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Objective@#To investigate the difference of temporary memory system and brain biochemical metabolites between patients with depressive obsessive-compulsive disorder and simple obsessive-compulsive disorder.@*Methods@#From June 2017 to June 2018, 31 patients with simple obsessive-compulsive disorder, 33 patients with depressive obsessive-compulsive disorder and 25 healthy volunteers were selected as subjects. The temporary memory ability of the three groups was tested by n-back, Stoop color association test and digital breadth test. Three brain sublimation metabolites, N-acetylaspartate acid (NAA), choline complex (Cho) and creatine (Cr), were detected by proton magnetic resonance pop (1H-MRS) in bilateral prefrontal white matter, anterior cingulate cortex and anterior cingulate cortex. The ratio of NAA/Cr and Cho/Cr was calculated with Cr as reference material.@*Results@#The scores of Yale-brown obsessive-compulsive severity scale (Y-BOCS) and Hamilton depression rating scale 24 (HAMD24) in the patients with simple obsessive-compulsive disorder and depression obsessive-compulsive disorder group were significantly higher than those in the healthy control group, and the scores of HAMD24 in the patients with depression obsessive-compulsive disorder group were significantly higher than those in the patients with simple obsessive-compulsive disorder group, with statistically significant difference (P<0.05). The number of correct n-back in the simple obsessive-compulsive group and the depressive obsessive-compulsive group was significantly lower than that in the healthy control group (P<0.05). The digital span test (DST) scores of the patients in the simple obsessive-compulsive disorder group and the depressive obsessive-compulsive disorder group were (14.37±2.96) and (12.39±2.14), which were significantly lower than those in the healthy control group (17.46±3.28) (P<0.05). There was no significant difference in NAA/Cr and Cho/Cr between the three groups (P>0.05). Compared with the healthy control group, the NAA/Cr value of bilateral prefrontal white matter in the simple obsessive-compulsive group and the depression obsessive-compulsive group was significantly lower, and the difference was statistically significant (P<0.05).@*Conclusions@#Both patients with simple obsessive-compulsive disorder and depressive obsessive-compulsive disorder had speech memory impairment and bilateral prefrontal white matter nerve function decline, while depressive obsessive-compulsive disorder patients also had central executive memory impairment.
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italic>N-Acetylaspartate (NAA) is a highly abundant brain metabolite. Nowadays, as an important marker reflecting the function of nervous system, NAA is widely used in the results analysis of nuclear magnetic resonance spectroscopy (1H MRS). NAA is synthesized in mitochondria of neurons and metabolized in oligodendrocytes. Additionally, NAA may be converted to the dipeptide N-acetylaspartylglutamate (NAAG), and catabolized into NAA and glutamate in astrocytes. NAA is related to a variety of central nervous system diseases, including Canavan disease, multiple sclerosis, depression, schizophrenia and other mental diseases. Therefore, NAA may be a biomarker of these diseases, and its related enzymes may be used as therapeutic targets for drug screening. Here, we combined the current research on the molecular mechanisms of NAA to reveal the process of NAA generation, metabolism and transport in the brain, explain the possible physiological effects of NAA and discuss its relationship with central nervous system diseases, explore the prospect of NAA in disease prediction and diagnosis, as well as the targeted treatment that may become the breakthrough of refractory diseases.
