Toward a dynamic immunopsychiatry.

In this article, we briefly clarify several points regarding immunopsychiatry. In particular, we argue that higher density data and a greater focus on temporal dynamics are both important, and that studies incorporating these features have the potential to greatly advance the field. We also respond to recent comments made on our original article on this topic (Moriarity and Slavich, 2023), including the contention that our perspective on immunopsychiatry is reductionistic. To the contrary, we believe that strong immunopsychiatry studies are highly integrative and include data from multiple major levels of analysis to form a more complete picture of how processes that are relevant for mental health and behavior emerge and dynamically change over time in relation to one another.

Hormonal contraceptive use is associated with differences in women's inflammatory and psychological reactivity to an acute social stressor.

Women using hormonal contraceptives (HCs) exhibit numerous signs of chronic inflammation, including elevated C-reactive protein levels and greater risk of developing mood and autoimmune disorders. However, users and non-users of HCs often have similar circulating proinflammatory cytokine levels, making the mechanism of association unclear. One possible explanation for this paradox is that HC users exhibit differences in their inflammatory responses to psychosocial stress that, over time, could contribute to chronic inflammation and its pathologies. Here, we tested this possibility by examining women's glucocorticoid, inflammatory, and psychological responses to the Trier Social Stress Test (TSST) in 67 naturally cycling (NC) and 60 oral HC-using women (Mage = 19.31, SDage = 1.95). As hypothesized, HC users and NC women exhibited different glucocorticoid and proinflammatory cytokine responses to the TSST. For NC women, TSST-induced increases in glucocorticoids were uncommon, and increases in glucocorticoids were accompanied by elevations in IL-6. In contrast, for women using HCs, increases in glucocorticoids in response to the TSST were common, and increases in glucocorticoids were accompanied by increases in TNF-α. HC users and NC women also differed in their psychological responses to the TSST, with HC users reporting elevated stress levels compared to NC women. Together, these results suggest that HC use impacts women's glucocorticoid, inflammatory, and psychological responses to psychosocial stress, potentially contributing to observed differences in these women's mental and physical health.

The biology of hope: Inflammatory and neuroendocrine profiles in ovarian cancer patients.

INTRODUCTION: Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers. METHOD: Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey items from established scales (Center for Epidemiological Studies Depression Scale; Profile of Mood States, Functional Assessment of Cancer Therapy). Two hopeless items were z-scored and combined into a composite for analysis. Regression models related these variables to nocturnal cortisol, cortisol slope, plasma and ascites IL-6, adjusting for cancer stage, BMI, age, and depression. RESULTS: Greater hope was significantly related to a steeper cortisol slope, ß = -0.193, p = 0.046, and lower night cortisol, ß = -0.227, p = 0.018, plasma IL-6, ß = -0.142, p = 0.033, and ascites IL-6, ß = -0.290, p = 0.002. Secondary analyses including both hope and hopelessness showed similar patterns, with distinct relationships of hope with significantly lower nocturnal cortisol ß = -0.233,p = 0.017 and ascites IL-6, ß = -0.282,p = 0.003, and between hopelessness and a flatter cortisol slope, ß = 0.211, p = 0.031. CONCLUSIONS: These data suggest a biological signature of hope associated with less inflammation and more normalized diurnal cortisol in ovarian cancer. These findings have potential clinical utility but need replication with more diverse samples and validated assessments of hope.

The Stress Phenotyping Framework: A multidisciplinary biobehavioral approach for assessing and therapeutically targeting maladaptive stress physiology.

Although dysregulated stress biology is becoming increasingly recognized as a key driver of lifelong disparities in chronic disease, we presently have no validated biomarkers of toxic stress physiology; no biological, behavioral, or cognitive treatments specifically focused on normalizing toxic stress processes; and no agreed-upon guidelines for treating stress in the clinic or evaluating the efficacy of interventions that seek to reduce toxic stress and improve human functioning. We address these critical issues by (a) systematically describing key systems and mechanisms that are dysregulated by stress; (b) summarizing indicators, biomarkers, and instruments for assessing stress response systems; and (c) highlighting therapeutic approaches that can be used to normalize stress-related biopsychosocial functioning. We also present a novel multidisciplinary Stress Phenotyping Framework that can bring stress researchers and clinicians one step closer to realizing the goal of using precision medicine-based approaches to prevent and treat stress-associated health problems.

Multi-omics in stress and health research: study designs that will drive the field forward.

