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Article ; Online: Psychoneuroimmunology: An Introduction to Immune-to-Brain Communication and Its Implications for Clinical Psychology.

Bower, Julienne E / Kuhlman, Kate R

2023 Volume 19, Page(s) 331–359

Abstract: Research conducted over the past several decades has revolutionized our understanding of the role of the immune system in neural and psychological development and function across the life span. Our goal in this review is to introduce this dynamic area of ...

Abstract	Research conducted over the past several decades has revolutionized our understanding of the role of the immune system in neural and psychological development and function across the life span. Our goal in this review is to introduce this dynamic area of research to a psychological audience and highlight its relevance for clinical psychology. We begin by introducing the basic physiology of immune-to-brain signaling and the neuroimmune network, focusing on inflammation. Drawing from preclinical and clinical research, we then examine effects of immune activation on key psychological domains, including positive and negative valence systems, social processes, cognition, and arousal (fatigue, sleep), as well as links with psychological disorders (depression, posttraumatic stress disorder, anxiety, schizophrenia). We also consider psychosocial stress as a critical modulator of neuroimmune activity and focus on early life adversity. Finally, we highlight psychosocial and mind-body interventions that influence the immune system and may promote neuroimmune resilience.
MeSH term(s)	Humans ; Psychology, Clinical ; Psychoneuroimmunology ; Brain ; Communication ; Anxiety
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2194815-X
ISSN	1548-5951 ; 1548-5943
ISSN (online)	1548-5951
ISSN	1548-5943
DOI	10.1146/annurev-clinpsy-080621-045153
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Article ; Online: Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

Antici, Elizabeth E / Kuhlman, Kate R / Treanor, Michael / Craske, Michelle G

Brain, behavior, and immunity

2024 Volume 118, Page(s) 300–309

Abstract: Background: Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving ... ...

Abstract	Background: Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. Method: Adult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. Results: CRP decreased over the course of treatment, b = -0.03 (SE = 0.01), p =.02 95 %CI [-0.06, -0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = -0.45 (SE = 0.15), p =.004 95 %CI [-0.74, -0.15], and avoidance, b = -0.62 (SE = 0.19), p =.002 95 %CI [-1.01, -0.23], and in-session subjective distress from pre-treatment to post-treatment, b = -0.42 (SE = 0.21), p =.05 95 %CI [-0.83, -0.001]. However, declines in CRP were not correlated with declines in fear, r = -0.07, p =.61, or avoidance, r = -0.10, p =.49, within-persons. Conclusions: Virtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.
MeSH term(s)	Adult ; Humans ; Female ; Male ; Phobia, Social/therapy ; C-Reactive Protein ; Virtual Reality Exposure Therapy ; Fear ; Inflammation/therapy ; Anxiety/therapy
Chemical Substances	C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2024-03-10
Publishing country	Netherlands
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2024.03.002
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Article ; Online: Childhood Maltreatment and Immune Cell Gene Regulation during Adolescence: Transcriptomics Highlight Non-Classical Monocytes.

Kuhlman, Kate R / Cole, Steve W / Tan, Ece N / Swanson, James A / Rao, Uma

Biomolecules

2024 Volume 14, Issue 2

Abstract: Childhood maltreatment has been repeatedly linked to a higher incidence of health conditions with an underlying proinflammatory component, such as asthma, chronic obstructive pulmonary disease, stroke, and cardiovascular disease. Childhood maltreatment ... ...

Abstract	Childhood maltreatment has been repeatedly linked to a higher incidence of health conditions with an underlying proinflammatory component, such as asthma, chronic obstructive pulmonary disease, stroke, and cardiovascular disease. Childhood maltreatment has also been linked to elevated systemic inflammation prior to the onset of disease. However, childhood maltreatment is highly comorbid with other risk factors which have also been linked to inflammation, namely major depression. The present analysis addresses this issue by assessing the association of maltreatment with genome-wide transcriptional profiling of immune cells collected from four orthogonal groups of adolescents (aged 13-17): maltreated and not maltreated in childhood, with and without major depressive disorder. Maltreatment and psychiatric history were determined using semi-structured clinical interviews and cross-validated using self-report questionnaires. Dried whole blood spots were collected from each participant (
MeSH term(s)	Humans ; Adolescent ; Child ; Depressive Disorder, Major/genetics ; Monocytes ; Inflammation ; Gene Expression Profiling ; Child Abuse/psychology
Language	English
Publishing date	2024-02-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom14020220
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Article ; Online: Women with lower systemic inflammation demonstrate steeper cognitive decline with age: Results from a large prospective, longitudinal sample.

