Cancer-related cognitive impairment and associated factors in a sample of older male oral-digestive cancer survivors.

OBJECTIVE: This study examines the demographic and clinical variables associated with cancer-related cognitive impairment (CRCI) in a sample of older, male, oral-digestive cancer survivors at VA Medical Centers in Boston and Houston. METHODS: A two-time point, longitudinal design was used, with cognitive assessment conducted at 6 and 18 months post-diagnosis. Using ANCOVA, the cognitive functioning of 88 older adults with head and neck, esophageal, gastric, or colorectal cancers was compared with that of 88 healthy controls. Paired t-tests examined cognitive change over time in the cancer group. Hierarchical linear regression examined variables potentially associated with cognitive impairment at 18 months. RESULTS: Forty-eight percent of cancer patients exhibited cognitive impairment 6 months post-cancer diagnosis, and 40% at 18 months. Cancer survivors were impaired relative to controls on measures of sustained attention, memory, and verbal fluency at 18 months, controlling for age. Older age, low hemoglobin, and cancer-related PTSD were associated with worse cognition at 18 months. CONCLUSIONS: CRCI is more frequent in older adults than reported in studies of younger adults and may be more frequent in men. Potential areas of intervention for CRCI include psychotherapy for cancer-related PTSD, treatment of anemia, and awareness of particularly vulnerable cognitive domains such as sustained attention, memory, and verbal fluency.

Development of a Bereavement Group in a Geriatric Mental Health Clinic for Veterans.

OBJECTIVES: This article describes the development and program evaluation of an 8-session outpatient geriatric mental health clinic bereavement group for United States military veterans who experienced the death of a loved one. METHODS: Group materials were developed based on a review of literature, with a focus on the dual process model of coping with bereavement and complicated grief treatment. Data are presented from 19 veterans who attended at least 4 of the 8 sessions across the five offerings of this group between 2013 and 2015. RESULTS: Self-report measures of complicated grief and depressive symptoms decreased significantly from the first to the final session. Veterans indicated that the group met their treatment goals and that they would recommend it to others. Adaptations made to the group over time based on feedback from members and facilitators are discussed. CONCLUSIONS: Preliminary evidence suggests that the group described in this manuscript is effective for bereaved older, male veterans. Future research would be helpful including larger samples and controlled studies. CLINICAL IMPLICATIONS: Most bereaved individuals do not require formal mental health treatment. However, for individuals with distressing symptoms, time-limited group therapy may be an effective treatment.

Program Evaluation of Group-based Cognitive Behavioral Therapy for Insomnia: a Focus on Treatment Adherence and Outcomes in Older Adults with Co-morbidities.

OBJECTIVE: To describe a program evaluation of the interrelationship of adherence and treatment outcomes in a sample of veteran older adults with co-morbidities who participated in group-based cognitive behavioral therapy for insomnia. METHODS: Retrospective data extraction was performed for 14 older adults. Adherence measures and sleep outcomes were measured with sleep diaries and Insomnia Severity Index. Demographic and clinical information was extracted through chart review. RESULTS: Adherence with prescribed time in bed, daily sleep diaries, and maintaining consistent time out of bed and time in bed was generally high. There were moderate, though not significant, improvements in consistency of time in bed and time out of bed over time. Adherence was not significantly associated with sleep outcomes despite improvements in most sleep outcomes. CONCLUSIONS: The non-significant relationship between sleep outcomes and adherence may reflect the moderating influence of co-morbidities or may suggest a threshold effect beyond which stricter adherence has a limited impact on outcomes. CLINICAL IMPLICATIONS: Development of multi-method adherence measures across all treatment components will be important to understand the influence of adherence on treatment outcomes as monitoring adherence to time in bed and time out of bed had limited utility for understanding treatment outcomes in our sample.

Valued life abilities among veteran cancer survivors.

