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1.
Personal Neurosci ; 6: e4, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107780

RESUMO

The aim of this study was to better understand the relation of schizotypy traits with sensory gating ability in a sample of community-dwelling individuals with high and low schizotypy traits. Sensory gating was assessed through the paired click paradigm and mid-latency evoked responses (i.e., P50, N100, P200), while schizotypy traits were assessed through the SPQ-BR which was used to classify participants into "high" and "low" schizotypy groups. Based on prior work, we hypothesized that those with the highest schizotypy scores would have reduced sensory gating ability. While this study does not show differences between relatively low and high schizotypy groups on sensory gating ability, it does suggest that our participants may have been experiencing deficits in attention allocation, a downstream cognitive processing measure. Scores on the SPQ-BR suggest that our sample was not close to the high end of the schizotypy traits which may help explain why no differences were found. This research shows the importance of including all levels of schizotypy ratings in clinical research as we can gain a clearer view of the impact of schizotypy on the brain and cognitive functioning in those with "high" levels of schizotypy. Additionally, this work highlights the importance of including measures of important factors such as impulsivity and sensation-seeking to better understand what aspects of schizotypy may be driving these sensory gating alterations reported in the literature.

2.
Front Cell Infect Microbiol ; 13: 1202245, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37404720

RESUMO

The ability to genetically manipulate a pathogen is fundamental to discovering factors governing host-pathogen interactions at the molecular level and is critical for devising treatment and prevention strategies. While the genetic "toolbox" for many important bacterial pathogens is extensive, approaches for modifying obligate intracellular bacterial pathogens were classically limited due in part to the uniqueness of their obligatory lifestyles. Many researchers have confronted these challenges over the past two and a half decades leading to the development of multiple approaches to construct plasmid-bearing recombinant strains and chromosomal gene inactivation and deletion mutants, along with gene-silencing methods enabling the study of essential genes. This review will highlight seminal genetic achievements and recent developments (past 5 years) for Anaplasma spp., Rickettsia spp., Chlamydia spp., and Coxiella burnetii including progress being made for the still intractable Orientia tsutsugamushi. Alongside commentary of the strengths and weaknesses of the various approaches, future research directions will be discussed to include methods for C. burnetii that should have utility in the other obligate intracellular bacteria. Collectively, the future appears bright for unraveling the molecular pathogenic mechanisms of these significant pathogens.


Assuntos
Chlamydia , Coxiella burnetii , Rickettsia , Humanos , Rickettsia/genética , Coxiella burnetii/genética , Chlamydia/genética , Interações Hospedeiro-Patógeno/genética , Anaplasma/genética
3.
Psychiatry Res Neuroimaging ; 333: 111661, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37331318

RESUMO

Given the association between major depressive disorder (MDD) and cortical inefficiency related to executive control, specifically in the sense that individuals with MDD may recruit more cognitive resources to complete tasks at the same capacity as those without MDD, the current study was interested in examining the attention networks and executive functioning of those with MDD. Past research has used the Attention Network Test (ANT) to measure changes of attention in clinical vs. healthy populations; however, theoretical concerns have been raised regarding the task. The Combined Attention Systems Task (CAST) was developed to address these concerns and was used in our study in combination with quantitative-electroencephalography (QEEG) to assess both behavioural and neurophysiological changes in participants with MDD (n = 18) compared to healthy controls (HCs; n = 22). We found no behavioural differences between MDD and HC groups suggesting individuals with MDD in our sample were not experiencing the executive functioning deficits previously reported in the literature. Neurophysiological measures of attention revealed that MDD participants had greater theta and alpha1 activity relative to HCs, suggesting that although individuals with MDD do not show deficits in behavioural attention, they exhibit altered neural processing which underlies cognitive function.


