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.
Aiming to improve the standardized screening, diagnosis, and treatment of depressive disorders in China, promote the standardization of clinical practice, and enhance the prevention and intervention of depressive disorders in China, the Chinese Society of Psychiatry of the Chinese Medical Association, and the National Center for Mental Disorders & the National Clinical Research Center for Mental Disorders(affiliated with The Second Xiangya Hospital of Central South University and Beijing Anding Hospital, Capital Medical University)have jointly initiated the Chinese Guideline for the Diagnosis and Treatment of Depressive Disorders: 2024 Edition. The Peking University Center for Evidence-Based Medical and Clinical Research will provide methodological support. The Guidelines Development Committee will follow international standards for developing and reporting guidelines, build a multidisciplinary team of experts, and adopt the GRADE method to develop an evidence-based guideline for the prevention and management of depressive disorders in China. This proposal introduces the significance and purpose of developing a new edition of the guideline, the methods of evidence retrieval and quality evaluation, the process of guideline development, and the plan for publication, implementation, and dissemination of the guideline.
Pinealoma often comorbid with obstructive hydrocephalus due to their specific location and type, therefore, patients with pinealoma need to be treated by a combined ventriculoperitoneal shunt (VPS) along with surgical resection. Shunt failure is the most common complication after surgery. In this paper, we report a case of obstructive hydrocephalus caused by shunt obstruction after pineal gland tumor resection combined with ventriculoperitoneal shunt. The patient first showed low mood, decreased interest and energy, and gradually developed into manifestations of less eating, less talking, less movement, repeated psychiatric visits, and showed no improvement after treatment with antidepressants. The purpose of the current study is to increase the knowledge of these diseases and reduce misdiagnosis.
Ketamine at sub-anesthetic doses has rapid and potent antidepressant properties. Its enantiomers also exhibit the same antidepressant effect. However, the adverse reactions to ketamine, such as dissociative symptoms, nausea, headaches, dizziness, hallucinations, taste disorders, and transient blood pressure elevation, still limit its widespread use. Dissociation is a common side effect of both ketamine and S-ketamine. The mechanism of dissociation and its correlation with the antidepressant effect has received considerable attention. This review focuses on the relationship between dissociation and antidepressant effect, and how to manage dissociative symptoms.
Objective:This study explored whether digital multi-dimensional parent-child training combined with medication is more effective than medication alone in treating symptoms and social function in children with attention deficit hyperactivity disorder (ADHD).Methods:In this pre-post parallel controlled study from October 2020 to August 2022, 192 children diagnosed with ADHD based on DSM-5 criteria were selected from three hospitals: Chaohu Hospital of Anhui Medical University, the Second Affiliated Hospital of Anhui Medical University, and the Fourth People′s Hospital of Hefei City. Subjects were 6-15 years old (140 males, 52 females) and divided into study ( n=125) and control ( n=67) groups based on guardian preferences. The study group received 12 weeks of digital multi-dimensional parent-child training at 5 times weekly plus medication; and the control group received medication only. Symptoms, behavior, executive function, emotions, and social function were evaluated at baseline and study end by using five standardized scales: Swanson,Nolan,and Pelham-Ⅳ Rating Scale-Parent Version (SNAP-Ⅳ-P), Parent Symptom Questionnaire (PSQ), Behavior Rating Inventory of Executive Function-Parent Version (BRIEF-P), Strengths and Difficulties Questionnaire-Parent Version (SDQ-P), Weiss Functional Impairment Rating Scale-Parent Report(WFIRS-P). Independent-sample t-test was used to compare the differences at baseline between the two groups, and a t-test of paired samples was used to compare the differences before and after the intervention within both groups accordingly. The covariance analysis was used to compare the differences between the two groups after intervention. Results:Compared to the baseline, the study group showed statistically significant differences in the scores of SNAP-Ⅳ-P (1.1±0.5 vs 0.8±0.4), PSQ (33.6±20.3 vs 26.4±15.3), BRIEF-P (158.7±37.3 vs 151.2±33.8), SDQ-P (19.6±6.7 vs 15.9±5.1), and WFIRS-P (29.4±16.8 vs 24.3±14.6) after 12 weeks of treatment (all P<0.001), but there was no significant difference between the two groups in SNAP-IV-P and PSQ with its all dimensions ( F=0.85, P=0.357; F=0.01, P=0.956, all P>0.05); the study group had significantly lower scores in total BRIEF-P (151.2±33.8 vs 180.9±23.3) and the dimensions of inhibition, conversion, task initiation, working memory, planning and tissue score ( F=38.63, P<0.05); the SDQ-P (15.9±5.1 vs 22.1±5.5) and its subscales of emotional symptoms, conduct problems, peer communication problems and social behavior scores were significantly lower in the study group than the control group ( F=45.28, P<0.001); the WFIRS-P (24.3±14.6 vs 35.1±12.5) and its all dimensions were also lower in the study group ( F=57.22, P<0.01). Conclusion:Digital multi-dimensional parent-child training combined with drug therapy is more effective than medication alone for ADHD children, particularly in improving executive function, emotional problems and social function.