Despite decades of stress research, there still exist substantial gaps in our understanding of how social, environmental, and biological factors interact and combine with developmental stressor exposures, cognitive appraisals of stressors, and psychosocial coping processes to shape individuals' stress reactivity, health, and disease risk. Relatively new biological profiling approaches, called multi-omics, are helping address these issues by enabling researchers to quantify thousands of molecules from a single blood or tissue sample, thus providing a panoramic snapshot of the molecular processes occurring in an organism from a systems perspective. In this review, we summarize two types of research designs for which multi-omics approaches are best suited, and describe how these approaches can help advance our understanding of stress processes and the development, prevention, and treatment of stress-related pathologies. We first discuss incorporating multi-omics approaches into theory-rich, intensive longitudinal study designs to characterize, in high-resolution, the transition to stress-related multisystem dysfunction and disease throughout development. Next, we discuss how multi-omics approaches should be incorporated into intervention research to better understand the transition from stress-related dysfunction back to health, which can help inform novel precision medicine approaches to managing stress and fostering biopsychosocial resilience. Throughout, we provide concrete recommendations for types of studies that will help advance stress research, and translate multi-omics data into better health and health care.

Rural-urban disparities in psychosocial functioning in epithelial ovarian cancer patients.

OBJECTIVE: Although rural residence has been related to health disparities in cancer patients, little is known about how rural residence impacts mental health and quality of life (QOL) in ovarian cancer patients over time. This prospective longitudinal study investigated mental health and QOL of ovarian cancer patients in the first-year post-diagnosis. METHOD: Women with suspected ovarian cancer completed psychosocial surveys pre-surgery, at 6 months and one-year; clinical data were obtained from medical records. Histologically confirmed high grade epithelial ovarian cancer patients were eligible. Rural/urban residence was categorized from patient counties using the USDA Rural-Urban Continuum Codes. Linear mixed effects models examined differences in psychosocial measures over time, adjusting for covariates. RESULTS: Although disparities were not observed at study entry for any psychosocial variable (all p-values >0.22), urban patients showed greater improvement in total distress over the year following diagnosis than rural patients (p = 0.025) and were significantly less distressed at one year (p = 0.03). Urban patients had a more consistent QOL improvement than their rural counterparts (p = 0.006). There were no differences in the course of depressive symptoms over the year (p = 0.17). Social support of urban patients at 12 months was significantly higher than that of rural patients (p = 0.04). CONCLUSION: Rural patients reported less improvement in psychological functioning in the year following diagnosis than their urban counterparts. Clinicians should be aware of rurality as a potential risk factor for ongoing distress. Future studies should examine causes of these health disparities and potential long-term inequities and develop interventions to address these issues.

Sex Differences in Stress Susceptibility as a Key Mechanism Underlying Depression Risk.

PURPOSE OF REVIEW: Although females are at relatively greater risk for a variety of disorders, including depression, the biological mechanisms underlying this striking health disparity remain unclear. To address this issue, we highlight sex differences in stress susceptibility as a key mechanism potentially driving this effect and describe the interacting inflammatory, hormonal, epigenomic, and social-environmental mechanisms involved. RECENT FINDINGS: Using the Social Signal Transduction Theory of Depression as a theoretical framework, women's elevated risk for depression may stem from a tight link between life stress, inflammation, and depression in women. Further, research finds hormonal contraceptive use alters cortisol and inflammatory reactivity to acute stress in ways that may increase depression risk in females. Finally, beyond established epigenetic mechanisms, mothers may transfer risk for depression to their female offspring through stressful family environments, which influence stress generation and stress-related gene expression. Together, these findings provide initial, biologically plausible clues that may help explain the relatively greater risk for depression in females vs. males. Looking forward, much more research is needed to address the longstanding underrepresentation of females in biomedical research on the biology of stress and depression.

Black-white differences in chronic stress exposures to predict preterm birth: interpretable, race/ethnicity-specific machine learning model.