Noss, Melody Moloci / Millwood, Summer N / Kuhlman, Kate R

Brain, behavior, & immunity - health

2022 Volume 22, Page(s) 100465

Abstract: Background: Men and women experience large disparities in prevalence, detection, and clinical course of neurodegenerative diseases. Inflammation has been implicated in the pathogenesis of neurodegenerative diseases, yet there is a paucity of literature ... ...

Abstract	Background: Men and women experience large disparities in prevalence, detection, and clinical course of neurodegenerative diseases. Inflammation has been implicated in the pathogenesis of neurodegenerative diseases, yet there is a paucity of literature documenting sex differences in this phenomenon in prospective, longitudinal studies. Methods: Participants were 4217 non-smoking individuals (62.2% female; aged 46-91 at enrollment) enrolled in the Health and Retirement Study who provided dried blood spots and completed a standardized assessment of cognitive function 3 times across 8 years. Inflammation was indexed using C-reactive protein (CRP). Results: Higher CRP was associated with lower concurrent cognitive function, Conclusions: Women with lower systemic inflammation as measured by CRP may be at risk of going undetected for neurodegenerative disease, especially given their overall higher cognitive scores. This may perpetuate sex-related disparities in prevention and clinical course. Attention to the underlying biological mechanisms explaining the link between lower CRP and risk for cognitive decline for women and its potential clinical implications are needed.
Language	English
Publishing date	2022-05-02
Publishing country	United States
Document type	Journal Article
ISSN	2666-3546
ISSN (online)	2666-3546
DOI	10.1016/j.bbih.2022.100465
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Article ; Online: Psychoneuroimmunology in the time of COVID-19: Why neuro-immune interactions matter for mental and physical health.

Bower, Julienne E / Radin, Arielle / Kuhlman, Kate R

Behaviour research and therapy

2022 Volume 154, Page(s) 104104

Abstract: The brain and immune system are intricately connected, and perturbations in one system have direct effects on the other. This review focuses on these dynamic psychoneuroimmune interactions and their implications for mental and physical health in the ... ...

Abstract	The brain and immune system are intricately connected, and perturbations in one system have direct effects on the other. This review focuses on these dynamic psychoneuroimmune interactions and their implications for mental and physical health in the context of the COVID-19 pandemic. In particular, we describe how psychological states influence antiviral immunity and the vaccine response, and how immune changes triggered by COVID (either via infection with SARS-CoV-2 or associated stressors) can influence the brain with effects on cognition, emotion, and behavior. We consider negative psychological states, which have been the primary focus of psychological research in the context of COVID-19 (and psychoneuroimmunology more generally). We also consider positive psychological states, including positive affect and eudaimonic well-being, given increasing evidence for their importance as modulators of immunity. We finish with a discussion of interventions that may be effective in improving immune function, the neuro-immune axis, and ultimately, mental and physical health.
MeSH term(s)	COVID-19 ; Humans ; Neuroimmunomodulation ; Pandemics ; Psychoneuroimmunology ; SARS-CoV-2
Language	English
Publishing date	2022-05-06
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	211997-3
ISSN	1873-622X ; 0005-7967
ISSN (online)	1873-622X
ISSN	0005-7967
DOI	10.1016/j.brat.2022.104104
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Article ; Online: Dysregulated arousal as a pathway linking childhood neglect and clinical sleep disturbances in adulthood.

Semsar, Neda / Mousavi, Zahra / Tran, Mai-Lan M / Kuhlman, Kate R

Child abuse & neglect

2021 Volume 122, Page(s) 105306

Abstract: Background: A history of childhood maltreatment has a well-established association with clinical sleep disturbances in adulthood, which is a transdiagnostic contributor to many chronic diseases.: Objective: Determine whether actigraphy-measured ... ...