Assuntos
Transtorno Depressivo Maior , Humanos , Depressão , Função Executiva/fisiologia , Cognição , Eletroencefalografia
4.
J Bacteriol ; 205(5): e0009923, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37092988

RESUMO

The obligate intracellular human pathogen Chlamydia trachomatis (Ctr) undergoes a complex developmental cycle in which the bacterium differentiates between two functionally and morphologically distinct forms: the elementary body (EB) and the reticulate body (RB). The EB is the smaller, infectious, nondividing form which initiates infection of a susceptible host cell, whereas the RB is the larger, non-infectious form which replicates within a membrane-bound vesicle called an inclusion. The mechanism(s) which drives differentiation between these developmental forms is poorly understood. Bulk protein turnover is likely required for chlamydial differentiation given the significant differences in the protein repertoires and functions of the EB and RB. We hypothesize that periplasmic protein turnover is also critical for the reorganization of an RB into an EB, referred to as secondary differentiation. Ct441 is a periplasmic protease ortholog of tail-specific proteases (i.e., Tsp, Prc) and is expressed in Ctr during secondary differentiation. We investigated the effect of altering Tsp expression on developmental cycle progression. Through assessment of bacterial morphology and infectious progeny production, we found that both overexpression and CRISPR interference/dCas9 (CRISPRi)-mediated knockdown of Tsp negatively impacted chlamydial development through different mechanisms. We also confirmed that catalytic activity is required for the negative effect of overexpression and confirmed the effect of the mutation in in vitro assays. Electron microscopic assessments during knockdown experiments revealed a defect in EB morphology, directly linking Tsp function to secondary differentiation. These data implicate Ct441/Tsp as a critical factor in secondary differentiation. IMPORTANCE The human pathogen Chlamydia trachomatis is the leading cause of preventable infectious blindness and bacterial sexually transmitted infections worldwide. This pathogen has a unique developmental cycle that alternates between distinct forms. However, the key processes of chlamydial development remain obscure. Uncovering the mechanisms of differentiation between its metabolically and functionally distinct developmental forms may foster the discovery of novel Chlamydia-specific therapeutics and limit development of resistant bacterial populations derived from the clinical use of broad-spectrum antibiotics. In this study, we investigate chlamydial tail-specific protease (Tsp) and its function in chlamydial growth and development. Our work implicates Tsp as essential to chlamydial developmental cycle progression and indicates that Tsp is a potential drug target for Chlamydia infections.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Humanos , Chlamydia trachomatis/metabolismo , Endopeptidases/metabolismo , Antibacterianos/farmacologia , Proteólise , Proteínas de Bactérias/metabolismo
5.
Biol Psychol ; 180: 108570, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37116608

RESUMO

BACKGROUND: MMN and P3a are EEG-derived event related potentials that are thought to be prospective biomarkers for schizophrenia and, potentially, early-phase psychosis (EPP). METHODS: EPP (n = 12) and healthy control (HC; n = 35) participants listened to a multi-feature optimal paradigm with five deviant types (gap, duration, location, intensity, and frequency). RESULTS: There was a significant amplitude difference between the EPP and HC group with duration MMN (p = .02). No significant amplitude differences between groups were found for the P3a waveform. There were several correlations for the EPP group with the BNSS, SOFAS, and PANSS-general questionnaires. Length of illness was not associated with MMN or P3a. CONCLUSIONS: The optimal paradigm is suitable for eliciting multiple deviant types within a short amount of time in both clinical and healthy populations. This study confirms duration MMN deficits within an EPP group and that MMN is related to functional outcomes and positive and negative symptomology.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Estimulação Acústica , Eletroencefalografia , Potenciais Evocados , Potenciais Evocados Auditivos
6.
Exp Brain Res ; 241(5): 1319-1327, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37004533

RESUMO

Multiple sclerosis (MS) is one of the most common neurological diseases in North America and it is frequently associated with sensory processing difficulties, cognitive deficits, and psychiatric illness. While many studies have examined cognitive deficits in MS measured by behavioural responses and neuroimaging techniques, only a few studies have examined neurophysiological measures of auditory functioning in MS, such as the mismatch negativity (MMN). The MMN is an event-related potential that indicates automatic auditory change detection. This study examined whether MMN endpoints measured by electroencephalography (EEG) differ in individuals with relapsing-remitting MS compared to healthy controls and whether the symptomatology of MS, including symptoms of depression and fatigue, are related to MMN measures. A multi-feature MMN paradigm, which includes five distinct deviant tones, was used to assess auditory cortex function in MS. There were no significant differences in MMN amplitudes or latencies between the MS and control group (p < 0.05) and corresponding effect sizes were small. However, there was a correlation between reduced MMN amplitudes in response to an intensity deviant and physician-reported disability. The intensity MMN may be more sensitive to deterioration in this population. Ultimately, this study provides a comprehensive profile of early auditory processing abilities in MS and suggests that a reduction in the MMN response may be representative of disease severity in MS.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Estimulação Acústica/métodos , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Percepção Auditiva/fisiologia , Potenciais Evocados/fisiologia , Eletroencefalografia/métodos , Potenciais Evocados Auditivos/fisiologia
7.
mBio ; 14(2): e0007523, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-36975997

