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B Mohanty - One of the best experts on this subject based on the ideXlab platform.
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study of charged particle multiplicity average transverse momentum and azimuthal anisotropy in xe xe collisions at sqrt s_ nn 5 44 snn 5 44 tev using AMPT model
European Physical Journal A, 2019Co-Authors: Sourav Kundu, Dukhishyam Mallick, B MohantyAbstract:We have studied the average charged particle density ($\langle \mathrm{d} \mathrm{N}_{ch}/\mathrm{d} \eta\rangle$), transverse momentum ($ p_{\mathrm{T}}$) spectra, average transverse momentum ($ \langle p_{\mathrm{T}}\rangle$) and azimuthal anisotropies of inclusive charged particles produced in Xe+Xe collisions at $\sqrt{s_{\mathrm{NN}}} = 5.44$ TeV using A Multiphase Transport Model (AMPT), which includes the deformation of 129Xe nucleus. Calculations have been performed with the string melting version of AMPT model and compared with the recent measurements from the ALICE experiment. The model result overestimates the measured $ \langle \mathrm{d} \mathrm{N}_{ch}/\mathrm{d} \eta\rangle$ for central collisions, agrees with the data for mid-central collisions and underestimates the measurements for the peripheral collisions. The centrality dependence of $ \langle p_{\mathrm{T}}\rangle$ of charged particles measured in ALICE is not reproduced by the model results. The calculated elliptic flow ($v_{2}$) from AMPT model is larger than the ALICE measurements in central collisions but is consistent with the data for 30-50% collisions centrality. We find that the model shows a mild centrality dependence of triangular flow and overestimates the ALICE measurements. Within the model framework, we have also studied various collision configurations of Xe nuclei such as body-body, tip-tip, side-side and random. We find a strong dependence of the above observable on the collision configurations.
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study of charged particle multiplicity average transverse momentum and azimuthal anisotropy in xe xe collisions at sqrt s_ nn 5 44 tev using AMPT model
arXiv: Nuclear Experiment, 2018Co-Authors: Sourav Kundu, Dukhishyam Mallick, B MohantyAbstract:We have studied the average charged particle density ($ $), transverse momentum ($p_{\mathrm{T}}$) spectra, $ $ and azimuthal anisotropies of inclusive charged particles produced in Xe+Xe collisions at $\sqrt{s_{NN}}$ = 5.44 TeV using A Multiphase Transport Model (AMPT), which includes the deformation of Xe$^{129}$ nucleus. Calculations have been performed with the string melting version of AMPT model and compared with the recent measurements from the ALICE experiment. The model results over predict the measured $ $ for central collisions, agree with the data for mid-central collisions and under predict the measurements for peripheral collisions. The centrality dependence of $ $ of charged particles measured in ALICE is not reproduced by the model results. The calculated elliptic flow ($v_{2}$) from AMPT model overpredicts the ALICE measurements in central collisions but are consistent with the data in mid central collisions. We find that the model shows a mild centrality dependence of triangular flow and overestimates the ALICE measurements. Within the model framework, we have also studied various collision configurations of Xe nuclei such as body-body, tip-tip, side-side and random. We find a strong dependence of the above observable on the collision configurations.
Gregor Hasler - One of the best experts on this subject based on the ideXlab platform.
