Neuroanatomical changes in people with high schizotypy: relationship to glutamate levels

BackgroundCortical glutamatergic dysfunction is thought to be fundamental for psychosis development, and may lead to structural degeneration through excitotoxicity. Glutamate levels have been related to gray matter volume (GMV) alterations in people at ultra-high risk of psychosis, and we previously reported GMV changes in individuals with high schizotypy (HS), which refers to the expression of schizophrenia-like characteristics in healthy people. This study sought to examine whether GMV changes in HS subjects are related to glutamate levels.MethodsWe selected 22 healthy subjects with HS and 23 healthy subjects with low schizotypy (LS) based on their rating on a self-report questionnaire for psychotic-like experiences. Glutamate levels were measured in the bilateral anterior cingulate cortex (ACC) using proton magnetic resonance spectroscopy, and GMV was assessed using voxel-based morphometry.ResultsSubjects with HS showed GMV decreases in the rolandic operculum/superior temporal gyrus (pFWE = 0.045). Significant increases in GMV were also detected in HS, in the precuneus (pFWE = 0.043), thereby replicating our previous finding in a separate cohort, as well as in the ACC (pFWE = 0.041). While the HS and LS groups did not differ in ACC glutamate levels, in HS subjects ACC glutamate was negatively correlated with ACC GMV (pFWE = 0.026). Such association was absent in LS.ConclusionsOur study shows that GMV findings in schizotypy are related to glutamate levels, supporting the hypothesis that glutamatergic function may lead to structural changes associated with the expression of psychotic-like experiences.

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The Relationship between the Level of Anterior Cingulate Cortex Metabolites, Brain-Periphery Redox Imbalance, and the Clinical State of Patients with Schizophrenia and Personality Disorders

Biomolecules ◽

10.3390/biom10091272 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1272

Author(s):

Amira Bryll ◽

Wirginia Krzyściak ◽

Paulina Karcz ◽

Natalia Śmierciak ◽

Tamas Kozicz ◽

...

Keyword(s):

Personality Disorders ◽

Structural Changes ◽

Clinical Symptoms ◽

Anterior Cingulate ◽

Clinical State ◽

Antioxidant Systems ◽

Resonance Spectroscopy ◽

Redox Imbalance ◽

The Relationship ◽

The Brain

Schizophrenia is a complex mental disorder whose course varies with periods of deterioration and symptomatic improvement without diagnosis and treatment specific for the disease. So far, it has not been possible to clearly define what kinds of functional and structural changes are responsible for the onset or recurrence of acute psychotic decompensation in the course of schizophrenia, and to what extent personality disorders may precede the appearance of the appropriate symptoms. The work combines magnetic resonance spectroscopy imaging with clinical evaluation and laboratory tests to determine the likely pathway of schizophrenia development by identifying peripheral cerebral biomarkers compared to personality disorders. The relationship between the level of metabolites in the brain, the clinical status of patients according to International Statistical Classification of Diseases and Related Health Problems, 10th Revision ICD-10, duration of untreated psychosis (DUP), and biochemical indices related to redox balance (malondialdehyde), the efficiency of antioxidant systems (FRAP), and bioenergetic metabolism of mitochondria, were investigated. There was a reduction in the level of brain N-acetyl-aspartate and glutamate in the anterior cingulate gyrus of patients with schisophrenia compared to the other groups that seems more to reflect a biological etiopathological factor of psychosis. Decreased activity of brain metabolites correlated with increased peripheral oxidative stress (increased malondialdehyde MDA) associated with decreased efficiency of antioxidant systems (FRAP) and the breakdown of clinical symptoms in patients with schizophrenia in the course of psychotic decompensation compared to other groups. The period of untreated psychosis correlated negatively with glucose value in the brain of people with schizophrenia, and positively with choline level. The demonstrated differences between two psychiatric units, such as schizophrenia and personality disorders in relation to healthy people, may be used to improve the diagnosis and prognosis of schizophrenia compared to other heterogenous psychopathology in the future. The collapse of clinical symptoms of patients with schizophrenia in the course of psychotic decompensation may be associated with the occurrence of specific schizotypes, the determination of which is possible by determining common relationships between changes in metabolic activity of particular brain structures and peripheral parameters, which may be an important biological etiopathological factor of psychosis. Markers of peripheral redox imbalance associated with disturbed bioenergy metabolism in the brain may provide specific biological factors of psychosis however, they need to be confirmed in further studies.