RESUMO

Bacterial AAA+ unfoldases are crucial for bacterial physiology by recognizing specific substrates and, typically, unfolding them for degradation by a proteolytic component. The caseinolytic protease (Clp) system is one example where a hexameric unfoldase (e.g., ClpC) interacts with the tetradecameric proteolytic core ClpP. Unfoldases can have both ClpP-dependent and ClpP-independent roles in protein homeostasis, development, virulence, and cell differentiation. ClpC is an unfoldase predominantly found in Gram-positive bacteria and mycobacteria. Intriguingly, the obligate intracellular Gram-negative pathogen Chlamydia, an organism with a highly reduced genome, also encodes a ClpC ortholog, implying an important function for ClpC in chlamydial physiology. Here, we used a combination of in vitro and cell culture approaches to gain insight into the function of chlamydial ClpC. ClpC exhibits intrinsic ATPase and chaperone activities, with a primary role for the Walker B motif in the first nucleotide binding domain (NBD1). Furthermore, ClpC binds ClpP1P2 complexes via ClpP2 to form the functional protease ClpCP2P1 in vitro, which degraded arginine-phosphorylated ß-casein. Cell culture experiments confirmed that higher order complexes of ClpC are present in chlamydial cells. Importantly, these data further revealed severe negative effects of both overexpression and depletion of ClpC in Chlamydia as revealed by a significant reduction in chlamydial growth. Here, again, NBD1 was critical for ClpC function. Hence, we provide the first mechanistic insight into the molecular and cellular function of chlamydial ClpC, which supports its essentiality in Chlamydia. ClpC is, therefore, a potential novel target for the development of antichlamydial agents. IMPORTANCE Chlamydia trachomatis is an obligate intracellular pathogen and the world's leading cause of preventable infectious blindness and bacterial sexually transmitted infections. Due to the high prevalence of chlamydial infections along with negative effects of current broad-spectrum treatment strategies, new antichlamydial agents with novel targets are desperately needed. In this context, bacterial Clp proteases have emerged as promising new antibiotic targets, since they often play central roles in bacterial physiology and, for some bacterial species, are even essential for survival. Here, we report on the chlamydial AAA+ unfoldase ClpC, its functional reconstitution and characterization, individually and as part of the ClpCP2P1 protease, and establish an essential role for ClpC in chlamydial growth and intracellular development, thereby identifying ClpC as a potential target for antichlamydial compounds.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Humanos , Chlamydia trachomatis/metabolismo , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Proteólise , Peptídeo Hidrolases/metabolismo , Biologia , Proteínas de Bactérias/metabolismo
8.
J Med Chem ; 66(3): 2116-2142, 2023 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-36696579

RESUMO

Chlamydia trachomatis (CT) causes the most prevalent sexually transmitted bacterial disease in the United States. The lack of drug selectivity is one of the main challenges of the current antichlamydial pharmacotherapy. The metabolic needs of CT are controlled, among others, by cylindrical proteases and their chaperones (e.g., ClpX). It has been shown that dihydrothiazepines can disrupt CT-ClpXP. Based on this precedent, we synthesized a dihydrothiazepine library and characterized its antichlamydial activity using a modified semi-high-throughput screening assay. Then, we demonstrated their ability to inhibit ClpX ATPase activity in vitro, supporting ClpX as a target. Further, our lead compound displayed a promising selectivity profile against CT, acceptable cytotoxicity, no mutagenic potential, and good in vitro stability. A two-dimensional quantitative structure-activity relationship (2D QSAR) model was generated as a support tool in the identification of more potent antichlamydial molecules. This study suggests dihydrothiazepines are a promising starting point for the development of new and selective antichlamydial drugs.


