•A single dose of ketamine infusion reduces TNF-α levels at 40 min and 240 min postinfusion.•There is a positive correlation between changes in cytokine levels after ketamine infusion and ...improvements in depressive symptoms.•The rapid suppression of proinflammatory cytokines may contribute to the rapid antidepressant effect of the ketamine infusion.
Increasing evidence supports the rapid antidepressant effect of a low-dose ketamine infusion in treatment-resistant depression (TRD). Proinflammatory cytokines play a crucial role in the pathophysiology of TRD. However, it is unknown whether the rapid antidepressant effect of ketamine is related to the rapid suppression of proinflammatory cytokines. Seventy-one patients with TRD were randomized into three groups according to the treatment received: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and normal saline infusion. Proinflammatory markers, including C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were examined at baseline and at 40 min, 240 min, Day 3, and Day 7 postinfusion. Montgomery–Åsberg Depression Rating Scale (MADRS) was assessed for depressive symptoms across time. Log-transformed IL-6 and TNF-α levels differed significantly over time. The decrease in TNF-α between baseline and 40 min postinfusion was positively correlated with a decrease in MADRS scores across time in the 0.5 mg/kg ketamine group. This is the first clinical study to support a positive correlation between changes in cytokine levels after ketamine infusion and improvements in depressive symptoms with TRD. The rapid suppression of proinflammatory cytokines may contribute to the rapid antidepressant effect of the ketamine infusion.
Cephalometric analysis is an essential clinical and research tool in orthodontics for the orthodontic analysis and treatment planning. This paper presents the evaluation of the methods submitted to ...the Automatic Cephalometric X-Ray Landmark Detection Challenge, held at the IEEE International Symposium on Biomedical Imaging 2014 with an on-site competition. The challenge was set to explore and compare automatic landmark detection methods in application to cephalometric X-ray images. Methods were evaluated on a common database including cephalograms of 300 patients aged six to 60 years, collected from the Dental Department, Tri-Service General Hospital, Taiwan, and manually marked anatomical landmarks as the ground truth data, generated by two experienced medical doctors. Quantitative evaluation was performed to compare the results of a representative selection of current methods submitted to the challenge. Experimental results show that three methods are able to achieve detection rates greater than 80% using the 4 mm precision range, but only one method achieves a detection rate greater than 70% using the 2 mm precision range, which is the acceptable precision range in clinical practice. The study provides insights into the performance of different landmark detection approaches under real-world conditions and highlights achievements and limitations of current image analysis techniques.
We present an analysis of version 5.1 of the Community Atmospheric Model (CAM5.1) at a high horizontal resolution. Intercomparison of this global model at approximately 0.25°, 1°, and 2° is presented ...for extreme daily precipitation as well as for a suite of seasonal mean fields. In general, extreme precipitation amounts are larger in high resolution than in lower‐resolution configurations. In many but not all locations and/or seasons, extreme daily precipitation rates in the high‐resolution configuration are higher and more realistic. The high‐resolution configuration produces tropical cyclones up to category 5 on the Saffir‐Simpson scale and a comparison to observations reveals both realistic and unrealistic model behavior. In the absence of extensive model tuning at high resolution, simulation of many of the mean fields analyzed in this study is degraded compared to the tuned lower‐resolution public released version of the model.
Key Points
The effects of increasing resolution in an atmospheric model are presented
Global models at 25 km can realistically simulate tropical cyclone statistics
Increased resolution alone does not improve model defects
Theta‐burst stimulation (TBS) is a varied form of repetitive transcranial magnetic stimulation (rTMS) and has more rapid and powerful effects than rTMS. Experiments on the human motor cortex have ...demonstrated that intermittent TBS has facilitatory effects, whereas continuous TBS has inhibitory effects. Huang's simplified model provides a solid basis for elucidating such after‐effects. However, evidence increasingly indicates that not all after‐effects of TBS are as expected, and high variability among individuals has been observed. Studies have suggested that the GABAergic and glutamatergic neurotransmission play a vital role in the aforementioned after‐effects, which might explain the interindividual differences in these after‐effects. Herein, we reviewed the latest findings on TBS from animal and human experiments on glutamatergic and GABAergic neurotransmissions in response to TBS. Furthermore, an updated theoretical model integrating glutamatergic and GABAergic neurotransmissions is proposed.
This study explores responses to ketamine in patients with treatment-resistant depression (TRD) using a wearable forehead electroencephalography (EEG) device. We recruited and randomly assigned 55 ...outpatients with TRD into three approximately equal-sized groups (A: 0.5-mg/kg ketamine; B: 0.2-mg/kg ketamine; and C: normal saline) under double-blind conditions. The ketamine responses were measured by EEG signals and Hamilton depression rating scale scores. At baseline, the responders showed significantly weaker EEG theta power than the non-responders (p <; 0.05). Compared to the baseline, the responders exhibited higher EEG alpha power but lower EEG alpha asymmetry and theta cordance post-treatment (p <; 0.05). Furthermore, our baseline EEG predictor classified the responders and non-responders with 81.3 ± 9.5% accuracy, 82.1 ± 8.6% sensitivity, and 91.9 ± 7.4% specificity. In conclusion, the rapid antidepressant effects of mixed doses of ketamine are associated with prefrontal EEG power, asymmetry, and cordance at baseline and early post-treatment changes. Prefrontal EEG patterns at baseline may serve as indicators of ketamine effects. Our randomized double-blind placebo-controlled study provides information regarding the clinical impacts on the potential targets underlying baseline identification and early changes from the effects of ketamine in patients with TRD.
