scholarly journals Dissection of neuroinflammation in schizophrenia

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S274-S275
Author(s):  
Fizah Muratib ◽  
Yuya Mizuno ◽  
Ines Carreira Figueiredo ◽  
Oliver Howes ◽  
Tiago Reis Marques
Keyword(s):  
Risk Factor ◽  
Grey Matter ◽  
Psychotic Disorders ◽  
Positive Association ◽  
Brain Regions ◽  
Regions Of Interest ◽  
Cannabis Use ◽  
Similar Response ◽  
Frequency Of Use ◽  
The Brain

AimsSchizophrenia is notoriously becoming one of the world's most debilitating mental disorders, affecting 1 in 100 people. There is increasing evidence that neuroinflammation plays a part in the pathogenesis of schizophrenia and other psychotic disorders; microglial activity acting as a marker for neuroinflammatory reactions in the brain. Furthermore, cannabis is an illicit substance that also evokes a similar response in the neuroimmune activity. This project explores how cannabis exposure influences an elevation in neuroinflammatory responses through TSPO levels, and whether this information can help us determine if cannabis use and increased TSPO levels can be associated with a risk factor for developing psychosis.Method55 participants (36 males and 19 females) were recruited from the community by the IRIS (Inflammatory Reaction in Schizophrenia) team at the IoPPN, King's College London, from which 34 patients with a diagnosis of schizophrenia and 21 healthy controls took part in the study. The eligible participants underwent clinical assessments and PET scanning, from which cannabis use history and PET data were collected. Participant neuroinflammatory levels are represented by [18F]DPA-714 volume and different regions of grey matter in the brain were analysed through multivariate analyses, the confounding variables being age and TSPO genotype.ResultA statistically significant association is shown between participants who have had exposure to cannabis and participants who have not had any exposure in their lifetime. The differences across the prioritised brain regions of interest were robust, the association appearing more apparent and statistically significant in the total (p = .00) and temporal grey matter (p = .00) regions of the brain. This may suggest that cannabis exposure influences the [18F]DPA-714 VT in the significant regions of interest. However, a negative association is seen with current use, the quantity of use, and the frequency of use.ConclusionThe initial findings for cannabis exposure show us a positive association with increased TSPO levels, however, limitations must be taken into account. Although we cannot readily establish that elevated TSPO levels in cannabis users can presently act as a risk factor marker for developing psychosis from this particular study, we can utilise this data to continue our research in disclosing a new system to predict the occurrence of psychosis.

scholarly journals Grey matter correlates of minor physical anomalies in the ÆSOP first-episode psychosis study

2006 ◽  
Vol 189 (3) ◽  
pp. 221-228 ◽  
Author(s):  
K. Dean ◽  
P. Fearon ◽  
K. Morgan ◽  
G. Hutchinson ◽  
K. Orr ◽  
...  
Keyword(s):  
Grey Matter ◽  
Psychotic Disorders ◽  
Brain Regions ◽  
First Episode Psychosis ◽  
Magnetic Resonance Images ◽  
First Episode ◽  
Lingual Gyrus ◽  
Episode Psychosis ◽  
Minor Physical Anomalies ◽  
The Brain

BackgroundMinor physical anomalies are more prevalent among people with psychosis. This supports a neurodevelopmental aetiology for psychotic disorders, since these anomalies and the brain are both ectodermally derived. However, little is understood about the brain regions implicated in this association.AimsTo examine the relationship between minor physical anomalies and grey matter structure in a sample of patients with first-episode psychosis.MethodSixty patients underwent assessment of minor physical anomalies with the Lane scale. High-resolution magnetic resonance images and voxel-based methods of image analysis were used to investigate brain structure in these patients.ResultsThe total anomalies score was associated with a grey matter reduction in the prefrontal cortex and precuneus and with a grey matter excess in the basal ganglia, thalamus and lingual gyrus.ConclusionsMinor physical anomalies in a sample of patients with first-episode psychosis are associated with regional grey matter changes. These regional changes may be important in the pathogenesis of psychotic disorder.

scholarly journals Sex differences in neural correlates of common psychopathological symptoms in early adolescence

2021 ◽  
pp. 1-11
Author(s):  
Francesca Biondo ◽  
Charlotte Nymberg Thunell ◽  
Bing Xu ◽  
Congying Chu ◽  
Tianye Jia ◽  
...  
Keyword(s):  
Internalizing Symptoms ◽  
Grey Matter ◽  
Neural Correlates ◽  
Brain Regions ◽  
Female Adolescents ◽  
Grey Matter Volume ◽  
Community Based ◽  
Psychopathological Symptom ◽  
Strengths And Difficulties ◽  
The Brain

Abstract Background Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence. Methods Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ). Results We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = −0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = −0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = −0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = −0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls. Conclusions Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.

