University of Molise

Reactive oxygen and nitrogen species (RONS) are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress occurs from the imbalance between RONS production and these antioxidant defenses. Aging is a process characterized by the progressive loss of tissue and organ function. The oxidative stress theory of aging is based on the hypothesis that age-associated functional losses are due to the accumulation of RONS-induced damages. At the same time, oxidative stress is involved in several age-related conditions (ie, cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases, and cancer), including sarcopenia and frailty. Different types of oxidative stress biomarkers have been identified and may provide important information about the efficacy of the treatment, guiding the selection of the most effective drugs/dose regimens for patients and, if particularly relevant from a pathophysiological point of view, acting on a specific therapeutic target. Given the important role of oxidative stress in the pathogenesis of many clinical conditions and aging, antioxidant therapy could positively affect the natural history of several diseases, but further investigation is needed to evaluate the real efficacy of these therapeutic interventions. The purpose of this paper is to provide a review of literature on this complex topic of ever increasing interest.

We present the first results of the Fermilab National Accelerator Laboratory (FNAL) Muon g -2 Experiment for the positive muon magnetic anomaly a g -2=2. The anomaly is determined from the precision measurements of two angular frequencies. Intensity variation of high-energy positrons from muon decays directly encodes the difference frequency a between the spin-precession and cyclotron frequencies for polarized muons in a magnetic storage ring. The storage ring magnetic field is measured using nuclear magnetic resonance probes calibrated in terms of the equivalent proton spin precession frequency 0

In mountainous regions, climate warming is expected to shift species' ranges to higher altitudes. Evidence for such shifts is still mostly from revisitations of historical sites. We present recent (2001 to 2008) changes in vascular plant species richness observed in a standardized monitoring network across Europe's major mountain ranges. Species have moved upslope on average. However, these shifts had opposite effects on the summit floras' species richness in boreal-temperate mountain regions (+3.9 species on average) and Mediterranean mountain regions (-1.4 species), probably because recent climatic trends have decreased the availability of water in the European south. Because Mediterranean mountains are particularly rich in endemic species, a continuation of these trends might shrink the European mountain flora, despite an average increase in summit species richness across the region.

OBJECTIVE: To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA). METHODS: GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face-to-face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire. RESULTS: Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of >80% was reached for approval of the individual recommendations and the overall schema. CONCLUSION: We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves.

Soil provides ecosystem services, supports human health and habitation, stores carbon and regulates emissions of greenhouse gases. Unprecedented pressures on soil from degradation and urbanization are threatening agro-ecological balances and food security. It is important that we learn more about soil to sustainably manage and preserve it for future generations. To this end, we developed and analyzed a global soil visible–near infrared (vis–NIR) spectral library. It is currently the largest and most diverse database of its kind. We show that the information encoded in the spectra can describe soil composition and be associated to land cover and its global geographic distribution, which acts as a surrogate for global climate variability. We also show the usefulness of the global spectra for predicting soil attributes such as soil organic and inorganic carbon, clay, silt, sand and iron contents, cation exchange capacity, and pH. Using wavelets to treat the spectra, which were recorded in different laboratories using different spectrometers and methods, helped to improve the spectroscopic modelling. We found that modelling a diverse set of spectra with a machine learning algorithm can find the local relationships in the data to produce accurate predictions of soil properties. The spectroscopic models that we derived are parsimonious and robust, and using them we derived a harmonized global soil attribute dataset, which might serve to facilitate research on soil at the global scale. This spectroscopic approach should help to deal with the shortage of data on soil to better understand it and to meet the growing demand for information to assess and monitor soil at scales ranging from regional to global. New contributions to the library are encouraged so that this work and our collaboration might progress to develop a dynamic and easily updatable database with better global coverage. We hope that this work will reinvigorate our community's discussion towards larger, more coordinated collaborations. We also hope that use of the database will deepen our understanding of soil so that we might sustainably manage it and extend the research outcomes of the soil, earth and environmental sciences towards applications that we have not yet dreamed of.

