Dietary Exposure to Environmentally Relevant Levels of Chemical Contaminants Reduces Growth and Survival in Juvenile Chinook Salmon.

Chemical pollution can degrade aquatic ecosystems. Chinook salmon in contaminated habitats are vulnerable to health impacts from toxic exposures. Few studies have been conducted on adverse health outcomes associated with current levels and mixtures of contaminants. Fewer still address effects specific to the juvenile life-stage of salmonids. The present study evaluated contaminant-related effects from dietary exposure to environmentally relevant concentrations and mixture profiles in juvenile Chinook salmon from industrialized waterways in the U.S. Pacific Northwest using two end points: growth assessment and disease susceptibility. The dose and chemical proportions were reconstituted based on environmental sampling and analysis using the stomach contents of juvenile Chinook salmon recently collected from contaminated, industrialized waterways. Groups of fish were fed a mixture with fixed proportions of 10 polychlorinated biphenyls (PCBs), 3 dichlorodiphenyltrichloroethanes (DDTs), and 13 polycyclic aromatic hydrocarbons (PAHs) at five concentrations for 35 days. These contaminant compounds were selected because of elevated concentrations and the widespread presence in sediments throughout industrialized waterways. Fork length and otolith microstructural growth indicators were significantly reduced in fish fed environmentally relevant concentrations of these contaminants. In addition, contaminant-exposed Chinook salmon were more susceptible to disease during controlled challenges with the pathogen Aeromonas salmonicida. Our results indicate that dietary exposure to contaminants impairs growth and immune function in juvenile Chinook salmon, thereby highlighting that current environmental exposure to chemicals of potential management concern threatens the viability of exposed salmon.

A review of the toxicology of oil in vertebrates: what we have learned following the Deepwater Horizon oil spill.

In the wake of the Deepwater Horizon (DWH) oil spill, a number of government agencies, academic institutions, consultants, and nonprofit organizations conducted lab- and field-based research to understand the toxic effects of the oil. Lab testing was performed with a variety of fish, birds, turtles, and vertebrate cell lines (as well as invertebrates); field biologists conducted observations on fish, birds, turtles, and marine mammals; and epidemiologists carried out observational studies in humans. Eight years after the spill, scientists and resource managers held a workshop to summarize the similarities and differences in the effects of DWH oil on vertebrate taxa and to identify remaining gaps in our understanding of oil toxicity in wildlife and humans, building upon the cross-taxonomic synthesis initiated during the Natural Resource Damage Assessment. Across the studies, consistency was found in the types of toxic response observed in the different organisms. Impairment of stress responses and adrenal gland function, cardiotoxicity, immune system dysfunction, disruption of blood cells and their function, effects on locomotion, and oxidative damage were observed across taxa. This consistency suggests conservation in the mechanisms of action and disease pathogenesis. From a toxicological perspective, a logical progression of impacts was noted: from molecular and cellular effects that manifest as organ dysfunction, to systemic effects that compromise fitness, growth, reproductive potential, and survival. From a clinical perspective, adverse health effects from DWH oil spill exposure formed a suite of signs/symptomatic responses that at the highest doses/concentrations resulted in multi-organ system failure.

Cannabis use in patients with early psychosis is associated with alterations in putamen and thalamic shape.

Around half of patients with early psychosis have a history of cannabis use. We aimed to determine if there are neurobiological differences in these the subgroups of persons with psychosis with and without a history of cannabis use. We expected to see regional deflations in hippocampus as a neurotoxic effect and regional inflations in striatal regions implicated in addictive processes. Volumetric, T1w MRIs were acquired from people with a diagnosis psychosis with (PwP + C = 28) or without (PwP - C = 26) a history of cannabis use; and Controls with (C + C = 16) or without (C - C = 22) cannabis use. We undertook vertex-based shape analysis of the brainstem, amygdala, hippocampus, globus pallidus, nucleus accumbens, caudate, putamen, thalamus using FSL FIRST. Clusters were defined through Threshold Free Cluster Enhancement and Family Wise Error was set at p < .05. We adjusted analyses for age, sex, tobacco and alcohol use. The putamen (bilaterally) and the right thalamus showed regional enlargement in PwP + C versus PwP - C. There were no areas of regional deflation. There were no significant differences between C + C and C - C. Cannabis use in participants with psychosis is associated with morphological alterations in subcortical structures. Putamen and thalamic enlargement may be related to compulsivity in patients with a history of cannabis use.