To standardize clinical treatment decisions and improve the comprehensive diagnosis and treatment of bipolar disorder in China, the Psychiatric Branch of the Chinese Medical Association initiated the Guidelines for the Prevention and Treatment of Bipolar disorder in China (2025 edition). This protocol summary describes the background and purpose of the guideline, the formulation method, working group members, division of responsibilities, guideline registration, conflicts of interest, collection and selection of clinical issues, the evidence-based foundation of the guideline, writing and external review, as well as publishing, dissemination, and other aspects.
Objective:The current study aims to explore the factors related to the efficacy of cognitive behavior therapy for insomnia (CBT-I) from the perspective of patients and to provide references for more effective implementation of CBT-I.Methods:Using qualitative research methods, 21 insomnia patients with depression/anxiety were treated with CBT-I for 8 consecutive times. Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Scale (HAMD 17), and Hamilton Anxiety Scale (HAMA) were assessed at baseline and the end of the 8th week of treatment. The paired sample t-test was conducted. Semi-structured interviews were performed at week 2, week 4, and week 8 respectively and thematic analysis was used to code and analyze the interview data. Results:Compared with baseline data, the symptoms of insomnia (13.6±2.0 vs. 6.9±2.4), depression (14.6±5.5 vs. 5.0±3.6), and anxiety (17.2±3.4 vs. 5.3±3.9) were significantly improved after 8 weeks of CBT-I treatment ( t=-3.31, -3.19, -2.94, all P<0.01). The patient factors influencing the efficacy of CBT-I were treatment expectation and approval, motivation, compliance, and internalization of treatment content. The therapist factors were professionalism, well-directed, treatment style, supervision, and giving hope. Conclusion:Compliance and high levels of participation of the patients can benefit the treatment efficacy of CBT-I. Therapists should have sufficient experience, stimulate patients′ motivation, improve patients′ compliance, and carry out adequate psychological education in the early stage to increase the efficacy of CBT-I.
Objective:This study aims to develop a scale for ruminative tendency and style in Chinese adolescents and tests its reliability and validity.Methods:Referring to the stress-reactive model, the goal progress theory, and problem-solving theory, ruminative tendency and style were defined and differentiated, based on which the Ruminative Tendency-style Scale for Adolescents was developed and validated. In May 2022, 499 adolescents from a middle school in Sichuan province participated in the preliminary survey, during which the scale items were selected through item analysis. In November 2022, the main survey was conducted on 1 299 adolescents in a junior high school in Beijing. The Cronbach α coefficient was used to evaluate the internal consistency reliability, while the Pearson correlation analysis was used to verify the retest reliability. A structured equation model was applied to verify the structural validity of the scale by using the AMOS software. The Pearson correlation analysis was used to test criterion validity with the Trait Depression Scale (STDEP) and the conscientiousness of the Chinese Big Five Personality Inventory-brief version (CBF-PI-B) as the criterion.Results:The ruminative tendency subscale contained 3 factors constructed from 19 items. The ruminative style subscale contained 3 factors constructed from 16 items. For the total score and each factor score of the ruminative tendency subscale, Cronbach′s α coefficients ranged from 0.776 to 0.951 and the test-retest reliabilities ranged from 0.704 to 0.807. For the total score and each factor score of the ruminative style subscale, the Cronbach′s α coefficients ranged from 0.785 to 0.904 and the test-retest reliabilities ranged from 0.719 to 0.846. The confirmatory factor analysis showed that the normed fit index (NFI), incremental fit index (IFI), Tucker-Lewis index (TLI), and comparative fit index (CFI) of two subscales were>0.9 and the value of root mean square error of approximation (RMSEA) and the standardized root mean square residual (SRMR) of two subscales were less than 0.08, indicating great construct validity of these two scales. The correlation coefficients between the total score and each factor score of the ruminative tendency subscale and the trait depression scale ranged from 0.364 to 0.612. The correlation coefficients between the total score and each factor score of the ruminative style subscale and the conscientiousness score ranged from 0.336 to 0.587, indicating that the criterion validity was satisfactory.Conclusion:The Ruminative Tendency-style Scale for Adolescents scale has good reliability and validity. It is an effective tool to measure the ruminative tendencies and ruminative style in Chinese adolescents.
