Shared and specific patterns of structural and functional thalamo-frontal disturbances in manic and euthymic pediatric bipolar disorder

Bipolar disorder (BD) is clinically defined by alternating depressive and manic episodes with a separated period of euthymia. Thalamo-frontal loop plays vital role in psychotic symptoms, altered motor control and executive difficulties in BD. It remains unclear that structural and functional alterations of thalamo-frontal loop among the different mood states in BD, especially in pediatric BD(PBD). Twenty manic PBD (mPBD), 20 euthymic PBD (ePBD) and 19 healthy controls (HCs) were included in the study. By analyzing the T1 images and fMRI signals, thalamus volume and frontal grey matter cortical thickness were tested, and functional connectivity (FC) between bilateral thalamus and frontal cortex was calculated. Relationship between clinical indices and thalamo-frontal FC was also evaluated in mPBD and ePBD adolescents. Compared to HCs, the cortical thickness of left middle frontal gyrus (MFG), bilateral superior frontal gyrus (SFG) was significantly decreased in both mPBD and ePBD patients, and volume of left thalamus and cortical thickness of right MFG significantly decreased in mPBD patients. Compared to that of the HCs and ePBD subjects, thalamo-frontal hyperconnectivity with MFG was found in mPBD, and compared with that of HCs, thalamo-frontal hypoconnectivity with precentral gyrus/SFG was found in ePBD. In ePBD patients, episode times positively correlated with FC values between thalamus and precentral gyrus. The findings of the present study demonstrate detailed knowledge regarding shared and specific structural and functional disruption in thalamo-frontal loop in mPBD and ePBD subjects. Thalamo-frontal abnormalities reported in adult BD subjects were also observed in adolescent BD patients, and thalamo-frontal dysfunction may be a crucial treatment target in BD.