Longitudinal Measurement Invariance of the ASEBA Youth/Adult Self-Reports Across the Transition From Adolescence to Adulthood.

The ability to quantify within-person changes in mental health is central to the mission of clinical psychology. Typically, this is done using total or mean scores on symptom measures; however, this approach assumes that measures quantify the same construct, the same way, each time the measure is completed. Without this quality, termed longitudinal measurement invariance, an observed difference between timepoints might be partially attributable to changing measurement properties rather than changes in comparable symptom measurements. This concern is amplified in research using different forms of a measure across developmental periods due to potential differences in reporting styles, item-wording, and developmental context. This study provides the strongest support for the longitudinal measurement invariance of the Anxiety Scale, Depression/Affective Problems: Cognitive Subscale, and the Attention Deficit Hyperactivity Disorder (ADHD) Scale; moderate support for the Depression/Affective Problems Scale and the Somatic Scale, and poor support for the Depression/Affective Problems: Somatic Symptoms Subscale of the Dutch Achenbach System of Empirically Based Assessment Youth Self-Report and Adult Self-Report in a sample of 1,309 individuals (N = 1,090 population-based, N = 219 clinic-based/referred to an outpatient clinic before age 11 years) across six waves of data (mean ages = 11 years at Wave 1 and 26 years at Wave 6).

Characterizing the hierarchical depression phenotype in sexually diverse individuals.

INTRODUCTION: Sexual diverse individuals are at high risk for internalizing psychopathologies, such as depression. Understanding how symptom profiles of heterogeneous psychiatric disorders such as depression differ for sexually diverse vs. heterosexual individuals is thus critical to advance precision psychiatry and maximize our ability to effectively treat members of this population. Research has failed to consider the possibility of hierarchical phenotypes, wherein sexual orientation status may be uniquely and simultaneously associated with both depression broadly and with individual symptoms. METHOD: To address these issues, we conducted a moderated nonlinear factor analysis in Wave IV of the Add Health study, using sexual diversity status as a predictor of (a) latent depression, (b) factor loadings, and (c) individual symptoms, with and without controlling for race. RESULTS: Sexual diversity status was positively and simultaneously associated with latent depression, concentration difficulties, and happiness. DISCUSSION: These findings suggest that sexually diverse populations not only face greater depression, broadly defined, but are disproportionately more likely to experience concentration difficulties and be happier compared to heterosexual counterparts. Methodologically, these models indicate that the CES-D is scalar noninvariant as a function of sexual diversity status (i.e., identical scores on the CES-D may represent different manifestations of depression for sexually diverse and heterosexual participants). Studies examining disparities in depression across heterosexual and sexually diverse samples should thus consider depression broadly as well as specific symptoms. Further, it is critical to examine whether these relations function via different mechanisms.

How is inflammation biology truly associated with depression in patients with stable coronary heart disease?: Insights from the heart and Soul study.

Depression is known to be associated with inflammation among patients with established coronary heart disease (CHD), but it is unclear whether this is due to individual depression symptoms or to the broader construct of depression. We addressed this gap by using moderated non-linear factor analysis (MNLFA) to determine the extent that inflammation is associated with latent depression and/or individual symptoms in this patient group. We evaluated 1,024 outpatients with stable CHD from the baseline cross-sectional data of the Heart and Soul Study. Depression was assessed using the 9-item Patient Health Questionnaire, while inflammation was evaluated via C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels. MNLFA is based on the concept of model parameter moderation with regard to individual characteristics. Using the MNLFA approach, we simultaneously tested for differences in (1) latent depression, (2) individual depression items, and (3) the factor loading of the item on latent depression as a function of inflammatory markers, with and without covariate adjustment. Higher TNF-α levels were associated with both higher levels of a latent depression factor and greater endorsement of an individual symptom (appetite changes). Increased CRP levels were significantly associated with greater appetite changes, lower concentration difficulty, and greater fatigue. Elevated IL-6 levels were only related to greater fatigue, while increased MCP-1 levels were linked to greater sleep disturbance. After adjusting for covariates, some associations became insignificant. Inflammatory markers were not consistent predictors of factor loadings. This study represents the initial step to discussing how inflammation biology is truly related to depression among patients with established CHD.