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Objective To investigate the difference of temporary memory system and brain biochemical metabolites between patients with depressive obsessive-compulsive disorder and simple obsessivecompulsive disorder.Methods From June 2017 to June 2018,31 patients with simple obsessive-compulsive disorder,33 patients with depressive obsessive-compulsive disorder and 25 healthy volunteers were selected as subjects.The temporary memory ability of the three groups was tested by n-back,Stoop color association test and digital breadth test.Three brain sublimation metabolites,N-acetylaspartate acid (NAA),choline complex (Cho) and creatine (Cr),were detected by proton magnetic resonance pop (1 H-MRS) in bilateral prefrontal white matter,anterior cingulate cortex and anterior cingulate cortex.The ratio of NAA/Cr and Cho/Cr was calculated with Cr as reference material.Results The scores of Yale-brown obsessivecompulsive severity scale (Y-BOCS) and Hamilton depression rating scale 24 (HAMD24) in the patients with simple obsessive-compulsive disorder and depression obsessive-compulsive disorder group were significantly higher than those in the healthy control group,and the scores of HAMD24 in the patients with depression obsessive-compulsive disorder group were significantly higher than those in the patients with simple obsessive-compulsive disorder group,with statistically significant difference (P ＜ 0.05).The number of correct n-back in the simple obsessive-compulsive group and the depressive obsessive-compulsive group was significantly lower than that in the healthy control group (P ＜0.05).The digital span test (DST) scores of the patients in the simple obsessive-compulsive disorder group and the depressive obsessive-compulsive disorder group were (14.37 ± 2.96) and (12.39 ± 2.14),which were significantly lower than those in the healthy control group (17.46 ± 3.28) (P ＜ 0.05).There was no significant difference in NAA/Cr and Cho/Cr between the three groups (P ＞ 0.05).Compared with the healthy control group,the NAA/Cr value of bilateral prefrontal white matter in the simple obsessive-compulsive group and the depression obsessivecompulsive group was significantly lower,and the difference was statistically significant (P ＜ 0.05).Conclusions Both patients with simple obsessive-compulsive disorder and depressive obsessive-compulsive disorder had speech memory impairment and bilateral prefrontal white matter nerve function decline,while depressive obsessive-compulsive disorder patients also had central executive memory impairment.
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BACKGROUND: To investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain. METHODS: The paw withdrawal threshold was measured by mechanical stimulation the right hind paw with the von frey hair in the rats of CCI-induced neuropathic pain. The N-acetylaspartate (NAA) and Glutamate (Glu) in thalamus were detected by magnetic resonance spectrum (MRS) process. The thalamic functional connectivity with other brain regions was scanned by functional magnetic resonance image (fMRI). RESULTS: The paw withdrawal threshold of the ipsilateral side showed a noticeable decline during the pathological process. Increased concentrations of Glu and decreased levels of NAA in the thalamus were significantly correlated with mechanical allodynia in the neuropathic pain states. The thalamic regional homogeneity (ReHo) decreased during the process of neuropathic pain. The functional connectivity among the thalamus with the insula and somatosensory cortex were significantly increased at different time points (7, 14, 21 days) after CCI surgery. CONCLUSION: Our study suggests that dynamic changes in thalamic NAA and Glu levels contribute to the thalamic functional connection hyper-excitation during CCI-induced neuropathic pain. Enhanced thalamus-insula functional connection might have a significant effect on the occurrence of neuropathic pain.
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Animals , Rats , Thalamus/metabolism , Wounds and Injuries/physiopathology , Neurotransmitter Agents/metabolism , Neuralgia , Thalamus/physiopathology , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Glutamic Acid/metabolism , Constriction , HyperalgesiaABSTRACT
Objective:To explore the mechanism of Sailuotong capsules in treating acute cerebral ischemia from the perspective of metabonomics. Method:A total of 24 SD rats were randomly divided into 3 groups, including sham-operated group, model group and Sailuotong group (33 mg·kg-1). The rat model of acute multiple cerebral infarction was established by injecting fluorescent microspheres into internal carotid artery. After the successful operation, rats in Sailuotong group were administered by duodenal injection immediately, and the dosage volume was 2 mL·kg-1. Endogenous metabolites in rat brain tissues of each group were determined by UPLC-Q-TOF-MS. The relevant data and biomarkers were analyzed by principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). Result:The analysis of pattern recognition indicated that the metabolite profiles in model group and sham-operated group were separated obviously, and ten biomarkers related to acute cerebral ischemia were also identified. Compared with the sham-operated group, contents of N-acetylaspartate (NAA), fumaric acid, glutathione, dehydroascorbic acid, aspartic acid and S-adenosylhomocysteine were decreased, while the contents of arginine, citrulline, saccharopine and hydantoin-5-propionic acid were increased in the model group. Meanwhile, the ten abnormal biomarkers mentioned above got restoration in Sailuotong group. Conclusion:The main regulated metabolic pathways of Sailuotong capsules are NAA metabolism, arginine metabolism, energy metabolism, oxidative stress, etc.
