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Enrico Smeraldi - One of the best experts on this subject based on the ideXlab platform.
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Catechol-O-methyltransferase (COMT) genotype biases neural correlates of empathy and perceived personal distress in schizophrenia.
Comprehensive Psychiatry, 2012Co-Authors: Sara Poletti, Daniele Radaelli, Cristina Lorenzi, Adele Pirovano, Enrico Smeraldi, Roberto Cavallaro, Marta Bosia, Francesco BenedettiAbstract:Abstract Background The catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism (Rs4680) influences enzyme activity with valine (Val) allele associated with higher enzymatic activity. Several studies suggest that factors influencing dopaminergic transmission could control response to stressful situations. Empathy is an essential element of human behavior, requires the ability to adopt another person's perspective, and has been found to be dysfunctional in schizophrenia. Methods Twenty-eight schizophrenic patients underwent functional magnetic resonance imaging performing an empathy task. Perceived empathy has been evaluated with the Interpersonal Reactivity Index. Results An effect of COMT on perceived distress subscale has been shown, with methionine (Met)/Met subjects reporting lower rates of stress compared with Val/Val. Moreover, imaging results showed an effect of genotype on empathy processing in the anterior cingulate with Val/Val subjects showing the lowest activation. Discussion This is the first study of the effect of Rs4680 on interpersonal distress and neural correlates of empathy in schizophrenia. We found a decrease in neural responses in areas that ensure a cognitive control of emotion that is paralleled by perceived distress in interpersonal situation; this functional pattern seems to be influenced by Rs4680 COMT polymorphism.
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Recurrence of bipolar mania is associated with catechol-O-methyltransferase Val(108/158)Met polymorphism.
Journal of Affective Disorders, 2011Co-Authors: Francesco Benedetti, Sara Dallaspezia, Clara Locatelli, Daniele Radaelli, Sara Poletti, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Background Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G-A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. In patients affected by bipolar disorder Rs4680 can influence antidepressant response and the propensity to develop psychotic symptoms, with the Met/Met genotype exerting a protective role. The same genotype could influence other dopamine-associated psychopathological features, such as mania. Methods We genotyped Rs4680 in a sample of 163 patients affected by bipolar disorder type I, and assessed the personal history of recurrence of the illness. Results We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced recurrence of manic, but not depressive, episodes during the course of the illness. Conclusions We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that influence the individual susceptibility of patients with bipolar disorder to develop manic episodes of illness.
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Recurrence of bipolar mania is associated with catechol-O-methyltransferase Val(108/158)Met polymorphism.
Journal of affective disorders, 2011Co-Authors: Francesco Benedetti, Sara Dallaspezia, Clara Locatelli, Daniele Radaelli, Sara Poletti, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G-A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. In patients affected by bipolar disorder Rs4680 can influence antidepressant response and the propensity to develop psychotic symptoms, with the Met/Met genotype exerting a protective role. The same genotype could influence other dopamine-associated psychopathological features, such as mania. We genotyped Rs4680 in a sample of 163 patients affected by bipolar disorder type I, and assessed the personal history of recurrence of the illness. We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced recurrence of manic, but not depressive, episodes during the course of the illness. We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that influence the individual susceptibility of patients with bipolar disorder to develop manic episodes of illness. Copyright © 2011 Elsevier B.V. All rights reserved.
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Association between catechol-O-methyltransferase Val(108/158)Met polymorphism and psychotic features of bipolar disorder
Journal of Affective Disorders, 2010Co-Authors: Francesco Benedetti, Sara Dallaspezia, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Background Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G–A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. Studies in healthy participants and in patients affected by schizophrenia suggested that Rs4680 can influence the propensity to develop psychotic symptoms, with the Met low-activity allele exerting a protective role. Previous studies in bipolar patients reported non-significant trends in the same direction. Methods We genotyped Rs4680 in a sample of 467 patients affected by bipolar disorder type I with or without a previous illness episode with psychotic features (DSM-IV criteria: delusions or hallucinations). Results We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced risk of experiencing illness episodes with psychotic features during the course of the illness. The Met/Met genotype was more common among patients without psychotic features, and while in the non-psychotic group the Val/Val genotype had a distribution similar to Met/Met, in the group of patients who experienced episodes with psychotic symptoms the proportion of Val/Val homozygotes was the double of Met/Met. Conclusions We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that could influence the individual susceptibility of patients with bipolar disorder to develop psychotic symptoms.
