The Pharmacology of Visual Hallucinations in Synucleinopathies

Frontiers in Pharmacology

卷:10

Fedele Dono¹  Martina Di Pietro¹  Laura Bonanni¹  Claudia Carrarini¹  Marianna Gabriella Rispoli¹  Vincenzo Di Stefano¹  Mirella Russo¹  Laura Ferri¹  Marco Onofrj¹  Stefano Luca Sensi³ 

[1] Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy;

[2] Behavioral Neurology and Molecular Neurology Units, Center of Excellence on Aging and Translational Medicine—CeSI-MeT, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy;

[3] Departments of Neurology and Pharmacology, Institute for Mind Impairments and Neurological Disorders—iMIND, University of California, Irvine, Irvine, CA, United States;

关键词: visual hallucination;    dementia with Lewy bodies;    Parkinson's disease;    synucleinopathy;    default mode network;   

DOI  :  10.3389/fphar.2019.01379

来源: DOAJ

【 摘 要 】

Visual hallucinations (VH) are commonly found in the course of synucleinopathies like Parkinson's disease and dementia with Lewy bodies. The incidence of VH in these conditions is so high that the absence of VH in the course of the disease should raise questions about the diagnosis. VH may take the form of early and simple phenomena or appear with late and complex presentations that include hallucinatory production and delusions. VH are an unmet treatment need. The review analyzes the past and recent hypotheses that are related to the underlying mechanisms of VH and then discusses their pharmacological modulation. Recent models for VH have been centered on the role played by the decoupling of the default mode network (DMN) when is released from the control of the fronto-parietal and salience networks. According to the proposed model, the process results in the perception of priors that are stored in the unconscious memory and the uncontrolled emergence of intrinsic narrative produced by the DMN. This DMN activity is triggered by the altered functioning of the thalamus and involves the dysregulated activity of the brain neurotransmitters. Historically, dopamine has been indicated as a major driver for the production of VH in synucleinopathies. In that context, nigrostriatal dysfunctions have been associated with the VH onset. The efficacy of antipsychotic compounds in VH treatment has further supported the notion of major involvement of dopamine in the production of the hallucinatory phenomena. However, more recent studies and growing evidence are also pointing toward an important role played by serotonergic and cholinergic dysfunctions. In that respect, in vivo and post-mortem studies have now proved that serotonergic impairment is often an early event in synucleinopathies. The prominent cholinergic impairment in DLB is also well established. Finally, glutamatergic and gamma aminobutyric acid (GABA)ergic modulations and changes in the overall balance between excitatory and inhibitory signaling are also contributing factors. The review provides an extensive overview of the pharmacology of VH and offers an up to date analysis of treatment options.

【 授权许可】

Unknown