Since ancient times, folk medicine and agro-food science have benefitted from the use of plant derivatives, such as essential oils, to combat different diseases, as well as to preserve food. In Nature, essential oils play a fundamental role in protecting the plant from biotic and abiotic attacks to which it may be subjected. Many researchers have analyzed in detail the modes of action of essential oils and most of their components. The purpose of this brief review is to describe the properties of essential oils, principally as antifungal agents, and their role in blocking cell communication mechanisms, fungal biofilm formation, and mycotoxin production.

Aging is accompanied by remodeling of the immune system. With time, this leads to a decline in immune efficacy, resulting in increased vulnerability to infectious diseases, diminished responses to vaccination, and a susceptibility to age-related inflammatory diseases. An age-associated immune alteration, extensively reported in previous studies, is the reduction in the number of peripheral blood naïve cells, with a relative increase in the frequency of memory cells. These two alterations, together with inflamm-aging, are considered the hallmarks of immunosenescence. Because aging is a plastic process, it is influenced by both nutritional and pharmacological interventions. Therefore, the role of nutrition and of immunomodulation in immunosenescence is discussed, due to the multifactorial influence on these hallmarks. The close connection between nutrition, intake of bioactive nutrients and supplements, immune function, and inflammation demonstrate the key role of dietary strategies as regulators of immune response and inflammatory status, hence as possible modulators of the rate of immunosenescence. In addition, potential options for therapeutic intervention are clarified. In particular, the use of interleukin-7 as growth factor for naïve T cells, the function of checkpoint inhibitors in improving T cell responses during aging and, the potential of drugs that inhibit mitogen-activated protein kinases and their interaction with nutrient signaling pathways are discussed. Finally, it is suggested that the inclusion of appropriate combinations of toll-like receptor agonists may enhance the efficacy of vaccination in older adults.

Free radicals have acquired growing importance in the fields of biology and medicine. They are produced during many different endogenous and exogenous processes. Mitochondria are the main source of endogenous reactive oxygen species (ROS) produced at cell level. The overproduction of free radicals can damage macromolecules such as nucleic acids, proteins and lipids. This leads to tissue damage in various chronic and degenerative diseases. Antioxidants play a crucial role in the body’s defense against free radicals. This review concerns the main properties of free radicals, their sources and deleterious effects. It highlights the potential role of the dietary supplementation of antioxidants and discusses unsolved problems regarding antioxidant supplements in the prevention and therapy of diseases.

AIMS: To investigate the prevalence of pathological internet use (PIU) and maladaptive internet use (MIU) among adolescents in 11 European countries in relation to demographic, social factors and internet accessibility. DESIGN: Cross-sectional survey. SETTING: The 7th Framework European Union (EU) funded project, Saving and Empowering Young Lives in Europe (SEYLE), is a randomized controlled trial (RCT) evaluating interventions for risk behaviours among adolescents in Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain, with Sweden serving as the coordinating centre. PARTICIPANTS: A total of 11 956 adolescents (female/male: 6731/5225; mean age: 14.9 ± 0.89) recruited from randomly selected schools within the 11 study sites. MEASUREMENTS: Internet users were classified by gender into three categories: adaptive, maladaptive and pathological, based on their score in the Young Diagnostic Questionnaire for Internet Addiction (YDQ). FINDINGS: The overall prevalence of PIU was 4.4%; it was higher among males than females (5.2% versus 3.8%) and differed between countries (χ(2) = 309.98; d.f. = 20; P < 0.001). PIU correlated significantly with mean hours online and male gender. The highest-ranked online activities were watching videos, frequenting chatrooms and social networking; significantly higher rates of playing single-user games were found in males and social networking in females. Living in metropolitan areas was associated with PIU. Students not living with a biological parent, low parental involvement and parental unemployment showed the highest relative risks of both MIU and PIU. CONCLUSIONS: Across a range of countries in Europe, using the Young Diagnostic Questionnaire for Internet Addiction yields a prevalence of 'pathological internet use' of 4.4% among adolescents, but varies by country and gender; adolescents lacking emotional and psychological support are at highest risk.

Chronic leg ulcers affect 1-2% of the general population and are related to increased morbidity and health costs. Staphylococcus aureus and Pseudomonas aeruginosa are the most common bacteria isolated from chronic wounds. They can express virulence factors and surface proteins affecting wound healing. The co-infection of S. aureus and P. aeruginosa is more virulent than single infection. In particular, S. aureus and P. aeruginosa have both intrinsic and acquired antibiotic resistance, making clinical management of infection a real challenge, particularly in patients with comorbidity. Therefore, a correct and prompt diagnosis of chronic wound infection requires a detailed knowledge of skin bacterial flora. This is a necessary prerequisite for tailored pharmacological treatment, improving symptoms, and reducing side effects and antibiotic resistance.

