1,721,031 research outputs found
Current and potential pharmacological and psychosocial interventions for anxiety symptoms and disorders in patients with schizophrenia: structured review
No full textCapacity for cortical excitation is reduced in psychotic disorders:: an investigation of the TMS-EMG cortical silent period
No full textA Role for glutamate and Gaba in attention-deficit/hyperactivity disorder: a study of the spontaneously hypertensive rat
No full textIncludes bibliographical references.Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous, developmental disorder characterised by behavioural symptoms of inattention, hyperactivity, and impulsivity. The present thesis investigated how the main excitatory and inhibitory neurotransmitters in the brain, glutamate and GABA respectively, play a role in the dysregulation of the norepinephrine system in a rat model of ADHD, the spontaneously hypertensive rat (SHR), compared to its control strain, the Wistar-Kyoto rat (WKY), and a third comparator strain, Sprague-Dawley rats (SD). Release of radio-actively labelled norepinephrine from hippocampal slices of SHR, WKY, and in some experiments SD, by glutamate, GABA, potassium, and nicotine, were measured, and the involvement of glutamate and GABA receptors and transporters in the stimulated release of hippocampal norepinephrine were investigated, using an in vitro superfusion technique. Since early life stress has been shown to increase the risk of developing ADHD, the present thesis also investigated how a model of early life stress (maternal separation) affects behavioural responses to novelty (behavioural assays), plasma corticosterone (ELISA kit), and neurochemical regulation of hippocampal norepinephrine release by glutamate and GABA (in vitro superfusion) in SHR, as well as in control strains. Effects of early life stress on hippocampal protein profile of SHR, WKY and SD were also investigated using proteomic analysis, followed by Western blot analysis to confirm main proteomic findings related to the glutamate transporter GLT-1, and the potassium-chloride co-transporter KCC2. The main findings of the present thesis were that glutamate-stimulated release of norepinephrine was elevated in SHR hippocampus compared to WKY and SD, and was via glutamate AMPA receptors. Elevating tonic levels of GABA in WKY and SD hippocampi increased glutamate-stimulated release of hippocampal norepinephrine to be equivalent to that of SHR, while elevating tonic levels of glutamate in SHR hippocampus reduced glutamate-stimulated release of hippocampal norepinephrine to be equivalent to that of control strains, suggesting that GABA tonic levels are reduced while glutamate tonic levels are elevated in SHR hippocampus in vivo compared to control strains. GABAA receptor inhibition of norepinephrine release, and GABA evoked release of norepinephrine, was reduced in SHR hippocampus compared to WKY. Nicotine stimulated release of norepinephrine was reduced in SHR, compared to WKY and SD, and lacked a GABAA receptor component that was evident in WKY hippocampus. Proteomic analysis showed that the expression of the glutamate transporter GLT1b splice variant and KCC2 was increased in SHR hippocampus compared to WKY, while GLT1 total was reduced in SHR hippocampus compared to WKY and SD. Experiencing early life stress did not influence behaviour of SHR, and had limited effect on the behaviour of WKY, suggesting that SHR may be resilient to the long -term behavioural effects of early life stress. Early life stress did, however, increase NMDA receptor- and GABAA receptor-mediated inhibition of locus coeruleus-norepinephrine varicosities in SHR hippocampus, while reducing the role of these receptors in WKY hippocampus. Early life stress increased GLT1 expression in all 3 strains and reduced the GLT1b splice variant in SHR hippocampus only. These neurochemical changes following early life stress possibly involved adaptations that prevented long-term changes in behaviours of these rats. In conclusion, the results of the present thesis provide evidence supporting a role for glutamate and GABA dysfunction in the hippocampus of an animal model of ADHD, SHR, and also provide evidence for altered glutamate and GABA neurotransmission in the hippocampus of SHR following early life stress
Investigating the Influence of Methamphetamine on brain metabolism using 1H-MRS
No full textMethamphetamine (MA) has been shown to have a detrimental relationship with on neuronal integrity and viability, and has been associated with decreased executive function. The association of acute and short-term MA abstinence on brain metabolism, in adult MA abusers, is understudied. Negative relationships with brain metabolism, cognitive development and executive functioning in prenatally MA exposed children are reported, however these studies are limited. The aim of this study was to investigate the relationship between MA and brain metabolism in adults after acute and short-term abstinence. An additional aim was to investigate neurometabolite changes and relationship with general cognitive ability over time in prenatally MA exposed children
Electroencephalographic delta/alpha frequency activity differentiates psychotic disorders: a study of schizophrenia, bipolar disorder, and methamphetamine-induced psychotic disorder
