Soluble receptor for advanced glycation end products as a biomarker of symptomatic vasospasm in subarachnoid hemorrhage.
Impact factor: 3.968
Level of evidence: III
Sample Size/Population: 27 patients after excluding those with significant impairments that could affect the study such as cancer, renal dysfunction, etc. These were then split into non-symptomatic vasospasm and symptomatic vasospasm groups. A rat subarachnoid hemorrhage model was also conducted where the bifurcation of the left anterior and middle cerebral arteries was perforated mimicking a subarachnoid hemorrhage.
Protocol: Blood samples on days 5, 7, 10 and 14 after subarachnoid hemorrhage. Patient assessed on arrival (Hunt and Kosnik system) and discharge (Glasgow Outcome Scale). Blood sRAGE levels were measured using ELISA. In the rat study, neurobehavioral testing was completed and sRAGE levels were tested using ELISA.
Statistical Analysis: Student T-test, chi square test, Mann-Whitney U-test, two-way ANOVA with Tukey-Kramer test with a p-value of .05 being significant.
Study Type: Experimental Results: sRAGE was significantly lower in the SVS group vs non-SVS group, .84 being the cut-off value. In the rat models, there was significantly lower plasma sRAGE in comparison to the sham group.
Limitation: Sample size
Conclusion: sRAGE levels can be used as a potential biomarker for predicting SVS after SAH.
Aida Y, Kamide T, Ishii H, Kitao Y, Uchiyama N, Nakada M, Hori O. Soluble receptor for advanced glycation end products as a biomarker of symptomatic vasospasm in subarachnoid hemorrhage. J Neurosurg. 2019 Nov 1:1-9. doi: 10.3171/2019.8.JNS191269. Epub ahead of print. PMID: 31675694.
Receptor for Advanced Glycation End Products and its Inflammatory Ligands are Upregulated in Amyotrophic Lateral Sclerosis
Impact Factor: 3.921
Level of evidence: IV
Study type: Retrospective
Sample size: 11 donors up to 2-5 samples each depending on part of study
Intro: Enhanced oxidative stress and neuroinflammation are key contributors in ALS pathogenesis. RAGE is shown to increase these factors the majority of the time. This study looks at RAGE and its ligands (Advanced glycation end products, HMGB1 and S100/calgranulin family) in a person with ALS vs a normal control. It also discussed sRAGE levels being low in ALS patients due to it being a natural competitor.
Material/Methods: Tissue collection for immunohistochemistry, mRNA analysis and western blot were collected from deceased individuals with ALS and with no neurodegenerative disease diagnosis.
Statistical Analysis: Two-tailed T-test, significant p-value as <.05.
Results: Increased RAGE, increased mRNA expression of AGER (gene encoding RAGE), increased immunostaining of S100B, HMGB1 and CML (AGE prototype) and higher protein levels of RAGE, S100B and HMGB1 in ALS samples in comparison to controls.
Conclusion: There is increased expression of inflammatory RAGE in the human spinal cord affected by ALS. Limitation being this is the end-stage of ALS since these were deceased individuals and since this is the first study of its kind there is no comparison. Overall this shows that RAGE might be a possible mediator in ALS and this is a rational hypothesis.