Continental-scale assessments of 21st century global impacts of climate change on biodiversity have forecasted range contractions for many species. These coarse resolution studies are, however, of limited relevance for projecting risks to biodiversity in mountain systems, where pronounced microclimatic variation could allow species to persist locally, and are ill-suited for assessment of species-specific threat in particular regions. Here, we assess the impacts of climate change on 2632 plant species across all major European mountain ranges, using high-resolution (ca. 100 m) species samples and data expressing four future climate scenarios. Projected habitat loss is greater for species distributed at higher elevations; depending on the climate scenario, we find 36–55% of alpine species, 31–51% of subalpine species and 19–46% of montane species lose more than 80% of their suitable habitat by 2070–2100. While our high-resolution analyses consistently indicate marked levels of threat to cold-adapted mountain florae across Europe, they also reveal unequal distribution of this threat across the various mountain ranges. Impacts on florae from regions projected to undergo increased warming accompanied by decreased precipitation, such as the Pyrenees and the Eastern Austrian Alps, will likely be greater than on florae in regions where the increase in temperature is less pronounced and rainfall increases concomitantly, such as in the Norwegian Scandes and the Scottish Highlands. This suggests that change in precipitation, not only warming, plays an important role in determining the potential impacts of climate change on vegetation.

BACKGROUND: Pathological Internet use (PIU) has been conceptualized as an impulse-control disorder that shares characteristics with behavioral addiction. Research has indicated a potential link between PIU and psychopathology; however, the significance of the correlation remains ambiguous. The primary objective of this systematic review was to identify and evaluate studies performed on the correlation between PIU and comorbid psychopathology; the secondary aims were to map the geographical distribution of studies, present a current synthesis of the evidence, and assess the quality of available research. SAMPLING AND METHODS: An electronic literature search was conducted using the following databases: MEDLINE, PsycARTICLES, PsychINFO, Global Health, and Web of Science. PIU and known synonyms were included in the search. Data were extracted based on PIU and psychopathology, including depression, anxiety, symptoms of attention deficit and hyperactivity disorder (ADHD), obsessive-compulsive symptoms, social phobia and hostility/aggression. Effect sizes for the correlations observed were identified from either the respective publication or calculated using Cohen's d or R(2). The potential effect of publication bias was assessed using a funnel plot model and evaluated by Egger's test based on a linear regression. RESULTS: The majority of research was conducted in Asia and comprised cross-sectional designs. Only one prospective study was identified. Twenty articles met the preset inclusion and exclusion criteria; 75% reported significant correlations of PIU with depression, 57% with anxiety, 100% with symptoms of ADHD, 60% with obsessive-compulsive symptoms, and 66% with hostility/aggression. No study reported associations between PIU and social phobia. The majority of studies reported a higher rate of PIU among males than females. The relative risks ranged from an OR of 1.02 to an OR of 11.66. The strongest correlations were observed between PIU and depression; the weakest was hostility/aggression. CONCLUSIONS: Depression and symptoms of ADHD appeared to have the most significant and consistent correlation with PIU. Associations were reported to be higher among males in all age groups. Limitations included heterogeneity in the definition and diagnosis of PIU. More studies with prospective designs in Western countries are critically needed.

In recent decades, Mediterranean landscapes have been affected by human-induced drivers, such as land use and climate change. Forest ecosystems and landscapes have been particularly affected in mountainous regions due to limited management and stewardship, especially in remote areas. Therefore, there is a need to set up new strategies to enhance ecosystem services in forested areas which, in turn, will benefit local communities and economies. In this study, we implemented a new approach—Multiscale Mapping of Ecosystem Services (MIMOSE)—to assess ecosystem services in Mediterranean forests located in a mountainous region of Italy. We spatially assessed timber provision and carbon sequestration according to three forest management strategies: business-as-usual, maximizing economic values, and prioritizing conservation. Sustainable strategies for forest planning were identified at the landscape scale. We found that (i) timber provision is a conflicting service, especially when adaptation strategies are promoted; (ii) the most balanced set of forest ecosystem services is achieved through prioritizing conservation; and (iii) the ecosystem services availability is enhanced by optimizing the spatial allocation of different management strategies. Our approach is suitable to support landscape planning for balancing forest ecosystem potentialities while respecting local community needs and promoting sustainable development goals in the Mediterranean area.

