The aim of the present study was to investigate the gray matter alterations in bipolar patients with severe mania, and also the heterogeneous patterns of these structural abnormalities.Sixty first-episode manic bipolar adolescents and twenty-nineage-, sex- and years of education-matched healthy comparison (HC) participantswererecruited. MRI examinations were performed on a 4-T Varian Unity INOVA scanner with Modified Driven Equilibrium Fourier Transform (MDEFT) pulse sequence (TR=13.0 ms, TE=5.3 ms, tau (magnetization preparation time)=1.1 ms, FOV=256x192x192 mm3, matrix=256x192x96). Cortical modeling and volumetric segmentation of structural MRI data were performed with the FreeSurfer package (version 5.1.0, http://surfer.nmr.mgh.harvard.edu/). Sincethe surface-based analysis was restricted to thecortical mantle, volumetric analyses were conducted toassess deep gray matter using theexponentiated lie algebra (DARTEL) toolbox. Agglomerative hierarchical clustering 1 was performedon manicpatients by the cortical thickness extracted from 48 frontal and temporal brain regions. The optimal cluster number wasdetermined using Silhouette, Dunn, and connectivity indices, which reflect the compactness, separation, and connectedness of the generated clusters.In relation to the HC, the manic adolescents showed significantly reduced cortical thickness in the left superior temporal gyrus (Monte Carlo simulation P<0.05, corrected, Figure 1). VBM-DARTEL analysis revealed decreased grey matter volume in left middle temporal gyrus, left amygdala, bilateral cerebellum, right inferior occipital gyrus, bilateral precentral gyri, right superior temporal gyrus, right fusiform and left orbital frontal gyrus as well as increased grey matter volume in right middle temporal gyrus and left inferior frontal gyrusin manic compare to HC participants(Figure 2).The result of hierarchical clustering is shown as a combination of dendrogram and heat map illustration in Figure 3.Fifty-six patients (93.3%) were placed in subgroup 1 and 4 patients(6.7%) were placed in subgroup 2. The patients in subgroup 2 showed relatively thinner cortical thickness in all examined frontal and temporal brain areas compared with those in subgroup 1.Our findings indicate grey matter reduction, mainly within temporal lobe, prefrontal cortex, amygdala, fusiform and cerebellum, which could possibly underlie mood dysregulation and cognitive dysfunction in bipolar adolescents with first-episodemania2,3,4. The increased volume of middle temporal gyrus and inferior frontal gyrus may represent a compensatory factor. The cortical thickness deficits were showed in left superior temporal gyrus which plays a crucial role in emotion processing and social cognition5. Furthermore, thecortical thickness alternations showed homogeneous patterns in the clustering analysis, supporting the manic bipolar adolescents have an illness with mostly the same pattern of cerebral changes. And, the reduction of cortical thickness in the superior temporal gyrus may act as potential imaging biomarker of mania in this population.Our findings confirmed the homogeneous patterns of brain deficits mainly involving the affective processing and social cognition in bipolar adolescents with first-episode mania. Specially, the reduced cortical thickness of left superior temporal gyrus may be an illness biomarker.