scholarly journals Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junchao Huang ◽  
Jinghui Tong ◽  
Ping Zhang ◽  
Yanfang Zhou ◽  
Yimin Cui ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Impairment ◽  
Cortical Thickness ◽  
Serum Levels ◽  
Healthy Controls ◽  
Tryptophan Pathway ◽  
Liquid Chromatography Tandem Mass ◽  
Therapeutic Development ◽  
Tryptophan Metabolites ◽  
Insight Into

AbstractA number of tryptophan metabolites known to be neuroactive have been examined for their potential associations with cognitive deficits in schizophrenia. Among these metabolites, kynurenic acid (KYNA), 5-hydroxyindole (5-HI), and quinolinic acid (QUIN) are documented in their diverse effects on α-7 nicotinic acetylcholine receptor (α7nAChR) and/or N-methyl-D-aspartate receptor (NMDAR), two of the receptor types thought to contribute to cognitive impairment in schizophrenia. In this study, serum levels of KYNA, 5-HI, and QUIN were measured in 195 patients with schizophrenia and in 70 healthy controls using liquid chromatography-tandem mass spectrometry; cognitive performance in MATRICS Consensus Cognitive Battery and cortical thickness measured by magnetic resonance imaging were obtained. Patients with schizophrenia had significantly lower serum KYNA (p < 0.001) and QUIN (p = 0.02) levels, and increased 5-HI/KYNA (p < 0.001) and QUIN/KYNA ratios (p < 0.001) compared with healthy controls. Multiple linear regression showed that working memory was positively correlated with serum 5-HI levels (t = 2.10, p = 0.04), but inversely correlated with KYNA concentrations (t = −2.01, p = 0.05) in patients. Patients with high 5-HI and low KYNA had better working memory than other subgroups (p = 0.01). Higher 5-HI levels were associated with thicker left lateral orbitofrontal cortex (t = 3.71, p = 2.94 × 10−4) in patients. The different effects of 5-HI and KYNA on working memory may appear consistent with their opposite receptor level mechanisms. Our findings appear to provide a new insight into the dynamic roles of tryptophan pathway metabolites on cognition, which may benefit novel therapeutic development that targets cognitive impairment in schizophrenia.

Brain Cortical Thickness and Surface Area Correlates of Neurocognitive Performance in Patients with Schizophrenia, Bipolar Disorder, and Healthy Adults

2011 ◽  
Vol 17 (6) ◽  
pp. 1080-1093 ◽  
Author(s):  
C.B. Hartberg ◽  
K. Sundet ◽  
L.M. Rimol ◽  
U.K. Haukvik ◽  
E.H. Lange ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Working Memory ◽  
Surface Area ◽  
Cortical Thickness ◽  
Negative Relationship ◽  
Anterior Cingulate ◽  
Neurocognitive Functioning ◽  
Healthy Controls ◽  
Neurocognitive Performance ◽  
Mri Scans

AbstractRelationships between cortical brain structure and neurocognitive functioning have been reported in schizophrenia, but findings are inconclusive, and only a few studies in bipolar disorder have addressed this issue. This is the first study to directly compare relationships between cortical thickness and surface area with neurocognitive functioning in patients with schizophrenia (n = 117) and bipolar disorder (n = 121) and healthy controls (n = 192). MRI scans were obtained, and regional cortical thickness and surface area measurements were analyzed for relationships with test scores from 6 neurocognitive domains. In the combined sample, cortical thickness in the right rostral anterior cingulate was inversely related to working memory, and cortical surface area in four frontal and temporal regions were positively related to neurocognitive functioning. A positive relationship between left transverse temporal thickness and processing speed was specific to schizophrenia. A negative relationship between right temporal pole thickness and working memory was specific to bipolar disorder. In conclusion, significant cortical structure/function relationships were found in a large sample of healthy controls and patients with schizophrenia or bipolar disorder. The differences that were found between schizophrenia and bipolar may indicate differential relationship patterns in the two disorders, which may be of relevance for understanding the underlying pathophysiology. (JINS, 2011, 17, 1080–1093)

scholarly journals T1 Relaxation Times in the Cortex and Thalamus Are Associated With Working Memory and Information Processing Speed in Patients With Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Christian Thaler ◽  
Isabelle Hartramph ◽  
Jan-Patrick Stellmann ◽  
Christoph Heesen ◽  
Maxim Bester ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Working Memory ◽  
Cognitive Impairment ◽  
Information Processing ◽  
Processing Speed ◽  
T1 Mapping ◽  
Relaxation Times ◽  
Healthy Controls ◽  
Information Processing Speed ◽  
T1 Relaxation

