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Anissa Abi-Dargham

Ragy R Girgis, Mark Slifstein, Deepak D'Souza, Yih Lee, Antonia Periclou, Parviz Ghahramani, István Laszlovszky, Suresh Durgam, Nika Adham, Nabeel Nabulsi, Yiyun Huang, Richard E Carson, Béla Kiss, Margit Kapás, Anissa Abi-Dargham, Ashok Rakhit
RATIONALE: Second-generation antipsychotics occupy dopamine D2 receptors and act as antagonists or partial agonists at these receptors. While these drugs alleviate positive symptoms in patients with schizophrenia, they are less effective for treating cognitive deficits and negative symptoms. Dopamine D3 receptors are highly expressed in areas of the brain thought to play a role in the regulation of motivation and reward-related behavior. Consequently, the dopamine D3 receptor has become a target for treating negative symptoms in combination with D2 antagonism to treat positive symptoms in patients with schizophrenia...
October 2016: Psychopharmacology
Joshua L Roffman, Alexandra S Tanner, Hamdi Eryilmaz, Anais Rodriguez-Thompson, Noah J Silverstein, New Fei Ho, Adam Z Nitenson, Daniel B Chonde, Douglas N Greve, Anissa Abi-Dargham, Randy L Buckner, Dara S Manoach, Bruce R Rosen, Jacob M Hooker, Ciprian Catana
Local prefrontal dopamine signaling supports working memory by tuning pyramidal neurons to task-relevant stimuli. Enabled by simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI), we determined whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory. Among network territories, mean cortical D1 receptor densities differed substantially but were strongly interrelated, suggesting cross-network regulation. Indeed, mean cortical D1 density predicted working memory-emergent decoupling of the frontoparietal and default networks, which respectively manage task-related and internal stimuli...
June 2016: Science Advances
John H Krystal, Anissa Abi-Dargham, Schahram Akbarian, Amy F T Arnsten, Deanna M Barch, Carrie E Bearden, David L Braff, E Sherwood Brown, Edward T Bullmore, William A Carlezon, Cameron S Carter, Edwin H Cook, Zafiris Jeff Daskalakis, Ralph J DiLeone, Ronald S Duman, Anthony A Grace, Ahmad R Hariri, Paul J Harrison, Noboru Hiroi, Paul J Kenny, Joel E Kleinman, Andrew D Krystal, David A Lewis, Barbara K Lipska, Stephen R Marder, Graeme F Mason, Daniel H Mathalon, Colleen A McClung, Christopher J McDougle, Andrew M McIntosh, Francis J McMahon, Károly Mirnics, Lisa M Monteggia, Rajesh Narendran, Eric J Nestler, Alexander Neumeister, Michael C O'Donovan, Dost Öngür, Carmine M Pariante, Martin P Paulus, Godfrey Pearlson, Mary L Phillips, Daniel S Pine, Diego A Pizzagalli, Mikhail V Pletnikov, J Daniel Ragland, Judith L Rapoport, Kerry J Ressler, Scott J Russo, Gerard Sanacora, Akira Sawa, Alan F Schatzberg, Yavin Shaham, Simone G Shamay-Tsoory, Pamela Sklar, Matthew W State, Murray B Stein, Stephen M Strakowski, Stephan F Taylor, Gustavo Turecki, Bruce I Turetsky, Myrna M Weissman, Venetia Zachariou, Carlos A Zarate, Jon-Kar Zubieta
No abstract text is available yet for this article.
July 15, 2016: Biological Psychiatry
John H Krystal, Anissa Abi-Dargham, Deanna M Barch, Edward T Bullmore, Cameron S Carter, Daniel H Geschwind, Paul J Harrison, Eric J Nestler, Murray B Stein
No abstract text is available yet for this article.
July 1, 2016: Biological Psychiatry
Jodi J Weinstein, Muhammad O Chohan, Mark Slifstein, Lawrence S Kegeles, Holly Moore, Anissa Abi-Dargham
In light of the clinical evidence implicating dopamine in schizophrenia and the prominent hypotheses put forth regarding alterations in dopaminergic transmission in this disease, molecular imaging has been used to examine multiple aspects of the dopaminergic system. We review the imaging methods used and compare the findings across the different molecular targets. Findings have converged to suggest early dysregulation in the striatum, especially in the rostral caudate, manifesting as excess synthesis and release...
