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

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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Abnormal resting-state brain activity and connectivity of brain-bladder control network in overactive bladder syndrome

Acta Radiologica ◽

10.1177/02841851211057278 ◽

2021 ◽

pp. 028418512110572

Author(s):

Wang Biao ◽

Zuo Long ◽

Zhou Yang ◽

Gu Hua ◽

Wang Shuangkun

Keyword(s):

Overactive Bladder ◽

Resting State ◽

Clinical Symptoms ◽

Pearson Correlation ◽

Functional Integration ◽

Anterior Cingulate ◽

Control Network ◽

Bladder Control ◽

The Brain ◽

Left Insula

Background Neuroimaging studies have shown that the brain is involved in the mechanism of overactive bladder disease (OAB). Purpose To explorer spatial patterns of spontaneous neural activities and functional integration in patients with OAB. Material and Methods In total, 28 patients with OAB and 28 matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging and completed questionnaires to assess clinical symptoms. The amplitude of low-frequency ﬂuctuation (ALFF) and ROI-based functional connectivity (FC) within the brain-bladder control network (BBCN) were calculated and compared between the two groups using a two-sample t-test. Pearson correlation analysis was performed to investigate the relationship between ALFF and the clinical score of patients with OAB. Results Compared with HCs, patients with OAB exhibited significantly decreased ALFF in the left superior medial middle gyrus (SFGmed) and superior dorsal frontal gyrus (SFGdor), and increased ALFF in the right hippocampus. Furthermore, ALFF values in the left SFGmed were negatively correlated with OABSS scores. FC in patients with OAB was significantly increased between the bilateral caudate nucleus (CAU) and bilateral SFGdor, the bilateral CAU and bilateral supplementary motor area (SMA), the bilateral thalamus and SMA; the left CAU and bilateral SFGmed, the left CAU and bilateral anterior cingulate gyrus, and the left CAU and left insula. Additionally, decreased FC was found between the bilateral amygdala and bilateral SFGmed and the left SMA and left insula. Conclusion These abnormal activities and connectivities of BBCN may indicate impaired cortical control of micturition in OAB, suggesting a possible neural mechanism of OAB.

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Baseline measures of cerebral glutamate and GABA levels in individuals at ultrahigh risk for psychosis: Implications for clinical outcome after 12 months

European Psychiatry ◽

10.1192/j.eurpsy.2020.77 ◽

2020 ◽

Vol 63 (1) ◽

Author(s):

C. Wenneberg ◽

B. Y. Glenthøj ◽

L. B. Glenthøj ◽

B. Fagerlund ◽

K. Krakauer ◽

...

Keyword(s):

Clinical Outcome ◽

Functional Outcome ◽

Clinical Symptoms ◽

Mental States ◽

Anterior Cingulate ◽

Resonance Spectroscopy ◽

Global Improvement ◽

Long Term Outcome ◽

Remission Status ◽

Baseline Levels

Abstract Background. Cerebral glutamate and gamma-aminobutyric acid (GABA) levels might predict clinical outcome in individuals at ultrahigh risk (UHR) for psychosis but have previously primarily been investigated in smaller cohorts. We aimed to study whether baseline levels of glutamate and GABA in anterior cingulate cortex (ACC) and glutamate in thalamus could predict remission status and whether baseline metabolites differed in the remission versus the nonremission group. We also investigated the relationship between baseline metabolite levels and severity of clinical symptoms, functional outcome, and cognitive deficits at follow-up. Methods. About 124 UHR individuals were recruited at baseline. In this, 74 UHR individuals were clinically and cognitively assessed after 12 months, while remission status was available for 81 (25 remission/56 nonremission). Glutamate and GABA levels were assessed at baseline using 3 T proton magnetic resonance spectroscopy. Psychopathology, symptom severity, and remission were assessed with the Comprehensive Assessment of At-Risk Mental States and Clinical Global Impression and functional outcome with the Social and Occupational Functioning Assessment Scale. Cognitive function was estimated with the Cambridge Neuropsychological Test Automated Battery. Results. There were no differences between baseline glutamate and GABA levels in subjects in the nonremission group compared with the remission group, and baseline metabolites could not predict remission status. However, higher baseline levels of GABA in ACC were associated with clinical global improvement (r = −0.34, N = 51, p = 0.01) in an explorative analysis. Conclusions. The variety in findings across studies suggests a probable multifactorial influence on clinical outcome in UHR individuals. Future studies should combine multimodal approaches to attempt prediction of long-term outcome.

