Post-traumatic stress disorder as a neurocognitive condition

Post-traumatic stress disorder (PTSD) is a serious mental health condition with potentially severe deleterious effects on social, mental, and physical well-being. Since first recognized as a formal diagnosis in 1980, the diagnostic criteria for this disorder have been focused on psychological and behavioral symptoms such as intrusion/recurrence symptoms, avoidance behaviors, hyperarousal/reactivity, and mood changes. The Diagnostic and Statistical Manual - Fifth Edition (DSM-5) criteria include concentration, intrusive memories, and difficulties with recall of key aspects of the traumatic event, but the latter two are framed in terms of trauma-related content rather than reflecting difficulties with memory as a neurocognitive process (American Psychiatric Association, 2013). None of the other 17 PTSD symptoms in DSM-5 refer to neurocognitive abilities. Although reduction and management of the primary symptoms of PTSD are obviously critical components of effective treatment, the importance of neurocognitive functioning has been well documented in other forms of serious mental illness and may have parallel relevance in the context of prevention and treatment of PTSD (Nemeroff, Reference Harvey, Gould, Nemeroff and Marmar2018).

Associations between PTSD and neurocognitive functions

Meta-analytic reviews of studies comparing people with and without PTSD, including older adults, indicate PTSD is associated with slightly lower group mean neuropsychological test performance, particularly in the domains of attention, learning/memory, processing speed, and executive control (Schuitevoerder et al., Reference Schuitevoerder2013; Scott et al., Reference Scott2015). As with other biological dimensions of PTSD (Pitman et al., Reference Pitman2006), key questions remain regarding the causal direction(s) between PTSD and neurocognitive functioning (Jacob et al., Reference Jacob, Dodge and Vasterling2019). Studies of people in high-risk occupations, before and after exposure to major traumas (e.g. before and after combat deployment among military personnel), have found subtly lower mean premorbid neurocognitive scores among those who developed PTSD relative to those who did not (Marx et al., Reference Marx, Doron-LaMarca, Proctor and Vasterling2009; Parslow and Jorm, Reference Parslow and Jorm2007; Samuelson et al., Reference Samuelson2020; Vasterling et al., Reference Vasterling2018). Although it is possible that premorbid differences in cognitive test performance reflect other confounded factors that are more directly involved in vulnerability to PTSD (Jacob et al., Reference Jacob, Dodge and Vasterling2019; Nissen et al., Reference Nissen2017), the identification of sensitive and specific cognitive markers of risk for PTSD could be helpful in primary prevention efforts.

In addition to premorbid differences, there is also evidence that PTSD may have a toxic effect on subsequent neurocognitive functioning (Jacob et al., Reference Jacob, Dodge and Vasterling2019). This is most strongly evident in terms of the association of PTSD with risk for dementia, as summarized below. However, even mild deficits, if involving critical cognitive processes, may impact the severity, maintenance, and/or course of illness (Jak et al., Reference Jak, Crocker, Aupperle, Clausen and Bomyea2018). The impact of the mild neurocognitive deficits in PTSD on everyday functioning has received less attention than in other disorders, but it is apparent from research in other chronic disorders that neurocognitive deficits may be among the strongest predictors of functional capacity and independent in everyday functioning (Bourgeois et al., Reference Bourgeois, John, Zepf, Greene, Frankel and Hessol2020; Nemeroff, Reference Harvey, Gould, Nemeroff and Marmar2018).

Normal age-related declines in neurocognitive functioning also have relevance to reemergence of PTSD symptoms in later life. For example, in an analyses of data from the National Health and Resilience in Veterans Study, Mota et al. (Reference Mota2016) found 9.9% of older Veterans experienced an exacerbation in PTSD symptoms with an average span of 3 decades since their most severe trauma. Post hoc analyses suggested this recurrence to be related to a decline in executive functions, which may itself result in reduced coping ability. Other factors to consider include that among the “oldest-old” persons with PTSD, the index trauma may have occurred many decades before the condition was formally recognized, and these individuals may have been more likely to live with the long-term psychological sequelae without recognition or treatment (Glaesmer et al., Reference Glaesmer, Kuwert, Braehler and Kaiser2017; Palmer et al., Reference Palmer2019; Vasiliadis et al., Reference Vasiliadis, Lamoureux-Lamarche, Pitrou and Berbiche2020).

In their recent meta-analysis, Kang et al. (Reference Kang, Xu and McConnell2019) found that the risk (hazard ratio [HR]) of subsequent dementia among people with PTSD ranged from HR = 1.21 to 1.77. For example, in retrospective examination of data from Veterans aged 55 years and older in the VA National Patient Care Database, Yaffe et al. (Reference Yaffe2010) found that the 7-year incidence rate of dementia for Veterans with PTSD to be 10.6% which is approximately 1.6 times higher than the 6.6% rate found among those Veterans without PTSD.

There are a number of potential confounding factors linking PTSD to elevated risk of dementia, including premorbid brain reserve, comorbid traumatic brain injury, and the potential effects of PTSD on positive and negative health behaviors and exposure to other environmental risks. However, the pattern of elevated risks for dementia in later life is also consistent with a larger body of research suggesting that PTSD is associated with a form of accelerated biological aging (Lohr et al., Reference Lohr, Palmer and Eidt2015; Wolf and Schnurr, Reference Wolf and Schnurr2016). In a prior comprehensive review (Lohr et al., Reference Lohr, Palmer and Eidt2015), we found evidence that PTSD is associated with earlier all-cause mortality (mean HR = 1.29) and an elevated number of age-related medical comorbidities, including heart/cardiovascular diseases, metabolic syndrome, type 2 diabetes, as well as dementia. We also found a medium to large effect size (Cohen’s d = 0.76) difference in studies comparing leukocyte telomere length between people with vs. without PTSD. The latter is consistent with other recent reviews finding evidence of accelerated cellular aging in PTSD (Wolf and Morrison, Reference Wolf and Morrison2017).