Schizophrenia is a type of mental illness characterized by delusions and hallucinations. Computational psychiatry, as a novel clinical approach, integrates principles and theories from multiple disciplines such as computational anatomy and cognitive neuroscience into research and practice of clinical psychiatry. By using hypothesis-driven or data-driven computational models, it explains the mechanisms of mental illnesses and improves or develops new treatment options. With the improvement of hardware levels such as artificial intelligence specific integrated circuit, neuroimaging and neuroelectrophysiology techniques, and the enhancement of model interpretability, a large number of models are applied to schizophrenia-related research. This review summarizes the hypotheses and data foundations of computational psychiatry related to schizophrenia and discusses the application of computational psychiatry research strategies in the study of schizophrenia.
Ten years have passed since the implementation of China′s Mental Health Law. This law stipulates the basic principle of involuntary hospitalization for patients with mental disorders and regulates the standards and procedures of involuntary hospitalization. The implementation of this law safeguards the primary legal rights of patients with mental disorders by legislation, sustainedly increases the resources of mental health services, promotes the improvement and development of the mental health service system, and popularizes mental health knowledge in public. At the same time, during the process of implementation of the law, some ambiguous spaces still exist. In this paper, we elaborate on the problems and confusions we encountered at work to provide references for the revision of the law.
This article describes a female patient with treatment-resistant schizophrenia (TRS) who experienced persistent auditory hallucinations and self-laughter. Despite receiving adequate amounts and courses of risperidone and aripiprazole, the patient′s symptoms remained poorly controlled. The combined use of amisulpride and olanzapine resulted in hypotension and elevated levels of amisulpride in the blood. However, after switching to bunanserin in combination with low-dose olanzapine, the patient′s symptoms improved significantly. This case report aims to guide the rational use of medication in TRS patients who have poor tolerance to traditional therapies.
Objective:This study aims to investigate the impact of individual and family factors on non-suicidal self-injury (NSSI) behaviors in adolescents with mood disorders.Methods:Adolescents with mood disorders were included according to the ICD-10 diagnostic criteria, while the NSSI behaviors were assessed according to the DSM-5. The patients were divided into mood disorders with ( n=147) and without NSSI group ( n=56). Healthy adolescents were included as the control group ( n=107). The General Information Questionnaire, the Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, the Emotion Regulation Difficulties Scale, the Childhood Trauma Questionnaire, and the Parenting Style Scale were assessed. The three groups were compared using the χ 2 test and the analysis of variance, while the difference between two groups was compared using the t-test. Multiple logistic regression was used to explore the influence of various factors on NSSI behaviors. Results:Patients in the mood disorder with NSSI group scored significantly higher on depression, difficulties in emotion regulation, emotional abuse, and parental control than those in the mood disorder without NSSI group and the healthy control group. The multiple logistic regression analysis revealed that NSSI behaviors were positively correlated with depression ( OR=1.407, P<0.001), emotional abuse ( OR=1.186, P=0.03), and maternal encourage autonomy ( OR=1.302, P=0.035), and negatively correlated with paternal encourage autonomy ( OR=0.805, P=0.038), maternal care ( OR=0.731, P=0.025), and adolescent′s age (OR=0.656, P<0.001); adolescent′s age ( OR=0.851, P=0.042), paternal age ( OR=0.891, P=0.049) and male gender ( OR=0.435, P=0.040) were negatively correlated with NSSI behaviors. Conclusions:Gender, age, depression level, emotion regulation ability, personality traits, and parenting style had significant effects on adolescents′ NSSI behaviors.
