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Background: Previous research has reported evidence that patients with major depressive disorder (MDD) show anxiety symptoms and neurocognitive impairments. However, the influence of anxiety on neurocognitive function in MDD patients during antidepressant treatment is unclear., Method: MDD patients (n=164) completed a 12-week, multicenter, randomized trial assigned in a 1:1 ratio to either tianeptine or escitalopram. Changes of anxiety symptoms were assessed by the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D), self-rated subjective cognitive impairment on memory and concentration, the Mini-Mental Status Examination (MMSE), Continuous Performance Test (CPT), Verbal Learning Test (VLT), and Raven's Progressive Matrices (RPM) were assessed every 4 weeks., Results: During 12 weeks of treatment, decrease in the HAM-A score was significantly associated with improvement of subjective cognitive impairments on memory (p<0.001) and concentration (p<0.001), and objective measures on delayed memory (p=0.006) and reasoning ability (p=0.002), after adjusting for covariates such as baseline HAM-A scores, time, sex, age, education years and assigned medication using the Mixed effects and Generalized Estimated Equation model analysis. However, the other cognitive outcome variables, immediate memory, commission error, and MMSE, which showed significant improvement through 12-week study period, showed no significant association with improvement of anxiety., Conclusion: Improvement of anxiety symptoms was significantly associated with improvement in subjective and objective neurocognitive functions such as delayed memory and reasoning ability in elderly MDD patients during antidepressant treatment, but not significantly associated with improvement of immediate memory and commission error., Trial Registration: ClinicalTrials.gov identifier NCT01309776., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Panic disorder (PD) has a critical impact on productivity at the workplace. This study aimed to identify the lost productivity time (LPT) for patients with PD. It also assessed change in LPT for patients with PD after 12 weeks of treatment with Selective Serotonin Reuptake Inhibitors (SSRIs), compared with healthy controls., Methods: Working patients diagnosed with PD without other major medical or psychiatric illness were enrolled at outpatient psychiatric clinics (N=108). Age and sex-matched healthy controls were recruited through advertisement (N=108). Health and productivity, PD symptoms, and depressive symptoms were assessed using the Korean version of the World Health Organization's Health and Work Performance Questionnaire (HPQ), the Panic Disorder Severity Scale (PDSS), and the Hamilton Rating Scales for Depression (HAM-D), respectively at baseline, week 4, and week 12., Results: At baseline, the PD group showed significantly higher LPT compared to the control group (103.02 vs. 47.28h in the past 4 weeks). After 12 weeks of treatment, the PD group displayed significant clinical improvement as well as improved productivity with a marked reduction in LPT. Among the patients who completed the treatment, LPT due to PD was reduced from 104.38 to 55.15h in the past 4 weeks., Limitations: There may be selection bias due to case-control study design., Conclusions: These data suggest that, after the treatment, there was significant improvement in clinical symptoms, and that productivity loss due to PD was almost entirely recovered to the level of healthy controls after 12 weeks of psychiatric outpatient treatment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We aimed to examine whether anxiety sensitivity and agoraphobic fear could affect the time taken to remission after 24 weeks of open-label escitalopram treatment of patients with panic disorder (PD). We recruited 158 patients, and 101 patients completed the study. Clinical severity and psychological characteristics were assessed at baseline and 4, 12, and 24 weeks after the treatment, using the Clinical Global Impression-Severity (CGI-S), the Hamilton Rating Scales for Anxiety and Depression, the Anxiety Sensitivity Index-Revised (ASI-R), the Albany Panic and Phobia Questionnaire (APPQ), and the Panic Disorder Severity Scale (PDSS). Remission was defined as the absence of full panic attacks and PDSS scores of 7 or less. Completing patients were stratified according to the time taken to remit: early (n=20) and late (n=58) remission and non-remission groups (n=23). There were no significant differences among the three groups at baseline on the CGI-S and the PDSS mean scores. However, early remitters had significantly lower scores than late remitters and non-remitters on the ASI-R and APPQ. In conclusion, anxiety sensitivity and agoraphobic fear can affect the time to remission after pharmacotherapy, and clinicians should consider the psychological characteristics of PD patients in order to achieve an optimal response to pharmacotherapy., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Somatic symptoms are often important in the treatment of major depressive disorder (MDD). The aim of this open-labeled trial was to examine the efficacy of mirtazapine for the treatment of MDD with clinically significant somatic symptoms, as compared with venlafaxine. A total of 126 patients with MDD (score >/=18 on the Hamilton Rating Scale for Depression-17) were included in both the intent-to-treat (n=73 in the mirtazapine group and n=53 in the venlafaxine group) and completer analysis (n=51 and n=37, respectively). After treatment, both treatment groups showed similar improvements in depressive symptoms. Repeated measures analysis of variance for the intent-to-treat population revealed that there were no significant differences in mean change of the Symptom Check List-90-Revised (SCL-90-R) somatization subscores between the two groups. For completers, there was a significant timextreatment interaction in the SCL-90-R somatization subscores, but the differences between the two groups at endpoint did not reach statistical significance in post-hoc analysis. In conclusion, this study suggests that overall efficacies of mirtazapine and venlafaxine are similar for the treatment of overall symptoms in MDD, and both drugs may be useful for the treatment of somatic symptoms in MDD patients.