BACKGROUND: When patients have multiple chronic illnesses, it is not feasible to provide disease-based care when treatments for one condition adversely affect another. Instead, health-care delivery requires a broader person-centred treatment plan based on collaborative, patient-oriented values and goals. OBJECTIVE: We examined the individual variability, thematic content, and sociodemographic correlates of valued life abilities and activities among multimorbid veterans diagnosed with life-altering cancer. SETTING AND PARTICIPANTS: Participants were 144 veterans in the 'Vet-Cares' study who completed a health-care values and goals scale 12 months after diagnosis of head and neck, gastro-oesophageal, or colorectal cancer. They had mean age of 65 years and one quarter identified as Hispanic and/or African American. DESIGN: At twelve months post-diagnosis, participants rated 16 life abilities/activities in their importance to quality of life on a 10-point Likert scale, during an in-person interview. Scale themes were validated via exploratory factor analysis and examining associations with sociodemographic variables. RESULTS: Participants rated most life abilities/activities as extremely important. Variability in responses was sufficient to identify three underlying values themes in exploratory factor analysis: self-sufficiency, enjoyment/comfort, and connection to family, friends and spirituality. Veterans with a spouse/partner rated self-sufficiency as less important. African American veterans rated connection as more important than did White veterans. CONCLUSIONS: It is feasible yet challenging to ask older, multimorbid patients to rate relative importance of values associated with life abilities/activities. Themes related to self-sufficiency, enjoyment/comfort in daily life and connection are salient and logically consistent with sociodemographic traits. Future studies should explore their role in goal-directed health care.

Developmental Differences in Relations Between Episodic Memory and Hippocampal Subregion Volume During Early Childhood.

Episodic memory shows striking improvement during early childhood. However, neural contributions to these behavioral changes are not well understood. This study examined associations between episodic memory and volume of subregions (head, body, and tail) of the hippocampus-a structure known to support episodic memory in school-aged children and adults-during early childhood (n = 45). Results revealed significant positive relations between episodic memory and volume of the hippocampal head in both the left and right hemispheres for 6- but not 4-year-old children, suggesting brain-behavior relations vary across development. These findings add new information regarding neural mechanisms of change in memory development during early childhood and suggest that developmental differences in hippocampal subregions may contribute to age-related differences in episodic memory ability.

Cancer-related PTSD symptoms in a veteran sample: association with age, combat PTSD, and quality of life.

OBJECTIVE: The diagnosis and treatment of cancer is a potentially traumatic experience that may evoke posttraumatic stress symptoms (PTSS) among survivors. This paper describes the rates of endorsement of cancer-related PTSS along with the relationship of demographic, cancer, and combat variables on PTSS and quality of life. METHODS: Veterans (N = 166) with head and neck, esophageal, gastric, or colorectal cancers were recruited through tumor registries at two regional Veterans Administration Medical Centers. Standardized scales were used to assess self-report of PTSS, combat, and quality of life. RESULTS: Most participants (86%) reported experiencing at least some cancer-related PTSS; 10% scored above a clinical cutoff for probable PTSD. In linear regressions, younger age and current combat PTSS were associated with cancer-related PTSS, whereas disease and treatment characteristics were not; in turn, cancer-related PTSS were negatively associated with physical and social quality of life. CONCLUSIONS: Individual characteristics and psychosocial factors may play a larger role than disease-related variables in determining how an individual responds to the stress of cancer diagnosis and treatment. Given the rates of reported cancer-related PTSS in this sample, and other non-veteran samples, clinicians should consider screening these following diagnosis and treatment, particularly in younger adults and those with previous trauma histories.

Characterizing within-person variance in, and menstrual cycle associations with, event-related potentials associated with positive and negative valence systems: The reward positivity and the error-related negativity.

