Hippocampal Dynamic Functional Connectivity, HPA Axis Activity, and Personality Trait in Bipolar Disorder with Suicidal Attempt.

INTRODUCTION: Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associated with suicide-related personality traits. The objective of our study was to clarify this. METHODS: Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA), and 40 without SA, and 35 healthy controls (HCs). The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). RESULTS: BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression, and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. CONCLUSION: These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits.

Aberrant dynamic functional connectivity in corticostriatal circuitry in depressed bipolar II disorder with recent suicide attempt.

BACKGROUND: The underlying neurobiological mechanisms on suicidal behavior in bipolar disorder remain unclear. We aim to explore the mechanisms of suicide by detecting dynamic functional connectivity (dFC) of corticostriatal circuitry and cognition in depressed bipolar II disorder (BD II) with recent suicide attempt (SA). METHODS: We analyzed resting-state functional magnetic resonance imaging (fMRI) data from 68 depressed patients with BD-II (30 with SA and 38 without SA) and 35 healthy controls (HCs). The whole-brain dFC variability of corticostriatal circuitry was calculated using a sliding-window analysis. Their correlations with cognitive dysfunction were further detected. Support vector machine (SVM) classification tested the potential of dFC to differentiate BD-II with SA from HCs. RESULTS: Increased dFC variability between the right vCa and the right insula was found in SA compared to non-SA and HCs, and negatively correlated with speed of processing. Decreased dFC variability between the left dlPu and the right postcentral gyrus was found in non-SA compared to SA and HCs, and positively correlated with reasoning problem-solving. Both SA and non-SA exhibited decreased dFC variability between the right dCa and the left MTG, and between the right dlPu and the right calcarine when compared to HCs. SVM classification achieved an accuracy of 75.24 % and AUC of 0.835 to differentiate SA from non-SA, while combining the abnormal dFC features between SA and non-SA. CONCLUSIONS: Aberrant dFC variability of corticostriatal circuitry may serve as potential neuromarker for SA in BD-II, which might help to discriminate suicidal BD-II patients from non-suicidal patients and HCs.

Thyroid hormones disturbances, cognitive deficits and abnormal dynamic functional connectivity variability of the amygdala in unmedicated bipolar disorder.

OBJECTIVE: Accumulating evidence suggests that hypothalamus-pituitary-thyroid (HPT) axis dysfunction is relevant to the neuropsychological and pathophysiology functions of bipolar disorder (BD). However, no research has investigated the inter-relationships among thyroid hormones disturbance, neurocognitive deficits, and aberrant brain function (particularly in the amygdala) in patients with BD. MATERIALS AND METHODS: Data of dynamic resting-state functional connectivity (rs-dFC) were gathered from 59 patients with unmedicated BD II during depressive episodes and 52 healthy controls (HCs). Four seeds were selected (the bilateral lateral amygdala and the bilateral medial amygdala). The sliding-window analysis was applied to investigate dynamic functional connectivity (dFC). Additionally, the serum thyroid hormone (free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4) and thyroid-stimulating hormone (TSH)) levels, and cognitive scores on the MATRICS Consensus Cognitive Battery (MCCB) in patients and HCs were detected. RESULTS: The BD group exhibited increased dFC variability between the left medial amygdala and right medial prefrontal cortex (mPFC) when compared with the HC group. Additionally, the BD group showed lower FT3, TT3, and TSH level, higher FT4 level, and poorer cognitive score. Moreover, a significant negative correlation was observed between the dFC variability of the left medial amygdala-right mPFC and TSH level, or reasoning and problem solving of MCCB score in BD group. Multiple regression analysis showed that the TSH level × dFC variability of the medial amygdala-mPFC was an independent predictor for cognitive processing speed in BD group. CONCLUSIONS: This study revealed patients with BD II depression had excessive variability in dFC between the medial amygdala and mPFC. Moreover, both HPT axis dysfunction and abnormal dFC of the amygdala-mPFC might be implicated in cognitive impairment in the early stages of BD.

Reduced myelin density in unmedicated major depressive disorder: An inhomogeneous magnetization transfer MRI study.

OBJECTIVES: To detect the whole-brain reduced myelin density in unmedicated patients with major depressive disorder (MDD) using the inhomogeneous magnetization transfer (ihMT) imaging technology. Compared to other technologies, the ihMT provides high specificity and sensitivity to detect myelin. METHOD: In this prospective study, fifty unmedicated patients (mean age 25.36 years, 40% men) with MDD and 57 age- and sex-matched healthy controls (HCs) (mean age 25.02 years, 53% men) were recruited between January 2019 and December 2019. All participants underwent ihMT imaging, and pseudo-quantitative ihMT (qihMT) and ihMT ratio (ihMTR) were obtained. The mean values of qihMT and ihMTR extracted from the 50 WM masks (extracted from the International Consortium for Brain Mapping, ICBM-152) in each participant were compared between participants in the MDD and HCs groups. The symptoms of patients were evaluated using the 24-item Hamilton Depression Rating scale (HDRS). RESULTS: Compared with the HC group, the MDD group showed significantly decreased qihMT and ihMTR values in the left inferior fronto-occipital fasciculus (IFOF) (t = -4.057, p < 0.001; t = -3.662, p < 0.001) and the left uncinate fasciculus (UF) (t = -4.776, p < 0.001; t = -3.800, p < 0.001) after Bonferroni correction. The correlation analysis displayed a significant negative correlation between qihMT values of the left IFOF and HDRS total scores in patients with MDD (r = -0.390, p = 0.012). LIMITATIONS: This was a cross-sectional study with a relative small sample. CONCLUSIONS: These findings suggest the reduced myelin density in the IFOF and UF in patients with MDD, which might be associated with the pathophysiology of MDD.

Psychological Effects of People Isolated in Hubei Due to COVID-19 Epidemic.

The Coronavirus Disease 2019 (COVID-19) epidemic broke out from Wuhan in Hubei province, China, spread nationwide and then gradually developed into other countries in the world. The implementation of unprecedented strict isolation measures has affected many aspects of people's lives and posed a challenge to psychological health. To explore whether people isolated for 14 days due to having contact with COVID-19 patients had more psychosocial problems. We conducted an online survey from February 29 to March 10, 2020. Depression, anxiety, post-traumatic stress disorder (PTSD) symptoms, and coping style were assessed by the Patient Health Questionnaire-9 (PHQ-9), 7-item Generalized Anxiety Disorder Scale (GAD-7), Impact of Event Scale-Revised (IES-R), and Simplified Coping Style Questionnaire-20-Chinese Version. This study included 1,315 isolated respondents in Hubei province (58.5% located in Wuhan). 69.3% respondents isolated at home, 30.7% respondents isolated at centralized quarantined spot. Of all respondents, 66.8% reported depressive symptoms, 49.7% reported anxiety symptoms, 89.0% reported PTSD symptoms. The Cronbach α of the IES-R, PHQ-9, GAD-7, and total SCSQ-20 were 0.935, 0.847, 0.843, and 0.888, respectively. Persons who isolated at home were associated with a lower risk of PTSD, depressive and anxiety symptoms (P < 0.01). People who knew someone to have COVID-19 were associated with severe symptoms of PTSD symptoms (P = 0.001). As for coping style, higher level of passive coping style was associated with severe symptoms of PTSD, depression and anxiety (P < 0.001). Our findings identify that person isolated during the COVID-19 epidemic was associated with high proportion of depression, anxiety, and PTSD symptoms. Public health officials should be aware of and prepared to take necessary measures.