Publications by authors named "Peter J Gianaros"

116 Publications

Dual impedance cardiography: An inexpensive and reliable method to assess arterial stiffness.

Psychophysiology 2021 Jan 26:e13772. Epub 2021 Jan 26.

Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.

Pulse wave velocity (PWV) is a common measure of arterial stiffness. Non-invasive methods to measure PWV are widely used in biomedical studies of aging and cardiovascular disease, but they are rarely used in psychophysiology. Barriers to wider use include the prohibitive costs of specialized equipment and need for trained technicians (e.g., ultrasonographers). Here, we describe an impedance cardiography method to measure PWV. By this method, impedance signals are dually collected from the thorax and calf. Combined with ensemble averaging of vascular signals, this dual impedance cardiography (d-ICG) method allows for the measurement of aortic flow onset and the arrival time of peripheral pulse waveforms to compute PWV. In a community sample of adults (aged 19-78 years), PWV measured with d-ICG exhibited a strong positive correlation with age. Moreover, age-specific mean PWV values were within the normative reference intervals established by large scale studies using other techniques. PWV derived from d-ICG exhibited high test-retest reliability across several days, as well as excellent inter-rater reliability. Last, PWV exhibited expected associations with known cardiovascular disease risk factors and indicators of autonomic cardiovascular control. d-ICG is an inexpensive and reliable method to assess arterial stiffness.
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http://dx.doi.org/10.1111/psyp.13772DOI Listing
January 2021

Is stressor-evoked cardiovascular reactivity a pathway linking positive and negative emotionality to preclinical cardiovascular disease risk?

Psychophysiology 2021 Mar 5;58(3):e13741. Epub 2020 Dec 5.

Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.

Stressor-evoked cardiovascular reactivity, trait positive emotionality, and negative emotionality are all associated with cardiovascular disease. It is unknown, however, whether cardiovascular reactivity may constitute a pathway by which trait positive or negative emotionality relates to disease risk. Accordingly, this study modeled the cross-sectional relationships between trait positive and negative emotionality, stressor-evoked cardiovascular reactivity, and severity of a subclinical vascular marker of cardiovascular risk, carotid artery intima-media thickness (CA-IMT). The sample consisted of healthy, midlife adults free from clinical cardiovascular disease (N = 286; ages 30-54; 50% female). Trait positive and negative emotionality were measured by three questionnaires. Heart rate and blood pressure reactivity were assessed across three stressor tasks. CA-IMT was assessed by ultrasonography. Latent factors of positive and negative emotionality, blood pressure reactivity, heart rate reactivity, and CA-IMT were created using structural equation modeling. Greater negative emotionality was marginally associated with more CA-IMT (β = .21; p = .049), but lower blood pressure reactivity (β = -.19; p = .03). However, heightened blood pressure (β = .21; p = .03), but not heart rate reactivity (β = -.05; p = .75), associated with greater CA-IMT. Positive emotionality was uncorrelated with cardiovascular reactivity (blood pressure: β = -.04; p = .61; heart rate: β = .16; p = .11) and CA-IMT (β = .16; p = .07). Although trait negative emotionality associates with a known marker of cardiovascular disease risk, independent of positive emotionality, it is unlikely to occur via a stressor-evoked cardiovascular reactivity pathway.
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http://dx.doi.org/10.1111/psyp.13741DOI Listing
March 2021

Relationship between Dispositional Mindfulness, Psychological Health, and Diet Quality among Healthy Midlife Adults.

Nutrients 2020 Nov 6;12(11). Epub 2020 Nov 6.

Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.

Mindfulness, a practice of non-judgmental awareness of present experience, has been associated with reduced eating psychopathology and emotion-driven eating. However, it remains unclear whether mindfulness relates to diet quality. Thus, the purpose of this study was to examine whether dispositional mindfulness is associated with diet quality and to explore psychological factors relating dispositional mindfulness to diet quality. Community-dwelling adults ( = 406; = 43.19, = 7.26; = 27.08, = 5.28; 52% female) completed ratings of dispositional mindfulness, depressive symptoms, perceived stress, positive affect (PA), and negative affect (NA). Dietary intake was assessed using the Block Food Frequency Questionnaire, from which the 2015 Healthy Eating Index was derived. Analyses were conducted using the "lavaan" package in R with bias-corrected bootstrapped confidence intervals (BootCI). Age, sex, race, education, and BMI were entered as covariates in all models. Higher dispositional mindfulness was associated with higher diet quality ( = 0.11, = 0.03), and this effect was mediated through lower depressive symptoms (indirect effect = 0.06, = 0.02, BootCI = 0.104-1.42, = 0.03). Dispositional mindfulness was negatively correlated with perceived stress ( = -0.31, < 0.01) and NA ( = -0.43, < 0.01), as well as positively correlated with PA ( = -0.26, < 0.01). However, these factors were unrelated to diet quality. These cross-sectional data provide initial evidence that dispositional mindfulness relates to diet quality among midlife adults, an effect that may be explained in part by less depressive symptomatology. Given that lifestyle behaviors in midlife are leading determinants of risk for cardiovascular disease and neurocognitive impairment in late life, interventions to enhance mindfulness in midlife may mitigate disease risk. Additional research assessing the impact of mindfulness interventions on diet quality are warranted.
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http://dx.doi.org/10.3390/nu12113414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695007PMC
November 2020

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Psychophysiology 2020 Oct 10. Epub 2020 Oct 10.

Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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http://dx.doi.org/10.1111/psyp.13688DOI Listing
October 2020

Cerebrovascular function in hypertension: Does high blood pressure make you old?

Psychophysiology 2020 Aug 24:e13654. Epub 2020 Aug 24.

Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.

The majority of individuals over an age of 60 have hypertension. Elevated blood pressure and older age are associated with very similar changes in brain structure and function. We review the parallel brain changes associated with increasing age and blood pressure. This review focuses on joint associations of aging and elevated blood pressure with neuropsychological function, regional cerebral blood flow responses to cognitive and metabolic challenges, white matter disruptions, grey matter volume, cortical thinning, and neurovascular coupling. Treatment of hypertension ameliorates many of these changes but fails to reverse them. Treatment of hypertension itself appears more successful with better initial brain function. We show evidence that sympathetic and renal influences known to increase blood pressure also impact brain integrity. Possible central mechanisms contributing to the course of hypertension and aging are then suggested. An emphasis is placed on psychologically relevant factors: stress, cardiovascular reactions to stress, and diet/obesity. The contribution of some of these factors to biological aging remains unclear and may provide a starting point for defining the independent and interacting effects of aging and increasing blood pressure on the brain.
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http://dx.doi.org/10.1111/psyp.13654DOI Listing
August 2020

In Memoriam: Robert M. Stern.

Neurogastroenterol Motil 2020 09 18;32(9):e13970. Epub 2020 Aug 18.

Division of Research and Economic Development, North Carolina Agricultural and Technical State University, Greensboro, NC, USA.

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http://dx.doi.org/10.1111/nmo.13970DOI Listing
September 2020

Does well-being associate with stress physiology? A systematic review and meta-analysis.

Health Psychol 2020 Oct 20;39(10):879-890. Epub 2020 Jul 20.

Department of Psychology, University of Pittsburgh.

Objective: The current meta-analysis tested whether trait indicators of well-being associate with stressor-evoked physiological reactivity and recovery in healthy adults.

Method: Medline, PsycINFO, and PubMed were used to identify relevant articles. Articles were included if they (a) measured cardiovascular or neuroendocrine (but not immune) physiology during or after an acute laboratory stress paradigm (b) measured indicators of hedonic well-being, eudaimonic well-being, or optimism, and (c) included healthy adult participants. Laboratory stress tasks included frustrating cognitive tasks, emotional recall tasks, and tasks involving social evaluation. Physiological variables were aggregated across cardiac (heart rate and cardiac output), hemodynamic (mean arterial pressure, systolic blood pressure, and diastolic blood pressure), HPA (cortisol), and autonomic (high frequency heart rate variability, skin conductance, and catecholamines) markers. Twenty-seven studies were included (n = 3,390; 54.6% women). Effect sizes and confidence intervals were estimated using a random-effects model with pooled variance.

Results: Contrary to expectations, optimism was associated with greater cardiac reactivity to cognitive stressors but did not associate with stress recovery. By contrast, hedonic well-being was associated with enhanced hemodynamic recovery following laboratory stressors but was not associated with stress reactivity.

Conclusions: Hedonic well-being, but not optimism, could potentially buffer against the effects of psychological stressors on physiological responding by relating to more complete recovery. Identifying the mechanisms contributing to these patterns of association may provide insights into psychological interventions for well-being and stress-related disease risk. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/hea0000979DOI Listing
October 2020

Adiposity covaries with signatures of asymmetric feedback learning during adaptive decisions.

Soc Cogn Affect Neurosci 2020 Nov;15(10):1145-1156

Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.

Unhealthy weight gain relates, in part, to how people make decisions based on prior experience. Here we conducted post hoc analysis on an archival data set to evaluate whether individual differences in adiposity, an anthropometric construct encompassing a spectrum of body types, from lean to obese, associate with signatures of asymmetric feedback learning during value-based decision-making. In a sample of neurologically healthy adults (N = 433), ventral striatal responses to rewards, measured using fMRI, were not directly associated with adiposity, but rather moderated its relationship with feedback-driven learning in the Iowa gambling task, tested outside the scanner. Using a biologically inspired model of basal ganglia-dependent decision processes, we found this moderating effect of reward reactivity to be explained by an asymmetrical use of feedback to drive learning; that is, with more plasticity for gains than for losses, stronger reward reactivity leads to decisions that minimize exploration for maximizing long-term outcomes. Follow-up analysis confirmed that individual differences in adiposity correlated with signatures of asymmetric use of feedback cues during learning, suggesting that reward reactivity may especially relate to adiposity, and possibly obesity risk, when gains impact future decisions more than losses.
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http://dx.doi.org/10.1093/scan/nsaa088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657458PMC
November 2020

Frontostriatal Brain Activation Is Associated With the Longitudinal Progression of Cardiometabolic Risk.

Psychosom Med 2020 06;82(5):454-460

From the Department of Psychology (Allen), University of Tennessee, Knoxville, Tennessee; Department of Psychiatry and Psychology (Jennings), University of Pittsburgh; Heart and Vascular Institute (Muldoon), University of Pittsburgh School of Medicine; and Department of Psychology (Gianaros), University of Pittsburgh, Pittsburgh, Pennsylvania.

