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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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behavioral responses to Catecholamine Depletion in unmedicated remitted subjects with bulimia nervosa and healthy subjects
Biological Psychiatry, 2015Co-Authors: Simona Grob, Gabriella Milos, Ulrich Schnyder, Jair Stern, Lara Gamper, Hanspeter Moergeli, Gregor HaslerAbstract:Abstract Background Bulimia nervosa (BN) has been associated with dysregulation of the central Catecholaminergic system. An instructive way to investigate the relationship between Catecholaminergic function and psychiatric disorder has involved behavioral responses to experimental Catecholamine Depletion (CD). The purpose of this study was to examine a possible Catecholaminergic dysfunction in the pathogenesis of bulimia nervosa. Methods CD was achieved by oral administration of alpha-methyl-para-tyrosine (AMPT) in 18 remitted female subjects with BN (rBN) and 31 healthy female control subjects. The study design consisted of a randomized, double blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were bulimic symptoms assessed by the Eating Disorder Examination—Questionnaire. Measures were assessed before and 26, 30, 54, 78, 102 hours after the first AMPT or placebo administration. Results In the experimental environment (controlled environment with a low level of food cues) rBN subjects had a greater increase in eating disorder symptoms during CD compared with healthy control subjects (condition × diagnosis interaction, p p Conclusions This study suggests that rBN is associated with vulnerability for developing eating disorder symptoms in response to reduced Catecholamine neurotransmission after CD. The findings support the notion of Catecholaminergic dysfunction as a possible trait abnormality in BN.
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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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neural correlates of free t3 alteration after Catecholamine Depletion in subjects with remitted major depressive disorder and in controls
Psychopharmacology, 2014Co-Authors: Philipp Homan, Wayne C Drevets, Gregor HaslerAbstract:Thyroid hormones and their interactions with Catecholamines play a potentially important role in alterations of mood and cognition. This study aimed to examine the neurobiological effects of Catecholamine Depletion on thyroid hormones by measuring endocrine and cerebral metabolic function in unmedicated subjects with remitted major depressive disorder (RMDD) and in healthy controls. This was a randomized, placebo-controlled, and double-blind crossover trial that included 15 unmedicated RMDD subjects and 13 healthy control subjects. The participants underwent two 3-day-long sessions at 1-week intervals; each participant was randomly administered oral α-methyl-para-tyrosine in one session (Catecholamine Depletion) and an identical capsule containing hydrous lactose (sham Depletion) in the other session prior to a [18F]-fluorodeoxyglucose positron emission tomography scan. Serum concentrations of free T3 (FT3), free T4 (FT4), and TSH were obtained and assessed with respect to their relationship to regional cerebral glucose metabolism. Both serum FT3 (P = 0.002) and FT4 (P = 0.0009) levels were less suppressed after Catecholamine Depletion compared with placebo treatment in the entire study sample. There was a positive association between both FT3 (P = 0.0005) and FT4 (P = 0.002) and depressive symptoms measured using the Montgomery–Asberg Depression Rating Scale. The relative elevation in FT3 level was correlated with a decrease in regional glucose metabolism in the right dorsolateral prefrontal cortex (rDLPFC; P < 0.05, corrected). This study provided evidence of an association between a thyroid–Catecholamine interaction and mood regulation in the rDLPFC.
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comparative behavioral and neural effects of tryptophan and Catecholamine Depletion in remitted depression
2014Co-Authors: Gregor Hasler, Dennis S Charney, Allison C Nugent, Alexander Neumeister, Philipp Homan, Wayne C DrevetsAbstract:Background: Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catechominergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or Catecholamine neurotransmission hold the potential to optimize the prescriber’s selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus Catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Methods: Using identical neuroimaging procedures with [18F] fluorodeoxyglucose positron emission tomography after tryptophan Depletion (TD) and Catecholamine Depletion (CD), subjects with remitted depression were compared to healthy controls in a double-blind, randomized, crossover design. Results: While TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex (PCC). While we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. Conclusions: In conclusion, this study showed that serotonin and Catecholamines play common and differential roles in the pathophysiology of depression.