No full textElectroencephalography (EEG) has been proposed as a neurophysiological biomarker to delineate psychotic disorders. It is known that increased delta and decreased alpha, which are apparent in psychosis, are indicative of inappropriate arousal state, which leads to reduced ability to attend to relevant information. On this premise, we investigated delta/alpha frequency activity, as this ratio of frequency activity may serve as an effective neurophysiological biomarker. The current study investigated differences in delta/alpha frequency activity, in schizophrenia (SCZ), bipolar I disorder with psychotic features and methamphetamine-induced psychosis. One hundred and nine participants, including individuals with SCZ (n = 28), bipolar I disorder with psychotic features (n = 28), methamphetamine-induced psychotic disorder (MPD) (n = 24) and healthy controls (CON, n = 29). Diagnosis was ascertained with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition disorders and current medication was recorded. EEG was undertaken in three testing conditions: resting eyes open, resting eyes closed and during completion of a simple cognitive task (visual continuous performance task). EEG delta/alpha frequency activity was investigated across these conditions. First, delta/alpha frequency activity during resting eyes closed was higher in SCZ and MPD globally, when compared to CON, then lower for bipolar disorder (BPD) than MPD for right hemisphere. Second, delta/alpha frequency activity during resting eyes open was higher in SCZ, BPD and MPD for all electrodes, except left frontal, when compared to CON. Third, delta/alpha frequency activity during the cognitive task was higher in BPD and MPD for all electrodes, except left frontal, when compared to CON. Assessment of EEG delta/alpha frequency activity supports the delineation of underlying neurophysiological mechanisms present in psychotic disorders, which are likely related to dysfunctional thalamo-cortical connectivity. Delta/alpha frequency activity may provide a useful neurophysiological biomarker to delineate psychotic disorders
Modelling the pathophysiology of schizophrenia and methamphetamine-induced psychosis: A structural magnetic resonance imaging and cytokine study
Full text linkBackground: There is overlap in the symptomatology and psychobiology of schizophrenia (SCZ) and methamphetamine-induced psychosis (MAP). In schizophrenia there are reports of significant associations of increased severity of psychotic symptoms with thinner frontal cortex and decreased hippocampus and amygdala volume, and there is evidence of increased TNF-α and interleukin (IL)-1β concentrations compared to healthy controls. However, no studies to date have 1) compared structural findings in SCZ and MAP, 2) investigated the associations of psychotic symptom severity and duration with brain volumes and cytokine concentrations in SCZ and MAP and 3) determined the effect of antipsychotic type on brain measures in SCZ compared to MAP. Methods: 36 patients with SCZ, 27 with MAP, and 32 healthy controls underwent clinical interview, structural magnetic resonance imaging (MRI) and phlebotomy. Symptom severity was assessed with the positive and negative symptom scales (PANSS). Volumes of the amygdala, hippocampus and basal ganglia and frontal cortical thickness and surface area were processed with FreeSurfer. TNF-α, IL-1β, -8, -12 and IFN-γ concentrations in serum, were assessed with a Luminex assay. ANOVAs were used to compare structural findings across groups, group differences for cytokine concentrations, number of psychotic episodes, symptom severity and to determine the effect of antipsychotics (AP) type on structural brain volumes and frontal cortical thickness in SCZ and MAP. Spearman's Rank and Pearson's correlations were used to determine associations of symptom severity, number of psychotic episodes and duration of illness with structural brain measures and cytokine concentrations. Results: 1) Decreased left amygdala volumes were reported in SCZ and MAP compared to CON, 2) increased right caudate and bilateral putamen and NAcc (nucleus accumbens) volumes were reported in SCZ compared to MAP and CON , with increased right pallidus volumes in SCZ compared to MAP, 3) decreased frontal cortical thickness was reported in SCZ and MAP compared to CON, 4) decreased frontal cortical surface area of the right pars opercularis and left pars triangularis was reported in SCZ compared to CON, 5) duration of illness was negatively correlated to decreased left amygdala volumes and frontal cortical thickness and surface area in SCZ, 6) there was a significant association between longer MA duration of use with decreased hippocampal and amygdala volumes and decreased frontal cortical thickness and surface areas in MAP, 7) significant effects of AP type were reported for frontal cortical thickness, 8) cytokine concentrations did not differ significantly between CON, SCZ and MAP and 9) number of psychotic episodes were greater in SCZ compared to MAP. Conclusions: These findings are consistent with the presence of both overlaps (e.g., in amygdala volume and frontal cortical thickness) and differences (e.g., in basal ganglia volume,) in the neurobiology of SCZ and MAP. It is noteworthy that longer illness duration is associated with decreased left amygdala volumes and frontal cortical thickness in SCZ and not MAP, suggesting that illness duration does not impart gray matter volume decreases in MAP. In MAP, MA use duration has significant associations with decreased left amygdala volumes, frontal cortical thickness and surface area in MAP. Decreased left amygdala volumes and frontal cortical thickness in both disorders suggest neurobiological overlap across these conditions, which may signify clinical importance in treatment of these conditions. Future studies involving magnetic resonance spectroscopy and imaging on the brain regions investigated in this study are encouraged to provide a better understanding of neuronal damage, neuroinflammatory processes and brain deficits of regions of interest in MAP and SCZ
