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BACKGROUND: ATP6V1B2 (ATPase, H+ transporting, lysosomal VI subunit B, isoform 2) encodes for a subunit of a ubiquitous transmembrane lysosomal proton pump, implicated in the acidification of intracellular organelles and in several additional cellular functions. Variants in ATP6V1B2 have been related to a heterogeneous group of multisystemic disorders sometimes associated with variable neurological involvement. However, our knowledge of genotype-phenotype correlations and the neurological spectrum of ATP6V1B2-related disorders remain limited due to the few numbers of reported cases. CASE STUDY: We hereby report the case of an 18-year-old male Sicilian patient affected by a global developmental delay, skeletal abnormalities, and epileptic encephalopathy featuring Lennox-Gastaut syndrome (LGS), in which exome sequencing led to the identification of a novel de novo variant in ATP6V1B2 (NM_001693.4: c.973G > C, p.Gly325Arg). CONCLUSIONS: Our report provides new insights on the inclusion of developmental epileptic encephalopathies (DEEs) within the continuum group of ATP6V1B2-related disorders, expanding the phenotypic and molecular spectrum associated with these conditions.
Subject(s)
Epilepsy, Generalized , Epilepsy , Lennox Gastaut Syndrome , Vacuolar Proton-Translocating ATPases , Male , Humans , Adolescent , Lennox Gastaut Syndrome/genetics , Epilepsy/genetics , Genetic Association Studies , Adenosine Triphosphatases , Vacuolar Proton-Translocating ATPases/geneticsABSTRACT
BACKGROUND AIMS: The proapoptotic protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is physiologically expressed by immune cells and performs regulatory functions in infections, autoimmune diseases and cancer, where it acts as a tumor suppressor. Adipose-derived mesenchymal stromal cells (AD-MSCs) also may play immunomodulatory roles in both primary and acquired immune responses. We have previously demonstrated the efficacy of an anticancer gene therapy based on AD-MSC engineered to secrete a soluble TRAIL variant (sTRAIL) against pancreatic cancer. However, the impact of AD-MSC sTRAIL on leukocyte subsets has been not yet considered also to predict a possible immunotoxicity profile in the clinical translation of this cell-based anticancer strategy. METHODS: Monocytes, polymorphonuclear cells and T lymphocytes were freshly isolated from the peripheral blood of healthy donors. Immunophenotype and functional (DR4 and DR5) and decoy (DcR1 and DcR2) TRAIL receptors were tested by flow cytometry. The viability of white blood cells treated with sTRAIL released by gene-modified AD-MSC or co-cultured with AD-MSC sTRAIL was then evaluated by both metabolic assays and flow cytometry. In addition, cytokine profile in co-cultures was analyzed by multiplex enzyme-linked immunosorbent assay. RESULTS: Monocytes and polymorphonuclear cells showed high positivity for DR5 and DcR2, respectively, whereas T cells revealed negligible expression of all TRAIL receptors. Irrespective of TRAIL receptors' presence on the cell membrane, white blood cells were refractory to the proapoptotic effect displayed by sTRAIL secreted by gene-modified AD-MSC, and direct cell-to-cell contact with AD-MSC sTRAIL had negligible impact on T-cell and monocyte viability. Cytokine crosstalk involving interleukin 10, tumor necrosis factor alpha, and interferon gamma secreted by T lymphocytes and vascular endothelial growth factor A and interleukin 6 released by AD-MSC was highlighted in T-cell and AD-MSC sTRAIL co-cultures. CONCLUSIONS: In summary, this study demonstrates the immunological safety and thus the clinical feasibility of an anticancer approach based on AD-MSC expressing the proapoptotic molecule sTRAIL.
