Glial Purinergic Signals and Psychiatric Disorders

Emotion-related neural networks are regulated in part by the activity of glial cells, and glial dysfunction can be directly related to emotional diseases such as depression. Here, we discuss three different therapeutic strategies involving astrocytes that are effective for treating depression. First, the antidepressant, fluoxetine, acts on astrocytes and increases exocytosis of ATP. This has therapeutic effects via brain-derived neurotrophic factor-dependent mechanisms. Second, electroconvulsive therapy is a well-known treatment for drug-resistant depression. Electroconvulsive therapy releases ATP from astrocytes to induce leukemia inhibitory factors and fibroblast growth factor 2, which leads to antidepressive actions. Finally, sleep deprivation therapy is well-known to cause antidepressive effects. Sleep deprivation also increases release of ATP, whose metabolite, adenosine, has antidepressive effects. These independent treatments share the same mechanism, i.e., ATP release from astrocytes, indicating an essential role of glial purinergic signals in the pathogenesis of depression.

Temporoparietal Connectivity Within Default Mode Network Associates With Clinical Improvements in Schizophrenia Following Modified Electroconvulsive Therapy

Although modified electroconvulsive therapy (ECT) has been reported to be effective for the treatment of schizophrenia (SCZ), its action mechanism is unclear. To elucidate the underlying ECT mechanisms of SCZ, this study used a longitudinal cohort including 21 SCZ patients receiving only antipsychotics (DSZ group) and 21 SCZ patients receiving a regular course of ECT combining with antipsychotics (MSZ group) for 4 weeks. All patients underwent magnetic resonance imaging (MRI) scans at baseline (t1) and follow-up (t2) time points. A matched healthy control (HC) group included 23 individuals who were only scanned at baseline. Functional connectivity (FC) within the default mode network (DMN) was evaluated before and after ECT. Significant interaction of the group over time was found in FC between angular gyrus (AG) and middle temporal gyrus (MTG). Post-hoc analysis showed a significantly enhanced FC of left AG(AG.L) and right MTG (MTG.R) in the MSZ group relative to the DSZ group. In addition, the right AG (AG.R) showed significantly enhanced FC between MTG.R and left MTG (MTG.L) after ECT in the MSZ group, but no in the DSZ group. In particular, the FCs change in AG.L-MTG.R and AG.R-MTG.R were positively correlated with the Positive and Negative Syndrome Scale (PANSS) negative score reduction. Furthermore, the FC change in AG.L-MTG.R was also positively correlated with the PANSS general psychopathology score reduction. These findings confirmed a potential relationship between ECT inducing hyperconnectivity within DMN and improvements in symptomatology of SCZ, suggesting that ECT controls mental symptoms by regulating the temporoparietal connectivity within DMN.

The Effectiveness of Non-clozapine Antipsychotics Combined with Electroconvulsive Therapy versus Clozapine Combined with Electroconvulsive Therapy for Treatment-resistant Schizophrenia

The study aimed to compare the effectiveness and safety of other atypical antipsychotics (non-clozapine) plus electroconvulsive therapy (ECT) (NC+ECT) versus clozapine plus ECT (C+ECT) for treating treatment-resistant schizophrenia (TRS). Data of 32 patients with TRS who was receiving ECT were analysed. We compared clinical characteristics, response to treatment [defined as an improvement of 40% in the Brief Psychotic Rating Scale (BPRS) psychotic symptom subscale from pretreatment scores], change of Mini-mental Status Exam (MMSE) scores, and other adverse effects between the NC+ECT group (N= 16) and C+ECT group (N =16). We found that the overall response rate was 65.6% (75.8% for the NC+ECT group and 56.3% for the C+ECT group, p=0.26). The overall BPRS score in both groups decreased significantly. The mean difference in total BPRS psychotic subscale score between pre-ECT and after last ECT was 10.4 + 5.8 (p<0.001) for the NC+ECT group and 6.6 + 7.3 (p = 0.002) for the C+ECT group. When comparing the NC+ECT group to the C+ECT group, the mean difference in total BPRS psychotic subscale score was not significant. (p = 0.104). The mean difference in MMSE score between pre-ECT and after the last ECT was -1.1 + 5.1 (p =0.45) for the NC+ECT group and 0.2 + 4.3 (p=0.855) for the C+ECT group. The change of MMSE score in the NC+ECT group was not significant different compare to the C+ECT group (p = 0.461). We concluded the combination of antipsychotics and ECT is an effective and safe treatment option for patients with TRS. Other NC+ECT groups’ efficacy may be comparable to that of clozapine plus ECT.