Juranek, J. K., Daffu, G. K., Wojtkiewicz, J., Lacomis, D., Kofler, J., & Schmidt, A. M. (2015). Receptor for Advanced Glycation End Products and its Inflammatory Ligands are Upregulated in Amyotrophic Lateral Sclerosis. Frontiers in cellular neuroscience, 9, 485. https://doi.org/10.3389/fncel.2015.00485
Glycation exacerbates the neuronal toxicity of β-amyloid
Impact Factor: 6.304
Study: Experimental, in vitro
Level of evidence: VII
Sample size: Mice, n=3-n=8 depending on portion of study as many studies were conducted in this article
Discussion/conclusion: 𝛃-amyloids (AB) are a major component in neurotoxicity related to alzheimer's disease. This study aimed to discover the difference in neurotoxic exacerbation between normal 𝛃-amyloids and glycated 𝛃-amyloids (AB-AGE) since it is an ideal substrate for glycation. It was found that AB was glycated to AB-AGE with an age-dependent elevation of AGEs in the brains of mice. It was found that AB-AGE was more toxic by decreasing cell viability, increasing cell apoptosis, inducing tau hyperphosphorylation, and reducing synaptic proteins more than the regular AB. The receptor for advanced glycation end products (RAGE) was increased in hippocampal neurons treated with AB-AGE than AB. When RAGE antibody was used it nearly abolished the AB-AGE effects with the combined above results showing that AB-AGE is likely a more suitable ligand for RAGE causing an increased neurotoxicity over AB. When looking at activity-dependent phosphorylation of GSK-3 there was higher activity with AB-AGE that when inhibited showed higher cell viability, decreased apoptosis and more showing that GSK-3 may mediate the Ab-AGE-induced exacerbation of neural impairments. Aminoguanidine (AG) is a prototype agent that prevents the formation of AGEs. In this study they injected mice for 3 months and measured the levels of AGEs, AB-AGEs and ABs in comparison to controls injected with saline. The results of this showed that this treatment decreased AGE levels, AB, AGE-associated ABs and AB-associated AGEs showing it inhibited the formation of AB-AGE in mice. Mice were then neurologically tested by memory retention and the AG treated groups showed that AG possibly could rescue memory and learning.
Limitation: Rat study Statistical significance: determined by one-way ANOVA procedure followed by Duncan’s post hoc test with 95% confidence and two-tailed Student’s t-test.
Li XH, Du LL, Cheng XS, Jiang X, Zhang Y, Lv BL, Liu R, Wang JZ, Zhou XW. Glycation exacerbates the neuronal toxicity of β-amyloid. Cell Death Dis. 2013 Jun 13;4(6):e673. doi: 10.1038/cddis.2013.180. PMID: 23764854; PMCID: PMC3698547.
Soluble RAGE Treatment Delays Progression of Amyotrophic Lateral Sclerosis in SOD1 Mice
Impact factor: 3.921
Level of evidence: VII
Sample Size: n=3-n=12 depending on experiment
Introduction: The purpose is to see if sRAGE treatment offers protection against premature cell death in motor neurons of SOD1 transgenic mouse (SOD1 being mutated ALS by familial inheritance 15-20% of the time), thereby delaying the onset and progression of ALS and improving overall health status of these mice. sRAGE is a natural competitor of RAGE that sequesters RAGE ligands (such as advanced glycation end products) and blocks their interaction with cell surface RAGE.
Methods: Mice were injected with either sRAGE or murine serum albumin beginning at 8 weeks until termination. Final stage of disease was determined by 20% weight loss or the animal’s inability to right itself within 20 s when placed on its side. Disease onset accompanied by posture and gait impairment, was defined as the time when animals lost ∼10% of their maximal weight, before any noticeable decrease in motor performance tests. Only male mice were used for the sRAGE studies due to the protective effects of estrogen on onset and progression of disease. Immunohistochemistry was performed to see the amount of normal RAGE expression for comparison before injection in the SOD1 mice and were sacrificed at that time. Immunostaining was performed for quantification of lumbar ventral horn motor neurons and glial cells. RNA and RT-PCR was conducted on lumbar spinal samples. Motor function tests were performed using standard well-established procedures and scored by a naive scorer and was handed by a person who was understanding of the treatment codes to differentiate. Muscle strength test was measured by the hanging wire test. Grip strength was measured by manufacturer’s training guidelines.
Statistical analysis: Wilcoxin Signed-Rank test for RNA RT-PCR comparisons. Kaplan-Meier estimate was used to calculate probability of survival over a specific length of time. All values are presented as mean ± standard error (SEM). The statistical significance of differences (p < 0.05) was evaluated by non-parametric ANOVA with Student-Newman–Keuls post-test.
Results: There was increased expression of RAGE in ALS mouse lumbar spinal cord. sRAGE treated mice displayed a higher probability of surviving after disease onset with a p value of 0.007 and in comparison to the MSA-treated group with a p value of 0.01. They had significantly higher body weight at typical disease onset (p=0.01) and days lived (p=0.02) in comparison to MSA mice. sRAGE treated mice also had better grip and muscle strength. sRAGE treated mice had a significantly higher number of neurons at the terminal stage of disease and also a significantly lower amount of astrocytes indicating less progression of disease.
