Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

Farb, David H.; Ratner, Marcia H.

doi:10.1124/pr.114.009126

Cited by 55Neuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on BehaviorAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

Farb, David H., Ratner, Marcia H.·2014·Pharmacological Reviews

DOI 10.1124/pr.114.009126

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Abstract

Anxiety disorders are a major public health concern. Here, we examine the familiar area of anxiolysis in the context of a systems-level understanding that will hopefully lead to revealing an underlying pharmacological connectome. The introduction of benzodiazepines nearly half a century ago markedly improved the treatment of anxiety disorders. These agents reduce anxiety rapidly by allosterically enhancing the postsynaptic actions of GABA at inhibitory type A GABA receptors but side effects limit their use in chronic anxiety disorders. Selective serotonin reuptake inhibitors and serotonin/norepinephrine reuptake inhibitors have emerged as an effective first-line alternative treatment of such anxiety disorders. However, many individuals are not responsive and side effects can be limiting. Research into a relatively new class of agents known as neurosteroids has revealed novel modulatory sites and mechanisms of action that are providing insights into the pathophysiology of certain anxiety disorders, potentially bridging the gap between the GABAergic and serotonergic circuits underlying anxiety. However, translating the pharmacological activity of compounds targeted to specific receptor subtypes in rodent models of anxiety to effective therapeutics in human anxiety has not been entirely successful. Since modulating any one of several broad classes of receptor targets can produce anxiolysis, we posit that a systems-level discovery platform combined with an individualized medicine…

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“Importantly, the same brain regions and neurotransmitter systems that underlie ADHD are also implicated in the psychiatric disorders that are frequently comorbid with ADHD (19-21).”
From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [19]
Several psychiatric comorbidities, such as depression and anxiety, are believed to be partly mediated by shared neurobiological pathways that also play a role in ADHD pathophysiology.
“Multiple psychiatric comorbidities, including depression and anxiety (16, 17), are thought to be mediated in part by shared neurobiological pathways that are also implicated in the pathophysiology of ADHD (19, 20).”
From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [19]

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Result
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Authors: Farb, D. H., & Ratner, M. H.
Affiliations: Boston University (US)
ORCID: Farb, David H.
Ratner, Marcia H.
Venue: Pharmacological Reviews
Publisher: Elsevier BV
Published: 2014-10
Volume: 66
Issue: 4
Pages: 1002-1032
ISSN: 0031-6997 (ISSN-L)
DOI: 10.1124/pr.114.009126
OpenAlex: W2048222841
Cited by: 55
References: 37
Citations by year: 2026: 2 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 10 · 2019: 6 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 11
FWCI: 0.72
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Pharmacological Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords: anxiety disorders, anxiolysis, benzodiazepines, GABAA receptor, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, neurosteroids, neural circuits, GABAergic circuits, personalized medicine, non-invasive brain imaging, translational drug development
MeSH terms: Animals, Anxiety Disorders, Brain, Humans, Receptors, GABA-A, Anti-Anxiety Agents, Drug Design, Molecular Targeted Therapy

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Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

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