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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comparative behavioral and neural effects of tryptophan and Catecholamine Depletion in remitted depression
2014Co-Authors: Gregor Hasler, Dennis S Charney, Allison C Nugent, Alexander Neumeister, Philipp Homan, Wayne C DrevetsAbstract:Background: Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catechominergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or Catecholamine neurotransmission hold the potential to optimize the prescriber’s selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus Catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Methods: Using identical neuroimaging procedures with [18F] fluorodeoxyglucose positron emission tomography after tryptophan Depletion (TD) and Catecholamine Depletion (CD), subjects with remitted depression were compared to healthy controls in a double-blind, randomized, crossover design. Results: While TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex (PCC). While we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. Conclusions: In conclusion, this study showed that serotonin and Catecholamines play common and differential roles in the pathophysiology of depression.
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neural correlates of free t3 alteration after Catecholamine Depletion in subjects with remitted major depressive disorder and in controls
Psychopharmacology, 2014Co-Authors: Philipp Homan, Wayne C Drevets, Gregor HaslerAbstract:Thyroid hormones and their interactions with Catecholamines play a potentially important role in alterations of mood and cognition. This study aimed to examine the neurobiological effects of Catecholamine Depletion on thyroid hormones by measuring endocrine and cerebral metabolic function in unmedicated subjects with remitted major depressive disorder (RMDD) and in healthy controls. This was a randomized, placebo-controlled, and double-blind crossover trial that included 15 unmedicated RMDD subjects and 13 healthy control subjects. The participants underwent two 3-day-long sessions at 1-week intervals; each participant was randomly administered oral α-methyl-para-tyrosine in one session (Catecholamine Depletion) and an identical capsule containing hydrous lactose (sham Depletion) in the other session prior to a [18F]-fluorodeoxyglucose positron emission tomography scan. Serum concentrations of free T3 (FT3), free T4 (FT4), and TSH were obtained and assessed with respect to their relationship to regional cerebral glucose metabolism. Both serum FT3 (P = 0.002) and FT4 (P = 0.0009) levels were less suppressed after Catecholamine Depletion compared with placebo treatment in the entire study sample. There was a positive association between both FT3 (P = 0.0005) and FT4 (P = 0.002) and depressive symptoms measured using the Montgomery–Asberg Depression Rating Scale. The relative elevation in FT3 level was correlated with a decrease in regional glucose metabolism in the right dorsolateral prefrontal cortex (rDLPFC; P < 0.05, corrected). This study provided evidence of an association between a thyroid–Catecholamine interaction and mood regulation in the rDLPFC.
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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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Catecholamine Depletion in first degree relatives of individuals with mood disorders an 18f fluorodeoxyglucose positron emission tomography study
NeuroImage: Clinical, 2013Co-Authors: Jonathan Savitz, Allison C Nugent, Patrick S F Bellgowan, Niara Wright, Ruth Tinsley, Carlos A Zarate, Peter Herscovitch, Wayne C DrevetsAbstract:Catecholamine Depletion with alpha-methylparatyrosine (AMPT) has previously been shown to induce depressive symptoms in currently remitted patients with major depressive disorder (MDD) but not healthy controls. Thus sensitivity to Catecholamine Depletion has been hypothesized to be an endophenotype of MDD. Here we tested this hypothesis in the context of a randomized, double-blinded, placebo-controlled design by measuring changes in mood in a group of psychiatrically-healthy individuals at risk of mood disorders by virtue of family history (high-risk subjects, HRs). In addition, we tested whether HRs differed from healthy controls with no family-history of mood disorders (low-risk controls, LRs) in their cerebral metabolic response when undergoing Catecholamine Depletion. Eight healthy LRs (6 males, mean age = 34.1 ± 7.1) and 6 healthy HRs (3 males, mean age = 29.3 ± 4.6) participated in two, 3-day-long identical sessions during which they completed standardized measures of depression, anxiety and fatigue and an [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scan. On one occasion participants received 4 weight-adjusted doses of AMPT and on the other occasion participants received 4 doses of placebo. The LR and HR groups did not differ from each other in their mood during sham Depletion. However, during the period of peak Catecholamine Depletion, the HR group reported significantly more depression, anxiety and fatigue than the LR group. A region-of-interest analysis showed that during Catecholamine Depletion versus placebo the combined LR and HR groups displayed a significant increase in cerebral metabolic rate in the left and right ventral striata, left and right amygdalae, and left and right hippocampi (FWE-corrected p < 0.05). Whole brain voxel-wise analyses indicated significantly increased glucose metabolism in the left and right putamina (FWE-corrected p < 0.05) in the combined LR and HR groups in the AMPT versus the placebo session. In the LR group, alone, no significant elevation in glucose metabolism was observed in the regions-of-interest in the Catecholamine Depletion versus placebo condition. In the HR group, alone, the region-of-interest analysis showed a significant increase in cerebral metabolic rate in the left and right ventral striata (FWE-corrected p < 0.05). No regions-of-interest showed significantly different metabolism in the HR group versus the LR group in the placebo condition, however compared with the LR group, the HR group displayed nominally increased glucose metabolism in the left amygdala during Catecholamine Depletion (SVC-corrected p = 0.05). A region-of-interest analysis for the interaction contrast confirmed that Catecholamine Depletion had differential effects on HR and LR participants. Compared with the LR group, the HR group displayed significantly increased glucose metabolism in the left ventral striatum, left amygdala, and left lateral orbitofrontal cortex (OFC) (FWE-corrected p < 0.05). Our results suggest that sensitivity to Catecholamine Depletion may be a phenotypic marker of vulnerability to mood disorders that is characterized at the neurophysiological level by disinhibition of the striatum and its efferent projections comprising the limbic–cortical–striatal–pallidal–thalamic circuitry.