Assuntos
Chlamydia trachomatis , Peptídeo Hidrolases , Computadores
9.
J Biol Chem ; 299(1): 102762, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36463962

RESUMO

Chlamydia trachomatis (ct) is the most reported bacterial sexually transmitted infection worldwide and the leading cause of preventable blindness. Caseinolytic proteases (ClpP) from pathogenic bacteria are attractive antibiotic targets, particularly for bacterial species that form persister colonies with phenotypic resistance against common antibiotics. ClpP functions as a multisubunit proteolytic complex, and bacteria are eradicated when ClpP is disrupted. Although crucial for chlamydial development and the design of agents to treat chlamydia, the structures of ctClpP1 and ctClpP2 have yet to be solved. Here, we report the first crystal structure of full-length ClpP2 as an inactive homotetradecamer in a complex with a candidate antibiotic at 2.66 Å resolution. The structure details the functional domains of the ClpP2 protein subunit and includes the handle domain, which is integral to proteolytic activation. In addition, hydrogen-deuterium exchange mass spectroscopy probed the dynamics of ClpP2, and molecular modeling of ClpP1 predicted an assembly with ClpP2. By leveraging previous enzymatic experiments, we constructed a model of ClpP2 activation and its interaction with the protease subunits ClpP1 and ClpX. The structural information presented will be relevant for future rational drug design against these targets and will lead to a better understanding of ClpP complex formation and activation within this important human pathogen.


Assuntos
Chlamydia trachomatis , Endopeptidase Clp , Modelos Moleculares , Humanos , Antibacterianos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Chlamydia trachomatis/enzimologia , Endopeptidase Clp/química , Endopeptidase Clp/metabolismo , Cristalização , Domínios Proteicos
10.
Neuropsychobiology ; 81(6): 506-515, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36380625

RESUMO

INTRODUCTION: The present study compared the mismatch negativity (MMN) and P3a waveforms among early-phase psychosis (EPP; n = 13) individuals and healthy controls (n = 30) to contribute to the research on these waveforms as potential biomarkers for schizophrenia. METHODS: MMN and P3a were elicited with a novelty paradigm using complex stimuli with electrophysiological technology. RESULTS: No significant group differences of amplitude were observed with either waveform. Increased asociality and blunted affect were associated with a reduction in both MMN and P3a waveforms indicating a relationship between these negative symptoms and cognitive deficits. Good social and occupational functioning correlated with improved MMN and P3a waveforms in the EPP group. CONCLUSIONS: This study suggests that MMN and P3a may be more appropriately used as an indicator of illness progression and symptomology rather than a biomarker in the early phase of the illness.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Potenciais Evocados P300/fisiologia , Eletroencefalografia , Transtornos Psicóticos/psicologia , Esquizofrenia/diagnóstico , Transtornos do Humor , Potenciais Evocados Auditivos/fisiologia , Estimulação Acústica
11.
Pathog Dis ; 80(1)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36385643

RESUMO

The obligate intracellular bacterial pathogen Chlamydia trachomatis is a leading cause of sexually transmitted infections and infectious blindness. Chlamydia undergo a biphasic developmental cycle alternating between the infectious elementary body (EB) and the replicative reticulate body (RB). The molecular mechanisms governing RB growth and RB-EB differentiation are unclear. We hypothesize that the bacterium senses host cell and bacterial energy levels and metabolites to ensure that development and growth coincide with nutrient availability. We predict that a partner switching mechanism (PSM) plays a key role in the sensing and response process acting as a molecular throttle sensitive to metabolite levels. Using purified wild type and mutant PSM proteins, we discovered that metal type impacts enzyme activity and the substrate specificity of RsbU and that RsbW prefers ATP over GTP as a phosphate donor. Immunoblotting analysis of RsbV1/V2 demonstrated the presence of both proteins beyond 20 hours post infection and we observed that an RsbV1-null strain has a developmental delay and exhibits differential growth attenuation in response to glucose levels. Collectively, our data support that the PSM regulates growth in response to metabolites and further defines biochemical features governing PSM-component interactions which could help in the development of novel PSM-targeted therapeutics.