Objective: Cardiometabolic risk refers to a set of interconnected factors of vascular and metabolic origin associated with both cardiovascular disease and various brain disorders. Although midlife cardiometabolic risk is associated with future brain dysfunction, emerging evidence suggests that alterations in autonomic and central nervous system function may precede increases in cardiometabolic risk.

Methods: The present study tested whether patterns of cerebral blood flow in brain areas associated with autonomic regulation were associated with increases in overall cardiometabolic risk. A community sample of 109 adults with resting systolic blood pressure between 120 and 139 mm Hg, diastolic blood pressure between 80 and 89 mm Hg, or both underwent pseudocontinuous arterial spin labeling to quantify cerebral blood flow responses to cognitively challenging tasks. Cardiometabolic risk and cerebral blood flow measurements were collected at baseline and at a 2-year follow-up.

Results: Regression analyses showed that greater frontostriatal cerebral blood flow responses to cognitive challenge were associated with higher cardiometabolic risk at follow-up (β = 0.26 [95% confidence interval = 0.07 to 0.44], t = 2.81, p = .006, ΔR = 0.04). These findings were specific to frontostriatal brain regions, as frontoparietal, insular-subcortical, and total cerebral blood flow were not associated with progression of cardiometabolic risk. Moreover, cardiometabolic risk was not associated with frontostriatal cerebral blood flow responses 2 years later.

Conclusions: Frontostriatal brain function may precede and possibly forecast the progression of cardiometabolic risk.
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http://dx.doi.org/10.1097/PSY.0000000000000811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283003PMC
June 2020

Affective brain patterns as multivariate neural correlates of cardiovascular disease risk.

Soc Cogn Affect Neurosci 2020 Nov;15(10):1034-1045

Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA 15213, USA.

This study tested whether brain activity patterns evoked by affective stimuli relate to individual differences in an indicator of pre-clinical atherosclerosis: carotid artery intima-media thickness (CA-IMT). Adults (aged 30-54 years) completed functional magnetic resonance imaging (fMRI) tasks that involved viewing three sets of affective stimuli. Two sets included facial expressions of emotion, and one set included neutral and unpleasant images from the International Affective Picture System (IAPS). Cross-validated, multivariate and machine learning models showed that individual differences in CA-IMT were partially predicted by brain activity patterns evoked by unpleasant IAPS images, even after accounting for age, sex and known cardiovascular disease risk factors. CA-IMT was also predicted by brain activity patterns evoked by angry and fearful faces from one of the two stimulus sets of facial expressions, but this predictive association did not persist after accounting for known cardiovascular risk factors. The reliability (internal consistency) of brain activity patterns evoked by affective stimuli may have constrained their prediction of CA-IMT. Distributed brain activity patterns could comprise affective neural correlates of pre-clinical atherosclerosis; however, the interpretation of such correlates may depend on their psychometric properties, as well as the influence of other cardiovascular risk factors and specific affective cues.
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http://dx.doi.org/10.1093/scan/nsaa050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657455PMC
November 2020

The effects of omega-3 fatty acids on neuropsychological functioning and brain morphology in mid-life adults: a randomized clinical trial.

Psychol Med 2020 10 4;50(14):2425-2434. Epub 2019 Oct 4.

University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background: The diet of most adults is low in fish and, therefore, provides limited quantities of the long-chain, omega-3 fatty acids (LCn-3FAs), eicosapentaenoic and docosahexaenoic acids (EPA, DHA). Since these compounds serve important roles in the brain, we sought to determine if healthy adults with low-LCn-3FA consumption would exhibit improvements in neuropsychological performance and parallel changes in brain morphology following repletion through fish oil supplementation.

Methods: In a randomized, controlled trial, 271 mid-life adults (30-54 years of age, 118 men, 153 women) consuming ⩽300 mg/day of LCn-3FAs received 18 weeks of supplementation with fish oil capsules (1400 mg/day of EPA and DHA) or matching placebo. All participants completed a neuropsychological test battery examining four cognitive domains: psychomotor speed, executive function, learning/episodic memory, and fluid intelligence. A subset of 122 underwent neuroimaging before and after supplementation to measure whole-brain and subcortical tissue volumes.

Results: Capsule adherence was over 95%, participant blinding was verified, and red blood cell EPA and DHA levels increased as expected. Supplementation did not affect performance in any of the four cognitive domains. Exploratory analyses revealed that, compared to placebo, fish oil supplementation improved executive function in participants with low-baseline DHA levels. No changes were observed in any indicator of brain morphology.

Conclusions: In healthy mid-life adults reporting low-dietary intake, supplementation with LCn-3FAs in moderate dose for moderate duration did not affect neuropsychological performance or brain morphology. Whether salutary effects occur in individuals with particularly low-DHA exposure requires further study.
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http://dx.doi.org/10.1017/S0033291719002617DOI Listing
October 2020

Cerebrovascular disease: Neuroimaging of cerebral small vessel disease.

