scholarly journals Focal changes in brain energy and phospholipid metabolism in first-episode schizophrenia

2004 ◽  
Vol 184 (5) ◽  
pp. 409-415 ◽  
Author(s):  
J. Eric Jensen ◽  
Jodi Miller ◽  
Peter C. Williamson ◽  
Richard W J. Neufeld ◽  
Ravi S. Menon ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Imaging Techniques ◽  
High Energy ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Membrane Breakdown ◽  
First Episode Schizophrenia

BackgroundMembrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy (31P-MRS) have been reported in patients with schizophrenia in several brain regions.AimsUsing improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T 31P-MRS.MethodBrain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm3 effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex.ResultsPeople with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group.ConclusionsThe increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.

scholarly journals Longitudinal changes in brain metabolites in healthy subjects and patients with first episode psychosis (FEP): a 7-Tesla MRS study

2020 ◽  
Author(s):  
Min Wang ◽  
Peter B. Barker ◽  
Nicola Cascella ◽  
Jennifer M. Coughlin ◽  
Gerald Nestadt ◽  
...  
Keyword(s):  
Young Adulthood ◽  
Brain Regions ◽  
First Episode Psychosis ◽  
Anterior Cingulate ◽  
7 Tesla ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Invasive Approach ◽  
Longitudinal Changes ◽  
Episode Psychosis

AbstractObjective7 Tesla (T) longitudinal magnetic resonance spectroscopy (MRS) offers a precise measurment of metabolic levels in human brain via a non-invasive approach. Studying longitudinal changes in neurometabolites could help identify trait and state markers for diseases and understand inconsistent findings from different researchers due to differences in the age of study participants and duration of illness. This study is the first to report novel longitudinal patterns in young adulthood from both physiological and pathological viewpoints using 7T MRS.MethodsUtilizing a four-year longitudinal cohort with 38 first episode psychosis (FEP) patients (onset within 2 years) and 48 healthy controls (HC), the authors examined the annual percentage changes of 9 neurometabolites in 5 brain regions.ResultsBoth FEP patients and HC subjects were found to have significant longitudinal reductions in glutamate (Glu) in the anterior cingulate cortex (ACC). Only FEP patients were found to have a significant decrease over time in γ-aminobutyric acid (GABA), N-acetyl aspartate (NAA), myo-inositol (mI), and total choline (tCho: phosphocholine plus glycerophosphocholine) in the ACC. Uniquely, glutathione (GSH) was found to have a near zero annual percentage change in both FEP patients and HC subjects in all 5 brain regions over a four-year timespan in young adulthood.ConclusionsGSH could be a trait marker for diagnostic applications at least in young adulthood. Glu, GABA, NAA, mI, and tCho in the ACC are associated with the patient’s status and could be state markers for mechanistic studies of psychotic disorders, including those for progressive pathological changes and medication effects in young adulthood.

scholarly journals Anterior cingulate grey-matter deficits and cannabis use in first-episode schizophrenia

2007 ◽  
Vol 190 (3) ◽  
pp. 230-236 ◽  
Author(s):  
Philip R. Szeszko ◽  
Delbert G. Robinson ◽  
Serge Sevy ◽  
Sanjiv Kumra ◽  
Claudia I. Rupp ◽  
...  
Keyword(s):  
White Matter ◽  
Healthy Volunteers ◽  
Grey Matter ◽  
Magnetic Resonance Images ◽  
Cannabis Use ◽  
Anterior Cingulate ◽  
First Episode ◽  
History Of ◽  
First Episode Schizophrenia ◽  
First Episode Of Schizophrenia

BackgroundDespite the high prevalence of cannabis use in schizophrenia, few studies have examined the potential relationship between cannabis exposure and brain structural abnormalities in schizophrenia.AimsTo investigate prefrontal grey and white matter regions in patients experiencing a first episode of schizophrenia with an additional diagnosis of cannabis use or dependence (n=20) compared with similar patients with no cannabis use (n=31) and healthy volunteers (n=56).MethodVolumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous magnetic resonance images and automatically segmented into grey and white matter.ResultsPatients who used cannabis had less anterior cingulate grey matter compared with both patients who did not use cannabis and healthy volunteers.ConclusionsA defect in the anterior cingulate is associated with a history of cannabis use among patients experiencing a first episode of schizophrenia and could have a role in poor decision-making and in choosing more risky outcomes.

scholarly journals Reducedγ-Aminobutyric Acid and Glutamate+Glutamine Levels in Drug-Naïve Patients with First-Episode Schizophrenia but Not in Those at Ultrahigh Risk

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Junjie Wang ◽  
Yingying Tang ◽  
Tianhong Zhang ◽  
Huiru Cui ◽  
Lihua Xu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Proton Magnetic Resonance ◽  
Proton Magnetic Resonance Spectroscopy ◽  
Aminobutyric Acid ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Healthy Controls ◽  
Drug Naïve ◽  
First Episode Schizophrenia

