Somatic disturbances that occur in parallel with psychiatric diseases are a major challenge in clinical practice.Various factors contribute to the development of mental and somatic disorders.Type 2 diabetes mellitus(T...Somatic disturbances that occur in parallel with psychiatric diseases are a major challenge in clinical practice.Various factors contribute to the development of mental and somatic disorders.Type 2 diabetes mellitus(T2DM)is a significant health burden worldwide,and the prevalence of diabetes in adults is increasing.The comorbidity of diabetes and mental disorders is very common.By sharing a bidirectional link,both T2DM and mental disorders influence each other in various manners,but the exact mechanisms underlying this link are not yet elucidated.The potential mechanisms of both mental disorders and T2DM are related to immune and inflammatory system dysfunction,oxidative stress,endothelial dysfunction,and metabolic disturbances.Moreover,diabetes is also a risk factor for cognitive dysfunction that can range from subtle diabetesassociated cognitive decline to pre-dementia and dementia.A complex relationship between the gut and the brain also represents a new therapeutic approach since gut-brain signalling pathways regulate food intake and hepatic glucose production.The aim of this minireview is to summarize and present the latest data on mutual pathogenic pathways in these disorders,emphasizing their complexity and interweaving.We also focused on the cognitive performances and changes in neurodegenerative disorders.The importance of implementing integrated approaches in treating both of these states is highlighted,along with the need for individual therapeutic strategies.展开更多
In recent years,epidemiological and genetic studies have shown an association between autoimmune diseases and psychosis.The question arises whether patients with schizophrenia are more likely to develop multiple scler...In recent years,epidemiological and genetic studies have shown an association between autoimmune diseases and psychosis.The question arises whether patients with schizophrenia are more likely to develop multiple sclerosis(MS)later in life.It is well known that the immune system plays an important role in the etiopathogenesis of both disorders.Immune disturbances may be similar or very different in terms of different types of immune responses,disturbed myelination,and/or immunogenetic predispositions.A psychotic symptom may be a consequence of the MS diagnosis itself or a separate entity.In this review article,we discussed the timing of onset of psychotic symptoms and MS and whether the use of corticosteroids as therapy for acute relapses in MS is unfairly neglected in patients with psychiatric comorbidities.In addition,we discussed that the anti-inflammatory potential of antipsychotics could be useful and should be considered,especially in the treatment of psychosis that coexists with MS.Autoimmune disorders could precipitate psychotic symptoms,and in this context,autoimmune psychosis must be considered as a persistent symptomatology that requires continuous and specific treatment.展开更多
Recently,specific immunometabolic profiles have been postulated in patients with schizophrenia,even before full-blown disease and independent of antipsychotic treatment.Proteomic profiling studies offer a promising po...Recently,specific immunometabolic profiles have been postulated in patients with schizophrenia,even before full-blown disease and independent of antipsychotic treatment.Proteomic profiling studies offer a promising potential for elucidating the cellular and molecular pathways that may be involved in the onset and progression of schizophrenia symptoms,and co-occurrent metabolic changes.In view of all this,we were intrigued to explore galectin-3(Gal-3)as a glycan,and in our previous study,we measured its elevated levels in remission of schizophrenia.The finding may be a consequence of antipsychotic treatment and may have an impact on the onset of inflammation,the development of obesity,and the presumed cognitive changes in schizophrenia.In the animal study,it was shown that downregulation of Gal-3 was beneficial in insulin regulation of obesity and cognitive preservation.Strategies involving plasma exchange are discussed in this review,particularly in the context of Gal-3 elimination.展开更多
BACKGROUND Evidence suggests that cytokines cause immune disturbances,shape immunological sequelae later in life,and modulate the risk of schizophrenia(SC).Galectin-3(Gal-3),a multifaceted molecule of the glycan famil...BACKGROUND Evidence suggests that cytokines cause immune disturbances,shape immunological sequelae later in life,and modulate the risk of schizophrenia(SC).Galectin-3(Gal-3),a multifaceted molecule of the glycan family,is involved in the formation of the immunological synapse and modulates the signalling pathway and effector functions of T lymphocytes,which are major producers of cytokines.We have previously reported elevated serum Gal-3 levels in stable SC patients.However,Gal-3 as a link between cognitive functioning and inflammation has not yet been investigated in SC.AIM To investigate the relationship between serum Gal-3 levels and cognitive performance,serum cytokines,and white blood cell count in three-month stably treated SC patients.METHODS Twenty-seven patients with SC in remission and 18 healthy volunteers participated in this casecontrol and correlational study.Clinical assessment was performed using the Positive and Negative Syndrome Scale and the Montreal-Cognitive Assessment.The results of previously measured serum levels of Gal-3,interleukin(IL)-33,soluble