Dennis S Charney - One of the best experts on this subject based on the ideXlab platform.
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comparative behavioral and neural effects of tryptophan and Catecholamine Depletion in remitted depression
2014Co-Authors: Gregor Hasler, Dennis S Charney, Allison C Nugent, Alexander Neumeister, Philipp Homan, Wayne C DrevetsAbstract:Background: Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catechominergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or Catecholamine neurotransmission hold the potential to optimize the prescriber’s selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus Catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Methods: Using identical neuroimaging procedures with [18F] fluorodeoxyglucose positron emission tomography after tryptophan Depletion (TD) and Catecholamine Depletion (CD), subjects with remitted depression were compared to healthy controls in a double-blind, randomized, crossover design. Results: While TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex (PCC). While we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. Conclusions: In conclusion, this study showed that serotonin and Catecholamines play common and differential roles in the pathophysiology of depression.
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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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neural response to Catecholamine Depletion in unmedicated subjects with major depressive disorder in remission and healthy subjects
Archives of General Psychiatry, 2008Co-Authors: Gregor Hasler, David A Luckenbaugh, Noah Meyers, Tracy Waldeck, Marilla Geraci, Jonathan P Roiser, Alexander Neumeister, Stephen J Fromm, Paul J Carlson, Dennis S CharneyAbstract:Context: The pathophysiologic mechanism of major depressive disorder (MDD) has been consistently associated with altered Catecholaminergic function, especially with decreased dopamine neurotransmission, by various sources of largely indirect evidence. An instructive paradigm for more directly investigating the relationship between Catecholaminergic function and depression has involved the mood response to experimental Catecholamine Depletion (CD). Objectives: To determine whether Catecholaminergic dysfunction represents a trait abnormality in MDD and to identify brain circuitry abnormalities involved in the pathophysiologic mechanism of MDD. Design: Randomized, d ouble-blind, p lacebocontrolled, crossover, single-site experimental trial.
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transient depressive relapse induced by Catecholamine Depletion potential phenotypic vulnerability marker
Archives of General Psychiatry, 1999Co-Authors: Robert M Berman, Meera Narasimhan, Helen L Miller, Amit Anand, Angela Cappiello, Dan A Oren, George R Heninger, Dennis S CharneyAbstract:Background Although state-related alterations in Catecholamine function have been well-described in depressed subjects, enduring abnormalities have been less reliably identified. In our study, medication-free subjects with fully remitted major depression underwent a paradigm of Catecholamine Depletion, via use of the tyrosine hydroxylase inhibitor α-methylparatyrosine. Method Subjects underwent 2 sets of testing conditions in a double-blind, random-ordered, crossover design, approximately 1 week apart. They underwent active Catecholamine Depletion (via oral administration of 5 g α-methylparatyrosine) or sedation-controlled, sham Catecholamine Depletion (via oral administration of 250 mg diphenhydramine hydrochloride), during a 2-day observation. Serial mood ratings and blood samples were obtained. Results Fourteen subjects completed the active testing condition; 13 completed sham testing. Subjects experienced marked, transient increases in core depressive and anxiety symptoms, as demonstrated by a mean 21-point increase on Hamilton Depression Rating Scale scores. Furthermore, 10 (71%) of 14 subjects fulfilled relapse criteria during active testing, whereas 1 (8%) of 13 subjects did so during sham testing. The severity of the depressive reaction correlated with baseline plasma cortisol levels ( r =0.59; P =.04). Conclusions Euthymic, medication-free subjects with a history of major depression demonstrate significant depressive symptoms when undergoing testing with α-methylparatyrosine. This depressive reaction may represent a reliable marker for a history of depression. Further work is needed to clarify the significance of this finding.
