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Papers by Jean King

PubMed, Aug 1, 2005

Objectives: Many studies assessing the role of sex hormones, like testosterone, on stress and hos... more Objectives: Many studies assessing the role of sex hormones, like testosterone, on stress and hostility factors have been primarily conducted in selected atypical populations such as violent criminals as well as androgen users and abusers. Therefore, the main aim of the current study was to investigate the association between testosterone levels and two psychosocial variables: stress and hostility in a cohort of healthy individuals who were members of a health maintenance organization (HMO). Methods: At five quarterly visits, psychosocial scales and blood draws were collected. Psychological stress was measured by using several scales that assessed different types of stress, including daily hassles, major life events and perceived stress. Similarly, different aspects of hostility were measured, among them cynicism, hostile affect and aggressive responding. Plasma collected from each visit was used for testosterone level determinations. Results: Testosterone levels were significantly associated with stress in both males and females. However, whereas this association exhibited a "threshold effect" in males, it demonstrated a direct and continuous linear relationship between these variables in females. Hostility was not correlated with testosterone levels in neither males nor females. Conclusions: These results suggest that testosterone levels in normal males and females may be more reflective of an intricate balance between physiological responding and emotional coping to stressors than the hostility profile of the individual.

Behavioral Medicine, 2000

Assessments of cortisol levels in saliva have been widely used by both researchers and clinicians... more Assessments of cortisol levels in saliva have been widely used by both researchers and clinicians as an index of adrenal functioning. Quarterly measurements of morning and evening cortisol levels were determined in a longitudinal study of 147 participants (72 women and 75 men) followed for 1 year each. The analysis of salivary cortisol revealed no significant gender or age differences in the sample. There was a sequence effect in quarterly cortisol values with a progressive decrease in serial measurements, especially notable in the morning values; as well as a seasonal variation in cortisol levels with significantly higher levels found in winter and fall, compared with spring and summer. The findings in this study suggest that repeated saliva sampling and seasonal variation in cortisol levels may independently affect adrenal response and, therefore, need to be accounted for in longitudinal studies.

medRxiv (Cold Spring Harbor Laboratory), Nov 17, 2020

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. Mindfulness in weight loss changes brain functional connectivity 2

Hypertension-related illnesses are a leading cause of disability and death in the United States, ... more Hypertension-related illnesses are a leading cause of disability and death in the United States, where 46% of adults have hypertension and only half have it controlled. It is critical to reduce hypertension, and either new classes of interventions are required, or we need to develop enhanced approaches to improve medical regimen adherence. The Mindfulness-Based Blood Pressure Reduction program (MB-BP) is showing novel mechanisms and early evidence of efficacy, but the neural correlates are unknown. The objectives of this study were to identify structural neural correlates of MB-BP using diffusion tensor magnetic resonance imaging (DTI) and assess potential correlations with key clinical outcomes. In a subset of participants from a larger randomized controlled trial, MB-BP participants exhibited increased interoception and decreased depressive symptoms compared to controls. Analyses of DTI data revealed significant group differences in several white matter neural tracts associated wi...

Pain Medicine, 2021

Background Chronic pain is one of the most common reason adults seek medical care in the United S... more Background Chronic pain is one of the most common reason adults seek medical care in the United States, with prevalence estimates ranging from 11% to 40%. Mindfulness meditation has been associated with significant improvements in pain, depression, physical and mental health, sleep, and overall quality of life. Group medical visits are increasingly common and are effective at treating myriad illnesses, including chronic pain. Integrative Medical Group Visits (IMGV) combine mindfulness techniques, evidence based integrative medicine, and medical group visits and can be used as adjuncts to medications, particularly in diverse underserved populations with limited access to non-pharmacological therapies. Objective and Design The objective of the present study was to use a blended analytical approach of machine learning and regression analyses to evaluate the potential relationship between depression and chronic pain in data from a randomized clinical trial of IMGV in diverse, income-dis...

