PARTAKE survey of public knowledge and perceptions of clinical research in India.

BACKGROUND: A public that is an informed partner in clinical research is important for ethical, methodological, and operational reasons. There are indications that the public is unaware or misinformed, and not sufficiently engaged in clinical research but studies on the topic are lacking. PARTAKE - Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment is a program aimed at increasing public awareness and partnership in clinical research. The PARTAKE Survey is a component of the program. OBJECTIVE: To study public knowledge and perceptions of clinical research. METHODS: A 40-item questionnaire combining multiple-choice and open-ended questions was administered to 175 English- or Hindi-speaking individuals in 8 public locations representing various socioeconomic strata in New Delhi, India. RESULTS: Interviewees were 18-84 old (mean: 39.6, SD ± 16.6), 23.6% female, 68.6% employed, 7.3% illiterate, 26.3% had heard of research, 2.9% had participated and 58.9% expressed willingness to participate in clinical research. The following perceptions were reported (% true/% false/% not aware): 'research benefits society' (94.1%/3.5%/2.3%), 'the government protects against unethical clinical research' (56.7%/26.3%/16.9%), 'research hospitals provide better care' (67.2%/8.7%/23.9%), 'confidentiality is adequately protected' (54.1%/12.3%/33.5%), 'participation in research is voluntary' (85.3%/5.8%/8.7%); 'participants treated like 'guinea pigs'' (20.7%/53.2%/26.0%), and 'compensation for participation is adequate' (24.7%/12.9%/62.3%). CONCLUSIONS: Results suggest the Indian public is aware of some key features of clinical research (e.g., purpose, value, voluntary nature of participation), and supports clinical research in general but is unaware of other key features (e.g., compensation, confidentiality, protection of human participants) and exhibits some distrust in the conduct and reporting of clinical trials. Larger, cross-cultural surveys are required to inform educational programs addressing these issues.

Is chronic asthma associated with shorter leukocyte telomere length at midlife?

RATIONALE: Asthma is prospectively associated with age-related chronic diseases and mortality, suggesting the hypothesis that asthma may relate to a general, multisystem phenotype of accelerated aging. OBJECTIVES: To test whether chronic asthma is associated with a proposed biomarker of accelerated aging, leukocyte telomere length. METHODS: Asthma was ascertained prospectively in the Dunedin Multidisciplinary Health and Development Study cohort (n = 1,037) at nine in-person assessments spanning ages 9-38 years. Leukocyte telomere length was measured at ages 26 and 38 years. Asthma was classified as life-course-persistent, childhood-onset not meeting criteria for persistence, and adolescent/adult-onset. We tested associations between asthma and leukocyte telomere length using regression models. We tested for confounding of asthma-leukocyte telomere length associations using covariate adjustment. We tested serum C-reactive protein and white blood cell counts as potential mediators of asthma-leukocyte telomere length associations. MEASUREMENTS AND MAIN RESULTS: Study members with life-course-persistent asthma had shorter leukocyte telomere length as compared with sex- and age-matched peers with no reported asthma. In contrast, leukocyte telomere length in study members with childhood-onset and adolescent/adult-onset asthma was not different from leukocyte telomere length in peers with no reported asthma. Adjustment for life histories of obesity and smoking did not change results. Study members with life-course-persistent asthma had elevated blood eosinophil counts. Blood eosinophil count mediated 29% of the life-course-persistent asthma-leukocyte telomere length association. CONCLUSIONS: Life-course-persistent asthma is related to a proposed biomarker of accelerated aging, possibly via systemic eosinophilic inflammation. Life histories of asthma can inform studies of aging.

A neural biomarker of psychological vulnerability to future life stress.

We all experience a host of common life stressors such as the death of a family member, medical illness, and financial uncertainty. While most of us are resilient to such stressors, continuing to function normally, for a subset of individuals, experiencing these stressors increases the likelihood of developing treatment-resistant, chronic psychological problems, including depression and anxiety. It is thus paramount to identify predictive markers of risk, particularly those reflecting fundamental biological processes that can be targets for intervention and prevention. Using data from a longitudinal study of 340 healthy young adults, we demonstrate that individual differences in threat-related amygdala reactivity predict psychological vulnerability to life stress occurring as much as 1 to 4 years later. These results highlight a readily assayed biomarker, threat-related amygdala reactivity, which predicts psychological vulnerability to commonly experienced stressors and represents a discrete target for intervention and prevention.

Cardiorespiratory fitness and cognitive function in midlife: neuroprotection or neuroselection?