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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.
Alexander Neumeister - One of the best experts on this subject based on the ideXlab platform.
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comparative behavioral and neural effects of tryptophan and Catecholamine Depletion in remitted depression
2014Co-Authors: Gregor Hasler, Dennis S Charney, Allison C Nugent, Alexander Neumeister, Philipp Homan, Wayne C DrevetsAbstract:Background: Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catechominergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or Catecholamine neurotransmission hold the potential to optimize the prescriber’s selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus Catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Methods: Using identical neuroimaging procedures with [18F] fluorodeoxyglucose positron emission tomography after tryptophan Depletion (TD) and Catecholamine Depletion (CD), subjects with remitted depression were compared to healthy controls in a double-blind, randomized, crossover design. Results: While TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex (PCC). While we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. Conclusions: In conclusion, this study showed that serotonin and Catecholamines play common and differential roles in the pathophysiology of depression.
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neural response to Catecholamine Depletion in unmedicated subjects with major depressive disorder in remission and healthy subjects
Archives of General Psychiatry, 2008Co-Authors: Gregor Hasler, David A Luckenbaugh, Noah Meyers, Tracy Waldeck, Marilla Geraci, Jonathan P Roiser, Alexander Neumeister, Stephen J Fromm, Paul J Carlson, Dennis S CharneyAbstract:Context: The pathophysiologic mechanism of major depressive disorder (MDD) has been consistently associated with altered Catecholaminergic function, especially with decreased dopamine neurotransmission, by various sources of largely indirect evidence. An instructive paradigm for more directly investigating the relationship between Catecholaminergic function and depression has involved the mood response to experimental Catecholamine Depletion (CD). Objectives: To determine whether Catecholaminergic dysfunction represents a trait abnormality in MDD and to identify brain circuitry abnormalities involved in the pathophysiologic mechanism of MDD. Design: Randomized, d ouble-blind, p lacebocontrolled, crossover, single-site experimental trial.
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effects of tryptophan Depletion and Catecholamine Depletion on immune parameters in patients with seasonal affective disorder in remission with light therapy
Biological Psychiatry, 2003Co-Authors: J Stastny, Siegfried Kasper, Norman E Rosenthal, A Konstantinidis, Markus J Schwarz, Oliver Vitouch, Alexander NeumeisterAbstract:Abstract Background Altered immunologic parameters are found in symptomatic depressed patients relative to remitted depressed patients and healthy controls. We investigated whether tryptophan Depletion and Catecholamine Depletion induce alterations in immunologic parameters in patients with seasonal affective disorder remitted on light therapy, and whether these changes are associated with changes in mood. Methods Remitted patients with seasonal affective disorder underwent tryptophan Depletion, Catecholamine Depletion, and sham Depletion in a prospective randomized, double-blind crossover design. Measures of depression, plasma levels of tryptophan and Catecholamine metabolites, and plasma levels of cytokines (sIL-4, IL-6, neopterin, sTNF-R1 and sTNF-R2) were obtained at baseline, and 7, 24, and 30 hours after monoamine Depletion. Results Tryptophan Depletion decreased plasma total and free tryptophan levels; Catecholamine Depletion decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels. Tryptophan Depletion and Catecholamine Depletion, but not sham Depletion, induced a transient exacerbation of depressive symptoms ( p p p r = −.61, p Conclusions The monoamine Depletion-induced alterations of humoral and cellular immunity suggest a potential role of immunologic parameters in the pathophysiology of seasonal affective disorder; however, the results must be considered preliminary and require further study.
