Search

Nikolas Aho, Marie Proczkowska Björklund, Carl Göran Svedin Division of Child and Adolescent Psychiatry, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden Abstract: The main objective of this article was to study the relationship between the different areas of victimization (eg, sexual victimization) and psychological symptoms, taking into account the full range of victimization domains. The final aim was to contribute further evidence regarding the bias that studies that focus on just one area of victimization may be introduced into our psychological knowledge. The sample included 5,960 second-year high school students in Sweden with a mean age of 17.3 years (range =16–20 years, standard deviation =0.652), of which 49.6% were females and 50.4% males. The Juvenile Victimization Questionnaire and the Trauma Symptom Checklist for Children were used to assess victimization and psychological problems separately. The results show that a majority of adolescents have been victimized, females reported more total events and more sexual victimization and childhood maltreatment, and males were more often victims of conventional crime. The majority of victimization domains as well as the sheer number of events (polyvictimization [PV]) proved to be harmful to adolescent health, affecting females more than males. PV explained part of the health effect and had an impact on its own and in relation to each domain. This suggests the possibility that PV to a large degree explains trauma symptoms. In order to understand the psychological effects of trauma, clinicians and researchers should take into account the whole range of possible types of victimization. Keywords: victimization, childhood trauma, psychological symptoms, JVQ, TSCC

Floristic Diversity, Ethno-botanic and Local Taxonomy of Onion's Weeds in the North East of Benin. A study has been conducted in order to document scientific names, local names and their significations, and also to apprehend onion's weed species nomenclature adopted by farmers in the North East of Benin. Thirty onion's households have been surveyed through semi-structured interviews and a floristic inventory was carried out in each of them. Weeds'species and their botanic families and also the criteria of their local names have been identified and have served to elaborate a local taxonomy typology. 71 species which belong to 26 botanic families and 17 species belonging to six families constitute respectively the general flora and the flora associated to onion in vegetation.Poaceae,Cyperaceae, Commelinaceae, Malvaceae, Fabaceae and Portulacaceae are the most important families according to their number of species. Ecology, morphology, resistance to hoe weeding and socio-cultural usages are the criteria that were used to develop the local denomination of 39 among 71 identified species, and have served to elaborate the typology of local taxonomy. The other 32 species without local names do not have any major agroecological, nor socio-cultural interest for farmers. The evaluation of the agronomic importance of the flora associated to onion's vegetation can contribute to a better control of the weeds of this crop.

X-ray crystallography is an important technique to determine the positions of atoms in a protein crystal. However, because the native environment in which proteins function, is not a crystal, but a solution, it is not a priori clear if the crystal structure represents the functional form of the protein. Because the protein structure and function often depend critically on the pH, the question arises whether proton affinities are affected by crystallization. X-ray diffraction usually does not reveal protons, which makes it difficult to experimentally measure p K a shifts in crystals. Here, we investigate whether this challenge can be addressed by performing in silico titration with constant pH molecular dynamics (MD) simulations. We compare the computed p K a values of proteins between solution and crystal environment and analyze these differences in the context of molecular interactions. For the proteins considered in this work, p K a shifts were mostly found for residues at the crystal interfaces, where the environment is more apolar in the crystal than in water. Although convergence was an obstacle, our simulations suggest that in principle it is possible to apply constant pH MD to protein crystals routinely and assess the effect of crystallization on protein function more systematically than with standard MD simulations. We also highlight technical challenges that need to be addressed to make MD simulations of crystals more reliable.

Molecular dynamics (MD) simulations are widely applied to estimate absolute binding free energies of protein-ligand and protein-protein complexes. A routinely used method for binding free energy calculations with MD is umbrella sampling (US), which calculates the potential of mean force (PMF) along a single reaction coordinate. Surprisingly, in spite of its widespread use, few validation studies have focused on the convergence of the free energy computed along a single path for specific cases, not addressing the reproducibility of such calculations in general. In this work, we therefore investigate the reproducibility and convergence of US along a standard distance-based reaction coordinate for various protein-protein and protein-ligand complexes, following commonly used guidelines for the setup. We show that repeating the complete US workflow can lead to differences of 2-20 kcal/mol in computed binding free energies. We attribute those discrepancies to small differences in the binding pathways. While these differences are unavoidable in the established US protocol, the popularity of the latter could hint at a lack of awareness of such reproducibility problems. To test if the convergence of PMF profiles can be improved if multiple pathways are sampled simultaneously, we performed additional simulations with an adaptive-biasing method, here the accelerated weight histogram (AWH) approach. Indeed, the PMFs obtained from AHW simulations are consistent and reproducible for the systems tested. To the best of our knowledge, our work is the first to attempt a systematic assessment of the pitfalls in one the most widely used protocols for computing binding affinities. We anticipate therefore that our results will provide an incentive for a critical reassessment of the validity of PMFs computed with US, and make a strong case to further benchmark the performance of adaptive-biasing methods for computing binding affinities.