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predicting relapse in bulimia nervosa neural and behavioral response to catecholamine depletion
2016Co-Authors: Stefanie Verena Muller, Yoan Mihov, Andrea Federspiel, Roland Wiest, Gregor HaslerAbstract:Background: Bulimia nervosa (BN) is a severe psychiatric disorder characterized by recurrent binge eating episodes followed by inappropriate compensatory behavior such as purging or excessive exercise. Frank proposed in his model of eating disorders that BN is associated with a desensitized dopamine system (Frank, 2016). However, direct investigations on the causal effect of a hypofunction of the dopamine system on neural activity, bulimic and depressive symptoms, and on the course of the illness are still missing. Catecholamine depletion induced by alpha-methyl-paratyrosine (AMPT) is an instructive paradigm to investigate directly the relationship between dopaminergic neurotransmission and the symptoms and course of BN. In our previous behavioral study, experimental catecholamine depletion provoked mild eating disorder symptoms in fully remitted BN (Grob et al, 2015). The purpose of this study was to examine the effect of catecholamine depletion on neural activity in BN. Furthermore, we were interested in the relationship between this effect and the risk for relapse. Methods: In a randomized, double-blind, crossover design, catecholamine depletion was achieved using the oral administration of AMPT over 24 hours in 18 remitted bulimic (rBN) and 22 healthy (HC) female participants. Cerebral blood flow (CBF) was measured using a pseudo continuous arterial spin labeling (pCASL) sequence. AMPT-induced mood and eating disorder symptoms were examined using the Montgomery-Asberg Depression Scale (MADRS) (Schmidtke et al, 1988), the Eating Disorder Examination-Questionnaire (EDE-Q) (Hilbert and Tuschen-Caffier, 2006), and the vigor subscale of the Profile of Mood States (POMS) (McNair et al, 1981). Bulimic relapse was assessed in a follow-up telephone interview (latency varied between 18 and 42 months) after study participation. Results: RBN participants revealed no increases of eating disorder symptoms following AMPT administration. However, AMPT reduced POMS vigor in both groups, and this effect was stronger in rBN participants. Furthermore, in rBN participants, AMPT decreased CBF in the pallidum and posterior midcingulate cortex (pMCC), whereas in HC participants, we did not find AMPT-induced alterations in CBF in these brain regions. AMPT-induced depressive symptoms and reductions in CBF in the hippocampus/ parahippocampal gyrus predicted relapse in rBN participants. In contrast, AMPT-induced CBF increase in the hippocampus/ parahippocampal gyrus predicted remission. Conclusions: We demonstrated that AMPT decreased CBF in the pallidum and pMCC in rBN participants. In the context of the Frank model (Frank, 2016), these regions can be considered as neural correlates of the desensitized dopamine system in BN. In contrast to our previous study (Grob et al, 2015), we did not observe an AMPT-induced increase of eating disorder symptoms. However, our earlier investigation was carried out in a controlled environment, without food cues and with regular, standardized meals (Grob et al, 2015). The uncontrolled environment in which this study was conducted might have overridden the effect of AMPT on eating disorder symptoms. In rBN participants, AMPT reduced vigor more strongly than in healthy individuals. This vigor reduction might trigger eating disorder symptoms to counteract dopamine deficiency and the related depression-like mental state. AMPT-induced depressive symptoms and CBF reduction in the hippocampus predicted bulimic relapse. Binge eating was reported to have an anti-depressive and dopamine elevating effect (Jahng et al, 2012). Therefore, dopamine deficiency and a dysfunctional hippocampus activity might trigger inappropriate behavior, such as binge eating to reduce negative emotions and anhedonia. Our findings expand Frank’s model of eating disorders (Frank, 2016), and emphasize the importance of depressive symptoms and the stress system in the course of bulimia nervosa. Keywords: Bulimia Nervosa, Catecholamine Depletion, Relapse, Cerebral Blood Flow, Neuroimaging. Disclosure: Nothing to disclose.
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the effects of catecholamine depletion on the neural response to fearful faces in remitted depression
The International Journal of Neuropsychopharmacology, 2014Co-Authors: Philipp Homan, Wayne C Drevets, Gregor HaslerAbstract:Recent evidence suggests that increased psychophysiological response to negatively valenced emotional stimuli found in major depressive disorder (MDD) may be associated with reduced catecholaminergic neurotransmission. Fourteen unmedicated, remitted subjects with MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebocontrolled, double-blind crossover trial. Subjects were exposed to fearful (FF) and neutral faces (NF) during a scan with [ 15 O]H2O positron emission tomography to assess the brain–catecholamine interaction in brain regions previously associated with emotional face processing. Treatment with AMPT resulted in significantly increased, normalized cerebral blood flow (CBF) in the left inferior temporal gyrus (ITG) and significantly decreased CBF in the right cerebellum across conditions and groups. In RMDD, flow in the left posterior cingulate cortex (PCC) increased significantly in the FF compared to the NF condition after AMPT, but remained unchanged after placebo, whereas healthy controls showed a significant increase under placebo and a significant decrease under AMPT in this brain region. In the left dorsolateral prefrontal cortex (DLPFC), flow decreased significantly in the FF compared to the NF condition under AMPT, and increased significantly under placebo in RMDD, whereas healthy controls showed no significant differences. Differences between AMPT and placebo of within-session changes in worry-symptoms were positively correlated with the corresponding changes in CBF in the right subgenual prefrontal cortex in RMDD. In conclusion, this study provided evidence for a catecholamine-related modulation of the neural responses to FF expressions in the left PCC and the left DLPFC in subjects with RMDD that might constitute a persistent, trait-like abnormality in MDD.