Conclusion: sRAGE treatment could be a potential supplementary candidate for those with ALS. With no significant therapeutic options for this incurable disease, the improvement of lifespan, motor performance and less neuronal death, this could be a potential candidate with further research.
Limitations: Rat model is not equivalent to human model
Juranek, J. K., Daffu, G. K., Geddis, M. S., Li, H., Rosario, R., Kaplan, B. J., Kelly, L., & Schmidt, A. M. (2016). Soluble RAGE Treatment Delays Progression of Amyotrophic Lateral Sclerosis in SOD1 Mice. Frontiers in cellular neuroscience, 10, 117. https://doi.org/10.3389/fncel.2016.00117
Sulforaphane Inhibits MGO-AGE-Mediated Neuroinflammation by Suppressing NF-κB, MAPK, and AGE-RAGE Signaling Pathways in Microglial Cells
Impact Factor: 5.014
Level of Evidence: VII
Intro: Sulforaphane (SFN) is a natural isothiocyanate found in cruciferous vegetables that is known to have antioxidant, anti-inflammatory, anti-apoptotic, cytoprotective, and anti-diabetic effects. This study aims to see the effects of SFN on neuroinflammatory reactions.
Methods: This study looked at Sulforaphane and its effect on AGE inhibition, breakdown, nitrate production, cell viability effects, lactate dehydrogenase production, reactive oxygen species, NF-κB translocation/activation, proinflammatory cytokines, and receptors using western blot, ELISA, and assays.
Statistical analysis: Results are expressed as mean ± standard error of the mean (SEM). One-way analysis of variance followed by Tukey post-hoc test. p < 0.05 was considered statistically significant.
Results/Conclusion: SFN can be used to prevent MGO-AGE formation but cannot be used to alter formation and breakdown of MGO-AGEs. SFN significantly reduced MGO-AGEs nitrate production showing that it could antagonize MGO-AGEs-induced oxidative stress in activated microglia. A dramatically high amount of intracellular AGEs was observed in the MGO-AGEs and SFN treatment significantly lowered the level of AGE inside the microglial cells. Reactive oxygen species produced by MGO-AGEs were significantly reduced in SFN treatment in microglial cells. SFN inhibited NFLP3, decreased activation of GSK3β and p38 phosphorylation and decreased expression of the receptor for AGE all involved in inflammatory processes. SFN also decreased NF-κB activation/translocation which is involved in proinflammatory cytokines. All of these processes were all increased due to AGE-mediated processes. Therefore, SFN may be a strong candidate against neuroinflammation induced by MGO-AGEs or neurodegenerative diseases caused by chronic glycative stress.
Limitations: Preparation of AGEs can vary between batches, unknown concentration of pathological AGEs and need a protocol for AGE development/preparation.
Subedi, L., Lee, J. H., Gaire, B. P., & Kim, S. Y. (2020). Sulforaphane Inhibits MGO-AGE-Mediated Neuroinflammation by Suppressing NF-κB, MAPK, and AGE-RAGE Signaling Pathways in Microglial Cells. Antioxidants (Basel, Switzerland), 9(9), 792. https://doi.org/10.3390/antiox9090792
The advanced glycation end-product N epsilon-(carboxymethyl)lysine level is elevated in cerebrospinal fluid of patients with amyotrophic lateral sclerosis
Impact factor: 2.274
Level of evidence: IV
Study: Prospective Cohort
Sample Size: 67 patients
Population: Group 1: patients with sporadic definite and probable ALS according to the revised El Escorial diagnostic criteria (18 male, 7 female; age range 27.5–74.5 years); Group 2: patients who showed clinical signs only of the lower motoneuron (LMN) representing a possible ALS (7 male, 6 female; age range 27.4–78.2 years); (3) patients with clinically probable and possible AD (3 male, 6 female; age range 52.8–79.6 years); and (4) controls with other neurological diseases not affecting the central nervous system. Routine work up of the control patients revealed normal clinical neurological status and imaging results (8 male, 12 female; age range 33.4–71.2 years.)
Intro: Compare AGE in ALS, other neurological diseases affecting CNS and non affecting CNS. This is different compared to other studies because most are post-mortem, while this study is antemortem.
