Cognitive impairment and posttraumatic stress in breast cancer patients during the first year after diagnosis

Cancer patients frequently report symptoms of cognitive impairment and posttraumatic stress. Until recently, it was assumed that cognitive deteriorations in cancer patients are attributable to neurotoxic effects of chemotherapy. However, new research indicates that cognitive impairment cannot be caused by cancer treatment alone – most likely also cancer-related posttraumatic stress affects cognition. Elucidating the causes of cognitive dysfunction and posttraumatic stress in cancer patients is crucial for prevention and effective psychological intervention. This cumulative dissertation summarizes two publications of the prospective, longitudinal and controlled COGNICARES-study, which were published in peer-reviewed international journals with current impact factors that rank among the top 80% in the Journal Citation Report. COGNICARES is the first large study that applied an extensive neuropsychological test battery and a validated clinical interview at three assessment times, to measure cognitive functioning and posttraumatic stress in women with mamma carcinoma and in a control group. Prior to the start of any cancer treatment, limited cognitive impairment was found in cancer patients, which was mediated by posttraumatic stress. Only few patients were diagnosed with a full-blown acute or posttraumatic stress disorder (ASD, PTSD) but shortly after the cancer diagnosis, more than 80% of patients experienced symptoms of PTSD, which did not completely resolve during the first year after cancer diagnosis in the majority of patients. Implications of the findings are discussed in the context of the recently published Diagnostic and Statistical Manual of Mental Diseases-V (DSM-V).Krebspatienten klagen häufig über kognitive Probleme und Symptome einer posttraumatischen Belastungsstörung. Bis vor kurzem wurde die Beeinträchtigung kognitiver Funktionen ausschließlich auf die neurotoxische Wirkung von Chemotherapie zurückgeführt. Jüngste Studien weisen hingegen darauf hin, dass kognitive Störungen bei Krebspatienten nicht ausschließlich durch Chemotherapie verursacht sein können – vermutlich beeinflusst zusätzlich krebsspezifischer, posttraumatischer Stress die kognitiven Fähigkeiten. Die Aufklärung der Ursachen von kognitiver Dysfunktion und posttraumatischem Stress bei Krebspatienten ist relevant für Prävention und Therapie. Diese kumulative Dissertation fasst zwei Artikel der prospektiven, kontrollierten Längsschnittstudie COGNICARES zusammen, die in referierten (peer-reviewed) Fachzeitschriften von internationalem Niveau veröffentlicht wurden. Die Zeitschriften haben jeweils einen fachspezifischen Impact-Faktor, der dem Journal Citation Report zufolge zu den besten 80% zählt. COGNICARES ist die erste großangelegte Studie, in der eine umfangreiche neuropsychologische Testbatterie und ein validiertes klinisches Interview zu drei Messzeitpunkten eingesetzt wurden, um kognitive Funktionen und posttraumatischen Stress bei Patientinnen mit Mamakarzinom und bei einer Kontrollgruppe zu untersuchen. Vor Therapiebeginn wurden bei den Patientinnen lediglich geringfügige kognitive Defizite festgestellt, die durch posttraumatischen Stress beeinflusst waren. Eine geringe Anzahl an Patientinnen wurde mit einer voll ausgeprägten akuten Belastungsreaktion (ABR) oder posttraumatischen Belastungsstörung (PTBS) diagnostiziert. Allerdings zeigten mehr als 80% der Patientinnen kurz nach der Diagnose posttraumatische Belastungssymptome, die bei der Mehrheit der Patientinnen ein Jahr nach der Diagnose noch vorhanden waren. Die Relevanz der Ergebnisse wird im Kontext des in 2013 erschienen Diagnostic and Statistical Manual of Mental Diseases-V (DSM-V) diskutiert

Impairment in active navigation from trauma and Post-Traumatic Stress Disorder.