Obesity is a major health problem strongly increasing the risk for various severe related complications such as metabolic syndrome, cardiovascular diseases, respiratory disorders, diabetic retinopathy, and cancer. Adipose tissue is an endocrine organ that produces biologically active molecules defined "adipocytokines," protein hormones with pleiotropic functions involved in the regulation of energy metabolism as well as in appetite, insulin sensitivity, inflammation, atherosclerosis, cell proliferation, and so forth. In obesity, fat accumulation causes dysregulation of adipokine production that strongly contributes to the onset of obesity-related diseases. Several advances have been made in the treatment and prevention of obesity but current medical therapies are often unsuccessful even in compliant patients. Among the adipokines, adiponectin shows protective activity in various processes such as energy metabolism, inflammation, and cell proliferation. In this review, we will focus on the current knowledge regarding the protective properties of adiponectin and its receptors, AdipoRs ("adiponectin system"), on metabolic complications in obesity and obesity-related diseases. Adiponectin, exhibiting antihyperglycemic, antiatherogenic, and anti-inflammatory properties, could have important clinical benefits in terms of development of therapies for the prevention and/or for the treatment of obesity and obesity-related diseases.

CAPELLO R. (1999) Spatial transfer of knowledge in high technology milieux: learning versus collective learning processes, Reg. Studies 33 , 353‐365 . An analysis of the definitions provided so far in the literature shows ambiguities in the conceptualization of collective learning. A parallel analysis of the concepts of learning and collective learning is provided, and similarities and differences underlined. One of the main distinguishing features of collective learning is embedded in the element of ‘club externality', while ‘continuity' and ‘dynamic synergies' are common properties of learning and collective learning. These reflections lead to some interesting empirical questions which are investigated in the empirical part of the paper. In particular, the empirical analysis addresses the questions: (1) is it true that collective learning is not the result of co-operative behaviour, but of a collective behaviour; and (2) is it true that collective learning is the way of achieving new creative resources for SMEs in local areas, and not other kinds of learning? The empirical analysis is based on three Italian high technology milieux. Descriptive and interpretative statistical methodologies are used in this part of the paper. CAPELLO R. (1999) Le transfert spatial de la connaissance dans des technopôles: l'apprentissage contre les processus d'apprentissage collectif, Reg. Studies 33 , 353-365 . Puisant dans la documentation, il en résulte d'une analyse des définitions disponibles quelques ambiguités àpropos de la conceptualisation de l'apprentissage collectif. On fournit une analyse parallèle des concepts d'apprentissage et d'apprentisage collectif et souligne les similarités et les différences. L'une des principales caractéristiques de l'apprentissage collectif est ancrée dans la notion de 'retombée commune', tandis que les notions de 'continuité' et de 'synergies dynamiques' sont des traits particuliers de l'apprentissage et de l'apprentissage collectif. Ces remarques laissent supposer des questions empiriques intéressantes qui se voient aborder dans la partie empirique de l'article. En particulier, l'analyse empirique remet en cause la vérité des affirmations suivantes: a). l'apprentissage collectif ne résulte pas d'un comportement coopératif mais d'un comportement collectif; b). par rapport aux autres genres d'apprentissage, c'est par l'apprentissage collectif que l'on peut engendrer de nouvelles ressources dynamiques en faveur des PME situées dans les collectivités locales. L'analyse empirique est fondée sur trois technopoles en Italie. Cette partie de l'article se sert des méthodologies de description et d'interprétation statistiques. CAPELLO R. (1999)Ra ¨umliche Wissensvermittlung in hoch technisierten Milieus: Lernen gegen kollektive Lernprozesse, Reg. Studies 33 , 353‐365 . Eine Analyse der Definitionen, die bisher von der Literatur angeboten wurden, weist Ambiguita ¨ten in der begrifflichen Fassung kollektiven Lernens auf. Es wird eine Parallelanalyse der Konzepte des Lernens und kollectiven Lernens vorgestellt, und A ¨hnlichkeiten sowie Unterschiede hervorgehoben. Einer der Hauptunterschiede kollektiven Lernens ist in dem Element des a ¨ußeren Zuges der geschlossenen Gesellschaft verankert, wa ¨hrend ‘Kontinuita ¨t' und ‘dynamische Zusammenfassung der Kra ¨fte zum gleichen Zweck' gemeinsame Eigenschaften des Lernens und des kollektiven Lernens sind. Diese U¨berlegungen fu¨hren zu interessanten empirischen Fragen, die im empirischen Teil des Aufsatzes behandelt werden. Die empirische Analyse bescha ¨ftigt sich vorallem mit den folgenden Fragen: a)trifft es zu, daß kollektives Lernen nicht das Ergebnis ko-operativen Verhaltens ist, sondern das eines kollektiven Verhaltens? b) trifft es zu, daß kollektives Lernen der Weg fu¨r kleine und mittlere Unternehmen ist, am Orte neue scho ¨pferische Reserven anzuzapfen, die andere Arten des Lernens nicht ero¨ffnen? Die empirische Analyse stu¨tzt sich auf drei italienische, hoch technisierte Milieus. In diesem Teil des Aufsatzes werden deskriptive und interpretative statistische Methodiken benutzt.

