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Convergent neural substrates of inattention in bipolar disorder patients and dopamine transporter-deficient mice using the 5-choice CPT
- Source :
- van derMarkt, A, Klumpers, U, Dols, A & Kupka, R 2020, ' Convergent neural substrates of inattention in bipolar disorder patients and dopamine transporter-deficient mice using the 5-choice CPT ', Bipolar Disorders, vol. 22, no. 1, pp. 46-58 . https://doi.org/10.1111/bdi.12786, Bipolar Disord, Bipolar Disorders, 22(1), 46-58. Blackwell Munksgaard
- Publication Year :
- 2020
-
Abstract
- Objectives: Bipolar disorder (BD) is a debilitating psychiatric illness affecting 2%-5% of the population. Although mania is the cardinal feature of BD, inattention and related cognitive dysfunction are observed across all stages. Since cognitive dysfunction confers poor functional outcome in patients, understanding the relevant neural mechanisms remains key to developing novel-targeted therapeutics. Methods: The 5-choice continuous performance test (5C-CPT) is a mouse and fMRI-compatible human attentional task, requiring responding to target stimuli while inhibiting responding to nontarget stimuli, as in clinical CPTs. This task was used to delineate systems-level neural deficits in BD contributing to inattentive performance in human subjects with BD as well as mouse models with either parietal cortex (PC) lesions or reduced dopamine transporter (DAT) expression. Results: Mania BD participants exhibited severe 5C-CPT impairment. Euthymic BD patients exhibited modestly impaired 5C-CPT. High impulsivity BD subjects exhibited reduced PC activation during target and nontarget responding compared with healthy participants. In mice, bilateral PC lesions impaired both target and nontarget responding. In the DAT knockdown mouse model of BD mania, knockdown mice exhibited severely impaired 5C-CPT performance versus wildtype littermates. Conclusions: These data support the role of the PC in inattention in BD—specifically regarding identifying the appropriate response to target vs nontarget stimuli. Moreover, the findings indicate that severely reduced DAT function/hyperdopaminergia recreates the attentional deficits observed in BD mania patients. Determining the contribution of DAT in the PC to attention may provide a future target for treatment development.
- Subjects :
- Adult
Male
Bipolar Disorder
media_common.quotation_subject
Population
Posterior parietal cortex
Impulsivity
Synaptic Transmission
Article
03 medical and health sciences
Mice
0302 clinical medicine
Cognition
Task Performance and Analysis
medicine
Animals
Humans
Attention
Bipolar disorder
education
Biological Psychiatry
Dopamine transporter
media_common
Mice, Knockout
education.field_of_study
Dopamine Plasma Membrane Transport Proteins
biology
business.industry
Middle Aged
medicine.disease
Magnetic Resonance Imaging
030227 psychiatry
Psychiatry and Mental health
Disease Models, Animal
biology.protein
Female
medicine.symptom
business
Mania
Neuroscience
030217 neurology & neurosurgery
Vigilance (psychology)
Subjects
Details
- Language :
- English
- ISSN :
- 13985647
- Database :
- OpenAIRE
- Journal :
- van derMarkt, A, Klumpers, U, Dols, A & Kupka, R 2020, ' Convergent neural substrates of inattention in bipolar disorder patients and dopamine transporter-deficient mice using the 5-choice CPT ', Bipolar Disorders, vol. 22, no. 1, pp. 46-58 . https://doi.org/10.1111/bdi.12786, Bipolar Disord, Bipolar Disorders, 22(1), 46-58. Blackwell Munksgaard
- Accession number :
- edsair.doi.dedup.....a1a9da9504c3d1ad7e34718a61ffe5c2