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Effect of catechol-O-methyltransferase Val(108/158)Met polymorphism on antidepressant efficacy of fluvoxamine
European Psychiatry, 2010Co-Authors: Francesco Benedetti, Sara Dallaspezia, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Rationale The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (Rs4680) influences the enzyme activity. Recent clinical studies found a significant effect of Rs4680 on antidepressant response to fluoxetine and paroxetine, but several other studies were negative. No study considered drug plasma levels as possible nuisance covariate. Objectives We studied the effect of Rs4680 on response to fluvoxamine antidepressant monotherapy. Patients and methods Forty-one consecutively admitted inpatients affected by a major depressive episode in course of major depressive disorder were administered fluvoxamine for 6 weeks. Changes in severity of depression were assessed with weekly Hamilton Depression ratings and analyzed with repeated measures ANOVA in the context of General Linear Model, with Rs4680 and fluvoxamine plasma levels as factors. Results Rs4680 significantly interacted with time in affecting antidepressant response to fluvoxamine, with outcome being inversely proportional to the enzyme activity: better effects in Met-carriers, worse effects in Val/Val homozygotes. The effect became significant at the fourth week of treatment, and influence final response rates. Fluvoxamine plasma levels had marginal effects on outcome. Conclusions This is the first study that reports a positive effect of Rs4680 on response to fluvoxamine, and the third independent report of its influence on response to selective 5-HT reuptake inhibitors (SSRIs). Our findings support the hypothesis that factors affecting catecholaminergic neurotransmission might contribute to shape the individual response to antidepressants irrespective of their primary molecular target.
Francesco Benedetti - One of the best experts on this subject based on the ideXlab platform.
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Catechol-O-methyltransferase (COMT) genotype biases neural correlates of empathy and perceived personal distress in schizophrenia.
Comprehensive Psychiatry, 2012Co-Authors: Sara Poletti, Daniele Radaelli, Cristina Lorenzi, Adele Pirovano, Enrico Smeraldi, Roberto Cavallaro, Marta Bosia, Francesco BenedettiAbstract:Abstract Background The catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism (Rs4680) influences enzyme activity with valine (Val) allele associated with higher enzymatic activity. Several studies suggest that factors influencing dopaminergic transmission could control response to stressful situations. Empathy is an essential element of human behavior, requires the ability to adopt another person's perspective, and has been found to be dysfunctional in schizophrenia. Methods Twenty-eight schizophrenic patients underwent functional magnetic resonance imaging performing an empathy task. Perceived empathy has been evaluated with the Interpersonal Reactivity Index. Results An effect of COMT on perceived distress subscale has been shown, with methionine (Met)/Met subjects reporting lower rates of stress compared with Val/Val. Moreover, imaging results showed an effect of genotype on empathy processing in the anterior cingulate with Val/Val subjects showing the lowest activation. Discussion This is the first study of the effect of Rs4680 on interpersonal distress and neural correlates of empathy in schizophrenia. We found a decrease in neural responses in areas that ensure a cognitive control of emotion that is paralleled by perceived distress in interpersonal situation; this functional pattern seems to be influenced by Rs4680 COMT polymorphism.
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Recurrence of bipolar mania is associated with catechol-O-methyltransferase Val(108/158)Met polymorphism.
Journal of Affective Disorders, 2011Co-Authors: Francesco Benedetti, Sara Dallaspezia, Clara Locatelli, Daniele Radaelli, Sara Poletti, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Background Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G-A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. In patients affected by bipolar disorder Rs4680 can influence antidepressant response and the propensity to develop psychotic symptoms, with the Met/Met genotype exerting a protective role. The same genotype could influence other dopamine-associated psychopathological features, such as mania. Methods We genotyped Rs4680 in a sample of 163 patients affected by bipolar disorder type I, and assessed the personal history of recurrence of the illness. Results We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced recurrence of manic, but not depressive, episodes during the course of the illness. Conclusions We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that influence the individual susceptibility of patients with bipolar disorder to develop manic episodes of illness.
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Recurrence of bipolar mania is associated with catechol-O-methyltransferase Val(108/158)Met polymorphism.
Journal of affective disorders, 2011Co-Authors: Francesco Benedetti, Sara Dallaspezia, Clara Locatelli, Daniele Radaelli, Sara Poletti, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G-A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. In patients affected by bipolar disorder Rs4680 can influence antidepressant response and the propensity to develop psychotic symptoms, with the Met/Met genotype exerting a protective role. The same genotype could influence other dopamine-associated psychopathological features, such as mania. We genotyped Rs4680 in a sample of 163 patients affected by bipolar disorder type I, and assessed the personal history of recurrence of the illness. We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced recurrence of manic, but not depressive, episodes during the course of the illness. We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that influence the individual susceptibility of patients with bipolar disorder to develop manic episodes of illness. Copyright © 2011 Elsevier B.V. All rights reserved.