OBJECTIVE: A study was undertaken to determine whether better cognitive functioning at midlife among more physically fit individuals reflects neuroprotection, by which fitness protects against age-related cognitive decline, or neuroselection, by which children with higher cognitive functioning select more active lifestyles. METHODS: Children in the Dunedin Longitudinal Study (N = 1,037) completed the Wechsler Intelligence Scales and the Trail Making, Rey Delayed Recall, and Grooved Pegboard tasks as children and again at midlife (age = 38 years). Adult cardiorespiratory fitness was assessed using a submaximal exercise test to estimate maximum oxygen consumption adjusted for body weight in milliliters/minute/kilogram. We tested whether more fit individuals had better cognitive functioning than their less fit counterparts (which could be consistent with neuroprotection), and whether better childhood cognitive functioning predisposed to better adult cardiorespiratory fitness (neuroselection). Finally, we examined possible mechanisms of neuroselection. RESULTS: Participants with better cardiorespiratory fitness had higher cognitive test scores at midlife. However, fitness-associated advantages in cognitive functioning were already present in childhood. After accounting for childhood baseline performance on the same cognitive tests, there was no association between cardiorespiratory fitness and midlife cognitive functioning. Socioeconomic and health advantages in childhood and healthier lifestyles during young adulthood explained most of the association between childhood cognitive functioning and adult cardiorespiratory fitness. INTERPRETATION: We found no evidence for a neuroprotective effect of cardiorespiratory fitness as of midlife. Instead, children with better cognitive functioning are selecting healthier lives. Fitness interventions may enhance cognitive functioning. However, observational and experimental studies testing neuroprotective effects of physical fitness should consider confounding by neuroselection.

Schema-driven construction of future autobiographical traumatic events: the future is much more troubling than the past.

Research on future episodic thought has produced compelling theories and results in cognitive psychology, cognitive neuroscience, and clinical psychology. In experiments aimed to integrate these with basic concepts and methods from autobiographical memory research, 76 undergraduates remembered past and imagined future positive and negative events that had or would have a major impact on them. Correlations of the online ratings of visual and auditory imagery, emotion, and other measures demonstrated that individuals used the same processes to the same extent to remember past and construct future events. These measures predicted the theoretically important metacognitive judgment of past reliving and future "preliving" in similar ways. On standardized tests of reactions to traumatic events, scores for future negative events were much higher than scores for past negative events. The scores for future negative events were in the range that would qualify for a diagnosis of posttraumatic stress disorder (PTSD); the test was replicated (n = 52) to check for order effects. Consistent with earlier work, future events had less sensory vividness. Thus, the imagined symptoms of future events were unlikely to be caused by sensory vividness. In a second experiment, to confirm this, 63 undergraduates produced numerous added details between 2 constructions of the same negative future events; deficits in rated vividness were removed with no increase in the standardized tests of reactions to traumatic events. Neuroticism predicted individuals' reactions to negative past events but did not predict imagined reactions to future events. This set of novel methods and findings is interpreted in the contexts of the literatures of episodic future thought, autobiographical memory, PTSD, and classic schema theory.

Narrative centrality and negative affectivity: independent and interactive contributors to stress reactions.

Reactions to stressful negative events have long been studied using approaches based on either the narrative interpretation of the event or the traits of the individual. Here, we integrate these 2 approaches by using individual-differences measures of both the narrative interpretation of the stressful event as central to one's life and the personality characteristic of negative affectivity. We show that they each have independent contributions to stress reactions and that high levels on both produce greater than additive effects. The effects on posttraumatic stress symptoms are substantial for both undergraduates (Study 1, n = 2,296; Study 3, n = 488) and veterans (Study 2, n = 104), with mean levels for participants low on both measures near floor on posttraumatic stress symptoms and those high on both measures scoring at or above diagnostic thresholds. Study 3 included 3 measures of narrative centrality and 3 of negative affectivity to demonstrate that the effects were not limited to a single measure. In Study 4 (n = 987), measures associated with symptoms of posttraumatic stress correlated substantially with either measures of narrative centrality or measures of negative affectivity. The concepts of narrative centrality and negative affectivity and the results are consistent with findings from clinical populations using similar measures and with current approaches to therapy. In broad nonclinical populations, such as those used here, the results suggest that we might be able to substantially increase our ability to account for the severity of stress response by including both concepts.

Age-related effects on the neural correlates of autobiographical memory retrieval.