Excessive glutamate release has been linked to stress and many neurodegenerative diseases. Evidence indicates abnormalities of glutamatergic neurotransmission or glutamatergic dysfunction as playing ...an important role in the development of many major psychiatric disorders (e.g., schizophrenia, bipolar disorder, and major depressive disorder). Recently, ketamine, an
-methyl-d-aspartate antagonist, has been demonstrated to have promisingly rapid antidepressant efficacy for treatment-resistant depression. Many compounds that target the glutamate system have also become available that possess potential in the treatment of major psychiatric disorders. In this review, we update evidence from recent human studies that directly or indirectly measured glutamatergic neurotransmission and function in major psychiatric disorders using modalities such as magnetic resonance spectroscopy, positron emission tomography/single-photon emission computed tomography, and paired-pulse transcranial magnetic stimulation. The newer generation of antidepressants that target the glutamatergic system developed in human clinical studies is also reviewed.
Background and aims
Nicotine is a highly addictive substance in tobacco products that dysregulates several neurotransmitters in the brain and impairs executive function. Non‐invasive brain ...stimulation (NIBS) methods such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising treatments for nicotine dependence. We investigated the efficacy and acceptability of NIBS in managing smoking cessation through a systematic review and network meta‐analysis (NMA).
Methods
We conducted a systematic review to identify randomized controlled trials (RCTs) that investigated the efficacy of NIBS for smoking cessation. All pairwise meta‐analyses and NMA procedures were conducted using random‐effects and frequentist models. The co‐primary outcomes were (1) the change in number of cigarettes smoked per day (change in frequency of smoking) in patients with nicotine dependence after NIBS and (2) acceptability (the dropout rate). The effect sizes for co‐primary outcomes of change in frequency of smoking and acceptability were assessed according to standardized mean difference (SMD) and odds ratio, respectively.
Results
Twelve RCTs with 710 participants (mean age: 44.2 years, 31.2% female) were included. Compared with the sham control, 10‐Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) was associated with the largest changes in smoking frequency SMD = −1.22, 95% confidence interval (95% CI) = −1.77 to −0.66. The 2‐mA bifrontal tDCS (SMD = −0.97, 95% CI = −1.32 to −0.62) and 10‐Hz deep rTMS over the bilateral DLPFC with cue provocation (SMD = −0.77, 95% CI = −1.20 to −0.34) were associated with a significantly larger decrease in smoking frequency versus the sham. None of the investigated NIBSs was associated with dropout rates significantly different from those of the sham control groups.
Conclusion
Prefrontal non‐invasive brain stimulation interventions appear to reduce the number of cigarettes smoked with good acceptability.
Increasing evidence suggests that patients with bipolar disorder are more likely to develop malignant cancer than in the general population. However, the overall cancer risk in the unaffected ...siblings of such patients remains unknown. From the National Health Insurance Research Database of Taiwan, 25 356 patients with bipolar disorder, 25 356 age‐matched unaffected siblings of patients with bipolar disorder and 101 422 age‐matched controls without severe mental disorders between 1996 and 2010 were enrolled in our study. Patients who developed cancer between the time of enrollment and the end of 2011 were identified. Cancers were divided into three subgroups based on the related layer of embryonic development: ectodermal, mesodermal and endodermal cancers. Patients with bipolar disorder (odds ratio OR = 1.22, 95% confidence interval CI: 1.06, 1.40) and unaffected siblings of such patients (OR = 1.17, 95% CI 1.02, 1.34) had greater risk of developing malignant cancer than did controls. Furthermore, only those aged <50 years, for both patients with bipolar disorder (OR = 1.90, 95% CI 1.38, 2.61) and unaffected siblings (OR = 1.65, 95% CI 1.19, 2.28), were more likely to develop the ectodermal cancer, especially breast cancer, than the control group. The associations of bipolar disorder and susceptibility to bipolar disorder with increased cancer risk in the younger population may imply a genetic overlap in neurodevelopment and malignancy pathogenesis. Our findings may encourage clinicians to monitor cancer risk factors and warning signs closely in patients with bipolar disorder and unaffected siblings of such patients.
What's new?
Increasing evidence suggests that patients with bipolar disorder are more likely to develop malignant cancer than the general population. However, the overall cancer risk in the unaffected siblings of such patients remains unknown. This study found that patients with bipolar disorder and their unaffected siblings were more likely to develop cancer than controls without severe mental disorders. Furthermore, only participants aged <50 were more likely to develop ectodermal cancers. The findings imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.
Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved technique for treating medication-resistant depression. Conventional rTMS includes high frequency (HF) to left dorsolateral ...prefrontal cortex (DLPFC) and low frequency to right DLPFC. However, not all depressed patients could benefit from standard rTMS protocols. Meta-analytical evidence indicated that there was an average response rate of 29.3% for patients receiving the most commonly adopted HF rTMS to the left DLPFC. Hence, newer forms of rTMS paradigms are warranted to improve antidepressant response and remission rate in patients with depression, especially those who are refractory to adequate antidepressant trials. In the current chapter, we review newer forms of rTMS paradigms and the content will cover standard theta burst stimulation (TBS), prolonged iTBS (piTBS), accelerated rTMS (aTMS), deep TMS (dTMS), priming TMS (pTMS), synchronized TMS (sTMS), and magnetic seizure therapy (MST).
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