Prog Mol Biol Transl Sci 2019 8;165:225-255. Epub 2019 Aug 8.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, United States. Electronic address:

The cerebral microvasculature is exceptionally vulnerable to changes due to aging. Both the radiological and clinical manifestations of cerebral small vessel disease (cSVD) in older age are highly heterogeneous, ranging from no symptomatology to devastating neurocognitive complications, including stroke, dementia, and depression. To date, the exact pathogenesis of cSVD is unknown; neither prevention nor treatments are currently available for this potentially very disabling condition. This chapter reviews recent advances in neuroimaging methodologies that have improved our understanding of the appearance of cSVD and the underlying mechanisms. We will discuss new venues for future research focusing on: (a) methodologies to measure early stages of cSVD, examining damage primarily in small vessels and secondarily in parenchyma; and (b) lifespan study designs to capture the onset and evolution of cSVD over time, as well as the temporality of exposure to risk factors.
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http://dx.doi.org/10.1016/bs.pmbts.2019.07.008DOI Listing
April 2020

Retrospectively reported childhood physical abuse, systemic inflammation, and resting corticolimbic connectivity in midlife adults.

Brain Behav Immun 2019 11 22;82:203-213. Epub 2019 Aug 22.

Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA; Center for the Neural Basis of Cognition, Pittsburgh, PA, USA.

Childhood abuse confers risk for psychopathology and pathophysiology in midlife through intermediate pathways that remain unclear. Systemic inflammation was tested in the present study as one pathway that may link physical abuse in childhood to the adult functioning of corticolimbic brain circuits broadly implicated in risk for poor mental and physical health. Midlife adults (N = 303; 30-51 years of age; 149 women) without psychiatric, immune, or cardiovascular diagnoses provided retrospective reports of childhood physical abuse. Functional connectivity between corticolimbic brain areas (amygdala, hippocampus, ventromedial prefrontal cortex [vmPFC], anterior cingulate cortex [ACC]) was measured at rest using functional magnetic resonance imaging. Circulating levels of interleukin(IL)-6, a pro-inflammatory cytokine previously linked to childhood abuse and corticolimbic functionality, were measured via blood draw. Consistent with prior studies, retrospectively reported childhood physical abuse was associated positively with circulating IL-6, and negatively with connectivity between the amygdala and vmPFC. IL-6 was also associated negatively with several corticolimbic functional connections, including amygdala-vmPFC connectivity. Moreover, path analyses revealed an indirect effect of IL-6 that partially explained the association between childhood physical abuse and adult amygdala-vmPFC connectivity. Consistent with recent neurobiological models of early life influences on disease risk across the lifespan, associations between childhood physical abuse and adulthood corticolimbic circuit functionality may be partially explained by inflammatory processes.
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http://dx.doi.org/10.1016/j.bbi.2019.08.186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956859PMC
November 2019

Ventromedial prefrontal cortex connectivity during and after psychological stress in women.

Psychophysiology 2019 11 3;56(11):e13445. Epub 2019 Aug 3.

Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania.

The ventromedial prefrontal cortex (vmPFC) integrates sensory, affective, memory-related, and social information from diverse brain systems to coordinate behavioral and peripheral physiological responses according to contextual demands that are appraised as stressful. However, the functionality of the vmPFC during stressful experiences is not fully understood. Among 40 female participants, the present study evaluated (a) functional connectivity of the vmPFC during exposure to and recovery following an acute psychological stressor, (b) associations among vmPFC functional connectivity, heart rate, and subjective reports of stress across individuals, and (c) whether patterns of vmPFC functional connectivity were associated with distributed brain networks. Results showed that psychological stress increased vmPFC functional connectivity with individual brain areas implicated in stressor processing (e.g., insula, amygdala, anterior cingulate cortex) and decreased connectivity with the posterior cingulate cortex and thalamus. There were no statistical differences in vmPFC connectivity to individual brain areas during recovery, as compared with baseline. Spatial similarity analyses revealed stressor-evoked increased connectivity of the vmPFC with the so-called dorsal attention, ventral attention, and frontoparietal networks, as well as decreased connectivity with the default mode network. During recovery, vmPFC connectivity increased with the frontoparietal network. Finally, individual differences in heart rate and perceived stress were associated with vmPFC connectivity to the ventral attention, frontoparietal, and default mode networks. Psychological stress appears to alter network-level functional connectivity of the vmPFC in a manner that further relates to individual differences in stressor-evoked cardiovascular and affective reactivity.
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http://dx.doi.org/10.1111/psyp.13445DOI Listing
November 2019

Socioeconomic disparities of depressive symptoms and cytokines in hepatocellular carcinoma.

Psychooncology 2019 08 18;28(8):1624-1632. Epub 2019 Jun 18.

Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.

Objective: To examine the associations among socioeconomic factors, depressive symptoms, and cytokines in patients diagnosed with hepatocellular carcinoma (HCC).

Methods: A total of 266 patients diagnosed with HCC were administered a battery of questionnaires including a sociodemographic questionnaire and the Center for Epidemiologic StudiesDepression (CES-D) scale. Blood samples were collected to assess serum levels of cytokines using Luminex. Descriptive statistics, Mann-Whitney U, Kruskal-Wallis, linear regression, and Bonferroni corrections were performed to test the hypotheses.

Results: Of the 266 patients, 24% reported depressive symptoms in the clinical range (CES-D ≥ 22). Females had higher CES-D score than males (Mann-Whitney U = 7135, P = .014, P  = .028). Being unemployed/disabled (Kruskal-Wallis = 14.732, P = .001, P  = .005) was found to be associated with higher depressive symptoms in males but not in females. Serum level of IL-2 (Kruskal-Wallis = 17.261, P = .001, P  = .005) were found to be negatively associated with education level. Gender (β = .177, P = .035), income (β = -.252, P = .004), whether the patient's income met their basic needs (β = .180, P = .035), and IL-1β (β = -.165, P = .045) independently predicted depressive symptoms and together explained 19.4% of variance associated with depressive symptoms.

