potential neural correlates. To our knowledge, this is the first neurocognitive study in an all-female U.S. veteran sample, some of whom had PTSD. We examined neurocognitive performance and assessed whether learning deficits, common in PTSD, were associated with executive functioning. Veterans with PTSD (n = 56) and without (n = 53) were evaluated for psychiatric and neurocognitive status. The PTSD group had a lower estimated IQ (d = 0.53) and performed more poorly on all neurocognitive domains (d range = 0.57–0.88), except verbal retention (d = 0.04). A subset of the 2 groups that were matched on IQ and demographics similarly demonstrated poorer performance for the PTSD group on all neurocognitive domains (d range = 0.52–0.79), except verbal retention (d = 0.15). Within the PTSD group, executive functioning accounted for significant variance in verbal learning over and above IQ and processing speed (R2 = .06), as well as depression (R2 = .07) and PTSD severity (R2 = .06). This study demonstrated that female veterans with PTSD performed more poorly than females without PTSD on several neurocognitive domains, including verbal learning, processing speed, and executive functioning. Replication of these results using a control group of veterans with more similar trauma exposure, history of mild traumatic brain injury, and psychiatric comorbidities would solidify these findings.

Posttraumatic stress disorder (PTSD) is a health crisis in U.S. veterans due to recent military conflicts. Beyond the psychological symptoms of the disorder, neurocognitive symptoms are common. Neurocognitive problems in PTSD (Dolan et al., 2012; Vasterling & Brailey, 2005) have been attributed to neurobiological changes associated with the trauma (Southwick

et al., 2010), pretrauma vulnerabilities (Gilbertson et al., 2006), or both. Regardless of etiology, neuropsychological characteristics are important as poorer neurocognitive performance has been associated with worse PTSD treatment outcome (Wild & Gur, 2008) and may have neurobiological implications such as decreased volume of brain regions (Karl et al., 2006) or differential brain activation (Anderson et al., 2004). Although the neurocognitive characteristics of PTSD have been studied in men and women, most have relied on male veterans with combat trauma or female nonveterans with sexual trauma (e.g., see Brewin, Kleiner, Vasterling, & Field, 2007). The focus on men is emphasized by a meta-analysis of 27 memory studies in PTSD (Brewin et al., 2007) of which only three examined women alone and none studied female veterans alone. In contrast, the 12 studies that examined only men included 10 that assessed only male veterans. These statistics reflect the dearth of neurocognitive studies in female veterans with PTSD. This is a significant gap because females have a higher (10% vs. 5%) lifetime prevalence of PTSD than males (Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995) though these differences may disappear in veterans, which has been attributed to increased

Portions of this manuscript were previously featured in a paper entitled “Neuropsychological Deficits in Female Veterans with PTSD: Preliminary Findings” presented at the 26 Annual Meeting of the International Society for Traumatic Stress Studies, Montreal, Quebec, Canada, November 4–6, 2010. This study was supported by the Department of Defense (Grant #PT074309, Award Number W81XWH-08-2-0022 to DC), Department of Veterans Affairs Research Career Scientist Award (KYH), a grant from the Research Service at the NMVAHCS (KYH), and Department of Veterans Affairs VISN 1 Career Development Award–Mentored (NHS). Correspondence concerning this article should be addressed to Kathleen Y. Haaland, Psychiatry & Behavioral Sciences, University of New Mexico School of Medicine, Family Practice and Psychiatry & Behavioral Sciences Building, 2230 Tucker Ave. NE, Albuquerque, New Mexico 87131. E-mail: [email protected] Published 2015. This article is a U.S. Government work and is in the public domain in the USA. View this article online at wileyonlinelibrary.com DOI: 10.1002/jts.22000