suppression of tumorigenicity 2(sST2),tumor necrosis factor-alpha(TNF-α),IL-6 and IL-17 were used for further statistical analyses,and IL-4,IL-23,IL-1βand transforming growth factor-beta(TGF-β)were now additionally measured with a sensitive enzyme-linked immunosorbent assay.The number of leukocytes in the blood and the percentage of neutrophils,lymphocytes,and monocytes were determined with a standardized routine measurement procedure(Sysmex Technology).Statistical analyses were performed using SPSS 20.0 software.RESULTS We found no correlation between serum Gal-3 levels and cognitive functioning in SC patients.A positive correlation was found between the levels of Gal-3 and TNF-α(r=0.476;P=0.012),Gal-3and IL-23(r=0.417;P=0.031),and Gal-3 and sST2(r=0.402;P=0.038).The binary logistic model,which included all nine cytokines measured in this patient sample,indicated the particular role of Gal-3 and TGF-βin the duration of SC.In the stabilization phase of SC,we observed a moderate and negative correlation between serum Gal-3 levels and leukocytes(r=-0.449;P<0.019).Additional linear regression analysis showed a positive correlation between Gal-3 expression and risperidone dose(F:4.467;P<0.045;r^(2)=0.396).CONCLUSION The combined activity of Gal-3 and proinflammatory cytokines,TGF-βdownregulation and lower counts of leukocytes influence the SC duration.Gal-3 likely manifests indirect immunometabolic regulation of cognition in SC.展开更多
Recent epidemiological and genetic studies have revealed an interconnection between schizophrenia and breast cancer.The mutual underlying pathophysiological mechanisms may be immunologically driven.A new cluster of mo...Recent epidemiological and genetic studies have revealed an interconnection between schizophrenia and breast cancer.The mutual underlying pathophysiological mechanisms may be immunologically driven.A new cluster of molecules called alarmins may be involved in sterile brain inflammation,and we have already reported the potential impact of interleukin-33(IL-33)on positive symptoms onset and the role of its soluble trans-membranes full length receptor(sST2)on amelioration of negative symptoms in schizophrenia genesis.Furthermore,these molecules have already been shown to be involved in breast cancer etiopathogenesis.In this review article,we aim to describe the IL-33/suppressor of tumorigenicity 2(ST2)axis as a crossroad in schizophreniabreast cancer comorbidity.Considering that raloxifene could be tissue-specific and improve cognition and that tamoxifen resistance in breast carcinoma could be improved by strategies targeting IL-33,these selective estrogen receptor modulators could be useful in complementary treatment.These observations could guide further somatic,as well as psychiatric therapeutical protocols by incorporating what is known about immunity in schizophrenia.展开更多
文摘Somatic disturbances that occur in parallel with psychiatric diseases are a major challenge in clinical practice.Various factors contribute to the development of mental and somatic disorders.Type 2 diabetes mellitus(T2DM)is a significant health burden worldwide,and the prevalence of diabetes in adults is increasing.The comorbidity of diabetes and mental disorders is very common.By sharing a bidirectional link,both T2DM and mental disorders influence each other in various manners,but the exact mechanisms underlying this link are not yet elucidated.The potential mechanisms of both mental disorders and T2DM are related to immune and inflammatory system dysfunction,oxidative stress,endothelial dysfunction,and metabolic disturbances.Moreover,diabetes is also a risk factor for cognitive dysfunction that can range from subtle diabetesassociated cognitive decline to pre-dementia and dementia.A complex relationship between the gut and the brain also represents a new therapeutic approach since gut-brain signalling pathways regulate food intake and hepatic glucose production.The aim of this minireview is to summarize and present the latest data on mutual pathogenic pathways in these disorders,emphasizing their complexity and interweaving.We also focused on the cognitive performances and changes in neurodegenerative disorders.The importance of implementing integrated approaches in treating both of these states is highlighted,along with the need for individual therapeutic strategies.
基金Supported by Ministry of Science and Technological Development of the Republic of Serbia,No.175069.
文摘In recent years,epidemiological and genetic studies have shown an association between autoimmune diseases and psychosis.The question arises whether patients with schizophrenia are more likely to develop multiple sclerosis(MS)later in life.It is well known that the immune system plays an important role in the etiopathogenesis of both disorders.Immune disturbances may be similar or very different in terms of different types of immune responses,disturbed myelination,and/or immunogenetic predispositions.A psychotic symptom may be a consequence of the MS diagnosis itself or a separate entity.In this review article,we discussed the timing of onset of psychotic symptoms and MS and whether the use of corticosteroids as therapy for acute relapses in MS is unfairly neglected in patients with psychiatric comorbidities.In addition,we discussed that the anti-inflammatory potential of antipsychotics could be useful and should be considered,especially in the treatment of psychosis that coexists with MS.Autoimmune disorders could precipitate psychotic symptoms,and in this context,autoimmune psychosis must be considered as a persistent symptomatology that requires continuous and specific treatment.
