A growing body of evidence now proposes that machine learning and deep learning techniques can serve as a vital foundation for the pharmacogenomics of antidepressant treatments in patients with major depressive disorder (MDD). In this review, we focus on the latest developments for pharmacogenomics research using machine learning and deep learning approaches together with neuroimaging and multi-omics data. First, we review relevant pharmacogenomics studies that leverage numerous machine learning and deep learning techniques to determine treatment prediction and potential biomarkers for antidepressant treatments in MDD. In addition, we depict some neuroimaging pharmacogenomics studies that utilize various machine learning approaches to predict antidepressant treatment outcomes in MDD based on the integration of research on pharmacogenomics and neuroimaging. Moreover, we summarize the limitations in regard to the past pharmacogenomics studies of antidepressant treatments in MDD. Finally, we outline a discussion of challenges and directions for future research. In light of latest advancements in neuroimaging and multi-omics, various genomic variants and biomarkers associated with antidepressant treatments in MDD are being identified in pharmacogenomics research by employing machine learning and deep learning algorithms.

Neuroleptic malignant syndrome (NMS) is one of the most severe iatrogenic emergencies in clinical service. The symptoms including sudden consciousness change, critical temperature elevation and electrolytes imbalance followed by mutli-organ system failure were common in NMS. In addition to aggressive interventions with intravenous fluid resuscitation and antipyretics, several antidotes have been suggested to prevent further progression of the muscle damage. Dantrolene has been reported to be one of the most effective treatments for NMS. However, the adverse effects of dantrolene treatment for NMS have not yet been evaluated thoroughly. Here we report a young male patient with bipolar I disorder who developed NMS after rapid tranquilization with haloperidol. Dantrolene was given intravenously for the treatment of NMS. However, fever accompanied with local tenderness, hardness with clear border and swelling with heat over the patient's left forearm occurred on the sixth day of dantrolene treatment. Venous thromboembolism (VTE) over intravenous indwelling site at the patient's forearm was noted and confirmed by Doppler ultrasound. The patient's VTE recovered after heparin and warfarin thrombolytic therapy. To our knowledge, this is the first case report demonstrating the possible relationship between dantrolene use and VTE in a patient with antipsychotic treatment. Although the causal relationship and the underlying pathogenesis require further studies, dantrolene should be used with caution for patients with NMS.
Antidotes ; Antipyretics ; Consciousness ; Dantrolene* ; Electrolytes ; Emergencies ; Fever ; Forearm ; Haloperidol ; Hardness ; Heparin ; Hot Temperature ; Humans ; Male ; Neuroleptic Malignant Syndrome* ; Resuscitation ; Thrombolytic Therapy ; Ultrasonography ; Venous Thromboembolism* ; Warfarin

Low bone mineral density (BMD) and osteoporosis are common in patients with schizophrenia and detrimental to illness prognosis and life quality. Although the pathogenesis is not fully clear, series of studies have revealed factors related to low BMD such as life style, psychotic symptoms, medication use and the activity of bone absorption markers. It has been known that antipsychotic-induced hyperprolactinemia plays a critical role on decreased BMD. However, it remains uncertain whether the risk factors differ between men and women. According to the effect on prolactin, antipsychotics can be classified into two groups: prolactin-sparing (PS) and prolactin-raising (PR). Our previous study has demonstrated that clozapine which is among the PS antipsychotics is beneficial for BMD when compared with PR antipsychotics in women with chronic schizophrenia. We have also found that risks factors associated with low BMD are different between men and women, suggesting that gender-specific risk factors should be considered for intervention of bone loss in patients with schizophrenia. This article reviews the effects of antipsychotics use on BMD with particular discussion for the differences on gender and age, which implicate the alterations of sex and other related hormones. In addition, currently reported protective and risk factors, as well as the effects of medication use on BMD including the combination of antipsychotics and other psychotropic agents and other potential medications are also reviewed.
Absorption ; Antipsychotic Agents* ; Bone Density* ; Clozapine ; Female ; Humans ; Hyperprolactinemia ; Life Style ; Male ; Osteoporosis ; Prognosis ; Prolactin ; Quality of Life ; Risk Factors ; Schizophrenia*