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PTSD incidence in veteran males associated with greater combat exposure than civilian males (Zinzow, Grubaugh, Monnier, Suffoletta-Maierle, & Frueh, 2007). Female veterans have different trauma histories with greater sexual trauma (27%–49%) than male veterans (7%) and greater than 50% with premilitary physical or sexual abuse (Zinzow et al., 2007). Childhood trauma has emotional (Bremner, Southwick, Johnson, Yehuda, & Charney, 1993), neurocognitive (Bremner, Vermetten, Afzal, & Vythilingam, 2004), and neuroanatomical (Corbo et al., 2014) sequelae in adults. Therefore, the high incidence of childhood sexual trauma in female veterans may be associated with greater neurocognitive weaknesses in female than male veterans with PTSD. Neurobiological differences between men and women could also lead to different patterns of neurocognitive performance (Andreano & Cahill, 2009), though the small number of neurocognitive studies in female nonveterans with PTSD related to sexual assault have identified problems similar to men (Jenkins, Langlais, Delis, & Cohen, 2000; Stein, Kennedy, & Twamley, 2002). These issues along with the expected future increases in PTSD in female veterans (Street, Vogt, & Dutra, 2009) suggest there is a vital need to examine their neurocognitive performance. The pattern of neurocognitive performance in individuals with PTSD includes weaknesses in processing speed/sustained attention, memory, and executive functions relative to control samples (Aupperle, Melrose, Stein, & Paulus, 2012; Dolan et al., 2012), with emphasis on executive functioning, including specific weaknesses in response inhibition (Leskin & White, 2007; Shucard, McCabe, & Szymanski, 2008; Swick, Honzel, Larsen, Ashley, & Justus, 2012), set switching (Gilbertson et al., 2006; Leskin & White, 2007; Stein et al., 2002), and working memory (Jenkins et al., 2000; Vasterling et al., 2002). Veterans with PTSD have shown poorer sustained attention and working memory relative to control participants, but no differences on selective attention or shifting set (Vasterling, Brailey, Constans, & Sutker, 1998). Poorer performance on measures of verbal learning and memory has consistently been reported in individuals with PTSD relative to control samples, and is presumed to be associated with executive functioning (Brewin et al., 2007; Vasterling et al., 1998, 2002). The finding that poor encoding of new information is prominent in PTSD, with little evidence of rapid forgetting (Brewin et al., 2007; Vasterling et al., 2002), supports a possible association between poorer verbal memory and poorer executive functioning. It is a common clinical assumption that verbal learning and memory are related to executive functions, and studies have demonstrated this relationship in patients referred to medical center neuropsychology clinics (Hill, Alosco, Bauer, & Tremont, 2012; Tremont, Halpert, Javorsky, & Stern, 2000). Other studies have not supported this relationship in a healthy adolescent sample (Beebe, Ris, & Dietrich, 2000) and a sample of active duty military personnel and veterans with a history of traumatic brain injury (TBI; Busch, McBride, Curtiss, & Vanderploeg, 2005). No study, to our knowledge, has examined this relationship in PTSD; because it is common to

attribute memory impairment in PTSD to executive dysfunction (Vasterling et al., 1998, 2002), this is an important association to test. The hypotheses of this study were (a) the pattern of neurocognitive weaknesses associated with PTSD in an all-veteran group of women would be similar to previous studies in male veterans with PTSD that show lower, but still normal general intelligence and poorer performance in all neurocognitive domains except verbal retention (Aupperle et al., 2012; Dolan et al., 2012); and (b) variance in memory and learning would be associated with executive functions in the PTSD and control groups. Method Participants and Procedure The PTSD group (n = 56) included female veterans who served during the Iraq and Afghanistan conflicts and were enrolled in a psychotherapy study. Exclusions from this group included lifetime or current bipolar or psychotic disorder (n = 1), selfreported learning disability (n = 6), scored below 45 on Trial 1 of the Test of Memory and Malingering (Hilsabeck, Gordon, Hietpas-Wilson, & Zartman, 2011; Tombaugh, 1997; n = 1) or neurologic diagnoses (n = 0), except for mild traumatic brain injury (mTBI; n = 32). Sexual trauma alone or in combination with combat trauma was the most common trauma type (n = 46); participants reported sexual trauma only (n = 17), combat trauma only (n = 10), or combat and sexual trauma (n = 29). Of those reporting sexual trauma, 14 reported both childhood and adult trauma, and 32 reported adult-only trauma. Other traumas included transportation accidents (n = 47), the death of someone close (n = 28), physical assault (n = 45), natural disaster (n = 30), serious accident or injury (n = 19), weapon assault (n = 24), and fire/explosion (n = 26). In the PTSD group, 25 participants were on no psychotropic medications, 31 were on psychotropics, primarily antidepressants (selective serotonin reuptake inhibitors, n = 24, and/or other types, n = 8), but also prazosin (n = 10), benzodiazepines (n = 8), hypnotics (n = 6), atypical antipsychotics (n = 4), or mood stabilizers (n = 2). We found no neurocognitive differences between individuals with PTSD who were or were not taking psychotropic medications, multivariate analysis of covariance (MANCOVA) with age and Clinician-Administered PTSD Scale (CAPS; Blake et al., 1995) score in the model, F (3, 52) = 2.14, p = .090, η2 = .15. The control group (n = 53) comprised healthy nonveterans (n = 36) and community-recruited veterans of Operation Enduring Freedom and Operation Iraqi Freedom without PTSD (n = 17) who were screened by telephone, and then completed the same battery of questionnaires and neuropsychological measures as the PTSD group. Potential controls were excluded if they reported current or previous history of psychiatric (n = 21) or neurologic (n = 10) diagnoses (including mTBI), substance abuse (n = 3), sexual trauma (n = 19), learning disability (n = 6), or scored below 45 on Trial 1 of