Differential neural reward mechanisms in treatment-responsive and treatment-resistant schizophrenia.

BACKGROUND: The significant proportion of schizophrenia patients refractory to treatment, primarily directed at the dopamine system, suggests that multiple mechanisms may underlie psychotic symptoms. Reinforcement learning tasks have been employed in schizophrenia to assess dopaminergic functioning and reward processing, but these have not directly compared groups of treatment-refractory and non-refractory patients. METHODS: In the current functional magnetic resonance imaging study, 21 patients with treatment-resistant schizophrenia (TRS), 21 patients with non-treatment-resistant schizophrenia (NTR), and 24 healthy controls (HC) performed a probabilistic reinforcement learning task, utilizing emotionally valenced face stimuli which elicit a social bias toward happy faces. Behavior was characterized with a reinforcement learning model. Trial-wise reward prediction error (RPE)-related neural activation and the differential impact of emotional bias on these reward signals were compared between groups. RESULTS: Patients showed impaired reinforcement learning relative to controls, while all groups demonstrated an emotional bias favoring happy faces. The pattern of RPE signaling was similar in the HC and TRS groups, whereas NTR patients showed significant attenuation of RPE-related activation in striatal, thalamic, precentral, parietal, and cerebellar regions. TRS patients, but not NTR patients, showed a positive relationship between emotional bias and RPE signal during negative feedback in bilateral thalamus and caudate. CONCLUSION: TRS can be dissociated from NTR on the basis of a different neural mechanism underlying reinforcement learning. The data support the hypothesis that a favorable response to antipsychotic treatment is contingent on dopaminergic dysfunction, characterized by aberrant RPE signaling, whereas treatment resistance may be characterized by an abnormality of a non-dopaminergic mechanism - a glutamatergic mechanism would be a possible candidate.

Transcriptional changes in innate immunity genes in head kidneys from Aeromonas salmonicida-challenged rainbow trout fed a mixture of polycyclic aromatic hydrocarbons.

We previously observed that exposure to a complex mixture of high molecular weight polycyclic aromatic hydrocarbons (PAHs) increased sensitivity of rainbow trout (Oncorhynchus mykiss) to subsequent challenge with Aeromonas salmonicida, the causative agent of furunculosis. In this study, we evaluate potential mechanisms associated with disease susceptibility from combined environmental factors of dietary PAH exposure and pathogen challenge. Rainbow trout were fed a mixture of ten high molecular weight PAHs at an environmentally relevant concentration (7.82µg PAH mixture/g fish/day) or control diet for 50 days. After 50 days of PAH exposure, fish were challenged with either Aeromonas salmonicida at a lethal concentration 30 (LC30) or growth media without the pathogen (mock challenge). Head kidneys were collected 2, 4, 10 and 20 days after challenge and gene expression (q<0.05) was evaluated among treatments. In animals fed the PAH contaminated diet, we observed down-regulation of expression for innate immune system genes in pathways (p<0.05) for the terminal steps of the complement cascade (complement component C6) and other bacteriolytic processes (lysozyme type II) potentially underlying increased disease susceptibility after pathogen challenge. Increased expression of genes associated with hemorrhage/tissue remodeling/inflammation pathways (p<0.05) was likely related to more severe head kidney damage due to infection in PAH-fed compared to control-fed fish. This study is the first to evaluate transcriptional signatures associated with the impact of chronic exposure to an environmentally relevant mixture of PAHs in disease susceptibility and immunity.

Unexpectedly high mortality in Pacific herring embryos exposed to the 2007 Cosco Busan oil spill in San Francisco Bay.