Image-based deep learning models are used to extract new information from standard hematoxylin and eosin pathology slides; however, biological interpretation of the features detected by artificial intelligence (AI) remains a challenge. High-grade serous carcinoma of the ovary (HGSC) is characterized by aggressive behavior and chemotherapy resistance, but also exhibits striking variability in outcome. Our understanding of this disease is limited, partly due to considerable tumor heterogeneity. We previously trained an AI model to identify HGSC tumor regions that are highly associated with outcome status but are indistinguishable by conventional morphologic methods. Here, we applied spatially resolved transcriptomics to further profile the AI-identified tumor regions in 16 patients (8 per outcome group) and identify molecular features related to disease outcome in patients who underwent primary debulking surgery and platinum-based chemotherapy. We examined formalin-fixed paraffin-embedded tissue from (1) regions identified by the AI model as highly associated with short or extended chemotherapy response, and (2) background tumor regions (not identified by the AI model as highly associated with outcome status) from the same tumors. We show that the transcriptomic profiles of AI-identified regions are more distinct than background regions from the same tumors, are superior in predicting outcome, and differ in several pathways including those associated with chemoresistance in HGSC. Further, we find that poor outcome and good outcome regions are enriched by different tumor subpopulations, suggesting distinctive interaction patterns. In summary, our work presents proof of concept that AI-guided spatial transcriptomic analysis improves recognition of biologic features relevant to patient outcomes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Constant pH molecular dynamics (MD) is a powerful technique that allows the protonation state of residues to change dynamically, thereby enabling the study of pH dependence in a manner that has not been possible before. Recently, a constant pH implementation was incorporated into the GROMACS MD package. Although this implementation provides good accuracy and performance, manual modification and the preparation of simulation input files are required, which can be complicated, tedious, and prone to errors. To simplify and automate the setup process, we present phbuilder, a tool that automatically prepares constant pH MD simulations for GROMACS by modifying the input structure and topology as well as generating the necessary parameter files. phbuilder can prepare constant pH simulations from both initial structures and existing simulation systems, and it also provides functionality for performing titrations and single-site parametrizations of new titratable group types. The tool is freely available at www.gitlab.com/gromacs-constantph. We anticipate that phbuilder will make constant pH simulations easier to set up, thereby making them more accessible to the GROMACS user community.

In search of novel breast cancer (BC) risk variants, we performed a whole-exome sequencing and variant analysis of 69 Finnish BC patients as well as analysed loss-of-function variants identified in DNA repair genes in the Finns from the Genome Aggregation Database. Additionally, we carried out a validation study of SERPINA3 c.918-1G>C, recently suggested for BC predisposition. We estimated the frequencies of 41 rare candidate variants in 38 genes by genotyping them in 2482-4101 BC patients and in 1273-3985 controls. We further evaluated all coding variants in the candidate genes in a dataset of 18,786 BC patients and 182,927 controls from FinnGen. None of the variants associated significantly with cancer risk in the primary BC series; however, in the FinnGen data, NTHL1 c.244C>T p.(Gln82Ter) associated with BC with a high risk for homozygous (OR = 44.7 [95% CI 6.90-290], P = 6.7 × 10 -5 ) and a low risk for heterozygous women (OR = 1.39 [1.18-1.64], P = 7.8 × 10 -5 ). Furthermore, the results suggested a high risk of colorectal, urinary tract, and basal-cell skin cancer for homozygous individuals, supporting NTHL1 as a recessive multi-tumour susceptibility gene. No significant association with BC risk was detected for SERPINA3 or any other evaluated gene., (© 2023. The Author(s).)