Background: Cortical and thalamic pathologies have been associated with cognitive impairment in patients with multiple sclerosis (MS).Objective: We aimed to quantify cortical and thalamic damage in patients with MS using a high-resolution T1 mapping technique and to evaluate the association of these changes with clinical and cognitive impairment.Methods: The study group consisted of 49 patients with mainly relapsing-remitting MS and 17 age-matched healthy controls who received 3T MRIs including a T1 mapping sequence (MP2RAGE). Mean T1 relaxation times (T1-RT) in the cortex and thalami were compared between patients with MS and healthy controls. Additionally, correlation analysis was performed to assess the relationship between MRI parameters and clinical and cognitive disability.Results: Patients with MS had significantly decreased normalized brain, gray matter, and white matter volumes, as well as increased T1-RT in the normal-appearing white matter, compared to healthy controls (p &lt; 0.001). Partial correlation analysis with age, sex, and disease duration as covariates revealed correlations for T1-RT in the cortex (r = −0.33, p &lt; 0.05), and thalami (right thalamus: r = −0.37, left thalamus: r = −0.50, both p &lt; 0.05) with working memory and information processing speed, as measured by the Symbol-Digit Modalities Test.Conclusion: T1-RT in the cortex and thalamus correlate with information processing speed in patients with MS.

scholarly journals Elevated Angiopoietin-1 Serum Levels in Patients with Alzheimer’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Brigitte Schreitmüller ◽  
Thomas Leyhe ◽  
Elke Stransky ◽  
Niklas Köhler ◽  
Christoph Laske
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Serum Levels ◽  
Cognitive Status ◽  
Potential Candidate ◽  
Healthy Controls ◽  
Healthy Elderly ◽  
Significant Difference ◽  
Angiopoietin 1

Background. Alzheimer's disease (AD) is the most common cause of dementia in the elderly. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles and by massive neuronal loss in the brain. There is epidemiologic and pathologic evidence that AD is associated with vascular risk factors and vascular diseases, contributing to cerebral hypoperfusion with consecutive stimulation of angiogenesis and upregulation of proangiogenic factors such as Angiopoietin-1 (Ang-1).Methods. In the present study, we measured Ang-1 serum levels in 42 patients with AD, 20 patients with mild cognitive impairment (MCI), and in 40 healthy elderly controls by ELISA.Results. We found significantly increased Ang-1 serum levels in patients with AD compared to control subjects(P=0.003). There was no significant difference between MCI patients and healthy controls(P=0.553)or between AD and MCI patients(P=0.054). The degree of cognitive impairment as measured by the mini-mental status examination (MMSE) score was significantly correlated with the Ang-1 serum levels in all patients and healthy controls.Conclusions. We found significantly increased Ang-1 serum levels in AD patients. We could also show an association between Ang-1 serum levels and the cognitive status in all patients and healthy controls. Thus, serum Ang-1 could be a potential candidate for a biomarker panel for AD diagnosis.

scholarly journals Metabolomic Profiling Identified Serum Metabolite Biomarkers and Related Metabolic Pathways of Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Chengjian Zhang ◽  
Shengnan Zhou ◽  
Huijing Chang ◽  
Feng Zhuang ◽  
Yang Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metabolic Pathways ◽  
Roc Curves ◽  
Serum Levels ◽  
Serum Biomarkers ◽  
Healthy Controls ◽  
Dodecylbenzenesulfonic Acid ◽  
Metabolomic Profiling ◽  
Liquid Chromatography Tandem Mass ◽  
Healthy Control

Background. The screening and early detection of colorectal cancer (CRC) still remain a challenge due to the lack of reliable and effective serum biomarkers. Thus, this study is aimed at identifying serum biomarkers of CRC that could be used to distinguish CRC from healthy controls. Methods. A prospective 1 : 2 individual matching case-control study was performed which included 50 healthy control subjects and 98 CRC patients. Untargeted metabolomic profiling was conducted with liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify CRC-related metabolites and metabolic pathways. Results. In total, 178 metabolites were detected, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish CRC patients from healthy controls. Nine metabolites showed significantly differential serum levels in CRC patients under the conditions of variable importance in projection VIP > 1 , p < 0.05 using Student’s t -test, and fold change FC ≥ 1.2 or ≤0.5. The above nine metabolites were 3-hydroxybutyric acid, hexadecanedioic acid, succinic acid semialdehyde, 4-dodecylbenzenesulfonic acid, prostaglandin B2, 2-pyrocatechuic acid, xanthoxylin, 12-hydroxydodecanoic acid, and formylanthranilic acid. Four potential biomarkers were identified to diagnose CRC through ROC curves: hexadecanedioic acid, 4-dodecylbenzenesulfonic acid, 2-pyrocatechuic acid, and formylanthranilic acid. All AUC values of these four serum biomarkers were above 0.70. In addition, the exploratory analysis of metabolic pathways revealed the activated states for the vitamin B metabolic pathway and the alanine, aspartate, and glutamate metabolic pathways associated with CRC. Conclusion. The 4 identified potential metabolic biomarkers could discriminate CRC patients from healthy controls, and the 2 metabolic pathways may be activated in the CRC tissues.

scholarly journals The Effect of Task-Irrelevant Fearful-Face Distractor on Working Memory Processing in Mild Cognitive Impairment versus Healthy Controls: An Exploratory fMRI Study in Female Participants

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Amer M. Burhan ◽  
Udunna C. Anazodo ◽  
Jun Ku Chung ◽  
Amanda Arena ◽  
Ariel Graff-Guerrero ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Anterior Cingulate ◽  
Healthy Controls ◽  
Bold Signal ◽  
Fearful Face ◽  
Task Irrelevant ◽  
Emotional Face ◽  
The Impact