Objective: Melatonin has been considered to have an essential role in the pathophysiology of Alzheimer’s disease (AD) for its regulatory function on circadian rhythm and interaction with glutamate for the modulation of learning and memory. Previous studies revealed that melatonin levels decreased in patients with AD. However, melatonin supplement didn’t show promising efficacy for AD. This study compared trough melatonin levels among elderly people with different severities of cognitive deficits. Methods: We enrolled 270 elder individuals (consisting four groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild AD, and moderate-severe AD) in the learning cohort. Trough melatonin levels in plasma were measured using ELISA. Cognitive function was evaluated by Clinical Dementia Rating Scale (CDR) and Mini-Mental State Examination (MMSE). An independent testing cohort, also consisting of four groups, was enrolled for ascertainment. Results: In the learning cohort, trough melatonin levels decreased in the MCI group but elevated in the mild and moderate to severe AD groups. Trough melatonin levels were associated with CDR and MMSE in MCI or AD patients significantly. In the testing cohort, the results were similar to those in the learning cohort. Conclusion This study demonstrated that trough melatonin levels in the peripheral blood were decreased in MCI but increased with the severity of AD. The finding supports the trials indicating that melatonin showed efficacy only in MCI but not in AD. Whether trough melatonin level has potential to be a treatment response biomarker for AD, especially its early phase needs further studies.

Early detection and prevention of Alzheimer's disease (AD) is important. The current treatment for early AD is acetylcholine esterase inhibitors (AChEIs); however, the efficacy is poor. Besides, AChEI did not show efficacy in mild cognitive impairment (MCI). Beta-amyloid (Aβ) deposits have been regarded to be highly related to the pathogenesis of AD. However, many clinical trials aiming at the clearance of Aβ deposits failed to improve the cognitive decline of AD, even at its early phase. There should be other important mechanisms unproven in the course of AD and MCI. Feasible biomarkers for the diagnosis and treatment response of AD are lacking to date. The N-methyl-D-aspartate receptor (NMDAR) activation plays an important role in learning and memory. On the other hand, oxidative stress has been regarded to contribute to aging with the assumption that free radicals damage cell constituents and connective tissues. Our recent study found that an NMDAR enhancer, sodium benzoate (the pivotal inhibitor of D-amino acid oxidase [DAAO]), improved the cognitive and global function of patients with early-phase AD. Further, we found that peripheral DAAO levels were higher in patients with MCI and AD than healthy controls. We also found that sodium benzoate was able to change the activity of antioxidant. These pieces of evidence suggest that the NMDAR function is associated with anti-oxidation, and have potential to be biomarkers for the diagnosis and treatment response of AD.

Early detection and prevention of Alzheimer's disease (AD) is important. The current treatment for early AD is acetylcholine esterase inhibitors (AChEIs); however, the efficacy is poor. Besides, AChEI did not show efficacy in mild cognitive impairment (MCI). Beta-amyloid (Aβ) deposits have been regarded to be highly related to the pathogenesis of AD. However, many clinical trials aiming at the clearance of Aβ deposits failed to improve the cognitive decline of AD, even at its early phase. There should be other important mechanisms unproven in the course of AD and MCI. Feasible biomarkers for the diagnosis and treatment response of AD are lacking to date. The N-methyl-D-aspartate receptor (NMDAR) activation plays an important role in learning and memory. On the other hand, oxidative stress has been regarded to contribute to aging with the assumption that free radicals damage cell constituents and connective tissues. Our recent study found that an NMDAR enhancer, sodium benzoate (the pivotal inhibitor of D-amino acid oxidase [DAAO]), improved the cognitive and global function of patients with early-phase AD. Further, we found that peripheral DAAO levels were higher in patients with MCI and AD than healthy controls. We also found that sodium benzoate was able to change the activity of antioxidant. These pieces of evidence suggest that the NMDAR function is associated with anti-oxidation, and have potential to be biomarkers for the diagnosis and treatment response of AD.

