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SO246

Striatal serotonin 2A receptor availability and functional network organization in major depressive disorder

STRIATAL SEROTONIN 2A RECEPTOR AVAILABILITY AND FUNCTIONAL NETWORK ORGANIZATION IN MAJOR DEPRESSIVE DISORDER

Striatal 5-HT2A receptor binding potential is increased in drug-naive patients with major depressive disorder, and this increase is associated with disrupted network organization.

The aim was to jointly examine regional serotonin 2A receptor (5-HT2AR) availability and functional network organization in drug-naive patients with major depressive disorder (MDD). The study included 21 drug-naive patients with MDD diagnosed using the MINI-Plus and 25 healthy controls; depressive symptoms were assessed using the HAMD-17 and BDI. Participants underwent positron emission tomography (PET) with [11C]MDL100907 and resting-state functional magnetic resonance imaging. Binding potential (BPND) was calculated in 22 predefined regions, followed by functional connectivity and graph theory analyses. The groups were similar in age (37.1 (11.2) and 32.1 (7.5); p=0.090) and sex (p=0.592). In patients, the HAMD-17 score was 20.5 (3.6), and the BDI score was 26.6 (8.7), compared with 3.5 (3.0) in controls (p<0.001). BPND was higher in the MDD group than in controls in the right hippocampus, right amygdala, right caudate, and bilateral putamen (Bonferroni threshold p<0.00227). No significant differences in functional connectivity remained after false discovery rate (FDR) correction. Uncorrected analyses showed reduced connectivity between the right caudate and the right putamen (t=-3.99; p_unc<0.001; p_FDR=0.164), right anterior insula (t=-2.54; p_unc=0.015), and left anterior insula (t=-2.44; p_unc=0.019) (cluster mass 66.94; p_unc=0.035; p_FDR=0.598). Graph analyses showed reduced closeness centrality in the right putamen and right rostral prefrontal cortex in MDD (t=-3.75 and t=-3.70; p_FDR=0.011), increased average path length (right putamen t=4.78, p_FDR<0.001; left putamen t=3.73, p_FDR=0.010; right rostral prefrontal cortex t=3.31, p_FDR=0.023), and increased eccentricity in the anterior cingulate cortex, right putamen, and anterior cerebellum (t=3.81, 3.72, and 3.28; p_FDR=0.010, 0.010, and 0.025). Elevated putaminal BPND was associated with reduced network integration in an exploratory analysis (p_unc<0.05). The authors report that striatal 5-HT2AR alterations are linked to disrupted network organization in MDD and suggest a possible molecular basis underlying large-scale network dysfunction.

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