Skip to main content

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Blog
    • Collections
    • Podcast
  • TOPICS
    • Cognition and Behavior
    • Development
    • Disorders of the Nervous System
    • History, Teaching and Public Awareness
    • Integrative Systems
    • Neuronal Excitability
    • Novel Tools and Methods
    • Sensory and Motor Systems
  • ALERTS
  • FOR AUTHORS
  • ABOUT
    • Overview
    • Editorial Board
    • For the Media
    • Privacy Policy
    • Contact Us
    • Feedback
  • SUBMIT

User menu

Search

  • Advanced search
eNeuro

eNeuro

Advanced Search

 

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Blog
    • Collections
    • Podcast
  • TOPICS
    • Cognition and Behavior
    • Development
    • Disorders of the Nervous System
    • History, Teaching and Public Awareness
    • Integrative Systems
    • Neuronal Excitability
    • Novel Tools and Methods
    • Sensory and Motor Systems
  • ALERTS
  • FOR AUTHORS
  • ABOUT
    • Overview
    • Editorial Board
    • For the Media
    • Privacy Policy
    • Contact Us
    • Feedback
  • SUBMIT
PreviousNext
Research ArticleFeature: Research Highlights, Cognition and Behavior

Functional Coupling within the Mesolimbic Circuit in First-Episode Psychosis

Or Duek
eNeuro 29 April 2021, 8 (2) ENEURO.0097-21.2021; DOI: https://doi.org/10.1523/ENEURO.0097-21.2021
Or Duek
Departement of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Or Duek
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Psychosis disorder is a debilitating disorder characterized by multiple admissions to psychiatric care facilities, higher unemployment rates, and decreased life expectancy. All of which create a high burden on the patient, their family, and the healthcare system. Understanding the basic mechanisms of psychotic disorder is essential for early discovery and facilitating better care for those suffering from it (Correll et al., 2018).

The dopamine hypothesis of schizophrenia (Howes et al., 2009) suggests that dysregulation in dopamine signaling is the main cause of psychosis. Consistent with this theory, the ventral-tegmental area (VTA) is a pivoting region in psychosis in both animals and humans (Modinos et al., 2015). Individuals suffering from psychosis have elevated dopaminergic activity in the VTA. Such dysregulations were also found in prodromal syndromes (before full-blown development of psychosis; Howes et al., 2009), suggesting a causal effect of dopaminergic dysregulation in psychosis. In animal models of psychosis, hyperactivity of the hippocampus was associated with upregulation of tonic activity in the VTA (Modinos et al., 2015), suggesting that the dopaminergic dysregulation might be presented within the coupling of the hippocampus and VTA, not only their activation. One aspect of the aberrant functional connectivity in the mesolimbic circuit that was less studied is during first-episode psychosis. Such examination might shed light on possible neural mechanisms that underlie psychosis, especially as in first-episode psychosis, people are less likely to be influenced by medications or the chronicity of the disease.

A recent eNeuro paper by Gregory et al. (2021) was set to do exactly this. The authors examined the functional connectivity in the mesolimbic circuit at resting state, in individuals suffering from first-episode psychosis and healthy controls. Their analysis focused on the three main regions of interest in that circuit: VTA, hippocampus, and nucleus accumbens (NAc). This analysis revealed higher functional connectivity between VTA and right anterior hippocampus in individuals with first-episode psychosis; the connectivity strength was also correlated with psychotic symptoms, measured by the Brief Psychiatric Rating Scale. Conversely, functional connectivity between VTA and NAc was reduced in individuals with first-episode psychosis compared with controls.

Increased functional connectivity of VTA with the hippocampus and decreased functional connectivity of the same brain structure with the striatum were also found in individuals at high risk for psychosis in a task-based paradigm (Modinos et al., 2020). In the task, participants looked at novel versus neutral stimuli. Combining the findings from Modinos et al. (2020) and the recent eNeuro paper by Gregory et al. (2021) can help us understand the paradoxical patterns of psychosis disorder. Some of the symptoms are associated with the upregulation of dopamine (delusions and hallucinations), while others are associated with downregulation (negative symptoms such as anhedonia). The higher VTA-hippocampus coupling and lower VTA-striatal coupling in individuals who either suffer from psychosis or are at risk for the disorder, compared with healthy controls, suggest a possible neural mechanism for this paradox.

Studies in individuals at later stages of psychotic disorders show some differences in the pattern of results. A recent study by Nakamura et al. (2020) did not find a difference in VTA-hippocampus functional connectivity between individuals diagnosed with schizophrenia and healthy controls, at resting state. They did find a positive correlation between this coupling and positive symptoms, in the individuals suffering from psychosis. Taken together, these differences may point to the effect of chronicity, medication, or other variables in the course of psychosis illness, all of which emphasize the relevance of examination in the early stages of psychosis.

This recent paper presents a promising and interesting direction in understanding the mechanisms associated with psychosis, by evaluating resting-state functional connectivity in first-episode psychosis. The alignment of these resting-state findings with task-based results could point toward a possible direction for further investigation. Future studies may focus on longitudinal data, using the previous findings as a model to predict the onset, risk, and course of psychosis based on both task-based and resting-state connectivity. Such a model will enable us to promote better care for individuals suffering from psychosis and their families.