Structural magnetic resonance imaging markers of susceptibility and transition to schizophrenia: A review of familial and clinical high risk population studies

2014 ◽  
Vol 29 (2) ◽  
pp. 144-154 ◽  
Author(s):  
C Bois ◽  
HC Whalley ◽  
AM McIntosh ◽  
SM Lawrie
Keyword(s):  
High Risk ◽  
Grey Matter ◽  
Brain Regions ◽  
High Risk Population ◽  
Clinical High Risk ◽  
Cross Sectional ◽  
Structural Abnormalities ◽  
Neuroimaging Data ◽  
Imaging Markers ◽  
The Brain

There is a growing consensus that a symptomatology as complex and heterogeneous as schizophrenia is likely to be produced by widespread perturbations of brain structure, as opposed to isolated deficits in specific brain regions. Structural brain-imaging studies have shown that several features of the brain, such as grey matter, white matter integrity and the morphology of the cortex differ in individuals at high risk of the disorder compared to controls, but to a lesser extent than in patients, suggesting that structural abnormalities may form markers of vulnerability to the disorder. Research has had some success in delineating abnormalities specific to those individuals that transition to psychosis, compared to those at high risk that do not, suggesting that a general risk for the disorder can be distinguished from alterations specific to frank psychosis. In this paper, we review cross-sectional and longitudinal studies of individuals at familial or clinical high risk of the disorder. We conclude that the search for reliable markers of schizophrenia is likely to be enhanced by methods which amalgamate structural neuroimaging data into a coherent framework that takes into account the widespread distribution of brain alterations, and relates this to leading hypotheses of schizophrenia.

Gray matter blood flow change is unevenly distributed during moderate isocapnic hypoxia in humans

2008 ◽  
Vol 104 (1) ◽  
pp. 212-217 ◽  
Author(s):  
Andrew P. Binks ◽  
Vincent J. Cunningham ◽  
Lewis Adams ◽  
Robert B. Banzett
Keyword(s):  
Blood Flow ◽  
Nucleus Accumbens ◽  
Positron Emission Tomography Imaging ◽  
Occipital Lobe ◽  
Brain Regions ◽  
Functional Brain Imaging ◽  
Regions Of Interest ◽  
Breath Hold ◽  
Obstructive Sleep ◽  
The Brain

Hypoxia increases cerebral blood flow (CBF), but it is unknown whether this increase is uniform across all brain regions. We used H215O positron emission tomography imaging to measure absolute blood flow in 50 regions of interest across the human brain ( n = 5) during normoxia and moderate hypoxia. Pco2 was kept constant (∼44 Torr) throughout the study to avoid decreases in CBF associated with the hypocapnia that normally occurs with hypoxia. Breathing was controlled by mechanical ventilation. During hypoxia (inspired Po2 = 70 Torr), mean end-tidal Po2 fell to 45 ± 6.3 Torr (means ± SD). Mean global CBF increased from normoxic levels of 0.39 ± 0.13 to 0.45 ± 0.13 ml/g during hypoxia. Increases in regional CBF were not uniform and ranged from 9.9 ± 8.6% in the occipital lobe to 28.9 ± 10.3% in the nucleus accumbens. Regions of interest that were better perfused during normoxia generally showed a greater regional CBF response. Phylogenetically older regions of the brain tended to show larger vascular responses to hypoxia than evolutionary younger regions, e.g., the putamen, brain stem, thalamus, caudate nucleus, nucleus accumbens, and pallidum received greater than average increases in blood flow, while cortical regions generally received below average increases. The heterogeneous blood flow distribution during hypoxia may serve to protect regions of the brain with essential homeostatic roles. This may be relevant to conditions such as altitude, breath-hold diving, and obstructive sleep apnea, and may have implications for functional brain imaging studies that involve hypoxia.

scholarly journals Human brain anatomy reflects separable genetic and environmental components of socioeconomic status

2021 ◽  
Author(s):  
Hyeokmoon Kweon ◽  
Gokhan Aydogan ◽  
Alain Dagher ◽  
Danilo Bzdok ◽  
Christian C Ruff ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Grey Matter ◽  
Brain Regions ◽  
Grey Matter Volume ◽  
Brain Anatomy ◽  
Additive Effects ◽  
Common Genetic Variation ◽  
Matter Volume ◽  
Underlying Causes ◽  
The Brain