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growth hormone response to catecholamine depletion in unmedicated remitted subjects with major depressive disorder and healthy controls
Journal of Clinical Psychopharmacology, 2013Co-Authors: Philipp Homan, Wayne C Drevets, Gregor HaslerAbstract:We investigated whether the human growth hormone (HGH) response to catecholamine depletion differs between fully remitted patients with major depressive disorder and healthy control subjects. Fourteen unmedicated subjects with remitted major depressive disorder (RMDD) and 11 healthy control subjects underwent catecholamine depletion with oral α-methylparatyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover study. The main outcome measure was the serum level of HGH. The diagnosis × drug interaction for HGH serum concentration was significant (F₁,₂₃ = 7.66, P < 0.02). This interaction was attributable to the HGH level increasing after AMPT administration in the RMDD subjects but not in the healthy subjects. In the RMDD sample, the AMPT-induced increase in HGH concentration correlated inversely with AMPT-induced anxiety symptoms as assessed using the Beck Anxiety Inventory (r = -0.63, P < 0.02). There was a trend toward an inverse correlation of the AMPT-induced HGH concentration changes with AMPT-induced depressive symptoms as measured by the BDI (r = -0.53, P = 0.05). Following catecholamine depletion, the RMDD subjects were differentiated from control subjects by their HGH responses. This finding, together with the negative correlation between HGH response and AMPT-induced anxiety symptoms in RMDD subjects, suggests that AMPT administration results in a deeper nadir in central catecholaminergic transmission, as reflected by a greater disinhibition of HGH secretion, in RMDD subjects versus control subjects.
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reduction in total plasma ghrelin levels following catecholamine depletion relation to bulimic and depressive symptoms
Psychoneuroendocrinology, 2013Co-Authors: Philipp Homan, Simona Grob, Gabriella Milos, Ulrich Schnyder, Gregor HaslerAbstract:There is increasing preclinical and clinical evidence of the important role played by the gastric peptide hormone ghrelin in the pathogenesis of symptoms of depression and eating disorders. To investigate the role of ghrelin and its considered counterpart, peptide tyrosine tyrosine (PYY), in the development of bulimic and depressive symptoms induced by catecholamine depletion, we administered the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine (AMPT) in a randomized, double-blind, placebo-controlled crossover, single-site experimental trial to 29 healthy controls and 20 subjects with fully recovered bulimia nervosa (rBN). We found a decrease between preprandial and postprandial plasma ghrelin levels (p<0.0001) and a postprandial rise in plasma PYY levels (p<0.0001) in both conditions in the entire study population. Plasma ghrelin levels decreased in the entire study population after treatment with AMPT compared to placebo (p<0.006). AMPT-induced changes in plasma ghrelin levels were negatively correlated with AMPT-induced depressive symptoms (p<0.004). Plasma ghrelin and plasma PYY levels were also negatively correlated (p<0.05). We did not observe a difference in ghrelin or PYY response to catecholamine depletion between rBN subjects and healthy controls, and there was no correlation between plasma ghrelin and PYY levels and bulimic symptoms induced by catecholamine depletion. These findings suggest a relationship between catecholamines and ghrelin with depressive symptoms.
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reward processing after catecholamine depletion in unmedicated remitted subjects with major depressive disorder
Biological Psychiatry, 2009Co-Authors: Gregor Hasler, Dennis S Charney, David A Luckenbaugh, Joseph Snow, Noah Meyers, Tracy Waldeck, Marilla Geraci, Jonathan P Roiser, Brian Knutson, Wayne C DrevetsAbstract:Background We investigated whether performance on a reward processing task differs between fully remitted patients with major depressive disorder (MDD) and healthy control subjects after catecholamine depletion. Methods Seventeen unmedicated subjects with remitted MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover study. The main outcome measure was the reaction time on the monetary incentive delay (MID) task. Results A diagnosis × drug interaction was evident ( p = .001), which was attributable to an increase in reaction time across all incentive levels after AMPT in RMDD subjects ( p = .001) but no significant AMPT effect on reaction time in control subjects ( p = .17). There was no drug × diagnosis interaction on control tasks involving working memory or attention. In the RMDD sample the AMPT-induced depressive symptoms correlated with AMPT-induced changes in reaction time at all incentive levels of the MID task ( r values=.58–.82, p Conclusions Under catecholamine depletion the RMDD subjects were robustly differentiated from control subjects by development of performance deficits on a reward processing task. These performance deficits correlated directly with the return of depressive symptoms after AMPT administration. The sensitivity of central reward processing systems to reductions in brain catecholamine levels thus seems to represent a trait-like marker in MDD.