Abstract	Background: A history of childhood maltreatment has a well-established association with clinical sleep disturbances in adulthood, which is a transdiagnostic contributor to many chronic diseases. Objective: Determine whether actigraphy-measured indices of dysregulated arousal during sleep explain associations between abuse or neglect in childhood and clinical sleep disturbances in adulthood. Participants and setting: Participants were 646 individuals, ages 25-83 (59.3% female) from the MIDUS II Biomarker, Refresher studies. Methods: Participants completed the Childhood Trauma Questionnaire, wore an actigraph for seven days, and rated sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Results: Both neglect (b = 0.66, SE = 0.33, p = .04) and abuse (b = 1.09, SE = 0.32, p < .001) were associated with clinical sleep disturbance. Actigraphy-measured sleep efficiency mediated the link between neglect and clinical sleep disturbances (ab = 0.33, SE = 0.12, 95%CI [0.12, 0.57]). However, no such link between abuse and clinical sleep disturbances was mediated by actigraphy-measured indices. Sleep onset latency did not mediate the link between neglect or abuse and sleep disturbance. Models covaried for other maltreatment, gender, and age. Conclusions: While the unique associations between abuse or neglect and clinical sleep disturbances were robust in this sample, only sleep efficiency emerged as a mediator linking maltreatment and clinical sleep disturbances. Critically, this mediation was specific to neglect. Abuse and neglect may lead to disease through distinct pathways. Moreover, potential dysregulation in arousal that leads to sleep inefficiency may be a specific pathway through which experiences of neglect in childhood contribute to chronic disease.
MeSH term(s)	Adult ; Adult Survivors of Child Abuse ; Aged ; Aged, 80 and over ; Arousal ; Child ; Child Abuse ; Female ; Humans ; Male ; Middle Aged ; Sleep ; Sleep Wake Disorders/epidemiology
Language	English
Publishing date	2021-09-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	799143-5
ISSN	1873-7757 ; 0145-2134
ISSN (online)	1873-7757
ISSN	0145-2134
DOI	10.1016/j.chiabu.2021.105306
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Article ; Online: The moderating role of gender in the association between quality of social relationships and sleep.

Mousavi, Zahra / Tran, Mai-Lan / Borelli, Jessica L / Dent, Amy L / Kuhlman, Kate R

Journal of behavioral medicine

2022 Volume 45, Issue 3, Page(s) 378–390

Abstract: To determine whether the association between perceived social support or strain in close relationships and sleep outcomes varies by gender. Participants were selected from the Biomarker projects of either the MIDUS II or MIDUS Refresher study if they ... ...

Abstract	To determine whether the association between perceived social support or strain in close relationships and sleep outcomes varies by gender. Participants were selected from the Biomarker projects of either the MIDUS II or MIDUS Refresher study if they were in a married-or married-like relationship and shared a bed with their partner (N = 989). A subsample also participated in a seven-day sleep study (n = 282). Perceived social support and strain from partner, family, and friends were examined by self-report questionnaires. We used the Pittsburgh Sleep Quality Index, sleep daily diary, and actigraphy to measure both subjective and objective sleep. Social support and strain were both associated with sleep outcomes. Specifically, higher social support was associated with fewer daily reports of light sleep and feeling more rested in the morning, while higher social strain was associated with higher clinical sleep disturbance. For women, but not men, social support was significantly associated with lower daily sleep disturbance while perceived social strain was significantly associated with higher daily sleep disturbance, lighter sleep, feeling less rested in the morning, lower sleep efficiency, and longer sleep onset latency. Mainly among women, social support and strain are associated with an important transdiagnostic health outcome-sleep-which may have implications for a wide range of health disparities. Interpersonal stressors may increase health risks differently for women compared to men and one mechanism that may link social relationships to long-term health outcomes is sleep.
MeSH term(s)	Actigraphy ; Female ; Humans ; Interpersonal Relations ; Male ; Self Report ; Sleep ; Sleep Wake Disorders ; Surveys and Questionnaires
Language	English
Publishing date	2022-02-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	441827-x
ISSN	1573-3521 ; 0160-7715
ISSN (online)	1573-3521
ISSN	0160-7715
DOI	10.1007/s10865-022-00286-6
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Article ; Online: The role of early life adversity and inflammation in stress-induced change in reward and risk processes among adolescents.