Scientific Reports, 2020

Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understandin... more Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5–6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations...

eneuro, 2019

Sex differences in human cognitive performance are well characterized. However, the neural correl... more Sex differences in human cognitive performance are well characterized. However, the neural correlates of these differences remain elusive. This issue may be clarified using nonhuman primates, for which sociocultural influences are minimized. We used the marmoset (Callithrix jacchus) to investigate sex differences in two aspects of executive function: reversal learning and intradimensional/extradimensional (ID/ED) set shifting. Stress reactivity and motor function were also assessed. In agreement with human literature, females needed more trials than males to acquire the reversals. No sex differences in ED set shifting or motivational measures were observed. The findings suggest enhanced habit formation in females, perhaps due to striatal estrogenic effects. Both sexes showed increased urinary cortisol during social separation stressor, but females showed an earlier increase in cortisol and a greater increase in agitated locomotion, possibly indicating enhanced stress reactivity. Ind...

Behavioral Medicine, Apr 1, 2004

An association between stress and health has been hypothesized. However, the association pathways... more An association between stress and health has been hypothesized. However, the association pathways are unclear. In this article, the authors examined the associations between stress, social support, and cortisol and the mediating effect of several psychosocial variables. Adult men and women (n = 146) completed psychosocial surveys and provided saliva samples for cortisol assessments, quarterly, for 1 year Cross-sectional analysis results showed an inverse relationship between basal cortisol and stress (Model 1: coefficient = -.068, SE = .024, p = .006). After controlling for stress, the authors also found an inverse relationship between basal cortisol and social support among individuals with high social support (upper tertile compared with 1st and 2nd tertiles) (Model 2: coefficient = -.440, SE = .155, p = .005). Longitudinal models showed similar findings for both associations. These findings do not support the general hypothesis of a negative effect of chronic intermittent stress on health through Hypothalamic Pituitary Adrenal (HPA) axis activation, but do support a positive effect of social support on the HPA axis. Both findings deserve further investigation.

Prostate cancer is the second leading cause of all male cancer deaths. One of the factors present... more Prostate cancer is the second leading cause of all male cancer deaths. One of the factors present in malignant prostate cells and shown to support its metastatic growth is the neuropeptide neurotensin (NT). The primary goal of the present study was to establish the feasibility of using a newly developed paramagnetic receptor ligand for NT and non-invasive ultrahigh-field magnetic resonance (MR) imaging to visualize prostate cancer in rodents. Orthotropic xenografts were initiated in six-week old male BALB/c nu/nu athymic mice (n = 28) by intra-prostatic (ventral lobe) inoculation of human prostate cancer cells (10 μL of PC3 cells (10^6/100 μL)). Palpable tumors developed within 30-60 days. A micro-imager utilized in these studies was an actively shielded 9.4T, 89 mm bore, Oxford superconducting magnet with a 100 gauss/cm gradient system. Prior to contrast injection, T2 weighted anatomy scans were done to localize the tumor with a spin-echo multi-slice sequence with TR: 2000 TE: 40 a...

Neuron, Jan 2, 2016

The greatest challenge in moving neuroscience research forward in the 21st century is recruiting,... more The greatest challenge in moving neuroscience research forward in the 21st century is recruiting, training, and retaining the brightest, rigorous, and most diverse scientists. The MBL research training courses Neurobiology and Neural Systems & Behavior, and the Summer Program in Neuroscience, Excellence, and Success provide a model for full immersion, discovery-based training while enhancing cultural, geographic, and racial diversity.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, Jan 2, 2015

It is unknown how the timing between doses might affect nicotine's impact on neural activity.... more It is unknown how the timing between doses might affect nicotine's impact on neural activity. Our objective was to examine how the interdose interval affects…

