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1.
Environ Sci Technol ; 58(1): 132-142, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38154032

ABSTRACT

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.


Subject(s)
Polychlorinated Biphenyls , Water Pollutants, Chemical , Animals , Dietary Exposure/analysis , Salmon/metabolism , Ecosystem , Environmental Exposure/analysis , Polychlorinated Biphenyls/toxicity , Polychlorinated Biphenyls/analysis , Polychlorinated Biphenyls/metabolism , Water Pollutants, Chemical/analysis
2.
Sci Total Environ ; 820: 152892, 2022 May 10.
Article in English | MEDLINE | ID: mdl-35051468

ABSTRACT

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.


Subject(s)
Ecosystem , Fishes , Petroleum Pollution , Water Pollutants, Chemical , Animals , Fishes/physiology , Gulf of Mexico , Mexico , Oil and Gas Industry , Reproduction , Species Specificity
3.
BMJ Open ; 11(11): e054160, 2021 11 25.
Article in English | MEDLINE | ID: mdl-34824121

ABSTRACT

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.


Subject(s)
Antipsychotic Agents , Cognition Disorders , Schizophrenia , Antipsychotic Agents/therapeutic use , Cognition , Cross-Sectional Studies , Humans , Neuropsychological Tests , Schizophrenia/drug therapy , Schizophrenia, Treatment-Resistant
4.
J Toxicol Environ Health B Crit Rev ; 24(8): 355-394, 2021 11 17.
Article in English | MEDLINE | ID: mdl-34542016

ABSTRACT

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.


Subject(s)
Environmental Exposure/adverse effects , Petroleum Pollution/adverse effects , Water Pollutants, Chemical/toxicity , Animals , Birds , Environmental Monitoring/methods , Fishes , Humans , Multiple Organ Failure/etiology , Petroleum/toxicity , Turtles , Vertebrates
5.
NPJ Schizophr ; 7(1): 24, 2021 May 12.
Article in English | MEDLINE | ID: mdl-33980870

ABSTRACT

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.

6.
Schizophr Bull ; 47(2): 505-516, 2021 03 16.
Article in English | MEDLINE | ID: mdl-32910150

ABSTRACT

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.


Subject(s)
Antipsychotic Agents/pharmacology , Corpus Striatum , Dopamine/metabolism , Glutamic Acid/metabolism , Gyrus Cinguli , Psychotic Disorders , Schizophrenia , Adult , Corpus Striatum/diagnostic imaging , Corpus Striatum/metabolism , Cross-Sectional Studies , Female , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/metabolism , Humans , Male , Middle Aged , Positron-Emission Tomography , Proton Magnetic Resonance Spectroscopy , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/drug therapy , Psychotic Disorders/metabolism , Schizophrenia/diagnostic imaging , Schizophrenia/drug therapy , Schizophrenia/metabolism , Young Adult
7.
Sci Total Environ ; 763: 142986, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33168243

ABSTRACT

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.


Subject(s)
Biodiversity , Ecosystem , Animals , Gulf of Mexico , Invertebrates , Mexico , Vertebrates
8.
Front Public Health ; 8: 578463, 2020.
Article in English | MEDLINE | ID: mdl-33178663

ABSTRACT

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.


Subject(s)
COVID-19 , Disasters , Gulf of Mexico , Humans , Longitudinal Studies , Pandemics , Public Health , SARS-CoV-2
9.
Hum Brain Mapp ; 41(15): 4386-4396, 2020 10 15.
Article in English | MEDLINE | ID: mdl-32687254

ABSTRACT

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.


Subject(s)
Marijuana Use/pathology , Psychotic Disorders/pathology , Putamen/physiology , Thalamus/pathology , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Psychotic Disorders/diagnostic imaging , Putamen/diagnostic imaging , Thalamus/diagnostic imaging , Young Adult
10.
Transl Psychiatry ; 10(1): 111, 2020 04 21.
Article in English | MEDLINE | ID: mdl-32317625

ABSTRACT

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.