Kuhlman, Kate R / Cole, Steve W / Irwin, Michael R / Craske, Michelle G / Fuligni, Andrew J / Bower, Julienne E

Brain, behavior, and immunity

2023 Volume 109, Page(s) 78–88

Abstract: Background: Early life adversity (ELA) has long been associated with increased risk for stress-related psychopathology, particularly depression. The neuroimmune network hypothesis posits that ELA increases sensitivity to psychosocial stress, moderating ... ...

Abstract	Background: Early life adversity (ELA) has long been associated with increased risk for stress-related psychopathology, particularly depression. The neuroimmune network hypothesis posits that ELA increases sensitivity to psychosocial stress, moderating the association between increases in peripheral markers of inflammation and decreases in reward outcomes linked to anhedonia and risk-taking behaviors. The present study examined this hypothesis in a sample of adolescents by using acute psychosocial stress to probe the role of inflammatory signaling in behavioral measures of reward and risk processing. Method: 80 adolescents [13.86 years (SD = 1.54); 45 % female], oversampled for ELA, underwent the Trier Social Stress Test for Children while providing blood samples immediately before and 60-minutes after stress onset. Blood samples were assayed for plasma IL-6. One hour before stress onset, and then 60 min after, participants completed computer-administered behavioral tasks measuring reward (Pirate Task) and risk (Balloon Analog Risk Task). Results: ELA moderated the association between increases in IL-6 and decreases in risk tolerance in pursuit of rewards (p = 0.003) and reward response bias (p = 0.04). Stress-induced increases in IL-6 were associated with decreases in pumps for rewards among adolescents exposed to high, relative to little or no, ELA. Further, greater IL-6 increases were associated with increases in bias toward high relative to low value rewards among adolescents with low adversity exposure but not among those exposed to higher adversity. Conclusions: The present study provides the first evidence in a pediatric sample that ELA may alter the role of stress-induced inflammation in reward and risk processing, and may extend our understanding of why stress leads to depression in this high-risk population.
MeSH term(s)	Humans ; Child ; Female ; Adolescent ; Male ; Stress, Psychological/psychology ; Interleukin-6 ; Adverse Childhood Experiences ; Inflammation ; Reward
Chemical Substances	Interleukin-6
Language	English
Publishing date	2023-01-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2023.01.004
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Article ; Online: Predictors of Adolescent Resilience During the COVID-19 Pandemic in a Community Sample of Hispanic and Latinx Youth: Expressive Suppression and Social Support.

Kuhlman, Kate R / Antici, Elizabeth / Tan, Ece / Tran, Mai-Lan / Rodgers-Romero, Emma L / Restrepo, Nazly

Research on child and adolescent psychopathology

2023 Volume 51, Issue 5, Page(s) 639–651

Abstract: The COVID-19 pandemic has created unprecedented disruptions in the daily lives and mental health of adolescents. Less attention has been given to the psychosocial resources that may mitigate the impact of COVID-19 on adolescent mental health, ... ...