Dennis S Charney - One of the best experts on this subject based on the ideXlab platform.
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reward processing after catecholamine depletion in unmedicated remitted subjects with major depressive disorder
Biological Psychiatry, 2009Co-Authors: Gregor Hasler, Dennis S Charney, David A Luckenbaugh, Joseph Snow, Noah Meyers, Tracy Waldeck, Marilla Geraci, Jonathan P Roiser, Brian Knutson, Wayne C DrevetsAbstract:Background We investigated whether performance on a reward processing task differs between fully remitted patients with major depressive disorder (MDD) and healthy control subjects after catecholamine depletion. Methods Seventeen unmedicated subjects with remitted MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover study. The main outcome measure was the reaction time on the monetary incentive delay (MID) task. Results A diagnosis × drug interaction was evident ( p = .001), which was attributable to an increase in reaction time across all incentive levels after AMPT in RMDD subjects ( p = .001) but no significant AMPT effect on reaction time in control subjects ( p = .17). There was no drug × diagnosis interaction on control tasks involving working memory or attention. In the RMDD sample the AMPT-induced depressive symptoms correlated with AMPT-induced changes in reaction time at all incentive levels of the MID task ( r values=.58–.82, p Conclusions Under catecholamine depletion the RMDD subjects were robustly differentiated from control subjects by development of performance deficits on a reward processing task. These performance deficits correlated directly with the return of depressive symptoms after AMPT administration. The sensitivity of central reward processing systems to reductions in brain catecholamine levels thus seems to represent a trait-like marker in MDD.
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effect of catecholamine depletion on lithium induced long term remission of bipolar disorder
Biological Psychiatry, 1999Co-Authors: Amit Anand, Robert M Berman, Helen L Miller, Angela Cappiello, Dan A Oren, Adam Darnell, Scott W Woods, Dennis S CharneyAbstract:Abstract Background: This study investigated the effects of catecholamine depletion with alpha-methylparatyrosine (AMPT) on mood indices in patients with bipolar disorder who were in long-term remission with lithium therapy. Methods: Eight subjects with DSM-IV bipolar disorder currently in remission for >3 months on lithium were included in the study. Subjects were given either AMPT or placebo, in a randomized double-blind manner, in two test sessions of 4 days each. Results: Subjects did not have any significant changes in mood during AMPT or placebo administration; however, 24–48 hours after the last active AMPT dose subjects had a transient relapse of hypomanic symptoms. Relapse of hypomanic symptoms did not correlate with increases in serum levels of homovanillic acid or 3-methoxy-4hydroxyphenylglycol. Conclusions: These findings suggest that the mechanism of prevention of manic relapse by long-term lithium therapy may be dependent on stability of the catecholamine system.
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AMPT effects on cue induced craving for cocaine
American Journal on Addictions, 1996Co-Authors: Ismene L Petrakis, Dennis S Charney, Sally L Satel, Susan M Stine, Thomas R Kosten, Sheila Namanworth, John H KrystalAbstract:The authors evaluated the effect of an acute reduction in catecholamine synthesis, produced by alpha methyl para tyrosine (AMPT), on cue-induced craving for cocaine in cocaine-dependent patients. AMPT and diphenhydramine were administered under double-blind conditions in a randomized, crossover design. Two cue exposure sessions were conducted 1 week apart. Self-reported assessments of cocaine craving were administered before and after cue exposure. AMPT, but not diphenhydramine, significantly decreased plasma levels of the dopamine metabolite, ho-movanillic acid and the norepinephrine metabolite, 3-methoxy-4-hydroxyphenylethylene glycol. However, AMPT's effects on cue-induced craving interacted with the test-day order in a complex manner.
