Schizophrenia is a disorder of brain dysconnectivity, and both the connection strength and connection number are disrupted in patients with schizophrenia. The functional connectivity density (FCD) can reflect alterations in the connection number. Alterations in the global FCD (gFCD) in schizophrenia were previously demonstrated; however, alterations in two other indices of the pathological characteristics of the brain, local FCD (lFCD) and long-range FCD (lrFCD), have not been revealed. To investigate lFCD and lrFCD alterations in patients with schizophrenia, 95 patients and 93 matched healthy controls were examined using structural and resting-state functional magnetic resonance imaging scanning. lFCD and lrFCD were measured using FCD mapping, and differences were identified using a two-sample t-test in a voxel-wise manner, with age and gender considered to increase variability. Multiple comparisons were performed using a false discovery rate method with a corrected threshold of P<0.05. Our analysis showed that lFCD was primarily decreased in the postcentral gyrus, right calcarine sulcus, and inferior occipital gyrus lobule, but increased in the bilateral subcortical regions. The differences in lFCD were more pronounced and complicated than those in lrFCD. In summary, in contrast with previous studies that focused on the connection strength, our findings, from the perspective of connection number, indicate that schizophrenia is a disorder of brain dysconnectivity, particularly affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions.
Cognitive impairment is a core clinical feature of schizophrenia, exerting profound adverse effects on social functioning and quality of life in a large proportion of patients with schizophrenia. However, the mechanisms underlying the pathogenesis of schizophrenia-related cognitive impairment are not well understood. Microglia, the primary resident macrophages in the brain, have been shown to play important roles in psychiatric disorders, including schizophrenia. Increasing evidence has revealed excessive microglial activation in cognitive deficits related to a broad range of diseases and medical conditions. Relative to that about age-related cognitive deficits, current knowledge about the roles of microglia in cognitive impairment in neuropsychiatric disorders, such as schizophrenia, is limited, and such research is in its infancy. Thus, we conducted this review of the scientific literature with a focus on the role of microglia in schizophrenia-associated cognitive impairment, aiming to gain insight into the roles of microglial activation in the onset and progression of such impairment and to consider how scientific advances could be translated to preventive and therapeutic interventions. Research has demonstrated that microglia, especially those in the gray matter of the brain, are activated in schizophrenia. Upon activation, microglia release key proinflammatory cytokines and free radicals, which are well-recognized neurotoxic factors contributing to cognitive decline. Thus, we propose that the inhibition of microglial activation holds potential for the prevention and treatment of cognitive deficits in patients with schizophrenia. This review identifies potential targets for the development of new treatment strategies and eventually the improvement of care for these patients. It might also help psychologists and clinical investigators in planning future research.
Brain pathological features during manic/hypomanic and depressive episodes in the same patients with bipolar disorder (BPD) have not been described precisely. The study aimed to investigate depressive and manic-phase-specific brain neural activity patterns of BPD in the same murine model to provide information guiding investigation of the mechanism of phase switching and tailored prevention and treatment for patients with BPD. In vivo two-photon imaging was used to observe brain activity alterations in the depressive and manic phases in the same murine model of BPD. Two-photon imaging showed significantly reduced Ca2+ activity in temporal cortex pyramidal neurons in the depression phase in mice exposed to chronic unpredictable mild stress (CUMS), but not in the manic phase in mice exposed to CUMS and ketamine. Total integrated calcium values correlated significantly with immobility times. Brain Ca2+ hypoactivity was observed in the depression and manic phases in the same mice exposed to CUMS and ketamine relative to naïve controls. The novel object recognition preference ratio correlated negatively with the immobility time in the depression phase and the total distance traveled in the manic phase. With recognition of its limitations, this study revealed brain neural activity impairment indicating that intrinsic emotional network disturbance is a mechanism of BPD and that brain neural activity is associated with cognitive impairment in the depressive and manic phases of this disorder. These findings are consistent with those from macro-imaging studies of patients with BPD. The observed correlation of brain neural activity with the severity of depressive, but not manic, symptoms need to be investigated further.
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