Molecular dynamics (MD) computer simulations are used routinely to compute atomistic trajectories of complex systems. Systems are simulated in various ensembles, depending on the experimental conditions one aims to mimic. While constant energy, temperature, volume, and pressure are rather straightforward to model, pH, which is an equally important parameter in experiments, is more difficult to account for in simulations. Although a constant pH algorithm based on the λ-dynamics approach by Brooks and co-workers [Kong, X.; Brooks III, C. L. J. Chem. Phys. 1996 , 105 , 2414-2423] was implemented in a fork of the GROMACS molecular dynamics program, uptake has been rather limited, presumably due to the poor scaling of that code with respect to the number of titratable sites. To overcome this limitation, we implemented an alternative scheme for interpolating the Hamiltonians of the protonation states that makes the constant pH molecular dynamics simulations almost as fast as a normal MD simulation with GROMACS. In addition, we implemented a simpler scheme, called multisite representation, for modeling side chains with multiple titratable sites, such as imidazole rings. This scheme, which is based on constraining the sum of the λ-coordinates, not only reduces the complexity associated with parametrizing the intramolecular interactions between the sites but also is easily extendable to other molecules with multiple titratable sites. With the combination of a more efficient interpolation scheme and multisite representation of titratable groups, we anticipate a rapid uptake of constant pH molecular dynamics simulations within the GROMACS user community.

Various approaches have been proposed to include the effect of pH in molecular dynamics (MD) simulations. Among these, the λ-dynamics approach proposed by Brooks and co-workers [Kong, X.; Brooks III, C. L. J. Chem. Phys. 1996 , 2414-2423] can be performed with little computational overhead and hfor each typeence be used to routinely perform MD simulations at microsecond time scales, as shown in the accompanying paper [Aho, N. et al. 105 , 2414-2423] can be performed with little computational overhead and hfor each typeence be used to routinely perform MD simulations at microsecond time scales, as shown in the accompanying paper [Aho, N. et al. J. Chem. Theory Comput. 2022 , DOI: 10.1021/acs.jctc.2c00516]. At such time scales, however, the accuracy of the molecular mechanics force field and the parametrization becomes critical. Here, we address these issues and provide the community with guidelines on how to set up and perform long time scale constant pH MD simulations. We found that barriers associated with the torsions of side chains in the CHARMM36m force field are too high for reaching convergence in constant pH MD simulations on microsecond time scales. To avoid the high computational cost of extending the sampling, we propose small modifications to the force field to selectively reduce the torsional barriers. We demonstrate that with such modifications we obtain converged distributions of both protonation and torsional degrees of freedom and hence consistent p K a estimates, while the sampling of the overall configurational space accessible to proteins is unaffected as compared to normal MD simulations. We also show that the results of constant pH MD depend on the accuracy of the correction potentials. While these potentials are typically obtained by fitting a low-order polynomial to calculated free energy profiles, we find that higher order fits are essential to provide accurate and consistent results. By resolving problems in accuracy and sampling, the work described in this and the accompanying paper paves the way to the widespread application of constant pH MD beyond p K a prediction.

Nonsuicidal self-injury (NSSI) is a robust predictor of suicidal thoughts and behaviors; however, while there are typically only small differences observed in the prevalence of NSSI between men and women, this condition has been largely overlooked and underestimated among men. Assessing NSSI methods more common in men may address misidentification as well as allow for more precise NSSI prevalence estimates. Survey data from a national sample of Gulf War I-Era veterans (N = 1063) was used to estimate the prevalence of NSSI and compare prevalence of NSSI methods between men and women veterans. Demographic and clinical correlates of NSSI engagement were also examined. The national lifetime prevalence rate of NSSI among Gulf War I-Era veterans was 22.40%, whereas the past year prevalence rate was 8.10%. In both men and women, wall/object punching was the most common NSSI method endorsed across the lifetime. Men had slightly higher overall NSSI prevalence rates compared with women. This study highlights the need to systematically assess NSSI, particularly among veterans, to better identify, and consequently treat, NSSI in men. This is the first available prevalence estimate of NSSI to include the assessment of wall/object punching in a national sample of adult veterans., (Copyright © 2022. Published by Elsevier B.V.)

Competing Interests: The authors have no conflicts of interest or financial disclosures to report.