12.
mBio ; 13(5): e0185822, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36154190

RESUMO

Despite having a highly reduced genome, Chlamydia trachomatis undergoes a complex developmental cycle in which the bacteria differentiate between the following two functionally and morphologically distinct forms: the infectious, nonreplicative elementary body (EB) and the noninfectious, replicative reticulate body (RB). The transitions between EBs and RBs are not mediated by division events that redistribute intracellular proteins. Rather, both primary (EB to RB) and secondary (RB to EB) differentiation likely require bulk protein turnover. One system for targeted protein degradation is the trans-translation system for ribosomal rescue, where polypeptides stalled during translation are marked with an SsrA tag encoded by a hybrid tRNA-mRNA, tmRNA. ClpX recognizes the SsrA tag, leading to ClpXP-mediated degradation. We hypothesize that ClpX functions in chlamydial differentiation through targeted protein degradation. We found that mutation of a key residue (R230A) within the specific motif in ClpX associated with the recognition of SsrA-tagged substrates resulted in abrogated secondary differentiation while not reducing chlamydial replication or developmental cycle progression as measured by transcripts. Furthermore, inhibition of trans-translation through chemical and targeted genetic approaches also impeded chlamydial development. Knockdown of tmRNA and subsequent complementation with an allele mutated in the SsrA tag closely phenocopied the overexpression of ClpXR230A, thus suggesting that ClpX recognition of SsrA-tagged substrates plays a critical function in secondary differentiation. Taken together, these data provide mechanistic insight into the requirements for transitions between chlamydial developmental forms. IMPORTANCE Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections and preventable infectious blindness. This unique organism undergoes developmental transitions between infectious, nondividing forms and noninfectious, dividing forms. Therefore, the chlamydial developmental cycle is an attractive target for Chlamydia-specific antibiotics, which would minimize effects of broad-spectrum antibiotics on the spread of antibiotic resistance in other organisms. However, the lack of knowledge about chlamydial development on a molecular level impedes the identification of specific, druggable targets. This work describes a mechanism through which both the fundamental processes of trans-translation and proteomic turnover by ClpXP contribute to chlamydial differentiation, a critical facet of chlamydial growth and survival. Given the almost universal presence of trans-translation and ClpX in eubacteria, this mechanism may be conserved in developmental cycles of other bacterial species. Additionally, this study expands the fields of trans-translation and Clp proteases by emphasizing the functional diversity of these systems throughout bacterial evolution.


Assuntos
Chlamydia trachomatis , Proteômica , Chlamydia trachomatis/metabolismo , Endopeptidase Clp/genética , Endopeptidase Clp/metabolismo , Peptídeos/metabolismo , Antibacterianos/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Bactérias/metabolismo
13.
Psychopharmacology (Berl) ; 239(10): 3161-3170, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35904580

RESUMO

RATIONALE: Caffeine is the most consumed stimulant worldwide, and there is great interest in understanding its neurophysiological effects. Resting-state electroencephalography (EEG) studies suggest that caffeine enhances arousal, which suppresses the spectral power of alpha frequencies associated with reduced alertness. However, it is unclear whether caffeine's neurophysiological effects vary across the human menstrual cycle. OBJECTIVE: The objective of our study was to test whether caffeine's effect on EEG activity differs across the human menstrual cycle. METHODS: Fifty-six female participants were randomly assigned to complete the experiment while in either their menstrual (n = 21), follicular (n = 19), or luteal (n = 16) phase. Each participant completed two study sessions in the same menstrual phase, approximately 1 month apart, during which they were administered either a caffeine pill (200 mg, oral) or a placebo pill in a counterbalanced order using a randomized double-blinded procedure. We measured their eyes-closed resting-state EEG approximately 30 min after pill administration and conducted a spectral power analysis at different frequency bands. RESULTS: Caffeine reduced EEG power in the alpha1 frequency band (8-10 Hz), but only for participants who self-reported higher weekly caffeine consumption. Importantly, caffeine's effects did not differ by menstrual phase. CONCLUSIONS: We conclude that when studying caffeine's effects on resting-state EEG, participants' baseline caffeine consumption is more influential than their menstrual cycle phase. This study has important implications for the inclusion of menstruating individuals in neurophysiological studies of caffeine.


