Imipramine for vestibular dysfunction in panic disorder: a prospective case series

OBJECTIVE: The purpose of this study was to evaluate the efficacy and effectiveness of imipramine on the treatment of comorbid chronic dizziness and panic disorder. METHOD: Nine patients with panic disorder and agoraphobia associated with chronic dizziness underwent otoneurological screening and were treated with a 3-months course of imipramine. Anxiety levels were measured with the Hamilton Anxiety Scale (HAM-A), dizziness levels were evaluated using the Dizziness Handicap Inventory (DHI), and panic severity and treatment outcome were assessed with the Clinical Global Impression Scale (CGI). RESULTS: At the baseline 33.3% (n=3) had a bilateral peripheral deficit vestibulopathy, the mean scores for HAM-A were 27.2±10.4, for DHI were 51.7±22.7, and for CGI-S were 4.8±0.9. All patients had a significant reduction in their HAM-A (11.1±5.5, p=0.008), DHI (11.5±8.1, p=0.008) and CGI-I (1.8±0.7, p=0.011) levels after 3-months imipramine treatment (mean=72.2±23.2 mg/day). CONCLUSION: This study found a decrease in anxiety levels and in the impact of dizziness in the patients' quality of life after a 3-months treatment course with imipramine

Increased Serotonin Transporter Expression Reduces Fear and Recruitment of Parvalbumin Interneurons of the Amygdala

Genetic association studies suggest that variations in the 5-hydroxytryptamine (5-HT; serotonin) transporter (5-HTT) gene are associated with susceptibility to psychiatric disorders such as anxiety or posttraumatic stress disorder. Individuals carrying high 5-HTT-expressing gene variants display low amygdala reactivity to fearful stimuli. Mice overexpressing the 5-HTT (5-HTTOE), an animal model of this human variation, show impaired fear, together with reduced fear-evoked theta oscillations in the basolateral amygdala (BLA). However, it is unclear how variation in 5-HTT gene expression impacts on the microcircuitry of the BLA to change behavior. We addressed this issue by investigating the activity of parvalbumin (PV)-expressing interneurons (PVINs), the biggest IN population in the basal amygdala (BA). We found that increased 5-HTT expression impairs the recruitment of PVINs (measured by their c-Fos immunoreactivity) during fear. Ex vivo patch-clamp recordings demonstrated that the depolarizing effect of 5-HT on PVINs was mediated by 5-HT2A receptor. In 5-HTTOE mice, 5-HT-evoked depolarization of PVINs and synaptic inhibition of principal cells, which provide the major output of the BA, were impaired. This deficit was because of reduced 5-HT2A function and not because of increased 5-HT uptake. Collectively, these findings provide novel cellular mechanisms that are likely to contribute to differences in emotional behaviors linked with genetic variations of the 5-HTT