Purpose: Protective ileostomy and colostomy are performed in patients undergoing low anterior resection with a high leakage risk. We aimed to compare surgical, medical, and daily care complications between these 2 ostomies in order to make individual choice. Methods: Patients who underwent low anterior resection for rectal tumors with protective stomas between January 2011 and September 2018 were enrolled. Stoma-related complications were prospectively recorded by wound, ostomy, and continence nurses. The cancer stage and treatment data were obtained from the Taiwan Cancer Database of our Big Data Center. Other demographic data were collected retrospectively from medical notes. The complications after stoma creation and after the stoma reversal were compared. Results: There were 176 patients with protective colostomy and 234 with protective ileostomy. Protective ileostomy had higher proportions of high output from the stoma for 2 consecutive days than protective colostomy (11.1% vs. 0%, P<0.001). Protective colostomy resulted in more stoma retraction than protective ileostomy (21.6% vs. 9.4%, P=0.001). Female, open operation, ileostomy, and carrying stoma more than 4 months were also significantly associated with a higher risk of stoma-related complications during diversion. For stoma retraction, the multivariate analysis revealed that female (odds ratio [OR], 4.00; 95% confidence interval [CI], 2.13–7.69; P<0.001) and long diversion duration (≥4 months; OR, 2.33; 95% CI, 1.22–4.43; P=0.010) were independent risk factors, but ileostomy was an independent favorable factor (OR, 0.40; 95% CI, 0.22–0.72; P=0.003). The incidence of complication after stoma reversal did not differ between colostomy group and ileostomy group (24.3% vs. 20.9%, P=0.542). Conclusion We suggest avoiding colostomy in patients who are female and potential prolonged diversion when stoma retraction is a concern. Otherwise, ileostomy should be avoided for patients with impaired renal function. Wise selection and flexibility are more important than using one type of stoma routinely.

Purpose: Protective ileostomy and colostomy are performed in patients undergoing low anterior resection with a high leakage risk. We aimed to compare surgical, medical, and daily care complications between these 2 ostomies in order to make individual choice. Methods: Patients who underwent low anterior resection for rectal tumors with protective stomas between January 2011 and September 2018 were enrolled. Stoma-related complications were prospectively recorded by wound, ostomy, and continence nurses. The cancer stage and treatment data were obtained from the Taiwan Cancer Database of our Big Data Center. Other demographic data were collected retrospectively from medical notes. The complications after stoma creation and after the stoma reversal were compared. Results: There were 176 patients with protective colostomy and 234 with protective ileostomy. Protective ileostomy had higher proportions of high output from the stoma for 2 consecutive days than protective colostomy (11.1% vs. 0%, P<0.001). Protective colostomy resulted in more stoma retraction than protective ileostomy (21.6% vs. 9.4%, P=0.001). Female, open operation, ileostomy, and carrying stoma more than 4 months were also significantly associated with a higher risk of stoma-related complications during diversion. For stoma retraction, the multivariate analysis revealed that female (odds ratio [OR], 4.00; 95% confidence interval [CI], 2.13–7.69; P<0.001) and long diversion duration (≥4 months; OR, 2.33; 95% CI, 1.22–4.43; P=0.010) were independent risk factors, but ileostomy was an independent favorable factor (OR, 0.40; 95% CI, 0.22–0.72; P=0.003). The incidence of complication after stoma reversal did not differ between colostomy group and ileostomy group (24.3% vs. 20.9%, P=0.542). Conclusion We suggest avoiding colostomy in patients who are female and potential prolonged diversion when stoma retraction is a concern. Otherwise, ileostomy should be avoided for patients with impaired renal function. Wise selection and flexibility are more important than using one type of stoma routinely.