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Objective The objective of this study was to utilize proton magnetic resonance spectroscopy (1H-MRS) to assess metabolites in cerebellar nuclei in unmedicated patients with insomnia disorder. Methods 1H-MRS was performed on cerebellar nuclei in 23 unmedicated patients with insomnia disorder (insomnia group) and 18 normal sleepers (control group). N-acetylaspartate (NAA), choline-containing compound (Cho) and creatine (Cr) were measured and the ratios of NAA/Cr and Cho/Cr were determined.Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) were used to assess the subjective sleep quality and insomnia severity of all subjects, while State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI) were used to assess the levels of anxiety and depression of all subjects. Sleep parameters of all subjects were measured by polysomnography (PSG). Results Mean NAA/Cr ratio of right cerebellar nuclei in insomnia group was significantly lower than that in control group (1.72±0.37 vs. 2.03±0.50, t=2.280, P=0.028). Mean NAA/Cr ratio of right cerebellar nuclei was significantly higher than that of left cerebellar nuclei within control group (2.03±0.50 vs. 1.68±0.21, t=3.386, P=0.004). There was no significant difference with regard to NAA/Cr ratio between bilateral cerebellar nuclei within insomnia group (t=1.416, P=0.171). Across all subjects, PSQI global scores (r=-0.369, P=0.018), and sleep latency (r=-0.437, P=0.004) and number of awakenings after sleep onset (r=-0.432, P=0.005) measured by PSG were negatively correlated with NAA/Cr ratios of right cerebellar nuclei, while percentages of stage 3 sleep (r=0.377,P=0.015) measured by PSG were positively correlated with NAA/Cr ratios of right cerebellar nuclei,respectively. Conclusion Patients with insomnia disorder have a hemispherically lateralized metabolic disturbance of NAA/Cr in right cerebellar nuclei,indicating that patients with insomnia disorder have neuronal damage in right cerebellar nuclei.
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OBJECTIVE: To explore the precise mechanism of electroacupuncture (EA) to delay cognitive impairment in Alzheimer disease. Methods N -Acetylaspartate (NAA), glutamate (Glu) and myoinositol (mI) metabolism were measured by magnetic resonance spectroscopy, learning and memory of APP/PS1 mouse was evaluated by the Morris water maze test and the step-down avoidance test, neuron survival number and neuronal structure in the hippocampus were observed by Nissl staining, and BDNF and phosphorylated TrkB detected by Western blot. RESULTS: EA at DU20 acupuncture significantly improve learning and memory in behavioral tests, up-regulate NAA, Glu and mI metabolism, increase the surviving neurons in hippocampus, and promote the expression of BDNF and TrkB in the APP/PS1 transgenic mice. CONCLUSION: These findings suggested that EA is a potential therapeutic for ameliorate cognitive dysfunction, and it might be due to EA could improve NAA and Glu metabolism by upregulation of BDNF in APP/PS1 mice.
