Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a special kind of clinical entity that characteristically affects the bones, joints, and skin ^1. This syndrome always destroys the sternocostoclavicular region (65%-90%), followed by the spine (32%-52%) ² [figure1].SAHPO is a rare disease and its prevalence is generally considered less than 1/10,000, although sufficient data on it are unavailable ³ .Most of researchers focus on dermatological and osteoarticular changes of SAPHO patients. However, there have been no papers published concerned about psychiatric symptoms in SAPHO. We observed that patients suffering from SAPHO syndrome had depression and also we tried to use rs-fMRI to confirm our hypothesis.The purpose of this study is to investigate depression in SAPHO and identify ALFF and FC that underlie the depression in SAPHO.Twenty-four (twelve males, twelve females) SAPHO patients and fifteen（seven males, eight females）age- and gender-matched NC were recruited. The diagnosis of SAPHO syndrome used the diagnostic criteria proposed by Kahn, modified in 2003, for SAPHO syndrome diagnosis ⁴ .Additionally, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ⁵ and Bath Ankylosing Spondylitis Functional Index (BASFI) ⁶ were recorded for describing the severity of the SAPHO. All of the SAPHO patients underwent psychiatric tests including the Mini-International Neuropsychiatric Interview (M.I.N.I) ⁷ and the 17-item Hamilton Depression Rating Scale (HDRS) by an experienced psychiatrist. SAPHO patients were further divided into two groups on the basis of M.I.N.I: the depressed SAPHO patients (D-SAPHO), the non-depressed SAPHO patients (ND-SAPHO) .At the same time, all of the subjects went through functional images using an echo-planar imaging sequence and structural images using a T1-weighted magnetization-prepared rapidly acquired gradient-echo sequence. The image preprocessing was performed on Data Processing Assistant for Resting-State fMRI (DPARSF) (http://www.restfmri.net) ⁸ . Then two sample t-tests were conducted to compare the ALFF differences among D-SAPHO, ND-SAPHO and NC (voxel-level p < 0.05, cluster size > 6156 mm ³ /228 voxels, corresponding to a corrected p < 0.05 as determined by AlphaSim correction) implemented on the REST software ⁹ . The FC between left dorsolateral prefrontal cortex(dPFC) based on ALFF findings and all the other voxels in the brain were further calculated (voxel-level p < 0.05, cluster size > 2538 mm ³ /94 voxels, corresponding to a corrected p < 0.05 as determined by AlphaSim correction). A correlation analysis was performed between HDRS scores in D-SAPHO and the ALFF value which was extracted in regions with significant differences between D-SAPHO and ND-SAPHO. The FC between the left d-PFC and regions showing significant differences in D-SAPHO relative to ND- SAPHO and HDRS scores of the D-SAPHO were also compared with the correlation analysis.

1) Twelve patients were diagnosed with D-SAPHO according to M.I.N.I. There were no significant differences in gender , age , BASDAI and BASFI between D-SAPHO and ND-SAPHO. HDRS scores were significantly different in D-SAPHO relative to ND-SAPHO (p＜0.0001).

2) Compared with ND-SAPHO, D-SAPHO patients showed decreased ALFF in the bilateral prefrontal cortex (PFC), right middle frontal gyrus, right postcentral cortex, increased ALFF in the bilateral cerebellum hemisphere and inferior temporal gyrus[Figure2]. We could also found altered ALFF in the left PFC in the D-SAPHO compared with NC.

3) Compared with ND-SAPHO, D-SAPHO showed stronger FC between the left dPFC and the right parahippocampal gyrus (PHG), left Hippocampus (HIP)[Figure4].

4) Correlation analysis revealed that both the ALFF value in the bilateral PFC （mainly located in the medial PFC and left dPFC）and the FC between the left dPFC and the left HIP were significantly correlated with the HDRS score[Figure3,4].

To the best of our knowledge, it is the first study to demonstrate that depressed symptoms may be seen in SAPHO and reveal that D-SAPHO had abnormal regional spontaneous activities involved in the regional brain changes which showed correlations with HDRS score. These findings suggest the rs- fMRI as an ideal imaging tool to understand the neural mechanism and identify depression in SAPHO patients. Future studies are needed to admit a larger sample size and utilize different methodologies of rs-fMRI to investigate depressed SAPHO.