Methods: Paired lumbar CSF and serum samples were collected from 67 patients. ELISA using a CML-specific monoclonal antibody
Statistical analysis: Mann–Whitney U test and Spearman’s rank correlation coefficient (rs). The level of significance was established at p<0.05.
Results: Significantly elevated CML levels in CSF in ALS and LMN disease when compared to control subjects. CSF levels of CML were even higher than in AD patients. Compared to controls, normalized CSF values of CML were increased in ALS, LMN disease and AD by a factor of 1.7, 1.5 and 1.2, respectively. CSF/serum ratio of CML is significantly elevated in both the ALS and LMN disease compared to controls by a factor of 2.3 and 1.9, respectively, whereas for AD an elevation by a factor of 1.4 was seen. For ALS, the CSF/serum ratio was also significantly higher compared to AD (p = 0.029)
Conclusion: significant increases of AGE products in CSF of motor neuron disease patients, especially in ALS, providing further evidence for the involvement of oxidative stress in the pathogenesis of ALS. Results on CML levels in CSF and serum samples suggest that these products are of intrathecal origin, i.e. oxidative stress in ALS patients is most likely confined to the CNS. Furthermore, increased CML CSF levels may provide a novel diagnostic tool as a surrogate marker for glycloxidative mechanisms in ALS.
Limitations: First of its kind, no comparisons.
Kaufmann E, Boehm BO, Süssmuth SD, Kientsch-Engel R, Sperfeld A, Ludolph AC, Tumani H. The advanced glycation end-product N epsilon-(carboxymethyl)lysine level is elevated in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Neurosci Lett. 2004 Nov 23;371(2-3):226-9. doi: 10.1016/j.neulet.2004.08.071. PMID: 15519762.
Detection of (CML) and non-CML advanced glycation end-products in the anterior horn of amyotrophic lateral sclerosis spinal cord
Impact factor: 3.286
Level of evidence: VI
Sample Size: 3 ALS + deceased patients and 3 ALS - control deceased patients that were age matched
Intro: The purpose of this paper was to determine if late-stage glycation reaction follows the early glycation reaction these authors had identified previously which leads to the formation of AGEs in the ALS spinal cord.
Methods: The presence of CML and non-CML AGE was examined in ALS spinal cords by using antibodies for CML and non-CML and immunohistochemical staining was performed.
Statistical analysis: Observation only
Results and Conclusion: In the present study, by observation using anti-CML and anti-non-CML AGE antibodies, the presence of AGEs in the anterior horn of the sporadic ALS spinal cord was confirmed. The presence of non-CML AGE in the anterior horn of the ALS spinal cord indicates that the later stage of the glycation reaction is involved in the pathogenesis of ALS. The presence of CML in the anterior horn of the ALS spinal cord was also confirmed. The presence of CML may reflect augmented oxidative stress and not be specific to AGE production only. Therefore, non-CML AGEs were a better indicator of pathogenesis of ALS.
Limitations: One problem is the sensitivity of the antibodies, and the difference in sensitivity may result in different intensity of staining of the target proteins. Some target proteins may be specifically localized in microglia, in which case they would not be able to remain in the early glycation products but would quickly proceed to the formation of non-CML AGE. Alternatively, there may be a special environment in microglial cells that facilitates the rapid progress of the glycation reaction to the later stage. Also it was a relatively small study size.
Kikuchi S, Shinpo K, Ogata A, Tsuji S, Takeuchi M, Makita Z, Tashiro K. Detection of N epsilon-(carboxymethyl)lysine (CML) and non-CML advanced glycation end-products in the anterior horn of amyotrophic lateral sclerosis spinal cord. Amyotroph Lateral Scler Other Motor Neuron Disord. 2002 Jun;3(2):63-8. doi: 10.1080/146608202760196020. PMID: 12215227.
Selective formation of certain advanced glycation end products in spinal cord astrocytes of humans and mice with superoxide dismutase-1 mutation
Impact factor: 14.256
Level of evidence: VI and VII
Study: Experimental + observational
Sample Size: 6 ALS spinal cords at autopsy and 6 SOD1 mice spinal cords + controls Introduction: The aim of the present study was to assess a role for carbonyl stress in motor neuron degeneration associated with superoxide dismutase-1 (SOD1) mutant familial ALS and its transgenic mouse model, using an immunohistochemical investigation of advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs).