Subject(s)
Cannabis , Carcinoma, Hepatocellular , Liver Neoplasms , Psychotic Disorders , Glutamic Acid , Humans , Magnetic Resonance Imaging , Psychotic Disorders/diagnostic imaging
11.
PLoS One ; 15(1): e0227201, 2020.
Article in English | MEDLINE | ID: mdl-31895939

ABSTRACT

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.


Subject(s)
Fish Diseases/metabolism , Gadus morhua/metabolism , Thiamine Deficiency/veterinary , Thiamine/metabolism , Animals , Brain/metabolism , Female , Liver/metabolism , Male , Thiamine/analysis , Thiamine Deficiency/metabolism
12.
Psychopharmacology (Berl) ; 237(2): 443-451, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31786651

ABSTRACT

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.


Subject(s)
Acetylcysteine/administration & dosage , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Nerve Net/diagnostic imaging , Rest/physiology , Schizophrenia/diagnostic imaging , Adult , Brain/drug effects , Brain/metabolism , Cross-Over Studies , Double-Blind Method , Female , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/drug effects , Gyrus Cinguli/metabolism , Humans , Male , Middle Aged , Nerve Net/drug effects , Nerve Net/metabolism , Proton Magnetic Resonance Spectroscopy/methods , Schizophrenia/drug therapy , Schizophrenia/metabolism
15.
Psychopharmacology (Berl) ; 235(10): 3045-3054, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30141055

ABSTRACT

RATIONALE: N-Acetylcysteine (NAC) is currently under investigation as an adjunctive treatment for schizophrenia. The therapeutic potential of NAC may involve modulation of brain glutamate function, but its effects on brain glutamate levels in schizophrenia have not been evaluated. OBJECTIVES: The aim of this study was to examine whether a single dose of NAC can alter brain glutamate levels. A secondary aim was to characterise its effects on regional brain perfusion. METHODS: In a double-blind placebo-controlled crossover study, 19 patients with a diagnosis of schizophrenia underwent two MRI scans, following oral administration of 2400 mg NAC or matching placebo. Proton magnetic resonance spectroscopy was used to investigate the effect of NAC on glutamate and Glx (glutamate plus glutamine) levels scaled to creatine (Cr) in the anterior cingulate cortex (ACC) and in the right caudate nucleus. Pulsed continuous arterial spin labelling was used to assess the effects of NAC on resting cerebral blood flow (rCBF) in the same regions. RESULTS: Relative to the placebo condition, the NAC condition was associated with lower levels of Glx/Cr, in the ACC (P < 0.05), but not in the caudate nucleus. There were no significant differences in CBF in the NAC compared to placebo condition. CONCLUSIONS: These data provide preliminary evidence that NAC can modulate ACC glutamate in patients with schizophrenia. In contrast, physiological effects of NAC on the brain were not detectable as between session changes in rCBF. Future studies assessing the effects of a course of treatment with NAC on glutamate metabolites in schizophrenia are indicated.


Subject(s)
Acetylcysteine/pharmacology , Caudate Nucleus/metabolism , Cerebrovascular Circulation/drug effects , Glutamic Acid/metabolism , Gyrus Cinguli/metabolism , Schizophrenia/drug therapy , Adult , Brain/blood supply , Brain/metabolism , Caudate Nucleus/drug effects , Creatine/metabolism , Cross-Over Studies , Double-Blind Method , Female , Gyrus Cinguli/drug effects , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Proton Magnetic Resonance Spectroscopy , Regional Blood Flow/drug effects , Rest , Schizophrenia/metabolism , Schizophrenia/physiopathology
16.
Psychol Med ; 48(14): 2418-2427, 2018 10.
Article in English | MEDLINE | ID: mdl-29439750

ABSTRACT

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.


Subject(s)
Antipsychotic Agents/pharmacology , Cerebellum/physiopathology , Cerebral Cortex/physiopathology , Functional Neuroimaging/methods , Reinforcement, Psychology , Reward , Schizophrenia/drug therapy , Schizophrenia/physiopathology , Adult , Cerebellum/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Emotions/physiology , Facial Expression , Facial Recognition/physiology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Schizophrenia/diagnostic imaging
17.
Environ Sci Pollut Res Int ; 24(36): 27631-27633, 2017 12.
Article in English | MEDLINE | ID: mdl-29235016
18.
Ecotoxicol Environ Saf ; 142: 157-163, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28407501

ABSTRACT

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.