Alteredγ-aminobutyric acid (GABA), glutamate (Glu) levels, and an imbalance between GABAergic and glutamatergic neurotransmissions have been involved in the pathophysiology of schizophrenia. However, it remains unclear how these abnormalities impact the onset and course of psychosis. In the present study, 21 drug-naïve subjects at ultrahigh risk for psychosis (UHR), 16 drug-naïve patients with first-episode schizophrenia (FES), and 23 healthy controls (HC) were enrolled. In vivo GABA and glutamate+glutamine (Glx) levels in the medial prefrontal cortex were measured using proton magnetic resonance spectroscopy. Medial prefrontal GABA and Glx levels in FES patients were significantly lower than those in HC and UHR, respectively. GABA and Glx levels in UHR were comparable with those in HC. In each group, there was a positive correlation between GABA and Glx levels. Reduced medial prefrontal GABA and Glx levels thus may play an important role in the early stages of schizophrenia.

scholarly journals Counteracting Effects of Glutathione on the Glutamate-Driven Excitation/Inhibition Imbalance in First-Episode Schizophrenia: A 7T MRS and Dynamic Causal Modeling Study

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 75
Author(s):  
Roberto Limongi ◽  
Peter Jeon ◽  
Jean Théberge ◽  
Lena Palaniyappan
Keyword(s):  
Magnetic Resonance ◽  
Inhibitory Activity ◽  
Blood Oxygenation ◽  
Causal Modeling ◽  
Anterior Cingulate ◽  
7 Tesla ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Dynamic Causal Modeling ◽  
First Episode Schizophrenia

Oxidative stress plays a key role in the pathophysiology of schizophrenia. While free radicals produced by glutamatergic excess and oxidative metabolism have damaging effects on brain tissue, antioxidants such as glutathione (GSH) counteract these effects. The interaction between glutamate (GLU) and GSH is centered on N-Methyl-D-aspartate (NMDA) receptors. GSH levels increase during glutamate-mediated excitatory neuronal activity, which serves as a checkpoint to protect neurons from oxidative damage and reduce excitatory overdrive. We studied the possible influence of GSH on the glutamate-mediated dysconnectivity in 19 first-episode schizophrenia (FES) patients and 20 healthy control (HC) subjects. Using ultra-high field (7 Tesla) magnetic resonance spectroscopy (MRS) and resting state functional magnetic resonance imaging (fMRI), we measured GSH and GLU levels in the dorsal anterior cingulate cortex (dACC) and blood-oxygenation level-dependent activity in both the dACC and the anterior insula (AI). Using spectral dynamic causal modeling, we found that when compared to HCs, in FES patients inhibitory activity within the dACC decreased with GLU levels whereas inhibitory activity in both the dACC and AI increased with GSH levels. Our model explains how higher levels of GSH can reverse the downstream pathophysiological effects of a hyperglutamatergic state in FES. This provides an initial insight into the possible mechanistic effect of antioxidant system on the excitatory overdrive in the salience network (dACC-AI).

scholarly journals The trajectory of putative astroglial dysfunction in first episode schizophrenia: A longitudinal 7-Tesla MRS study

2021 ◽  
Author(s):  
Peter Jeon ◽  
Michael MacKinley ◽  
Jean Theberge ◽  
Lena Palaniyappan
Keyword(s):  
Anterior Cingulate ◽  
7 Tesla ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
1H Mrs ◽  
Early Stages ◽  
Metabolic Marker ◽  
Time Period ◽  
The Status ◽  
First Episode Schizophrenia

Abstract Astroglial pathology has been long suspected in schizophrenia. Myo-inositol, a metabolic marker particularly abundant in astroglia, is reduced in the anterior cingulate cortex (ACC) of patients with schizophrenia. We investigate the status of astroglial integrity indexed by ACC myo-inositol at the onset and over the first 6 months of treatment of first episode schizophrenia. We employed 7T magnetic resonance spectroscopy (1H-MRS) and quantified myo-inositol spectra at the dorsal ACC in 31 participants; 21 patients with schizophrenia with median lifetime antipsychotic exposure of less than 3 days, followed up after 6 months of treatment, and 10 healthy subjects scanned twice over the same time period. We studied the time by group interaction for myo-inositol after adjusting for gender and age. We report significant reduction in myo-inositol concentration in the ACC in schizophrenia at an early, untreated state of acute illness that improves over time. This trajectory indicates that dynamic astroglial changes are likely to operate in the early stages of schizophrenia. MRS myo-inositol may be a critical marker of amelioration of active psychosis in early stages of schizophrenia.

scholarly journals Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia

2011 ◽  
Vol 198 (6) ◽  
pp. 448-456 ◽  
Author(s):  
Naoko Aoyama ◽  
Jean Théberge ◽  
Dick J. Drost ◽  
Rahul Manchanda ◽  
Sandra Northcott ◽  
...  
Keyword(s):  
Social Functioning ◽  
Grey Matter ◽  
Rating Scale ◽  
Anterior Cingulate ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Brain Metabolite ◽  
Left Thalamus ◽  
Profile Rating ◽  
First Episode Schizophrenia