BACKGROUND: Differential exposure to chronic stressors by race/ethnicity may help explain Black-White inequalities in rates of preterm birth. However, researchers have not investigated the cumulative, interactive, and population-specific nature of chronic stressor exposures and their possible nonlinear associations with preterm birth. Models capable of computing such high-dimensional associations that could differ by race/ethnicity are needed. We developed machine learning models of chronic stressors to both predict preterm birth more accurately and identify chronic stressors and other risk factors driving preterm birth risk among non-Hispanic Black and non-Hispanic White pregnant women. METHODS: Multivariate Adaptive Regression Splines (MARS) models were developed for preterm birth prediction for non-Hispanic Black, non-Hispanic White, and combined study samples derived from the CDC's Pregnancy Risk Assessment Monitoring System data (2012-2017). For each sample population, MARS models were trained and tested using 5-fold cross-validation. For each population, the Area Under the ROC Curve (AUC) was used to evaluate model performance, and variable importance for preterm birth prediction was computed. RESULTS: Among 81,892 non-Hispanic Black and 277,963 non-Hispanic White live births (weighted sample), the best-performing MARS models showed high accuracy (AUC: 0.754-0.765) and similar-or-better performance for race/ethnicity-specific models compared to the combined model. The number of prenatal care visits, premature rupture of membrane, and medical conditions were more important than other variables in predicting preterm birth across the populations. Chronic stressors (e.g., low maternal education and intimate partner violence) and their correlates predicted preterm birth only for non-Hispanic Black women. CONCLUSIONS: Our study findings reinforce that such mid or upstream determinants of health as chronic stressors should be targeted to reduce excess preterm birth risk among non-Hispanic Black women and ultimately narrow the persistent Black-White gap in preterm birth in the U.S.

Lifetime adversity predicts depression, anxiety, and cognitive impairment in a nationally representative sample of older adults in the United States.

OBJECTIVE: Although life stress and adversity are well-known risk factors for mental health problems and cognitive impairment among older adults, limited research has comprehensively examined the impact of both childhood and adulthood adversity on psychiatric and cognitive impairment symptoms over a prolonged period. To address this issue, we investigated how lifetime adversity exposure is related to symptoms of depression, anxiety, and cognitive impairment in a nationally representative, longitudinal sample of older adults in the United States. METHOD: We analyzed data from the Health and Retirement Study (1992-2016). The sample included 3496 individuals (59.9% female), aged ≥64 years old (Mage = 76.0 ± 7.6 years in 2016). We used the individual-level panel data and ordinary least squares regressions to estimate associations between childhood and adulthood adversities, and later-life depression, anxiety, and cognitive impairment. RESULTS: Many participants experienced a significant early life (38%) or adulthood (79%) stressor. Moreover, experiencing one childhood adversity (vs. none) was associated with a 17.4% increased risk of adulthood adversity. Finally, as hypothesized, childhood adversity exposure was related to experiencing more depression and anxiety symptoms in later life, whereas adulthood stressor exposure predicted more cognitive impairment as well as more depression and anxiety symptoms. DISCUSSION: These findings demonstrate significant associations between lifetime adversity and symptoms of depression, anxiety, and cognitive impairment in older adults. Screening for lifetime stressors may thus help healthcare professionals and policymakers identify individuals who could potentially benefit from interventions designed to reduce stress and enhance resilience.

Stress-related cellular pathophysiology as a crosstalk risk factor for neurocognitive and psychiatric disorders.

In this narrative review, we examine biological processes linking psychological stress and cognition, with a focus on how psychological stress can activate multiple neurobiological mechanisms that drive cognitive decline and behavioral change. First, we describe the general neurobiology of the stress response to define neurocognitive stress reactivity. Second, we review aspects of epigenetic regulation, synaptic transmission, sex hormones, photoperiodic plasticity, and psychoneuroimmunological processes that can contribute to cognitive decline and neuropsychiatric conditions. Third, we explain mechanistic processes linking the stress response and neuropathology. Fourth, we discuss molecular nuances such as an interplay between kinases and proteins, as well as differential role of sex hormones, that can increase vulnerability to cognitive and emotional dysregulation following stress. Finally, we explicate several testable hypotheses for stress, neurocognitive, and neuropsychiatric research. Together, this work highlights how stress processes alter neurophysiology on multiple levels to increase individuals' risk for neurocognitive and psychiatric disorders, and points toward novel therapeutic targets for mitigating these effects. The resulting models can thus advance dementia and mental health research, and translational neuroscience, with an eye toward clinical application in cognitive and behavioral neurology, and psychiatry.

Social threat, fronto-cingulate-limbic morphometry, and symptom course in depressed adolescents: a longitudinal investigation.