Since the second version of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations were published in 2015, therapeutic options for psoriatic arthritis (PsA) have advanced considerably. This work reviews the literature since the previous recommendations (data published 2013-2020, including conference presentations between 2017 and 2020) and reports high-quality, evidence-based, domain-focused recommendations for medication selection in PsA developed by GRAPPA clinicians and patient research partners. The overarching principles for the management of adults with PsA were updated by consensus. Principles considering biosimilars and tapering of therapy were added, and the research agenda was revised. Literature searches covered treatments for the key domains of PsA: peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis; additional searches were performed for PsA-related conditions (uveitis and inflammatory bowel disease) and comorbidities. Individual subcommittees used a GRADE-informed approach, taking into account the quality of evidence for therapies, to generate recommendations for each of these domains, which were incorporated into an overall schema. Choice of therapy for an individual should ideally address all disease domains active in that patient, supporting shared decision-making. As safety issues often affect potential therapeutic choices, additional consideration was given to relevant comorbidities. These GRAPPA treatment recommendations provide up-to-date, evidence-based guidance on PsA management for clinicians and people with PsA.

BACKGROUND: Subthreshold-depression and anxiety have been associated with significant impairments in adults. This study investigates the characteristics of adolescent subthreshold-depression and anxiety with a focus on suicidality, using both categorical and dimensional diagnostic models. METHODS: Data were drawn from the Saving and Empowering Young Lives in Europe (SEYLE) study, comprising 12,395 adolescents from 11 countries. Based on self-report, including Beck Depression Inventory-II (BDI-II), Zung Self-Rating Anxiety Scale (SAS), Strengths and Difficulties Questionnaire (SDQ) and Paykel Suicide Scale (PSS) were administered to students. Based on BDI-II, adolescents were divided into three groups: nondepressed, subthreshold-depressed and depressed; based on the SAS, they were divided into nonanxiety, subthreshold-anxiety and anxiety groups. Analyses of Covariance were conducted on SDQ scores to explore psychopathology of the defined groups. Logistic regression analyses were conducted to explore the relationships between functional impairments, suicidality and subthreshold and full syndromes. RESULTS: Thirty-two percent of the adolescents were subthreshold-anxious and 5.8% anxious, 29.2% subthreshold-depressed and 10.5% depressed, with high comorbidity. Mean scores of SDQ of subthreshold-depressed/anxious were significantly higher than the mean scores of the nondepressed/nonanxious groups and significantly lower than those of the depressed/anxious groups. Both subthreshold and threshold-anxiety and depression were related to functional impairment and suicidality. CONCLUSIONS: Subthreshold-depression and subthreshold-anxiety are associated with an increased burden of disease and suicide risk. These results highlight the importance of early identification of adolescent subthreshold-depression and anxiety to minimize suicide. Incorporating these subthreshold disorders into a diagnosis could provide a bridge between categorical and dimensional diagnostic models.

