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Purpose Perigenual anterior cingulate cortex (pACC) is a neural convergence site for social stress-related risk factors for mental health, including ethnic minority status. Current social status, a strong predictor of mental and somatic health, has been related to gray matter volume in this region, but the effects of social mobility over the lifespan are unknown and may differ in minorities. Recent studies suggest a diminished health return of upward social mobility for ethnic minority individuals, potentially due to sustained stress-associated experiences and subsequent activation of the neural stress response system. Methods To address this issue, we studied an ethnic minority sample with strong upward social mobility. In a cross-sectional design, we examined 64 young adult native German and 76 ethnic minority individuals with comparable sociodemographic attributes using whole-brain structural magnetic resonance imaging. Results Results showed a significant group-dependent interaction between perceived upward social mobility and pACC gray matter volume, with a significant negative association in the ethnic minority individuals. Post-hoc analysis showed a significant mediation of the relationship between perceived upward social mobility and pACC volume by perceived chronic stress, a variable that was significantly correlated with perceived discrimination in our ethnic minority group. Conclusion Our findings extend prior work by pointing to a biological signature of the “allostatic costs” of socioeconomic attainment in socially disadvantaged upwardly mobile individuals in a key neural node implicated in the regulation of stress and negative affect.

Naphthalene, originating from anthropogenic activities, is a toxic contaminant commonly found in urban stormwater runoff. This study investigated the adsorption and desorption potential of naphthalene in a bioretention cell soil at various temperatures and salinities representative of cold-climate winter conditions. In all experiments, more than 70% of the initially added naphthalene was adsorbed on the bioretention soil at equilibrium. Temperature and salinity showed little but inconsistent effects on the adsorption of naphthalene, and the adsorption of naphthalene was partially reversible under some conditions, e.g., at higher temperature. Despite its reversibility, naphthalene desorption may allow for the regeneration of the sorption capacity of the soil media, and transformation processes to take place. Overall, these results suggest that bioretention cells are able to temporarily retain a large portion of the inflowing naphthalene over short periods.

Migration status is one of the best-established risk factors for schizophrenia. An increase in risk is observed in both first- and second-generation immigrants, with a varying magnitude depending on the ethnic background of the individuals. The underlying mechanisms for the increased risk are only recently coming into focus. A causal role for social stress has been widely proposed, and recent work indicated altered neural stress processing in the perigenual anterior cingulate cortex (pACC) in migrants. Since previous work shows that social stress may lead to enduring changes in the gray matter volume of vulnerable brain regions, we investigated the impact of migration background on brain structure. We studied healthy young adults (N = 124), native Germans and second-generation migrants, using whole-brain structural magnetic resonance imaging. Groups were matched for a broad range of sociodemographic characteristics including age, gender, urban exposure, and education. We found a significant group by sex interaction effect in pACC gray matter volume, which was reduced in males with migration background only. This mirrors previous findings in urban upbringing, another risk factor for schizophrenia. Our results provide convergent evidence for an impact of environmental risk factors linked to schizophrenia on gray matter volume and extend prior data by highlighting the possibility that the pACC structure may be particularly sensitive to the convergent risk factors linked to schizophrenia.

We have previously shown that urban upbringing and city living were associated with stress-induced activity in the amygdala and the perigenual anterior cingulate cortex (pACC). This finding might link the epidemiological risk factor "urbanicity" to neurobiological mechanisms of psychiatric disorders. However, given the heritability of stress-related phenotypes, it appears likely that genetic factors can modulate the effect of urbanicity on social stress processing. In the present exploratory study, we investigated if a functional sequence variation in the neuropeptide S receptor gene (NPSR1 rs324981) is associated with brain activation patterns under acute psychosocial stress and if it modulates the link between urbanicity and central stress processing. In animals, neuropeptide S has strong anxiolytic effects and it induces hypothalamus-pituitary-adrenal (HPA) axis activation. In humans, rs324981 was found to be associated with anxiety and stress-related phenotypes. Forty-two subjects were exposed to a psychosocial stress task for scanner environments (ScanSTRESS). While no main effect of rs324981 on amygdala and pACC activity was detected, we found a distinct interaction between rs324981 and urban upbringing modulating right amygdala responses. Moreover, right amygdala responses were significantly higher in subjects who also showed a salivary cortisol response to the stress exposure. The present finding of a gene × environment interaction further supports the view that the brain NPS system is involved in central stress regulation. This study provides first evidence for the assumption that a NPSR1 variant modulates brain activation under stress, interacting with the environmental risk factor urban upbringing.