March 31, 2016: Biological Psychiatry
Corinde E Wiers, Ehsan Shokri-Kojori, Christopher T Wong, Anissa Abi-Dargham, Şükrü B Demiral, Dardo Tomasi, Gene-Jack Wang, Nora D Volkow
The extent to which cannabis is deleterious to the human brain is not well understood. Here, we test whether cannabis abusers (CA) have impaired frontal function and reactivity to dopaminergic signaling, which are fundamental to relapse in addiction. We measured brain glucose metabolism using PET and [(18)F]FDG both at baseline (placebo) and after challenge with methylphenidate (MP), a dopamine-enhancing drug, in 24 active CA (50% female) and 24 controls (HC; 50% female). Results show that (i) CA had lower baseline glucose metabolism than HC in frontal cortex including anterior cingulate, which was associated with negative emotionality...
September 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Guillermo Horga, Clifford M Cassidy, Xiaoyan Xu, Holly Moore, Mark Slifstein, Jared X Van Snellenberg, Anissa Abi-Dargham
IMPORTANCE: Despite the well-established role of striatal dopamine in psychosis, current views generally agree that cortical dysfunction is likely necessary for the emergence of psychotic symptoms. The topographic organization of striatal-cortical connections is central to gating and integration of higher-order information, so a disruption of such topography via dysregulated dopamine could lead to cortical dysfunction in schizophrenia. However, this hypothesis remains to be tested using multivariate methods ascertaining the global pattern of striatal connectivity and without the confounding effects of antidopaminergic medication...
August 1, 2016: JAMA Psychiatry
Jenna M Reinen, Jared X Van Snellenberg, Guillermo Horga, Anissa Abi-Dargham, Nathaniel D Daw, Daphna Shohamy
BACKGROUND: Recent findings demonstrate that patients with schizophrenia are worse at learning to predict rewards than losses, suggesting that motivational context modulates learning in this disease. However, these findings derive from studies in patients treated with antipsychotic medications, D2 receptor antagonists that may interfere with the neural systems that underlie motivation and learning. Thus, it remains unknown how motivational context affects learning in schizophrenia, separate from the effects of medication...
April 22, 2016: Schizophrenia Bulletin
Clifford M Cassidy, Jared X Van Snellenberg, Caridad Benavides, Mark Slifstein, Zhishun Wang, Holly Moore, Anissa Abi-Dargham, Guillermo Horga
UNLABELLED: Connectivity between brain networks may adapt flexibly to cognitive demand, a process that could underlie adaptive behaviors and cognitive deficits, such as those observed in neuropsychiatric conditions like schizophrenia. Dopamine signaling is critical for working memory but its influence on internetwork connectivity is relatively unknown. We addressed these questions in healthy humans using functional magnetic resonance imaging (during ann-back working-memory task) and positron emission tomography using the radiotracer [(11)C]FLB457 before and after amphetamine to measure the capacity for dopamine release in extrastriatal brain regions...
April 13, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jared X Van Snellenberg, Ragy R Girgis, Guillermo Horga, Elsmarieke van de Giessen, Mark Slifstein, Najate Ojeil, Jodi J Weinstein, Holly Moore, Jeffrey A Lieberman, Daphna Shohamy, Edward E Smith, Anissa Abi-Dargham
BACKGROUND: The neural correlates of working memory (WM) impairment in schizophrenia remain a key puzzle in understanding the cognitive deficits and dysfunction of dorsolateral prefrontal cortex observed in this disorder. We sought to determine whether patients with schizophrenia exhibit an alteration in the inverted-U relationship between WM load and activation that we recently observed in healthy individuals and whether this could account for WM deficits in this population. METHODS: Medicated (n = 30) and unmedicated (n = 21) patients with schizophrenia and healthy control subjects (n = 45) performed the self-ordered WM task during functional magnetic resonance imaging...