Event-related potentials (ERPs) are widely employed as measures of transdiagnostic cognitive processes that are thought to underlie various clinical disorders (Hajcak et al., 2019). Despite their prevalent use as individual difference measures, the effects of within-person processes, such as the human menstrual cycle, on a broad range of ERPs are poorly understood. The present study leveraged a within-subject design to characterize between- and within-person variance in ERPs as well as effects of the menstrual cycle in two frequently studied ERPs associated with positive and negative valence systems underlying psychopathology-the Reward Positivity (RewP) and the Error- Related Negativity (ERN). Seventy-one naturally-cycling participants completed repeated EEG and ecological momentary assessments of positive and negative affect in the menstrual cycle's early follicular, periovulatory, and mid-luteal phases. We examined the mean degree of change between cycle phases in both ERPs, the between-person variability in the degree of change in both ERPs, and whether an individual's degree of cyclical change in these ERPs show coherence with their degree of cyclical change in positive and negative affect recorded across the cycle. Results revealed no significant changes in positive and negative affect across the cycle and rather small changes in ERP amplitudes. Significant random slopes in our model revealed larger individual differences in trajectories of change in ERP amplitudes and affect, in agreement with prior evidence of heterogeneity in dimensional hormone sensitivity. Additionally, state-variance in these ERPs correlated with positive and negative affect changes across the cycle, suggesting that cycle-mediated ERP changes may have relevance for affect and behavior. Finally, exploratory latent class growth mixture modeling revealed subgroups of individuals that display disparate patterns of change in ERPs that should be further investigated.

Antenatal anxiety symptoms outperform antenatal depression symptoms and suicidal ideation as a risk factor for postpartum suicidal ideation.

BACKGROUND AND OBJECTIVES: Suicidal ideation (SI) during the postpartum phase is linked with suicide, a leading cause of death during this period. Antenatal depression and anxiety symptoms have both been linked with increased risk for postpartum SI. However, research aimed at examining the relative contributions of antenatal anxiety and depression symptoms towards postpartum SI remains nascent. In this study, we investigated the relative contribution of antenatal anxiety symptoms, depression symptoms, and SI towards postpartum SI. DESIGN: These data are from a longitudinal study in which American mothers were assessed during pregnancy and again at six- to eight weeks postpartum. METHODS: Data were analyzed using correlations and logistic regression models. RESULTS: Antenatal anxiety symptoms and antenatal depression symptoms were significantly correlated with postpartum SI. Results from a logistic regression model indicated that antenatal anxiety symptoms (T1; OR = 1.185 [1.125, 1.245], p = .004), but not antenatal depression symptoms (T1; OR = 1.018 [0.943, 1.093], p = .812) or antenatal SI (T1; OR = 1.58 [0.11, 22.29], p = 0.73), were significantly associated with postpartum SI. CONCLUSIONS: Antenatal anxiety symptoms, depression symptoms, and SI were positively associated with postpartum SI. When examined simultaneously, anxiety symptoms during the antenatal phase (but not depression symptoms or SI) predicted SI in the postpartum phase.

Effects of acute estradiol administration on perimenstrual worsening of working memory, verbal fluency, and inhibition in patients with suicidal ideation: A randomized, crossover clinical trial.

Accumulating evidence indicates that most female patients with suicidal ideation (SI) experience a dimensional worsening of depressive symptoms and SI in the perimenstrual phase of the menstrual cycle. Experimental trials demonstrate that acute perimenstrual administration of estradiol (E2; with or without progesterone/P4), can prevent these recurring episodes of increased risk. In this archival sample drawn from one of these clinical trials, we examined whether these beneficial E2 effects extend to specific types of cognition. For a double-blind, placebo-controlled experiment, we recruited transdiagnostic psychiatric outpatients with natural menstrual cycles who experienced past-month SI (N(per-protocol sample)=23; N(intent-to-treat sample)=44). In each of two counterbalanced conditions (perimenstrual administration of 0.1mg/d transdermal E2 vs. placebo), participants completed three cognitive tasks in three menstrual cycle phases (mid-luteal, perimenstrual, mid-follicular). Multilevel models revealed a significant interaction of condition and phase: E2 administration prevented mid-luteal-to-perimenstrual drops in working memory (p=.006) and verbal fluency (p=.005) observed under placebo. No effects were found for inhibitory control. In conclusion, we find perimenstrual declines in working memory and verbal fluency in patients with SI, which can be prevented by administering E2. This study contributes to our understanding of the hormone-brain pathways involved in the cyclical worsening of suicidality.