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the Test of Memory and Malingering (Hilsabeck et al., 2011; Tombaugh, 1997; n = 1). We excluded for mTBI in the control group because neurocognitive deficits 1-year post mTBI are unusual in civilians (Belanger, Curtiss, Demery, Lebowitz, & Vanderploeg, 2005), but more common in military samples with PTSD (Vanderploeg, Belanger, & Brenner, 2013). Trauma breakdown for the control group included combat (n = 10), transportation accidents (n = 34), the death of someone close (n = 17), physical assault (n = 12), natural disaster (n = 17), serious accident or injury (n = 7), weapon assault (n = 6), and fire/explosion (n = 7). No controls were taking psychotropic medications. The veteran and nonveteran controls were pooled to form a single control group because they did not demonstrate any significant demographic (p > .705) or neurocognitive differences, MANOVA, F (5, 47) = 0.89, p = .498, η2 = .09. All participants provided written informed consent, and were compensated for participation. This study was approved by the institutional review board of the New Mexico VA Healthcare System. The PTSD and control groups did not differ in alcohol use or demographics (see Table 1) including ethnicity, χ2 (2, N = 109) = 1.20, p = .547. The PTSD group reported significantly more types of trauma, a greater number of PTSD symptoms, and greater depression. Although the PTSD group’s estimated IQ was within the average range, it was significantly lower than the estimated IQ of the control group, t = 2.74, p = .007. Therefore, we individually matched participants in each group on estimated IQ, age, and years of education for a supplemental analysis. The resulting sample of 42 matched pairs did not significantly differ on IQ (p = .909), age (p = .759), or years of education (p = .542). Both PTSD samples had scores on the CAPS (Blake et al., 1995) that reflected active PTSD symptoms (full sample n = 56, M = 72.13, SD = 18.46; IQ-matched PTSD sample n = 42, M = 71.00, SD = 19.86). We also separated the PTSD group into those who did (n = 32) and did not (n = 24) self-report an mTBI to assess this variable. No significant (p < .05) group differences were observed for any of the demographic or psychological variables except that the CAPS was higher for those with mTBI (M = 78.91, SD = 17.99) than those without (M = 67.0, SD = 17.66), F(1, 53) = 5.91, p = .019. Measures All participants in the PTSD group were administered the CAPS (Blake et al., 1995) to determine the presence of a diagnosis of current PTSD (all scored above 50) and the Structured Clinical Interview for DSM-IV (First, Spitzer, Gibbon, & Williams, 2002) to identify comorbid psychiatric disorders. Both groups self-reported PTSD symptoms with the PTSD Checklist (PCLM or PCL-C depending on whether the index trauma was military or civilian; Blanchard, Jones-Alexander, Buckley, & Forneris, 1996), trauma exposure with the Life Events Checklist (Gray, Litz, Hsu, & Lombardo, 2004), depression with the Beck Depression Inventory–Second Edition (BDI-II; Beck, 1996),