Schizophrenia is a severe and complex brain disorder that usually manifests in early adulthood and disturbs a wide range of human functions. More than 100 years after its initial description, the pathophysiology of the disorder is still incompletely understood. Many epidemiological studies strongly suggest a complex interaction between genetic and environmental risk factors for the development of the disorder. While there is considerable evidence for a social environmental component of this risk, the links between adverse social factors and altered brain function have just come into focus. In the present review, we first summarize epidemiological evidence for the significance of social environmental risk factors, outline the role of altered social stress processing in mental illness, and review the latest experimental evidence for the neural correlates of social environmental risk for schizophrenia. The studies we have discussed in this review provide a selection of the current work in the field. We suggest that many of the social environmental risk factors may impact on perceived social stress and engage neural circuits in the brain whose functional and structural architecture undergoes detrimental change in response to prolonged exposure. We conclude that multidisciplinary approaches involving various fields and thoroughly constructed longitudinal designs are necessary to capture complex structure of social environmental risks.

The brain neuropeptide S (NPS) system has recently generated substantial interest and may be of major relevance for central stress regulation. The NPS receptor (NPSR1) is highly expressed in the limbic system, exogenous NPS exerts pronounced anxiolytic and fear-attenuating effects in rodents and extensive close crosstalk between the NPS system and the hypothalamic-pituitary-adrenal (HPA) axis has been demonstrated. In humans, associations between NPSR1 variants and anxiety and panic disorder, as well as amygdala responsiveness to fear- relevant faces and prefrontal cortex activity in a fear conditioning paradigm have been reported. Moreover, a NPSR1 sequence variant was found to be associated with cortisol stress responses in males. Here, we performed a haplotype-based analysis covering three functional NPSR1 single nucleotide polymorphisms in the promoter (rs2530547), in exon 3 (rs324981) and exon 6 (rs727162) in 277 healthy subjects who were exposed to the Trier Social Stress Test (TSST). A significant sex-specific association with salivary cortisol responses to acute psychosocial stress was detected for the common TTC haplotype 2 (frequency of about 20%). In an additional study using an imaging genetics approach, 65 healthy subjects were exposed to a stress paradigm for scanner environments (“ScanSTRESS”). We found a significant and, again, sex-specific interaction between rs324981 (whose minor T-allele is harbored by haplotype 2) and the neural stress response in a cluster close to the parahippocampal gyrus (whole brain corrected). Moreover, as in the TSST sample, NPSR1 variation was associated with salivary cortisol responses (on a trend level) in a sex-specific way. In summary, our preliminary findings in two independent cohorts exposed to different stress paradigms suggest that the NPS system significantly influences acute stress responses and that sequence variation in NPSR1 may contribute to sex differences in stress regulation.

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender’s and receiver’s temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions.