Assuntos
Cafeína , Estimulantes do Sistema Nervoso Central , Nível de Alerta , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Eletroencefalografia , Feminino , Humanos , Ciclo Menstrual/fisiologia
14.
Neurosci Lett ; 781: 136654, 2022 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-35469822

RESUMO

The mismatch negativity (MMN) and P3a waveforms are both markers of auditory change detection. MMN indicates deficits in performing auditory change-detection tasks, while the P3a reflects the evaluative and conscious aspect of orienting to the sound. Understanding the role biological sex has concerning these waveforms would provide insight into overall brain-based differences, but whether sex differences exist to such a degree that it can moderate the effect of auditory change detection is not certain. Thus, the purpose of this study was to examine potential sex differences in MMN and P3a elicited by a novelty paradigm in a healthy population. The results showed no significant differences between males and females. This study proves to be useful by adding to the limited literature on the topic and by providing a foundation of knowledge regarding sex differences in auditory change detection mechanisms within the population.


Assuntos
Eletroencefalografia , Esquizofrenia , Estimulação Acústica/métodos , Encéfalo , Eletroencefalografia/métodos , Potenciais Evocados Auditivos , Feminino , Humanos , Masculino , Esquizofrenia/diagnóstico , Caracteres Sexuais
15.
Clin EEG Neurosci ; 53(4): 335-343, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35257622

RESUMO

Individuals with schizophrenia use on average twice as much caffeine than the healthy population, but the underlying cortical effects of caffeine in this population are still not well understood. Using resting electroencephalography (EEG) data, we can determine recurrent configurations of the electric field potential over the cortex. These configurations, referred to as microstates, are reported to be altered in schizophrenia and can give us insight into the functional dynamics of large-scale brain networks. In the current study, we use a placebo-controlled, randomized, double-blind, repeated-measures design to examine the effects of a moderate dose of caffeine (200mg) on microstate classes A, B, C, and D in a sample of individuals within the first five years of psychosis onset compared to healthy controls. The results support the reduction of microstate class C and D, as well as the increase of microstate class A and B in schizophrenia. Further, acute caffeine administration appears to exacerbate these group differences by reducing class D, and increasing occurrences of class A and B states in the patient group only. The current results support the hypothesis of a microstate class D reduction as an endophenotypic marker for psychosis and provide the first descriptive account of how caffeine is affecting these microstate classes in an early phase psychosis sample.


Assuntos
Eletroencefalografia , Transtornos Psicóticos , Encéfalo , Mapeamento Encefálico/métodos , Cafeína , Eletroencefalografia/métodos , Humanos
16.
Brain Neurosci Adv ; 6: 23982128211073431, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35097219

RESUMO

Cannabis has been shown to cause structural and functional neurocognitive changes in heavy users. Cannabis use initiation aligns with brain development trajectories; therefore, it is imperative that the potential neurological implications of cannabis use are understood. Males and females reach neurodevelopmental milestones at different rates making it necessary to consider biological sex in all cannabis and brain-based research. Through use of a systamatic review in accordance with PRISMA guidelines, we aimed to understand the interaction between biological sex and cannabis use on brain-based markers. In total, 18 articles containing a sex-based analysis of cannabis users were identified. While the majority of studies (n = 11) reported no sex by cannabis use interactions on brain-based markers, those that reported findings (n = 8) suggest females may be more susceptible to cannabis' neurotoxic effects. Unfortunately, a large portion of the literature was excluded due to no sex-based analysis. In addition, studies that reported no sex differences often contained a reduced number of females which may result in some studies being underpowered for sex-based analyses, making it difficult to draw firm conclusions. Suggestions to improve cannabis and sex-based reseach are proposed.