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The Association between Gray Matter Volume and Reading Proficiency: A Longitudinal Study of Beginning Readers

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00710 ◽

2015 ◽

Vol 27 (2) ◽

pp. 308-318 ◽

Cited By ~ 17

Author(s):

Janosch Linkersdörfer ◽

Alina Jurcoane ◽

Sven Lindberg ◽

Jochen Kaiser ◽

Marcus Hasselhorn ◽

...

Keyword(s):

Reading Instruction ◽

Gray Matter ◽

Structural Changes ◽

Gray Matter Volume ◽

Negative Relationship ◽

Reading Proficiency ◽

Superior Temporal Gyrus ◽

Measurement Time ◽

Cortical Volume ◽

Matter Volume

Neural systems involved in the processing of written language have been identified by a number of functional imaging studies. Structural changes in cortical anatomy that occur in the course of literacy acquisition, however, remain largely unknown. Here, we follow elementary school children over their first 2 years of formal reading instruction and use tensor-based morphometry to relate reading proficiency to cortical volume at baseline and follow-up measurement as well as to intraindividual longitudinal volume development between the two measurement time points. A positive relationship was found between baseline gray matter volume in the left superior temporal gyrus and subsequent changes in reading proficiency. Furthermore, a negative relationship was found between reading proficiency at the second measurement time point and intraindividual cortical volume development in the inferior parietal lobule and the precentral and postcentral gyri of the left hemisphere. These results are interpreted as evidence that reading acquisition is associated with preexisting structural differences as well as with experience-dependent structural changes involving dendritic and synaptic pruning.

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Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and thalamus as a function of mild depressive symptoms: a voxel-based morphometric analysis

Psychological Medicine ◽

10.1017/s0033291714000348 ◽

2014 ◽

Vol 44 (13) ◽

pp. 2833-2843 ◽

Cited By ~ 52

Author(s):

C. A. Webb ◽

M. Weber ◽

E. A. Mundy ◽

W. D. S. Killgore

Keyword(s):

Depressive Symptoms ◽

Gray Matter ◽

Orbitofrontal Cortex ◽

Gray Matter Volume ◽

Superior Temporal Gyrus ◽

Brain Regions ◽

Anterior Cingulate ◽

Dimensional Approach ◽

Matter Volume ◽

Conjunction Analysis

BackgroundStudies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e. comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD)v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g. DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e. severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research.MethodTo examine the extent to which depressive symptoms – even at subclinical levels – are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxel-based morphometry in a sample of 54 participants.ResultsThe severity of mild depressive symptoms, even in a subclinical population, was associated with reduced gray matter volume in the orbitofrontal cortex, anterior cingulate, thalamus, superior temporal gyrus/temporal pole and superior frontal gyrus. A conjunction analysis revealed concordance across two separate measures of depression.ConclusionsReduced gray matter volume in theoretically important brain regions can be observed even in a sample that does not meet DSM criteria for MDD, but who nevertheless report relatively elevated levels of depressive symptoms. Overall, these findings highlight the need for additional research using dimensional conceptual and analytic approaches, as well as further investigation of subclinical populations.

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No regional gray matter volume reduction observed in young Japanese people at ultra-high risk for psychosis: A voxel-based morphometry study

Asian Journal of Psychiatry ◽

10.1016/j.ajp.2018.09.009 ◽

2018 ◽

Vol 37 ◽

pp. 167-171 ◽

Cited By ~ 2

Author(s):

Atsushi Sakuma ◽

Chika Obara ◽

Masahiro Katsura ◽

Fumiaki Ito ◽

Noriyuki Ohmuro ◽

...