Recent studies report that socioeconomic status (SES) correlates with brain structure. Yet, such findings are variable and little is known about underlying causes. We present a well-powered voxel-based analysis of grey matter volume (GMV) across levels of SES, finding many small SES effects widely distributed across the brain, including cortical, subcortical and cerebellar regions. We also construct a polygenic index of SES to control for the additive effects of common genetic variation related to SES, which attenuates observed SES-GMV relations, to different degrees in different areas. Remaining variance, which may be attributable to environmental factors, is substantially accounted for by body mass index, a marker for lifestyle related to SES. In sum, SES affects multiple brain regions through measurable genetic and environmental effects.

scholarly journals Correlations Among mRNA Expression Levels of ATP7A, Serum Ceruloplasmin Levels, and Neuronal Metabolism in Unmedicated Major Depressive Disorder

2020 ◽  
Vol 23 (10) ◽  
pp. 642-652 ◽  
Author(s):  
Xuanjun Liu ◽  
Shuming Zhong ◽  
Lan Yan ◽  
Hui Zhao ◽  
Ying Wang ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mrna Expression ◽  
Brain Regions ◽  
Regions Of Interest ◽  
Major Depressive ◽  
Expression Levels ◽  
Neuronal Metabolism ◽  
The Brain ◽  
Mrna Expression Levels

Abstract Background Previous studies have found that elevated copper levels induce oxidation, which correlates with the occurrence of major depressive disorder (MDD). However, the mechanism of abnormal cerebral metabolism of MDD patients remains ambiguous. The main function of the enzyme ATPase copper-transporting alpha (ATP7A) is to transport copper across the membrane to retain copper homeostasis, which is closely associated with the onset of mental disorders and cognitive impairment. However, less is known regarding the association of ATP7A expression in MDD patients. Methods A total of 31 MDD patients and 21 healthy controls were recruited in the present study. Proton magnetic resonance spectroscopy was used to assess the concentration levels of N-acetylaspartate, choline (Cho), and creatine (Cr) in brain regions of interest, including prefrontal white matter (PWM), anterior cingulate cortex (ACC), thalamus, lentiform nucleus, and cerebellum. The mRNA expression levels of ATP7A were measured using polymerase chain reaction (SYBR Green method). The correlations between mRNA expression levels of ATP7A and/or ceruloplasmin levels and neuronal biochemical metabolite ratio in the brain regions of interest were evaluated. Results The decline in the mRNA expression levels of ATP7A and the increase in ceruloplasmin levels exhibited a significant correlation in MDD patients. In addition, negative correlations were noted between the decline in mRNA expression levels of ATP7A and the increased Cho/Cr ratios of the left PWM, right PWM, and right ACC in MDD patients. A positive correlation between elevated ceruloplasmin levels and increased Cho/Cr ratio of the left PWM was noted in MDD patients. Conclusions The findings suggested that the decline in the mRNA expression levels of ATP7A and the elevated ceruloplasmin levels induced oxidation that led to the disturbance of neuronal metabolism in the brain, which played important roles in the pathophysiology of MDD. The decline in the mRNA expression levels of ATP7A and the elevated ceruloplasmin levels affected neuronal membrane metabolic impairment in the left PWM, right PWM, and right ACC of MDD patients.

scholarly journals A tool for analyzing electrode tracks from slice histology

2018 ◽  
Author(s):  
Philip Shamash ◽  
Matteo Carandini ◽  
Kenneth D Harris ◽  
Nicholas A Steinmetz
Keyword(s):  
Data Analysis ◽  
Brain Slices ◽  
Brain Regions ◽  
Regions Of Interest ◽  
Brain Atlas ◽  
Essential Step ◽  
Pass Through ◽  
Manual Input ◽  
The Brain ◽  
Allen Mouse Brain Atlas

It is now possible to record from hundreds of neurons across multiple brain regions in a single electrophysiology experiment. An essential step in the ensuing data analysis is to assign recorded neurons to the correct brain regions. Brain regions are typically identified after the recordings by comparing images of brain slices to a reference atlas by eye. This introduces error, in particular when slices are not cut at a perfectly coronal angle or when electrode tracks span multiple slices. Here we introduce SHARP-Track, a tool to localize regions of interest and plot the brain regions they pass through. SHARP-Track offers a MATLAB user interface to explore the Allen Mouse Brain Atlas, register asymmetric slice images to the atlas using manual input, and interactively analyze electrode tracks. We find that it reduces error compared to localizing electrodes in a reference atlas by eye. See github.com/cortex-lab/allenCCF for the software and wiki.