BACKGROUND: Psychosocial stressors characterized by social threat, such as interpersonal loss and social rejection, are associated with depression in adolescents. Few studies, however, have examined whether social threat affects fronto-cingulate-limbic systems implicated in adolescent depression. METHODS: We assessed lifetime stressor severity across several domains using the Stress and Adversity Inventory (STRAIN) in 57 depressed adolescents (16.15 ± 1.32 years, 34 females), and examined whether the severity of social threat and non-social threat stressors was associated with gray matter volumes (GMVs) in the anterior cingulate cortex (ACC), amygdala, hippocampus, and nucleus accumbens (NAcc). We also examined how lifetime social threat severity and GMVs in these regions related to depressive symptoms at baseline and over 9 months. RESULTS: General stressor severity was related to greater depression severity at baseline and over 9 months. Moreover, greater severity of social threat (but not non-social threat) stressors was associated with smaller bilateral amygdala and NAcc GMVs, and smaller bilateral surface areas of caudal and rostral ACC (all pFDR ⩽ 0.048). However, neither social threat nor non-social threat stressor severity was related to hippocampal GMVs (all pFDR ⩾ 0.318). All fronto-cingulate-limbic structures that were associated with the severity of social threat were negatively associated with greater depression severity over 9 months (all pFDR ⩽ 0.014). Post-hoc analyses suggested that gray matter morphometry of bilateral amygdala, NAcc, and rostral and caudal ACC mediated the association between social threat and depression severity in adolescents over 9 months (all pFDR < 0.048). CONCLUSIONS: Social threat specifically affects fronto-cingulate-limbic pathways that contribute to the maintenance of depression in adolescents.

Cumulative lifetime acute stressor exposure interacts with reward responsiveness to predict longitudinal increases in depression severity in adolescence.

BACKGROUND: Life stress and blunted reward processing each have been associated with the onset and maintenance of major depressive disorder. However, much of this work has been cross-sectional, conducted in separate lines of inquiry, and focused on recent life stressor exposure, despite the fact that theories of depression posit that stressors can have cumulative effects over the lifespan. To address these limitations, we investigated whether acute and chronic stressors occurring over the lifespan interacted with blunted reward processing to predict increases in depression over time in healthy youth. METHOD: Participants were 245 adolescent girls aged 8-14 years old (Mage = 12.4, s.d. = 1.8) who were evaluated at baseline and two years later. The reward positivity (RewP), an event-related potential measure of reward responsiveness, was assessed at baseline using the doors task. Cumulative lifetime exposure to acute and chronic stressors was assessed two years later using the Stress and Adversity Inventory for Adolescents (Adolescent STRAIN). Finally, depressive symptoms were assessed at both baseline and follow-up using the Children's Depression Inventory. RESULTS: As hypothesized, greater lifetime acute stressor exposure predicted increases in depressive symptoms over two years, but only for youth exhibiting a blunted RewP. This interaction, however, was not found for chronic stressors. CONCLUSIONS: Lifetime acute stressor exposure may be particularly depressogenic for youth exhibiting a blunted RewP. Conversely, a robust RewP may be protective in the presence of greater acute lifetime stressor exposure.

Associations between acute and chronic lifetime stressors and psychosis-risk symptoms in individuals with 22q11.2 copy number variants.

BACKGROUND: The 22q11.2 deletion (22q11Del) is among the strongest known genetic risk factors for psychosis. Stress, a known risk factor for psychosis in the general population, has seldom been studied in 22q11Del. We investigated how lifetime stressors related to symptomatic outcomes in patients with 22q11Del. We also explored this association in individuals with 22q11.2 duplications (22q11Dup), which may be potentially protective against psychosis. METHOD: One hundred individuals (46 with 22q11Del, 30 with 22q11Dup, and 24 healthy controls; Mage = 17.30 years±10.15) were included. Logistic models were used to examine cross-sectional associations between lifetime acute and chronic stressors (severity and count) and the presence (score ⩾3) of positive, negative, and general symptoms, assessed via the Structured Interview for Psychosis-risk Syndromes (SIPS). RESULTS: The 22q11Dup group reported the greatest number and severity of acute lifetime stressors, but did not differ from 22q11Del in chronic stressor count or severity. Lifetime chronic and acute stressors were uniquely associated with positive symptoms in 22q11Del (chronic count: odds ratio [OR] = 2.35, p = 0.02; chronic severity: OR = 1.88, p = 0.03; acute count: OR = 1.78, p = 0.03), but not with negative or general symptoms (ps > 0.05). CONCLUSION: Findings suggest that stress may play a role in psychotic symptoms in 22q1Del, while the 22q11Dup CNV appears protective against psychotic symptoms despite higher rates of stressors. Interventions that mitigate effects of stressors in 22qDel may reduce the odds of psychosis in this group. Prospective longitudinal research is needed to replicate these findings.