Subject(s)
Mesenchymal Stem Cells , Pancreatic Neoplasms , Humans , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Ligands , Apoptosis/physiology , Pancreatic Neoplasms/therapy , Leukocytes/metabolism , TNF-Related Apoptosis-Inducing Ligand/genetics , TNF-Related Apoptosis-Inducing Ligand/metabolismABSTRACT
Monitoring the state of the economy in a short time is a crucial aspect for designing appropriate and timely policy responses in the presence of shocks and crises. Short-term confidence indicators can help policymakers in evaluating both the effect of policies and the economic activity condition. The indicator commonly used in the EU to evaluate the public opinion orientation is the Economic Sentiment Indicator (ESI). Nevertheless, the ESI shows some drawbacks, particularly in the adopted weighting scheme that is static and not country-specific. This paper proposes an approach to construct novel composite confidence indicators, focusing on both the weights and the information set to use. We evaluate these indicators by studying their response to the policies introduced to contain the COVID-19 pandemic in some selected EU countries. Furthermore, we carry out an experimental study where the proposed indicators are used to forecast economic activity.
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Academic Health Centers (AHCs) have an enormous impact on health, society, and national competitiveness. They have a threefold strategic mission and heterogeneous models of governance. Our aim is to investigate how different AHC configurations are associated with research performance. The method we adopted follows two steps. First, we identify organizational configurations through cluster analysis of nine variables. Second, we correlate these configurations to bibliometric measures of research outputs. Findings show that AHCs, that are specialty-focused and not mainly involved in educational activities are more productive and have more research impact than fully integrated and affiliated AHCs. Those AHCs also share secondary contextual features.
Subject(s)
Academic Medical Centers , Organizations , HumansABSTRACT
OBJECTIVES: After exceptional research efforts, several vaccines were developed against SARS-CoV-2 which sustains the pandemic COVID-19. The Comirnaty vaccine showed high efficacy in clinical trials and was the first to be approved for its distribution to the general population. We evaluated the immune response induced by the first vaccine dose in different sex/age groups and subjects with or without naturally present anti-SARS-CoV-2 antibodies. METHODS: As part of an Italian multicenter project (Covidiagnostix), serum samples from 4,290 health-professionals were serologically tested the day of the first vaccination dose, and 21 days later, using two different instrumentations (Siemens-Healthineers and Roche). RESULTS: In total, 97% of samples showed the presence of specific antibodies 21 days after the vaccination dose; the percentage of non-responders increased with age in both genders. Remarkably, naturally seropositive individuals showed antibody persistence up to 11 months and an exceptionally higher vaccination response compared to subjects never infected by SARS-CoV-2. CONCLUSIONS: This study highlighted the importance of the serological test i) to identify naturally SARS-CoV-2 seropositive individuals and ii) to evaluate the antibody level elicited by the first vaccination dose. Both tests, highlighted differences in the immune response, when subjects were stratified by sex and age, and between naturally seropositive and seronegative subjects. The data obtained show how serological tests could play a crucial role in the triage of the population subjected to the vaccination campaign for COVID-19. The definition of suitable instrumentation-specific thresholds is needed to correctly follow eventually acquired post-vaccination immunity in the general population.
Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization Programs , Adult , Aged , Aged, 80 and over , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Female , Health Personnel , Humans , Immunity, Humoral , Immunoassay , Male , Middle Aged , SARS-CoV-2/isolation & purification , Young AdultABSTRACT
This study assesses the expression of all TNF-related apoptosis-inducing ligand (TRAIL) receptors in pancreatic ductal adenocarcinoma (PDAC) tumor tissue. We aimed to include TRAIL receptor expression as an inclusion parameter in a future clinical study using a TRAIL-based therapy approach for PDAC patients. Considering the emerging influence of PDAC desmoplastic stroma on the efficacy of anti-PDAC therapies, this analysis was extended to tumor stromal cells. Additionally, we performed PDAC stroma characterization. Our retrospective cohort study (N=50) included patients with histologically confirmed PDAC who underwent surgery. The expression of TRAIL receptors (DR4, DR5, DcR1, DcR2, and OPG) in tumor and stromal cells was evaluated by immunohistochemistry (IHC). The amount of tumor stroma was assessed by anti-vimentin IHC and Mallory's trichrome staining. The prognostic impact was determined by the univariate Cox proportional hazards regression model. An extensive expression of functional receptors DR4 and DR5 and a variable expression of decoy receptors were detected in PDAC tumor and stromal cells. Functional receptors were detected also in metastatic tumor and stromal cells. A poor prognosis was associated with low or absent expression of decoy receptors in tumor cells of primary PDAC. After assessing that almost 80% of tumor mass was composed of stroma, we correlated a cellular-dense stroma in primary PDAC with reduced relapse-free survival. We demonstrated that TRAIL functional receptors are widely expressed in PDAC, representing a promising target for TRAIL-based therapies. Further, we demonstrated that a low expression of DcR1 and the absence of OPG in tumor cells, as well as a cellular-dense tumor stroma, could negatively impact the prognosis of PDAC patients.
