Publications by authors named "Anissa Abi-Dargham"

Article Synopsis
  • The study investigates the relationship between midbrain dopamine function and substance use frequency and severity in young adults aged 20-24, particularly focusing on women.
  • Researchers used neuromelanin-sensitive MRI (NM-MRI) to measure lifetime dopamine function in the substantia nigra/ventral tegmentum area (SN-VTA) among 135 participants.
  • Results indicate that higher cumulative substance use correlates with increased NM-MRI signal in the SN-VTA, suggesting altered dopamine function is associated with substance use history, but not with individual reward function traits.
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Neuroimaging plays a crucial role in understanding brain structure and function, but the lack of transparency, reproducibility, and reliability of findings is a significant obstacle for the field. To address these challenges, there are ongoing efforts to develop reporting checklists for neuroimaging studies to improve the reporting of fundamental aspects of study design and execution. In this review, we first define what we mean by a neuroimaging reporting checklist and then discuss how a reporting checklist can be developed and implemented.

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The kappa opioid receptor (KOR) and its endogenous agonist dynorphin have been implicated in multiple psychiatric conditions including psychotic disorders. We tested the hypotheses that kappa expression is elevated and associated with psychotic symptoms in schizophrenia. We measured kappa expression in unmedicated patients with schizophrenia (7 female, 6 male) and matched controls (7 female, 6 male) with positron emission tomography (PET).

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Background: Individuals with substance use disorder show impaired self-awareness of ongoing behavior. This deficit suggests problems with metacognition, which has been operationalized in the cognitive neuroscience literature as the ability to monitor and evaluate the success of one's own cognition and behavior. However, the neural mechanisms of metacognition have not been characterized in a population with drug addiction.

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Functional magnetic resonance imaging (fMRI) of the auditory and visual sensory systems of the human brain is an active area of investigation in the study of human health and disease. The medial geniculate nucleus (MGN) and lateral geniculate nucleus (LGN) are key thalamic nuclei involved in the processing and relay of auditory and visual information, respectively, and are the subject of blood-oxygen-level-dependent (BOLD) fMRI studies of neural activation and functional connectivity in human participants. However, localization of BOLD fMRI signal originating from neural activity in MGN and LGN remains a technical challenge, due in part to the poor definition of boundaries of these thalamic nuclei in standard T1-weighted and T2-weighted magnetic resonance imaging sequences.

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Background: Despite longstanding interest in the central cholinergic system in schizophrenia (SCZ), cholinergic imaging studies with patients have been limited to receptors. Here, we conducted a proof-of-concept positron emission tomography study using [F]-VAT, a new radiotracer that targets the vesicular acetylcholine transporter as a proxy measure of acetylcholine transmission capacity, in patients with SCZ and explored relationships of vesicular acetylcholine transporter with clinical symptoms and cognition.

Methods: A total of 18 adult patients with SCZ or schizoaffective disorder (the SCZ group) and 14 healthy control participants underwent a positron emission tomography scan with [F]-VAT.

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Background: Schizophrenia (SCZ) is marked by working memory (WM) deficits, which predict poor functional outcome. While most functional magnetic resonance imaging studies of WM in SCZ have focused on the dorsolateral prefrontal cortex (PFC), some recent work suggests that the medial PFC (mPFC) may play a role. We investigated whether task-evoked mPFC deactivation is associated with WM performance and whether it mediates deficits in SCZ.

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The field of psychiatry is hampered by a lack of robust, reliable and valid biomarkers that can aid in objectively diagnosing patients and providing individualized treatment recommendations. Here we review and critically evaluate the evidence for the most promising biomarkers in the psychiatric neuroscience literature for autism spectrum disorder, schizophrenia, anxiety disorders and post-traumatic stress disorder, major depression and bipolar disorder, and substance use disorders. Candidate biomarkers reviewed include various neuroimaging, genetic, molecular and peripheral assays, for the purposes of determining susceptibility or presence of illness, and predicting treatment response or safety.

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Rationale: Characterizing the neuroanatomical basis of serotonergic abnormalities in severe, chronic, impulsive aggression will allow for rational treatment selection, development of novel therapeutics, and biomarkers to identify at-risk individuals.

Objectives: The aim of this study is to identify associations between regional serotonin transporter (5-HTT) availability and trait and state aggression, as well as response to the anti-aggressive effects of fluoxetine.

Methods: We examined 5-HTT availability using positron emission tomography (PET) imaging with [C]DASB in personality disordered patients with current physical intermittent explosive disorder (IED; n = 18), and healthy comparison participants (HC; n = 11), in the anterior cingulate cortex (ACC), amygdala (AMY), ventral striatum (VST), and midbrain (MID).

