The major results of the study show that in this sample of well-educated combat veterans with chronic PTSD and non-PTSD participants, carefully chosen to minimize the impact of comorbid depression, substance, and alcohol abuse, there were no significant group differences in standard measures of attention or memory for word-lists, realistic scenes, abstract designs, or unfamiliar faces. In addition there was no correlation of attention or memory with hippocampal volume or NAA.
Our sample differs from previously published studies of PTSD and cognition on four variables. First, mean years of education level in our sample (15.1 years for PTSD) was the highest of any of the above cited studies in which the mean years of education ranged from 12.7 to 14.2. Second, the mean age of our participants (51–52 years) was older than the participants in the studies referenced above; however, this is not likely to bias our negative finding. Third, our participants, as previously reported did not differ from comparison participants with respect to hippocampal volume (Schuff et al., 2001
). Finally, our sample met the most stringent entry criteria, relative to the studies listed above, for excluding participants who had a major depressive episode in the past 3 months, or a diagnosis of alcohol or substance abuse in the past 5 years.
One implication of these results is that prior reports of impaired attention and declarative memory in PTSD, utilizing neurocognitive measures similar to those used in this study, may have been confounded by comorbid diagnoses of substance abuse and/or depression. An examination of the positive studies demonstrating significant differences in attention, learning, and memory show a range of effect sizes for PTSD status on neurocognitive functioning from 0.7 to 2.0 (Bremner et al., 1993
; Bremner, Randall, Scott, Capelli, et al., 1995
; Gil, Calev, Greenberg, Kugelmass, & Lerer, 1990
; Gilbertson, Gurvits, Lasko, Orr, & Pitman, 2001
; Jenkins, Langlais, Delis, & Cohen, 1998
; Moradi, Doost, Taghavi, Yule, & Dalgleish, 1999
; Roca & Freeman, 2001
; Sachinvala et al., 2000
; Uddo, Vasterling, Brailey, & Sutker, 1993
; Vasterling et al., 2002
; Vasterling, Brailey, Constans, & Sutker, 1998
; Yehuda et al., 1995
). Our study was not sufficiently powered to detect small effect sizes for cognitive performance; however, we did have adequate power to find effects similar in magnitude to most of those reported in the literature. The exclusion criteria regarding alcohol abuse in the prior literature with both positive and negative findings ranges from having no exclusions (but often with matching PTSD and comparison participants on alcohol abuse) to 1 year without alcohol abuse or dependence. Hence, recent alcohol abuse does not appear to explain the variability in effect sizes across these studies. Although the effects of alcohol abuse on the brain are in part reversible within the first 3 months of abstinence (Pfefferbaum et al., 1995
), the study by Gilbertson et al. (2001)
that excluded participants with a history of alcohol abuse in the past year, demonstrated that the effects of alcohol on cognition are still measurable for at least a year after abstinence.
The presence of current comorbid major depression is a problem in most studies of PTSD and neurocognitive functioning. The exclusion of participants with current major depression in this sample potentially could have biased the sample to having milder PTSD symptoms. However, the mean CAPS score of our PTSD participants (64.7) is above 60, which has been defined as the threshold for severe PTSD symptomatology by Weathers, Keane, and Davidson (2001)
. Although some investigators have suggested that depression is inextricably linked to PTSD, this study as well as recent neurobiological data (Yehuda, Halligan, Grossman, Golier, & Wong, 2002
), suggest that major depression must still be carefully considered as a possible confound.
A careful review of the literature demonstrated that the three studies of cognition conducted to date with the largest sample sizes have yielded negative findings (Barrett, Green, Morris, Giles, & Croft, 1996
; Crowell et al., 2002
; Zalewski, Thompson, & Gottesman, 1994
). The study by Barrett is particularly noteworthy because they found that veterans with PTSD alone (N
= 236) did not show lower scores on measures of cognitive functioning compared to normal comparison participants (N
= 1,835), whereas veterans with both PTSD and a concurrent diagnosis of depression, another anxiety disorder, or substance abuse (N
= 128) performed significantly less well. These results suggest that a diagnosis of PTSD alone is not strongly associated with cognitive impairment as assessed by these methods.
Similar to a study of women victimized by childhood sexual abuse (Stein et al., 1997
), we found no relationship between hippocampal volume and measures of declarative memory function. Stein and colleagues suggested that the relatively young age of their women with childhood sexual abuse (mean age = 32) may have accounted for the lack of relationship between hippocampal volume and declarative memory. We found similar results in a sample that is approximately 20 years older with normal hippocampal volume. It remains possible that the relationship between hippocampal measures and cognitive performance are not discernible until advanced ages, or in subjects with dementia. For example, the study that showed the largest reduction in hippocampal volume, 26% (Gurvits et al., 1996
), did not show an association of hippocampal size with verbal declarative memory. Finally, it is possible that measures of gross brain structure and neurochemistry (e.g., NAA) are too insensitive to relate to subtle differences in neurocognition that may exist in samples of participants who perform within the normal range of cognitive function.
Although the association between hippocampal volume and performance on the Benton Visual Form Discrimination did not remain significant after correcting for multiple comparisons, the correlation is similar to a finding by Gurvits et al. (1996)
for a different test format using BVFD stimuli. In their study of combat PTSD (N
= 7) and combat normal comparison participants (N
= 7) a relationship was observed between Benton 15-s delayed recall performance and total hippocampal volume. Similarly, in our study, performance on the Benton visual form discrimination was correlated with hippocampal volume. These findings are consistent with preclinical data that demonstrate an important role of the hippocampus in regulating visuospatial processing (for review see Sewards & Sewards, 2002
Finally, it is important to note that performance measures in both of our groups are within the normal range. The similar scores on measures of attention in the two groups are noteworthy, because decreased attention may account for differences in performance on many neuropsychological measures (Gilbertson et al., 2001
). It is also possible that our measures (e.g., subtests of the WMS-III and CVLT) are not sufficiently challenging for higher-functioning, ambulatory PTSD patients, and thus may fail to detect subtle memory deficits in this subgroup. For example, Bremner and colleagues detected strong group differences in PTSD versus comparison participants in logical memory performance, which involves a relatively challenging test of paragraph recall (Bremner, Randall, Scott, Bronen, et al., 1995
). Future studies might assess a broader range of cognitive functions, such as narrative recall, other measures of concentration and working memory, planning, and organizational skills that may be more sensitive to differences in neurocognitive performance in higher-functioning individuals.