Intergenerational effects of maternal lifetime stressor exposure on offspring telomere length in Black and White women.

BACKGROUND: Although maternal stressor exposure has been associated with shorter telomere length (TL) in offspring, this literature is based largely on White samples. Furthermore, timing of maternal stressors has rarely been examined. Here, we examined how maternal stressors occurring during adolescence, pregnancy, and across the lifespan related to child TL in Black and White mothers. METHOD: Mothers (112 Black; 110 White; Mage = 39) and their youngest offspring (n = 222; Mage = 8) were part of a larger prospective cohort study, wherein mothers reported their stressors during adolescence (assessed twice during adolescence for the past year), pregnancy (assessed in midlife for most recent pregnancy), and across their lifespan (assessed in midlife). Mother and child provided saliva for TL measurement. Multiple linear regression models examined the interaction of maternal stressor exposure and race in relation to child TL, controlling for maternal TL and child gender and age. Race-stratified analyses were also conducted. RESULTS: Neither maternal adolescence nor lifespan stressors interacted with race in relation to child TL. In contrast, greater maternal pregnancy stressors were associated with shorter child TL, but this effect was present for children of White but not Black mothers. Moreover, this effect was significant for financial but not social pregnancy stressors. Race-stratified models revealed that greater financial pregnancy stressors predicted shorter telomeres in offspring of White, but not Black mothers. CONCLUSIONS: Race and maternal stressors interact and are related to biological aging across generations, but these effects are specific to certain races, stressors, and exposure time periods.

Wearable technologies for health research: Opportunities, limitations, and practical and conceptual considerations.

One of the most notable limitations of laboratory-based health research is its inability to continuously monitor health-relevant physiological processes as individuals go about their daily lives. As a result, we have generated large amounts of data with unknown generalizability to real-world situations and also created a schism between where data are collected (i.e., in the lab) and where we need to intervene to prevent disease (i.e., in the field). Devices using noninvasive wearable technology are changing all of this, however, with their ability to provide high-frequency assessments of peoples' ever-changing physiological states in daily life in a manner that is relatively noninvasive, affordable, and scalable. Here, we discuss critical points that every researcher should keep in mind when using these wearables in research, spanning device and metric decisions, hardware and software selection, and data quality and sampling rate issues, using research on stress and health as an example throughout. We also address usability and participant acceptability issues, and how wearable "digital biomarker" and behavioral data can be integrated to enhance basic science and intervention studies. Finally, we summarize 10 key questions that should be addressed to make every wearable study as strong as possible. Collectively, keeping these points in mind can improve our ability to study the psychobiology of human health, and to intervene, precisely where it matters most: in peoples' daily lives.

The future is dynamic: A call for intensive longitudinal data in immunopsychiatry.

The long-term value of immunopsychiatry will be based on its ability to translate basic science into effective clinical interventions. In this article, we discuss a key obstacle to achieving this important translational goal-namely, the preponderance of studies that are cross-sectional, or that have months-to-years long follow-up periods. Immunopsychiatric processes such as stress, inflammation, and depression symptoms are inherently dynamic and fluctuate over hours, days, and weeks. This fact suggests that higher-density data collection with only days between measurements is necessary to capture-with adequate resolution-the actual dynamics of these systems, determine optimal time lags with which to observe associations between variables of interest, and maximize the translational potential of these data. To illustrate these points, we use pilot data from our own intensive longitudinal immunopsychiatric study. We then conclude by making several recommendations for future research. By learning how to better use existing data for dynamically informative studies as well as collecting intensive longitudinal data, we believe immunopsychiatry will be much better positioned to advance our causal understanding of the interplay between the immune system and health.

Incorporating causal inference perspectives into psychoneuroimmunology: A simulation study highlighting concerns about controlling for adiposity in immunopsychiatry.

Psychoneuroimmunology and immunopsychiatry are quickly approaching a critical point where the clinical translatability of their evidence base will be tested. To maximize chances for translational success, we believe researchers must adopt causal inference techniques that augment the causal relevance of estimates given theorized causal structures. To illustrate the utility of incorporating causal inference perspectives into psychoneuroimmunology, we applied directed acyclic graphs and a combination of empirical and simulated data to demonstrate the consequences of controlling for adiposity when testing the association between inflammation and depression under the plausible causal structure of increases in adipose tissue leading to greater inflammation that in turn promotes depression. Effect size estimates were pulled from a dataset combining the Midlife in the United States 2 (MIDUS-2) and MIDUS Refresher datasets. Data were extracted and used to simulate data reflecting an adiposity â†’ inflammation â†’ depression causal structure. Next, a Monte Carlo simulation study with 1,000 iterations and three sample size scenarios (Ns = 100, 250, and 500) was conducted testing whether controlling for adiposity when estimating the relation between inflammation and depression influenced the precision of this estimate. Across all simulation scenarios, controlling for adiposity reduced precision of the inflammation â†’ depression estimate, suggesting that researchers primarily interested in quantifying inflammation â†’ depression associations should not control for adiposity. This work thus underscores the importance of incorporating causal inference approaches into psychoneuroimmunological research.