Chronic inflammation is associated with worsening working memory performance: Preliminary evidence from a diverse, longitudinal cohort of adolescents and young adults.

Many depressed individuals experience cognitive difficulties that persist when depression is in remission. Inflammation is hypothesized to play a role in cognitive dysfunction in depression; however, many aspects of this relationship are not well characterized. The current study examined whether inflammation is associated with specific cognitive deficits in individuals with a history of depression and with progressively worsening working memory over time. Adolescents who participated in a prospective, longitudinal study of adolescent-onset depression were recruited to complete a follow-up cognitive assessment. The sample was comprised of 82 participants (52.4% female; 37.8% white; 42.7% low socioeconomic status) who were aged 22.61 years (SD = 1.50) at the time of the follow-up cognitive assessment. Prior to the follow-up cognitive assessment, they had completed an average of 6.24 (SD = 1.80) prior annual assessments over 6.24 years (SD = 2.08) as part of the parent longitudinal study in which C-reactive protein (CRP), depressive symptoms, and working memory were assessed repeatedly. First, using linear regression, we tested whether individuals exhibiting inflammation (CRP ≥3 mg/L) at multiple timepoints and a history of likely depression (Children's Depression Inventory ≥19) exhibited differentially worse executive functioning, episodic memory, or psychomotor speed. Second, using hierarchical linear modeling, we tested whether the combination of inflammation and likely past depression was associated with poorer working memory over time. Chronic inflammation was associated with worsening working memory over time, but no significant associations were observed in cross-sectional analyses. These preliminary data indicate that chronic inflammation may lead to progressive decline in working memory over time.

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.

Reward sensitivity and social rhythms during goal-striving: An ecological momentary assessment investigation of bipolar spectrum disorders.

BACKGROUND: The reward/circadian rhythm model of bipolar spectrum disorders (BSDs) posits that when individuals with hypersensitive reward systems encounter reward-relevant events, they experience social and circadian rhythm disruption, leading to mood symptoms. The aim of the current study is to test an element of this theoretical model by investigating changes in social rhythms during and after an ecologically-valid reward-relevant event and evaluating whether the strength of these associations differ by trait reward sensitivity and BSD diagnostic group. METHODS: Young adults from three groups (low BSD risk with moderate reward sensitivity [MRew], high BSD risk with high reward sensitivity [HRew], and high reward sensitivity with BSD [HRew+BSD]) completed a reward responsiveness task and 20-day ecological momentary assessment study structured around a participant-specific goal occurring on day 15. Social rhythm disruption (SRD) and social rhythm regularity (SRR) were assessed daily. Multilevel models examined whether reward sensitivity and group moderated associations between study phase (baseline [days 1-5], goal-striving [days 16-20], or outcome [days 16-20]) and social rhythms. RESULTS: Participants experienced greater SRD after the goal-striving event during the outcome phase, compared to the baseline phase. The HRew+BSD group had significant decreases in SRR during the outcome phase, and this pattern differed significantly from the low-risk and high-risk groups. Greater task reward responsiveness also was associated with significant decreases in SRR during the outcome phase. LIMITATIONS: This study did not test whether social rhythm irregularity was associated with subsequent mood change. CONCLUSIONS: Participants exhibited social rhythm changes over the course of this ecologically valid goal-striving period, providing evidence for the interplay between reward-activating events and social rhythms. The HRew+BSD group showed a distinct pattern in which their social rhythms were more irregular after completing reward-relevant goal-striving that was not observed for the low-BSD risk or high-BSD risk groups. These findings provide additional support for Interpersonal and Social Rhythms Therapy.

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.

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.

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.

A systematic review of associations between emotion regulation characteristics and inflammation.

