This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
"Zoletil 50" is a veterinary anesthetic, a compound preparation of tiletamine and zolazepam. This report describes a case involving mental and behavioral abnormalities after prolonged use of this drug. The patient had been regularly inhaling "Zoletil 50" nasally for 4 months. Following inhalation, symptoms emerged including abundant visions, dissociation, ataxia, muscle jerking, inability to walk and lung infection, along with changes of consciousness. The symptoms were eventually relieved through the administration of benzodiazepines, low-dose antipsychotic medications, and other medications. This case illustrates the potential mental effects of inhaling "Zoletil 50" and may help clinical physicians identify and manage similar psychotic disorders resulting from the use of this veterinary anesthetic.
Klein-Levin syndrome (KLS) is a rare disease characterized by recurrent episodes of hypersomnia and cognitive and behavioral dysfunction. In addition, all functions remain intact during the intermittent period. Infection is a common risk factor for its onset. In this case, a 17-year-old patient with KLS was admitted to our hospital in March 2023 who first developed KLS symptoms and relapsed after being infected with influenza A Virus (H1N1). Based on the typical symptoms occurred during the patient′s attack, the absence of symptoms and signs during the interval, and the absence of other triggers, the patient was diagnosed with KLS recurrence secondary to influenza A Virus (H1N1). This case report aims to reveal that influenza A Virus (H1N1) may be contribute to the recurrence of KLS and that preventing infection is important in the treatment of KLS to draw the attention of clinical physicians.
Objective:This study aims to explore the expression characteristics of mitochondrial function-related genes in patients with manic episodes of bipolar disorder and the correlation between differentially expressed genes and clinical metabolic indicators.Methods:Twenty patients with manic episodes of bipolar disorder (patient group) and 20 healthy controls (control group) were included. Quantitative real-time PCR was used to detect mitochondrial quality control and oxidative phosphorylation-related gene expression in peripheral blood leukocytes, and several metabolic indicators were collected. Mann-Whitney test or independent sample t-test was used for comparison between groups. Spearman correlation test was used to analyze the correlation between gene expression and metabolic indicators. Results:Mitochondria function-related genes, including NRF2, P62, MFN1, MFN2, YME1L, MFF, MTATP8, and AIF, were significantly lower in patients with bipolar disorder than in healthy controls ( P<0.05, U=86, 90, 97, 93, 106, 89, 93, 105, FDR=0.038). The expression level of MTATP8 was negatively correlated with BMI, total cholesterol, and globulin level in the patient group ( r=-0.49, -0.58, -0.46, P=0.028, 0.009, 0.050). The expression level of MFF was significantly negatively correlated with waist circumference in healthy controls ( r=-0.53, P=0.020) and with globulin level in the patient group ( r=-0.48, P=0.040). The expression level of AIF was significantly and positively correlated with high-density lipoprotein cholesterol in healthy controls ( r=0.53, P=0.036). Conclusion:The expression of several genes involved in mitochondrial quality control and oxidative phosphorylation processes was significantly downregulated, and differentially expressed genes were significantly associated with metabolic index, suggesting that mitochondrial dysfunction may be related to the high risk of metabolic disease in patients with manic episodes of bipolar disorder.
Mood disorders are a group of mental conditions characterized by significant and lasting mood or emotional changes, which seriously affect patients′ normal lives. However, the pathogenesis of mood disorders is still unclear, and the specific biological markers to assist the diagnosis are still not determined, and this affects the diagnosis, treatment and prognosis. With the development of molecular imaging, positron emission tomography (PET) has been widely used in clinical research on mood disorders, which is helpful for their clinical diagnosis and treatment. This paper aims to review the research progress on PET imaging principles, the pathogenesis and treatment mechanism of mood disorders, and to summarize the application prospect of PET in mood disorders.