scholarly journals Pharmaco-Magnetic Resonance as a Tool for Monitoring the Medication-Related Effects in the Brain May Provide Potential Biomarkers for Psychotic Disorders

2021 ◽  
Vol 22 (17) ◽  
pp. 9309
Author(s):  
Katrin Aryutova ◽  
Drozdstoy Stoyanov
Keyword(s):  
Magnetic Resonance ◽  
Psychotic Disorders ◽  
Brain Regions ◽  
Complex Interaction ◽  
Resonance Imaging ◽  
Therapeutic Results ◽  
Dopamine Hypothesis ◽  
The Neural Networks ◽  
The Brain ◽  
Insight Into

The neurodegenerative and neurodevelopmental hypotheses represent the basic etiological framework for the origin of schizophrenia. Additionally, the dopamine hypothesis, adopted more than two decades ago, has repeatedly asserted the position of dopamine as a pathobiochemical substrate through the action of psychostimulants and neuroleptics on the mesolimbic and mesocortical systems, giving insight into the origin of positive and negative schizophrenic symptoms. Meanwhile, cognitive impairments in schizophrenia remain incompletely understood but are thought to be present during all stages of the disease, as well as in the prodromal, interictal and residual phases. On the other hand, observations on the effects of NMDA antagonists, such as ketamine and phencyclidine, reveal that hypoglutamatergic neurotransmission causes not only positive and negative but also cognitive schizophrenic symptoms. This review aims to summarize the different hypotheses about the origin of psychoses and to identify the optimal neuroimaging method that can serve to unite them in an integral etiological framework. We systematically searched Google scholar (with no concern to the date published) to identify studies investigating the etiology of schizophrenia, with a focus on impaired central neurotransmission. The complex interaction between the dopamine and glutamate neurotransmitter systems provides the long-needed etiological concept, which combines the neurodegenerative hypothesis with the hypothesis of impaired neurodevelopment in schizophrenia. Pharmaco-magnetic resonance imaging is a neuroimaging method that can provide a translation of scientific knowledge about the neural networks and the disruptions in and between different brain regions, into clinically applicable and effective therapeutic results in the management of severe psychotic disorders.

scholarly journals A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens

2020 ◽  
Author(s):  
Anna J. Stevenson ◽  
Daniel L. McCartney ◽  
Gemma L. Shireby ◽  
Robert F. Hillary ◽  
Declan King ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Positive Association ◽  
Brain Regions ◽  
Preliminary Evidence ◽  
Epigenetic Clock ◽  
Significant Positive Association ◽  
Epigenetic Age ◽  
Lothian Birth Cohort ◽  
Epigenetic Age Acceleration ◽  
The Brain

AbstractInflammation and ageing-related DNA methylation patterns in the blood have been linked to a variety of morbidities, including cognitive decline and neurodegenerative disease. However, it is unclear how these blood-based patterns relate to patterns within the brain, and how each associates with central cellular profiles. In this study, we profiled DNA methylation in both the blood and in five post-mortem brain regions (BA17, BA20/21, BA24, BA46 and hippocampus) in 14 individuals from the Lothian Birth Cohort 1936. Microglial burdens were additionally quantified in the same brain regions. DNA methylation signatures of five epigenetic ageing biomarkers (‘epigenetic clocks’), and two inflammatory biomarkers (DNA methylation proxies for C-reactive protein and interleukin-6) were compared across tissues and regions. Divergent correlations between the inflammation and ageing signatures in the blood and brain were identified, depending on region assessed. Four out of the five assessed epigenetic age acceleration measures were found to be highest in the hippocampus (β range=0.83-1.14, p≤0.02). The inflammation-related DNA methylation signatures showed no clear variation across brain regions. Reactive microglial burdens were found to be highest in the hippocampus (β=1.32, p=5×10-4); however, the only association identified between the blood- and brain-based methylation signatures and microglia was a significant positive association with acceleration of one epigenetic clock (termed DNAm PhenoAge) averaged over all five brain regions (β=0.40, p=0.002). This work highlights a potential vulnerability of the hippocampus to epigenetic ageing and provides preliminary evidence of a relationship between DNA methylation signatures in the brain and differences in microglial burdens.

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