Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study
Background: Social anhedonia is common within major depressive disorder (MDD) and associated with worse treatment outcomes. The orbitofrontal cortex (OFC) is implicated in both reward (medial OFC) and punishment (lateral OFC) in social decision making. Therefore, to understand the biology of social...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | NeuroImage: Clinical |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158223002449 |
| _version_ | 1797263613478567936 |
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| author | Brianna M. Donnelly David T. Hsu John Gardus Junying Wang Jie Yang Ramin V. Parsey Christine DeLorenzo |
| author_facet | Brianna M. Donnelly David T. Hsu John Gardus Junying Wang Jie Yang Ramin V. Parsey Christine DeLorenzo |
| author_sort | Brianna M. Donnelly |
| collection | DOAJ |
| description | Background: Social anhedonia is common within major depressive disorder (MDD) and associated with worse treatment outcomes. The orbitofrontal cortex (OFC) is implicated in both reward (medial OFC) and punishment (lateral OFC) in social decision making. Therefore, to understand the biology of social anhedonia in MDD, medial/lateral OFC metabolism, volume, and thickness, as well as structural connectivity to the striatum, amygdala, and ventral tegmental area/nucleus accumbens were examined. A positive relationship between social anhedonia and these neurobiological outcomes in the lateral OFC was hypothesized, whereas an inverse relationship was hypothesized for the medial OFC. The association between treatment-induced changes in OFC neurobiology and depression improvement were also examined. Methods: 85 medication-free participants diagnosed with MDD were assessed with Wisconsin Schizotypy Scales to assess social anhedonia and received pretreatment simultaneous fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI), including structural and diffusion. Participants were then treated in an 8-week randomized placebo-controlled double-blind course of escitalopram. PET/MRI were repeated following treatment. Metabolic rate of glucose uptake was quantified from dynamic FDG-PET frames using Patlak graphical analysis. Structure (volume and cortical thickness) was quantified from structural MRI using Freesurfer. To assess structural connectivity, probabilistic tractography was performed on diffusion MRI and average FA was calculated within the derived tracts. Linear mixed models with Bonferroni correction were used to examine the relationships between variables. Results: A significantly negative linear relationship between pretreatment social anhedonia score and structural connectivity between the medial OFC and the amygdala (estimated coefficient: −0.006, 95 % CI: −0.0108 – −0.0012, p-value = 0.0154) was observed. However, this finding would not survive multiple comparisons correction. No strong evidence existed to show a significant linear relationship between pretreatment social anhedonia score and metabolism, volume, thickness, or structural connectivity to any of the regions examined. There was also no strong evidence to suggest significant linear relationships between improvement in depression and percent change in these variables. Conclusions: Based on these multimodal findings, the OFC likely does not underlie social anhedonia in isolation and therefore should not be the sole target of treatment for social anhedonia. This is consistent with previous reports that other areas of the brain such as the amygdala and the striatum are highly involved in this behavior. Relatedly, amygdala-medial OFC structural connectivity could be a future target. The results of this study are crucial as, to our knowledge, they are the first to relate structure/function of the OFC with social anhedonia severity in MDD. Future work may need to involve a whole brain approach in order to develop therapeutics for social anhedonia. |
| first_indexed | 2024-03-08T21:12:27Z |
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| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-04-25T00:15:47Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
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| series | NeuroImage: Clinical |
| spelling | doaj.art-780951da789f44078726c6b0a0d988872024-03-13T04:45:33ZengElsevierNeuroImage: Clinical2213-15822024-01-0141103553Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal studyBrianna M. Donnelly0David T. Hsu1John Gardus2Junying Wang3Jie Yang4Ramin V. Parsey5Christine DeLorenzo6Zucker School of Medicine, 500 Hofstra Blvd, Hempstead, NY 11549, USADepartment of Psychiatry and Behavioral Health, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USADepartment of Psychiatry and Behavioral Health, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USADepartment of Applied Mathematics and Statistics, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USADepartment of Family, Population & Preventive Medicine, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USADepartment of Psychiatry and Behavioral Health, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USADepartment of Psychiatry and Behavioral Health, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USA; Department of Biomedical Engineering, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USA; Corresponding author at: Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USA.Background: Social anhedonia is common within major depressive disorder (MDD) and associated with worse treatment outcomes. The orbitofrontal cortex (OFC) is implicated in both reward (medial OFC) and punishment (lateral OFC) in social decision making. Therefore, to understand the biology of social anhedonia in MDD, medial/lateral OFC metabolism, volume, and thickness, as well as structural connectivity to the striatum, amygdala, and ventral tegmental area/nucleus accumbens were examined. A positive relationship between social anhedonia and these neurobiological outcomes in the lateral OFC was hypothesized, whereas an inverse relationship was hypothesized for the medial OFC. The association between treatment-induced changes in OFC neurobiology and depression improvement were also examined. Methods: 85 medication-free participants diagnosed with MDD were assessed with Wisconsin Schizotypy Scales to assess social anhedonia and received pretreatment simultaneous fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI), including structural and diffusion. Participants were then treated in an 8-week randomized placebo-controlled double-blind course of escitalopram. PET/MRI were repeated following treatment. Metabolic rate of glucose uptake was quantified from dynamic FDG-PET frames using Patlak graphical analysis. Structure (volume and cortical thickness) was quantified from structural MRI using Freesurfer. To assess structural connectivity, probabilistic tractography was performed on diffusion MRI and average FA was calculated within the derived tracts. Linear mixed models with Bonferroni correction were used to examine the relationships between variables. Results: A significantly negative linear relationship between pretreatment social anhedonia score and structural connectivity between the medial OFC and the amygdala (estimated coefficient: −0.006, 95 % CI: −0.0108 – −0.0012, p-value = 0.0154) was observed. However, this finding would not survive multiple comparisons correction. No strong evidence existed to show a significant linear relationship between pretreatment social anhedonia score and metabolism, volume, thickness, or structural connectivity to any of the regions examined. There was also no strong evidence to suggest significant linear relationships between improvement in depression and percent change in these variables. Conclusions: Based on these multimodal findings, the OFC likely does not underlie social anhedonia in isolation and therefore should not be the sole target of treatment for social anhedonia. This is consistent with previous reports that other areas of the brain such as the amygdala and the striatum are highly involved in this behavior. Relatedly, amygdala-medial OFC structural connectivity could be a future target. The results of this study are crucial as, to our knowledge, they are the first to relate structure/function of the OFC with social anhedonia severity in MDD. Future work may need to involve a whole brain approach in order to develop therapeutics for social anhedonia.http://www.sciencedirect.com/science/article/pii/S2213158223002449Major depression disorderSocial anhedoniaBrain imagingOrbitofrontal cortexSSRI treatment |
| spellingShingle | Brianna M. Donnelly David T. Hsu John Gardus Junying Wang Jie Yang Ramin V. Parsey Christine DeLorenzo Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study NeuroImage: Clinical Major depression disorder Social anhedonia Brain imaging Orbitofrontal cortex SSRI treatment |
| title | Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study |
| title_full | Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study |
| title_fullStr | Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study |
| title_full_unstemmed | Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study |
| title_short | Orbitofrontal and striatal metabolism, volume, thickness and structural connectivity in relation to social anhedonia in depression: A multimodal study |
| title_sort | orbitofrontal and striatal metabolism volume thickness and structural connectivity in relation to social anhedonia in depression a multimodal study |
| topic | Major depression disorder Social anhedonia Brain imaging Orbitofrontal cortex SSRI treatment |
| url | http://www.sciencedirect.com/science/article/pii/S2213158223002449 |
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