Elevated inflammation is a risk factor for many psychiatric (e.g., depression) and somatic conditions (e.g., rheumatoid arthritis). Inflammation is influenced by psychosocial processes such as emotion regulation. Characterization of which emotion regulation characteristics impact inflammation could help refine psychosocial interventions aimed at normalizing health-harming inflammatory activity for individuals with psychiatric and somatic illnesses. To investigate this issue, we systematically reviewed the literature on associations between a variety of emotion regulation traits and inflammation. Out of 2816 articles identified, 38 were included in the final review. 28 (74%) found that (a) poor emotion regulation is associated with higher inflammation and/or (b) strong emotion regulation skills are associated with lower inflammation. Consistency of results differed as a function of the emotion regulation construct investigated and methodological characteristics. Results were most consistent for studies testing positive coping/social support seeking or broadly defined emotion regulation/dysregulation. Methodologically, studies testing reactivity to a stressor, adopting a vulnerability-stress framework, or using longitudinal data were most consistent. Implications for integrated, transdiagnostic psychoimmunological theories are discussed, as well as recommendations for clinical research.

Hierarchical Inflammatory Phenotypes of Depression: A Novel Approach Across Five Independent Samples and 27,730 Adults.

BACKGROUND: Although characterizing associations between inflammation and depression may prove critical for informing theory, research, and treatment decisions, extant research has been limited by ignoring the possibility that inflammation may be simultaneously associated with depression broadly and with a subset of symptoms. This lack of direct comparison has hampered attempts to understand inflammatory phenotypes of depression and critically fails to consider that inflammation might be uniquely associated with both depression broadly and individual symptoms. METHODS: We used moderated nonlinear factor analysis in 5 NHANES (National Health and Nutrition Examination Survey) cohorts (N = 27,730, 51% female, mean age = 46 years). RESULTS: C-reactive protein (CRP) is simultaneously associated with latent depression, appetite, and fatigue. Specifically, CRP was associated with latent depression in all 5 samples (rs: 0.044-0.089; ps: < .001-.002) and was associated with both appetite (significant rs: 0.031-0.049, significant ps: .001-.007) and fatigue (significant rs: 0.030-0.054, significant ps: < .001-.029) in 4 samples. These results were largely robust to covariates. CONCLUSIONS: Methodologically, these models indicate that the Patient Health Questionnaire-9 is scalar noninvariant as a function of CRP (i.e., identical Patient Health Questionnaire-9 scores may represent different constructs in those with high vs. low CRP levels). Therefore, mean comparisons of depression total scores and CRP might be misleading without accounting for symptom-specific associations. Conceptually, these findings indicate that studies investigating inflammatory phenotypes of depression should examine how inflammation is simultaneously related both to depression broadly and to specific symptoms, and whether these relations function via different mechanisms. This has the potential to yield new theoretical insights and may lead to the development of novel therapies for reducing inflammation-related symptoms of depression.

The Impact of Early and Recent Life Stress on Trajectories of Inflammatory Biomarkers in a Diverse Sample of Adolescents.

Elevated inflammatory activity is one possible pathway through which exposure to childhood adversity engenders risk for physical and psychiatric illnesses. Limited research has investigated the compounding effects of childhood and adolescent stress exposure on changes in circulating levels of inflammatory biomarkers. This study assessed whether childhood adversity interacted with chronic or acute stress during adolescence to affect the temporal trajectories of five inflammatory biomarkers across at least three blood draws in a diverse sample of adolescents (N = 134; observations = 462). Using multilevel modeling, the interaction of childhood adversity, time, and within-person variance of acute stressors significantly predicted trajectories of higher interleukin-10 levels, controlling for demographics, medication use, and body mass index. Adolescents with high levels of childhood adversity who were exposed to a higher frequency of acute stressors compared to their own average rate of stress exposure consistently had higher levels of IL-10 as they got older, but those with average and below frequency of acute stressors had decreasing trajectories of log IL-10 as they matured. The results demonstrate how events early in life shape biological responses to the adolescent environment. This study also highlights the importance of developmental timing on the body's enhanced reactivity to acute and sustained stressors following childhood adversity.

Social Safety Theory: Conceptual foundation, underlying mechanisms, and future directions.

