Disorder

tasks was compared between before and after escitalopram administration. Methods: subjects depressive outpatients (40.2 ± 7.6 years old) attending Kurume University Hospital. HAM-D was used to evaluate symptoms. Oxy-Hb value during the tasks were measured at bilateral recording points (22 on each side) using a multi-channel NIRS system. The subjects were instructed to phonate “a-i-u-e-o” for 12 seconds as a resting condition, and performed a verbal production task (VPT) or shiritori task (saying a word starting with the last syllable). The shiritori task involved two task patterns, i.e., standard shiritori (VST) and living creatures shiritori (VLT). From the data obtained at each measurement point during the 20 trials, an averaged waveform was prepared, and peak values of waveform were calculated and analyzed. These tasks were performed before escitalopram administration (session 1(S1)) and 3.6 (S2) and 8.5 (S3) months after initiation of escitalopram administration. Results: When HAM-D was compared between before and after escitalopram administration, it significantly decreased in S2 and S3. No significant difference was noted in the number of words in the verbal task between before and after administration. Oxy-Hb value was significantly increased in the bilateral middle frontal regions in S3 of VLT compared with those before administration (S1). In the left frontal pole region, Oxy-Hb value significantly increased in the VST and VLT. A significant inverse correlation was observed between HAM-D and oxy-Hb value in the left middle frontal region. Discussion: Escitalopram effective, and oxy-Hb value Abstract Objective: Lower heart rate variability (HRV), a measure of auto-nomic function, has been noted in depression and linked with cardiovascular disease risk. Evidence suggests that some anti-depressants, such as tricyclics and SNRIs, adversely impact HRV (Terhardt et al., 2013) while SSRIs appear to have no influence on HRV (Kemp et al., 2010). Desvenlafaxine is a newer SNRI used to treat depression, but there are no published studies on its benefits in chronic depression, or its influence on measure of HRV. The objectives of this pilot investigation were to investigate these issues. Methods: Twenty-three patients with persistent depressive disorder, who were enrolled in an open-label 8-week trial of monotherapy with desvenlafaxine, were included in this study. HRV was measured at baseline and post-treatment. Differences in HRV parameters were assessed pre-post treatment, as well as between those who responded to treatment (n=15) vs. non-responders (n=8). Results: Across the sample, HRV measures of time-and fre-quency-domains significantly decreased over the course of treatment, including SDNN (p<.01), RMSSD (p=.05), RR triangular index (p=.03), as well as total Power (p<.01) and LF/HF Power (p=.03). Significant increases in frequency-domain measures such as HF power (p=.04) were also noted. Further, comparisons between responders and non-responders revealed significant differences in time-domain measures (TINN, p=.04), and overall estimates of HRV (RR triangular index) (p=.02) post-treatment. Conclusions: The results suggest that treatment response to desvenlafaxine is associated with normalization of sympatho-vagal balance (HRV). Limitations of this study include small sample size and absence of a control group. Additional investi-gations are warranted. Abstract Objective: The objective of this study was to detect specific psychophysiological response to interpersonal stimulus in dysthymic patients, using a newly-designed interpersonal conditioning experiment, and to elucidate the impact of their clinical characteristics and prescribed medications on the response. Method: Twenty female dysthymic subjects underwent fear conditioning and extinction experiments in response to two types of stimuli: an aversive sound, and pictures of an actors’ face with recorded unpleasant verbal messages to cause interpersonal conflicts. Conditioned response was quantified by differential skin conductance response (SCR) between CS[+] and CS[-]. Regression analysis was performed to examine the effects of emotion regulation strategy measured by the Emotion Regulation Questionnaire (ERQ) and prescribed medications on the differential SCR. Result: Mean± ± sound interpersonal subjects Abstract Objectives: Venlafaxine is metabolized by CYP2D6 to