October 15, 2016: Biological Psychiatry
Ragy R Girgis, Jared X Van Snellenberg, Andrew Glass, Lawrence S Kegeles, Judy L Thompson, Melanie Wall, Raymond Y Cho, Cameron S Carter, Mark Slifstein, Anissa Abi-Dargham, Jeffrey A Lieberman
BACKGROUND: Evidence from preclinical and human studies indicates the presence of reduced dopamine-1 receptor (D1R) signaling in the cortex, where D1Rs predominate, in patients with schizophrenia (SCZ), which may contribute to their cognitive deficits. Furthermore, studies in nonhuman primates (NHP) have suggested that intermittent administration of low doses of D1R agonists produce long-lasting reversals in cognitive deficits. The purpose of this trial was to test whether a similar design, involving subacute intermittent administration of low doses of a full, selective agonist at D1Rs, DAR-0100A, would improve cognitive deficits in SCZ...
May 2016: Journal of Psychopharmacology
Tiziano Colibazzi, Guillermo Horga, Zhishun Wang, Yuankai Huo, Cheryl Corcoran, Kristin Klahr, Gary Brucato, Ragy Girgis, Kelly Gill, Anissa Abi-Dargham, Bradley S Peterson
Cognitive control, a set of functions that develop throughout adolescence, is important in the pathogenesis of psychotic disorders. Whether cognitive control has a role in conferring vulnerability for the development of psychotic illness is still unknown. The aim of this study was to investigate the neural systems supporting cognitive control in individuals deemed to be potentially prodromal for psychotic illness. We recruited 56 participants at clinical high-risk (CHR) for psychosis based on the Structured Interview for Psychosis-Risk Syndromes (SIPS) and 49 healthy controls...
April 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
William R Corbin, Anna Papova, Meghan E Morean, Stephanie S O'Malley, Suchitra Krishnan-Sarin, Anissa Abi-Dargham, Alan Anticevic, Godfrey Pearlson, Ismene Petrakis, Brian P Pittman, John H Krystal
The acquired preparedness model (APM) posits that alcohol expectancies mediate effects of personality traits on drinking outcomes, whereas the dual process model (DPM) suggests that top-down behavioral control (e.g., self-control) moderates the impact of bottom-up risk factors such as alcohol expectancies. This study sought to integrate the APM and DPM by examining the extent to which indirect effects of impulsive sensation seeking on drinking outcomes are moderated by self-control. We hypothesized that the APM may hold more strongly for people who are higher in self-control, as they may engage in alcohol use for the explicit purpose of meeting sensation-seeking goals...
December 2015: Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors
Ragy R Girgis, Xiaoyan Xu, Roberto B Gil, Elizabeth Hackett, Najate Ojeil, Jeffrey A Lieberman, Mark Slifstein, Anissa Abi-Dargham
BACKGROUND: All currently available antipsychotic medications bind to both the dopamine-2 (D2) and dopamine-3 (D3) receptors in vitro. However, there is conflicting evidence from in vivo studies about whether or not antipsychotic medications bind to the D3 receptor (D3R). The purpose of this study was to determine whether acute doses of risperidone bind to the D3R in humans. METHODS: We performed PET scans on an mCT scanner with [(11)C]-(+)-PHNO injected as a bolus, before and after a 2mg oral dose of risperidone in five medication free subjects with schizophrenia...
October 2015: Schizophrenia Research
Khanum Ridler, Vincent Cunningham, Mickael Huiban, Laurent Martarello, Sabina Pampols-Maso, Jan Passchier, Roger N Gunn, Graham Searle, Anissa Abi-Dargham, Mark Slifstein, Jeanette Watson, Marc Laruelle, Eugenii A Rabiner
BACKGROUND: The ability to quantify the capacity of a central nervous system (CNS) drug to cross the human blood-brain barrier (BBB) provides valuable information for de-risking drug development of new molecules. Here, we present a study, where a suitable positron emission tomography (PET) ligand was not available for the evaluation of a potent muscarinic acetylcholine receptor type-1 (M1) allosteric agonist (GSK1034702) in the primate and human brain. Hence, direct radiolabelling of the novel molecule was performed and PET measurements were obtained and combined with in vitro equilibrium dialysis assays to enable assessment of BBB transport and estimation of the free brain concentration of GSK1034702 in vivo...
