Cognitive Control as a 5-HT-Based Domain That Is Disrupted in Major Depressive Disorder.

Authors:
Scott A Langenecker
Scott A Langenecker
University of Illinois at Chicago
Chicago | United States
Brian J Mickey
Brian J Mickey
University of Michigan
United States
Peter Eichhammer
Peter Eichhammer
University of Regensburg
Germany
Srijan Sen
Srijan Sen
University of Michigan
United States
Susan E Kennedy
Susan E Kennedy
University of Michigan
Dearborn | United States
Mary M Heitzeg
Mary M Heitzeg
University of Michigan
United States

Front Psychol 2019 29;10:691. Epub 2019 Mar 29.

The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States.

Heterogeneity within Major Depressive Disorder (MDD) has hampered identification of biological markers (e.g., intermediate phenotypes, IPs) that might increase risk for the disorder or reflect closer links to the genes underlying the disease process. The newer characterizations of dimensions of MDD within Research Domain Criteria (RDoC) domains may align well with the goal of defining IPs. We compare a sample of 25 individuals with MDD compared to 29 age and education matched controls in multimodal assessment. The multimodal RDoC assessment included the primary IP biomarker, positron emission tomography (PET) with a selective radiotracer for 5-HT [(11C)WAY-100635], as well as event-related functional MRI with a Go/No-go task targeting the Cognitive Control network, neuropsychological assessment of affective perception, negative memory bias and Cognitive Control domains. There was also an exploratory genetic analysis with the serotonin transporter (5-HTTLPR) and monamine oxidase A (MAO-A) genes. In regression analyses, lower 5-HT binding potential (BP) in the MDD group was related to diminished engagement of the Cognitive Control network, slowed resolution of interfering cognitive stimuli, one element of Cognitive Control. In contrast, higher/normative levels of 5-HT BP in MDD (only) was related to a substantial memory bias toward negative information, but intact resolution of interfering cognitive stimuli and greater engagement of Cognitive Control circuitry. The serotonin transporter risk allele was associated with lower 1a BP and the corresponding imaging and cognitive IPs in MDD. Lowered 5HT 1a BP was present in half of the MDD group relative to the control group. Lowered 5HT 1a BP may represent a subtype including decreased engagement of Cognitive Control network and impaired resolution of interfering cognitive stimuli. Future investigations might link lowered 1a BP to neurobiological pathways and markers, as well as probing subtype-specific treatment targets.

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Source
https://www.frontiersin.org/article/10.3389/fpsyg.2019.00691
Publisher Site
http://dx.doi.org/10.3389/fpsyg.2019.00691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450211PMC
March 2019
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References

(Supplied by CrossRef)
Stressed and depressed.
Akil et al.
Nature Nat. Medicine Med. 2005
Article in Diagnostic and Statistical Manual of Mental Disorders
Diagnostic and Statistical Manual of Mental Disorders 1994
Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine.
Aune et al.
J. Immunol. 1993

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