European Community Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G x E), however, so far, thorough replication of findings is rare and G x E research still faces several conceptual and methodological challenges. in this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G x E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G x E in schizophrenia. While such investigations are now well underway, new challenges emerge for G x E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. 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Psychiat, New Haven, CT USA Middle E Tech Univ, Dept Psychol, TR-06531 Ankara, Turkey Diskapi YB Res & Training Hosp, Ankara, Turkey Turkish Federat Schizophrenia Assoc, Ankara, Turkey Ataturk Training & Res Hosp, Psychiat Clin, Ankara, Turkey Manisa Mental Hlth Hosp, Manisa, Turkey Istanbul Univ, Expt Med Res Inst, Dept Adv Neurol Sci, Istanbul Fac Med, Istanbul, Turkey Univ Complutense, IiSGM CIBERSAM, Dept Child & Adolescent Psychiat, Hosp Gen Univ Gregorio Maranon,Sch Med, E-28040 Madrid, Spain Univ Barcelona, Dept Psychiat, Hosp Clin, IDIBAPS,Ctr Invest Biomed Red Salud Mental CIBERS, Barcelona, Spain Univ Valencia, Sch Med, Dept Psychiat, Ctr Invest Biomed Red Salud Mental CIBERSAM, Valencia, Spain Univ Oviedo, Sch Med, Dept Med,Psychiat Area, Ctr Invest Biomed Red Salud Mental CIBERSAM, Oviedo, Spain Univ Santiago de Compostela, Dept Mental Hlth & Drug Addit Assistance, Hlth Serv Galicia,Psychiat Genet Grp IDIS, Hosp Clin,Ctr Invest Biomedica Red Salud Mental C, Santiago de 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Creteil, France Univ Paris Est, Fac Med, Creteil, France Fdn Fondamental, Creteil, France CMP B CHU, F-63003 Clermont Ferrand 1, France Univ Auvergne, EA 7280, Clermont Ferrand, France EPS Maison Blanche, Paris, France UPC KU Leuven, Dept Neurosci, UPC, Kortenberg, Belgium UPC, Dept Neurosci, Res Grp Psychiat, Leuven, Belgium Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Dept Human Genet, Leuven, Belgium Assoc Sci Res Multiple Births, Ghent, Belgium Univ Ghent, Dept Neurol, Ghent Univ Hosp, B-9000 Ghent, Belgium Univ Athens, Sch Med, Eginit Hosp, Athens 11528, Greece Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria Psychiat Univ Clin Basel, Ctr Gender Res & Early Detect, Basel, Switzerland Psychiat Univ Clin Basel, Diagnost & Crisis Intervent Ctr, Basel, Switzerland Univ Cologne, Dept Psychiat & Psychotherapy, D-50931 Cologne, Germany Univ Hong Kong, Li Ka Shing Fac Med, Ctr Genom Sci, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Li Ka Shing Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Queen Mary Hosp, Li Ka Shing Fac Med, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Queen Mary Hosp, Li Ka Shing Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China Univ Basque Country, Univ Deusto, Interuniv Chair Law & Human Genome Prov Govt Bisk, Bilbao, Bizkaia, Spain Univ Zaragoza, Zaragoza, Spain Univ Cambridge, Dept Psychiat, Cambridge, England UCL, Div Psychiat, London, England Royal Coll Surgeons Ireland, Beaumont Hosp, Educ & Res Ctr, Dept Psychiat, Dublin 9, Ireland Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, Munich, Germany Univ Bologna, Alma Mater Studiorium, Psychiat Unit, Dept Med & Surg Sci, Bologna, Italy Univ Bologna, Alma Mater Studiorium, Genet Unit, Dept Med & Surg Sci, Bologna, Italy Local Hlth Trust, Dept Mental Hlth & Pathol Addict, Bologna, Italy Univ Palermo, Sect Psychiat, Dept Expt Biomed & Clin Neurosci, Palermo, Italy P Giaccone Gen Hosp, Unit Psychiat, Palermo, Italy Univ Melbourne, Ctr Youth Mental Hlth, Parkville, Vic 3052, Australia Univ Melbourne, Melbourne Neuropsychiat Ctr, Carlton, Vic, Australia Univ São Paulo, Fac Med, Dept Med Prevent, BR-01246903 São Paulo, Brazil Univ São Paulo, Nucleo Pesquina Saude Mental Populac, São Paulo, Brazil Univ São Paulo, Fac Med Ribeirao Preto, Dept Neurociencias & Ciencias Comportamento, BR-14049 Ribeirao Preto, Brazil Univ Verona, Sect Psychiat, Dept Publ Hlth & Community Med, I-37100 Verona, Italy Copenhagen Univ Hosp, Res Unit, Mental Hlth Ctr Copenhagen, Copenhagen, Denmark Univ Paris 05, Fac Med, Serv Hosp Univ, Hop St Anne, Paris, France Univ Autonoma Barcelona, Dept Psicol Clin & Salut, E-08193 Barcelona, Spain St Pere Claver Fundacio Sanitaria, Dept Salut Mental, Barcelona, Spain Univ N Carolina, Dept Psychol, Greensboro, NC 27412 USA CIBERSAM, Spanish Mental Hlth Res Network, Barcelona, Spain Universidade Federal de São Paulo, Dept Psychiat, PRISMA Early Intervent Program, São Paulo, Brazil Univ Belgrade, Sch Med, Beograd, Serbia Universidade Federal de São Paulo, Dept Psychiat, PRISMA Early Intervent Program, São Paulo, Brazil European Community: HEALTH-F2-2009-241909 Web of Science