Methods: Immunohistochemistry to detect AGEs and ALEs
Statistical analysis: Observation
Results: The most noteworthy finding in this study was the presence of CEL, argpyrimidine, pyrraline and CML in the spinal cord astrocytes of the SOD1 A4V familial ALS patients and the G93A mutant SOD1 transgenic mice. As mentioned above, CEL and argpyrimidine are derived from methylglyoxal, and pyrraline is derived from 3-deoxyglucosone. protein glycation, but not lipid peroxidation, is enhanced in ALS patients with an SOD1 mutation and mutant SOD1 transgenic mice, in which certain AGEs are selectively formed in the spinal cord astrocytes. There was no reactivity in controls.
Shibata N, Hirano A, Hedley-Whyte ET, Dal Canto MC, Nagai R, Uchida K, Horiuchi S, Kawaguchi M, Yamamoto T, Kobayashi M. Selective formation of certain advanced glycation end products in spinal cord astrocytes of humans and mice with superoxide dismutase-1 mutation. Acta Neuropathol. 2002 Aug;104(2):171-8. doi: 10.1007/s00401-002-0537-5. Epub 2002 Apr 18. PMID: 12111360.
Analysis of serum of patients with Alzheimer's disease for the level of advanced glycation end products
Impact factor: 1.744
Level of evidence: IV
Sample Size: 30 aged 68-70 years (Had AD or vascular dementia) and 94 controls without signs of cognitive impairment split into 2 groups.
Intro: The purpose is to look for a biochemical marker for AD since AD is based usually on neuro tests. AGEs are involved in beta-amyloids and degeneration of the CNS. Methods: IgG and IgM anti-AGE antibodies in human serum were measured in the ELISA test using the model AGE-protein.
Statistical analysis: Parametric Student t test and 2-way ANOVA
Results: The level of circulating AGE was significantly lower in AD patients than in the 2 groups of controls. The difference between the groups with AD and VaD was not statistically significant, while differences between the group with VaD and control group 1 as well as control group 2 were statistically significant. The difference in mean AGE value between control groups 1 and 2 was also statistically significant. The AD group did not differ in immune complex values from control group 1 or from control group 2 but differed significantly from the VaD group. The VaD group differed from control group 1 but not from control group 2 . The difference in mean IC value between control groups 1 and 2 was not statistically significant.
Conclusion: These initial results of the study suggest a local accumulation of AGEs rather than their presence in the form of soluble circulating AGEs. There were lower levels of circulating serum AGEs in patients with AD in relation to healthy controls.
Limitations: Difficult to compare control groups
Leszek J, Malyszczak K, Bartys A, Staniszewska M, Gamian A. Analysis of serum of patients with Alzheimer's disease for the level of advanced glycation end products. Am J Alzheimers Dis Other Demen. 2006 Oct-Nov;21(5):360-5. doi: 10.1177/1533317506291075. PMID: 17062556.
Advanced glycation end products and oxidative stress in Alzheimer's disease
Impact factor: 3.694
Level of evidence: V
Summary: AGEs are present in amyloid plaques in AD, and its extracellular accumulation may be caused by an accelerated oxidation of glycated proteins. AGEs and oxidative stress promote the transformation of soluble proteins into insoluble proteins deposits. Measurement of protein carbonylation is thought to be a good estimation for the extent of oxidative damage of proteins associated with various conditions of oxidative stress, aging, physiological disorders and AD. Aβ induces lipoperoxidation of membranes and lipid peroxidation products. HNE is cytotoxic to neurons and that it impairs the function of membrane proteins including the neuronal glucose transporter GLUT 3, indicating that HNE is a characteristic marker and a toxin leading to neurodegeneration in AD. Increased levels of DNA strand breaks have been found in AD. They were first considered to be part of apoptosis, but it is now widely accepted that oxidative damage is responsible for DNA strand breaks and this is consistent with the increased free carbonyls in the nuclei of neurons and glia in AD. AGEs are formed from a wide variety of reactions afterwards. AGEs are composed of irreversibly cross-linked heterogeneous protein aggregates. There is increasing evidence that the insolubility of Aβ plaques is caused by extensive covalent protein cross-linking. Intracellular proteins deposits including NFTs, Lewy bodies of patients with Parkinson’s disease and Hirano bodies are also crosslinked by AGEs, which may explain their insolubility in detergents and resistance to proteases. Some studies have shown the presence of AGEs in association with two major proteins of AD, Aβ and MAP-tau. This supports that AGEs are involved in the pathogenesis of AD. Aβ and AGE both bind to the receptor for advanced glycation end-products which link both of them to the oxidative process that occurs next in AD. There are new pharmacological approaches that break the cycle of oxidative stress and neurodegeneration used for AD pts. These approaches include AGE-inhibitors, antioxidants, and nonsteroidal antiinflammatory substances. AGE inhibitors might be able to stop formation of AGE-modified Aβ deposits or modify their structure with subsequent loss of AGEs binding to RAGE.