Multi-omics approaches in psychoneuroimmunology and health research: Conceptual considerations and methodological recommendations.

The field of psychoneuroimmunology (PNI) has grown substantially in both relevance and prominence over the past 40 years. Notwithstanding its impressive trajectory, a majority of PNI studies are still based on a relatively small number of analytes. To advance this work, we suggest that PNI, and health research in general, can benefit greatly from adopting a multi-omics approach, which involves integrating data across multiple biological levels (e.g., the genome, proteome, transcriptome, metabolome, lipidome, and microbiome/metagenome) to more comprehensively profile biological functions and relate these profiles to clinical and behavioral outcomes. To assist investigators in this endeavor, we provide an overview of multi-omics research, highlight recent landmark multi-omics studies investigating human health and disease risk, and discuss how multi-omics can be applied to better elucidate links between psychological, nervous system, and immune system activity. In doing so, we describe how to design high-quality multi-omics studies, decide which biological samples (e.g., blood, stool, urine, saliva, solid tissue) are most relevant, incorporate behavioral and wearable sensing data into multi-omics research, and understand key data quality, integration, analysis, and interpretation issues. PNI researchers are addressing some of the most interesting and important questions at the intersection of psychology, neuroscience, and immunology. Applying a multi-omics approach to this work will greatly expand the horizon of what is possible in PNI and has the potential to revolutionize our understanding of mind-body medicine.

Unconsidered issues of measurement noninvariance in biological psychiatry: A focus on biological phenotypes of psychopathology.

There is increasing appreciation that certain biological processes may not be equally related to all psychiatric symptoms in a given diagnostic category. Research on the biological phenotyping of psychopathology has begun examining the etiological and treatment implications of identified biotypes; however, little attention has been paid to a critical methodological implication of these results: measurement noninvariance. Measurement invariance is the ability of an instrument to measure the same construct, the same way, across different people, or across different time points for the same individual. If what a measure quantifies differs across different people (e.g., those with or without a particular biotype) or time points, then it is invalid to directly compare means on that measure. Using a running example of inflammatory phenotypes of depression, we first describe the biological phenotyping of psychopathology. Second, we discuss three types of measurement invariance. Third, we demonstrate how differential biology-symptom associations invariably creates measurement noninvariance using a theoretical example and simulated data (for which code is provided). We also show how this issue can lead to false conclusions about the broader diagnostic construct. Finally, we provide several suggestions for addressing these important issues to help advance the field of biological psychiatry.

Lifetime stressor exposure, eating expectancy, and acute social stress-related eating behavior: A pre-registered study of the emotional eating cycle.

Eating behaviors in response to acute stressors are highly variable: whereas many individuals eat more following stressors, others eat less or show no change in food consumption. Understanding factors that predict individual differences in eating behaviors may help elucidate the psychosocial mechanisms underlying obesity, yet few experimental studies on this topic have been conducted to date. To address this issue, we conducted the present pre-registered study, where we investigated how lifetime stressor exposure moderates the extent to which eating expectancies enhance the learned association between stress-induced negative affect and snack intake. Participants were 44 women (30% non-White) between 18 and 50 years old (M = 27.9), with a mean body mass index of 25.6, who completed assessments of lifetime stressor exposure, eating behaviors, and eating expectancies (eating helps manage negative affect); in a subsequent visit, they were given snacks after an acute social stress task (TSST). The moderated moderation model (PROCESS model 3) yielded a significant three-way interaction. When eating expectancies were high, acute social stress-induced negative affect predicted greater M&M intake for women with very high total lifetime stressor exposure but less M&M intake for women with fewer lifetime stressors. These data thus highlight how lifetime stressor exposure interacts with eating expectancies and acute stress-induced negative affect to predict eating behavior. Replications in larger samples may help explain variability in stress-eating as well as how lifetime stressors contribute to obesity.