In November 2007, the container ship Cosco Busan released 54,000 gallons of bunker fuel oil into San Francisco Bay. The accident oiled shoreline near spawning habitats for the largest population of Pacific herring on the west coast of the continental United States. We assessed the health and viability of herring embryos from oiled and unoiled locations that were either deposited by natural spawning or incubated in subtidal cages. Three months after the spill, caged embryos at oiled sites showed sublethal cardiac toxicity, as expected from exposure to oil-derived polycyclic aromatic compounds (PACs). By contrast, embryos from the adjacent and shallower intertidal zone showed unexpectedly high rates of tissue necrosis and lethality unrelated to cardiotoxicity. No toxicity was observed in embryos from unoiled sites. Patterns of PACs at oiled sites were consistent with oil exposure against a background of urban sources, although tissue concentrations were lower than expected to cause lethality. Embryos sampled 2 y later from oiled sites showed modest sublethal cardiotoxicity but no elevated necrosis or mortality. Bunker oil contains the chemically uncharacterized remains of crude oil refinement, and one or more of these unidentified chemicals likely interacted with natural sunlight in the intertidal zone to kill herring embryos. This reveals an important discrepancy between the resolving power of current forensic analytical chemistry and biological responses of keystone ecological species in oiled habitats. Nevertheless, we successfully delineated the biological impacts of an oil spill in an urbanized coastal estuary with an overlapping backdrop of atmospheric, vessel, and land-based sources of PAC pollution.

Health of common bottlenose dolphins ( Tursiops truncatus ) in Barataria Bay, Louisiana, following the deepwater horizon oil spill.

The oil spill resulting from the explosion of the Deepwater Horizon drilling platform initiated immediate concern for marine wildlife, including common bottlenose dolphins in sensitive coastal habitats. To evaluate potential sublethal effects on dolphins, health assessments were conducted in Barataria Bay, Louisiana, an area that received heavy and prolonged oiling, and in a reference site, Sarasota Bay, Florida, where oil was not observed. Dolphins were temporarily captured, received a veterinary examination, and were then released. Dolphins sampled in Barataria Bay showed evidence of hypoadrenocorticism, consistent with adrenal toxicity as previously reported for laboratory mammals exposed to oil. Barataria Bay dolphins were 5 times more likely to have moderate-severe lung disease, generally characterized by significant alveolar interstitial syndrome, lung masses, and pulmonary consolidation. Of 29 dolphins evaluated from Barataria Bay, 48% were given a guarded or worse prognosis, and 17% were considered poor or grave, indicating that they were not expected to survive. Disease conditions in Barataria Bay dolphins were significantly greater in prevalence and severity than those in Sarasota Bay dolphins, as well as those previously reported in other wild dolphin populations. Many disease conditions observed in Barataria Bay dolphins are uncommon but consistent with petroleum hydrocarbon exposure and toxicity.

Sublethal exposure to crude oil during embryonic development alters cardiac morphology and reduces aerobic capacity in adult fish.

Exposure to high concentrations of crude oil produces a lethal syndrome of heart failure in fish embryos. Mortality is caused by cardiotoxic polycyclic aromatic hydrocarbons (PAHs), ubiquitous components of petroleum. Here, we show that transient embryonic exposure to very low concentrations of oil causes toxicity that is sublethal, delayed, and not counteracted by the protective effects of cytochrome P450 induction. Nearly a year after embryonic oil exposure, adult zebrafish showed subtle changes in heart shape and a significant reduction in swimming performance, indicative of reduced cardiac output. These delayed physiological impacts on cardiovascular performance at later life stages provide a potential mechanism linking reduced individual survival to population-level ecosystem responses of fish species to chronic, low-level oil pollution.

A perspective on the history and evolution of an Oceans and Human Health "metadiscipline" in the USA.

We review recent history and evolution of Oceans and Human Health programs and related activities in the USA from a perspective within the Federal government. As a result of about a decade of support by the US Congress and through a few Federal agencies, notably the National Science Foundation, National Institute of Environmental Health Sciences, and National Ocean and Atmospheric Administration, robust Oceans and Human Health (OHH) research and application activities are now relatively widespread, although still small, in a number of agencies and academic institutions. OHH themes and issues have been incorporated into comprehensive federal ocean research plans and are reflected in the new National Ocean Policy enunciated by Executive Order 13547. In just a decade, OHH has matured into a recognized "metadiscipline," with development of a small, but robust and diverse community of science and practice, incorporation into academic educational programs, regular participation in ocean and coastal science and public health societies, and active engagement with public health decision makers. In addition to substantial increases in scientific information, the OHH community has demonstrated ability to respond rapidly and effectively to emergency situations such as those associated with extreme weather events (e.g., hurricanes, floods) and human-caused disasters (e.g., the Deep Water Horizon oil spill). Among many other things, next steps include development and implementation of agency health strategies and provision of specific services, such as ecological forecasts to provide routine early warnings for ocean health threats and opportunities for prevention and mitigation of these risks.