Keyword(s):

High Risk ◽

Gray Matter ◽

Gray Matter Volume ◽

Volume Reduction ◽

Voxel Based Morphometry ◽

Japanese People ◽

Matter Volume ◽

Ultra High Risk

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Schizotypy and brain structure: a voxel-based morphometry study

Psychological Medicine ◽

10.1017/s0033291709991875 ◽

2009 ◽

Vol 40 (9) ◽

pp. 1423-1431 ◽

Cited By ~ 54

Author(s):

G. Modinos ◽

A. Mechelli ◽

J. Ormel ◽

N. A. Groenewold ◽

A. Aleman ◽

...

Keyword(s):

Gray Matter Volume ◽

Chronic Schizophrenia ◽

Posterior Cingulate Cortex ◽

Self Report ◽

Schizophrenia Spectrum Disorders ◽

Voxel Based Morphometry ◽

Schizotypal Personality ◽

Psychosis Proneness ◽

Schizophrenia Spectrum ◽

Spectrum Disorders

BackgroundSchizotypy is conceptualized as a subclinical manifestation of the same underlying biological factors that give rise to schizophrenia and other schizophrenia spectrum disorders. Individuals with psychometric schizotypy (PS) experience subthreshold psychotic signs and can be psychometrically identified among the general population. Previous research using magnetic resonance imaging (MRI) has shown gray-matter volume (GMV) abnormalities in chronic schizophrenia, in subjects with an at-risk mental state (ARMS) and in individuals with schizotypal personality disorder (SPD). However, to date, no studies have investigated the neuroanatomical correlates of PS.MethodSix hundred first- and second-year university students completed the Community Assessment of Psychic Experiences (CAPE), a self-report instrument on psychosis proneness measuring attenuated positive psychotic experiences. A total of 38 subjects with high and low PS were identified and subsequently scanned with MRI. Voxel-based morphometry (VBM) was applied to examine GMV differences between subjects with high and low positive PS.ResultsSubjects with high positive PS showed larger global volumes compared to subjects with low PS, and larger regional volumes in the medial posterior cingulate cortex (PCC) and the precuneus. There were no regions where GMV was greater in low than in high positive PS subjects.ConclusionsThese regions, the PCC and precuneus, have also been sites of volumetric differences in MRI studies of ARMS subjects and schizophrenia, suggesting that psychotic or psychotic-like experiences may have common neuroanatomical correlates across schizophrenia spectrum disorders.

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The neuroanatomical correlates of individual differences in delay discounting: A voxel-based morphometry study

Journal of Pacific Rim Psychology ◽

10.1017/prp.2019.22 ◽

2019 ◽

Vol 13 ◽

Author(s):

Xueting Li ◽

Ping Hu ◽

Jia Liu

Keyword(s):

Delay Discounting ◽

Gray Matter Volume ◽

Cool System ◽

Anterior Cingulate ◽

Voxel Based Morphometry ◽

Future Value ◽

Cortical Regions ◽

The One ◽

The Individual ◽

Monetary Choice Questionnaire

Abstract Delay discounting refers to the reduction in the present value of a future reward as the delay to that reward increases, which is related to various problematic behaviors, such as substance abuse. In this study, we explored the neuroanatomical correlates of delay discounting by employing voxel-based morphometry and the individual difference approach. We found that participants’ delay discounting, measured by the Monetary Choice Questionnaire, was correlated with the gray matter volume (GMV) of two cortical regions. On the one hand, individuals with a larger GMV of the orbitofrontal cortex (OFC) were likely to discount future values less steeply and choose large but delayed rewards. On the other hand, individuals with a larger GMV of the anterior cingulate cortex (ACC) are likely to discount the future value more steeply and prefer small but immediate rewards. Our study revealed the neuroanatomical correlates of delay discounting across the whole brain, and may help to understand the delay discounting in the frame of the hot versus cool system, which demonstrates the dynamics of resisting present temptation for future rewards.