Subject(s)
Aeromonas salmonicida/pathogenicity , Head Kidney/immunology , Immunity, Innate/drug effects , Oncorhynchus mykiss/microbiology , Polycyclic Aromatic Hydrocarbons/toxicity , Transcription, Genetic/drug effects , Animals , Down-Regulation , Immunity, Innate/genetics , Muramidase/metabolism , Oncorhynchus mykiss/immunology , Oncorhynchus mykiss/metabolism
19.
Brain Stimul ; 10(3): 560-566, 2017.
Article in English | MEDLINE | ID: mdl-28057452

ABSTRACT

BACKGROUND: Schizophrenia is characterized by prominent cognitive deficits, impacting on memory and learning; these are strongly associated with the prefrontal cortex. OBJECTIVE/HYPOTHESIS: To combine two interventions, transcranial direct current stimulation (tDCS) over the prefrontal cortex and cognitive training, to examine change in cognitive performance in patients with schizophrenia. METHODS: A double blind, sham-controlled pilot study of 49 patients with schizophrenia, randomized into real or sham tDCS stimulation groups. Subjects participated in 4 days of cognitive training (days 1, 2, 14, 56) with tDCS applied at day-1 and day-14. The primary outcome measure was change in accuracy on working memory and implicit learning tasks from baseline. The secondary outcome measure was the generalization of learning to non-trained task, indexed by the CogState neuropsychological battery. Data analysis was conducted using multilevel modelling and multiple regressions. RESULTS: 24 participants were randomized to real tDCS and 25 to sham. The working memory task demonstrated a significant mean difference in performance in the tDCS treatment group: at day-2 (b = 0.68, CI 0.14-1.21; p = 0.044) and at day-56 (b = 0.71, 0.16-1.26; p = 0.044). There were no significant effects of tDCS on implicit learning. Trend evidence of generalization onto untrained tasks of attention and vigilance task (b = 0.40, 0.43-0.77; p = 0.058) was found. CONCLUSIONS: This is the first study to show a significant longer-term effect of tDCS on working memory in schizophrenia. Given the current lack of effective therapies for cognitive deficits, tDCS may offer an important novel approach to modulating brain networks to ameliorate cognitive deficits in schizophrenia.


Subject(s)
Cognition , Memory, Short-Term , Schizophrenia/therapy , Transcranial Direct Current Stimulation/adverse effects , Adult , Attention , Double-Blind Method , Female , Humans , Male , Pilot Projects , Prefrontal Cortex/physiology , Transcranial Direct Current Stimulation/methods
20.
Geohealth ; 1(1): 17-36, 2017 Mar.
Article in English | MEDLINE | ID: mdl-30596189

ABSTRACT

Few conceptual frameworks attempt to connect disaster-associated environmental injuries to impacts on ecosystem services (the benefits humans derive from nature) and thence to both psychological and physiological human health effects. To our knowledge, this study is one of the first, if not the first, to develop a detailed conceptual model of how degraded ecosystem services affect cumulative stress impacts on the health of individual humans and communities. Our comprehensive Disaster-Pressure State-Ecosystem Services-Response-Health (DPSERH) model demonstrates that oil spills, hurricanes, and other disasters can change key ecosystem components resulting in reductions in individual and multiple ecosystem services that support people's livelihoods, health, and way of life. Further, the model elucidates how damage to ecosystem services produces acute, chronic, and cumulative stress in humans which increases risk of adverse psychological and physiological health outcomes. While developed and initially applied within the context of the Gulf of Mexico, it should work equally well in other geographies and for many disasters that cause impairment of ecosystem services. Use of this new tool will improve planning for responses to future disasters and help society more fully account for the costs and benefits of potential management responses. The model also can be used to help direct investments in improving response capabilities of the public health community, biomedical researchers, and environmental scientists. Finally, the model illustrates why the broad range of potential human health effects of disasters should receive equal attention to that accorded environmental damages in assessing restoration and recovery costs and time frames.

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