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Effects of α-Methyl-Para-Tyrosine (AMPT) in Drug-Free Depressed Patients
Neuropsychopharmacology, 1996Co-Authors: Helen L Miller, Pedro L Delgado, Ronald M Salomon, George R Heninger, Dennis S CharneyAbstract:A variety of biologic studies have demonstrated abnormal regulation of the norepinephrine (NE) system in patients with major depression, suggesting a role for NE in the etiology of depression. Brain NE and dopamine levels can be rapidly reduced by blocking synthesis with the tyrosine hydroxylase inhibitor α-methyl-para-tyrosine (AMPT). In the current investigation, AMPT was administered to drug-free depressed patients to evaluate the effect on mood of diminished catecholamine levels. Seventeen drug-free patients meeting DSM-III-R criteria for major depressive episode were tested with AMPT and an active placebo control, diphenhydramine. Testing was accomplished in a double-blind, crossover fashion, with random assignment to test conditions. Each test included baseline evaluation, 2 days with administration of either AMPT or diphenhydramine, and a follow-up day. Diphenhydramine was used as an active control because of the significant sedation associated with AMPT. Behavioral ratings, including visual analogue scales for a variety of feeling states, the Hamilton Depression Rating Scale (HDRS), and plasma for 3-methoxy-4-hydroxyphenelethyleneglycol (MPHG) and homovanillic acid (HVA) levels, were obtained. AMPT significantly reduced plasma HVA by 70% and MHPG by 50%, but it had no significant effects on the HDRS. AMPT also significantly increased visual analogue ratings of “tired” and decreased ratings of “energetic.” Diphenhydramine significantly decreased HDRS scores, but the change was small and was not clinically apparent. The lack of AMPT effects on depressed mood, in conjunction with a prior report that large reductions in plasma tryptophan do not systematically alter depressed mood, indicate that monoamine deficiency by itself is insufficient explanation of the cause of depression. The role of the noradrenergic system needs to be considered in relationship to the many other neurobiologic factors that could be involved in the pathophysiology of depression.
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monoamines and the mechanism of antidepressant action effects of catecholamine depletion on mood of patients treated with antidepressants
Psychopharmacology Bulletin, 1993Co-Authors: Pedro L Delgado, Helen L Miller, Ronald M Salomon, Alan J Gelenberg, Julio Licinio, G R Heninger, Dennis S CharneyAbstract:Brain catecholamines can be rapidly reduced by inhibiting their synthesis with alpha-methyl-para-tyrosine (AMPT). In order to assess the role of catecholamines in antidepressant action AMPT challenges were administered in a double-blind, placebo-controlled, crossover fashion to 14 depressed patients having maintained a therapeutic antidepressant response for > or = 2 weeks (3 desipramine, 2 mazindol, 5 fluoxetine, 4 sertraline). Each patient participated in two challenges one week apart. Each challenge included a baseline, two days of either AMPT or diphenhydramine (active placebo), and a followup. Antidepressant drugs were continued throughout testing. The 3 desipramine- and 2 mazindol-responders had a rapid increase in depression score during AMPT but not placebo (diphenhydramine) challenge whereas only 1 of 9 selective serotonin reuptake inhibitor (SSRI)-treated patients did. The implication of this is that the antidepressant response to desipramine may be more acutely dependent on brain catecholamine content than the response to SSRIs. In the context of our previous work with tryptophan depletion, these results suggest that the neurobiological mechanisms underlying the antidepressant responses to different drugs involve alterations in the functioning of different neurotransmitter systems and reinforce the importance of changes in both the serotonin and catecholamine systems for successful antidepressant responses.
Pedro L Delgado - One of the best experts on this subject based on the ideXlab platform.