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Association between catechol-O-methyltransferase Val(108/158)Met polymorphism and psychotic features of bipolar disorder
Journal of Affective Disorders, 2010Co-Authors: Francesco Benedetti, Sara Dallaspezia, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Background Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G–A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. Studies in healthy participants and in patients affected by schizophrenia suggested that Rs4680 can influence the propensity to develop psychotic symptoms, with the Met low-activity allele exerting a protective role. Previous studies in bipolar patients reported non-significant trends in the same direction. Methods We genotyped Rs4680 in a sample of 467 patients affected by bipolar disorder type I with or without a previous illness episode with psychotic features (DSM-IV criteria: delusions or hallucinations). Results We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced risk of experiencing illness episodes with psychotic features during the course of the illness. The Met/Met genotype was more common among patients without psychotic features, and while in the non-psychotic group the Val/Val genotype had a distribution similar to Met/Met, in the group of patients who experienced episodes with psychotic symptoms the proportion of Val/Val homozygotes was the double of Met/Met. Conclusions We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that could influence the individual susceptibility of patients with bipolar disorder to develop psychotic symptoms.
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Effect of catechol-O-methyltransferase Val(108/158)Met polymorphism on antidepressant efficacy of fluvoxamine
European Psychiatry, 2010Co-Authors: Francesco Benedetti, Sara Dallaspezia, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Rationale The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (Rs4680) influences the enzyme activity. Recent clinical studies found a significant effect of Rs4680 on antidepressant response to fluoxetine and paroxetine, but several other studies were negative. No study considered drug plasma levels as possible nuisance covariate. Objectives We studied the effect of Rs4680 on response to fluvoxamine antidepressant monotherapy. Patients and methods Forty-one consecutively admitted inpatients affected by a major depressive episode in course of major depressive disorder were administered fluvoxamine for 6 weeks. Changes in severity of depression were assessed with weekly Hamilton Depression ratings and analyzed with repeated measures ANOVA in the context of General Linear Model, with Rs4680 and fluvoxamine plasma levels as factors. Results Rs4680 significantly interacted with time in affecting antidepressant response to fluvoxamine, with outcome being inversely proportional to the enzyme activity: better effects in Met-carriers, worse effects in Val/Val homozygotes. The effect became significant at the fourth week of treatment, and influence final response rates. Fluvoxamine plasma levels had marginal effects on outcome. Conclusions This is the first study that reports a positive effect of Rs4680 on response to fluvoxamine, and the third independent report of its influence on response to selective 5-HT reuptake inhibitors (SSRIs). Our findings support the hypothesis that factors affecting catecholaminergic neurotransmission might contribute to shape the individual response to antidepressants irrespective of their primary molecular target.
Adele Pirovano - One of the best experts on this subject based on the ideXlab platform.
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Catechol-O-methyltransferase (COMT) genotype biases neural correlates of empathy and perceived personal distress in schizophrenia.
Comprehensive Psychiatry, 2012Co-Authors: Sara Poletti, Daniele Radaelli, Cristina Lorenzi, Adele Pirovano, Enrico Smeraldi, Roberto Cavallaro, Marta Bosia, Francesco BenedettiAbstract:Abstract Background The catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism (Rs4680) influences enzyme activity with valine (Val) allele associated with higher enzymatic activity. Several studies suggest that factors influencing dopaminergic transmission could control response to stressful situations. Empathy is an essential element of human behavior, requires the ability to adopt another person's perspective, and has been found to be dysfunctional in schizophrenia. Methods Twenty-eight schizophrenic patients underwent functional magnetic resonance imaging performing an empathy task. Perceived empathy has been evaluated with the Interpersonal Reactivity Index. Results An effect of COMT on perceived distress subscale has been shown, with methionine (Met)/Met subjects reporting lower rates of stress compared with Val/Val. Moreover, imaging results showed an effect of genotype on empathy processing in the anterior cingulate with Val/Val subjects showing the lowest activation. Discussion This is the first study of the effect of Rs4680 on interpersonal distress and neural correlates of empathy in schizophrenia. We found a decrease in neural responses in areas that ensure a cognitive control of emotion that is paralleled by perceived distress in interpersonal situation; this functional pattern seems to be influenced by Rs4680 COMT polymorphism.