Tree mortality is a key factor influencing forest functions and dynamics, but our understanding of the mechanisms leading to mortality and the associated changes in tree growth rates are still limited. We compiled a new pan-continental tree-ring width database from sites where both dead and living trees were sampled (2970 dead and 4224 living trees from 190 sites, including 36 species), and compared early and recent growth rates between trees that died and those that survived a given mortality event. We observed a decrease in radial growth before death in ca. 84% of the mortality events. The extent and duration of these reductions were highly variable (1-100 years in 96% of events) due to the complex interactions among study species and the source(s) of mortality. Strong and long-lasting declines were found for gymnosperms, shade- and drought-tolerant species, and trees that died from competition. Angiosperms and trees that died due to biotic attacks (especially bark-beetles) typically showed relatively small and short-term growth reductions. Our analysis did not highlight any universal trade-off between early growth and tree longevity within a species, although this result may also reflect high variability in sampling design among sites. The intersite and interspecific variability in growth patterns before mortality provides valuable information on the nature of the mortality process, which is consistent with our understanding of the physiological mechanisms leading to mortality. Abrupt changes in growth immediately before death can be associated with generalized hydraulic failure and/or bark-beetle attack, while long-term decrease in growth may be associated with a gradual decline in hydraulic performance coupled with depletion in carbon reserves. Our results imply that growth-based mortality algorithms may be a powerful tool for predicting gymnosperm mortality induced by chronic stress, but not necessarily so for angiosperms and in case of intense drought or bark-beetle outbreaks.

Astaxanthin, a xanthophyll carotenoid, is a secondary metabolite naturally synthesized by a number of bacteria, microalgae, and yeasts. The commercial production of this pigment has traditionally been performed by chemical synthesis, but the microalga Haematococcus pluvialis appears to be the most promising source for its industrial biological production. Due to its collective diverse functions in skin biology, there is mounting evidence that astaxanthin possesses various health benefits and important nutraceutical applications in the field of dermatology. Although still debated, a range of potential mechanisms through which astaxanthin might exert its benefits on skin homeostasis have been proposed, including photoprotective, antioxidant, and anti-inflammatory effects. This review summarizes the available data on the functional role of astaxanthin in skin physiology, outlines potential mechanisms involved in the response to astaxanthin, and highlights the potential clinical implications associated with its consumption.

BACKGROUND: Epidemiological research has shown that hallucinations and delusions, the classic symptoms of psychosis, are far more prevalent in the population than actual psychotic disorder. These symptoms are especially prevalent in childhood and adolescence. Longitudinal research has demonstrated that psychotic symptoms in adolescence increase the risk of psychotic disorder in adulthood. There has been a lack of research, however, on the immediate clinicopathological significance of psychotic symptoms in adolescence. AIMS: To investigate the relationship between psychotic symptoms and non-psychotic psychopathology in community samples of adolescents in terms of prevalence, co-occurring disorders, comorbid (multiple) psychopathology and variation across early v. middle adolescence. METHOD: Data from four population studies were used: two early adolescence studies (ages 11-13 years) and two mid-adolescence studies (ages 13-16 years). Studies 1 and 2 involved school-based surveys of 2243 children aged 11-16 years for psychotic symptoms and for emotional and behavioural symptoms of psychopathology. Studies 3 and 4 involved in-depth diagnostic interview assessments of psychotic symptoms and lifetime psychiatric disorders in community samples of 423 children aged 11-15 years. RESULTS: Younger adolescents had a higher prevalence (21-23%) of psychotic symptoms than older adolescents (7%). In both age groups the majority of adolescents who reported psychotic symptoms had at least one diagnosable non-psychotic psychiatric disorder, although associations with psychopathology increased with age: nearly 80% of the mid-adolescence sample who reported psychotic symptoms had at least one diagnosis, compared with 57% of the early adolescence sample. Adolescents who reported psychotic symptoms were at particularly high risk of having multiple co-occurring diagnoses. CONCLUSIONS: Psychotic symptoms are important risk markers for a wide range of non-psychotic psychopathological disorders, in particular for severe psychopathology characterised by multiple co-occurring diagnoses. These symptoms should be carefully assessed in all patients.