Conclusions: Sociodemographic and socioeconomic factors were predictive of inflammation and depressive symptoms. Recommendations include the development of gender-targeted interventions for patients diagnosed with HCC who have low socioeconomic status (SES) and may suffer from depressive symptoms.
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http://dx.doi.org/10.1002/pon.5127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241307PMC
August 2019

The prospective relationship between prehypertension, race, and whole-brain white matter microstructure.

J Hum Hypertens 2020 01 25;34(1):82-89. Epub 2019 Feb 25.

Department of Psychiatry & Psychology, University of Pittsburgh, Pittsburgh, PA, USA.

Compared with whites, blacks develop hypertension earlier in life, progress from prehypertension to hypertension at an accelerated rate, and exhibit greater hypertension-mediated organ damage (e.g., kidney disease, stroke). In this paper, we tested whether the longitudinal associations between elevated systolic blood pressure and disruption of brain white matter structural integrity differ as a function of race. A community sample of 100 middle-aged adults with prehypertension underwent diffusion imaging to quantify indirect metrics of white matter structural integrity, including fractional anisotropy. Blood pressure and diffusion imaging measurements were collected at baseline and at a 2-year follow-up. Regression analyses showed that higher systolic blood pressure at baseline was associated with a decrease in fractional anisotropy over 2 years in blacks only (β = -0.51 [95% CI = -0.85, -0.16], t = -2.93, p = 0.004, ΔR = 0.09). These findings suggest that blacks are more susceptible to the impact of systolic prehypertension on white matter structural integrity.
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http://dx.doi.org/10.1038/s41371-019-0184-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708769PMC
January 2020

Host in the machine: A neurobiological perspective on psychological stress and cardiovascular disease.

Am Psychol 2018 11;73(8):1031-1044

Department of Psychiatry, University of Pittsburgh.

Psychological stress still attracts scientific, clinical, and public interest because of its suspected connection to health, particularly cardiovascular health. Psychological stress is thought to arise from appraisal processes that imbue events and contexts with personal significance and threat-related meaning. These appraisal processes are also thought to be instantiated in brain systems that generate and control peripheral physiological stress reactions through visceral motor (brain-to-body) and visceral sensory (body-to-brain) mechanisms. In the short term, physiological stress reactions may enable coping and adaptive action. Among some individuals, however, the patterning of these reactions may predict or contribute to pathology in multiple organ systems, including the cardiovascular system. At present, however, we lack a precise understanding of the brain systems and visceral control processes that link psychological appraisals to patterns of stress physiology and physical health. This understanding is important: A mechanistic account of how the brain connects stressful experiences to bodily changes and health could help refine biomarkers of risk and targets for cardiovascular disease prevention and intervention. We review research contributing to this understanding, focusing on the neurobiology of cardiovascular stress reactivity and cardiovascular health. We suggest that a dysregulation of visceral motor and visceral sensory processes during stressful experiences may confer risk for poor cardiovascular health among vulnerable individuals. We further describe a need for new interpretive frameworks and markers of this brain-body dysregulation in cardiovascular behavioral medicine. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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http://dx.doi.org/10.1037/amp0000232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220680PMC
November 2018

Should heart rate variability be "corrected" for heart rate? Biological, quantitative, and interpretive considerations.

Psychophysiology 2019 02 25;56(2):e13287. Epub 2018 Oct 25.

Department of Psychology, The Ohio State University, Columbus, Ohio.

Metrics of heart period variability are widely used in the behavioral and biomedical sciences, although somewhat confusingly labeled as heart rate variability (HRV). Despite their wide use, HRV metrics are usually analyzed and interpreted without reference to prevailing levels of cardiac chronotropic state (i.e., mean heart rate or mean heart period). This isolated treatment of HRV metrics is nontrivial. All HRV metrics routinely used in the literature exhibit a known and positive relationship with the mean duration of the interval between two beats (heart period): as the heart period increases, so does its variability. This raises the question of whether HRV metrics should be "corrected" for the mean heart period (or its inverse, the heart rate). Here, we outline biological, quantitative, and interpretive issues engendered by this question. We provide arguments that HRV is neither uniformly nor simply a surrogate for heart period. We also identify knowledge gaps that remain to be satisfactorily addressed with respect to assumptions underlying existing HRV correction approaches. In doing so, we aim to stimulate further progress toward the rigorous use and disciplined interpretation of HRV. We close with provisional guidance on HRV reporting that acknowledges the complex interplay between the mean and variability of the heart period.
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http://dx.doi.org/10.1111/psyp.13287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378407PMC
February 2019

Taking rejection to heart: Associations between blood pressure and sensitivity to social pain.

Biol Psychol 2018 11 21;139:87-95. Epub 2018 Oct 21.

Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.