Ecological momentary assessment (EMA) is a useful tool to investigate antecedents and consequences of nonsuicidal self-injury (NSSI), a robust predictor of Veteran suicide risk. Despite elucidating temporal changes among dynamic variables, EMA remains underutilized to study NSSI among veterans, perhaps due to concerns of safety and utility. The present study analyzed data collected from semi-structured interviews of veterans following a 28-day EMA study of NSSI, including benefits, challenges, and recommendations for improvement. Participants included 34 veterans endorsing NSSI history, most meeting criteria for NSSI Disorder. Qualitative analysis of de-identified transcripts used the rigorous and accelerated data reduction (RADaR) technique and thematic analysis. Findings revealed all veterans reported at least one emotional/social benefit to participation, including finding it therapeutic, gaining self-awareness/insight, and improved social functioning. Challenges and recommendations were primarily technology-related, including adjustment to device use. Many expressed interest in incorporation of clinical resources, use of personal devices/VA app, and ability to share responses with providers. Assessment frequency/content was never described as triggering suicidal/nonsuicidal urges and over half of participants noted urge/behavior reduction. Results support acceptability and safety of EMA for NSSI among veterans and potential clinical utility as a psychotherapy adjunct to promote self-awareness and NSSI reduction., (Copyright © 2022. Published by Elsevier B.V.)

Background: The affective states most strongly associated with nonsuicidal self-injury (NSSI) remain poorly understood, particularly among veterans. This study used ecological momentary assessment (EMA) to examine relationships between affect ratings and NSSI urges and behaviors among veterans with NSSI disorder., Methods: Participants (N = 40) completed EMA entries via mobile phone for 28 days (3722 total entries). Entries included intensity ratings for five basic affective states, as well as NSSI urges and behaviors, during the past 4 hours., Results: Bivariate analyses indicated that each affect variable was significantly associated with both NSSI urges and behaviors. Angry/hostile and sad were most strongly associated with both NSSI urges and behaviors. A multivariate regression revealed that angry/hostile, disgusted with self, and happy (inversely related) were contemporaneously (within the same period) associated with NSSI behaviors, whereas all five basic affective states were contemporaneously associated with NSSI urges. In a lagged model, angry/hostile and sad were associated with subsequent NSSI urges but not behaviors., Conclusions: Findings highlight the relevance of particular affective states to NSSI and the potential utility of targeting anger in treatments for NSSI among veterans. There is a need for future EMA research study to further investigate temporal relationships between these variables., (wileyonlinelibrary.com/journal/sltb.)

Background: A significant proportion of variation in likelihood of neurodevelopmental conditions (NDCs) has been attributed to nonshared environmental (NSE) factors, although it remains unclear which NSE factors pose specific risks for certain NDCs., Methods: A monozygotic co-twin design was applied in a sample of 224 twins (mean age = 17.70 years, SD = 6.28) controlling for confounders such as genes and shared environment. Generalized estimating equation models were fitted, using perinatal and postnatal indications of NSEs as exposure, operationalized both as separate risk factors and as cumulative risk loads. Categorical and dimensional operationalizations of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disability and other NDCs were used as outcomes., Results: Birth weight discordance was associated with dimensional autism and ADHD for the smaller twin, and medication during infancy was associated with dimensional autism. Among postnatal factors scarlet fever during early childhood was associated with lower IQ. Especially autism was associated with a greater cumulative perinatal or postnatal risk load., Limitations: When exploring the associations between each condition and specific NSEs the risk of being statistically underpowered increases. Hence, we limit the reported findings on specific indicators of NSEs to trait levels and present descriptive data for categorical NDCs., Conclusions: The findings support previous research by indicating an association between exposure to perinatal and postnatal risks and subsequent NDCs within twin pairs and suggest that autism may be especially linked to accumulative early environmental risks. The findings are potentially important for developmental outcomes prognoses and may inform targeted prevention and early interventions., (© 2022. The Author(s).)

We previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1l p.S78G mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cyb p.D254N ), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1l p.S78G tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dynamics. In Rhodobacter cytochrome bc 1 complex the equivalent substitution causes a kinetics defect with longer occupancy of RISP head domain towards the quinol oxidation site. These findings represent a unique case of spontaneous mitonuclear epistasis and highlight the role of mtDNA variation as modifier of mitochondrial disease phenotypes.