O-desmethylvenlafaxine (ODV) and by CYP3A4 to N-desmethylvenlafaxine (NDV). CYP2C19 is also involved in the formation of ODV. The PPIs omeprazole and pantoprazole inhibit CYP2C19 to a different extent. Aim of this study was to investigate the potential effects of both PPIs on serum levels of VEN and ODV. Methods: From a therapeutic drug monitoring (TDM) database, serum concentrations of VEN, ODV and the active moiety (VEN + ODV), were analyzed. Data from 120 patients were available and splitted into three groups: patients without PPI [noPPI], with pantoprazole [PANTO] or with omeprazole [OMEP] (n=40 each). The ratio of (ODV/VEN) was calculated as a marker of the metab-olizer status. Results: Median test detected no differences regarding the median daily dosage of VEN between the three groups (p=0.995); the mean daily doses for VEN were 207.6mg/d, SD=79.96 in the control-group, 209.06mg/d, SD=78.24 for the pantoprazole group and 203.43mg/d, SD=91.41 for omeprazole group. Plasma concentrations for VEN + ODVEN in the PANTO group were significantly higher than in the control group (p=0.019 for Mann-Whitney U Test). Plasma concentrations for ODVEN and VEN + ODVEN in the OMEP group were significantly higher than in the control group (p=0.001 and p=0.017 for Mann-Whitney U Test) Conclusion: Both, omeprazole and pantoprazole led to a vary-ing extent in increases of the serum concentrations of the active moiety (sum of VEN+ODV). The increase is driven by significantly higher levels of ODV in the OMEP group. This might be due to distinct CYP2C19 blocking properties of both PPIs, hindering the 2C19 mediated metabolization of VEN to N-desmethylvenlafaxine (NDV). Abstract Purpose: This study investigated the pharmacokinetics of mirtazapine (MIR) and its hydroxylated metabolite in Japanese psychiatric patients. Patients and Methods: The subjects were 59 Japanese patients treated with racemic MIR. The steady-state plasma concentrations of MIR and N-desmethylmirtazapine (DMIR), 8-hydroxy-MIR (8-OH-MIR) were measured using high performance liquid chromatography. CYP2D6 genotypes were determined by poly-merase chain reaction. Three subjects whose plasma levels of MIR and DMIR were below the limit of detection were regarded as non-adherent and excluded. Multiple regression analysis (stepwise method) was performed to analyze the relationship between subject-independent variables (gender, age, smoking status and number of mutated CYP2D6 alleles) and subject-dependent variables such as plasma concentrations of MIR, DMIR, 8-OH-MIR (ng/ml/mg/kg; all corrected for dose and body weight) and 8-OH-MIR/MIR ratio. Results: Multiple regression analysis revealed that smoking (p=0.016) and gender (p=0.041) Abstract KYN pathway (KP) is activated by pro-inflammatory cytokines and can produce pro-oxidative metabolites in the brain of depressed patients. Antidepressant treatment reverses oxidative stress in animal models, we can hypothesize that In an animal model of “chronic stress induced depression” in mice, we previously showed that TRP/ KYN pathway activa-tion produced glutamatergic and pro-oxidative metabolites (3-HK), suggesting that chronic stress accelerates glutamatergic excitotoxicity and oxidative stress. We show here that a chronic treatment with the IDO (indole dioxygenase) inhibitor 1-methyl-tryptophan (1MT) or antidepressant fluoxetine were able to reverse TRP/KYN abnormalities caused by chronic stress. These data suggest that TRP/KYN pathway would play a central role in the pathophysiology of stress-induced bio-behavioural abnormalities. Methods: Mice were confronting the unpredictable chronic mild stress (UCMS) procedure and brain KP metabolites were ana-lysed in relevant brain structures and in the periphery, in saline, 1-MT and fluoxetine treated animals. Results: 1-MT and FLX reverse most of UCMS-induced behav-ioural abnormalities induced by UCMS and reverse various metabolic alterations of the KP (peripherally and centrally). Conclusions: Our results show that inhibition of the KP by 1MT is as effective as fluoxetine as an antidepressant treatment in the UCMS mice. They show that inhibiting KP subsequently reduces the production of pro-oxidative /neurotoxic metabolic substrates in relevant structures. They suggest that KP would play a central role in the link between neuroinflammation and oxidative stress abnormalities in chronic stress induced mood disorders.