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Animals , Male , Mice , Electroacupuncture/methods , Aspartic Acid/analogs & derivatives , Glutamic Acid/metabolism , Hippocampus/chemistry , Learning/physiology , Memory/physiology , Protein-Tyrosine Kinases/analysis , Magnetic Resonance Imaging , Membrane Glycoproteins/analysis , Mice, Transgenic , Magnetic Resonance Spectroscopy , Random Allocation , Blotting, Western , Aspartic Acid/metabolism , Maze Learning , Brain-Derived Neurotrophic Factor , Models, Animal , Exercise Test , Hippocampus/diagnostic imaging , Inositol/analysisABSTRACT
Purpose To evaluate 1H proton magnetic resonance spectroscopy (1H-MRS) in detecting traumatic brain injury (TBI) and its metabolic changes during the initial two weeks after trauma using rabbit modes. Materials and Methods Fifteen Chinese rabbits were randomly divided into sham control group (n=5) and TBI group (n=10), 1H-MRS was performed 1 hour, 6 hours, 24 hours and 2 days, 7 days, 14 days after trauma, the concentration of N-acetylaspartate (NAA), creatine (Cr), choline-compound (Cho), NAA/Cr and Cho/Cr in each group was evaluated. At 6 hours, 24 hours and 168 hours after injury, 1 rabbit was slaughtered after abdominal anesthesia at each time point, the sample was ifxed with left heart catheterization perfusion after death, brain tissue was obtained, blocked, dehydrated into frozen section, HE staining was used for observation. Results Compared with the control group, NAA/Cr ratio in the trauma region decreased by 29%1 hour after trauma, with maximal reduction of 40% (at 24 hours) before increasing slightly, the NAA/Cr ratio returned to control level gradually until 168 hours later. The Cho/Cr ratio decreased by 16% 1 hour after trauma, with maximal reduction of 30%(at 6 hours) and increased gradually until finally su rpassed control level (168 hours) for 20% and then became stable. NAA/Cr ratio and Cho/Cr ratio showed statistically significant changes between each observing time point (P<0.05). Conclusion 1H-MRS can be used for dynamic detection of cerebral metabolism without injury, and is superior to MRI in detecting early abnormality of the brain, with NAA/Cr as the most sensitive parameter. Detecting the changes of NAA/Cr, Cho/Cr ratios in the trauma region can be used as a guide for assessment of the clinical treatment effectiveness of TBI.
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Objective To investigate the changes of the N-acetylaspartate(NAA) concentrations in different brain regions and executive function skills in alcohol dependence,and to study the relationship between NAA levels and cognitive functions in subjects.Methods 49 male,non-smoking,alcohol-dependent patients and 45 healthy control subjects were measured with Proton 1H Magnetic resonance spectroscopy (MRS) and Wisconsin Card Sorting Test (WCST).Results Alcoholics had lower NAA/Cr ratios in prefrontal grey matter(GM) (1.59± 0.13) and white matter(WM) (1.58±0.12) regions and performed poorly on executive function tests compared to controls (P＜0.001).NAA/Cr in left prefrontal regions positively correlated with certain parameters of EF testing (number of correct responses 30.37± 3.73,perseverative errors 11.49± 3.39,random errors 6.18± 2.64,categories completed 2.08± 1.59)in alcoholic group (P＜0.01).NAA/Cr in prefrontal WM regions correlated with certain parameters of EF testing in alcoholic group (number of correct responses r=0.379,categories completed r=0.433,P＜ 0.05).Conclusion Long-term,chronic alcoholism will damage neuronal viability and cognitive functions,which suggests that NAA concentrations can reflect the extent of damage of cognitive functions with decreased levels reflecting neuronal loss.
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OBJECTIVE: In the present study, we measured hippocampal N-acetyl-l-aspartate (NAA), choline (CHO) and creatine (CRE) values in patients with panic disorder and healthy control subjects using in vivo 1H MRS. METHODS: We scanned 20 patients meeting Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for panic disorder and 20 matched healthy controls with a 1.5 Tesla GE Signa Imaging System and measured of NAA, CHO, and CRE in hippocampal regions. RESULTS: When NAA, CHO and CRE values were compared between groups, statistically significant lower levels for all ones were detected for both sides. CONCLUSION: Consequently, in the present study we found that NAA, CHO and CRE values of the patients with panic disorder were lower than those healthy controls. Future studies involving a large number of panic patients may shed further light on the generalizability of the current findings to persons with panic disorder.