Cancer survivor rehabilitation and recovery: protocol for the Veterans Cancer Rehabilitation Study (Vet-CaRes).

BACKGROUND: Cancer survivors are a rapidly growing and aging population in the U.S., but there are many challenges associated with the survivorship experience such as functional disabilities and psychosocial distress. When viewed next to the general population, Veterans are especially at risk for these challenges as they are older and have a high incidence of co-morbid conditions. While the Institute of Medicine (IOM) has called for further cancer survivorship research to address these challenges, we still know little about this experience from the perspective of aging Veterans. METHODS/DESIGN: We conducted a longitudinal, mixed-methods study over the course of three and a half years at the Boston and Houston VA Medical Centers. We recruited 170 Veterans diagnosed with head and neck, colorectal and esophageal/gastric cancers that were identified from the VA tumor registry. Veterans completed three in-depth interviews, conducted at 6, 12 and 18 months after pathology confirmation, measuring the physical, social and psychological factors related to cancer survivorship. The longitudinal design allowed us to assess any changes in cancer related disability and distress over time. DISCUSSION: Weekly teleconference study team meetings were a key aspect to the research process. Issues related to recruitment, data management and analysis, and the dissemination of research results was discussed. Interviewers presented detailed case reports of completed interviews that allowed us to refine our interview protocols. We also discussed issues relevant to the Veteran population of which we were previously unaware and some of the challenges of the research process itself. This novel study produced a robust data set that documents the functional and psychosocial cancer survivorship experiences of aging Veterans. The longitudinal design will help us more fully understand the recovery patterns for this specific population, and identify the unique needs and gaps in health services.

Influences of age and pubertal development on P300 amplitude trajectory across two years in female adolescents.

The P300 event-related potential (ERP) has been extensively studied across the human lifespan. However, many studies examining age-related effects are cross-sectional, and few have considered the unique role that pubertal development may have on P300 developmental trajectories. The current study examined whether age, pubertal maturation or their interaction predicted changes in P300 amplitude over two years among 129 females between the ages of 8 and 15 years at baseline. Participants completed a flanker task while EEG was recorded at a baseline and two-year follow-up visit. Both baseline age and increased pubertal development were associated with smaller P300 amplitude at follow-up. However, the influence of age was qualified by an interaction between age and pubertal maturation: among younger girls only, increased pubertal development predicted decreases in P300, whereas decreased pubertal development predicted increases in P300. These data indicate that pubertal timing impacts neurodevelopmental changes in P300 amplitude - such that high versus low pubertal development among 8- to 10-year-old girls predicted differential trajectories of neural activity. In light of links between reduced P300 and mental health disorders, such as depression, future studies might examine whether neurodevelopmental changes influenced by early-onset pubertal development could account for increases in these mental health problems.

Examining Blunted Initial Response to Reward and Recent Suicidal Ideation in Children and Adolescents Using Event-Related Potentials: Failure to Conceptually Replicate Across Two Independent Samples.

A recent study by Tsypes and colleagues (2019) found that children with recent suicidal ideation had blunted neural reward processing, as measured by the reward positivity (RewP), compared to matched controls, and that this difference was driven by reduced neural responses to monetary loss, rather than to reward. Here, we aimed to conceptually replicate and extend these findings in two samples (n = 264, 27 with suicidal ideation; and n = 314, 49 with suicidal ideation at baseline) of children and adolescents (11 to 15 years and 8 to 15 years, respectively). Results from both samples showed no evidence that children and adolescents with suicidal ideation have abnormal reward or loss processing, nor that reward processing predicts suicidal ideation two years later. The results highlight the need for greater statistical power, as well as continued research examining the neural underpinnings of suicidal thoughts and behaviors.

