Altered thalamic volumes and functional connectivity in the recovered patients with psychosis.

BACKGROUND: Investigating neural correlates in recovered patients with psychosis is important in terms of identifying biological markers associated with recovery status or predicting a possible future relapse. We sought to examine thalamic nuclei volumes and thalamus-centered functional connectivity (FC) in recovered patients with psychosis who discontinued their medication. METHODS: Thirty patients with psychosis who satisfied the criteria for full recovery and 50 healthy controls (HC) matched for age, sex, and education underwent magnetic resonance imaging and clinical evaluation. The recovered patients were divided into the maintained and relapsed subjects according to their clinical status on the follow-ups. Thalamic nuclei volumes and thalamus-centered FC were measured between the recovered patients and HC. Correlations between the thalamic nuclei or altered FC, and clinical symptoms and cognitive functioning were explored. RESULTS: Modest cognitive impairments and reduced thalamic nuclei volumes were evident in the recovered patients. Moreover, we found altered thalamo-cortical connectivity and its associations with negative symptoms and cognitive functioning in the recovered patients compared with HC. CONCLUSION: These findings suggest that there are still cognitive impairments, and aberrant neuronal changes in the recovered patients. The implication of differential FC patterns between the maintained and the relapsed patients remain to be further explored.

Deep Learning-based Brain Age Prediction in Patients With Schizophrenia Spectrum Disorders.

BACKGROUND AND HYPOTHESIS: The brain-predicted age difference (brain-PAD) may serve as a biomarker for neurodegeneration. We investigated the brain-PAD in patients with schizophrenia (SCZ), first-episode schizophrenia spectrum disorders (FE-SSDs), and treatment-resistant schizophrenia (TRS) using structural magnetic resonance imaging (sMRI). STUDY DESIGN: We employed a convolutional network-based regression (SFCNR), and compared its performance with models based on three machine learning (ML) algorithms. We pretrained the SFCNR with sMRI data of 7590 healthy controls (HCs) selected from the UK Biobank. The parameters of the pretrained model were transferred to the next training phase with a new set of HCs (n = 541). The brain-PAD was analyzed in independent HCs (n = 209) and patients (n = 233). Correlations between the brain-PAD and clinical measures were investigated. STUDY RESULTS: The SFCNR model outperformed three commonly used ML models. Advanced brain aging was observed in patients with SCZ, FE-SSDs, and TRS compared to HCs. A significant difference in brain-PAD was observed between FE-SSDs and TRS with ridge regression but not with the SFCNR model. Chlorpromazine equivalent dose and cognitive function were correlated with the brain-PAD in SCZ and FE-SSDs. CONCLUSIONS: Our findings indicate that there is advanced brain aging in patients with SCZ and higher brain-PAD in SCZ can be used as a surrogate marker for cognitive dysfunction. These findings warrant further investigations on the causes of advanced brain age in SCZ. In addition, possible psychosocial and pharmacological interventions targeting brain health should be considered in early-stage SCZ patients with advanced brain age.

Network biomarkers in recovered psychosis patients who discontinued antipsychotics.

There are no studies investigating topological properties of resting-state fMRI (rs-fMRI) in patients who have recovered from psychosis and discontinued medication (hereafter, recovered patients [RP]). This study aimed to explore topological organization of the functional brain connectome in the RP using graph theory approach. We recruited 30 RP and 50 age and sex-matched healthy controls (HC). The RP were further divided into the subjects who were relapsed after discontinuation of antipsychotics (RP-R) and who maintained recovered state without relapse (RP-M). Using graph-based network analysis of rs-fMRI signals, global and local metrics and hub information were obtained. The robustness of the network was tested with random failure and targeted attack. As an ancillary analysis, Network-Based Statistic (NBS) was performed. Association of significant findings with psychopathology and cognitive functioning was also explored. The RP showed intact network properties in terms of global and local metrics. However, higher global functional connectivity strength and hyperconnectivity in the interconnected component were observed in the RP compared to HC. In the subgroup analysis, the RP-R were found to have lower global efficiency, longer characteristic path length and lower robustness whereas no such abnormalities were identified in the RP-M. Associations of the degree centrality of some hubs with cognitive functioning were identified in the RP-M. Even though network properties of the RP were intact, subgroup analysis revealed more altered topological organizations in the RP-R. The findings in the RP-R and RP-M may serve as network biomarkers for predicting relapse or maintained recovery after the discontinuation of antipsychotics.

Differential effects of parental socioeconomic status on cortical thickness in patients with schizophrenia spectrum disorders and healthy controls.

OBJECTIVES: Widespread changes in cortical thickness (CT) have been repeatedly reported in schizophrenia (SZ). The nature of the pathophysiologic process underlying such changes remains to be elucidated. The aims of the present study were to measure the CT; evaluate parent socioeconomic status (pSES), childhood trauma (ChT) and premorbid adjustment (PA) in patients with schizophrenia spectrum disorders (SSDs); and investigate group differences in CT (i.e., SSD vs. healthy controls (HCs)), pSES, PA, and/or ChT, as well as the interactions among these factors. METHODS: 164 patients with SSD and 245 age-, sex- and education-matched healthy controls have participated. The pSES, ChT and PA were evaluated using Korean version of Polyenvironmental Risk Score, Early Trauma Inventory Self Report-Short Form and Premorbid Adjustment Scale, respectively. Vertex-wise measure of CT was estimated using the FreeSurfer. To investigate the main effects and interactions, multilevel regression was employed. RESULTS: We found widespread cortical thinning in patients with SSDs compared to HCs. The cortical thinning was associated with ChT, symptom severity and chlorpromazine equivalent dose and duration of illness in patients. In multilevel regression, main effects of group and pSES and interaction between group and pSES were found whereas a significant interaction between ChT and CPZ equivalent was found in patients. CONCLUSION: Our findings indicate that compared to HCs, patients with SSDs have cortical structural abnormalities, and that group and pSES interaction determines CT. Further studies are needed to explore the effects of psychosocial factors on brain structural and functional abnormalities in SZ.