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Background: Glycogen synthase kinase-3β (GSK-3β) plays important roles in intracellular signaling pathways. Phosphorylation at Ser-9 reduces the activity of GSK-3β, while phosphorylation at Tyr-216 enhances its activity. Mood stabilizing agents increase the phosphorylation of GSK-3β at Ser-9, and hence inhibit its activity. This property has been considered to be related to the therapeutic action of these drugs. The effect of electroconvulsive shock (ECS), an effective mood stabilizing treatment, on the phosphorylation of GSK-3β is not known yet. Methods: In this study, the effect of ECS on the phosphorylation of GSK-3β was examined in the rat frontal cortex, hippocampus, and cerebellum by Western blot analysis using antibodies specific for Ser-9 or Tyr-216 phosphorylated GSK-3β. Results: In all regions, the phosphorylation of GSK-3β at Ser-9 was decreased immediately after ECS, but then increased above basal level within 10 min and maintained at an increased level for more than 30 min. Meanwhile, the phosphorylation at Tyr-216 of GSK-3β did not show any significant changes after ECS. Conclusions: These results showed that ECS could induce biphasic changes in the Ser-9 phosphorylation of GSK-3β in the rat brain, suggesting some similarities, as well as differences, in the actions of mood stabilizers and ECS in the signal transduction mechanisms of the brain. [Copyright &y& Elsevier]

Both the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 and electroconvulsive shock (ECS) have been reported to induce c-Fos in rat brain. However, the former has anticonvulsant and psychotomimetic effects and the latter has proconvulsant and antipsychotic effects. To understand the mode of action of these treatments, the authors examined the effect of MK-801 and the interaction between MK-801 and ECS on the induction of c-Fos in the rat hippocampus and frontal cortex. MK-801 induced c-Fos in these brain regions in a nonlinear dose–response relationship. Maximum effect was achieved with 1–2 mg/kg of MK-801. The level of c-Fos paralleled animal hyperkinetic behavior, suggesting the role of c-Fos in the induced psychotomimetic behaviors. Pretreatment with MK-801 dose-dependently attenuated both the seizures and c-Fos expression by ECS. However, at an MK-801 pretreatment dose of 8 mg/kg, which completely blocked ECS-induced seizure, the induction of c-Fos was not completely blocked, suggesting non-NMDA mediated pathways of the induction of c-Fos by ECS. [Copyright &y& Elsevier]

Auditory verbal hallucinations (AVHs) constitute a frequent and distressing symptom of schizophrenia, associated with physical, emotional, and cognitive challenges. Despite their clinical importance, changes in the multiple dimensions of AVHs during treatment have rarely been examined, and subjective views thereof have received minimal attention. Here, we evaluated 87 patients with schizophrenia-related AVHs using the Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ; a self-report questionnaire) and the Psychotic Symptom Rating Scales-Auditory Hallucination Subscale (PSYRATS-AH; a clinician-rated scale) at baseline and after 6 months and 1 year of treatment. We explored dimensions that changed from the perspectives of both clinicians and patients and the relationships between these perceptions over the year. The test–retest reliabilities of the HPSVQ and PSYRATS-AH were generally fair. Improvements in AVHs were evident over the first 6 months; the PSYRATS-AH revealed a broader range of symptom improvement than did the HPSVQ. The "interference with life" dimension on the HPSVQ was not reduced, but the "disruption to life" score on the PSYRATS-AH was. At both baseline and 6 months, the physical characteristics of AVHs (frequency, duration, and loudness) were significantly correlated with both distress and life interference/disruption; all correlations except that for frequency were reduced at 1 year. The clinician-rated and self-reported personal perspectives on AVHs exhibited both differences and similarities; physical AVH components and subjective distressful experiences changed in different ways in those with chronic, persistent AVHs. The HPSVQ and PSYRATS-AH data were complementary, improving our understanding of the clinical implications of AVHs and subjective patient distress. • HPSVQ, a self-report questionnaire, effectively detected the 1-year changes in AVHs. • Changes in physical features of AVHs were distinguished from changes in subjective distress. • HPSVQ and PSYRATS-AH are complementary to understand the subjective distress of AVHs. [ABSTRACT FROM AUTHOR]