A reliable finding from the physical pain literature is that individuals with higher resting (i.e., tonic) blood pressure experience relatively less pain in response to nociceptive stimuli. Converging lines of evidence suggest that biological factors that influence the experience of physical pain may also relate to social pain. An open question, however, is whether higher blood pressure per se is a biological factor associated with lower sensitivity to social pain. This possible association was tested in three studies. Consistent with prior findings on physical pain, higher resting blood pressure was associated with lower self-reported sensitivity to social pain across individuals (Study 1 r = -.303, Study 2 r = -.262, -.246), even after adjusting for confounding factors related to blood pressure (Study 3 r = -.222). Findings suggest a previously unknown biological correlate of sensitivity to social pain, providing further evidence for possible shared substrates for physical and social pain.
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http://dx.doi.org/10.1016/j.biopsycho.2018.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295662PMC
November 2018

Neural Mechanisms Linking Emotion with Cardiovascular Disease.

Curr Cardiol Rep 2018 10 11;20(12):128. Epub 2018 Oct 11.

Department of Psychology, University of Pittsburgh, 210 South Bouquet Street, Pittsburgh, PA, 15260, USA.

Purpose Of Review: The present review discusses brain circuits that are engaged by negative emotions and possibly linked to cardiovascular disease risk. It describes recent human brain imaging studies that relate activity in these brain circuits to emotional processes, peripheral physiology, preclinical pathophysiology, as well as clinical outcomes.

Recent Findings: Negative emotions and the regulation of negative emotions reliably engage several brain regions that cross-sectional and longitudinal brain imaging studies have associated with CVD risk markers and outcomes. These brain regions include the amygdala, anterior cingulate cortex, medial prefrontal cortex, and insula. Other studies have applied advanced statistical techniques to characterize multivariate patterns of brain activity and brain connectivity that associate with negative emotion and CVD-relevant peripheral physiology. Brain imaging studies on emotion and cardiovascular disease risk are expanding our understanding of the brain-body bases of psychosocial and behavioral risk for cardiovascular disease.
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http://dx.doi.org/10.1007/s11886-018-1071-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444345PMC
October 2018

Increased stressor-evoked cardiovascular reactivity is associated with reduced amygdala and hippocampus volume.

Psychophysiology 2019 01 22;56(1):e13277. Epub 2018 Aug 22.

Department of Psychology and Neuroscience, Baylor University, Waco, Texas.

Exaggerated cardiovascular reactivity to acute psychological stress is associated with an increased risk of developing cardiovascular disease. The amygdala and hippocampus have been implicated in centrally mediating stressor-evoked cardiovascular reactivity. However, little is known about the associations of amygdala and hippocampus morphology with stressor-evoked cardiovascular reactivity. Forty (M = 19.05, SD = 0.22 years) healthy young women completed two separate testing sessions. Session 1 assessed multiple parameters of cardiovascular physiology at rest and during a validated psychological stress task (Paced Auditory Serial Addition Test), using electrocardiography, Doppler echocardiography, and blood pressure monitoring. In Session 2, 1 year later, structural MRI was conducted. Brain structural volumes were computed using automated segmentation methods. Regression analyses, following Benjamini-Hochberg correction, showed that greater heart rate and cardiac output reactivity were associated with reduced amygdala and hippocampus gray matter volume. Systolic blood pressure reactivity was associated with reduced hippocampus volume. In contrast, no associations between diastolic blood pressure, mean arterial blood pressure, stroke volume, or total peripheral resistance reactivity with amygdala or hippocampus volumes were apparent. Comparison analyses examining insula volume found no significant associations. Some indicators of greater stressor-evoked cardiovascular reactivity associate with reduced amygdala and hippocampus gray matter volume, but the mechanisms of this association warrant further study.
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http://dx.doi.org/10.1111/psyp.13277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849591PMC
January 2019

Perceived discrimination and cardiovascular health disparities: a multisystem review and health neuroscience perspective.

Ann N Y Acad Sci 2018 09 8;1428(1):170-207. Epub 2018 Aug 8.

Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania.

There are distinct racial disparities in cardiovascular disease (CVD) risk, with Black individuals at much greater risk than White individuals. Although many factors contribute to these disparities, recent attention has focused on the role of discrimination as a stress-related factor that contributes to racial disparities in CVD. As such, it is important to understand the mechanisms by which discrimination might affect CVD. Recent studies have examined these mechanisms by focusing on neurobiological mediators of CVD risk. Given this increase in studies, a systematic review of perceived discrimination and neurobiological mediators of CVD risk is warranted. Our review uses a multisystem approach to review studies on the relationship between perceived discrimination and (1) cardiovascular responses to stress, (2) hypothalamic-pituitary-adrenocortical axis function, and (3) the immune system, as well as (4) the brain systems thought to regulate these parameters of peripheral physiology. In addition to summarizing existing evidence, our review integrates these findings into a conceptual model describing multidirectional pathways linking perceived discrimination with a CVD risk.
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http://dx.doi.org/10.1111/nyas.13939DOI Listing
September 2018

Functional neuroanatomy of peripheral inflammatory physiology: A meta-analysis of human neuroimaging studies.

Neurosci Biobehav Rev 2018 11 29;94:76-92. Epub 2018 Jul 29.

Department of Psychology, University of Pittsburgh, Pittsburgh, PA, 15260, USA; Center for the Neural Basis of Cognition, Pittsburgh, PA, 15260, USA.