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Humans , Aspartic Acid , Choline , Creatine , Light , Panic , Panic DisorderABSTRACT
Objective To compare the metabolic measures on prefrontal lobe and thalamus among schizophrenics with or without mental disorder family history by proton magnetic resonance spectroscopy (1 H-MRS),and to explore the relationship among metabolic measures,clinical symptom,and executive functioning.Methods Thirty-one schizophrenics with schizophrenia family history,21 schizophrenics with the other mental disorder family history,and 78 schizophrenics without mental disorder family history were examined at prefrontal lobe and thalamus by multi-voxel 1H-MRS.The N-acetylaspartate (NAA),Choline-congtaining compounds (Cho),and Creatine compounds (Cr) were measured and the ratios of NAA/Cr and Cho/Cr were determined.Meanwhile,Positive and Negative Syndrome Scale (PANSS) and Wisconsin Card Sorting Test (WCST) were also assessed in all schizophrenics.Results Both in schizophrenics with schizophrenia family history and with the other mental disorder family history,the NAA/Cr ratios showed lower than those in schizophrenics without mental disorder family history both on left prefrontal lobe and on fight thalamus ( P ＜ 0.05 ).Compared with schizophrenics without mental disorder family history,the score of negative symptoms and the perseverative errors demonstrated higher ( P＜ 0.05 or 0.01 ),the categories completed showed lower both in schizophrenics with schizophrenia family history and with the other mental disorder family history ( P＜0.05 ).The NAA/Cr ratios on left prefrontal lobe in all schizophrenics were significantly negatively related with the total score of PANSS and the responses errors (P ＜ 0.05 or P＜ 0.01 ),and positively related with the categories completed and the conceptual level responses ( P＜ 0.05 or P＜ 0.01 ).On left prefrontal lobe both in schizophrenics with schizophrenia family history and with the other mental disorder family history,the ratios of NAA/Cr were negatively related with the score of negative symptoms and the perseverative errors ( P ＜ 0.05 or 0.01 ).Conclusion The damages of neurons on prefrontal lobe and thalamus in schizophrenics with mental disorder family history may be more severe than those in schizophrenics without family history,and the damages on prefrontal lobe are related with negative symptoms and executive functioning.
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The aim of the present study was to determine whether specific subgroups of schizophrenic patients, grouped according to electrodermal characteristics, show differences in the N-acetylaspartate/creatine plus choline (NAA / (Cr + Cho)) ratios in the frontal, cingulate and perirolandic cortices. Skin conductance levels (SCL) and skin conductance responses to auditory stimulation were measured in 38 patients with schizophrenia and in the same number of matched healthy volunteers (control). All subjects were submitted to multivoxel proton magnetic resonance spectroscopic imaging. When compared to the control group, patients presented significantly lower NAA / (Cr + Cho) ratios in the right dorsolateral prefrontal cortex (schizophrenia = 0.95 ± 0.03; control = 1.12 ± 0.04) and in the right (schizophrenia = 0.88 ± 0.02; control = 0.94 ± 0.03) and left (schizophrenia = 0.84 ± 0.03; control = 0.94 ± 0.03) cingulates. These ratios did not differ between electrodermally responsive and non-responsive patients. When patients were divided into two groups: lower SCL (less than the mean SCL of the control group minus two standard deviations) and normal SCL (similar to the control group), the subgroup with a lower level of SCL showed a lower NAA / (Cr + Cho) ratio in the left cingulate (0.78 ± 0.05) than the controls (0.95 ± 0.02, P < 0.05) and the subgroup with normal SCL (0.88 ± 0.03, P < 0.05). There was a negative correlation between the NAA / (Cr + Cho) ratio in the left cingulate of patients with schizophrenia and the duration of the disease and years under medication. These data suggest the existence of a schizophrenic subgroup characterized by low SCL that could be a consequence of the lower neuronal viability observed in the left cingulate of these patients.