Classic theories of stress and health are largely based on assumptions regarding how different psychosocial stressors influence biological processes that, in turn, affect human health and behavior. Although theoretically rich, this work has yielded little consensus and led to numerous conceptual, measurement, and reproducibility issues. Social Safety Theory aims to address these issues by using the primary goal and regulatory logic of the human brain and immune system as the basis for specifying the social-environmental situations to which these systems should respond most strongly to maximize reproductive success and survival. This analysis gave rise to the integrated, multi-level formulation described herein, which transforms thinking about stress biology and provides a biologically based, evolutionary account for how and why experiences of social safety and social threat are strongly related to health, well-being, aging, and longevity. In doing so, the theory advances a testable framework for investigating the biopsychosocial roots of health disparities as well as how health-relevant biopsychosocial processes crystalize over time and how perceptions of the social environment interact with childhood microbial environment, birth cohort, culture, air pollution, genetics, sleep, diet, personality, and self-harm to affect health. The theory also highlights several interventions for reducing social threat and promoting resilience.

Using Ecological Momentary Assessments to Study How Daily Fluctuations in Psychological States Impact Stress, Well-Being, and Health.

Despite great interest in how dynamic fluctuations in psychological states such as mood, social safety, energy, present-focused attention, and burnout impact stress, well-being, and health, most studies examining these constructs use retrospective assessments with relatively long time-lags. Here, we discuss how ecological momentary assessments (EMAs) address methodological issues associated with retrospective reports to help reveal dynamic associations between psychological states at small timescales that are often missed in stress and health research. In addition to helping researchers characterize daily and within-day fluctuations and temporal dynamics between different health-relevant processes, EMAs can elucidate mechanisms through which interventions reduce stress and enhance well-being. EMAs can also be used to identify changes that precede critical health events, which can in turn be used to deliver ecological momentary interventions, or just-in-time interventions, to help prevent such events from occurring. To enable this work, we provide examples of scales and single-item questions used in EMA studies, recommend study designs and statistical approaches that capitalize on EMA data, and discuss limitations of EMA methods. In doing so, we aim to demonstrate how, when used carefully, EMA methods are well poised to greatly advance our understanding of how intrapersonal dynamics affect stress levels, well-being, and human health.

Inflammation and depression symptoms are most strongly associated for Black adults.

Although race/ethnicity is associated with substantial differences in risk for depression and other diseases of aging in the United States, the processes underlying these health disparities remain poorly understood. We addressed this issue by examining how levels of a robust marker of inflammatory activity, C-reactive protein (CRP), and depression symptoms varied across racial/ethnic groups. Additionally, we tested whether the inflammation-depression association differed across groups. Data were drawn from the Chicago Community Adult Health Survey, an epidemiological survey examining biopsychosocial factors affecting health and well-being. Participants were 3105 Chicago community adults, of which 610 provided blood samples and were included in analyses. C-reactive protein was assayed from blood samples, and depression symptoms were assessed using the 11-item Center for Epidemiologic Studies-Depression scale. Race/ethnicity was self-reported and consisted of Black, Hispanic, White, and other racial/ethnic groups. Results revealed that these racial/ethnic groups differed in terms of both their CRP and depression levels. Specifically, Black Americans exhibited higher levels of CRP as compared to White and other race/ethnicity Americans. Moreover, Black Americans exhibited more depression symptoms than Hispanic Americans. Finally, we found that inflammatory levels were strongly related to depression symptoms but only for Black Americans, with CRP alone accounting for 8% of the variance in depression symptoms in this subgroup. These data thus point to a biological process that may help to explain disparities in mental health outcomes across race/ethnicity in the United States. At the same time, additional research is needed to understand the social and structural factors driving these effects.

Protocol for project MIME: Motivation, inflammation, and Mood in Emerging Adults.