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Effects of α-Methyl-Para-Tyrosine (AMPT) in Drug-Free Depressed Patients
Neuropsychopharmacology, 1996Co-Authors: Helen L Miller, Pedro L Delgado, Ronald M Salomon, George R Heninger, Dennis S CharneyAbstract:A variety of biologic studies have demonstrated abnormal regulation of the norepinephrine (NE) system in patients with major depression, suggesting a role for NE in the etiology of depression. Brain NE and dopamine levels can be rapidly reduced by blocking synthesis with the tyrosine hydroxylase inhibitor α-methyl-para-tyrosine (AMPT). In the current investigation, AMPT was administered to drug-free depressed patients to evaluate the effect on mood of diminished catecholamine levels. Seventeen drug-free patients meeting DSM-III-R criteria for major depressive episode were tested with AMPT and an active placebo control, diphenhydramine. Testing was accomplished in a double-blind, crossover fashion, with random assignment to test conditions. Each test included baseline evaluation, 2 days with administration of either AMPT or diphenhydramine, and a follow-up day. Diphenhydramine was used as an active control because of the significant sedation associated with AMPT. Behavioral ratings, including visual analogue scales for a variety of feeling states, the Hamilton Depression Rating Scale (HDRS), and plasma for 3-methoxy-4-hydroxyphenelethyleneglycol (MPHG) and homovanillic acid (HVA) levels, were obtained. AMPT significantly reduced plasma HVA by 70% and MHPG by 50%, but it had no significant effects on the HDRS. AMPT also significantly increased visual analogue ratings of “tired” and decreased ratings of “energetic.” Diphenhydramine significantly decreased HDRS scores, but the change was small and was not clinically apparent. The lack of AMPT effects on depressed mood, in conjunction with a prior report that large reductions in plasma tryptophan do not systematically alter depressed mood, indicate that monoamine deficiency by itself is insufficient explanation of the cause of depression. The role of the noradrenergic system needs to be considered in relationship to the many other neurobiologic factors that could be involved in the pathophysiology of depression.
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inhibition of presynaptic catecholamine synthesis with alpha methyl para tyrosine attenuates nocturnal melatonin secretion in humans
The Journal of Clinical Endocrinology and Metabolism, 1994Co-Authors: Ralf C. Zimmermann, George G Klee, Lois E Krahn, Pedro L DelgadoAbstract:The catecholamine dopamine (D) is involved in the regulation of LH and PRL secretion, whereas a dysregulated noradrenergic system may contribute significantly to symptoms encountered in affective disorders. This explains the attraction of using alpha-methyl-para-tyrosine (AMPT) in neuroendocrine and psychiatric research, as it inhibits both neurotransmitters. PRL has been used as a marker of the effectiveness of AMPT in blocking D function, but no good marker for the effectiveness of AMPT in blocking norepinephrine (NE) is available. The purpose of this study was to determine whether melatonin (M) might serve as such a marker, as its production and secretion are regulated by NE. Seven subjects were given either AMPT or promethazine, which does not alter M secretion, in a randomized, double blind fashion, and 24-h M secretion was studied. Two-way analysis of variance revealed a significant difference in M secretion (F = 13.2; df = 17,102; P = 0.0013), with the following time points being different: 22, 23,...
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monoamines and the mechanism of antidepressant action effects of catecholamine depletion on mood of patients treated with antidepressants
Psychopharmacology Bulletin, 1993Co-Authors: Pedro L Delgado, Helen L Miller, Ronald M Salomon, Alan J Gelenberg, Julio Licinio, G R Heninger, Dennis S CharneyAbstract:Brain catecholamines can be rapidly reduced by inhibiting their synthesis with alpha-methyl-para-tyrosine (AMPT). In order to assess the role of catecholamines in antidepressant action AMPT challenges were administered in a double-blind, placebo-controlled, crossover fashion to 14 depressed patients having maintained a therapeutic antidepressant response for > or = 2 weeks (3 desipramine, 2 mazindol, 5 fluoxetine, 4 sertraline). Each patient participated in two challenges one week apart. Each challenge included a baseline, two days of either AMPT or diphenhydramine (active placebo), and a followup. Antidepressant drugs were continued throughout testing. The 3 desipramine- and 2 mazindol-responders had a rapid increase in depression score during AMPT but not placebo (diphenhydramine) challenge whereas only 1 of 9 selective serotonin reuptake inhibitor (SSRI)-treated patients did. The implication of this is that the antidepressant response to desipramine may be more acutely dependent on brain catecholamine content than the response to SSRIs. In the context of our previous work with tryptophan depletion, these results suggest that the neurobiological mechanisms underlying the antidepressant responses to different drugs involve alterations in the functioning of different neurotransmitter systems and reinforce the importance of changes in both the serotonin and catecholamine systems for successful antidepressant responses.
Wayne C Drevets - One of the best experts on this subject based on the ideXlab platform.