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Recurrence of bipolar mania is associated with catechol-O-methyltransferase Val(108/158)Met polymorphism.
Journal of Affective Disorders, 2011Co-Authors: Francesco Benedetti, Sara Dallaspezia, Clara Locatelli, Daniele Radaelli, Sara Poletti, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Background Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G-A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. In patients affected by bipolar disorder Rs4680 can influence antidepressant response and the propensity to develop psychotic symptoms, with the Met/Met genotype exerting a protective role. The same genotype could influence other dopamine-associated psychopathological features, such as mania. Methods We genotyped Rs4680 in a sample of 163 patients affected by bipolar disorder type I, and assessed the personal history of recurrence of the illness. Results We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced recurrence of manic, but not depressive, episodes during the course of the illness. Conclusions We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that influence the individual susceptibility of patients with bipolar disorder to develop manic episodes of illness.
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Recurrence of bipolar mania is associated with catechol-O-methyltransferase Val(108/158)Met polymorphism.
Journal of affective disorders, 2011Co-Authors: Francesco Benedetti, Sara Dallaspezia, Clara Locatelli, Daniele Radaelli, Sara Poletti, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G-A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. In patients affected by bipolar disorder Rs4680 can influence antidepressant response and the propensity to develop psychotic symptoms, with the Met/Met genotype exerting a protective role. The same genotype could influence other dopamine-associated psychopathological features, such as mania. We genotyped Rs4680 in a sample of 163 patients affected by bipolar disorder type I, and assessed the personal history of recurrence of the illness. We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced recurrence of manic, but not depressive, episodes during the course of the illness. We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that influence the individual susceptibility of patients with bipolar disorder to develop manic episodes of illness. Copyright © 2011 Elsevier B.V. All rights reserved.
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Association between catechol-O-methyltransferase Val(108/158)Met polymorphism and psychotic features of bipolar disorder
Journal of Affective Disorders, 2010Co-Authors: Francesco Benedetti, Sara Dallaspezia, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Background Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G–A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. Studies in healthy participants and in patients affected by schizophrenia suggested that Rs4680 can influence the propensity to develop psychotic symptoms, with the Met low-activity allele exerting a protective role. Previous studies in bipolar patients reported non-significant trends in the same direction. Methods We genotyped Rs4680 in a sample of 467 patients affected by bipolar disorder type I with or without a previous illness episode with psychotic features (DSM-IV criteria: delusions or hallucinations). Results We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced risk of experiencing illness episodes with psychotic features during the course of the illness. The Met/Met genotype was more common among patients without psychotic features, and while in the non-psychotic group the Val/Val genotype had a distribution similar to Met/Met, in the group of patients who experienced episodes with psychotic symptoms the proportion of Val/Val homozygotes was the double of Met/Met. Conclusions We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that could influence the individual susceptibility of patients with bipolar disorder to develop psychotic symptoms.
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Effect of catechol-O-methyltransferase Val(108/158)Met polymorphism on antidepressant efficacy of fluvoxamine
European Psychiatry, 2010Co-Authors: Francesco Benedetti, Sara Dallaspezia, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Rationale The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (Rs4680) influences the enzyme activity. Recent clinical studies found a significant effect of Rs4680 on antidepressant response to fluoxetine and paroxetine, but several other studies were negative. No study considered drug plasma levels as possible nuisance covariate. Objectives We studied the effect of Rs4680 on response to fluvoxamine antidepressant monotherapy. Patients and methods Forty-one consecutively admitted inpatients affected by a major depressive episode in course of major depressive disorder were administered fluvoxamine for 6 weeks. Changes in severity of depression were assessed with weekly Hamilton Depression ratings and analyzed with repeated measures ANOVA in the context of General Linear Model, with Rs4680 and fluvoxamine plasma levels as factors. Results Rs4680 significantly interacted with time in affecting antidepressant response to fluvoxamine, with outcome being inversely proportional to the enzyme activity: better effects in Met-carriers, worse effects in Val/Val homozygotes. The effect became significant at the fourth week of treatment, and influence final response rates. Fluvoxamine plasma levels had marginal effects on outcome. Conclusions This is the first study that reports a positive effect of Rs4680 on response to fluvoxamine, and the third independent report of its influence on response to selective 5-HT reuptake inhibitors (SSRIs). Our findings support the hypothesis that factors affecting catecholaminergic neurotransmission might contribute to shape the individual response to antidepressants irrespective of their primary molecular target.
