A PET study on raphe connectivity alteration in Parkinson disease depression

1571 

Abstract Submission 

Seunggyun Ha¹, Yeongjoo Lee², Sang-Won Yoo², Joo Hyun O², Ie Ryung Yoo², Joong-Seok Kim²

¹The Catholic University of Korea, Seoul, Seocho-gu, ²The Catholic University of Korea, Seoul, Korea, Republic of

Seunggyun Ha  
The Catholic University of Korea
Seoul, Seocho-gu

Yeongjoo Lee  
The Catholic University of Korea
Seoul, Korea, Republic of

Sang-Won Yoo  
The Catholic University of Korea
Seoul, Korea, Republic of

Joo Hyun O  
The Catholic University of Korea
Seoul, Korea, Republic of

Ie Ryung Yoo  
The Catholic University of Korea
Seoul, Korea, Republic of

Joong-Seok Kim  
The Catholic University of Korea
Seoul, Korea, Republic of

While understanding brain networks based on specific neurotransmitters, which may be deficient or imbalanced, can be crucial for certain diseases, research in this area is lacking. Depression is a significant non-motor symptom in early Parkinson's disease (PD), often associated with the serotonergic system. However, its pathophysiology remains unclear. This study explores the relationship between metabolic connectivity and serotonergic connectivity in patients with Parkinson's disease, and investigates abnormalities in serotonergic connectivity that contribute to depressive mood.

We used bimodal imaging with early phase [¹⁸F]Florbetaben positron-emission tomography (PET) for perfusion and [¹⁸F]FP-CIT PET for extrastriatal serotonergic transporter (SERT) imaging to explore the relationship between the raphe-associated serotonergic system and metabolic connectivity in both depressive and non-depressive PD groups. Preprocessing of spatial normalization and smoothing for PET imaging was carried out using Statistical Parametric Mapping version 8. Intensity normalization of [¹⁸F]FP-CIT uptake was conducted by calculating the Standardized-Uptake-Value-Ratio (SUVR_FP-CIT) using the reference region of a composite occipital regions-of-interest (ROI). Intensity normalization of e[¹⁸F]FBB PET scan was carried out by calculating SUVR_eFBB, with the reference region being the whole cerebellum. The normalized PET images were parcellated by the extrastriatal ROIs using the AAL3 atlas. To extract group-wise raphe-associated ROI connectivity, we designated each of dorsal and median raphe nuclei as seed ROIs. Raphe-associated metabolic connectivity was derived from perfusion information on e[¹⁸F]FBB PET, based on the principle of brain perfusion-metabolism coupling. We assessed serotonergic connectivity by examining the synchronization of raphe-extrastriatal SERT-availability on [¹⁸F]FP-CIT PET. Connectivity was measured via a partial correlation coefficient for the mean SUVR of the ROIs, while controlling for age, sex, mH&Y stages, and amyloid deposition. The Pearson correlation test were applied to assess the linear association between raphe-associated serotonergic connectivity and metabolic connectivity. A paired t-test was used to compare gross tone of raphe-serotonergic transporter connectivity, calculated for each region over the gross brain, between the depressive and non-depressive groups. A permutation test with 20,000 randomizations was used to compare ROI-based raphe-associated serotonergic transporter connectivity between the depressive and non-depressive groups.

Raphe-associated serotonergic connectivity had a significant linear correlation with raphe-associated metabolic connectivity across the extrastriatal cortex for both depressive and non-depressive groups (seed: dorsal raphe r 0.502, p <0.0001 & r 0.642, p <0.0001, respectively; seed: median raphe, r 0.494, p <0.0001 & r 0.348, p = 0.0005, respectively).
The depressive group had grossly lower tone of connectivity than the non-depressive group (r, 0.153 ± 0.220 vs. 0.242 ± 0.255, p = 0.0004 for dorsal raphe seed; 0.125 ± 0.172 vs. 0.312 ± 0.280, p < 0.0001 for median raphe seed). Specifically, median raphe-associated serotonergic connectivity was significantly weakened in the right inferior frontal gyrus pars orbitalis, right anterior orbital gyrus, and left lateral orbital gyrus (all Bon-ferroni adjusted p <0.05).

Raphe-associated metabolic connectivity is linearly associated by underlying serotonergic connectivity. Weakening of raphe-associated serotonergic connectivity in the frontal lobe may contribute to depressive mood in Parkinson's disease.

Connectivity (eg. functional, effective, structural) ¹

Transmitter Systems

Physiology, Metabolism and Neurotransmission Other ²

Degenerative Disease

Movement Disorder

Neurotransmitter

Positron Emission Tomography (PET)

Seretonin