and alcohol use with the Alcohol Use Disorders Identification Test (AUDIT; Allen, Litten, Fertig, & Babor, 1997). Cronbach’s α in this sample was .85 for the PCL and .96 for the BDI. Mild TBI was assessed with a modification of a self-report measure (Fortier et al., 2013), based on neurologic change after the worst mTBI (Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine, 1993). The neuropsychological assessment used published tests with demonstrated reliability and validity. Raw scores for all primary measures were converted using test manual norms to normative-based z scores. The z scores from individual measures within each domain were averaged to obtain a domain score. The following measures were used to reflect each domain: the Wechsler Test of Adult Reading (Wechsler, 2001) estimated longstanding intelligence and the California Verbal Learning Test-II (CVLT-II; Delis, Kramer, Kaplan, & Ober, 2000) assessed verbal learning and memory. A composite measure from a previous PTSD study (Gilbertson et al., 2006) was calculated by averaging the derived z scores from the test manual for each of the following: List A Total Recall, List B Recall, Short-Delay Free and Cued Recall, Long-Delay Free and Cued Recall, Across-Trial Recall Consistency, Percent Recency Recall, Semantic Clustering, Recognition Hits, and percent change in recall between Short-Delay Free Recall and Trial 5 Recall (α = .85). The published contrast z score comparing LongDelay Free Recall and Trial 5 Recall was used to measure retention. The Processing Speed Index of the Wechsler Adult Intelligence Scale-IV (WAIS-IV) was the measure of processing speed (Wechsler, 2008). Executive functions comprised the following tests: Working Memory (average scaled score for Digit Span Backward, Digit Span Sequencing, and Arithmetic from the WAIS-IV, α = .74); Inhibition/Switching from the Delis-Kaplan executive function system (Delis, Kaplan, & Kramer, 2001) included Trails 4 (alpha-numeric sequencing), Color-Word Inhibition, Color-Word Switching, and Category Switching (α = .61). Because of inconsistencies regarding weaker executive functions in PTSD, with results sometimes varying by subcomponent (Aupperle et al., 2012), we also included a composite measure. The Working Memory and Inhibition/Switching components were combined into a single executive functions composite by averaging the z score composites for each (α = .78). Data Analysis A multivariate analysis of variance (MANOVA) was performed to investigate group differences across neuropsychological domains. Two follow-up MANOVAs were performed on (a) a subset of the PTSD and NC groups matched on estimated IQ, and (b) participants with PTSD with and without a history of mTBI. Hierarchical regression was conducted with all participants to examine associations with memory performance, with sequential entry of the following variables: group, estimated IQ,

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Table 1 Means, Standard Deviations, and Cohen’s d for Demographics, Psychiatric Characteristics, and Neurocognitive Domains (z Scores) Overall sample Healthy controls n = 53 Variable Age (years) Years of education Estimated IQ BDI-II Types of trauma PCL AUDIT Processing speed Executive functions Working memory Inhibition/switching Verbal learning Verbal retention

Subsample matched for estimated IQ

PTSD n = 56

Healthy controls n = 42

PTSD n = 42

M

SD

M

SD

d

M

SD

M

SD

d

37.13 15.21 106.30 2.83 2.89 17.06 2.04 0.64 0.42 0.35 0.50 0.42 0.12

11.67 1.94 11.11 3.00 1.51 0.41 1.76 0.83 0.58 0.73 0.56 0.44 0.57

36.77 14.68 99.98 26.30 7.71 59.87 2.73 0.15 0.03 0.24 0.18 0.04 0.15

11.48 1.75 12.86 10.12 2.85 18.93 2.65 0.75 0.51 0.62 0.57 0.59 0.99

0.03 0.29 0.53** 3.14** 2.12** 3.18** 0.31 0.63** 0.83** 0.88** 0.57** 0.73** 0.04

36.38 14.74 104.36 2.79 2.71 17.07 1.86 0.72 0.45 0.38 0.53 0.42 0.10

11.57 1.70 11.28 2.67 1.52 0.46 1.59 0.82 0.55 0.69 0.56 0.43 0.59

37.17 14.50 104.07 26.86 7.86 61.27 2.79 0.22 0.05 0.14 0.25 0.11 0.21

11.87 1.86 11.57 10.53 2.84 20.80 2.53 0.71 0.50 0.64 0.52 0.53 0.94

0.07 0.14 0.03 3.17** 2.29** 3.04** 0.45* 0.66** 0.77** 0.79** 0.52* 0.65** 0.15

Note. The z scores were based on test manual norms and averaged for each domain. Types of trauma derived from the Life Events Checklist (LEC). PTSD = posttraumatic stress disorder; CAPS = Clinician Administered PTSD Scale; BDI-II = Beck Depression Inventory–Second Revision; PCL = PTSD Symptom Checklist; AUDIT = Alcohol Use Disorders Identification Test. * p < .05. ** p < .01.