Endocrine Reviews, 2010

Fetal nutrient and growth restriction is associated with development of type 2 diabetes. Although... more Fetal nutrient and growth restriction is associated with development of type 2 diabetes. Although the exact mechanisms responsible for this association remain debated, intrauterine and/or postnatal maldevelopment of ␤-cell mass has been proposed as a potential mechanism. To address this hypothesis, ␤-cell mass development and turnover was assessed in rats exposed to either intrauterine and/or postnatal caloric/growth restriction. In total, four groups of male and female Sprague Dawley rats (n ϭ 69) were developed and studied: 1) control rats, i.e. control mothers rearing control pups; 2) intrauterine calorically and growth-restricted rats, i.e. 50% prenatal calorically restricted pups cross-fostered to control mothers; 3) postnatal calorically and growthrestricted rats, i.e. 50% calorically restricted mothers rearing pups born to control mothers; and 4) prenatal and postnatal calorically and growth restricted rats, i.e. 50% calorically restricted mothers rearing intrauterine 50% calorically restricted pups. Intrauterine growth restriction resulted in approximately 45% reduction of postnatal ␤-cell fractional area and mass characterized by reduced rate of ␤-cell replication and decreased evidence of neogenesis. In contrast, ␤-cell fractional area and weight-adjusted ␤-cell mass in postnatal growth restriction was approximately 30% higher than in control rats. Rats exposed to both intrauterine and postnatal caloric and growth restriction demonstrated approximately 80% decrease in ␤-cell mass, reduction in ␤-cell replication, and decreased evidence of neogenesis compared with control. Neither intrauterine nor postnatal caloric restriction significantly affected the rate of ␤-cell apoptosis. These data support the hypothesis that intrauterine maldevelopment of ␤-cell mass may predict the increased risk of type 2 diabetes in adult life.

Hemodynamic response, deoxyhemoglobin and MRI signal 49 Blood oxygenation level dependent fMRI 52... more Hemodynamic response, deoxyhemoglobin and MRI signal 49 Blood oxygenation level dependent fMRI 52 Resting state MRI 53 CHAPTER 4. MODEL DEVELOPMENT Animal Models of Parkinson's disease ..

Familial Adenomatous Polyposis (FAP) is an autosomal dominant disorder caused by mutation of the ... more Familial Adenomatous Polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene presenting with numerous colorectal adenomatous polyps and a near 100% risk of colon cancer. Preliminary research findings from our group indicate that FAP patients experience significant deficits across many cognitive domains. In the current study, fMRI brain metrics in a FAP population and matched controls were used to further the mechanistic understanding of reported cognitive deficits. This research identified and characterized any possible differences in resting brain networks and associations between neural network changes and cognition from 34 participants (18 FAP patients, 16 healthy controls). Functional connectivity analysis was performed using FSL with independent component analysis (ICA) to identify functional networks. Significant differences between cases and controls were observed in 8 well-established resting state networks. With the addition of an aggregate cogn...

Journal of affective disorders, Mar 2, 2018

Continued development and refinement of resting state functional connectivity (RSFC) fMRI techniq... more Continued development and refinement of resting state functional connectivity (RSFC) fMRI techniques in both animal and clinical studies has enhanced our comprehension of the adverse effects of stress on psychiatric health. The objective of the current study was to assess both maternal behavior and resting state functional connectivity (RSFC) changes in these animals when they were dams caring for their own young. It was hypothesized that ECSS exposed dams would express depressed maternal care and exhibit similar (same networks), yet different specific changes in RSFC (different individual nuclei) than reported when they were adult females. We have developed an ethologically relevant transgenerational model of the role of chronic social stress (CSS) in the etiology of postpartum depression and anxiety. Initial fMRI investigation of the CSS model indicates that early life exposure to CSS (ECSS) induces long term changes in functional connectivity in adult nulliparous female F1 offspr...

Psychiatry research, Jan 8, 2017

Mindfulness is paying attention, non-judgmentally, to experience in the moment. Mindfulness train... more Mindfulness is paying attention, non-judgmentally, to experience in the moment. Mindfulness training reduces depression and anxiety and influences neural processes in midline self-referential and lateralized somatosensory and executive networks. Although mindfulness benefits emotion regulation, less is known about its relationship to anger and the corresponding neural correlates. This study examined the relationship of mindful awareness and brain hemodynamics of angry face processing, and the impact of mindfulness training. Eighteen healthy volunteers completed an angry face processing fMRI paradigm and measurement of mindfulness and anger traits. Ten of these participants were recruited from a Mindfulness-Based Stress Reduction (MBSR) class and also completed imaging and other assessments post-training. Self-reported mindful awareness increased after MBSR, but trait anger did not change. Baseline mindful awareness was negatively related to left inferior parietal lobule activation t...