Sandra Zankert1,∗, Fabian Streit2,3, Leila Haddad2, Ceren Akdeniz2, Heike Trost2, Robert Kumsta4, Sonja Entringer5, Ilona S. Yim6, Stephanie Witt2, Peter Kirsch2, Marcella Rietschel2, Stefan Wust1 1 Institute of Experimental Psychology, University of Regensburg, Germany 2 Central Institute of Mental Health, Mannheim, Germany 3 Institute of Psychobiology, University of Trier, Germany 4 Department of Genetic Psychology, Ruhr University Bochum, Germany 5 Institute of Medical Psychology, Charite Universitatsmedizin Berlin, Germany 6 Department of Psychology and Social Behavior, University of California, Irvine, USA

Importance Relative risk for the brain disorder schizophrenia is more than doubled in ethnic minorities, an effect that is evident across countries and linked to socially relevant cues such as skin color, making ethnic minority status a well-established social environmental risk factor. Pathoepidemiological models propose a role for chronic social stress and perceived discrimination for mental health risk in ethnic minorities, but the neurobiology is unexplored. Objective To study neural social stress processing, using functional magnetic resonance imaging, and associations with perceived discrimination in ethnic minority individuals. Design, Setting, and Participants Cross-sectional design in a university setting using 3 validated paradigms to challenge neural social stress processing and, to probe for specificity, emotional and cognitive brain functions. Healthy participants included those with German lineage (n = 40) and those of ethnic minority (n = 40) from different ethnic backgrounds matched for sociodemographic, psychological, and task performance characteristics. Control comparisons examined stress processing with matched ethnic background of investigators (23 Turkish vs 23 German participants) and basic emotional and cognitive tasks (24 Turkish vs 24 German participants). Main Outcomes and Measures Blood oxygenation level–dependent response, functional connectivity, and psychological and physiological measures. Results There were significant increases in heart rate ( P P P = .006), and salivary cortisol level ( P = .004) during functional magnetic resonance imaging stress induction. Ethnic minority individuals had significantly higher perceived chronic stress levels ( P = .02) as well as increased activation (family-wise error–corrected [FWE] P = .005, region of interest corrected) and increased functional connectivity ( P FWE = .01, region of interest corrected) of perigenual anterior cingulate cortex (ACC). The effects were specific to stress and not explained by a social distance effect. Ethnic minority individuals had significant correlations between perceived group discrimination and activation in perigenual ACC ( P FWE = .001, region of interest corrected) and ventral striatum ( P FWE = .02, whole brain corrected) and mediation of the relationship between perceived discrimination and perigenual ACC–dorsal ACC connectivity by chronic stress ( P Conclusions and Relevance Epidemiologists proposed a causal role of social-evaluative stress, but the neural processes that could mediate this susceptibility effect were unknown. Our data demonstrate the potential of investigating associations from epidemiology with neuroimaging, suggest brain effects of social marginalization, and highlight a neural system in which environmental and genetic risk factors for mental illness may converge.