Gella A, Durany N. Oxidative stress in Alzheimer disease. Cell Adh Migr. 2009 Jan-Mar;3(1):88-93. doi: 10.4161/cam.3.1.7402. Epub 2009 Jan 13. PMID: 19372765; PMCID: PMC2675154.
Replication of enhanced carbonyl stress in a subpopulation of schizophrenia
Impact factor: 3.351
Level of evidence: IV
Sample Size: 156 patients with schizophrenia, 221 age-matched controls excluding DM and CKD
Intro: Pentosidine is a known marker for AGEs. This study looked at the serum level of pentosidine in schizophrenic patients and compared them to age matched controls.
Statistical analysis: T-Test
Results/Conclusion: Mean pentosidine levels were 1.6-fold higher in schizophrenics compared with controls. This showed schizophrenics had a higher rate of AGEs in comparison to controls and therefore higher carbonyl stress.
Limitations: It is possible that antipsychotic medication may affect plasma pentosidine levels. Second, clinical information was unavailable and therefore not considered when evaluating pentosidine levels.
Miyashita M, Arai M, Yuzawa H, Niizato K, Oshima K, Kushima I, Hashimoto R, Fukumoto M, Koike S, Toyota T, Ujike H, Arinami T, Kasai K, Takeda M, Ozaki N, Okazaki Y, Yoshikawa T, Amano N, Miyata T, Itokawa M. Replication of enhanced carbonyl stress in a subpopulation of schizophrenia. Psychiatry Clin Neurosci. 2014 Jan;68(1):83-4. doi: 10.1111/pcn.12081. Epub 2013 Oct 28. PMID: 24393354.
Increased advanced glycation end-products (AGEs) assessed by skin autofluorescence in schizophrenia
Impact factor: 3.745
Level of evidence: IV
Sample Size: 55 schizophrenia patients, 55 healthy controls. Study excluded those with alcohol dependence, drug dependence, mental retardation, diabetes, renal dysfunction or hx of head injury.
Methods: Measure AGEs through skin autofluorescence. Hypothesized that schizophrenia pts will have higher AGEs in comparison to controls and that a subgroup of patients with a more severe course of disease will be even higher. This is due to higher oxidative stress in schizophrenia.
Statistical analysis: Schizophrenia patients and controls were compared using Mann Whitney tests for quantitative variables and Fisher’s exact tests for qualitative variables. The relationships between skin AF and clinical variables were investigated in the schizophrenic group using Spearman’s rho correlation coefficients. Contributions of possible confounding variables were examined by multivariate analysis of covariance (MANCOVA) and logistic regression. p<0.05 is considered significant.
Results/Conclusion: AGEs were significantly elevated in schizophrenia patients in comparison to controls even when controlling for glomerular filtration rate, HDL and BMI. Skin AF in Kraepelinian patients (more severe course of disease) was significantly higher than in non-Kraepelinian patients. Kraepelinian patients were older than non-Kraepelinian patients and had a longer mean duration of disease than non-Kraepelinian patients. Therefore, when controlling for these it was no longer significant. Other interesting variables and AGEs were that they were higher with age and smoking.
Limitations: This study only included caucasian participants as dark skin can influence autofluorescence. A variety of skin compounds other than AGEs may also affect skin AF, and some AGEs (e.g., carboxymethyl-lysine) are not fluorescent. However, skin AF is considered to be a validated marker of the AGE pool.