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effects of tryptophan Depletion vs Catecholamine Depletion in patients with seasonal affective disorder in remission with light therapy
Archives of General Psychiatry, 1998Co-Authors: Alexander Neumeister, Erick H Turner, Jefferey R Matthews, Teodor T Postolache, Ronald L Barnett, Manfred Rauh, Rina G Vetticad, Siegfried Kasper, Norman E RosenthalAbstract:Methods: Sixteen patients with seasonal affective disorder who had responded to a standard regimen of daily 10 000-lux light therapy were enrolled in a doubleblind, placebo-controlled, randomized crossover study. We compared the effects of tryptophan Depletion with Catecholamine Depletion and sham Depletion. Ingestion of a tryptophan-free amino acid beverage plus amino acid capsules was used to deplete tryptophan. Administration of the tyrosine hydroxylase inhibitor a-methyl-paratyrosine was used to deplete Catecholamines. Diphenhydramine hydrochloride was used as an active placebo during sham Depletion. The effects of these interventions were evaluated with measures of depression, plasma tryptophan levels, and plasma Catecholamine metabolites. Results: Tryptophan Depletion significantly decreased plasma total and free tryptophan levels. Catecholamine Depletion significantly decreased plasma 3-methoxy-4hydroxyphenylethyleneglycol and homovanillic acid levels. Both tryptophan Depletion and Catecholamine Depletion, compared with sham Depletion, induced a robust increase (P,.001, repeated-measures analysis of variance) in depressive symptoms as measured with the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version. Conclusions: The beneficial effects of light therapy in the treatment of seasonal affective disorder are reversed by both tryptophan Depletion and Catecholamine Depletion. These findings confirm previous work showing that serotonin plays an important role in the mechanism of action of light therapy and provide new evidence that brain Catecholaminergic systems may also be involved.
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effects of tryptophan Depletion and Catecholamine Depletion on immune parameters in patients with seasonal affective disorder in remission with light therapy
Biological Psychiatry, 2003Co-Authors: J Stastny, Siegfried Kasper, Norman E Rosenthal, A Konstantinidis, Markus J Schwarz, Oliver Vitouch, Alexander NeumeisterAbstract:Abstract Background Altered immunologic parameters are found in symptomatic depressed patients relative to remitted depressed patients and healthy controls. We investigated whether tryptophan Depletion and Catecholamine Depletion induce alterations in immunologic parameters in patients with seasonal affective disorder remitted on light therapy, and whether these changes are associated with changes in mood. Methods Remitted patients with seasonal affective disorder underwent tryptophan Depletion, Catecholamine Depletion, and sham Depletion in a prospective randomized, double-blind crossover design. Measures of depression, plasma levels of tryptophan and Catecholamine metabolites, and plasma levels of cytokines (sIL-4, IL-6, neopterin, sTNF-R1 and sTNF-R2) were obtained at baseline, and 7, 24, and 30 hours after monoamine Depletion. Results Tryptophan Depletion decreased plasma total and free tryptophan levels; Catecholamine Depletion decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels. Tryptophan Depletion and Catecholamine Depletion, but not sham Depletion, induced a transient exacerbation of depressive symptoms ( p p p r = −.61, p Conclusions The monoamine Depletion-induced alterations of humoral and cellular immunity suggest a potential role of immunologic parameters in the pathophysiology of seasonal affective disorder; however, the results must be considered preliminary and require further study.
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effects of tryptophan Depletion vs Catecholamine Depletion in patients with seasonal affective disorder in remission with light therapy
Archives of General Psychiatry, 1998Co-Authors: Alexander Neumeister, Erick H Turner, Jefferey R Matthews, Teodor T Postolache, Ronald L Barnett, Manfred Rauh, Rina G Vetticad, Siegfried Kasper, Norman E RosenthalAbstract:Methods: Sixteen patients with seasonal affective disorder who had responded to a standard regimen of daily 10 000-lux light therapy were enrolled in a doubleblind, placebo-controlled, randomized crossover study. We compared the effects of tryptophan Depletion with Catecholamine Depletion and sham Depletion. Ingestion of a tryptophan-free amino acid beverage plus amino acid capsules was used to deplete tryptophan. Administration of the tyrosine hydroxylase inhibitor a-methyl-paratyrosine was used to deplete Catecholamines. Diphenhydramine hydrochloride was used as an active placebo during sham Depletion. The effects of these interventions were evaluated with measures of depression, plasma tryptophan levels, and plasma Catecholamine metabolites. Results: Tryptophan Depletion significantly decreased plasma total and free tryptophan levels. Catecholamine Depletion significantly decreased plasma 3-methoxy-4hydroxyphenylethyleneglycol and homovanillic acid levels. Both tryptophan Depletion and Catecholamine Depletion, compared with sham Depletion, induced a robust increase (P,.001, repeated-measures analysis of variance) in depressive symptoms as measured with the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version. Conclusions: The beneficial effects of light therapy in the treatment of seasonal affective disorder are reversed by both tryptophan Depletion and Catecholamine Depletion. These findings confirm previous work showing that serotonin plays an important role in the mechanism of action of light therapy and provide new evidence that brain Catecholaminergic systems may also be involved.