Broad umbrella concepts used to explain the relationship between psychological experiences and inflammatory markers carry a risk of conceptual clutter (Moriarity et al., 2023). Terms such as psychoneuroimmunology, immunopsychiatry, psychosomatics, and neuroinflammation share a conceptual ground, with each emphasizing a different level or direction; however, they contain uncertainties regarding the causal starting point. I introduce the term "Psychoinflammation" as a more mechanistic taxonomy to explain phenotypes in which mental processes initiate a clearly measurable inflammatory response in the immune system.Psychoinflammation refers to a peripheral-dominant inflammatory biotype within the inflammatory continuum, where etiological priority is attributed to a psychogenic trigger. This biotype can be clinically demonstrated more distinctly in cases where central inflammatory involvement is not dominant or not demonstrable."Psycho" denotes psychological experience, conscious content, and behavioral phenotypes. Operationally, it represents phenomena measured through validated scales, such as stress, trauma, or an individual's subjective experience. Stress here refers to "perceived stress" where the individual interprets events as threatening or unmanageable rather than objective stressors. Although the subjective nature of psychological processes may appear to be a limitation in terms of measurement, they can be measured using valid and standardized tools. Instruments used in the measurement of psychological triggers, such as the Perceived Stress Scale and the Childhood Trauma Questionnaire, convert subjective experience into quantitative data (Bernstein et al., 2003;Cohen et al., 1983). On the other hand, the objective and measurable nature of inflammation allows for the scientific validation of the etiological link. Subjective experiences are significantly associated with objective physiological criteria such as the allostatic load index, diurnal cortisol rhythm, and heart rate variability (Steptoe et al., 2007;McEwen, 1998). In the validation study of the Perceived Stress Questionnaire, Fliege et al. (2005) demonstrated significant correlations between subjective stress measurements and objective immune markers by showing that high stress scores were associated with immunological imbalances. In post-traumatic stress disorder, an algorithm based on serum cortisol and IL-6 levels was developed, and it was reported that this algorithm could distinguish patients with a 78% accuracy rate (Zorkina et al., 2025). It has been shown in COPD patients that high stress levels measured by the Perceived Stress Scale are distinctly associated with specific biological pathways such as platelet activation (urinary 11-dehydro-thromboxane B2) and oxidative stress (8isoprostane) (Offor et al., 2025). Acute social stress protocols (social pressure/stress stimulus) have been shown to produce robust effects on many inflammatory markers such as IL-5, IL-22, IL-8, and IL-10 (Hogenelst et al., 2024). All of these are evidence demonstrating that psychological stress can be associated not only with subjective scores but also with biological pathophysiological markers. Despite all this evidence, methodological challenges regarding the standardization of subjective psychological measurements persist. Therefore, as mentioned above, the concept of Psychoinflammation requires a multidimensional assessment based on the exclusion of central nervous system findings, in addition to the objective presence of peripheral inflammation markers.The critical point of this term is that it prioritizes the "psychological" trigger. In this respect, it offers a more mechanistic approach than the term "psychosomatic" and a clearer, distinct etiological starting point compared to the term "neuroinflammation." Attributing causal primacy to the psychological trigger is supported by experimental evidence, such as the rapid increase observed in inflammatory markers following acute stress exposure and the decrease in these markers following psychological interventions. Simultaneously, "psycho" indicates the "level" at which the phenomenon is observed. The aim of the term is not to create a new nosological category but to define a specific etiological biotype within existing psychopathologies. In this sense, Psychoinflammation defines cases that "demonstrate the effects of psychological processes through inflammation" and proposes a narrowed subset focused on the mechanism.The existing evidence in the literature directs us to the criteria listed below. In clinical practice, Psychoinflammation can be measured as follows. Furthermore, its empirical distinguishability and falsifiability are critical to the methodological strength of the concept.1. Trigger: The presence of subjective psychological triggers or history of a demonstrable intensity in the recent past; a significant level of psychological load validated by standardized scales. In the differential diagnosis of this biotype, the severity of inflammation is expected to correlate positively with psychological stress scores, while this relationship should be weak with metabolic parameters.2. Biological evidence: Observation of high levels of peripheral inflammatory markers. In their research using a "transdiagnostic inflammatory subgroup" approach, Byrne et al. (2022) identified an 'inflamed' biotype determined through cluster analyses in which multiple inflammatory markers were evaluated together. Cluster analyses using these criteria may enable the differentiation of the Psychoinflammation subtype from other inflammatory subtypes (e.g., inflammation related to autoimmunity or metabolic syndrome). For instance, high-sensitivity CRP > 3 mg/L is a practical criterion used in most studies to define a "high inflammation" subgroup (Pinzi et al., 2025). Psychoinflammation utilizes the requirement of a 'psychogenic initiator' as a methodological filter to distinguish this inflammatory subgroup from others.3. Central nervous system (CNS) dissociation: Incongruence of central inflammation with the peripheral load or its remaining in the secondary background. Heterogeneity of clinical symptoms and the dominance of peripheral biomarkers are frequently reported in the literature. Within current technological limitations, this dissociation can be evidenced by neuroimaging (e.g., TSPO-PET), as well as through the absence of neurological findings specific to central inflammation and the primary weight of peripheral inflammatory markers in explaining the clinical picture. This criterion represents the peripheral-dominant nature in which the model is limited to the peripheral area, as peripheral signals in this configuration cannot yet be associated with demonstrable parenchymal activation (Schubert et al. 2020).4. Psychological processes as the primary source of inflammatory load: Clinical exclusion of dominant alternative explanations for inflammation, such as active infection, cancer, or autoimmune diseases, or these conditions remaining secondary in explaining the current peripheral inflammatory picture. Psychoinflammation must be falsifiable at this point. If inflammatory markers remain elevated despite the reduction or control of the psychological burden, and