A comprehensive petrochemical vulnerability index for marine fishes in the Gulf of Mexico.

Oil and gas extraction activities occur across the globe, yet species-specific toxicological information on the biological and ecological impacts of exposure to petrochemicals is lacking for the vast majority of marine species. To help prioritize species for recovery, mitigation, and conservation in light of significant toxicological data gaps, a trait-based petrochemical vulnerability index was developed and applied to the more than 1700 marine fishes present across the entire Gulf of Mexico, including all known bony fishes, sharks, rays and chimaeras. Using life history and other traits related to likelihood of exposure, physiological sensitivity to exposure, and population resiliency, final calculated petrochemical vulnerability scores can be used to provide information on the relative sensitivity, or resilience, of marine fish populations across the Gulf of Mexico to oil and gas activities. Based on current knowledge of traits, marine fishes with the highest vulnerability scores primarily occur in areas of high petrochemical activity, are found at or near the surface, and have low reproductive turnover rates and/or highly specialized diet and habitat requirements. Relative population vulnerability scores for marine fishes can be improved with additional toxicokinetic studies, including those that account for the synergistic or additive effect of multiple stressors, as well as increased research on ecological and life history traits, especially for deep living species.

Reduced cytochrome P4501A activity and recovery from oxidative stress during subchronic benzo[a]pyrene and benzo[e]pyrene treatment of rainbow trout.

This study assessed the role of aryl hydrocarbon receptor (AHR) affinity, and cytochrome P4501A (CYP1A) protein and activity in polyaromatic hydrocarbon (PAH)-induced oxidative stress. In the 1-100nM concentration range benzo[a]pyrene (BaP) but not benzo[e]pyrene (BeP) competitively displaced 2nM [(3)H]2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin from rainbow trout AHR2α. Based on appearance of fluorescent aromatic compounds in bile over 3, 7, 14, 28 or 50days of feeding 3µg of BaP or BeP/g fish/day, rainbow trout liver readily excreted these polyaromatic hydrocarbons (PAHs) and their metabolites at near steady state rates. CYP1A proteins catalyzed more than 98% of ethoxyresorufin-O-deethylase (EROD) activity in rainbow trout hepatic microsomes. EROD activity of hepatic microsomes initially increased and then decreased to control activities after 50days of feeding both PAHs. Immunohistochemistry of liver confirmed CYP1A protein increased in fish fed both PAHs after 3days and remained elevated for up to 28days. Neither BaP nor BeP increased hepatic DNA adduct concentrations at any time up to 50days of feeding these PAHs. Comet assays of blood cells demonstrated marked DNA damage after 14days of feeding both PAHs that was not significant after 50days. There was a strong positive correlation between hepatic EROD activity and DNA damage in blood cells over time for both PAHs. Neither CYP1A protein nor 3-nitrotyrosine (a biomarker for oxidative stress) immunostaining in trunk kidney were significantly altered by BaP or BeP after 3, 7, 14, or 28days. There was no clear association between AHR2α affinity and BaP and BeP-induced oxidative stress.

Eye movements in patients in early psychosis with and without a history of cannabis use.

It is unclear whether early psychosis in the context of cannabis use is different from psychosis without cannabis. We investigated this issue by examining whether abnormalities in oculomotor control differ between patients with psychosis with and without a history of cannabis use. We studied four groups: patients in the early phase of psychosis with a history of cannabis use (EPC; n = 28); patients in the early phase of psychosis without (EPNC; n = 25); controls with a history of cannabis use (HCC; n = 16); and controls without (HCNC; n = 22). We studied smooth pursuit eye movements using a stimulus with sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz). Participants also performed 40 antisaccade trials. There were no differences between the EPC and EPNC groups in diagnosis, symptom severity or level of functioning. We found evidence for a cannabis effect (χ2 = 23.14, p < 0.001), patient effect (χ2 = 4.84, p = 0.028) and patient × cannabis effect (χ2 = 4.20, p = 0.04) for smooth pursuit velocity gain. There was a large difference between EPC and EPNC (g = 0.76-0.86) with impairment in the non cannabis using group. We found no significant effect for antisaccade error whereas patients had fewer valid trials compared to controls. These data indicate that impairment of smooth pursuit in psychosis is more severe in patients without a history of cannabis use. This is consistent with the notion that the severity of neurobiological alterations in psychosis is lower in patients whose illness developed in the context of cannabis use.