Proton diffusion (PD) across biological membranes is a fundamental process in many biological systems, and much experimental and theoretical effort has been employed for deciphering it. Here, we report on a spectroscopic probe, which can be tightly tethered to the membrane, for following fast (nanosecond) proton transfer events on the surface of membranes. Our probe is composed of a photoacid that serves as our light-induced proton source for the initiation of the PD process. We use our probe to follow PD, and its pH dependence, on the surface of lipid vesicles composed of a zwitterionic headgroup, a negative headgroup, a headgroup that is composed only from the negative phosphate group, or a positive headgroup without the phosphate group. We reveal that the PD kinetic parameters are highly sensitive to the nature of the lipid headgroup, ranging from a fast lateral diffusion at some membranes to the escape of protons from surface to bulk (and vice versa) at others. By referring to existing theoretical models for membrane PD, we found that while some of our results confirm the quasi-equilibrium model, other results are in line with the nonequilibrium model., Competing Interests: The authors declare no conflict of interest.

Organic dye-tagged lipid analogs are essential for many fluorescence-based investigations of complex membrane structures, especially when using advanced microscopy approaches. However, lipid analogs may interfere with membrane structure and dynamics, and it is not obvious that the properties of lipid analogs would match those of non-labeled host lipids. In this work, we bridged atomistic simulations with super-resolution imaging experiments and biomimetic membranes to assess the performance of commonly used sphingomyelin-based lipid analogs. The objective was to compare, on equal footing, the relative strengths and weaknesses of acyl chain labeling, headgroup labeling, and labeling based on poly-ethyl-glycol (PEG) linkers in determining biomembrane properties. We observed that the most appropriate strategy to minimize dye-induced membrane perturbations and to allow consideration of Brownian-like diffusion in liquid-ordered membrane environments is to decouple the dye from a membrane by a PEG linker attached to a lipid headgroup. Yet, while the use of PEG linkers may sound a rational and even an obvious approach to explore membrane dynamics, the results also suggest that the dyes exploiting PEG linkers interfere with molecular interactions and their dynamics. Overall, the results highlight the great care needed when using fluorescent lipid analogs, in particular accurate controls., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background : Exposure to traumatic events is clearly associated with a diversity of subsequent mental health problems, with posttraumatic stress disorder (PTSD) as the most prevalent disorder. Epidemiologically, trauma exposure rates are more prevalent than PTSD, indicating that most trauma victims do not develop PTSD. More knowledge is needed to understand the development of the different posttraumatic pathways including the significance of pretraumatic, peritraumatic and posttraumatic risk factors. Objective : To study peritraumatic reactions in relation to trauma exposure and symptoms of posttraumatic stress and to enhance our understanding of peritraumatic reactions as mediators between trauma and later symptomatology. Method : The study was composed of a representative community sample of 5332 second year high school students (mean age 17.3 years) who completed the Juvenile Victimization Questionnaire (SAQ/JVQ), Trauma Symptom Checklist for Children (TSCC) and answered questions about peritraumatic reactions. Mediation effects of peritraumatic reactions on the trauma exposure relationship to symptoms was tested using the PROCESS macro for SPSS. Results : Traumatic events are common (84.1%) and are accompanied in three-quarters of the students with at least one form of peritraumatic reaction. Peritraumatic reactions, especially peritraumatic dissociative reactions, mediate the relationship between trauma exposure and symptoms, and gender moderates the effect of peritraumatic dissociation. This moderating effect was found to be larger for boys than for girls, indicating gender differences in response to trauma. Conclusions : The results indicate the need to screen for peritraumatic reactions as early as possible after a traumatic event in order to identify those at risk for PTSD., Competing Interests: No potential conflict of interest was reported by the authors.