Differential binding of Escherichia coli McrA protein to DNA sequences that contain the dinucleotide m5CpG.

The Escherichia coli McrA protein, a putative C(5)-methylcytosine/C(5)-hydroxyl methylcytosine-specific nuclease, binds DNA with symmetrically methylated HpaII sequences (Cm5CGG), but its precise recognition sequence remains undefined. To determine McrA's binding specificity, we cloned and expressed recombinant McrA with a C-terminal StrepII tag (rMcrA-S) to facilitate protein purification and affinity capture of human DNA fragments with m5C residues. Sequence analysis of a subset of these fragments and electrophoretic mobility shift assays with model methylated and unmethylated oligonucleotides suggest that N(Y > R) m5CGR is the canonical binding site for rMcrA-S. In addition to binding HpaII-methylated double-stranded DNA, rMcrA-S binds DNA containing a single, hemimethylated HpaII site; however, it does not bind if A, C, T or U is placed across from the m5C residue, but does if I is opposite the m5C. These results provide the first systematic analysis of McrA's in vitro binding specificity.

Reduced P300 amplitude is consistently associated with trait anhedonia across repeated assessments.

Understanding how event-related potentials (ERPs) change following repeated assessments is critical to advance our understanding of neural mechanisms implicated in psychopathology. Specifically, it is unclear if associations between ERPs and individual differences can be reproduced when repeatedly measured within the same participants, or if clinical characteristics impact ERP trajectories over repeated assessments. The present study assessed P300 amplitude and latency from a flanker task at four time points over one month (M = 7.24 days between assessments [SD = 1.02]) in 79 female undergraduates to examine how P300 amplitude/latency changes across repeated assessments, the presence of associations between within- and between-subjects measures of current depressive symptoms and the P300, and if between-subjects depressive symptoms moderated change in P300 over repeated assessment. Results using multilevel modeling indicated a significant reduction in P300 amplitude and latency across assessments. Individuals with increased trait anhedonia (i.e., between-subjects) exhibited reduced P300 amplitudes across assessments; there were no associations of within-subjects fluctuations in anhedonia symptoms and P300 amplitude across assessments. There was also no interaction between number of assessments and between-subjects anhedonia in relation to P300 amplitude. Unlike anhedonia, between-subjects dysphoria was unrelated to P300. These results demonstrate a relatively specific and consistent association between an attenuated P300 amplitude and trait anhedonia across repeated assessments - data that may further suggest that flanker P300 amplitude reflects hedonic and motivational processes.

The P300 and late positive potential in pregnancy prospectively predict increases in depressive and anxious symptoms in the early postpartum period.

Postnatal depression and anxiety disorders pose a major burden on maternal mental health. While psychosocial risk factors for perinatal depression and anxiety are well-researched, there is a dearth of research examining neural biomarkers of risk for postnatal increases in depression and anxiety. Previous studies suggest two different event-related potentials, the P300 and the late positive potential (LPP), may predict the course of depressive and anxious symptoms in non-perinatal populations. In a sample of 221 perinatal women, the present study utilized an emotional interrupt task administered in pregnancy to examine whether antenatal P300 and LPP amplitudes may predict change in depressive and anxious symptoms from pregnancy to the early postpartum period. Zero-order correlations and linear regressions revealed that a reduced antenatal P300 to target stimuli and an enhanced LPP to positive infant images were uniquely associated with postnatal depressive and anxiety symptoms, respectively, and that these ERPs were independent predictors beyond antenatal self-report measures of psychological symptoms. Furthermore, individuals with increased depressive symptoms in pregnancy exhibited a stronger negative association between antenatal P300 amplitude and postnatal depressive symptoms. The present findings underscore the possibility that the measurement of ERPs during pregnancy could serve as a screening tool for risk for perinatal depression and anxiety, and thereby assist with identifying at-risk individuals who might benefit from prevention efforts.