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Voxel-Based Morphometry Analysis of Gray Matter on Quran Memorizers

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v16i1.1191 ◽

2017 ◽

Vol 16 (1) ◽

Author(s):

Iqbal Jamaludin ◽

Mohd Zulfaezal Che Azemin ◽

Abdul Halim Sapuan ◽

Radhiana Hassan

Keyword(s):

Gray Matter ◽

Brain Structure ◽

Structural Changes ◽

Gray Matter Volume ◽

Brodmann Area ◽

Voxel Based Morphometry ◽

Significant Difference ◽

Morphometry Analysis ◽

Current Sample ◽

The Brain

Introduction: The brain is the most complex organ in the human body. Robust and vigorous daily activities may cause changes to the brain structure. Huffaz, individuals who memorise the Quran undergo intensive memorization training which may lead to structural changes in specific regions of the brain. Materials and method: This study looked at possible change that occurred on gray matter by characterising the textual memorization of brain structure using voxel-based morphometry (VBM). It involves voxel-by-voxel comparison of gray matter intensity of the MRI images. Forty-seven subjects (23 huffaz, 24 non-huffaz) aged between 21-25 years were voluntarily recruited. Subjects were scanned by 3 Tesla MRI system. Images were then re-aligned according to standardised Montreal Neurological Institute (MNI) coordinates. The MRIs were then segmented into gray matter, white matter and cerebrospinal fluid. Independent sample t-test was performed between the two groups. Results: No significant difference was found between the brain region of the huffaz and non-huffaz with appropriate corrections for family-wise error (FWE) at a threshold of p = 0.05. However, with a more lenient criteria (p = 0.001, uncorrected, cluster size = 50 mm3 ), we found that gray matter volume in Brodmann Area 6 and Brodmann Area 7 of the huffaz were significantly higher than the non-huffaz group. Conclusion: VBM is not sensitive enough to detect complex anatomical differences between huffaz and non-huffaz with the current sample size. Future study to explore possible image processing tools that can measure subtle structural change in human brain is warranted.

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Neurobiological Correlates of Learning Potential in Healthy Subjects and in Schizophrenic Patients

Journal of Cognitive Education and Psychology ◽

10.1891/1945-8959.8.1.81 ◽

2009 ◽

Vol 8 (1) ◽

pp. 81-90 ◽

Cited By ~ 5

Author(s):

Anya Pedersen ◽

Karl H. Wiedl ◽

Patricia Ohrmann

Keyword(s):

Healthy Subjects ◽

Cerebral Metabolism ◽

Chronic Schizophrenia ◽

Wisconsin Card Sorting Test ◽

Anterior Cingulate ◽

First Episode ◽

Resonance Spectroscopy ◽

Card Sorting ◽

Learning Potential ◽

Schizophrenic Patients

Dynamic testing has increasingly been recognized as a measure of neurocognitive modifiability. For instance, executive function deficits as measured by the Wisconsin Card Sorting Test (WCST) can be ameliorated in a subgroup of schizophrenic patients by integrating instructions and feedback into the testing procedure. In the first study reported herein, we investigated the relation between learning typology on the WCST and chronicity in 60 first-episode patients and 44 patients with chronic schizophrenia. We found that nonretainer categorization of WCST performance is not related to chronic schizophrenia. In the second study, we investigated the relationship between learning potential on the WCST and cerebral metabolism, assessed by single-voxel proton magnetic resonance spectroscopy of the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC), in 43 schizophrenic patients and 37 matched healthy control subjects. The level of N-acetylaspartate (NAA), a marker of neuronal integrity, in the DLPFC correlated with performance on the dynamic WCST in healthy subjects. In schizophrenic patients, a significant correlation was observed between NAA in the ACC and learning potential (cf. Ohrmann et al., 2008). These data suggest the involvement of different neuronal networks in learning among schizophrenic patients as compared to healthy controls.