In mild cognitive impairment (MCI), a risk state for Alzheimer’s disease, patients have objective cognitive deficits with relatively preserved functioning. fMRI studies have identified anomalies during working memory (WM) processing in individuals with MCI. The effect of task-irrelevant emotional face distractor on WM processing in MCI remains unclear. We aim to explore the impact of fearful-face task-irrelevant distractor on WM processing in MCI using fMRI.Hypothesis. Compared to healthy controls (HC), MCI patients will show significantly higher BOLD signal ina prioriidentified regions of interest (ROIs) during a WM task with a task-irrelevant emotional face distractor.Methods. 9 right-handed female participants with MCI and 12 matched HC performed a WM task with standardized task-irrelevant fearful versus neutral face distractors randomized and counterbalanced across WM trials. MRI images were acquired during the WM task and BOLD signal was analyzed using statistical parametric mapping (SPM) to identify signal patterns during the task response phase.Results. Task-irrelevant fearful-face distractor resulted in higher activation in the amygdala, anterior cingulate, and frontal areas, in MCI participants compared to HC.Conclusions. This exploratory study suggests altered WM processing as a result of fearful-face distractor in MCI.

scholarly journals Altered Ethanolamine Plasmalogen and Phosphatidylethano-lamine Concentrations in Serum of Patients with Bipolar Disorder (P08-117-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Shintaro Ogawa ◽  
Kotaro Hattori ◽  
Dayan Goodenowe ◽  
Hiroshi Kunugi
Keyword(s):  
Bipolar Disorder ◽  
Symptom Severity ◽  
Serum Levels ◽  
Type I ◽  
Healthy Controls ◽  
Funding Sources ◽  
Neuropsychiatric Diseases ◽  
Liquid Chromatography Tandem Mass ◽  
Ethanolamine Plasmalogen ◽  
Medication Status

Abstract Objectives Growing evidence has suggested that metabolic alterations of plasmalogen ethanolamine (PlsEtn) are implicated in neuropsychiatric diseases. However, few studies examined the association of peripheral blood PlsEtn levels with bipolar disorder (BP). In this study, we measured serum PlsEtn and phosphatidylethanolamine (PtdEtn) levels in patients with BP and healthy controls. We investigated the relationships between serum PlsEtn and PtdEtn levels, diagnosis, symptom severity and medication status. Methods Subjects were 40 patients with BP (DSM-IV) and 40 healthy controls matched for age, sex, and ethnicity (Japanese). Informed consent was obtained from each subject. Serum levels of PlsEtn and PtdEtn were determined by liquid chromatography/tandem mass spectrometry. Results Serum PlsEtn were significantly lower in patients with BP compared with controls (P = 0.017). Serum PtdEtn levels were significantly lower in patients with a BP type I (n = 12) versus patients with BP type II (n = 24) diagnosis (P = 0.011). In the BP patients, symptom severity did not correlate with serum PlsEtn or PtdEtn levels. Conclusions Low serum PlsEtn might be involved in the pathophysiology of BP. PtdEtn might be related differently with BP I and BP II. Funding Sources This study was supported by an Intramural Research Grant for Neurological and Psychiatric Disorders by the National Center of Neurology and Psychiatry (H.K.).

scholarly journals Morphological Changes in Cortical and Subcortical Structures in Multiple System Atrophy Patients With Mild Cognitive Impairment

2021 ◽  
Vol 15 ◽  
Author(s):  
Chenghao Cao ◽  
Qi Wang ◽  
Hongmei Yu ◽  
Huaguang Yang ◽  
Yingmei Li ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Multiple System Atrophy ◽  
Cortical Thickness ◽  
Gray Matter ◽  
Middle Temporal Gyrus ◽  
Healthy Controls ◽  
Subcortical Structures ◽  
Middle Temporal ◽  
Left Middle

ObjectiveThis study aimed to investigate the morphometric alterations in the cortical and subcortical structures in multiple system atrophy (MSA) patients with mild cognitive impairment (MCI), and to explore the association with cognitive deficits.MethodsA total of 45 MSA patients (25 MSA-only, 20 MSA-MCI) and 29 healthy controls were recruited. FreeSurfer software was used to analyze cortical thickness, and voxel-based morphometry was used to analyze the gray matter volumes. Cortical thickness and gray matter volume changes were correlated with cognitive scores.ResultsCompared to healthy controls, both MSA subgroups exhibited widespread morphology alterations of brain structures in the fronto-temporal regions. Direct comparison of MSA-MCI and MSA-only patients showed volume reduction in the left superior and middle temporal gyrus, while cortical thinning was found in the left middle and inferior temporal gyrus in MSA-MCI patients. Cortical thinning in the left middle temporal gyrus correlated with cognitive assessment and disease duration.ConclusionStructural changes in the brain occur in MSA-MCI patients. The alteration of brain structure in the left temporal regions might be a biomarker of cognitive decline in MSA-MCI patients.

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