Abstract	The COVID-19 pandemic has created unprecedented disruptions in the daily lives and mental health of adolescents. Less attention has been given to the psychosocial resources that may mitigate the impact of COVID-19 on adolescent mental health, particularly among minoritized populations. In the present study, 259 youth (aged 11-18) were recruited from a community center for integrated prevention and intervention services in a predominantly Latinx and Hispanic community. Youth completed questionnaires about the impact COVID-19 has had on their lives, psychosocial resources (humor, optimism, emotion regulation, social support), and psychiatric symptoms (depressive symptoms, anxiety symptoms, sleep disturbances, aggression). After accounting for age, sex, and exposure to early life adversity, higher reported COVID-19 impact was associated with more depressive symptoms, b = 6.37 (SE = 1.67), 95% CI [3.08, 9.66], p < 0.001, more anxiety symptoms, b = 9.97 (SE = 1.63), 95% CI [6.75, 13.18], p < 0.001, and more sleep disturbances, b = 1.24 (SE = 0.34), 95% CI [0.57, 1.91], p < 0.001. Youth that reported infrequent expressive suppression and the lowest scores on giving social support were at the greatest risk for aggressive behavior in the context of high COVID-19 impact, ps < 0.007. Increasing emotion regulation skills, such as expressive suppression, and opportunities to give social support may promote resilience among high risk youth in the context of this ongoing community stressor.
MeSH term(s)	Adolescent ; Humans ; Adolescent Health/ethnology ; Adolescent Health/statistics & numerical data ; COVID-19/epidemiology ; COVID-19/psychology ; Hispanic or Latino/psychology ; Hispanic or Latino/statistics & numerical data ; Pandemics/prevention & control ; Social Support/psychology ; Social Support/statistics & numerical data ; Resilience, Psychological ; Child ; Child Health/ethnology ; Child Health/statistics & numerical data
Language	English
Publishing date	2023-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3041907-4
ISSN	2730-7174 ; 2730-7166
ISSN (online)	2730-7174
ISSN	2730-7166
DOI	10.1007/s10802-022-01019-8
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Article ; Online: Endogenous in-session cortisol during exposure therapy predicts symptom improvement: Preliminary results from a scopolamine-augmentation trial.

Kuhlman, Kate R / Treanor, Michael / Imbriano, Gabriella / Craske, Michelle G

Psychoneuroendocrinology

2020 Volume 116, Page(s) 104657

Abstract: The purpose of this study was to explore whether individual differences in glucocorticoid concentrations were associated with symptom improvement following exposure therapy for patients with social anxiety disorder. To do this, 60 participants with ... ...

Abstract	The purpose of this study was to explore whether individual differences in glucocorticoid concentrations were associated with symptom improvement following exposure therapy for patients with social anxiety disorder. To do this, 60 participants with social anxiety disorder completed a randomized-controlled trial of exposure therapy, where participants were randomized to receive scopolamine-augmentation or placebo during their 7 exposure sessions. Scopolamine is an antimuscarinic which blocks the effects of acetylcholine and reduces autonomic arousal. During sessions 1, 4, 7, and during the post-treatment extinction assessment, participants provided up to 16 saliva samples (4 in each session). Pre-treatment, post-treatment, and at 1-month follow-up, participants completed the Liebowitz Social Anxiety Scale to monitor change in fear and avoidance symptoms. Elevated endogenous in-session cortisol during exposure sessions was associated with less symptom improvement from pre- to post-treatment and at 1-month follow-up. The association between elevated endogenous in-session cortisol and attenuated symptom change was not moderated by scopolamine treatment condition. Individuals with social anxiety disorder who have elevated neuroendocrine signaling may under-benefit from exposure therapy. This is the first study, to our knowledge, to examine whether endogenous in-session cortisol concentrations predict symptom changes following exposure therapy for the treatment of social anxiety disorder. More investigation of non-invasive and reliable biological markers that explain variability in responses to effective treatments are needed.
MeSH term(s)	Adult ; Combined Modality Therapy ; Double-Blind Method ; Follow-Up Studies ; Humans ; Hydrocortisone/metabolism ; Implosive Therapy ; Individuality ; Muscarinic Antagonists/administration & dosage ; Muscarinic Antagonists/pharmacology ; Outcome Assessment, Health Care ; Phobia, Social/drug therapy ; Phobia, Social/metabolism ; Phobia, Social/therapy ; Saliva/metabolism ; Scopolamine/administration & dosage ; Scopolamine/pharmacology
Chemical Substances	Muscarinic Antagonists ; Scopolamine (DL48G20X8X) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2020-03-20
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
ZDB-ID	197636-9
ISSN	1873-3360 ; 0306-4530
ISSN (online)	1873-3360
ISSN	0306-4530
DOI	10.1016/j.psyneuen.2020.104657
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