ABSTRACT
Olanzapine is a second-generation antipsychotic that disrupts metabolism and is associated with an increased risk of type 2 diabetes. The hypothalamus is a key region in the control of whole-body metabolic homeostasis. The objective of the current study was to determine how acute peripheral olanzapine administration affects transcription and serine/threonine kinase activity in the hypothalamus. Hypothalamus samples from rats were collected following the pancreatic euglycemic clamp, thereby allowing us to study endpoints under steady state conditions for plasma glucose and insulin. Olanzapine stimulated pathways associated with inflammation, but diminished pathways associated with the capacity to combat endoplasmic reticulum stress and G protein-coupled receptor activity. These pathways represent potential targets to reduce the incidence of type 2 diabetes in patients taking antipsychotics.
Subject(s)
Antipsychotic Agents , Diabetes Mellitus, Type 2 , Humans , Rats , Animals , Olanzapine/pharmacology , Olanzapine/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Benzodiazepines/pharmacology , Benzodiazepines/metabolism , Antipsychotic Agents/pharmacology , Antipsychotic Agents/metabolism , Hypothalamus/metabolism , Gene Expression ProfilingABSTRACT
Impaired insight in schizophrenia patients has been linked with prefrontal deficits. In this open-label study, we examined for potential insight facilitation effects of add-on tDCS (with anodal stimulation of left DLPFC and cathodal stimulation over left temporo-parietal junction) in schizophrenia patients (N=21) with persistent auditory hallucinations despite adequate antipsychotic treatment. Following tDCS, there was a significant improvement in insight with concurrent significant reduction in auditory hallucination severity. Improvement in insight correlated significantly with improvement in severity of auditory hallucinations. These findings suggest improvement of insight with add-on tDCS in schizophrenia with persistent auditory hallucinations.
Subject(s)
Electric Stimulation Therapy/methods , Electric Stimulation Therapy/psychology , Schizophrenia/therapy , Schizophrenic Psychology , Adult , Antipsychotic Agents/therapeutic use , Female , Hallucinations/etiology , Hallucinations/therapy , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Schizophrenia/complications , Young AdultABSTRACT
Treatment of nonresponsive auditory hallucinations in schizophrenia have been reported to improve with transcranial direct-current stimulation. This case description illustrates the use of add-on transcranial direct-current stimulation for rapid amelioration of auditory hallucinations in schizophrenia during the acute phase. Because transcranial direct-current stimulation is safe, largely well tolerated, and relatively inexpensive, this add-on treatment option is worth exploring through further rigorous studies.