processing speed, executive composite, and Group × Executive Composite. Follow-up regressions were performed that (a) examined simple effects of the interaction, (b) added the BDI score as the first step of the model, and (3) added the CAPS score as the first step of the model. Both the outcome variable (verbal learning and memory) and the saved residuals for all regression analyses were normally distributed. There were no missing data. A family-wise α level of .05 was used for all analyses. Results The overall MANOVA investigating group differences across neuropsychological domains was significant, F(4, 104) = 6.53, p < .001, η2 = .20. Significant group differences (see Table 1) were observed for all domains except verbal retention (p = .852), including processing speed, F(1, 107) = 10.47, p = .002, verbal learning and memory, F(1, 107) = 14.74, p < .001, and executive functions, F(1, 107) = 18.57, p < .001. The PTSD group performed worse on both components of executive functioning: Working Memory, F(1,107) = 20.64, p < .001, and Inhibition/Switching, F(1, 107) = 8.62, p = .004. This pattern of results remained the same when we examined group differences using the subset of participants matched on estimated IQ. The overall MANOVA was significant, F(4, 79) = 4.95, p = .002, η2 = .20, with significant group differences for all neurocognitive domains: processing speed, F(1, 82) = 8.76, p = .004, executive function, F(1, 82) = 12.07, p = .001, and verbal

learning, F(1, 82) = 8.87, p = .004, except verbal retention, F(1, 82) = 0.49, p = .490. Comparison of PTSD participants with and without selfreported mTBI indicated that mTBI did not have a significant effect. No group differences were present for the neurocognitive variables, as reflected by a nonsignificant overall model, F(5, 49) = 0.26, p = .93, η2 = .03. The hierarchical regression analyses with all participants (N = 109) indicated that the interaction between group and executive functions accounted for significant variance in verbal learning and memory (β = .33, R2 = .05, p = .005), over and above the variance accounted for by all other variables. We therefore examined these relationships separately within each group. For the PTSD group (n = 56), the first step of the model showed that IQ accounted for significant variance in verbal learning (R2 = .25, p < .001). The second step showed that processing speed accounted for significant variance in verbal memory, over and above estimated IQ (R2 = .07, p = .026). The third step (see Table 2) showed that executive functions accounted for a significant amount of variance (R2 = .06, p = .027) in verbal learning over and above estimated IQ and information processing speed for the PTSD group. This relationship was not demonstrated within the normal control group (n = 53); no models were significant (all ps > .05). We conducted supplementary hierarchical regressions within the PTSD group (n = 56) to assess whether depression and PTSD severity accounted for the relationship between verbal learning and executive functions. The first step of the model

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Table 2 Regression Models by Group: Executive Functioning Accounts for Variance in Verbal Learning and Memory in PTSD but Not Control Group NC Group n = 53 Variables IQ PS EFC

B 0.00 0.10 0.04

SE B 0.01 0.08 0.13

β −.02 .19 .06

PTSD Group n = 56 t −0.13 1.22 0.33

B 0.02 0.10 0.36

SE B 0.01 0.10 0.16

β .32 .13 .32

t 2.62* 1.06 2.28*

Note. PTSD = posttraumatic stress disorder; NC = normal control; IQ = intelligence quotient; PS = processing speed; EFC = executive function composite. * p ࣘ .05.

indicated that depression alone did not account for a significant amount of variance in the PTSD group’s verbal learning (2.7%, R = .17, p = .226). The fourth step of the model demonstrated that inclusion of depression did not affect the overall model, as executive functions continued to account for significant variance (β = .34, R2 = .07, p = .016) in verbal learning over and above depression, estimated IQ, and information processing speed. A second analysis was identical except CAPS total was used instead of BDI. The first step of the model was not significant, indicating that PTSD severity did not account for a significant variance in the PTSD group’s verbal learning (R2 = .00, p = .926). The fourth step of the model demonstrated that inclusion of CAPS did not affect the overall model; as executive functions continued to explain a significant amount of variance (β = .31, R2 = .06, p = .029) in verbal learning over and above CAPS, estimated IQ, and information processing speed.