The study investigated the impact of trauma exposure and of Post-Traumatic Stress Disorder (PTSD) on spatial processing and active navigation in a sample (n = 138) comprising civilians (n = 91), police officers (n = 22) and veterans (n = 27). Individuals with previous trauma exposure exhibited significantly poorer hippocampal-dependent (allocentric) navigation performance on active navigation in a virtual environment (the Alternative Route task) regardless of whether or not they had PTSD (scoring above 20 on the PTSD Diagnostic Scale). No performance differences were found in static perspective taking (the Four Mountains task). Moreover, an associative information processing bias in those with PTSD interfered with ability to use hippocampal-dependent processing in active navigation. This study provides new evidence of impaired active navigation in individuals with trauma exposure and highlights the importance of considering the relationship between trauma and spatial processing in clinical and occupational settings

Traumatic Brain Injury Service, Walter Reed National Military Medical Center 4. National Intrepid Center of Excellence, Walter Reed National Military Medical Center 5. National Institute of Nursing Research , National Institutes of Health 6. RTI Internati

Abstract Traumatic brain injury, depression and posttraumatic stress disorder (PTSD) are neurocognitive syndromes often associated with impairment of physical and mental health, as well as functional status. These syndromes are also frequent in military service members (SMs) after combat, although their presentation is often delayed until months after their return. The objective of this prospective cohort study was the identification of independent predictors of neurocognitive syndromes upon return from deployment could facilitate early intervention to prevent disability. We completed a comprehensive baseline assessment, followed by serial evaluations at three, six, and 12 months, to assess for new-onset PTSD, depression, or postconcussive syndrome (PCS) in order to identify baseline factors most strongly associated with subsequent neurocognitive syndromes. On serial follow-up, seven participants developed at least one neurocognitive syndrome: five with PTSD, one with depression and PTSD, and one with PCS. On univariate analysis, 60 items were associated with syndrome development at p < 0.15. Decision trees and ensemble tree multivariate models yielded four common independent predictors of PTSD: right superior longitudinal fasciculus tract volume on MRI; resting state connectivity between the right amygdala and left superior temporal gyrus (BA41/42) on functional MRI; and single nucleotide polymorphisms in the genes coding for myelin basic protein as well as brain-derived neurotrophic factor. Our findings require follow-up studies with greater sample size and suggest that neuroimaging and molecular biomarkers may help distinguish those at high risk for post-deployment neurocognitive syndromes

Traumatic Brain Injury Service, Walter Reed National Military Medical Center 4. National Intrepid Center of Excellence, Walter Reed National Military Medical Center 5. National Institute of Nursing Research , National Institutes of Health 6. RTI Internati

Abstract Traumatic brain injury, depression and posttraumatic stress disorder (PTSD) are neurocognitive syndromes often associated with impairment of physical and mental health, as well as functional status. These syndromes are also frequent in military service members (SMs) after combat, although their presentation is often delayed until months after their return. The objective of this prospective cohort study was the identification of independent predictors of neurocognitive syndromes upon return from deployment could facilitate early intervention to prevent disability. We completed a comprehensive baseline assessment, followed by serial evaluations at three, six, and 12 months, to assess for new-onset PTSD, depression, or postconcussive syndrome (PCS) in order to identify baseline factors most strongly associated with subsequent neurocognitive syndromes. On serial follow-up, seven participants developed at least one neurocognitive syndrome: five with PTSD, one with depression and PTSD, and one with PCS. On univariate analysis, 60 items were associated with syndrome development at p < 0.15. Decision trees and ensemble tree multivariate models yielded four common independent predictors of PTSD: right superior longitudinal fasciculus tract volume on MRI; resting state connectivity between the right amygdala and left superior temporal gyrus (BA41/42) on functional MRI; and single nucleotide polymorphisms in the genes coding for myelin basic protein as well as brain-derived neurotrophic factor. Our findings require follow-up studies with greater sample size and suggest that neuroimaging and molecular biomarkers may help distinguish those at high risk for post-deployment neurocognitive syndromes

An Exploratory Study of Posttraumatic Stress Disorder, Sleep Disturbances, and 63 Executive Functioning in Veterans