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Relationship Between Type 2 Diabetes and White Matter Hyperintensity: A Systematic Review

Frontiers in Endocrinology ◽

10.3389/fendo.2020.595962 ◽

2020 ◽

Vol 11 ◽

Author(s):

Dan-Qiong Wang ◽

Lei Wang ◽

Miao-Miao Wei ◽

Xiao-Shuang Xia ◽

Xiao-Lin Tian ◽

...

Keyword(s):

Type 2 Diabetes ◽

White Matter ◽

Structural Changes ◽

White Matter Lesions ◽

Poor Performance ◽

White Matter Hyperintensity ◽

Diabetic Microangiopathy ◽

The Relationship ◽

The Brain

White matter (WM) disease is recognized as an important cause of cognitive decline and dementia. White matter lesions (WMLs) appear as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI) scans of the brain. Previous studies have shown that type 2 diabetes (T2DM) is associated with WMH. In this review, we reviewed the literature on the relationship between T2DM and WMH in PubMed and Cochrane over the past five years and explored the possible links among the presence of T2DM, the course or complications of diabetes, and WMH. We found that: (1) Both from a macro- and micro-scopic point of view, most studies support the relationship of a larger WMH and a decrease in the integrity of WMH in T2DM; (2) From the relationship between brain structural changes and cognition in T2DM, the poor performance in memory, attention, and executive function tests associated with abnormal brain structure is consistent; (3) Diabetic microangiopathy or peripheral neuropathy may be associated with WMH, suggesting that the brain may be a target organ for T2DM microangiopathy; (4) Laboratory markers such as insulin resistance and fasting insulin levels were significantly associated with WMH. High HbA1c and high glucose variability were associated with WMH but not glycemic control.

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Cerebral metabolic and histological effects of thioacetamide-induced liver failure

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.265.3.g572 ◽

1993 ◽

Vol 265 (3) ◽

pp. G572-G578 ◽

Cited By ~ 8

Author(s):

J. Peeling ◽

L. Shoemaker ◽

T. Gauthier ◽

A. Benarroch ◽

G. R. Sutherland ◽

...

Keyword(s):

Liver Failure ◽

Frontal Cortex ◽

Clinical Symptoms ◽

Neuronal Injury ◽

Acute Hepatic Failure ◽

Occipital Cortex ◽

Resonance Spectroscopy ◽

Histopathological Analysis ◽

Gamma Aminobutyric Acid ◽

The Brain

Acute liver failure was induced in rats by successive administrations of thioacetamide over 3 days. At progressing stages of hepatic encephalopathy (HE), brains were fixed with microwave irradiation for analysis of metabolite levels or with formaldehyde for histopathological analysis. Metabolite levels were determined using 1H-nuclear magnetic resonance spectroscopy of perchloric acid extracts of the frontal cortex, parietal or occipital cortex, hippocampus, striatum, brain stem, and cerebellum. After thioacetamide treatment, thioacetamide and its metabolites were detected in the brains at levels that did not correlate with the stage of HE. No changes were observed in the levels of N-acetylaspartate, alanine, gamma-aminobutyric acid, aspartate, or inositol in any brain region after thioacetamide treatment. HE was accompanied by elevated glutamine, glucose, and lactate throughout the brain. At all stages of HE, taurine was decreased in the neocortex and hippocampus, and glutamate and choline compounds were decreased in the frontal cortex. None of the metabolite changes showed progression with the stage of HE. Progressing HE was accompanied by increasing neuronal injury in layer III of the neocortex, in the Purkinje cells of the cerebellum, and in the hippocampus, particularly in the CA4 sector. The similarity of this distribution of injury to that associated with excitotoxic injury suggests that metabolic abnormalities after acute hepatic failure may give rise to adverse effects at excitatory (glutamatergic) neuronal receptors, leading to neuronal injury and clinical symptoms of progressing encephalopathy in this model. However, neuronal injury and the presence of thioacetamide and its metabolites in the brain raise questions about the validity of thioacetamide-induced liver failure as a model for clinical HE.