Objective:This study investigates the difference in the detection rate and symptomatology between ICD-10 and DSM-5 diagnostic criteria for bipolar disorder with mixed states.Methods:Based on the Phase Ⅰ (2012) and Phase Ⅱ (2021) databases of National Bipolar Mania Pathway Survey (BIPAS), patients with bipolar disorder were included. General demographic data, clinical characteristics, symptomatic phenotypes, and mixed characteristics were retrieved. The detection rates and symptomatic performances of patients with or without mixed states in Phase Ⅰ and Ⅱ were compared using the chi-square test.Results:For patients with mixed states, the detection rate during Phase Ⅱ (2021) using DSM-5 (18.79%, 199/1 059) criteria was significantly higher than that during Phase Ⅰ (2012) using ICD-10 (6.78%, 199/2 934; χ 2=125.05, P<0.001). Whether using ICD-10 or DSM-5 criteria, patients with mixed states had a significantly higher frequency of multiple symptomatic manifestations. Conclusion:The DSM-5 diagnostic criteria generate a high detection rate for bipolar disorder with mixed states. The clinical phenotypes of bipolar disorder with mixed states vary significantly using different diagnostic tools.
Objective:This study aims to explore the abnormal instantaneous coactivation pattern of the key nodes of default mode network (DMN) and its relationship with social deficits in participants with autism spectrum disorder (ASD).Methods:This study included participants (ASD: n=354, healthy control (HC): n=446) from the Autism Brain Imaging Data Exchange (ABIDE), which is a multi-center and large-sample resting-state functional magnetic resonance imaging (rs-fMRI) database. Coactivation pattern (CAP) analysis was used to explore the coactivation pattern characteristics of medial prefrontal cortex (mPFC), the key node of DMN, and its abnormal interaction with other key nodes of DMN as well as task-positive network. Network dissociation index (NDI) was used to capture the extent of functional dissociation within and between networks and predict the clinical symptoms of ASD based on multi-variable support vector regression. Results:When mPFC was activated, precuneus, another key node of DMN, showed lower activation in participants with ASD than those in the HC group ( t=-4.21, P<0.01). Instead, dorsal anterior cingulate cortex (dACC) and orbital fronto-insula junction, key nodes of the salience network (SN), showed higher activation in participants with ASD than those in the HC group ( t=2.93, 2.61, all P<0.05). Additionally, compared with HC, ASD showed significantly higher NDI within DMN ( t=3.63, P<0.01) and significantly lower NDI between DMN and SN (dACC and orbital fronto-insula junction) ( t=-2.97, -3.31, all P<0.01). Additionally, using multi-variable support vector regression model, altered NDI could well predict social, speech communication deficits and disease severity of ASD ( r=0.191,0.216,0.186, all P<0.01). Conclusion:The CAP of mPFC in ASD in resting state was abnormal, which reflected the decreased functional integration within DMN and the decreased functional segregation between DMN and task-positive network. Besides, this abnormal network function pattern was closely related to clinical symptoms of ASD.
Recent studies have shown that abnormal high-frequency brain activity represented by γ rhythms in schizophrenia severely affects patients′ low-level sensory processing and higher cognitive functions. The neurophysiological mechanisms of abnormal γ oscillations in schizophrenia patients, the progress of research on the EEG characteristics based on abnormal γ oscillations, the correlation between abnormal γ oscillations and symptoms, and the effects of different treatments on abnormal γ oscillations are comprehensively reviewed in this paper, and the current research status and problems are summarized to provide strong support for the clinical diagnosis and treatment of schizophrenia.
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder in children. Its clinical symptoms are diverse and often remain lifelong, resulting in uncertainty in adult outcomes. So far, there are few studies on ASD in adults. However, most patients, in their adulthood, have a high incidence of mental health problems, poor work prospects, and poor social function, which are susceptible to a variety of factors. These are urgent to be solved in clinical practice. By summarizing the clinical characteristics of ASD in adults and analyzing its outcomes and influencing factors, this article helps to improve the understanding of ASD in medical workers and to provide a reference for the diagnosis, treatment, and outcome improvement of ASD.
