First Evidence of Kv3.1b Potassium Channel Subtype Expression during Neuronal Serotonergic 1C11 Cell Line Development

Kv3.1 channel is abundantly expressed in neurons and its dysfunction causes sleep loss, neurodegenerative diseases and depression. Fluoxetine, a serotonin selective reuptake inhibitor commonly used to treat depression, acts also on Kv3.1. To define the relationship between Kv3.1 and serotonin receptors (SR) pharmacological modulation, we showed that 1C11, a serotonergic cell line, expresses different voltage gated potassium (VGK) channels subtypes in the presence (differentiated cells (1C11D)) or absence (not differentiated cells (1C11ND)) of induction. Only Kv1.2 and Kv3.1 transcripts increase even if the level of Kv3.1b transcripts is highest in 1C11D and, after fluoxetine, in 1C11ND but decreases in 1C11D. The Kv3.1 channel protein is expressed in 1C11ND and 1C11D but is enhanced by fluoxetine only in 1C11D. Whole cell measurements confirm that 1C11 cells express (VGK) currents, increasing sequentially as a function of cell development. Moreover, SR 5HT1b is highly expressed in 1C11D but fluoxetine increases the level of transcript in 1C11ND and significantly decreases it in 1C11D. Serotonin dosage shows that fluoxetine at 10 nM blocks serotonin reuptake in 1C11ND but slows down its release when cells are differentiated through a decrease of 5HT1b receptors density. We provide the first experimental evidence that 1C11 expresses Kv3.1b, which confirms its major role during differentiation. Cells respond to the fluoxetine effect by upregulating Kv3.1b expression. On the other hand, the possible relationship between the fluoxetine effect on the kinetics of 5HT1b differentiation and Kv3.1bexpression, would suggest the Kv3.1b channel as a target of an antidepressant drug as well as it was suggested for 5HT1b.

Current and Experimental Treatments for Anxiety Disorders

There are currently a range of treatments available for anxiety disorders, including pharmacological and behavior-based therapies. The most widely used medications, for which there is considerable evidence of efficacy across a range of anxiety disorders, are the serotonin-selective reuptake inhibitor antidepressants. Benzodiazepines are also widely prescribed and show efficacy for acute anxiety, but their use in the treatment of chronic anxiety syndromes is more problematic. Many patients are not adequately covered by the available range of medications, which is driving interest in potentially new pharmacological approaches. The best established non-pharmacological treatment of anxiety is cognitive behavioral therapy and several related behavioral approaches, which have been shown to be efficacious in a range of anxiety disorders. One of these related approaches is called cognitive bias modification, which aims to alter an individual’s responses to anxiety-provoking stimuli.

Escitalopram for antipsychotic nonresponsive visual hallucinosis: eight patients suffering from Charles Bonnet syndrome

ABSTRACTBackground: The Charles Bonnet syndrome (CBS) is characterized by distinct visual hallucinations and ocularpathology causing visual impairment in patients with insight and the absence of psychiatric comorbidity. The number of reported cases of CBS is expanding as the population ages and the prevalence of vision disorders increases. Antipsychotic medications are often prescribed. However, their efficacy in CBS has been based on sketchy evidence. The use of serotonin selective reuptake inhibitor (SSRI) for CBS was anecdotally reported. We herein describe effectiveness of escitalopram in a series of patients suffering from CBS who were unresponsive to antipsychotic treatment.Methods: Eight consecutive patients suffering from CBS who did not respond to standard antipsychotic treatment were switched to escitalopram. CBS severity prior to escitalopram treatment was quantified using the Clinical Global Impression (CGI) scale and again after eight weeks of treatment. All had undergone brain CT and cognitive assessment. Brain CT imaging was normal except for an incidental finding of a small frontal meningioma in one patient. All had Mini-Mental Status Examination scores of ≥ 27/30.Results: There were four men and four women, with a mean age of 81.7 ± 7.3 years. Previous antipsychotic treatment was mostly with risperidone, 1.0 to 3.0 mg/daily. Mean CGI-severity upon switching to escitalopram treatment was 5.7. This was significantly reduced to 1.8 (p < 0.001) after eight weeks of escitalopram treatment (mean dose: 11.8 mg/daily). There were no side effects, nor any adverse events were reported.Conclusions: This is the first case-series to show that SSRI is an effective and well-tolerated treatment for visual hallucinations associated with vision impairment such as in CBS.