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Relationship between Personality Disorders and Clinical Symptoms in Psychiatric Inpatients as Measured by the Millon Clinical Multiaxial Inventory

Psychological Reports ◽

10.2466/pr0.1994.74.1.331 ◽

1994 ◽

Vol 74 (1) ◽

pp. 331-336 ◽

Cited By ~ 6

Author(s):

David Chick ◽

Stephen K. Martin ◽

Robert Nevels ◽

C. Randy Cotton

Keyword(s):

Personality Disorders ◽

Clinical Symptoms ◽

Predictor Variables ◽

Stepwise Multiple Regression ◽

Regression Analyses ◽

Millon Clinical Multiaxial Inventory ◽

State Psychiatric ◽

Personality Disorder Scales ◽

The Relationship ◽

Criterion Variables

The Millon Clinical Multiaxial Inventory is a 175-item psychodiagnostic instrument which is based on Millon's theory of psychopathology, in which Millon suggests clinical symptoms result from an exacerbation of an individual's personality style when under stress. The purpose of the present study was to examine the relations of personality disorders to clinical symptoms as measured by the inventory. The sample of 245 inpatients from a state psychiatric hospital completed the Millon inventory between January, 1987 and April. 1989 Stepwise multiple-regression analyses were conducted to ascertain the relationship between personality disorders and symptoms. The 9 clinical symptom scales served as criterion variables while the personality-disorder scales served as predictor variables. The results were generally consistent with expectation and are discussed in terms of Millon's theory.

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

Psychological Medicine ◽

10.1017/s0033291717003403 ◽

2017 ◽

Vol 48 (11) ◽

pp. 1880-1889 ◽

Cited By ~ 7

Author(s):

Gemma Modinos ◽

Alice Egerton ◽

Anna McLaughlin ◽

Katrina McMullen ◽

Veena Kumari ◽

...

Keyword(s):

Healthy Subjects ◽

Structural Changes ◽

Gray Matter Volume ◽

Superior Temporal Gyrus ◽

Anterior Cingulate ◽

Self Report ◽

Resonance Spectroscopy ◽

Voxel Based Morphometry ◽

Ultra High Risk ◽

Separate Cohort

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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Resting-state functional connectivity, cortical GABA and neuroactive steroids in peripartum and peripartum depressed women: a functional magnetic imaging and resonance study

10.1101/411405 ◽

2018 ◽

Author(s):

Kristina M. Deligiannidis ◽

Christina L. Fales ◽

Aimee R. Kroll-Desrosiers ◽

Scott A. Shaffer ◽

Vanessa Villamarin ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Neuroactive Steroids ◽

Anterior Cingulate ◽

Resonance Spectroscopy ◽

Resting State Functional Connectivity ◽

Magnetic Imaging ◽

Temporal Pole ◽

The Right ◽

The Relationship

ABSTRACTPostpartum depression (PPD) is associated with abnormalities in resting-state functional connectivity (RSFC) but the underlying neurochemistry is unclear. We hypothesized that peripartum GABAergic neuroactive steroids (NAS) are related to cortical GABA concentrations and RSFC in PPD as compared to healthy comparison women (HCW). To test this, we measured RSFC with fMRI and GABA+/Creatine (Cr) concentrations with proton magnetic resonance spectroscopy (1H MRS) in the pregenual anterior cingulate (pgACC) and occipital cortices (OCC) and quantified peripartum plasma NAS. We examined between-group differences in RSFC and the relationship between cortical GABA+/Cr concentrations with RSFC. We investigated the relationship between NAS, RSFC and cortical GABA+/Cr concentrations. Within the default mode network (DMN) an area of the dorsomedial prefrontal cortex (DMPFC) had greater connectivity with the rest of the DMN in PPD (peak voxel: MNI coordinates (2, 58, 32), p=0.002) and was correlated to depression scores (peak HAM-D17 voxel: MNI coordinates (0, 60, 34), p=0.008). pgACC GABA+/Cr correlated positively with DMPFC RSFC in a region spanning the right anterior/posterior insula and right temporal pole (r=+0.661, p=0.000). OCC GABA+/Cr correlated positively with regions spanning both amygdalae (right amygdala: r=+0.522, p=0.000; left amygdala: r=+0.651, p=0.000) as well as superior parietal areas. Plasma allopregnanolone was higher in PPD (p=0.03) and positively correlated with intra DMPFC connectivity (r=+0.548, p=0.000) but not GABA+/Cr. These results provide initial evidence that PPD is associated with altered DMN connectivity; cortical GABA+/Cr concentrations are associated with postpartum RSFC and allopregnanolone is associated with postpartum intra-DMPFC connectivity.