Nicotine & Tobacco Research, 2017

Introduction: Individuals with attention deficit/hyperactivity disorder (ADHD) are susceptible to... more Introduction: Individuals with attention deficit/hyperactivity disorder (ADHD) are susceptible to earlier and more severe nicotine addiction. To shed light on the relationship between nicotine and ADHD, we examined nicotine's effects on functional brain networks in an animal model of ADHD. Methods: Awake magnetic resonance imaging was used to compare functional connectivity in adolescent (post-natal day 44 ± 2) males of the spontaneously hypertensive rat (SHR) strain and two control strains, Wistar-Kyoto and Sprague-Dawley (n = 16 each). We analyzed functional connectivity immediately before and after nicotine exposure (0.4 mg/kg base) in naïve animals, using a region-of-interest approach focussing on 16 regions previously implicated in reward and addiction. Results: Relative to the control groups, the SHR strain demonstrated increased functional connectivity between the ventral tegmental area (VTA) and retrosplenial cortex in response to nicotine, suggesting an aberrant response to nicotine. In contrast, increased VTA-substantia nigra connectivity in response to a saline injection in the SHR was absent following a nicotine injection, suggesting that nicotine normalized function in this circuit. Conclusions: In the SHR, nicotine triggered an atypical response in one VTA circuit while normalizing activity in another. The VTA has been widely implicated in drug reward. Our data suggest that increased susceptibility to nicotine addiction in individuals with ADHD may involve altered responses to nicotine involving VTA circuits. Implications: Nicotine addiction is more common among individuals with ADHD. We found that two circuits involving the VTA responded differently to nicotine in animals that model ADHD in comparison to two control strains. In one circuit, nicotine normalized activity that was abnormal in the ADHD animals, while in the other circuit nicotine caused an atypical brain response in the ADHD animals. The VTA has been implicated in drug reward. Our results would be consistent with an interpretation that nicotine may normalize abnormal brain activity in ADHD, and that nicotine may be more rewarding for individuals with ADHD.

BMJ Open, 2016

Keeping Weight Off: study protocol of an RCT to investigate brain changes associated with mindful... more Keeping Weight Off: study protocol of an RCT to investigate brain changes associated with mindfulness-based stress reduction.

Brain, 2016

Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. ... more Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptor Sarm1 (sterile a/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model. Sarm1 À/À mice developed fewer b-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared to Sarm1 + / + mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function in Sarm1 À/À animals. Finally, using in vivo proton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1 À/À mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury.

Neurological Bulletin, 2010

Dysosmia in PD (Parkinson's Disease) may result from changes in the olfactory apparatus or in str... more Dysosmia in PD (Parkinson's Disease) may result from changes in the olfactory apparatus or in structures involved in olfactory perception. Previous work 1,2 has suggested that deep brain stimulation (DBS) patients have improved odor discrimination in stimulation-on/medicationoff state in comparison to their own scores in a stimulation-off/ medication-off state. What remains unclear is whether it is the ON state itself or an effect of stimulation that leads to improved olfaction. In this study we evaluate dysosmia in two PD cohorts in the ON state, those treated with medication alone and those treated with medication and DBS. A prospective study geared at improving predictive value of olfactory testing with a battery of psychological tests enrolled 45 PD patients and 44 controls. Of the PD patients, 9 had bilateral STN (subthalamic nucleus) DBS and 36 were medically treated. Subset analysis of PD patients with and without DBS placement revealed no difference in apathy or depression. DBS patients had better olfaction on UPSIT (Univ of Pennsylvania Smell Identification Test) (p<0.05). No difference was noted in disease severity, gender, smoking status, medication dosing, use of dopamine agonists, or maximal olfactory sulcus depth on MRI. DBS patients were significantly younger, however inter-group differences in UPSIT scores exceeded those seen in our control cohort with similar ages. This study provides further data that DBS patients have improved olfaction. It also provides preliminary evidence that DBS with medication improves dysosmia to a greater extent than medication alone. This may result from indirect stimulation of olfactory processing centers or changes in olfactory circuitry metabolism.