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BACKGROUND: Nowadays there is an increasing use of transcranial magnetic stimulation (TMS) both in neurological and psychiatric fields. After Food and Drug Administration approval of TMS for the therapy of treatment-resistant depression, TMS has been widely used in the context of mood disorders (MD). However, growing reports regarding the possibility of developing hypomanic/manic switch (HMS) have generated concern regarding its use in MDs. AIM: To investigate the actual risk of developing HMS due to TMS in the treatment of MD. METHODS: We led our research on PubMed, Scopus and Web of Science on March 22, 2020, in accordance to the PRISMA guidelines for systematic review. Only double blind/single blind studies, written in English and focused on the TMS treatment of MD, were included. A meta-analysis of repetitive TMS protocol studies including HMS was conducted using RevMan 5.4 software. The assessment of Risk of Bias was done using Cochrane risk of bias tool. This protocol was registered on PROSPERO with the CRD42020175811 code. RESULTS: Twenty-five studies were included in our meta-analysis: Twenty-one double blind randomized controlled trials (RCT) and four single blind-RCT (no. of subjects involved in active stimulation = 576; no. of subjects involved in sham protocol = 487). The most frequently treated pathology was major depressive episode/major depressive disorder, followed by resistant depression, bipolar depression and other MD. The majority of the studies used a repetitive TMS protocol, and the left dorsolateral prefrontal cortex was the main target area. Side effects were reported in eight studies and HMS (described as greater energy, insomnia, irritability, anxiety, suicidal attempt) in four studies. When comparing active TMS vs sham treatment, the risk of developing HMS was not significantly different between conditions. CONCLUSION: Applying the most usual protocols and the appropriate precautionary measures, TMS seems not to be related to HMS development.
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Epilepsy is a rare clinical manifestation in Williams-Beuren syndrome patients. However, some studies report the presence of infantile spasms and epilepsy in patients carrying larger deletions. Herein, we describe a 13-year-old female affected by Williams-Beuren syndrome and pharmacoresistant epilepsy reporting a de novo large heterozygous 7q11.21q21 deletion (19.4 Mb) also including the YWHAG gene. Studies indicate that cannabidiol is effective as adjunctive therapy for seizures associated with tuberous sclerosis complex, and it is under investigation also in focal cortical dysplasia. When treated with cannabidiol, our patient showed a significant reduction in seizure frequency and intensity, and improved motor and social skills. We hypothesized that CBD could exert a gene/disease-specific effect.