18.
Psychopharmacology (Berl) ; 239(5): 1279-1288, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33932162

RESUMO

OBJECTIVES: Long-term cannabis use has been associated with the appearance of psychotic symptoms and schizophrenia-like cognitive impairments; however these studies may be confounded by concomitant use of tobacco by cannabis users. We aimed to determine if previously observed cannabis-associated deficits in sensory gating would be seen in cannabis users with no history of tobacco use, as evidenced by changes in the P50, N100, and P200 event-related potentials. A secondary objective of this study was to examine the effects of acute nicotine administration on cannabis users with no tobacco use history. METHODS: Three components (P50, N100, P200) of the mid-latency auditory-evoked response (MLAER) were elicited by a paired-stimulus paradigm in 43 healthy, non-tobacco smoking male volunteers between the ages of 18-30. Cannabis users (CU, n = 20) were administered nicotine (6 mg) and placebo gum within a randomized, double-blind design. Non-cannabis users (NU, n = 23) did not receive nicotine. RESULTS: Between-group sensory gating effects were only observed for the N100, with CUs exhibiting a smaller N100 to S1 of the paired stimulus paradigm, in addition to reduced dN100 (indicating poorer gating). Results revealed no significant sensory gating differences with acute administration of nicotine compared to placebo cannabis conditions. CONCLUSIONS: These findings suggest a relationship between gating impairment and cannabis use; however, acute nicotine administration nicotine does not appear to impact sensory gating function.


Assuntos
Cannabis , Alucinógenos , Estimulação Acústica/métodos , Adolescente , Adulto , Agonistas de Receptores de Canabinoides/farmacologia , Eletroencefalografia , Potenciais Evocados Auditivos , Alucinógenos/farmacologia , Humanos , Masculino , Nicotina/efeitos adversos , Filtro Sensorial , Nicotiana , Adulto Jovem
19.
Clin EEG Neurosci ; 53(4): 326-334, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34806929

RESUMO

Individuals with schizophrenia use twice as much caffeine on average when compared to healthy controls. Knowing the high rates of consumption, and the potential negative effects of such, it is important we understand the cortical mechanisms that underlie caffeine use, and the consequences of caffeine use on neural circuits in this population. Using a randomized, placebo controlled, double-blind, repeated measures design, the current study examines caffeine's effects on resting electroencephalography (EEG) power in those who have been recently diagnosed with schizophrenia (SZ) compared to regular-using healthy controls (HC). Correlations between average caffeine consumption, withdrawal symptoms, drug related symptoms and clinical psychosis symptoms were measured and significant correlations with neurophysiological data were examined. Results showed caffeine had no effect on alpha asymmetry in the SZ group, although caffeine produced a more global effect on the reduction of alpha2 power in the SZ group. Further, those with more positive symptoms were found to have a greater reduction in alpha2 power following caffeine administration. Caffeine also reduced beta power during eyes closed and eyes open resting in HC, but only during eyes closed resting conditions in the SZ group. These findings provide a descriptive profile of the resting EEG state following caffeine administration in individuals with schizophrenia. The findings ultimately suggest caffeine does not affect alpha or beta power as readily in this population and a higher dose may be needed to achieve the desired effects, which may elucidate motivational factors for high caffeine use.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Cafeína/farmacologia , Cafeína/uso terapêutico , Eletroencefalografia , Humanos , Descanso/fisiologia , Esquizofrenia/tratamento farmacológico
20.
Clin EEG Neurosci ; 52(3): 159-167, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33074718

RESUMO

Auditory hallucinations (AHs) are a common symptom of schizophrenia and contribute significantly to disease burden. Research on schizophrenia and AHs is limited and fails to adequately address the effect of AHs on resting EEG in patients with schizophrenia. This study assessed changes in frequency bands (delta, theta, alpha, beta) of resting EEG taken from hallucinating patients (n = 12), nonhallucinating patients (n = 11), and healthy controls (n = 12). Delta and theta activity were unaffected by AHs but differed between patients with schizophrenia and healthy controls. Alpha activity was affected by AHs: nonhallucinators had more alpha activity than hallucinators and healthy controls. Additionally, beta activity was inversely related to trait measures of AHs. These findings contribute to the literature of resting eyes closed EEG recordings of schizophrenia and AHs, and indicate the role of delta, theta, alpha, and beta as markers for schizophrenia and auditory hallucinations.


Assuntos
Esquizofrenia , Eletroencefalografia , Alucinações , Humanos , Descanso
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