Studying the extent to which children are exposed to victimizing events is important to fully understand the effect of such exposure in shaping them as adults. The aim of this study was to use self-report by adolescents to measure the prevalence of victimizing events and of poly-victimization. A representative sample of 5,960 students (aged 17) from high schools in Sweden was given the self-administrated version of the Juvenile Victimization Questionnaire (JVQ) along with questions concerning gender, birthplace, parents' birthplace and employment, residence, educational program, and municipality size. The results show that 84.1% (83.0% young men and 85.2% young women) of the students had experienced victimization during their lifetime, and 10.3% were categorized as poly-victims (8.1% young men and 12.5% young women; OR = 1.62, 95% confidence interval [CI] = [1.35, 1.94]). Adolescents living with both parents were at lower risk of any form of victimization for both genders, while females were at higher risk of maltreatment, peer victimization, and, most significantly, sexual victimization. In conclusion, the vast majority of young people have been victimized during their lifetime. A greater awareness of the impact of these victimizing events on children and adolescents is important as a basis for providing a safer milieu and establishing better interventions, especially for those that have been victimized on multiple occasions. The high-exposure group was determined by using ≥10 events as a cutoff. Findings on this group corresponded with findings in other international studies regarding distribution, elevated risk for females, and the possibility of limiting the effects of victimization by modifying living conditions., (© The Author(s) 2014.)

Psychiatric disorders are multi-factorial and their symptoms overlap. Constitutional and environmental factors influence each other, and this contributes to risk and resilience in mental ill-health. We investigated functional genetic variation of stress responsiveness, assessed as FKBP5 genotype, in relation to early life adversity and mental health in two samples of adolescents. One population-based sample of 909 12-year-old adolescents was assessed using the Life Incidence of Traumatic Events scale and the Strengths and Difficulties Questionnaire. One sample of 398 17-year-old adolescents, enriched for poly-victimized individuals (USSS), was assessed using the Juvenile Victimization Questionnaire and the Trauma Symptom Checklist for Children (TSCC). The FKBP5 rs1360780 and rs3800373 polymorphisms were genotyped using a fluorescence-based competitive allele-specific PCR. Most prominently among poly-victimized older male adolescents, the least common alleles of the polymorphisms, in interaction with adverse life events, were associated with psychiatric symptoms, after controlling for ethno-socio-economic factors. The interaction effect between rs3800373 and adverse life events on the TSCC sub-scales-anxiety, depression, anger, and dissociation-and with the rs1360780 on dissociation in the USSS cohort remained significant after Bonferroni correction. This pattern of association is in line with the findings of clinical and neuroimaging studies, and implies interactive effects of FKBP5 polymorphisms and early life environment on several psychiatric symptoms. These correlates add up to provide constructs that are relevant to several psychiatric symptoms, and to identify early predictors of mental ill-health.

Recent findings from studies on adults show similarities between social anxiety disorder (SAD) and posttraumatic stress in the form of recurrent memories and intrusive and distressing images of earlier aversive events. Further, treatment models for SAD in adults have been successfully developed by using transdiagnostic knowledge on posttraumatic stress symptoms (PTSS). Studies on adolescents are though missing. The present study aimed at exploring the association between PTSS and SAD in Swedish adolescents. A second aim was to study mental health services utilization in relation to these conditions. A total of 5,960 high-school students participated and reported on SAD, life time victimization, PTSS and mental health service utilization. Socially anxious adolescents reported significantly higher levels of PTSS than adolescents not reporting SAD and this difference was seen in victimized as well as non-victimized subjects. Contact with a school counselor was the most common mental health service utilization in subjects with SAD and those with elevated PTSS. In the prediction of contact with a CAP-clinic, significant odds ratios were found for a condition of SAD and elevated PTSS (OR = 4.88, 95% CI = 3.53-6.73) but not for SAD only. Screening of PTSS in adolescents with SAD is recommended. The service of school counselors is important in detecting and helping young people with SAD and elevated PTSS. Clinical studies on SAD and PTSS in adolescents could aid in modifying treatment models for SAD.

Despite high prevalence rates of social anxiety disorder (SAD) and high rates of victimization in adolescents, studies on the relationship between these phenomena are missing. In the present study we report associations between SAD and multiple victimization experiences in a community sample of adolescents. A cross-sectional study was conducted on 3211 Swedish high-school students. The prevalence rate of self-reported SAD was 10.6% (n=340). Significantly higher rates of lifetime victimization was found in subjects with self-reported SAD compared to non-cases, on the total score on the Juvenile Victimization Questionnaire, and on the subscales maltreatment, sexual victimization and victimization from peer/siblings. Different results emerged due to gender. In females, maltreatment and peer/sibling victimization was associated with an increased risk of SAD and, in males peer/sibling victimization increased the risk of reporting SAD. Further studies are needed to elaborate developmental models on SAD and to add to modification of prevention- and treatment interventions., (Copyright © 2010 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)