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The phenotype of schizophrenia, regardless of etiology, represents the most studied psychotic disorder with respect to neurobiology and distinct phases of illness. The early phase of illness represents a unique opportunity to provide effective and individualized interventions that can alter illness trajectories. Developmental age and illness stage, including temporal variation in neurobiology, can be targeted to develop phase-specific clinical assessment, biomarkers, and interventions.

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The Research Domain Criteria (RDoC) initiative aims to organize research according to domains of brain function. Dysfunction within these domains leads to psychopathology that is classically measured with rating scales. Examining the correspondence between the specific measures assessed within rating scales and RDoC domains is necessary to assess the needs for new RDoC-focused scales.

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Article Synopsis
  • Patients with schizophrenia tend to smoke a lot and often struggle with traditional treatments, which highlights the need for new therapies.
  • A study tested a new treatment called deep repetitive transcranial magnetic stimulation (dTMS) on 20 patients to see if it could help reduce smoking and improve brain function.
  • Results showed that those receiving active dTMS took longer to light their first cigarette, suggesting some success in stopping smoking, and imaging studies hinted at potential changes in brain activity and symptoms related to psychosis.
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Article Synopsis
  • Antipsychotics have been used for nearly 70 years, primarily targeting dopaminergic receptors, leading to side effects and unresolved symptoms in schizophrenia.
  • Research is shifting towards new drug targets, such as TAARs, muscarinic receptors, and serotonergic receptors, to develop safer and more effective treatments.
  • Promising phase 2 trial results for medications like ulotaront and KarXT indicate the potential launch of the first non-D2 blocking drugs, which could significantly improve treatment options for patients who struggle with existing antipsychotics.
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Multiple lines of evidence suggest a potential role for the kappa dynorphin system in schizophrenia and its therapeutics. Kappa stimulation acutely and chronically modulates dopamine in opposite ways, where acutely it decreases dopamine transmission and chronically it increases it and it can induce D2 sensitization. In addition, pharmacological evidence from studies using agonist and antagonists at KOR have indicated a therapeutic potential of KOR antagonists for psychosis.

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Major depressive disorder (MDD) is characterized by behavioral and neural abnormalities in processing both rewarding and aversive stimuli, which may impact motivational and affective symptoms. Learning paradigms have been used to assess reinforcement encoding abnormalities in MDD and their association with dysfunctional incentive-based behavior, but how the valence and context of information modulate this learning is not well understood. To address these gaps, we examined responses to positive and negative reinforcement across multiple temporal phases of information processing.

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Decades of research have highlighted the importance of optimal stimulation of cortical dopaminergic receptors, particularly the D1R receptor (D1R), for prefrontal-mediated cognition. This mechanism is particularly relevant to the cognitive deficits in schizophrenia, given the abnormalities in cortical dopamine (DA) neurotransmission and in the expression of D1R. Despite the critical need for D1R-based therapeutics, many factors have complicated their development and prevented this important therapeutic target from being adequately interrogated.

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Background: Recent studies have established a clear topographical and functional organization of projections to and from complex subdivisions of the striatum. Manual segmentation of these functional subdivisions is labor-intensive and time-consuming, and automated methods are not as reliable as manual segmentation.

Purpose: To utilize multitask learning (MTL) as a method to segment subregions of the striatum consisting of pre-commissural putamen (prePU), pre-commissural caudate (preCA), post-commissural putamen (postPU), post-commissural caudate (postCA), and ventral striatum (VST).

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Background: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) is a validated measure of neuromelanin concentration in the substantia nigra-ventral tegmental area (SN-VTA) complex and is a proxy measure of dopaminergic function with potential as a noninvasive biomarker. The development of generalizable biomarkers requires large-scale samples necessitating harmonization approaches to combine data collected across sites.

Purpose: To develop a method to harmonize NM-MRI across scanners and sites.

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The past four decades have seen enormous efforts placed on a search for molecular markers of schizophrenia using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In this narrative review, we cast a broad net to define and summarize what researchers have learned about schizophrenia from molecular imaging studies. Some PET studies of brain energy metabolism with the glucose analogue FDGhave have shown a hypofrontality defect in patients with schizophrenia, but more generally indicate a loss of metabolic coherence between different brain regions.

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Patients at clinical high-risk (CHR) for psychosis show elevations in [F]DOPA uptake, an estimate of dopamine (DA) synthesis capacity, in the striatum predictive of conversion to schizophrenia. Intrasynaptic DA levels can be inferred from imaging the change in radiotracer binding at D receptors due to a pharmacological challenge. Here, we used methylphenidate, a DA reuptake inhibitor, and [C]-(+)-PHNO, to measure synaptic DA availability in CHR both in striatal and extra-striatal brain regions.

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