Cross-sectional study comparing cognitive function in treatment responsive versus treatment non-responsive schizophrenia: evidence from the STRATA study.

BACKGROUND: 70%-84% of individuals with antipsychotic treatment resistance show non-response from the first episode. Emerging cross-sectional evidence comparing cognitive profiles in treatment resistant schizophrenia to treatment-responsive schizophrenia has indicated that verbal memory and language functions may be more impaired in treatment resistance. We sought to confirm this finding by comparing cognitive performance between antipsychotic non-responders (NR) and responders (R) using a brief cognitive battery for schizophrenia, with a primary focus on verbal tasks compared against other measures of cognition. DESIGN: Cross-sectional. SETTING: This cross-sectional study recruited antipsychotic treatment R and antipsychotic NR across four UK sites. Cognitive performance was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). PARTICIPANTS: One hundred and six participants aged 18-65 years with a diagnosis of schizophrenia or schizophreniform disorder were recruited according to their treatment response, with 52 NR and 54 R cases. OUTCOMES: Composite and subscale scores of cognitive performance on the BACS. Group (R vs NR) differences in cognitive scores were investigated using univariable and multivariable linear regressions adjusted for age, gender and illness duration. RESULTS: Univariable regression models observed no significant differences between R and NR groups on any measure of the BACS, including verbal memory (ß=-1.99, 95% CI -6.63 to 2.66, p=0.398) and verbal fluency (ß=1.23, 95% CI -2.46 to 4.91, p=0.510). This pattern of findings was consistent in multivariable models. CONCLUSIONS: The lack of group difference in cognition in our sample is likely due to a lack of clinical distinction between our groups. Future investigations should aim to use machine learning methods using longitudinal first episode samples to identify responder subtypes within schizophrenia, and how cognitive factors may interact within this. TRAIL REGISTRATION NUMBER: REC: 15/LO/0038.

Dopamine and Glutamate in Antipsychotic-Responsive Compared With Antipsychotic-Nonresponsive Psychosis: A Multicenter Positron Emission Tomography and Magnetic Resonance Spectroscopy Study (STRATA).

The variability in the response to antipsychotic medication in schizophrenia may reflect between-patient differences in neurobiology. Recent cross-sectional neuroimaging studies suggest that a poorer therapeutic response is associated with relatively normal striatal dopamine synthesis capacity but elevated anterior cingulate cortex (ACC) glutamate levels. We sought to test whether these measures can differentiate patients with psychosis who are antipsychotic responsive from those who are antipsychotic nonresponsive in a multicenter cross-sectional study. 1H-magnetic resonance spectroscopy (1H-MRS) was used to measure glutamate levels (Glucorr) in the ACC and in the right striatum in 92 patients across 4 sites (48 responders [R] and 44 nonresponders [NR]). In 54 patients at 2 sites (25 R and 29 NR), we additionally acquired 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (18F-DOPA) positron emission tomography (PET) to index striatal dopamine function (Kicer, min-1). The mean ACC Glucorr was higher in the NR than the R group after adjustment for age and sex (F1,80 = 4.27; P = .04). This was associated with an area under the curve for the group discrimination of 0.59. There were no group differences in striatal dopamine function or striatal Glucorr. The results provide partial further support for a role of ACC glutamate, but not striatal dopamine synthesis, in determining the nature of the response to antipsychotic medication. The low discriminative accuracy might be improved in groups with greater clinical separation or increased in future studies that focus on the antipsychotic response at an earlier stage of the disorder and integrate other candidate predictive biomarkers. Greater harmonization of multicenter PET and 1H-MRS may also improve sensitivity.

A multi-taxonomic framework for assessing relative petrochemical vulnerability of marine biodiversity in the Gulf of Mexico.