Footnotes

  • The author declares no competing conflict of interests.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

References

  1. ↵
    Correll CU, Galling B, Pawar A, Krivko A, Bonetto C, Ruggeri M, Craig TJ, Nordentoft M, Srihari VH, Guloksuz S, Hui CLM, Chen EYH, Valencia M, Juarez F, Robinson DG, Schooler NR, Brunette MF, Mueser KT, Rosenheck RA, Marcy P, et al. (2018) Comparison of early intervention services vs treatment as usual for early-phase psychosis: a systematic review, meta-analysis, and meta-regression. JAMA Psychiatry 75:555–565. doi:10.1001/jamapsychiatry.2018.0623
    OpenUrlCrossRef
  2. ↵
    Gregory DF, Rothrock JM, Jalbrzikowski M, Foran W, Montez DF, Luna B, Murty VP (2021) Increased functional coupling between VTA and hippocampus during rest in first-episode psychosis. eNeuro 8:ENEURO.0375-20.2021. doi:10.1523/ENEURO.0375-20.2021
    OpenUrlAbstract/FREE Full Text
  3. ↵
    Howes OD, Montgomery AJ, Asselin M-C, Murray RM, Valli I, Tabraham P, Bramon-Bosch E, Valmaggia L, Johns L, Broome M, McGuire PK, Grasby PM (2009) Elevated striatal dopamine function linked to prodromal signs of schizophrenia. Arch Gen Psychiatry 66:13–20. doi:10.1001/archgenpsychiatry.2008.514 pmid:19124684
    OpenUrlCrossRefPubMed
  4. ↵
    Modinos G, Allen P, Grace AA, McGuire P (2015) Translating the MAM model of psychosis to humans. Trends Neurosci 38:129–138. doi:10.1016/j.tins.2014.12.005 pmid:25554679
    OpenUrlCrossRefPubMed
  5. ↵
    Modinos G, Allen P, Zugman A, Dima D, Azis M, Samson C, Bonoldi I, Quinn B, Gifford GWG, Smart SE, Antoniades M, Bossong MG, Broome MR, Perez J, Howes OD, Stone JM, Grace AA, McGuire P (2020) Neural circuitry of novelty salience processing in psychosis risk: association with clinical outcome. Schizophr Bull 46:670–679. doi:10.1093/schbul/sbz089 pmid:32227226
    OpenUrlCrossRefPubMed
  6. ↵
    Nakamura Y, Okada N, Koshiyama D, Kamiya K, Abe O, Kunimatsu A, Okanoya K, Kasai K, Koike S (2020) Differences in functional connectivity networks related to the midbrain dopaminergic system-related area in various psychiatric disorders. Schizophr Bull 46:1239–1248.
    OpenUrlCrossRef

Synthesis

Reviewing Editor: Christophe Bernard, INSERM & Institut de Neurosciences des Systèmes

Back to top

In this issue

eneuro: 8 (2)
eNeuro
Vol. 8, Issue 2
March/April 2021
  • Table of Contents
  • Index by author
  • Ed Board (PDF)
Email

Thank you for sharing this eNeuro article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Functional Coupling within the Mesolimbic Circuit in First-Episode Psychosis
(Your Name) has forwarded a page to you from eNeuro
(Your Name) thought you would be interested in this article in eNeuro.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Citation Tools
Functional Coupling within the Mesolimbic Circuit in First-Episode Psychosis
Or Duek
eNeuro 29 April 2021, 8 (2) ENEURO.0097-21.2021; DOI: 10.1523/ENEURO.0097-21.2021

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Share
Functional Coupling within the Mesolimbic Circuit in First-Episode Psychosis
Or Duek
eNeuro 29 April 2021, 8 (2) ENEURO.0097-21.2021; DOI: 10.1523/ENEURO.0097-21.2021
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Footnotes
    • References
    • Synthesis
  • Info & Metrics
  • eLetters
  • PDF

Responses to this article

Respond to this article

Jump to comment:

No eLetters have been published for this article.

Related Articles

Cited By...

More in this TOC Section

Feature: Research Highlights

  • Under Pressure: A Microfluidic Chip for Prolonged, Anesthetic-Free Imaging of Neuronal Mitostasis in Caenorhabditis elegans
  • AMPA Receptors Exist in Tunable Mobile and Immobile Synaptic Fractions In Vivo
  • Behavioral Responses to Neural Circuit Control: Pitfalls and Possible Solutions
Show more Feature: Research Highlights

Cognition and Behavior

  • Under Pressure: A Microfluidic Chip for Prolonged, Anesthetic-Free Imaging of Neuronal Mitostasis in Caenorhabditis elegans
  • AMPA Receptors Exist in Tunable Mobile and Immobile Synaptic Fractions In Vivo
  • Behavioral Responses to Neural Circuit Control: Pitfalls and Possible Solutions
Show more Cognition and Behavior

Subjects

  • Cognition and Behavior
  • Research Highlights

  • Home
  • Alerts
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Latest Articles
  • Issue Archive
  • Blog
  • Browse by Topic

Information

  • For Authors
  • For the Media

About

  • About the Journal
  • Editorial Board
  • Privacy Policy
  • Contact
  • Feedback
(eNeuro logo)
(SfN logo)

Copyright © 2022 by the Society for Neuroscience.
eNeuro eISSN: 2373-2822

The ideas and opinions expressed in eNeuro do not necessarily reflect those of SfN or the eNeuro Editorial Board. Publication of an advertisement or other product mention in eNeuro should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in eNeuro.