BackgroundThalamic glutamine loss and grey matter reduction suggest neurodegeneration in first-episode schizophrenia, but the duration is unknown.AimsTo observe glutamine and glutamate levels, grey matter volumes and social functioning in patients with schizophrenia followed to 80 months after diagnosis.MethodGrey matter volumes and proton magnetic resonance spectroscopy metabolites in left anterior cingulate and left thalamus were measured in 17 patients with schizophrenia before medication and 10 and 80 months after diagnosis. Social functioning was assessed with the Life Skills Profile Rating Scale (LSPRS) at 80 months.ResultsThe sum of thalamic glutamate and glutamine levels decreased over 80 months, and correlated inversely with the LSPRS. Thalamic glutamine and grey matter loss were significantly correlated in frontal, parietal, temporal and limbic regions.ConclusionsBrain metabolite loss is correlated with deteriorated social functioning and grey matter losses in schizophrenia, consistent with neurodegeneration.

scholarly journals The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ellis Chika Onwordi ◽  
Thomas Whitehurst ◽  
Ayla Mansur ◽  
Ben Statton ◽  
Alaine Berry ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Healthy Volunteers ◽  
Imaging Study ◽  
Volume Ratio ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Synaptic Density ◽  
Positron Emission

AbstractGlutamatergic excitotoxicity is hypothesised to underlie synaptic loss in schizophrenia pathogenesis, but it is unknown whether synaptic markers are related to glutamatergic function in vivo. Additionally, it has been proposed that N-acetyl aspartate (NAA) levels reflect neuronal integrity. Here, we investigated whether synaptic vesicle glycoprotein 2 A (SV2A) levels are related to glutamatergic markers and NAA in healthy volunteers (HV) and schizophrenia patients (SCZ). Forty volunteers (SCZ n = 18, HV n = 22) underwent [11C]UCB-J positron emission tomography and proton magnetic resonance spectroscopy (1H-MRS) imaging in the left hippocampus and anterior cingulate cortex (ACC) to index [11C]UCB-J distribution volume ratio (DVR), and creatine-scaled glutamate (Glu/Cr), glutamate and glutamine (Glx/Cr) and NAA (NAA/Cr). In healthy volunteers, but not patients, [11C]UCB-J DVR was significantly positively correlated with Glu/Cr, in both the hippocampus and ACC. Furthermore, in healthy volunteers, but not patients, [11C]UCB-J DVR was significantly positively correlated with Glx/Cr, in both the hippocampus and ACC. There were no significant relationships between [11C]UCB-J DVR and NAA/Cr in the hippocampus or ACC in healthy volunteers or patients. Therefore, an appreciable proportion of the brain 1H-MRS glutamatergic signal is related to synaptic density in healthy volunteers. This relationship is not seen in schizophrenia, which, taken with lower synaptic marker levels, is consistent with lower levels of glutamatergic terminals and/or a lower proportion of glutamatergic relative to GABAergic terminals in the ACC in schizophrenia.

scholarly journals A review of altered biochemistry in the anterior cingulate cortex of first-episode psychosis

2017 ◽  
Vol 26 (2) ◽  
pp. 122-128 ◽  
Author(s):  
L. Squarcina ◽  
J. A. Stanley ◽  
M. Bellani ◽  
C. A. Altamura ◽  
P. Brambilla
Keyword(s):  
Anterior Cingulate Cortex ◽  
Psychotic Disorders ◽  
Cingulate Cortex ◽  
First Episode Psychosis ◽  
Anterior Cingulate ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Chronic Patients ◽  
Episode Psychosis

Relevant biochemicals of the brain can be quantified in vivo, non-invasively, using proton Magnetic Resonance Spectroscopy (¹H MRS). This includes metabolites associated with neural general functioning, energetics, membrane phospholipid metabolism and neurotransmission. Moreover, there is substantial evidence of implication of the frontal and prefrontal areas in the pathogenesis of psychotic disorders such as schizophrenia. In particular, the anterior cingulate cortex (ACC) plays an important role in cognitive control of emotional and non-emotional processes. Thus the study of its extent of biochemistry dysfunction in the early stages of psychosis is of particular interest in gaining a greater understanding of its aetiology. In this review, we selected ¹H MRS studies focused on the ACC of first-episode psychosis (FEP). Four studies reported increased glutamatergic levels in FEP, while other four showed preserved concentrations. Moreover, findings on FEP do not fully mirror those in chronic patients. Due to conflicting findings, larger longitudinal ¹H MRS studies are expected to further explore glutamatergic neurotransmission in ACC of FEP in order to have a better understanding of the glutamatergic mechanisms underlying psychosis, possibly using ultra high field MR scanners.

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