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Regional Gray Matter Volume Differences Between Adolescents With ADHD and Typically Developing Controls: Further Evidence for Anterior Cingulate Involvement

Journal of Attention Disorders ◽

10.1177/1087054715619682 ◽

2016 ◽

Vol 22 (7) ◽

pp. 627-638 ◽

Cited By ~ 14

Author(s):

Björn Bonath ◽

Jana Tegelbeckers ◽

Marko Wilke ◽

Hans-Henning Flechtner ◽

Kerstin Krauel

Keyword(s):

Gray Matter ◽

Matched Control ◽

Gray Matter Volume ◽

Occipital Cortex ◽

Individual Performance ◽

Attention Problems ◽

Anterior Cingulate ◽

Typically Developing ◽

Voxel Based Morphometry ◽

Matter Volume

Objective: The present study investigated structural brain differences between adolescents with ADHD and matched control participants. Method: Voxel-based morphometry (VBM) using the DARTEL approach was performed to assess regional gray matter (GM) volumes. Additionally, individual performance on tests of attention was recorded to correlate ADHD related cognitive impairments with regional gray matter abnormalities. Results: We found significantly smaller GM volume in subjects with ADHD compared to their matched controls within the anterior cingulate cortex (ACC), the occipital cortex, bilateral hippocampus/amygdala and in widespread cerebellar regions. Further, reductions of the ACC gray matter volume were found to correlate with scores of selective inattention. Conclusion: These findings underline that structural alterations in a widespread cortico-subcortical network seem to underlie the observable attention problems in patients with ADHD.

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Intra-Regional Glu-GABA vs Inter-Regional Glu-Glu Imbalance: A 1H-MRS Study of the Neurochemistry of Auditory Verbal Hallucinations in Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbz099 ◽

2019 ◽

Vol 46 (3) ◽

pp. 633-642 ◽

Cited By ~ 1

Author(s):

Helene Hjelmervik ◽

Alexander R Craven ◽

Igne Sinceviciute ◽

Erik Johnsen ◽

Kristiina Kompus ◽

...

Keyword(s):

Inferior Frontal Gyrus ◽

Superior Temporal Gyrus ◽

Significant Negative Correlation ◽

Brain Regions ◽

Anterior Cingulate ◽

Resonance Spectroscopy ◽

Healthy Controls ◽

1H Mrs ◽

Left Inferior Frontal Gyrus ◽

Auditory Verbal Hallucinations

Abstract Glutamate (Glu), gamma amino-butyric acid (GABA), and excitatory/inhibitory (E/I) imbalance have inconsistently been implicated in the etiology of schizophrenia. Elevated Glu levels in language regions have been suggested to mediate auditory verbal hallucinations (AVH), the same regions previously associated with neuronal hyperactivity during AVHs. It is, however, not known whether alterations in Glu levels are accompanied by corresponding GABA alterations, nor is it known if Glu levels are affected in brain regions with known neuronal hypo-activity. Using magnetic resonance spectroscopy (MRS), we measured Glx (Glu+glutamine) and GABA+ levels in the anterior cingulate cortex (ACC), left and right superior temporal gyrus (STG), and left inferior frontal gyrus (IFG), in a sample of 77 schizophrenia patients and 77 healthy controls. Two MRS-protocols were used. Results showed a marginally significant positive correlation in the left STG between Glx and AVHs, whereas a significant negative correlation was found in the ACC. In addition, high-hallucinating patients as a group showed decreased ACC and increased left STG Glx levels compared to low-hallucinating patients, with the healthy controls in between the 2 hallucinating groups. No significant differences were found for GABA+ levels. It is discussed that reduced ACC Glx levels reflect an inability of AVH patients to cognitively inhibit their “voices” through neuronal hypo-activity, which in turn originates from increased left STG Glu levels and neuronal hyperactivity. A revised E/I-imbalance model is proposed where Glu-Glu imbalance between brain regions is emphasized rather than Glu-GABA imbalance within regions, for the understanding of the underlying neurochemistry of AVHs.

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