Older adults recall less episodically rich autobiographical memories (AM), however, the neural basis of this effect is not clear. Using functional MRI, we examined the effects of age during search and elaboration phases of AM retrieval. Our results suggest that the age-related attenuation in the episodic richness of AMs is associated with difficulty in the strategic retrieval processes underlying recovery of information during elaboration. First, age effects on AM activity were more pronounced during elaboration than search, with older adults showing less sustained recruitment of the hippocampus and ventrolateral prefrontal cortex (VLPFC) for less episodically rich AMs. Second, there was an age-related reduction in the modulation of top-down coupling of the VLPFC on the hippocampus for episodically rich AMs. In sum, the present study shows that changes in the sustained response and coupling of the hippocampus and prefrontal cortex (PFC) underlie age-related reductions in episodic richness of the personal past.

The impact of the developmental timing of trauma exposure on PTSD symptoms and psychosocial functioning among older adults.

The present study examined the impact of the developmental timing of trauma exposure on posttraumatic stress disorder (PTSD) symptoms and psychosocial functioning in a large sample of community-dwelling older adults (N = 1,995). Specifically, we investigated whether the negative consequences of exposure to traumatic events were greater for traumas experienced during childhood, adolescence, young adulthood, midlife, or older adulthood. Each of these developmental periods is characterized by age-related changes in cognitive and social processes that may influence psychological adjustment following trauma exposure. Results revealed that older adults who experienced their currently most distressing traumatic event during childhood exhibited more severe symptoms of PTSD and lower subjective happiness compared with older adults who experienced their most distressing trauma after the transition to adulthood. Similar findings emerged for measures of social support and coping ability. The differential effects of childhood compared with later life traumas were not fully explained by differences in cumulative trauma exposure or by differences in the objective and subjective characteristics of the events. Our findings demonstrate the enduring nature of traumatic events encountered early in the life course and underscore the importance of examining the developmental context of trauma exposure in investigations of the long-term consequences of traumatic experiences.

The reminiscence bump in the temporal distribution of the best football players of all time: Pelé, Cruijff or Maradona?

The reminiscence bump is the tendency to recall more autobiographical memories from adolescence and early adulthood than from adjacent lifetime periods. In this online study, the robustness of the reminiscence bump was examined by looking at participants' judgements about the quality of football players. Dutch participants (N = 619) were asked who they thought the five best players of all time were. The participants could select the names from a list or enter the names when their favourite players were not on the list. Johan Cruijff, Pelé, and Diego Maradona were the three most often mentioned players. Participants frequently named football players who reached the midpoint of their career when the participants were adolescents (mode = 17). The results indicate that the reminiscence bump can also be identified outside the autobiographical memory domain.

Dynamic neural networks supporting memory retrieval.

How do separate neural networks interact to support complex cognitive processes such as remembrance of the personal past? Autobiographical memory (AM) retrieval recruits a consistent pattern of activation that potentially comprises multiple neural networks. However, it is unclear how such large-scale neural networks interact and are modulated by properties of the memory retrieval process. In the present functional MRI (fMRI) study, we combined independent component analysis (ICA) and dynamic causal modeling (DCM) to understand the neural networks supporting AM retrieval. ICA revealed four task-related components consistent with the previous literature: 1) medial prefrontal cortex (PFC) network, associated with self-referential processes, 2) medial temporal lobe (MTL) network, associated with memory, 3) frontoparietal network, associated with strategic search, and 4) cingulooperculum network, associated with goal maintenance. DCM analysis revealed that the medial PFC network drove activation within the system, consistent with the importance of this network to AM retrieval. Additionally, memory accessibility and recollection uniquely altered connectivity between these neural networks. Recollection modulated the influence of the medial PFC on the MTL network during elaboration, suggesting that greater connectivity among subsystems of the default network supports greater re-experience. In contrast, memory accessibility modulated the influence of frontoparietal and MTL networks on the medial PFC network, suggesting that ease of retrieval involves greater fluency among the multiple networks contributing to AM. These results show the integration between neural networks supporting AM retrieval and the modulation of network connectivity by behavior.

Imagery and retrieval of auditory and visual information: neural correlates of successful and unsuccessful performance.