Cristina Lorenzi - One of the best experts on this subject based on the ideXlab platform.
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Catechol-O-methyltransferase (COMT) genotype biases neural correlates of empathy and perceived personal distress in schizophrenia.
Comprehensive Psychiatry, 2012Co-Authors: Sara Poletti, Daniele Radaelli, Cristina Lorenzi, Adele Pirovano, Enrico Smeraldi, Roberto Cavallaro, Marta Bosia, Francesco BenedettiAbstract:Abstract Background The catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism (Rs4680) influences enzyme activity with valine (Val) allele associated with higher enzymatic activity. Several studies suggest that factors influencing dopaminergic transmission could control response to stressful situations. Empathy is an essential element of human behavior, requires the ability to adopt another person's perspective, and has been found to be dysfunctional in schizophrenia. Methods Twenty-eight schizophrenic patients underwent functional magnetic resonance imaging performing an empathy task. Perceived empathy has been evaluated with the Interpersonal Reactivity Index. Results An effect of COMT on perceived distress subscale has been shown, with methionine (Met)/Met subjects reporting lower rates of stress compared with Val/Val. Moreover, imaging results showed an effect of genotype on empathy processing in the anterior cingulate with Val/Val subjects showing the lowest activation. Discussion This is the first study of the effect of Rs4680 on interpersonal distress and neural correlates of empathy in schizophrenia. We found a decrease in neural responses in areas that ensure a cognitive control of emotion that is paralleled by perceived distress in interpersonal situation; this functional pattern seems to be influenced by Rs4680 COMT polymorphism.
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Recurrence of bipolar mania is associated with catechol-O-methyltransferase Val(108/158)Met polymorphism.
Journal of Affective Disorders, 2011Co-Authors: Francesco Benedetti, Sara Dallaspezia, Clara Locatelli, Daniele Radaelli, Sara Poletti, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Background Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G-A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. In patients affected by bipolar disorder Rs4680 can influence antidepressant response and the propensity to develop psychotic symptoms, with the Met/Met genotype exerting a protective role. The same genotype could influence other dopamine-associated psychopathological features, such as mania. Methods We genotyped Rs4680 in a sample of 163 patients affected by bipolar disorder type I, and assessed the personal history of recurrence of the illness. Results We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced recurrence of manic, but not depressive, episodes during the course of the illness. Conclusions We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that influence the individual susceptibility of patients with bipolar disorder to develop manic episodes of illness.
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Recurrence of bipolar mania is associated with catechol-O-methyltransferase Val(108/158)Met polymorphism.
Journal of affective disorders, 2011Co-Authors: Francesco Benedetti, Sara Dallaspezia, Clara Locatelli, Daniele Radaelli, Sara Poletti, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G-A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. In patients affected by bipolar disorder Rs4680 can influence antidepressant response and the propensity to develop psychotic symptoms, with the Met/Met genotype exerting a protective role. The same genotype could influence other dopamine-associated psychopathological features, such as mania. We genotyped Rs4680 in a sample of 163 patients affected by bipolar disorder type I, and assessed the personal history of recurrence of the illness. We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced recurrence of manic, but not depressive, episodes during the course of the illness. We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that influence the individual susceptibility of patients with bipolar disorder to develop manic episodes of illness. Copyright © 2011 Elsevier B.V. All rights reserved.
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Association between catechol-O-methyltransferase Val(108/158)Met polymorphism and psychotic features of bipolar disorder
Journal of Affective Disorders, 2010Co-Authors: Francesco Benedetti, Sara Dallaspezia, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Background Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G–A transition in the COMT gene (Rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. Studies in healthy participants and in patients affected by schizophrenia suggested that Rs4680 can influence the propensity to develop psychotic symptoms, with the Met low-activity allele exerting a protective role. Previous studies in bipolar patients reported non-significant trends in the same direction. Methods We genotyped Rs4680 in a sample of 467 patients affected by bipolar disorder type I with or without a previous illness episode with psychotic features (DSM-IV criteria: delusions or hallucinations). Results We observed a significant association between homozygosis for the Rs4680 COMT low-activity variant and a reduced risk of experiencing illness episodes with psychotic features during the course of the illness. The Met/Met genotype was more common among patients without psychotic features, and while in the non-psychotic group the Val/Val genotype had a distribution similar to Met/Met, in the group of patients who experienced episodes with psychotic symptoms the proportion of Val/Val homozygotes was the double of Met/Met. Conclusions We suggest that Rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that could influence the individual susceptibility of patients with bipolar disorder to develop psychotic symptoms.