if evidence of neuroinflammation coinciding with the peripheral load can be demonstrated at this stage, this clinical picture should be considered outside the scope of psychoinflammation. In this regard, psychoinflammation necessitates a multi-stage exclusion process. The inflammatory subgroup should be identified through multivariate classification or clustering methods. Subsequently, it must be tested whether the correlation between psychological load and inflammation is significantly stronger than its association with other metabolic parameters (insulin resistance, BMI, etc.). Thus, it transforms into an empirically distinguishable concept.These criteria represent an increasingly important approach to stratifying patient populations into more homogeneous subgroups. Indeed, the utilization of these criteria in determining inflammatory biotypes is steadily rising. Notably, a recent study using cluster analysis in patients with major depressive episodes identified three distinct immunological profiles and succeeded in distinguishing patients from healthy controls with an 83.8% accuracy rate using a Random Forest model. The cluster with the strongest inflammatory profile identified in this study (Cluster 3) was characterized by high levels of TNF-α, CX3CL1, IL-12p70, IL-17A, IL-23, and IL-33, indicating an active inflammatory process. These findings demonstrate that peripheral immune phenotyping is a powerful tool that can be used to differentiate homogeneous subgroups within mood disorders (Daray et al., 2024). Researchers can identify patients who fall into the Psychoinflammation biotype by using these criteria. In this way, the efficacy of anti-inflammatory treatments can be tested much more precisely in patients who belong to this biotype compared to those who do not. In clinical practice, screening for these criteria in cases of treatment non-responsiveness allows for the explanation of treatment resistance through the 'inflammatory barrier' hypothesis and brings integrated approaches focused on stress management to the agenda.Additionally, although psychoinflammation overlaps with low-grade inflammation (LGI) in some aspects, it is distinct from it. LGI refers to systemic, chronic, low-intensity, subclinical inflammation with many potential determinants, including lifestyle, aging, and stress. Psychoinflammation, however, aims to methodologically distinguish a peripheraldominant biotype within this heterogeneous cluster, where the inflammatory response is linked to a psychogenic trigger with causal priority, and metabolic or autoimmune explanations remain secondary. Its priority is not the severity of inflammation, but rather the initial direction and etiological precedence of the inflammatory process.Psychoinflammation, however, aims to methodologically delineate a peripheraldominant, potentially early-stage biotype within this heterogeneous cluster, in which the inflammatory response is hypothesized to be linked to a psychogenic trigger with causal precedence, while metabolic or autoimmune explanations are not considered primary. Its focus is not the severity of inflammation, but rather the initial direction and proposed etiological ordering of the inflammatory processThe scientific validity of psychoinflammation is based on measurable and reproducible biological processes, namely inflammatory pathways. However, the first step of the process, the "psycho" component, involves neurobiological conversion mechanisms that are not yet clear and require further research. The theoretical strength of the term actually lies in offering an etiological classification. This term is not a concept that fully explains "how" psychological experiences are transformed into neurobiological signals at the "initial moment." The mechanistic improvement provided by the term focuses not on the details of the initial steps, but on confirming the inflammatory pathway as the primary pathogenic mechanism in subgroups with psychological etiology. The most significant evidence for the validity of the term is the dissociation of peripheral inflammation from central inflammation observed in psychopathologies. However, peripheral and central inflammation are not entirely independent processes (Hosang et al., 2024), and this point must be addressed in a balanced manner in light of the extensive literature demonstrating bidirectional communication between the peripheral and central immune systems. At the same time, the concept of Psychoinflammation should evaluate this dissociation within a continuum where the psychological trigger primarily results at the peripheral level and central reflections are temporally delayed or exhibit individual differences. Peripheral signals do not always leave a measurable and/or consistent trace centrally. For example, high inflammation markers in the peripheral blood in depression and schizophrenia are not always consistent with inflammation in the CNS, and results are generally heterogeneous. In individuals with psychosis, no significant differences were detected in brain levels of translocator protein, a marker of microglial activation, even when grouped according to peripheral inflammatory clusters (Plavén-Sigray et al., 2018). Although serum IL-6 levels were found to be elevated in patients with anxious depression, structural CNS findings, such as gray matter volume changes, were observed only in specific regions (Vai et al., 2022).This empirical dissociation appears consistent with the hypothesis that the 'psycho' component may manifest as peripheral inflammation and that neuroinflammation may be a secondary and/or variable consequence. Psychoinflammation is much more suitable for classifying disease subgroups driven by a systemic inflammatory biotype, representing the biological cost of psychological processes, in cases lacking CNS findings. In this way, the efficacy of specific anti-inflammatory and immunomodulatory treatments can be tested with higher sensitivity compared to etiologically more heterogeneous groups. The most concrete counterpart of the concept in clinical practice is its potential to provide a prognostic prediction. This term can serve as a "warning sign" for clinicians. It can offer the clinician the opportunity to rationalize the cause of treatment non-responsiveness as a tangible "inflammatory barrier." This provides clinicians with an integrated approach focused on stress management.The fundamental basis for the idea of psychoinflammation is the causality ambiguity in the holistic approach of the term psychoneuroimmunology, the ambiguity in the term psychosomatic, and the site restriction in the term neuroinflammation (Androulakis, 2024).The term psychoneuroimmunology assigns equal weight to each in its the primary mechanism is not clear and it involves bidirectional Researchers must control for many potential to the theoretical causal which can the sensitivity of the primary This sensitivity has been demonstrated in causal relationship research (Moriarity et al., and the methodological of determining a clear etiological starting point in psychoneuroimmunology research has been (Moriarity et al., 2023). 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Aslı Kazğan Kılıçaslan (Wed,) studied this question.