Introduction: Hypervigilance, hyperarousal, and sleep disturbances are components in the diagnosis and treatment of Posttraumatic Stress Disorder (PTSD) and other trauma-related diagnoses. The current study explores the relationships between PTSD, sleep, and executive functioning among military veterans. Method: The Immediate Post-concussion Assessment and Cognitive Testing Battery (ImPACT) is utilized to examine the cognitive performance of 18 veterans. Dependent measures included composite scores of verbal memory, visual memory, processing speed, and reaction time from the ImPACT computerized test battery, as well as total symptom scores from the Clinician Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index, and the Pittsburgh Sleep Quality Index – Addendum for PTSD (PSQI-A). Results: Veterans showed significant deficits in verbal memory and slower reaction times relative to normative data. The veterans did not differ from the normative group on visual memory and processing speed indices. After adjusting for sleep disturbances, reaction time remained significantly correlated with PTSD symptom severity in veterans. Conclusions: Executive functioning deficits in verbal memory and reaction time are detectable in veterans who endorse clinical and subthreshold symptoms of PTSD

Psychobiological factors of resilience and depression in late life.

In contrast to traditional perspectives of resilience as a stable, trait-like characteristic, resilience is now recognized as a multidimentional, dynamic capacity influenced by life-long interactions between internal and environmental resources. We review psychosocial and neurobiological factors associated with resilience to late-life depression (LLD). Recent research has identified both psychosocial characteristics associated with elevated LLD risk (e.g., insecure attachment, neuroticism) and psychosocial processes that may be useful intervention targets (e.g., self-efficacy, sense of purpose, coping behaviors, social support). Psychobiological factors include a variety of endocrine, genetic, inflammatory, metabolic, neural, and cardiovascular processes that bidirectionally interact to affect risk for LLD onset and course of illness. Several resilience-enhancing intervention modalities show promise for the prevention and treatment of LLD, including cognitive/psychological or mind-body (positive psychology; psychotherapy; heart rate variability biofeedback; meditation), movement-based (aerobic exercise; yoga; tai chi), and biological approaches (pharmacotherapy, electroconvulsive therapy). Additional research is needed to further elucidate psychosocial and biological factors that affect risk and course of LLD. In addition, research to identify psychobiological factors predicting differential treatment response to various interventions will be essential to the development of more individualized and effective approaches to the prevention and treatment of LLD

Long-term negative emotional outcomes of warzone TBI

Objective: Many veterans of the Iraq and Afghanistan Wars have experienced traumatic brain injury (TBI). Although prior work has examined associations between TBI and development of psychi- atric syndromes, less is known about associations between TBI and component emotions constituting these syndromes, especially in the long term. The purpose of this study was to examine the long-term emotional consequences of deployment-related TBI. Methods: As part of VA Cooperative Studies Program #566, we assessed a sample of n1⁄4456US Army soldiers prior to an index deployment to Iraq, and again an average of 8.3 years (SD1⁄42.4years) after their deployment for a long-term follow-up assessment. In this report, we used adjusted regression analyses to examine the relationship of deployment TBI to depression, anxiety, and stress symptom severity measured at the long-term follow-up assessment. A structured interview was used to determine TBI history; the Depression, Anxiety, and Stress Scale, 21-item version (DASS-21) was used to determine emotional status at the follow-up evaluation. Results: Warzone TBI events, particularly when greater than mild in severity, were independently associated with depression, anx- iety, and stress severity at long-term follow-up, even after taking into account variance attributable to pre-deployment emotional distress and war-zone stress. Post-hoc analyses did not detect independent associations of either number of events or injury mechanism with outcomes. Conclusions: These findings highlight the potentially enduring and multi-faceted emotional effects of deployment TBI, underscor- ing the need for early assessment of negative affectivity in war- zone veterans reporting TBI

Long-term negative emotional outcomes of warzone TBI

Objective: Many veterans of the Iraq and Afghanistan Wars have experienced traumatic brain injury (TBI). Although prior work has examined associations between TBI and development of psychi- atric syndromes, less is known about associations between TBI and component emotions constituting these syndromes, especially in the long term. The purpose of this study was to examine the long-term emotional consequences of deployment-related TBI. Methods: As part of VA Cooperative Studies Program #566, we assessed a sample of n1⁄4456US Army soldiers prior to an index deployment to Iraq, and again an average of 8.3 years (SD1⁄42.4years) after their deployment for a long-term follow-up assessment. In this report, we used adjusted regression analyses to examine the relationship of deployment TBI to depression, anxiety, and stress symptom severity measured at the long-term follow-up assessment. A structured interview was used to determine TBI history; the Depression, Anxiety, and Stress Scale, 21-item version (DASS-21) was used to determine emotional status at the follow-up evaluation. Results: Warzone TBI events, particularly when greater than mild in severity, were independently associated with depression, anx- iety, and stress severity at long-term follow-up, even after taking into account variance attributable to pre-deployment emotional distress and war-zone stress. Post-hoc analyses did not detect independent associations of either number of events or injury mechanism with outcomes. Conclusions: These findings highlight the potentially enduring and multi-faceted emotional effects of deployment TBI, underscor- ing the need for early assessment of negative affectivity in war- zone veterans reporting TBI

Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders: Evidence Report

In April 2010, President Obama declared a space pioneering goal for the United States in general and NASA in particular. "Fifty years after the creation of NASA, our goal is no longer just a destination to reach. Our goal is the capacity for people to work and learn and operate and live safely beyond the Earth for extended periods of time, ultimately in ways that are more sustainable and even indefinite." Thus NASA's Strategic Objective 1.1 emerged as "expand human presence into the solar system and to the surface of Mars to advance exploration, science, innovation, benefits to humanity, and international collaboration" (NASA 2015b). Any space flight, be it of long or short duration, occurs in an extreme environment that has unique stressors. Even with excellent selection methods, the potential for behavioral problems among space flight crews remain a threat to mission success. Assessment of factors that are related to behavioral health can help minimize the chances of distress and, thus, reduce the likelihood of adverse cognitive or behavioral conditions and psychiatric disorders arising within a crew. Similarly, countermeasures that focus on prevention and treatment can mitigate the cognitive or behavioral conditions that, should they arise, would impact mission success. Given the general consensus that longer duration, isolation, and confined missions have a greater risk for behavioral health ensuring crew behavioral health over the long term is essential. Risk, which within the context of this report is assessed with respect to behavioral health and performance, is addressed to deter development of cognitive and behavioral degradations or psychiatric conditions in space flight and analog populations, and to monitor, detect, and treat early risk factors, predictors and other contributing factors. Based on space flight and analog evidence, the average incidence rate of an adverse behavioral health event occurring during a space mission is relatively low for the current conditions. While mood and anxiety disturbances have occurred, no behavioral emergencies have been reported to date in space flight. Anecdotal and empirical evidence indicate that the likelihood of an adverse cognitive or behavioral condition or psychiatric disorder occurring greatly increases with the length of a mission. Further, while cognitive, behavioral, or psychiatric conditions might not immediately and directly threaten mission success, such conditions can, and do, adversely impact individual and crew health, welfare, and performance

Theoretical Accounts of Gulf War Syndrome: From Environmental Toxins to Psychoneuroimmunology and Neurodegeneration

Non-specific illness includes a wide variety of symptoms: behavioural (e.g., reduced food and water intake), cognitive (e.g., memory and concentration problems) and physiological (e.g., fever). This paper reviews evidence suggesting that such symptoms can be explained more parsimoniously as a single symptom cluster than as a set of separate illnesses such as Gulf War Syndrome (GWS) and chronic fatigue syndrome (CFS). This superordinate syndrome could have its biological basis in the activity of pro-inflammatory cytokines (in particular interleukin-1: IL-1), that give rise to what has become known as the ‘sickness response’. It is further argued that the persistence of non-specific illness in chronic conditions like GWS may be (in part) attributable to a bio-associative mechanism (Ferguson and Cassaday, 1999). In the case of GWS, physiological challenges could have produced a non-specific sickness response that became associated with smells (e.g., petrol), coincidentally experienced in the Persian Gulf. On returning to the home environment, these same smells would act as associative triggers for the maintenance of (conditioned) sickness responses. Such associative mechanisms could be mediated through the hypothalamus and limbic system via vagal nerve innervation and would provide an explanation for the persistence of a set of symptoms (e.g., fever) that should normally be short lived and self-limiting. We also present evidence that the pattern of symptoms produced by the pro-inflammatory cytokines reflects a shift in immune system functioning towards a (T-helper-1) Th1 profile. This position contrasts with other immunological accounts of GWS that suggest that the immune system demonstrates a shift to a Th2 (allergy) profile. Evidence pertaining to these two contrasting positions is reviewed