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Adult , Female , Humans , Male , Aspartic Acid/analogs & derivatives , Cerebral Cortex/chemistry , Choline/analysis , Creatine/analysis , Galvanic Skin Response/physiology , Schizophrenia/metabolism , Acoustic Stimulation , Aspartic Acid/analysis , Case-Control Studies , Magnetic Resonance Spectroscopy/methods , Protons , Socioeconomic Factors , Schizophrenia/physiopathologyABSTRACT
This study was conducted to investigate the metabolic changes in the motor and motor association cortices following axonal injury in the internal capsule that was caused by deep intracerebral hematoma. Using proton magnetic resonance spectroscopy (1H MRS), the authors studied the primary motor cortices (M-1) and sup-plementary motor areas (SMA) of 9 hemiparetic patients with documentable hemi-paresis of varying severity, and we studied 10 normal volunteers as controls. To measure the M-1 and SMA biochemical changes, 4 separate single volumes of inter-est(VOIs) were located bilaterally in the affected and unaffected hemisphere (AH and UH).1H MRS provided a neuronal and axonal viability index by measuring levels of N-acetylaspartate (NAA) and creatine/phosphocreatine (Cr). The M-1/SMA NAA/Cr ratios of the AH and UH in patients, and the AH and normal volunteers were com-pared. The NAA/Cr ratios of the M-1 and SMA in AH, and the SMA in UH were sig-nificantly lower than those of normal volunteers. These 1H MRS findings indicate that axonal injury in the descending motor pathway at the level of internal capsule could induce metabolic changes in the higher centers of the motor pathway.
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Aspartic Acid/analogs & derivatives , Basal Ganglia Hemorrhage/metabolism , Creatine/metabolism , Magnetic Resonance Spectroscopy , Motor Cortex/metabolism , Paresis/metabolism , Phosphocreatine/metabolism , Protons , Pyramidal Tracts/metabolismABSTRACT
OBJECTIVES: Reductions of N-acetylaspartate (NAA), a putative marker of neuronal viability, within the subcortical structures in patients with obsessive-compulsive disorder (OCD) are well documented. However, there has been no report of the NAA level in cortical structures. The authors used proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess potential reductions of NAA in the frontal white matter, prefrontal gray matter, parietal gray and white matter, and the cingulate in drugnaive patients with OCD and explored the relationship between the brain metabolites and the degree to the dysfunction on the neuropsychological performances. METHODS : Thirteen drug-naive patients who met DSM-IV criteria for OCD and 13 healthy age-, sex-, handness- matched control subjects were studied. Subjects underwent MRI and 1H-MRSI and the peaks of NAA, creatine+phosphocreatine (Cr), and choline-containing compounds (Cho) were measured. Differences between patients and control subjects were tested for each metabolite ratio, and the relations between metabolite ratios and clinical symptoms, neuropsychological performances were examined. RESULTS : Upon comparison with normal controls, NAA/Cr ratio was significantly reduced in patients for the prefrontal gray matter, frontal white matter and anterior cingulate. There was no difference in Cho/Cr or NAA/Cho in any region. Also, a significant positive correlation was found between prefrontal NAA/Cr ratio and the delayed recall score of the Rey-Osterrieth Complex Figure Test in patients with OCD. CONCLUSION : The reduced NAA/Cr ratio in the prefrontal gray matter and frontal white matter suggests that OCD patients have lower neuronal viability than normal comparisons and it may be related to impaired organizational strategies in patients with OCD. These results support a role for the frontal-subcortical circuitry in a neurobiologic model of OCD.
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Humans , Brain , Diagnostic and Statistical Manual of Mental Disorders , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Neurons , Obsessive-Compulsive Disorder , Protons , RabeprazoleABSTRACT
0.05). Conclusions: There exists an abnormal reduction of neural viability and function on bilateral hippocampus of patients with first-episode MDD.