Discussion Our results suggested that the pattern of neurocognitive weaknesses in female veterans with PTSD appeared similar to published findings in male veterans and is characterized by poorer but still average general intelligence, verbal learning, executive functions, and processing speed with no differences in verbal retention relative to females without PTSD (Vasterling & Brailey, 2005). This pattern of findings did not change when subgroups of PTSD and control participants matched for estimated IQ were examined. The results were also unlikely to have been explained by mTBI, as we showed comparable neurocognitive performance in the PTSD group regardless of mTBI history. These findings were consistent with other studies reporting poorer verbal learning, processing speed (Aupperle et al., 2012; Samuelson et al., 2006), and executive functions including set switching, response inhibition, or attention/working memory in individuals with PTSD relative to controls (Gilbertson et al., 2006; Jenkins et al., 2000; Leskin & White, 2007; Parslow & Jorm, 2007; Stein et al., 2002; Swick et al., 2012; Vasterling et al., 1998, 2002). Reports of no neurocognitive weaknesses in PTSD have been based largely on nonclinical samples, and one examined participants many years after trauma (Crowell, Kieffer, Siders, & Vanderploeg, 2002), though their negative find-

ings may also be due to better control of confounding factors, such as psychiatric comorbidities. Although our results clearly demonstrated a pattern of neuropsychological weaknesses relative to control participants, individuals with PTSD may not meet typical criteria for a neurocognitive disorder because the PTSD group’s performance fell in the average range. Our findings for this female PTSD group showed that executive functions comprising working memory and response inhibition/switching were poorer compared to the control group. Although none of these measures are pure indicators of their label, there is evidence that working memory and response inhibition are dependent on lateral and medial prefrontal regions (Aron, Fletcher, Bullmore, Sahakian, & Robbins, 2003; Swick & Turken, 2002). Greater activation in the dorsolateral prefrontal cortex has also been associated with better inhibition of unwanted memories in healthy adults (Anderson et al., 2004), a potentially important coping mechanism for PTSD. In addition to decreased hippocampal volume, one meta-analysis also identified abnormalities in multiple frontolimbic structures (Karl et al., 2006). Decreased volume of lateral prefrontal regions (Geuze et al., 2008) in PTSD has been reported, and one study (Fennema-Notestine, Stein, Kennedy, Archibald, & Jernigan, 2002) reported decreased lateral prefrontal volume with no decrease in hippocampal volume. Importantly, the fact that all our neurocognitive domains except verbal retention were weaker in PTSD argues against a strictly focal neural substrate suggesting our findings do not have strong implications for localization of cerebral dysfunction in PTSD. As predicted, verbal learning and memory (Brewin et al., 2007) were associated with executive functions over and above processing speed, PTSD severity, and depression in the PTSD group. IQ also demonstrated a significant relationship with verbal learning and memory in the PTSD group though executive functions accounted for significant variance after controlling for IQ. The significant interaction between group and executive functions highlighted that this relationship may vary across different samples. The association of executive functioning and learning has been supported in neurologic samples (Hill et al., 2012; Shimamura, 2008; Tremont et al., 2000), but not in our control group or a group of normal adolescents (Beebe et al., 2000). This may reflect the possibilities that learning in control samples is less dependent on executive functions or that

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their more limited variance in executive functioning may not allow this relationship to emerge. The demonstrated relationship between verbal memory and executive functions in our PTSD group was consistent with evidence that prefrontal abnormalities are significant in PTSD and contribute to memory performance. From a clinical standpoint, such executive difficulties, especially those affecting inhibition, may influence the ability to block retrieval of unwanted memories in PTSD (Anderson et al., 2004). One model suggests that executive functioning weaknesses may influence the development and maintenance of PTSD by leading to maladaptive coping styles, such as avoidance due to poorer ability to inhibit emotional responses to trauma memories. In this framework, therapeutic strategies that enhance executive functions with the goal of inhibiting PTSD symptoms of reexperiencing and arousal to salient, but distracting internal and external stimuli would be predicted to be most effective (Amir et al., 2009; Aupperle et al., 2012). It is well accepted that learning and memory are not unidimensional, and PTSD is associated primarily with relative weaknesses in initial learning and retrieval of new information rather than rapid forgetting of information that was initially learned (Stein et al., 2002; Vasterling et al., 1998, 2002), consistent with our finding of intact retention. In addition, initial learning is dependent on the ability to maintain multiple pieces of information in working memory, to organize new information to facilitate a greater depth of encoding, and to filter and/or inhibit intrusive responses and retrieve correct responses (Shimamura, 2008), all of which are different aspects of executive functioning. Our findings suggested that the recent shift in the literature toward investigating executive functions in PTSD (Aupperle et al., 2012) is appropriate because the learning and memory weaknesses seen in our PTSD group were related to executive functioning. This study had a number of limitations. First, our veteran PTSD group had significant combat and/or sexual trauma exposure and psychiatric comorbidities, whereas our control group of veterans and nonveterans had less exposure to trauma, no exposure to sexual trauma, and no self-reported psychiatric diagnoses or symptoms of depression. Although veteran status did not appear to be critical as our veteran and nonveteran control participants demonstrated no statistically significant demographic, IQ, or neurocognitive differences, we could not exclude the possibility that greater trauma exposure in the PTSD group may help explain the neurocognitive differences across groups. Second, our PTSD and control groups demonstrated group differences on estimated premorbid intelligence, consistent with many prior studies (Gilbertson et al., 2006; Vasterling et al., 1998), but our results were unchanged when using smaller groups matched on this variable. Third, although we found no significant neurocognitive differences in the PTSD group as a function of psychotropic medications, we could not rule out the possibility of subtle medication effects that could contribute to these results. Fourth, the presence of mTBI in the PTSD group, but not in the control group limited our interpretation. Although