Remembering past events - or episodic retrieval - consists of several components. There is evidence that mental imagery plays an important role in retrieval and that the brain regions supporting imagery overlap with those supporting retrieval. An open issue is to what extent these regions support successful vs. unsuccessful imagery and retrieval processes. Previous studies that examined regional overlap between imagery and retrieval used uncontrolled memory conditions, such as autobiographical memory tasks, that cannot distinguish between successful and unsuccessful retrieval. A second issue is that fMRI studies that compared imagery and retrieval have used modality-aspecific cues that are likely to activate auditory and visual processing regions simultaneously. Thus, it is not clear to what extent identified brain regions support modality-specific or modality-independent imagery and retrieval processes. In the current fMRI study, we addressed this issue by comparing imagery to retrieval under controlled memory conditions in both auditory and visual modalities. We also obtained subjective measures of imagery quality allowing us to dissociate regions contributing to successful vs. unsuccessful imagery. Results indicated that auditory and visual regions contribute both to imagery and retrieval in a modality-specific fashion. In addition, we identified four sets of brain regions with distinct patterns of activity that contributed to imagery and retrieval in a modality-independent fashion. The first set of regions, including hippocampus, posterior cingulate cortex, medial prefrontal cortex and angular gyrus, showed a pattern common to imagery/retrieval and consistent with successful performance regardless of task. The second set of regions, including dorsal precuneus, anterior cingulate and dorsolateral prefrontal cortex, also showed a pattern common to imagery and retrieval, but consistent with unsuccessful performance during both tasks. Third, left ventrolateral prefrontal cortex showed an interaction between task and performance and was associated with successful imagery but unsuccessful retrieval. Finally, the fourth set of regions, including ventral precuneus, midcingulate cortex and supramarginal gyrus, showed the opposite interaction, supporting unsuccessful imagery, but successful retrieval performance. Results are discussed in relation to reconstructive, attentional, semantic memory, and working memory processes. This is the first study to separate the neural correlates of successful and unsuccessful performance for both imagery and retrieval and for both auditory and visual modalities.

Remembering from any angle: the flexibility of visual perspective during retrieval.

When recalling autobiographical memories, individuals often experience visual images associated with the event. These images can be constructed from two different perspectives: first person, in which the event is visualized from the viewpoint experienced at encoding, or third person, in which the event is visualized from an external vantage point. Using a novel technique to measure visual perspective, we examined where the external vantage point is situated in third-person images. Individuals in two studies were asked to recall either 10 or 15 events from their lives and describe the perspectives they experienced. Wide variation in spatial locations was observed within third-person perspectives, with the location of these perspectives relating to the event being recalled. Results suggest remembering from an external viewpoint may be more common than previous studies have demonstrated.

The coherence of memories for trauma: evidence from posttraumatic stress disorder.

Participants with posttraumatic stress disorder (PTSD) and participants with a trauma but without PTSD wrote narratives of their trauma and, for comparison, of the most-important and the happiest events that occurred within a year of their trauma. They then rated these three events on coherence. Based on participants' self-ratings and on naïve-observer scorings of the participants' narratives, memories of traumas were not more incoherent than the comparison memories in participants in general or in participants with PTSD. This study comprehensively assesses narrative coherence using a full two (PTSD or not) by two (traumatic event or not) design. The results are counter to most prevalent theoretical views of memory for trauma.

The temporal distribution of autobiographical memory: changes in reliving and vividness over the life span do not explain the reminiscence bump.

When autobiographical memories are elicited with word cues, personal events from middle childhood to early adulthood are overrepresented compared to events from other periods. It is, however, unclear whether these memories are also associated with greater recollection. In this online study, we examined whether autobiographical memories from adolescence and early adulthood are recollected more than memories from other lifetime periods. Participants rated personal events that were elicited with cue words on reliving or vividness. Consistent with previous studies, most memories came from the period in which the participants were between 6 and 20 years old. The memories from this period were not relived more or recalled more vividly than memories from other lifetime periods, suggesting that they do not involve more recollection. Recent events had higher levels of reliving and vividness than remote events, and older adults reported a stronger recollective experience than younger adults.

A comparison of dimensional models of emotion: evidence from emotions, prototypical events, autobiographical memories, and words.

The intensity and valence of 30 emotion terms, 30 events typical of those emotions, and 30 autobiographical memories cued by those emotions were each rated by different groups of 40 undergraduates. A vector model gave a consistently better account of the data than a circumplex model, both overall and in the absence of high-intensity, neutral valence stimuli. The Positive Activation - Negative Activation (PANA) model could be tested at high levels of activation, where it is identical to the vector model. The results replicated when ratings of arousal were used instead of ratings of intensity for the events and autobiographical memories. A reanalysis of word norms gave further support for the vector and PANA models by demonstrating that neutral valence, high-arousal ratings resulted from the averaging of individual positive and negative valence ratings. Thus, compared to a circumplex model, vector and PANA models provided overall better fits.