Background: Atypical inflammatory biology is gaining evidence as a risk factor for mood psychopathology; however, little work has attempted to integrate inflammation into extant psychosocial frameworks of risk. Recent work using secondary data analysis has investigated the possibility of an immunocognitive model of mood disorders, in which cognitive vulnerabilities (i.e., rumination on positive or negative affect) increase the effect that arousal-related characteristics (e.g., reward sensitivity) have on inflammatory biology in ways that may confer risk for depression and hypo/mania symptoms. Project MIME (Motivation, Inflammation, and Mood in Emerging Adults) was designed to test this model in the context of a novel, reward-salient stressor (the Anger Incentive Delay Task, AIDT). Methods: This NIMH-funded study will result in a dataset of approximately 100 college undergraduates from a large university in Pennsylvania, United States of America. Eligible participants are recruited from an online screener, have to be 18-22 years old, fluent in English, and successfully answer several items designed to test whether participants randomly answer questions on the screener. Eligible participants are invited to an in-person visit in which they completed the AIDT, blood draws pre- and 50 minutes post-AIDT, and self-report questionnaires. Participants also complete a set of online questionnaires two weeks after the in-person visit. Discussion: Consistent with calls from the NIH director, this study seeks to diversify the tools used in stress research by validating a novel reward-salient stressor (in contrast to the field's reliance on social stressors) with respect to affective and immunological stress reactivity. In addition to this methodological goal, Project MIME is the first study specifically designed to test the immunocognitive model of mood psychopathology. Given the integration of several malleable treatment targets (approach behavior, emotion regulation, inflammation) into this model, results from this study could inform comprehensive, flexible intervention strategies for mood disorder prevention and treatment.

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.

A physiometric investigation of inflammatory composites: Comparison of "a priori" aggregates, empirically-identified factors, and individual proteins.

Most research testing the association between inflammation and health outcomes (e.g., heart disease, diabetes, depression) has focused on individual proteins; however, some studies have used summed composites of inflammatory markers without first investigating dimensionality. Using two different samples (MIDUS-2: N â€‹= â€‹1255 adults, MIDUS-R: N â€‹= â€‹863 adults), this study investigates the dimensionality of eight inflammatory proteins (C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), fibrinogen, E-selectin, and intercellular adhesion molecule (ICAM)-1) and compared the resulting factor structure to a) an "a priori"/tau-equivalent factor structure in which all inflammatory proteins equally load onto a single dimension (comparable to the summed composites) and b) proteins modeled individually (i.e., no latent variable) in terms of model fit, replicability, reliability, and their associations with health outcomes. An exploratory factor analysis indicated a two-factor structure (Factor 1: CRP and fibrinogen; Factor 2: IL-8 and IL-10) in MIDUS-2 and was replicated in MIDUS-R. Results did not clearly indicate whether the empirically-identified factor structure or the individual proteins modeled without a latent variable had superior model fit, but both strongly outperformed the "a priori"/tau-equivalent structure (which did not achieve acceptable model fit in any models). Modeling the empirically-identified factors and individual proteins (without a latent factor) as outcomes of medical diagnoses resulted in comparable conclusions. However, modeling individual proteins resulted in findings more robust to correction for multiple comparisons despite more conservative adjustments. Further, reliability for all latent variables was poor. These results indicate that modeling inflammation as a unidimensional construct equally associated with all available proteins does not fit the data well. Instead, individual inflammatory proteins or, potentially (if empirically supported and biologically-plausible) empirically-identified inflammatory factors should be used in accordance with theory.

Building a replicable and clinically-impactful immunopsychiatry: Methods, phenotyping, and theory integration.

Immunopsychiatry is a subfield of psychoneuroimmunology that integrates immunological and psychopathological processes with promise for improving the classification, identification, and treatment of psychopathology. Using research on the relationship between inflammation and depression as a running example, this mini-review will discuss three areas of work that should be emphasized in future research to maximize the replicability and clinical impact of the field: 1) methodology with respect to planning data collection and statistical analyses with measurement properties and conceptually important sources of variance in mind, 2) characterizing inflammatory phenotypes of psychopathology, and 3) the integration of inflammatory processes into robust, extant psychosocial theoretical frameworks of psychopathology risk. Consistent, parallel growth in all three areas will ensure immunopsychiatry research is replicable, contributes to understanding of how (and for whom) the immune system is associated with psychiatric symptoms, and increases the flexibility and power of personalized treatment planning.