our finding of no significant neurocognitive differences between PTSD patients with and without mTBI suggested this was not a critical explanation of our results, consistent with other work (Soble, Spanierman, & Fitzgerald, 2013), this analysis could not completely rule out the possibility that an mTBI history could contribute to this interaction, particularly given that our relatively small subgroup sample sizes may have limited our power to reject the null hypothesis. Therefore, replication of these results using a control group of veterans with more similar trauma exposure, mTBI history, and psychiatric comorbidities would solidify these findings. Fifth, we did not include a separate measure of simple attention, which might have allowed a better delineation of our PTSD group’s neuropsychological performance, especially because most studies that have separately examined simple attention have not found weaknesses in this area (Jenkins et al., 2000; Vasterling et al., 1998, 2002). Rather difficulties labeled as attention have included measures labeled as executive functions by other studies (Aupperle et al., 2012; Jenkins et al., 2000; Qureshi et al., 2011; Vasterling et al., 1998, 2002). Our measures of executive functions encompassed some of the same measures these previous studies would have labeled as attention. Finally, our use of only one measure of memory was another limitation, as this measure may depend more heavily on executive functions relative to other available memory tests given the list learning format with semantic categories and inclusion of an interference trial. This is the first study of which we are aware that documented the neurocognitive performance of an all-female veteran sample with PTSD. Results suggested that the impact of executive functions on verbal learning in PTSD may be of particular importance. References Allen, J. P., Litten, R. Z., Fertig, J. B., & Babor, T. (1997). A review of research on the Alcohol Use Disorders Identification Test (AUDIT). Alcoholism: Clinical and Experimental Research, 21, 613–619. doi: 10.1111/j.15300277.1997.tb03811.x Amir, N., Beard, C., Taylor, C. T., Klumpp, H., Elias, J., Burns, M., & Chen, X. (2009). Attention training in individuals with generalized social phobia: A randomized controlled trial. Journal of Consulting and Clinical Psychology, 77, 961–973. doi:10.1037/a0016685 Anderson, M. C., Ochsner, K. N., Kuhl, B., Cooper, J., Robertson, E., Gabrieli, S. W., . . . Gabrieli, J. D. (2004). Neural systems underlying the suppression of unwanted memories. Science, 303, 232–235. doi:10.1126/science.1089504 Andreano, J. M., & Cahill, L. (2009). Sex influences on the neurobiology of learning and memory. Learning & Memory, 16, 248–266. doi:10.1101/lm.918309 Aron, A. R., Fletcher, P. C., Bullmore, E. T., Sahakian, B. J., & Robbins, T. W. (2003). Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans. Nature Neuroscience, 6, 115–116. doi:10.1038/nn1003 Aupperle, R. L., Melrose, A. J., Stein, M. B., & Paulus, M. P. (2012). Executive function and PTSD: Disengaging from trauma. Neuropharmacology, 62, 686–694. doi:10.1016/j.neuropharm.2011.02.008 Beck, A. T. (1996). Beck Depression Inventory- Second Edition. San Antonio, TX: Psychological Corporation.

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Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.

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