A fundamental understanding of the impact of petrochemicals and other stressors on marine biodiversity is critical for effective management, restoration, recovery, and mitigation initiatives. As species-specific information on levels of petrochemical exposure and toxicological response are lacking for the majority of marine species, a trait-based assessment to rank species vulnerabilities to petrochemical activities in the Gulf of Mexico can provide a more comprehensive and effective means to prioritize species, habitats, and ecosystems for improved management, restoration and recovery. To initiate and standardize this process, we developed a trait-based framework, applicable to a wide range of vertebrate and invertebrate species, that can be used to rank relative population vulnerabilities of species to petrochemical activities in the Gulf of Mexico. Through expert consultation, 18 traits related to likelihood of exposure, individual sensitivity, and population resilience were identified and defined. The resulting multi-taxonomic petrochemical vulnerability framework can be adapted and applied to a wide variety of species groups and geographic regions. Additional recommendations and guidance on the application of the framework to rank species vulnerabilities under specific petrochemical exposure scenarios, management needs or data limitations are also discussed.

Severe thiamine deficiency in eastern Baltic cod (Gadus morhua).

The eastern Baltic cod (Gadus morhua) population has been decreasing in the Baltic Sea for at least 30 years. Condition indices of the Baltic cod have decreased, and previous studies have suggested that this might be due to overfishing, predation, lower dissolved oxygen or changes in salinity. However, numerous studies from the Baltic Sea have demonstrated an ongoing thiamine deficiency in several animal classes, both invertebrates and vertebrates. The thiamine status of the eastern Baltic cod was investigated to determine if thiamine deficiency might be a factor in ongoing population declines. Thiamine concentrations were determined by chemical analyses of thiamine, thiamine monophosphate and thiamine diphosphate (combined SumT) in the liver using high performance liquid chromatography. Biochemical analyses measured the activity of the thiamine diphosphate-dependent enzyme transketolase to determine the proportion of apoenzymes in both liver and brain tissue. These biochemical analyses showed that 77% of the cod were thiamine deficient in the liver, of which 13% had a severe thiamine deficiency (i.e. 25% transketolase enzymes lacked thiamine diphosphate). The brain tissue of 77% of the cod showed thiamine deficiency, of which 64% showed severe thiamine deficiency. The thiamine deficiency biomarkers were investigated to find correlations to different biological parameters, such as length, weight, otolith weight, age (annuli counting) and different organ weights. The results suggested that thiamine deficiency increased with age. The SumT concentration ranged between 2.4-24 nmol/g in the liver, where the specimens with heavier otoliths had lower values of SumT (P = 0.0031). Of the cod sampled, only 2% of the specimens had a Fulton's condition factor indicating a healthy specimen, and 49% had a condition factor below 0.8, indicating poor health status. These results, showing a severe thiamine deficiency in eastern Baltic cod from the only known area where spawning presently occurs for this species, are of grave concern.

Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia.

RATIONALE: There is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce. OBJECTIVES: The aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC). METHODS: In a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions. RESULTS: Compared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6). CONCLUSIONS: These findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of interest.

Association of cannabis with glutamatergic levels in patients with early psychosis: Evidence for altered volume striatal glutamate relationships in patients with a history of cannabis use in early psychosis.

The associative striatum, an established substrate in psychosis, receives widespread glutamatergic projections. We sought to see if glutamatergic indices are altered between early psychosis patients with and without a history of cannabis use and characterise the relationship to grey matter. 92 participants were scanned: Early Psychosis with a history of cannabis use (EPC = 29); Early Psychosis with minimal cannabis use (EPMC = 25); Controls with a history of cannabis use (HCC = 16) and Controls with minimal use (HCMC = 22). Whole brain T1 weighted MR images and localised proton MR spectra were acquired from head of caudate, anterior cingulate and hippocampus. We examined relationships in regions with known high cannabinoid 1 receptor (CB1R) expression (grey matter, cortex, hippocampus, amygdala) and low expression (white matter, ventricles, brainstem) to caudate Glutamine+Glutamate (Glx). Patients were well matched in symptoms, function and medication. There was no significant group difference in Glx in any region. In EPC grey matter volume explained 31.9% of the variance of caudate Glx (p = 0.003) and amygdala volume explained 36.9% (p = 0.001) of caudate Glx. There was no significant relationship in EPMC. The EPC vs EPMC interaction was significant (p = 0.042). There was no such relationship in control regions. These results are the first to demonstrate association of grey matter volume and striatal glutamate in the EPC group. This may suggest a history of cannabis use leads to a conformational change in distal CB1 rich grey matter regions to influence striatal glutamatergic levels or that such connectivity predisposes to heavy cannabis use.

