Smartphone-Based Psychotherapeutic Micro-Interventions to Improve Mood in a Real-World Setting.

BACKGROUND: Using mobile communication technology as new personalized approach to treat mental disorders or to more generally improve quality of life is highly promising. Knowledge about intervention components that target key psychopathological processes in terms of transdiagnostic psychotherapy approaches is urgently needed. We explored the use of smartphone-based micro-interventions based on psychotherapeutic techniques, guided by short video-clips, to elicit mood changes. METHOD: As part of a larger neurofeedback study, all subjects-after being randomly assigned to an experimental or control neurofeedback condition-underwent daily smartphone-based micro-interventions for 13 consecutive days. They were free to choose out of provided techniques, including viscerosensory attention, emotional imagery, facial expression, and contemplative repetition. Changes in mood were assessed in real world using the Multidimensional Mood State Questionnaire (scales: good-bad, GB; awake-tired, AT; and calm-nervous, CN). RESULTS: Twenty-seven men participated on at least 11 days and were thus included in the analyses. Altogether, they underwent 335, generally well-tolerated, micro-intervention sessions, with viscerosensory attention (178 sessions, 53.13%) and contemplative repetition (68 sessions, 20.30%) being the most frequently applied techniques. Mixed models indicated that subjects showed better mood [GB: b = 0.464, 95%confidence interval (CI) [0.068, 0.860], t (613.3) = 2.298, p = 0.022] and became more awake [AT: b = 0.514, 95%CI [0.103, 0.925], t (612.4) = 2.456, p = 0.014] and calmer [CN: b = 0.685, 95%CI [0.360, 1.010], t (612.3) = 4.137, p < 0.001] from pre- to post-micro-intervention. These mood improvements from pre- to post-micro-intervention were associated with changes in mood from the 1st day until the last day with regard to GB mood (r = 0.614, 95%CI [0.297, 0.809], p < 0.001), but not AT mood (r = 0.279, 95%CI [-0.122, 0.602], p = 0.167) and CN mood (r = 0.277, 95%CI [0.124, 0.601], p = 0.170). DISCUSSION: Our findings provide evidence for the applicability of smartphone-based micro-interventions eliciting short-term mood changes, based on techniques used in psychotherapeutic approaches, such as mindfulness-based psychotherapy, transcendental meditation, and other contemplative therapies. The results encourage exploring these techniques' capability to improve mood in randomized controlled studies and patients. Smartphone-based micro-interventions are promising to modify mood in real-world settings, complementing other psychotherapeutic interventions, in line with the precision medicine approach. The here presented data were collected within a randomized trial, registered at ClinicalTrials.gov (Identifier: NCT01921088) https://clinicaltrials.gov/ct2/show/NCT01921088.

The effect of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of cilostazol and its active metabolites in healthy Korean subjects.

AIMS: The primary objective of this study was to evaluate the effects of Ginkgo biloba extracts (GBE) on the pharmacokinetics of cilostazol and its metabolites. The secondary objective was to assess the effect of GBE on the pharmacodynamics of cilostazol. METHODS: A randomized, double-blind, two-way crossover study was conducted with 34 healthy Korean subjects. All subjects were given an oral dose of cilostazol (100 mg) plus GBE (80 mg) or cilostazol (100 mg) plus placebo twice daily for 7 days. Plasma concentrations of cilostazol and its active metabolites (3,4-dehydrocilostazol and 4'-trans-hydroxycilostazol) were measured using liquid chromatography-tandem mass spectroscopy on day 7 for pharmacokinetic assessment. The adenosine diphosphate-induced platelet aggregation and bleeding time were measured at baseline and on day 7 for pharmacodynamic assessment. RESULTS: The geometric mean ratios of area under the concentration-time curve for dosing interval for cilostazol plus GBE vs. cilostazol plus placebo were 0.96 (90% confidence interval, 0.89-1.03; P = 0.20) for cilostazol, 0.96 (90% confidence interval, 0.90-1.02; P = 0.30) for 3,4-dehydrocilostazol and 0.98 (90% confidence interval, 0.93-1.03; P = 0.47) for 4'-trans-hydroxycilostazol. The change of aggregation after administration of cilostazol plus GBE seemed to be 1.31 times higher compared with cilostazol plus placebo, without statistical significance (P = 0.20). There were no significant changes in bleeding times and adverse drug reactions between the treatments. CONCLUSIONS: Co-administration of GBE showed no statistically significant effects on the pharmacokinetics of cilostazol in healthy subjects. A large cohort study with long-term follow-up may be needed to evaluate the possible pharmacodynamic interaction between cilostazol and GBE, given that there was a remarkable, but not statistically significant, increase in inhibition of platelet aggregation.