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Vaccination is a key protective factor against COVID-19. Some vaccines have already received emergency authorization from Health Agencies, but growing skepticism and vaccine hesitancy will probably affect COVID-19 vaccination campaigns. In the attempt to shed light on this issue, we conducted an online survey in a population of parents referring to 4 pediatric practices in Naples, Italy in whom we evaluated potential vaccine acceptability in relation to socio-demographic characteristics, perception of personal health and of the impact of COVID-19, and attitudes toward general vaccination practices. Vaccination rates were analyzed also in the corresponding pediatric population.Almost 27% of participants declared they were in favor of vaccinations, and in fact real life vaccination rates in children exceeded the national mean. Only 26.5% of respondents declared they would receive COVID-19 vaccine. Vaccine refusal was attributed to safety concerns in 76% of parents. Specific vaccine attributes further reduced the acceptance rate. Female gender, younger age and lower education level were associated with non-adherence to vaccination. Among extrinsic factors of COVID-19 vaccination, only information from National Health Authorities was significantly associated to vaccine acceptance.The rate of potential COVID-19 vaccine acceptability was very poor in our population of parents. Vaccine hesitancy was mainly due to safety concerns. Demographic and educational factors were correlated to vaccine acceptability. Health education and communication strategies are needed to achieve large-scale vaccine acceptability and finally herd immunity.
Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Child , Cross-Sectional Studies , Female , Humans , SARS-CoV-2 , Surveys and Questionnaires , VaccinationSubject(s)
Electroconvulsive Therapy , Transcranial Direct Current Stimulation , Anxiety , Craving , Depression , OpiumABSTRACT
INTRODUCTION: Anhedonia is a transdiagnostic psychopathological dimension, consisting in the impaired ability to experience pleasure. In order to further our understanding of its neural correlates and to explore its potential relevance as a predictor of treatment response, in this article we systematically reviewed studies involving anhedonia and neuromodulation interventions, across different disorders. METHODS: We included seven studies fulfilling inclusion/exclusion criteria and involving different measures of anticipatory and consummatory anhedonia, as well as different noninvasive brain stimulation interventions (transcranial magnetic stimulation and transcranial direct current stimulation). Studies not exploring hedonic measures or not involving neuromodulation intervention were excluded. RESULTS: All the included studies entailed the use of rTMS protocols in one of the diverse prefrontal targets. The limited amount of studies and the heterogeneity of stimulation protocols did not allow to draw any conclusion with regard to the efficacy of rTMS in the treatment of transnosographic anhedonia. A potential for anhedonia in dissecting possible endophenotypes of different psychopathological conditions preliminarily emerged. CONCLUSIONS: Anhedonia is an underexplored condition in neuromodulation trials. It may represent a valuable transdiagnostic dimension that requires further examination in order to discover new clinical predictors for treatment response.
Subject(s)
Anhedonia/physiology , Brain/physiology , Mental Disorders/therapy , Reward , Transcranial Direct Current Stimulation/trends , Transcranial Magnetic Stimulation/trends , Animals , Clinical Trials as Topic/methods , Endophenotypes , Humans , Mental Disorders/diagnosis , Mental Disorders/psychology , Transcranial Direct Current Stimulation/methods , Transcranial Magnetic Stimulation/methodsABSTRACT
OBJECTIVES: The use of transcranial direct current stimulation (tDCS) in addiction disorders is still on its rise in comparison with pharmacological and psychotherapeutic strategies that still show low level of evidence. In this study, we aimed to evaluate the efficacy of the anodic tDCS for the short-term treatment of substance craving and other psychiatric symptoms. METHODS: In this randomized, double-blind, sham-controlled trial, inclusion criteria included the diagnosis of substance use disorder and/or gambling disorder. The protocol includes 5 consecutive days of active or sham tDCS session. Cathode was placed over the left dorsolateral prefrontal cortex. Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Barratt Impulsiveness Scale, South Oaks Gambling Screen, and visual analog scale (VAS) 1 to 10 for craving were administered at the baseline (T0) and after 5 days of treatment (T1). RESULTS: Thirty-four treatment-seeking subjects were randomized to sham (n = 16) and active stimulation (n = 18) groups. A statistically significant reduction of values at T1 was found in all subjects considering VAS (P < 0.001), Hamilton Depression Rating Scale (P < 0.001), Hamilton Anxiety Rating Scale (P < 0.001), and Barratt Impulsiveness Scale 11 (P = 0.032). A significant reduction for VAS craving in favor of the active stimulation (P = 0.011) was found. CONCLUSIONS: Our findings reveal a statistically significant rapid reduction of craving in the active tDCS group on the right dorsolateral prefrontal cortex with respect to sham group, confirming the scientific literature trend. Large samples, with maintenance tDCS therapy and long-term follow-up, are required to establish the potential of this noninvasive and easily delivered brain stimulation strategy.
