1,721,257 research outputs found
Striatal presynaptic dopamine in schizophrenia, part i: Meta-analysis of dopamine active transporter (DAT) density
No full textBackground: Striatal dopaminergic neurotransmission has been postulated to be fundamental to the emergence of key symptoms of schizophrenia, such as psychotic symptoms, and is targeted by currently available dopaminergic drugs. A specific marker of the integrity of presynaptic dopamine neurons in the striatum, the density of striatal dopamine terminals, can be quantified through molecular neuroimaging of the dopamine active transporter (DAT). However, the currently available results using this approach in schizophrenia are inconsistent. Methods: Thirteen Single Photon Emission Tomography or Positron Emission Tomography (PET) studies investigating DAT density in the striatum of schizophrenic patients and matched controls were included in a quantitative meta-analysis. Binding potentials in the striatum, caudate, and putamen, as well as demographic, clinical, and methodological variables, were extracted from each publication. Hedges' g was used as a measure of effect size. Results: The overall database contained 202 subjects with schizophrenia and 147 controls, well matched with respect to sociodemographic variables. Striatal DAT density was not significantly different between patients and controls. Similar negative findings were regionally confirmed in the putamen and caudate. There was no moderating effect for external factors. Conclusions: Our meta-analysis uncovered no evidence indicating altered density of striatal dopamine terminals in schizophrenia. Moreover, striatal DAT density did not seem to be influenced by antipsychotic medication or illness duration. Our data suggest that altered integrity of striatal dopaminergic synapses is not critical for the emergence of schizophrenia or its treatment. These findings should be useful in further refining dopaminergic hypotheses of schizophrenia. © 2011 The Author
Striatal presynaptic dopamine in schizophrenia, part II: Meta-analysis of [18F/11C]-DOPA PET studies
No full textBackground: Alterations in striatal dopamine neurotransmission are central to the emergence of psychotic symptoms and to the mechanism of action of antipsychotics. Although the functional integrity of the presynaptic system can be assessed by measuring striatal dopamine synthesis capacity (DSC), no quantitative meta-analysis is available. Methods: Eleven striatal (caudate and putamen) [11C/18F]-DOPA positron emission tomography studies comparing 113 patients with schizophrenia and 131 healthy controls were included in a quantitative meta-analysis of DSC. Demographic, clinical, and methodological variables were extracted from each study or obtained from the authors and tested as covariates. Hedges' g was used as a measure of effect size in Comprehensive Meta-Analysis. Publication bias was assessed with funnel plots and Egger's intercept. Heterogeneity was addressed with the Q statistic and I2 index. Results: Patients and controls were well matched in sociodemographic variables (P >. 05). Quantitative evaluation of publication bias was nonsignificant (P =. 276). Heterogeneity across study was modest in magnitude and statistically nonsignificant (Q = 19.19; P =. 078; I2 = 39.17). Patients with schizophrenia showed increased striatal DSC as compared with controls (Hedges' g = 0.867, CI 95% from 0.594 to 1.140, Z = 6.222, P <. 001). The DSC schizophrenia/control ratio showed a relatively homogenous elevation of around 14% in schizophrenic patients as compared with controls. DSC elevation was regionally confirmed in both caudate and putamen. Controlling for potential confounders such as age, illness duration, gender, psychotic symptoms, and exposure to antipsychotics had no impact on the results. Sensitivity analysis confirmed robustness of meta-analytic findings. Conclusions: The present meta-analysis showed consistently increased striatal DSC in schizophrenia, with a 14% elevation in patients as compared with healthy controls. © 2011 The Author
Forty years of structural imaging in psychosis: promises and truth
Full text linkObjective: Since the first study published in the Lancet in 1976, structural neuroimaging has been used in psychosis with the promise of imminent clinical utility. The actual impact of structural neuroimaging in psychosis is still unclear. Method: We present here a critical review of studies involving structural magnetic resonance imaging techniques in patients with psychosis published between 1976 and 2015 in selected journals of relevance for the field. For each study, we extracted summary descriptive variables. Additionally, we qualitatively described the main structural findings of each article in summary notes and we employed a biomarker rating system based on quality of evidence (scored 1–4) and effect size (scored 1–4). Results: Eighty studies meeting the inclusion criteria were retrieved. The number of studies increased over time, reflecting an increased structural imaging research in psychosis. However, quality of evidence was generally impaired by small samples and unclear biomarker definitions. In particular, there was little attempt of replication of previous findings. The effect sizes ranged from small to modest. No diagnostic or prognostic biomarker for clinical use was identified. Conclusions: Structural neuroimaging in psychosis research has not yet delivered on the clinical applications that were envisioned
Multiparametric assessment of sensorimotor abnormalities in vulnerable populations: A window of opportunity
No full textThis commentary suggests that neuroscience research on young healthy heavy cannabis users and patients with cannabis-induced psychosis using multimodal assessment of sensorimotor dysfunction (e.g. neuroimaging, clinical rating scales, and instrumental assessments) may help to identify both biological resistance and vulnerability without constraints and confounder factors imposed by antipsychotic treatment or disease chronicity
Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication
No full textAbstractStructure and function in the human brain are closely related. At the onset of psychosis, brain imaging studies have identified robust changes in brain function and structure, but no data are available relating these two domains. After systematic literature searches, we included all available studies reporting whole-brain structural or cognitive functional imaging findings in first-episode (FEP) subjects in multimodal Signed Differential Mapping (SDM). Forty-three studies met the inclusion criteria. The structural database comprised 965 FEP subjects matched with 1040 controls whilst the functional cohort included 362 FEP subjects matched with 403 controls. The analysis identified conjoint structural and functional differences in the insula/superior temporal gyrus and the medial frontal/anterior cingulate cortex bilaterally. In these regions, large and robust decreases in grey matter volume were found with either reduced or enhanced activation. Meta-regression analyses indicated that grey matter volume in the anterior cingulate and left insular clusters was influenced by exposure to antipsychotics: patients receiving medication were more likely to show structural abnormalities in these regions
Progress in sensorimotor neuroscience of schizophrenia spectrum disorders: Lessons learned and future directions
No full textThe number of neuroimaging studies on movement disorders, sensorimotor, and psychomotor functioning in schizophrenia spectrum disorders (SSD) has steadily increased over the last two decades. Accelerated by the addition of the “sensorimotor domain” to the Research Domain Criteria (RDoC) framework in January 2019, neuroscience research on the role of sensorimotor dysfunction in SSD has gained greater scientific and clinical relevance. To draw attention to recent rapid progress in the field, we performed a triennial systematic review (PubMed search from January 1st, 2018 through December 31st, 2020), in which we highlight recent neuroimaging findings and discuss methodological pitfalls as well as challenges for future research. The identified magnetic resonance imaging (MRI) studies suggest that sensorimotor abnormalities in SSD are related to cerebello-thalamo-cortico-cerebellar network dysfunction. Longitudinal and interventional studies highlight the translational potential of the sensorimotor domain as putative biomarkers for treatment response and as targets for non-invasive neurostimulation techniques in SSD
Characterizing the sensorimotor domain in schizophrenia spectrum disorders
Full text linkThe rapidly evolving field of sensorimotor neuroscience reflects the scientific and clinical relevance of sensorimotor abnormalities as an intrinsic component of the disease process, e.g., in patients with schizophrenia spectrum disorders (SSD). Despite previous efforts, however, prevalence rates and relationships between different categories of sensorimotor abnormalities in SSD patients are still subject of ongoing debate. In this study, we examined five different categories of the sensorimotor domain (Neurological soft signs (NSS), parkinsonism, catatonia, akathisia, and tardive dyskinesia) according to well-established clinical ratings scales and the respective cut-off criteria in a sample of 131 SSD patients. We used a collection of statistical methods to better understand prevalence, overlap and heterogeneity, as well as psychopathological and cognitive correlates of sensorimotor abnormalities. 97.7% of the SSD patients considered by this study exhibited at least one categorically defined sensorimotor abnormality that tended to co-vary within three different sensorimotor subgroups (moderate, hyperkinetic and hypokinetic). Finally, hyperkinetic and hypokinetic groups differed significantly in their neurocognitive performance compared with the moderate group. The results suggest different patterns of clinical overlap, highlight the relationship between sensorimotor and cognitive domain and provide clues for further neurobiological studies
Intrinsic neural network dynamics in catatonia
Full text linkCatatonia is a transnosologic psychomotor syndrome with high prevalence in schizophrenia spectrum disorders (SSD). There is mounting neuroimaging evidence that catatonia is associated with aberrant frontoparietal, thalamic and cerebellar regions. Large-scale brain network dynamics in catatonia have not been investigated so far. In this study, resting-state fMRI data from 58 right-handed SSD patients were considered. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). Group spatial independent component analysis was carried out with a multiple analysis of covariance (MANCOVA) approach to estimate and test the underlying intrinsic components (ICs) in SSD patients with (NCRS total score ≥ 3; n = 30) and without (NCRS total score = 0; n = 28) catatonia. Functional network connectivity (FNC) during rest was calculated between pairs of ICs and transient changes in connectivity were estimated using sliding windowing and clustering (to capture both static and dynamic FNC). Catatonic patients showed increased static FNC in cerebellar networks along with decreased low frequency oscillations in basal ganglia (BG) networks. Catatonic patients had reduced state changes and dwelled more in a state characterized by high within-network correlation of the sensorimotor, visual, and default-mode network with respect to noncatatonic patients. Finally, in catatonic patients according to DSM-IV-TR (n = 44), there was a significant correlation between increased within FNC in cortico-striatal state and NCRS motor scores. The data support a neuromechanistic model of catatonia that emphasizes a key role of disrupted sensorimotor network control during distinct functional states
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