Vitamin C (ascorbate) is a water-soluble, low molecular weight antioxidant that works in conjunction with glutathione and other cellular antioxidants, and is effective against a variety of reactive oxygen species, including superoxide and hydroxyl radicals that have been implicated in the etiology of noise-induced hearing loss (NIHL). Whereas most animals can manufacture their own vitamin C, humans and a few other mammals such as guinea pigs lack the terminal enzyme for vitamin C synthesis and must obtain it from dietary sources. To determine if susceptibility to NIHL could be influenced by manipulating dietary levels of vitamin C, albino guinea pigs were raised for 35 days on a diet with normal, supplemented or deficient levels of ascorbate, then exposed to 4 kHz octave band noise at 114 dB SPL for 6 h to induce permanent threshold shifts (PTS) of the scalp-recorded auditory brainstem response. Animals that received the highest levels of dietary ascorbate developed significantly less PTS for click stimuli and 4, 8, 12, and 16 kHz tones than animals on normal and deficient diets. Outer hair cell loss was minimal in all groups after noise exposure, but permanent damage to stereocilia were observed in noise-exposed ears. The results support the hypothesis that dietary factors influence individual susceptibility to hearing loss, and suggest that high levels of vitamin C may be beneficial in reducing susceptibility to NIHL.

Although it is well known that ethacrynic acid (EA) can enhance gentamicin (GM) ototoxicity, there has been no systematic study of the relationship between dosing parameters and inner ear pathology. We examined the effects of two parameters, GM dose and time delay between GM and EA administration, on cochlear and vestibular hair cell loss in chinchillas. 'No delay' groups received one injection of GM (125, 40, 20, or 10 mg/kg i.m.) followed immediately by EA (40 mg/kg i.v.); 'delay' groups received GM (10 mg/kg i.m.) followed by EA 1 or 1.5 h later. Animals were sacrificed 7 days later for evaluation of hair cell loss in the cochlea and vestibular end organs (cristae, saccule and utricle). Vestibular function was assessed prior to sacrifice by measuring the duration of nystagmus induced by cold caloric stimulation. No delay groups had approximately 100% loss of outer hair cells and dose-dependent losses of inner hair cells, ranging from approximately 100% to 58%. In 1 and 1.5 h delay groups, inner hair cell losses were approximately 19% and 0%, outer hair cell losses were approximately 74% and 47%, and outer hair cell loss followed a typical base to apex gradient. Two results were remarkable. First, the three groups with partial inner hair cell loss showed an atypical lesion pattern in which losses were substantially greater in the apical half than in the basal half of the cochlea. Second, there was no vestibular pathology in any group. The results establish dosing parameters that can be used to produce animal models with defined patterns and magnitudes of cochlear hair cell damage, but normal vestibular function and morphology.

The mechanisms underlying the ototoxicity of ethacrynic acid (EA) are not fully understood. Previous studies have focused on morphologic and enzymatic changes in the stria vascularis. The current experiment shows that one of the earliest effects of EA is ischemia, resulting from impaired blood flow in vessels supplying the lateral wall of the cochlea. Inner ear microcirculation, endocochlear potentials, compound action potentials (CAP), cochlear microphonics (CM) and summating potentials (SP) were monitored over time in chinchillas following a single injection of EA (40 mg/kg i.v.). At all times after EA injection, blood vessels supplying the spiral lamina, modiolus, and vestibular end organs appeared normal. In contrast, lateral wall (spiral ligament and stria vascularis) vessels were poorly stained with eosin 2 min after EA injection, and devoid of red blood cells at 30 min post EA. Decline, but not recovery, of CAP, CM and SP followed the microcirculation changes in the lateral wall. Reperfusion was delayed in stria vascularis arterioles relative to other lateral wall vessels. The ischemia-reperfusion caused by EA would be expected to generate large quantities of free radicals, which may trigger or contribute to the cellular, enzymatic, and functional pathologies that have been described in detail previously.