Subject(s)
Craving , Substance-Related Disorders/psychology , Substance-Related Disorders/therapy , Transcranial Direct Current Stimulation/methods , Adult , Double-Blind Method , Female , Gambling/psychology , Gambling/therapy , Humans , Male , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Treatment OutcomeABSTRACT
OBJECTIVES: Bipolar disorder (BD) patients with a comorbid substance use disorder (SUD) are notoriously difficult to treat. Atypical antipsychotics (AAPs) are widely prescribed in BD, but their efficacy in patients with comorbid SUD is still debated. The aim of the present article is to systematically review the literature findings on the efficacy and safety of AAPs in BD patients with comorbid SUD. METHODS: We searched PubMed to identify original studies focused on the treatment of dual diagnosed BD with AAPs. RESULTS: Ten articles met our inclusion/exclusion criteria, involving a total of 969 subjects, 906 affected by BD and 793 with comorbid SUD: 4 were randomized controlled trials, 4 were open label trials and 2 were observational studies, published between 2002 and 2017. The most commonly abused substances were alcohol and cocaine. The AAPs used to treat patients were quetiapine (n = 337), asenapine (n = 119), olanzapine (n = 80), risperidone (n = 62), and aripiprazole (n = 48). In terms of safety, AAPs were usually well tolerated. Atypical antipsychotics were usually efficacious on acute mood symptoms, whereas their impact on substance-related issues was reported only in those studies without a placebo comparison. CONCLUSIONS: According to our results, even though AAPs are widely used and efficacious in treating the clinical symptoms of BD, there are not enough data to suggest their adjunctive benefit on craving and substance consumption.
Subject(s)
Antipsychotic Agents/therapeutic use , Bipolar Disorder/complications , Bipolar Disorder/drug therapy , Substance-Related Disorders/complications , Antipsychotic Agents/adverse effects , Comorbidity , Humans , Observational Studies as Topic , Prospective Studies , Randomized Controlled Trials as Topic , Retrospective Studies , Treatment OutcomeABSTRACT
Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, but it can arise in anyone, even after a single exposure to triggering drugs. The aims of the present study are to review all the original studies about HPPD in order to evaluate the following: (1) the possible suggested etiologies; (2) the possible hallucinogens involved in HPPD induction; (3) the clinical features of both HPPD I and II; (4) the possible psychiatric comorbidities; and (5) the available and potential therapeutic strategies. We searched PubMed to identify original studies about psychedelics and Hallucinogen Persisting Perception Disorder (HPPD). Our research yielded a total of 45 papers, which have been analyzed and tabled to provide readers with the most updated and comprehensive literature review about the clinical features and treatment options for HPPD.
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Several evidences support the hypothesis that glutamatergic dysfunction may be implicated in the pathogenesis of schizophrenia and in the last few years great interest has been focused on the role of the N-methyl-D-aspartate receptor (NMDAR). Glutamate is the main excitatory neurotransmitter in human CNS and it plays a prominent role in synaptic plasticity, learning, and memory and other cognitive functions. Increasing interest in memantine add-on therapy in schizophrenic patients with negative and cognitive symptoms may suggest that memantine could be a new promising treatment in schizophrenia. The aim of this update was to evaluate clinical data about the memantine effectiveness in schizophrenic patients. Our systematic review of the literature highlights that memantine therapy in schizophrenic patients seems to improve mainly negative symptoms while positive symptoms and cognitive symptoms did not improve significantly.