基金Supported by Ministry of Science and Technological Development of the Republic of Serbia,No.175069and Faculty of Medical Sciences,University of Kragujevac,No.JP15-05.
文摘Recently,specific immunometabolic profiles have been postulated in patients with schizophrenia,even before full-blown disease and independent of antipsychotic treatment.Proteomic profiling studies offer a promising potential for elucidating the cellular and molecular pathways that may be involved in the onset and progression of schizophrenia symptoms,and co-occurrent metabolic changes.In view of all this,we were intrigued to explore galectin-3(Gal-3)as a glycan,and in our previous study,we measured its elevated levels in remission of schizophrenia.The finding may be a consequence of antipsychotic treatment and may have an impact on the onset of inflammation,the development of obesity,and the presumed cognitive changes in schizophrenia.In the animal study,it was shown that downregulation of Gal-3 was beneficial in insulin regulation of obesity and cognitive preservation.Strategies involving plasma exchange are discussed in this review,particularly in the context of Gal-3 elimination.
基金Supported by Ministry of Science and Technological Development of the Republic of Serbia,No.175069Faculty of Medical SciencesUniversity of Kragujevac,No.JP15-05。
文摘BACKGROUND Evidence suggests that cytokines cause immune disturbances,shape immunological sequelae later in life,and modulate the risk of schizophrenia(SC).Galectin-3(Gal-3),a multifaceted molecule of the glycan family,is involved in the formation of the immunological synapse and modulates the signalling pathway and effector functions of T lymphocytes,which are major producers of cytokines.We have previously reported elevated serum Gal-3 levels in stable SC patients.However,Gal-3 as a link between cognitive functioning and inflammation has not yet been investigated in SC.AIM To investigate the relationship between serum Gal-3 levels and cognitive performance,serum cytokines,and white blood cell count in three-month stably treated SC patients.METHODS Twenty-seven patients with SC in remission and 18 healthy volunteers participated in this casecontrol and correlational study.Clinical assessment was performed using the Positive and Negative Syndrome Scale and the Montreal-Cognitive Assessment.The results of previously measured serum levels of Gal-3,interleukin(IL)-33,soluble suppression of tumorigenicity 2(sST2),tumor necrosis factor-alpha(TNF-α),IL-6 and IL-17 were used for further statistical analyses,and IL-4,IL-23,IL-1βand transforming growth factor-beta(TGF-β)were now additionally measured with a sensitive enzyme-linked immunosorbent assay.The number of leukocytes in the blood and the percentage of neutrophils,lymphocytes,and monocytes were determined with a standardized routine measurement procedure(Sysmex Technology).Statistical analyses were performed using SPSS 20.0 software.RESULTS We found no correlation between serum Gal-3 levels and cognitive functioning in SC patients.A positive correlation was found between the levels of Gal-3 and TNF-α(r=0.476;P=0.012),Gal-3and IL-23(r=0.417;P=0.031),and Gal-3 and sST2(r=0.402;P=0.038).The binary logistic model,which included all nine cytokines measured in this patient sample,indicated the particular role of Gal-3 and TGF-βin the duration of SC.In the stabilization phase of SC,we observed a moderate and negative correlation between serum Gal-3 levels and leukocytes(r=-0.449;P<0.019).Additional linear regression analysis showed a positive correlation between Gal-3 expression and risperidone dose(F:4.467;P<0.045;r^(2)=0.396).CONCLUSION The combined activity of Gal-3 and proinflammatory cytokines,TGF-βdownregulation and lower counts of leukocytes influence the SC duration.Gal-3 likely manifests indirect immunometabolic regulation of cognition in SC.
基金Supported by Ministry of Science and Technological Development of the Republic of Serbia(NO.175069)Faculty of Medical Sciences,University of Kragujevac(NO.JP15-05).
文摘Recent epidemiological and genetic studies have revealed an interconnection between schizophrenia and breast cancer.The mutual underlying pathophysiological mechanisms may be immunologically driven.A new cluster of molecules called alarmins may be involved in sterile brain inflammation,and we have already reported the potential impact of interleukin-33(IL-33)on positive symptoms onset and the role of its soluble trans-membranes full length receptor(sST2)on amelioration of negative symptoms in schizophrenia genesis.Furthermore,these molecules have already been shown to be involved in breast cancer etiopathogenesis.In this review article,we aim to describe the IL-33/suppressor of tumorigenicity 2(ST2)axis as a crossroad in schizophreniabreast cancer comorbidity.Considering that raloxifene could be tissue-specific and improve cognition and that tamoxifen resistance in breast carcinoma could be improved by strategies targeting IL-33,these selective estrogen receptor modulators could be useful in complementary treatment.These observations could guide further somatic,as well as psychiatric therapeutical protocols by incorporating what is known about immunity in schizophrenia.