The rewards of motherhood: Neural response to reward in pregnancy prospectively predicts maternal bonding with the infant in the postpartum period.

Mother-to-infant attachment is critical to the health of mothers and offspring. While reward circuitry is implicated in maternal attachment, no studies have yet examined whether antenatal (i.e., in pregnancy) reward responsiveness predicts mother-to-infant bonding in the postnatal period. In a sample of 63 women, we examined whether the Reward Positivity (RewP), an event-related potential elicited to feedback indicating monetary reward, measured in pregnancy prospectively predicts self-reported mother-to-infant attachment at approximately one year postpartum. An increased antenatal RewP was associated with increased postnatal pleasure in proximity with the infant. Furthermore, this association was independent of associations with depression, anxiety, and stress symptoms. This is the first study to find a prospective association between reward responsiveness in pregnancy and postnatal bonding with the infant. Future directions for attachment research are discussed.

Increased dehydroepiandrosterone (DHEA) is associated with anxiety in adolescent girls.

The pubertal period is a time of rapid increase in the incidence of anxiety disorders, and thus, pubertal hormones may play a role in the precipitation of anxious psychopathology. DHEA, a steroid hormone that surges in adolescence, has been previously linked to anxiety, although the direction of this effect has been mixed. Using a cross-sectional design in a sample of 286 adolescent girls, the present study examined associations between salivary DHEA concentrations and self-report and interview-based measures of anxiety while controlling for pubertal status, menarche status, assessment time of day, and other hormones including testosterone, estradiol, and progesterone. Increased salivary DHEA concentrations were associated with more self-reported anxiety symptoms, increased anxiety symptom counts based on clinical interview, and increased probability of an anxiety disorder. Out of all anxiety symptom domains examined, generalized anxiety disorder symptoms were the best predictor of salivary DHEA concentrations after controlling for pubertal development. Collectively, our findings suggest relevance for DHEA in the development of anxiety in the pubertal period, as well as a robust relationship between DHEA and emerging symptoms of pathological worry during adolescence. The present study underscores the importance of examining associations between DHEA concentrations and anxiety in longitudinal designs.

Developmental trajectory of the late positive potential: Using temporal-spatial PCA to characterize within-subject developmental changes in emotional processing.

The late positive potential (LPP) is characterized by temporal and spatial changes across development-though existing work has primarily relied on visual or statistical comparisons of relatively few electrodes and averaged activity over time. The current study used an empirically based approach to characterize temporal and spatial changes in ERPs over time. Data were utilized from a large longitudinal study (N = 380) in which the LPP was recorded to pleasant, neutral, and unpleasant pictures around age 9 and again around age 12. Age 9 ERPs were subtracted from age 12 ERPs for all three image types; the resulting ERPs for each subject at each electrode site were then submitted to a temporospatial principal component analysis (PCA). A PCA factor was greater in amplitude for emotional pictures compared to neutral pictures between ages 9 and 12, evident as an occipital negativity and frontocentral positivity that peaked approximately 850 ms following picture presentation. Furthermore, the factor scores to emotional pictures for this component increased as a function of age 12 pubertal development, consistent with the notion that the LPP shifts from occipital to more frontocentral sites in relation to developmental changes from childhood to adolescence. A similar factor was observed when PCA was applied to all ERPs from both ages 9 and 12. Using temporospatial PCA on ERPs collected from the same subjects over time-especially within-subject subtraction-based ERPs-provides a concise way of characterizing and quantifying within-subject developmental changes in both the timing and scalp distribution of ERPs.

Detection and quantification of hepatitis C virus (HCV) by MultiCode-RTx real-time PCR targeting the HCV 3' untranslated region.

A prototype, real-time reverse-transcription PCR assay, based on MultiCode-RTx technology, quantifying hepatitis C virus (HCV) RNA by targeting the HCV 3' untranslated region demonstrated linearity over 7 logs, with a good correlation between the quantitative results of this assay and the results of two commercially available comparator assays for 466 clinical specimens comprising all six HCV genotypes.