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Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene and is one of the most common human autosomal dominant disorders. The patient shows different signs on the skin and other organs from early childhood. The best known are six or more café au lait spots, axillary or inguinal freckling, increased risk of developing benign nerve sheath tumours and plexiform neurofibromas. Mutation detection is complex, due to the large gene size, the large variety of mutations and the presence of pseudogenes. Using Ion Torrent PGM™ Platform, 73 mutations were identified in 79 NF1 Italian patients, 51% of which turned out to be novel mutations. Pathogenic status of each variant was classified using "American College of Medical Genetics and Genomics" guidelines criteria, thus enabling the classification of 96% of the variants identified as being pathogenic. The use of Next Generation Sequencing has proven to be effective as for costs, and time for analysis, and it allowed us to identify a patient with NF1 mosaicism. Furthermore, we designed a new approach aimed to quantify the mosaicism percentage using electropherogram of capillary electrophoresis performed on Sanger method.
Subject(s)
Cafe-au-Lait Spots/genetics , Neurofibromatosis 1/genetics , Neurofibromin 1/genetics , Skin Abnormalities/genetics , Adolescent , Adult , Cafe-au-Lait Spots/pathology , Child , Child, Preschool , DNA Mutational Analysis , Female , Humans , Infant , Italy , Male , Middle Aged , Mosaicism , Mutation , Neurofibromatosis 1/pathology , Sequence Analysis, DNA , Skin Abnormalities/pathologyABSTRACT
BACKGROUND: Treatment-resistant schizophrenia (TRS) is a condition characterized by intense symptom severity and poor response to different antipsychotic agents. The first therapeutic option in TRS is clozapine, but often high/medium doses are not tolerated. Adding an oral antipsychotic to low doses of clozapine is a promising strategy in the management of TRS. On the contrary, there are few data on combined clozapine/long-acting injectable (LAI) medications, and none on clozapine/LAI-aripiprazole. CASE: A 21-year-old male schizophrenic patient, resistant to several oral and LAI medications, partially improved after clozapine 300 mg/d treatment. Unfortunately, he also reported excessive sedation and an episode of myoclonus, so clozapine was reduced to 150 mg/d, but no additional benefits were observed. Subsequently, LAI-aripiprazole (first 200 mg/mo, then 400 mg/mo) was added, and the patient's conditions dramatically improved over time. After 1 year of observation, symptoms reduction was 50% or greater, without significant adverse events. CONCLUSIONS: Clozapine use in TRS is often reduced or delayed due to the fear of serious adverse effects. Adding LAI-aripiprazole to low doses of clozapine may be a useful therapeutic option to obtain a good efficacy/tolerability balance.
Subject(s)
Aripiprazole/therapeutic use , Clozapine/therapeutic use , Schizophrenia/drug therapy , Drug Administration Schedule , Drug Therapy, Combination , Humans , Male , Young AdultABSTRACT
BACKGROUND: Alopecia has been shown to have a significant impact on quality of life (QoL), particularly in women. However, there are no data for African populations. This study was conducted to pilot an original questionnaire and a model-based methodology to measure QoL and its determinants in a sample of South African Black women of African ancestry with alopecia. METHODS: Fifty participants aged 21-79 years were randomly chosen from patients presenting to dermatologists with alopecia. We used an original questionnaire consisting of 24 items grouped into those assessing the respective impacts of subjective symptoms, objective signs, and relationship issues, measured on a four-level scale. These were then combined using component-based structural equation modeling to return a QoL index (QLI) and to rank the factors contributing to this. RESULTS: On a scale ranging from 0 (high QoL) to 100 (severely decreased QoL), we found a mean QLI of 67.7. The negative impact of alopecia on QoL was higher in younger patients than older patients. The factors with the highest impact were those relating to the subjective experience of alopecia and self-image (56.3%), followed by those relevant to relationships and interaction with other people (34.8%). The presence of objective symptoms and signs such as pruritus was of minor importance (8.9%). CONCLUSIONS: Although not a life-threatening condition, alopecia may seriously impair QoL, particularly by inducing anxiety and reducing self-esteem among African women. Healthcare practitioners should be mindful of this and intervene appropriately to mitigate these effects.