Communication between the brain and peripheral mediators of systemic inflammation is implicated in numerous psychological, behavioral, and physiological processes. Functional neuroimaging studies have identified brain regions that associate with peripheral inflammation in humans, yet there are open questions about the consistency, specificity, and network characteristics of these findings. The present systematic review provides a meta-analysis to address these questions. Multilevel kernel density analysis of 24 studies (37 statistical maps; 264 coordinates; 457 participants) revealed consistent effects in the amygdala, hippocampus, hypothalamus, striatum, insula, midbrain, and brainstem, as well as prefrontal and temporal cortices. Effects in some regions were specific to particular study designs and tasks. Spatial pattern analysis revealed significant overlap of reported effects with limbic, default mode, ventral attention, and corticostriatal networks, and co-activation analyses revealed functional ensembles encompassing the prefrontal cortex, insula, and midbrain/brainstem. Together, these results characterize brain regions and networks associated with peripheral inflammation in humans, and they provide a functional neuroanatomical reference point for future neuroimaging studies on brain-body interactions.
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http://dx.doi.org/10.1016/j.neubiorev.2018.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363360PMC
November 2018

Associations of immunometabolic risk factors with symptoms of depression and anxiety: The role of cardiac vagal activity.

Brain Behav Immun 2018 10 18;73:493-503. Epub 2018 Jun 18.

Department of Psychology, University of Pittsburgh, PA, United States.

Objectives: This study examined 1) the cross-sectional relationships between symptoms of depression/anxiety and immunometabolic risk factors, and 2) whether these relationships might be explained in part by cardiac vagal activity.

Methods: Data were drawn from the Adult Health and Behavior registries (n = 1785), comprised of community dwelling adults (52.8% women, aged 30-54). Depressive symptoms were measured with the Center for Epidemiological Studies Depression Scale (CES-D) and the Beck Depression Inventory-II (BDI-II), and anxious symptoms with the Trait Anxiety scale of the State-Trait Anxiety Inventory (STAI-T). Immunometabolic risk factors included fasting levels of triglycerides, high-density lipoproteins, glucose, and insulin, as well as blood pressure, waist circumference, body mass index, C-reactive protein, and interleukin-6. Measures of cardiac autonomic activity were high- and low-frequency indicators of heart rate variability (HRV), standard deviation of normal-to-normal R-R intervals, and the mean of absolute and successive differences in R-R intervals.

Results: Higher BDI-II scores, in contrast to CES-D and STAI-T scores, were associated with increased immunometabolic risk and decreased HRV, especially HRV likely reflecting cardiac vagal activity. Decreased HRV was also associated with increased immunometabolic risk. Structural equation models indicated that BDI-II scores may relate to immunometabolic risk via cardiac vagal activity (indirect effect: β = .012, p = .046) or to vagal activity via immunometabolic risk (indirect effect: β = -.015, p = .021).

Conclusions: Depressive symptoms, as measured by the BDI-II, but not anxious symptoms, were related to elevated levels of immunometabolic risk factors and low cardiac vagal activity. The latter may exhibit bidirectional influences on one another in a meditational framework. Future longitudinal, intervention, an nonhuman animal work is needed to elucidate the precise and mechanistic pathways linking depressive symptoms to immune, metabolic, and autonomic parameters of physiology that predispose to cardiovascular disease risk.
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http://dx.doi.org/10.1016/j.bbi.2018.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066576PMC
October 2018

Socioeconomic Position and Age-Related Disparities in Regional Cerebral Blood Flow Within the Prefrontal Cortex.

Psychosom Med 2018 05;80(4):336-344

From the USC Suzanne Dworak-Peck School of Social Work (Hackman), University of Southern California, Los Angeles, California; and Department of Psychology (Kuan, Manuck, Gianaros), Center for the Neural Basis of Cognition (Gianaros), University of Pittsburgh, Pittsburgh, Pennsylvania.

Objective: Socioeconomic position (SEP) is associated with cerebrovascular health and brain function, particularly in prefrontal cortex and medial temporal lobe regions that exhibit plasticity across the life course. However, it is unknown whether SEP associates with resting cerebral blood flow (CBF), an indicator of baseline brain function, in these regions in midlife, and whether the association is (a) period specific, with independent associations for childhood and adulthood SEP, or driven by life course SEP, and (b) explained by a persistent disparity, widening disparity, or the leveling of disparities with age.

Methods: To address these questions, we analyzed cerebral perfusion derived by magnetic resonance imaging in a cross-sectional study of healthy adults (N = 443) who reported on childhood and adult SEP. Main effects were examined as an index of persistent disparity and age by SEP interactions as reflecting widening or leveling disparities.

Results: Stable high SEP across the lifespan was associated with higher global CBF and regional CBF (rCBF) in inferior frontal gyrus. However, childhood SEP was associated with rCBF in middle frontal gyrus, as moderated by age (β = 0.04, p = .035): rCBF was inversely associated with age only for those whose parents had a high school education or below. No associations were observed for the hippocampus or amygdala.

Conclusions: Life course SEP associations with rCBF in prefrontal cortex are suggestive of persistent disparities, whereas the age by childhood SEP interaction suggests that childhood disadvantage relates to a widening disparity, independent of global differences. These differential patterns in midlife may relate to disparities in later-life cerebrovascular and neurocognitive outcomes.
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http://dx.doi.org/10.1097/PSY.0000000000000566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104768PMC
May 2018

A population neuroscience approach to the study of cerebral small vessel disease in midlife and late life: an invited review.