December 2014: EJNMMI Research
Mark Slifstein, Elsmarieke van de Giessen, Jared Van Snellenberg, Judy L Thompson, Rajesh Narendran, Roberto Gil, Elizabeth Hackett, Ragy Girgis, Najate Ojeil, Holly Moore, Deepak D'Souza, Robert T Malison, Yiyun Huang, Keunpoong Lim, Nabeel Nabulsi, Richard E Carson, Jeffrey A Lieberman, Anissa Abi-Dargham
IMPORTANCE: Multiple lines of evidence suggest a deficit in dopamine release in the prefrontal cortex (PFC) in schizophrenia. Despite the prevalence of the concept of prefrontal cortical hypodopaminergia in schizophrenia, in vivo imaging of dopamine release in the PFC has not been possible until now, when the validity of using the positron emission tomographic D2/3 radiotracer carbon 11-labeled FLB457 in combination with the amphetamine paradigm was clearly established. OBJECTIVES: To (1) test amphetamine-induced dopamine release in the dorsolateral PFC (DLPFC) in drug-free or drug-naive patients with schizophrenia (SCZ) and healthy control (HC) individuals matched for age, sex, race/ethnicity, and familial socioeconomic status;(2) test blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging activation during a working memory task in the same participants; and (3) examine the relationship between positron emission tomographic and functional magnetic resonance imaging outcome measures...
April 2015: JAMA Psychiatry
Anissa Abi-Dargham
Schizophrenia is a chronic, often disabling illness that affects approximately 24 million people worldwide. Unfortunately, while the majority of first-episode schizophrenia patients respond well to initial antipsychotic treatment, less than 1 in 5 will maintain recovery over 2 to 5 years, and most will experience at least 1 relapse. Dopamine dysfunction helps to explain the positive symptoms experienced by patients with schizophrenia, and targeting these pathways has made current antipsychotics effective treatments for this condition...
November 2014: Journal of Clinical Psychiatry
Jared X Van Snellenberg, Mark Slifstein, Christina Read, Jochen Weber, Judy L Thompson, Tor D Wager, Daphna Shohamy, Anissa Abi-Dargham, Edward E Smith
Despite significant advances in understanding how brain networks support working memory (WM) and cognitive control, relatively little is known about how these networks respond when cognitive capabilities are overtaxed. We used a fine-grained manipulation of memory load within a single trial to exceed WM capacity during functional magnetic resonance imaging to investigate how these networks respond to support task performance when WM capacity is exceeded. Analyzing correct trials only, we observed a nonmonotonic (inverted-U) response to WM load throughout the classic WM network (including bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and presupplementary motor areas) that peaked later in individuals with greater WM capacity...
April 2015: Human Brain Mapping
Shervin Ravan, Diana Martinez, Mark Slifstein, Anissa Abi-Dargham
The cellular mechanisms of alcohol's effects in the brain are complex, targeting multiple transmitter systems. Molecular imaging has been used to study the effects of alcohol and alcohol use disorders on these various systems. Studies of dopaminergic indices have provided robust evidence for deficits in D2-mediated transmission in the striatum of chronic recently detoxified alcoholics. Their presence in the at-risk state prior to excessive drinking, and their recovery after long-term sobriety, are unclear and represent an active area of current research...
2014: Handbook of Clinical Neurology
Elsmarieke van de Giessen, Daniel R Rosell, Judy L Thompson, Xiaoyan Xu, Ragy R Girgis, Yosefa Ehrlich, Mark Slifstein, Anissa Abi-Dargham, Larry J Siever
Serotonin (5-HT) has consistently been implicated in the pathophysiology of impulsive aggression. In the current study, we tested the hypothesis that 5-HT transporter (5-HTT) binding is reduced in the anterior cingulate cortex (ACC) in impulsive aggressive patients. Additionally, we characterized pathological personality dimensions, with a specific focus on callousness (i.e. emotional indifference, a facet of psychopathy). Callousness is putatively positively correlated with presynaptic 5-HT, and thus could potentially confound the hypothesized negative relation between 5-HTT levels and trait aggression...
November 2014: Journal of Psychiatric Research
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