Subject(s)
Alopecia/ethnology , Alopecia/psychology , Quality of Life , Self Concept , Surveys and Questionnaires , Adult , Aged , Alopecia/diagnosis , Anxiety/ethnology , Anxiety/physiopathology , Cross-Sectional Studies , Female , Humans , Interpersonal Relations , Middle Aged , Pilot Projects , Retrospective Studies , Risk Assessment , Severity of Illness Index , South Africa , Urban Population , Young AdultABSTRACT
RATIONALE: Salvinorin A is a recreational drug derived from Salvia divinorum, a sage species long used as an entheogen. While salvinorin A has potent hallucinogenic properties, its abuse potential has not been assessed consistently in controlled behavioural and neurochemical studies in rodents. OBJECTIVE: This study aimed to assess salvinorin A abuse potential by measuring its capacity to establish and maintain self-administration behaviour and to modify dopamine (DA) levels in the nucleus accumbens (NAcc) of rats. RESULTS: Male Lister Hooded (LH) and Sprague-Dawley (SD) rats were allowed to self-administer salvinorin A (0.5 or 1.0 µg/kg/infusion) intravenously 2 h/day for 20 days under a continuous schedule of reinforcement and lever pressing as operandum. LH rats discriminated between the active and inactive levers but did not reach the acquisition criterion for stable self-administration (≥12 active responses vs ≤5 inactive responses for at least 5 consecutive days). SD rats discriminated between the two levers at the lower dose only but, like LH rats, never acquired stable self-administration behaviour. Systemic salvinorin A increased extracellular DA in the NAcc shell of both LH (at ≥40 µg/kg) and SD rats (at ≥5 µg/kg), but injection into the ventral tegmental area (VTA) induced no significant change in NAcc DA concentration in LH rats and only brief elevations in SD rats. CONCLUSIONS: Salvinorin A differs from other commonly abused compounds since although it affects accumbal dopamine transmission, yet it is unable, at least at the tested doses, to sustain stable intravenous self-administration behaviour.
Subject(s)
Brain Chemistry/drug effects , Diterpenes, Clerodane/administration & dosage , Motor Activity/drug effects , Reinforcement, Psychology , Salvia , Substance-Related Disorders/metabolism , Animals , Brain Chemistry/physiology , Dopamine/metabolism , Male , Motor Activity/physiology , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Rats , Rats, Sprague-Dawley , Self Administration , Substance-Related Disorders/psychology , Ventral Tegmental Area/drug effects , Ventral Tegmental Area/metabolismABSTRACT
To provide a systematic review of scientific literature on functional magnetic resonance imaging (fMRI) studies on sustained attention in psychosis. We searched PubMed to identify fMRI studies pertaining sustained attention in both affective and non-affective psychosis. Only studies conducted on adult patients using a sustained attention task during fMRI scanning were included in the final review. The search was conducted on September 10(th), 2013. 15 fMRI studies met our inclusion criteria: 12 studies were focused on Schizophrenia and 3 on Bipolar Disorder Typeâ Iâ (BDI). Only half of the Schizophrenia studies and two of the BDI studies reported behavioral abnormalities, but all of them evidenced significant functional differences in brain regions related to the sustained attention system. Altered functioning of the insula was found in both Schizophrenia and BDI, and therefore proposed as a candidate trait marker for psychosis in general. On the other hand, other brain regions were differently impaired in affective and non-affective psychosis: alterations of cingulate cortex and thalamus seemed to be more common in Schizophrenia and amygdala dysfunctions in BDI. Neural correlates of sustained attention seem to be of great interest in the study of psychosis, highlighting differences and similarities between Schizophrenia and BDI.