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Effect of catechol-O-methyltransferase Val(108/158)Met polymorphism on antidepressant efficacy of fluvoxamine
European Psychiatry, 2010Co-Authors: Francesco Benedetti, Sara Dallaspezia, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Enrico SmeraldiAbstract:Abstract Rationale The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (Rs4680) influences the enzyme activity. Recent clinical studies found a significant effect of Rs4680 on antidepressant response to fluoxetine and paroxetine, but several other studies were negative. No study considered drug plasma levels as possible nuisance covariate. Objectives We studied the effect of Rs4680 on response to fluvoxamine antidepressant monotherapy. Patients and methods Forty-one consecutively admitted inpatients affected by a major depressive episode in course of major depressive disorder were administered fluvoxamine for 6 weeks. Changes in severity of depression were assessed with weekly Hamilton Depression ratings and analyzed with repeated measures ANOVA in the context of General Linear Model, with Rs4680 and fluvoxamine plasma levels as factors. Results Rs4680 significantly interacted with time in affecting antidepressant response to fluvoxamine, with outcome being inversely proportional to the enzyme activity: better effects in Met-carriers, worse effects in Val/Val homozygotes. The effect became significant at the fourth week of treatment, and influence final response rates. Fluvoxamine plasma levels had marginal effects on outcome. Conclusions This is the first study that reports a positive effect of Rs4680 on response to fluvoxamine, and the third independent report of its influence on response to selective 5-HT reuptake inhibitors (SSRIs). Our findings support the hypothesis that factors affecting catecholaminergic neurotransmission might contribute to shape the individual response to antidepressants irrespective of their primary molecular target.
Chunshui Yu - One of the best experts on this subject based on the ideXlab platform.
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znf804a rs1344706 interacts with comt Rs4680 to affect prefrontal volume in healthy adults
Brain Imaging and Behavior, 2018Co-Authors: Qiang Xu, Yongqin Xiong, Congcong Yuan, Fangshi Zhao, Junlin Shen, Chunshui YuAbstract:The biological function of ZNF804A rs1344706, the first genome-wide supported risk variant of schizophrenia, remains largely unknown. Based on the upregulating effect of ZNF804A on the expression of COMT, we hypothesize that ZNF804A may affect grey matter volume (GMV) by interacting with COMT. Voxel-based morphometry was applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT Rs4680 on brain GMV in 274 healthy young human subjects. The GMV of the left dorsolateral prefrontal cortex (DLPFC) showed a significant COMT Rs4680 × ZNF804A rs1344706 interaction, manifesting as an inverted U-shape modulation by the presumed dopamine signaling. In COMT Met-allele carriers, the ZNF804A TG heterozygotes showed greater GMV in the left DLPFC than both GG and TT homozygotes. In COMT Val/Val homozygotes, however, the ZNF804A TG heterozygotes exhibited smaller GMV in the left DLPFC than GG homozygotes and comparable GMV with TT homozygotes. These findings suggest that ZNF804A affects the GMV of the prefrontal cortex by interacting with COMT, which may improve our understanding of neurobiological effect of ZNF804A and its association with schizophrenia.
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interaction of comt Rs4680 and bdnf rs6265 polymorphisms on functional connectivity density of the left frontal eye field in healthy young adults
Human Brain Mapping, 2016Co-Authors: Wei Li, Jiayuan Xu, Tianzi Jiang, Chunshui YuAbstract:As modulators of dopamine availability and release in the brain, COMT and BDNF polymorphisms have demonstrated interactions on human cognition; however, the underlying neural mechanisms remain largely unknown. In this study, we aimed to investigate the interactions of COMT Rs4680 and BDNF rs6265 on global functional connectivity density (gFCD) of the brain in 265 healthy young subjects. We found a significant COMT × BDNF interaction on the gFCD in the left frontal eye field (FEF), showing an inverted U-shape modulation by the presumed dopamine signaling. This finding was consistently repeated in the gFCD analyses using other four connection thresholds. Our findings reveal a COMT × BDNF interaction on the FCD in the left FEF, which may be helpful for understanding the neural mechanisms of the COMT × BDNF interactions on the FEF-related cognitive functions. Hum Brain Mapp 37:2468-2478, 2016. © 2016 Wiley Periodicals, Inc.