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Alcohol and psychiatric and physical disorders

New Oxford Textbook of Psychiatry ◽

10.1093/med/9780199696758.003.0058 ◽

2012 ◽

pp. 442-447

Author(s):

Karl F. Mann ◽

Falk Kiefer

Keyword(s):

Clinical Symptoms ◽

Alcohol Intoxication ◽

Delirium Tremens ◽

Cerebellar Degeneration ◽

The Body ◽

Induced Mood ◽

Grand Mal ◽

Physical Disorders ◽

The Relationship ◽

The Brain

This chapter covers the clinical symptoms of alcohol intoxication, withdrawal (without complications and with perceptual disturbances, grand mal seizures, delirium tremens, and alcoholic hallucinosis), and psychiatric disorders, including alcohol-induced mood disorders and alcohol-induced anxiety disorders. The effects of alcohol on the brain are covered in detail, including Wernicke’s encephalopathy, Korsakoff’s syndrome, cerebellar degeneration, hepatocerebral degeneration, and foetal alcohol syndrome, as are the effects on the body, including malnutrition and vitamin deficiency, peripheral neuropathy, effects on the muscle, liver, pancreas, skin, and heart, and the relationship between alcohol and hypertension and cancer.

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OCT STUDIES IN SCHIZOPHRENIA: CURRENT EVIDENCE AND FUTURE PERSPECTIVES

International Journal of Advanced Research ◽

10.21474/ijar01/12068 ◽

2020 ◽

Vol 8 (11) ◽

pp. 769-777

Author(s):

Ushna Usman ◽

Keyword(s):

Structural Changes ◽

Neurodevelopmental Disorder ◽

Current Evidence ◽

Structural Alterations ◽

Comprehensive Search ◽

The Subject ◽

The Relationship ◽

The Brain ◽

Neuroimaging Techniques

Background: Schizophrenia is a detrimental neurodevelopmental disorder that affects nearly 1 % of the population worldwide. Although schizophrenia ranks among the leading causes of global disease-related disability, definitive investigations do not exist for its diagnosis at present. Since the retina is derived from the same neural layer that the brain develops from, OCT imaging of retina can provide valuable information regarding underlying pathology of schizophrenia. Objectives: This review aims at describing the potential relevance of OCT studies 1) in understanding current insights into retinal structural changes in schizophrenia 2) in understanding the relationship between retinal structural alterations and disease progression and chronicity 3) and to determine the potential role of retinal changes as biomarkers of schizophrenia. Methodology: A comprehensive search of databases such as PubMed, Google Scholar and Medline was conducted using the keywords: schizophrenia, retina, OCT and RNFL changes. Relevant articles were identified and their key findings summarized in this review. Conclusion: OCT studies in schizophrenia patients conducted in recent years continue to provide evidence of retinal structural alterations associated with schizophrenia. However, the findings of these studies vary and there is a need to conduct further studies for clarification regarding the subject. The application of OCT and other neuroimaging techniques to correlate retinal structural alterations with schizophrenia may potentially help establish the role of retinal variables as biomarkers for the disease, and may open a gateway for better diagnostic investigations in schizophrenia.

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The role of leptin mediating the relationship between ‘Somatic Anxiety’ symptoms and major depressive disorder

10.21203/rs.2.17147/v1 ◽

2019 ◽

Author(s):

Fei Wang ◽

Yue Zhu ◽

Yange Wei ◽

Jia Duan ◽

Ran Zhang ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Emotional Processing ◽

Clinical Symptoms ◽

Anxiety Symptoms ◽

Clinical State ◽

Major Depressive ◽

Somatic Anxiety ◽

Drug Naïve ◽

The Relationship

Abstract Background：Leptin is a multifunctional hormone with influences on neural circuitry in emotional processing, and it may play a role in the pathophysiology of major depressive disorder (MDD). In this study, we aimed to investigate whether leptin levels were differentiated in patients with MDD and those at genetic high risk of MDD (GHR-MDD) and the relationship between leptin and clinical symptoms. Methods: Participants (18 drug-naïve MDD, 15 GHR-MDD and 40 healthy controls) completed clinical assessments and provided blood samples for measurement of leptin levels. Leptin levels were compared across all groups and associations between leptin and clinical symptoms were explored and mediation models tested. Results: We found that leptin was increased in MDD. We also found a correlation between leptin and ‘Somatic Anxiety’ symptoms in MDD and that leptin was a significant and independent mediator of clinical state and ‘Somatic Anxiety’ symptoms. Conclusions: MDD patients occured with dysregulation of leptin. Additionally, there was a correlation between leptin and ‘Somatic Anxiety’ symptoms in MDD. The finding of leptin as a significant and independent mediator of clinical state and ‘Somatic Anxiety’ symptoms suggested leptin plays an indirect effect in somatic depressive symptoms in MDD.

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