Locus-coeruleus norepinephrine system function in a developmental animal model of schizophrenia: the socially isolated rat
Full text linkIntroduction: Schizophrenia is a chronic, debilitating mental disorder characterised by positive, negative and cognitive symptoms. Current treatment regimens fail to adequately address the cognitive and negative symptoms of the disorder. Social isolation rearing (SIR) is a well-established developmental adversity paradigm which is used as an animal model of schizophrenia and usually studied in male rats. Previous SIR studies have found attentional abnormalities in isolated rats in behavioural tests which correspond to the results of studies investigating the cognitive symptoms of schizophrenia in patient trials. Isolated rats also display abnormal social responses which may be of relevance to the negative symptoms of schizophrenia. The primary aim of this study was to build on existing SIR literature by performing behavioural tests in socially isolated rats to address attentional function. Neurochemical investigations were performed on projections of the locus coeruleus norepinephrine system, known to be involved in attentional function, as research on this system is surprisingly sparse. The secondary aim of the study was to address the negative symptoms of schizophrenia using ultrasonic vocalisation recording to investigate the calling behaviour of isolated rats in response to a novel context. The study included both male and female rats so that sex differences could be studied in the context of social isolation. Methodology: Sprague-Dawley rats were weaned at postnatal day (p) 21 and randomly allocated to one of four housing groups; female socialised (n=50), female isolated (n=50), male socialised (n=38) and male isolated (n=38). Socialised animals were housed 4 per cage (single sex) and isolated animals were housed alone. Animals were weighed and cages cleaned weekly as part of a minimal handling protocol required for SIR. After 8 weeks in their housing conditions (p78-82) rats underwent one of two behavioural paradigms: three phase novel object recognition or ultrasonic vocalisation recordings. Between p90-94 animals were rapidly decapitated and the hippocampus and prefrontal cortex were dissected out for use in one of two neurochemical analyses. For in-vitro superfusion experiments the tissue was used immediately to quantify functional release of radioactively-labelled norepinephrine when stimulated with glutamate under varying conditions. Enzyme linked immunosorbent assays (ELISA) and bicinchoninic acid (BCA) protein assays was performed to quantify norepinephrine and glutamate concentrations expressed in relation to the wet weight of the tissue and amount of protein in the tissue. Results: Behavioural and neurochemical changes were induced by the SIR model. Isolated animals were found to respond to novel objects abnormally compared to control animals. During initial exposure to a novel environment in the first phase of the novel object recognition test isolated animals demonstrated hypoactivity. An overall reduction in the fractional release of norepinephrine when stimulated with combinations of glutamate and gamma-aminobutyric acid (GABA) was demonstrated in the hippocampus of isolated rats. Sex differences were evident in a number of experiments. Female rats were found to be hyperactive in the three phases of the novel object recognition test compared to males and also had elevated hippocampal norepinephrine activity as well as an increased concentration of norepinephrine in this area. Male rats on the other hand had an elevated prefrontal cortex norepinephrine activity and concentration. Conclusion: The SIR paradigm is able to induce behavioural and neurochemical changes in both female and male rats. The results of this study reinforce the usefulness of SIR as a model for schizophrenia as the way in which isolated animals responded to novel objects was different to their socialised counterparts. This difference implies an abnormal attentional response which corresponds to the cognitive symptoms described in schizophrenia. Furthermore, the neurochemical experiments performed in this study are the first of their kind and provide preliminary evidence for the GABAergic mechanisms underlying attentional abnormalities associated with SIR. The prevalence of sex differences throughout testing also provides strong evidence for the inclusion of both sexes in future studies to avoid the omission of potentially important findings. Future studies to refine and build on neurochemical analyses in developmental models of schizophrenia, such as SIR will potentially provide a mechanistic understanding of cognitive dysfunction as well as useful translational information for treating the human disorder
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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