Further research is needed to identify the mechanisms by which PTSD affects neurocognitive function, risk of dementia, and overall accelerated biological aging. One potential mechanism warranting empirical attention is the effects of strain from chronically elevated physiologic stress responses. For example, in recent review, our research group considered evidence that PTSD is associated with problems in allostatic control mechanisms, as well as likely involvement of the endogenous cannabinoid system in allostatic load (Lohr et al., Reference Lohr, Chang, Sexton and Palmer2019). Our review was in no way an endorsement of “medicinal cannabis” or even clinical use of nonpsychoactive cannabinoids for management of PTSD. However, the model proposed within that paper provides an example of how clarification of the mechanisms underlying the association of PTSD with accelerated neurocognitive and other biologic aging may prove helpful in identification of novel biologic treatment targets to enhance long-term cognitive and other health outcomes among people with PTSD.

Whether reflecting the effects of premorbid cognitive differences on available resources for coping with trauma, neurobiological changes triggered by traumatic stress or the strain from PTSD itself, and/or other potential mechanisms, better understanding of the association of PTSD with neurocognitive functioning could lead to a number of novel and effective approaches to the prevention, treatment, management of, and recovery in the context of this disorder. Although research has and should continue examining the level of performance on measures of attention, learning/memory, processing speed, and executive functions, the search for more specific cognitive risk or disease markers in PTSD is ongoing. One plausible and interesting candidate is the focus of the report by Rutter and colleagues in the present volume.

Rutter et al. (Reference Rutter, Vahia, Passell, Forester and Germine2020) – intraindividual reaction time variability

The review and research agenda provided by Rutter et al. (Reference Rutter, Vahia, Passell, Forester and Germine2020) focuses on intraindividual reaction time variability (RTV) over successive within visit trials on reaction time tests as a candidate neurocognitive biomarker of PTSD. Rutter and colleagues provide a compelling argument that RTV is sensitive to executive control mechanisms, the latter being an important component in cognitive control theories of PTSD. They conducted a comprehensive search for empirical reports evaluating the potential of RTV as cognitive biomarker in the context of PTSD and aging. From that search, they identified and reviewed results from numerous studies documenting an increase in RTV with normal advancing age, as well as studies showing increases in RTV among persons meeting diagnostic criteria for mild cognitive impairment (MCI) or dementia. On the other hand, their search revealed a surprising absence of studies focused on RTV among older or younger people with PTSD. One important exception was a study by Swick et al. (Reference Swick, Honzel, Larsen and Ashley2013). Consistent with Rutter et al.’s hypothesis, Swick and colleagues found higher intraindividual RTV (measured with a go-no-go task) among Veterans with vs. without PTSD. Of particular note, Swick et al found no significant group mean differences in reaction time. The latter also supports Rutter et al.’s overall suggestion that RTV may provide useful information beyond that obtained from examination of mean level of performance alone.

Rutter et al.’s (Reference Rutter, Vahia, Passell, Forester and Germine2020) report also includes a proposed research agenda for future studies of RTV in the context of PTSD and aging. Their proposed agenda included testing of four hypothesized models: (1) RTV as a vulnerability marker for PTSD, (2) RTV as a reflection of trauma-related neurobiological changes, (3) RTV as a side effect of hyperarousal symptoms in PTSD, and (4) RTV as a marker of risk for neurodegeneration. Given the ubiquity of tasks with a reaction time component in neuropsychological research, there are likely a multitude of existing datasets from which such data could be readily compiled and examined in reference to one or more of their four proposed models. However, as reaction time-focused neurocognitive tests are typically computer administered, the minimal cost and burden of collecting information on RTV in the context of prospective randomized clinical psychotherapy and pharmacology trials for PTSD could be helpful in examining the potential of RTV as a predictor or marker of treatment response. Inclusion in longer-term follow-up observational research could also clarify any potential utility of RTV as a predictor of the long-term course of symptoms and psychosocial recovery from PTSD, as well as any relationship to more distal neurobiological and health outcomes.

Summary and conclusions

In short, PTSD has a clear, if generally mild, association with neurocognitive dysfunction, especially attention, learning/memory, processing speed, and executive control. The full impact of these associations in terms of treatment response, course, and everyday functioning warrants further empirical examination. But there is clear cause for concern in reference to the interaction with normal age-related changes in cognitive functioning in terms of potential age-appropriate modifications to existing evidence-based psychotherapies for PTSD (Palmer et al., Reference Palmer2019) and in light of documented elevated risk of dementia in later life (Kang et al., Reference Kang, Xu and McConnell2019). One potential barrier to widespread application of comprehensive neurocognitive testing in applied settings regards the relative time commitment/cost for such assessment. Although RTV is unlikely to supplant the value of comprehensive neuropsychological evaluation when clinically indicated, Rutter et al.’s suggestion to further examine RTV as a cognitive biomarker represents a novel and potentially important direction for further research. If such research reveals RTV or any other cognitive measure to be sufficiently sensitive and specific as a risk or disease marker for PTSD, the result would have substantial potential utility in primary, secondary, and tertiary prevention efforts.