Am J Physiol Heart Circ Physiol 2018 06 2;314(6):H1117-H1136. Epub 2018 Feb 2.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh , Pittsburgh, Pennsylvania.

Aging in later life engenders numerous changes to the cerebral microvasculature. Such changes can remain clinically silent but are associated with greater risk for negative health outcomes over time. Knowledge is limited about the pathogenesis, prevention, and treatment of potentially detrimental changes in the cerebral microvasculature that occur with advancing age. In this review, we summarize literature on aging of the cerebral microvasculature, and we propose a conceptual framework to fill existing research gaps and advance future work on this heterogeneous phenomenon. We propose that the major gaps in this area are attributable to an incomplete characterization of cerebrovascular pathology, the populations being studied, and the temporality of exposure to risk factors. Specifically, currently available measures of age-related cerebral microvasculature changes are indirect, primarily related to parenchymal damage rather than direct quantification of small vessel damage, limiting the understanding of cerebral small vessel disease (cSVD) itself. Moreover, studies seldom account for variability in the health-related conditions or interactions with risk factors, which are likely determinants of cSVD pathogenesis. Finally, study designs are predominantly cross-sectional and/or have relied on single time point measures, leaving no clear evidence of time trajectories of risk factors or of change in cerebral microvasculature. We argue that more resources should be invested in 1) developing methodological approaches and basic science models to better understand the pathogenic and etiological nature of age-related brain microvascular diseases and 2) implementing state-of-the-science population study designs that account for the temporal evolution of cerebral microvascular changes in diverse populations across the lifespan.
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http://dx.doi.org/10.1152/ajpheart.00535.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032084PMC
June 2018

Generalizable representations of pain, cognitive control, and negative emotion in medial frontal cortex.

Nat Neurosci 2018 02 1;21(2):283-289. Epub 2018 Jan 1.

Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.

The medial frontal cortex, including anterior midcingulate cortex, has been linked to multiple psychological domains, including cognitive control, pain, and emotion. However, it is unclear whether this region encodes representations of these domains that are generalizable across studies and subdomains. Additionally, if there are generalizable representations, do they reflect a single underlying process shared across domains or multiple domain-specific processes? We decomposed multivariate patterns of functional MRI activity from 270 participants across 18 studies into study-specific, subdomain-specific, and domain-specific components and identified latent multivariate representations that generalized across subdomains but were specific to each domain. Pain representations were localized to anterior midcingulate cortex, negative emotion representations to ventromedial prefrontal cortex, and cognitive control representations to portions of the dorsal midcingulate. These findings provide evidence for medial frontal cortex representations that generalize across studies and subdomains but are specific to distinct psychological domains rather than reducible to a single underlying process.
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http://dx.doi.org/10.1038/s41593-017-0051-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801068PMC
February 2018

Childhood maltreatment moderates the effect of combat exposure on cingulum structural integrity.

Dev Psychopathol 2017 12;29(5):1735-1747

University of Pittsburgh.

Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure.
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http://dx.doi.org/10.1017/S0954579417001365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773248PMC
December 2017

Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

Hypertension 2017 12 16;70(6):1132-1141. Epub 2017 Oct 16.

From the Departments of Psychiatry and Psychology, University of Pittsburgh, PA (J.R.J., A.F.H., L.K.S., M.F.M., C.R., C.S., P.J.G.); and Department of Radiation Oncology (H.M.G.), Department of Radiology (H.M.G.), and Department of Biomedical Engineering (H.M.G.),Washington University in St. Louis, MO (H.M.G.).

Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; =0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; =0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685165PMC
December 2017

A Brain Phenotype for Stressor-Evoked Blood Pressure Reactivity.

J Am Heart Assoc 2017 Aug 23;6(9). Epub 2017 Aug 23.

Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA.

Background: Individuals who exhibit large-magnitude blood pressure (BP) reactions to acute psychological stressors are at risk for hypertension and premature death by cardiovascular disease. This study tested whether a multivariate pattern of stressor-evoked brain activity could reliably predict individual differences in BP reactivity, providing novel evidence for a candidate neurophysiological source of stress-related cardiovascular risk.

Methods And Results: Community-dwelling adults (N=310; 30-51 years; 153 women) underwent functional magnetic resonance imaging with concurrent BP monitoring while completing a standardized battery of stressor tasks. Across individuals, the battery evoked an increase systolic and diastolic BP relative to a nonstressor baseline period (M ∆systolic BP/∆diastolic BP=4.3/1.9 mm Hg [95% confidence interval=3.7-5.0/1.4-2.3 mm Hg]). Using cross-validation and machine learning approaches, including dimensionality reduction and linear shrinkage models, a multivariate pattern of stressor-evoked functional magnetic resonance imaging activity was identified in a training subsample (N=206). This multivariate pattern reliably predicted both systolic BP (=0.32; <0.005) and diastolic BP (=0.25; <0.01) reactivity in an independent subsample used for testing and replication (N=104). Brain areas encompassed by the pattern that were strongly predictive included those implicated in psychological stressor processing and cardiovascular responding through autonomic pathways, including the medial prefrontal cortex, anterior cingulate cortex, and insula.

Conclusions: A novel multivariate pattern of stressor-evoked brain activity may comprise a phenotype that partly accounts for individual differences in BP reactivity, a stress-related cardiovascular risk factor.
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http://dx.doi.org/10.1161/JAHA.117.006053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634271PMC
August 2017