Cortical auditory evoked potential in aging: effects of stimulus intensity and noise.

OBJECTIVE: Older adults often have more difficulty understanding speech than younger adults do, particularly in the presence of noise. Such age-related speech perception difficulties may be related to declines in central auditory processing. Additionally, it has been hypothesized that impaired auditory processing might be related to neural dysynchrony. The purpose of this study was to examine the effects of stimulus intensity and noise on the N1-P2 response in younger and older normal-hearing adults. METHODS: Eight younger and 8 older normal-hearing adults participated in this study. Brief 100-ms tones (1.0 kHz, 100-60 dB SPL) in quiet and in continuous broadband noise (70 dB SPL) were used to evoke the N1-P2 responses. The N1-P2 components were analyzed as a function of stimulus intensity in both groups. RESULTS: N1 latencies to tones in quiet for older adults were delayed only at 60 dB SPL compared with those for younger adults. Additionally, N1 latencies to tones in noise were prolonged in older adults compared with those in younger adults even at 70 dB SPL (SNR = 0). No significant age effects were observed for the P2 latencies and N1-P2 amplitudes between the groups. CONCLUSION: N1 latency to tones with lower intensity and noise were delayed in older adults compared with those in younger adults. These stimulus intensity and noise issues can affect synchronized neural activity underlying the auditory processing and may provide a partial explanation for the difficulties shown by older adults in understanding speech.

Effect of CYP2C9 and VKORC1 genotypes on early-phase and steady-state warfarin dosing in Korean patients with mechanical heart valve replacement.

OBJECTIVES: The effect of CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1) genotypes was evaluated for the early-phase and steady-state warfarin dosing in Korean patients with mechanical heart valve replacement. METHODS: The genotypes of CYP2C9 variants including CYP2C9*3, CYP2C9*13, and CYP2C9*14, and VKORC1 1173C>T were assessed for the association with warfarin dosing in 265 patients whose data were collected for warfarin dose; international normalized ratio (INR), comedication, comorbidity, and other clinical characteristics. RESULTS: In the early phase of warfarin therapy, the combined genotypes of CYP2C9 and VKORC1 caused statistically significant difference in warfarin dose from day 7 of warfarin dosing and the subsequent time course of dose increase showed significant difference among the three different genotypes (P<0.001). Compared with patients with CYP2C9 wild type, the patients with heterozygous CYP2C9 variants have delayed time to reach stable dose [adjusted hazard ratio (HRadj): 0.48; 95% confidence interval (CI): 0.27-0.85] and tended to have high risk for the first INR greater than 3.5 (HRadj: 1.64; 95% CI: 0.98-2.75). The patients with the VKORC1 CT genotype showed no significant difference in the time to reach stable dose but statistically significant low HR for time to first INR greater than 3.5 compared with those with VKORC1 TT genotype (HRadj: 0.25; 95% CI: 0.13-0.51). The observed warfarin maintenance dose was best explained by a model including covariates of age, weight, concurrent congestive heart failure/cardiomyopathy, INR-increasing drugs, aspirin, dietary supplements, and CYP2C9 and VKORC1 genotypes (R=0.56). CONCLUSION: The heterozygous CYP2C9 and VKORC1 genotypes influence warfarin dosing in an early phase as well as steady state of warfarin therapy in Korean patients with mechanical heart valve replacement.