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the effects of catecholamine depletion on the neural response to fearful faces in remitted depression
The International Journal of Neuropsychopharmacology, 2014Co-Authors: Philipp Homan, Wayne C Drevets, Gregor HaslerAbstract:Recent evidence suggests that increased psychophysiological response to negatively valenced emotional stimuli found in major depressive disorder (MDD) may be associated with reduced catecholaminergic neurotransmission. Fourteen unmedicated, remitted subjects with MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebocontrolled, double-blind crossover trial. Subjects were exposed to fearful (FF) and neutral faces (NF) during a scan with [ 15 O]H2O positron emission tomography to assess the brain–catecholamine interaction in brain regions previously associated with emotional face processing. Treatment with AMPT resulted in significantly increased, normalized cerebral blood flow (CBF) in the left inferior temporal gyrus (ITG) and significantly decreased CBF in the right cerebellum across conditions and groups. In RMDD, flow in the left posterior cingulate cortex (PCC) increased significantly in the FF compared to the NF condition after AMPT, but remained unchanged after placebo, whereas healthy controls showed a significant increase under placebo and a significant decrease under AMPT in this brain region. In the left dorsolateral prefrontal cortex (DLPFC), flow decreased significantly in the FF compared to the NF condition under AMPT, and increased significantly under placebo in RMDD, whereas healthy controls showed no significant differences. Differences between AMPT and placebo of within-session changes in worry-symptoms were positively correlated with the corresponding changes in CBF in the right subgenual prefrontal cortex in RMDD. In conclusion, this study provided evidence for a catecholamine-related modulation of the neural responses to FF expressions in the left PCC and the left DLPFC in subjects with RMDD that might constitute a persistent, trait-like abnormality in MDD.
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growth hormone response to catecholamine depletion in unmedicated remitted subjects with major depressive disorder and healthy controls
Journal of Clinical Psychopharmacology, 2013Co-Authors: Philipp Homan, Wayne C Drevets, Gregor HaslerAbstract:We investigated whether the human growth hormone (HGH) response to catecholamine depletion differs between fully remitted patients with major depressive disorder and healthy control subjects. Fourteen unmedicated subjects with remitted major depressive disorder (RMDD) and 11 healthy control subjects underwent catecholamine depletion with oral α-methylparatyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover study. The main outcome measure was the serum level of HGH. The diagnosis × drug interaction for HGH serum concentration was significant (F₁,₂₃ = 7.66, P < 0.02). This interaction was attributable to the HGH level increasing after AMPT administration in the RMDD subjects but not in the healthy subjects. In the RMDD sample, the AMPT-induced increase in HGH concentration correlated inversely with AMPT-induced anxiety symptoms as assessed using the Beck Anxiety Inventory (r = -0.63, P < 0.02). There was a trend toward an inverse correlation of the AMPT-induced HGH concentration changes with AMPT-induced depressive symptoms as measured by the BDI (r = -0.53, P = 0.05). Following catecholamine depletion, the RMDD subjects were differentiated from control subjects by their HGH responses. This finding, together with the negative correlation between HGH response and AMPT-induced anxiety symptoms in RMDD subjects, suggests that AMPT administration results in a deeper nadir in central catecholaminergic transmission, as reflected by a greater disinhibition of HGH secretion, in RMDD subjects versus control subjects.
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reward processing after catecholamine depletion in unmedicated remitted subjects with major depressive disorder
Biological Psychiatry, 2009Co-Authors: Gregor Hasler, Dennis S Charney, David A Luckenbaugh, Joseph Snow, Noah Meyers, Tracy Waldeck, Marilla Geraci, Jonathan P Roiser, Brian Knutson, Wayne C DrevetsAbstract:Background We investigated whether performance on a reward processing task differs between fully remitted patients with major depressive disorder (MDD) and healthy control subjects after catecholamine depletion. Methods Seventeen unmedicated subjects with remitted MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover study. The main outcome measure was the reaction time on the monetary incentive delay (MID) task. Results A diagnosis × drug interaction was evident ( p = .001), which was attributable to an increase in reaction time across all incentive levels after AMPT in RMDD subjects ( p = .001) but no significant AMPT effect on reaction time in control subjects ( p = .17). There was no drug × diagnosis interaction on control tasks involving working memory or attention. In the RMDD sample the AMPT-induced depressive symptoms correlated with AMPT-induced changes in reaction time at all incentive levels of the MID task ( r values=.58–.82, p Conclusions Under catecholamine depletion the RMDD subjects were robustly differentiated from control subjects by development of performance deficits on a reward processing task. These performance deficits correlated directly with the return of depressive symptoms after AMPT administration. The sensitivity of central reward processing systems to reductions in brain catecholamine levels thus seems to represent a trait-like marker in MDD.