AI Article Synopsis
- Heterogeneity in Major Depressive Disorder (MDD) makes it difficult to find biological markers that can identify those at risk or explain the genetic basis of the disorder.
- A study compared 25 individuals with MDD to 29 matched controls using a multimodal assessment that included PET scans and functional MRI to evaluate cognitive control networks.
- Results showed that lower levels of serotonin (5-HT) binding in the MDD group were linked to poorer cognitive control, while higher levels were associated with a negative memory bias but better cognitive resolution, suggesting that different biological profiles may inform targeted treatments for subtypes of MDD.
Article Abstract
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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450211 | PMC |
| http://dx.doi.org/10.3389/fpsyg.2019.00691 | DOI Listing |
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