Framework for a Community Health Observing System for the Gulf of Mexico Region: Preparing for Future Disasters.

The Gulf of Mexico (GoM) region is prone to disasters, including recurrent oil spills, hurricanes, floods, industrial accidents, harmful algal blooms, and the current COVID-19 pandemic. The GoM and other regions of the U.S. lack sufficient baseline health information to identify, attribute, mitigate, and facilitate prevention of major health effects of disasters. Developing capacity to assess adverse human health consequences of future disasters requires establishment of a comprehensive, sustained community health observing system, similar to the extensive and well-established environmental observing systems. We propose a system that combines six levels of health data domains, beginning with three existing, national surveys and studies plus three new nested, longitudinal cohort studies. The latter are the unique and most important parts of the system and are focused on the coastal regions of the five GoM States. A statistically representative sample of participants is proposed for the new cohort studies, stratified to ensure proportional inclusion of urban and rural populations and with additional recruitment as necessary to enroll participants from particularly vulnerable or under-represented groups. Secondary data sources such as syndromic surveillance systems, electronic health records, national community surveys, environmental exposure databases, social media, and remote sensing will inform and augment the collection of primary data. Primary data sources will include participant-provided information via questionnaires, clinical measures of mental and physical health, acquisition of biological specimens, and wearable health monitoring devices. A suite of biomarkers may be derived from biological specimens for use in health assessments, including calculation of allostatic load, a measure of cumulative stress. The framework also addresses data management and sharing, participant retention, and system governance. The observing system is designed to continue indefinitely to ensure that essential pre-, during-, and post-disaster health data are collected and maintained. It could also provide a model/vehicle for effective health observation related to infectious disease pandemics such as COVID-19. To our knowledge, there is no comprehensive, disaster-focused health observing system such as the one proposed here currently in existence or planned elsewhere. Significant strengths of the GoM Community Health Observing System (CHOS) are its longitudinal cohorts and ability to adapt rapidly as needs arise and new technologies develop.

A fish of many scales: extrapolating sublethal pesticide exposures to the productivity of wild salmon populations.

For more than a decade, numerous pesticides have been detected in river systems of the western United States that support anadromous species of Pacific salmon and steelhead. Over the same interval, several declining wild salmon populations have been listed as either threatened or endangered under the U.S. Endangered Species Act (ESA). Because pesticides occur in surface waters that provide critical habitat for ESA-listed stocks, they are an ongoing concern for salmon conservation and recovery throughout California and the Pacific Northwest. Because pesticide exposures are typically sublethal, a key question is whether toxicological effects at (or below) the scale of the individual animal ultimately reduce the productivity and recovery potential of wild populations. In this study we evaluate how the sublethal impacts of pesticides on physiology and behavior can reduce the somatic growth of juvenile chinook salmon (Oncorhynchus tshawytscha) and, by extension, subsequent size-dependent survival when animals migrate to the ocean and overwinter in their first year. Our analyses focused on the organophosphate and carbamate classes of insecticides. These neurotoxic chemicals have been widely detected in aquatic environments. They inhibit acetylcholinesterase, an enzyme in the salmon nervous system that regulates neurotransmitter-mediated signaling at synapses. Based on empirical data, we developed a model that explicitly links sublethal reductions in acetylcholinesterase activity to reductions in feeding behavior, food ration, growth, and size at migration. Individual size was then used to estimate size-dependent survival during migration and transition to the sea. Individual survival estimates were then integrated into a life-history population projection matrix and used to calculate population productivity and growth rate. Our results indicate that short-term (i.e., four-day) exposures that are representative of seasonal pesticide use may be sufficient to reduce the growth and size at ocean entry of juvenile chinook. The consequent reduction in individual survival over successive years reduces the intrinsic productivity (lambda) of a modeled ocean-type chinook population. Overall, we show that exposures to common pesticides may place important constraints on the recovery of ESA-listed salmon species, and that simple models can be used to extrapolate toxicological impacts across several scales of biological complexity.