Kouidrat Y, Amad A, Desailloud R, Diouf M, Fertout E, Scoury D, Lalau JD, Loas G. Increased advanced glycation end-products (AGEs) assessed by skin autofluorescence in schizophrenia. J Psychiatr Res. 2013 Aug;47(8):1044-8. doi: 10.1016/j.jpsychires.2013.03.016. Epub 2013 Apr 21. PMID: 23615188.
Association between skin autofluorescence of advanced glycation end products and affective disorders in the lifelines cohort study
Impact factor: 4.839
Level of evidence: IV
Study: Cross sectional case control study of the lifelines cohort study
Sample Size: 81,041 (41.7% male, aged 18–91 years), 6676 (8.2%) were cases with an affective disorder. Participants reporting a diagnosis of bipolar disorder, schizophrenia, dementia or Parkinson's disease were excluded.
Introduction: Looks at affective disorders and their association with oxidative stress. Affective disorder patients typically have lower life spans that have corresponded with higher rates of cardiovascular disease and in turn relationships with higher oxidative stress. Previously this could not be measured but with advanced glycation end products and skin autofluorescence oxidative stress and disorders like depression, their relationship can be quantified because AGEs are considered stable biomarkers for oxidative stress.
Methods: The presence of an affective disorder was assessed using the Dutch translation of the MINI. The following classifications were assessed and used as outcome measures: major depressive episode, dysthymia, generalized anxiety disorder, panic disorder (with or without agoraphobia), or social phobia. Then SAF was measured. Information about somatic morbidities, lifestyle, work and education was obtained by self-administered questionnaires. Routine serum measures (including glucose, HbA1c, lipids, renal function) were made from fasting state blood samples. Anthropometric measurements were taken by a trained research nurse. Blood pressure was measured using an automated Dinamap Monitor.
Statistical analysis: Comparisons between individuals with versus without a current affective disorder regarding sociodemographic and lifestyle factors, cardiometabolic parameters and history of somatic morbidities were conducted using unpaired t-tests, Mann-Whitney U tests and X2 tests for normal distributed, non-normal distributed and categorical data, respectively. Associations between presence of affective disorders and SAF were analyzed through logistic regression analyses.
Results and Conclusion: There is a cross-sectional association between affective disorders and AGE concentration measured by SAF, the strongest being major depressive disorder. It was also stronger for those with more than one affective disorder showing that there is cumulative oxidative stress in affective disorders. There was no association between SAF and dysthymia. For generalized anxiety disorder, panic disorder or social phobia, the associations lost significance when adjusting for cardiometabolic factors and somatic morbidities.
Limitations: Persons of non-Western descent and severely (mentally or physically) ill individuals were underrepresented.
Hagen JM, Sutterland AL, da Fonseca Pereira de Sousa PAL, Schirmbeck F, Cohn DM, Lok A, Tan HL, Zwinderman AH, de Haan L. Association between skin autofluorescence of advanced glycation end products and affective disorders in the lifelines cohort study. J Affect Disord. 2020 Oct 1;275:230-237. doi: 10.1016/j.jad.2020.06.040. Epub 2020 Jul 14. PMID: 32734913.
Right treatment for the right schizophrenic patients based on carbonyl stress pathophysiology
Impact factor: 3.351
Level of evidence: VI
Sample Size: n/a
Introduction: To look at schizophrenia and carbonyl stress with its pathophysiology.
Results/Conclusion: This review concluded that AGEs are high in a lot of chronic diseases including psychiatric disorders like schizophrenia. There is a subgroup of schizophrenia with low activity of glyoxalase I that is used in AGE detoxification of pentoside and low pyridoxamine that inhibits AGE formation. This subgroup had a more severe course of disease with treatment resistant schizophrenia, longer hospitalizations, higher doses of antipsychotic meds and more. It is hypothesized that high dose pyridoxamine should help this subgroup of patients.
Limitations: Limited information, short article
Ozaki N. Right treatment for the right schizophrenic patients based on carbonyl stress pathophysiology. Psychiatry Clin Neurosci. 2018 Jan;72(1):2. doi: 10.1111/pcn.12620. PMID: 29314398.
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