Annals of General Psychiatry最新文献

The 5-hydroxytryptamine receptor (5-HTR) is a key protein responsible for the effects of 5-hydroxytryptamine (5-HT) and an important target for many antipsychotics. 5-HTR has a high degree of genetic polymorphism, and atypical antipsychotics are 5-HTR antagonists widely used in treating schizophrenia. With the increasing development of medical technology, antipsychotics are being updated rapidly, and their efficacy and safety are being optimised. However, owing to the complexity of patients' genetic polymorphisms and psychiatric disorders, there are still individual differences in clinical efficacy. This article reviews the typing of 5-HTR, a common target of clinical atypical antipsychotics, and the effects of 5-HTR gene single nucleotide polymorphisms (SNPs) on the efficacy of atypical antipsychotics. Specific genotypes of six types of 5-HTR genes are associated with differential responses to atypical antipsychotics, which may help guide the development of individualized clinical treatments for patients with schizophrenia.

Depression is associated with a significant burden on individuals, families, and communities. It leads to impaired social and occupational functioning, increased disability, decreased quality of life, and higher mortality rates, often due to suicide. A recent estimate from the World Health Organization (WHO) states that over 280 million people of all ages suffer from depression, which equals approximately 3.8% of the world population. Despite effective treatments for mental disorders, a dire treatment gap persists. This treatment gap could be reduced by effective and available diagnostic methods that have the potential to aid in depression diagnosis, stratification of patient subgroups, and treatment monitoring. In this regard, salivary hormones have been studied as potential markers for different types and etiologies of depression due to the convenience of non-invasive sample collection and their correlation with certain aspects of mood and mental health. The literature suggests they can help clinicians assess an individual's stress response, hormonal imbalances, and treatment response, leading to more personalized and effective interventions. In this review, we offer an up-to-date look at all studied salivary hormones associated with depression, including Cortisol, Melatonin, Oxytocin, Serotonin, Dehydroepiandrosterone, Testosterone, Progesterone, and Estradiol.

Introduction: Ostracism increases the risk of depression and suicidal behaviors. Mindfulness training, which is at the core of third-wave behavioral therapies such as acceptance and commitment therapy (ACT), might reduce social distress and inhibit negative affect.

Methods: This randomized controlled trial included 32 patients with a history of suicide attempt in the past year who followed seven weekly sessions of ACT or progressive relaxation therapy (PRT). To assess and compare the effects of ACT and PRT on social distress, patients performed a validated paradigm of social exclusion (the Cyberball Game) followed by completion of the Need Threat Scale (NTS) at inclusion (baseline) and within two weeks after the intervention ended (posttherapy).

Results: The included patients were mainly women (N = 28; 87.5%), and their mean age was 40 years (SD: 12 years). Twenty-six patients (81%) experienced current depression. The postintervention NTS score was greater (lower social distress) in the ACT group than in the PRT group (group × time interaction; β = 0.47, p < 0.05), even after controlling for depressive symptoms (β = 0.27, p < 0.05). The NTS score change (between baseline and posttherapy) was correlated with changes in dispositional mindfulness (r = 0.46, p = 0.03), cognitive fusion (r = - 0.61, p < 10^-3) and acceptance (r = 0.57, p < 10^-2).

Conclusion: ACT decreased social pain independently of its effect on depression. Reduced social pain was correlated with improved therapeutic processes and decreased suicidal ideation, highlighting the therapeutic potential of ACT for managing ostracism and suicide risk.

Introduction: Misdiagnosis of bipolar disorder (BD) can lead to ineffective treatment, increased risk of manic episodes, and increased severity. Objective diagnostic tests or precise tools to diagnose BD and distinguish it from major depressive disorder (MDD) in depressed patients are lacking.

Aim: To assess the external diagnostic validity of a blood-based test using an RNA epigenetic signature for the differential diagnosis of BD versus MDD in patients with depression.

Methods and analysis: Multicentre cross-sectional study including an adult sample of inpatients or outpatients diagnosed with BD or MDD, currently treated for a major depressive episode. A structured diagnostic interview based on validated scales will be conducted. Sociodemographic variables, clinical history, toxic consumption, current treatment and quality of life will be assessed. Blood samples will be obtained and stored at -80 °C until RNA sequencing analysis. The EDIT-B is a blood-based test that combines RNA editing biomarkers and individual data (e.g., age, sex, and tobacco consumption). The clinical validation performance of the EDIT-B will be evaluated using the area under the curve, sensitivity, specificity, positive and negative predictive values, and likelihood ratios.

Ethics and dissemination: The principles of the Declaration of Helsinki 2013, precision psychiatry research and good clinical practice will be followed. The Research Ethics Committees of the participating centres approved the study. Participants will receive an information sheet and must sign the informed consent before the interview. Participants' data will be pseudonymized at the research sites. Any publication will use fully anonymized data. Publications with the final study results will be disseminated in international peer-reviewed journals and presented at international conferences.

Study registration: This study has been registered on clinicaltrials.gov (NCT05603819). Registration date: 28-10-2022.

Objective: This study examined mental health literacy and predictors of disorder recognition among primary care providers (PCPs) in Hungary.

Methods: 208 PCPs in Hungary completed a survey assessing demographics, mental health stigma, and exposure to mental health (i.e., personal experiences and having a family member/friend with a mental health condition). Participants read six vignettes describing obsessive-compulsive disorder (OCD) harm/aggression subtype (OCD-Aggression), OCD order/symmetry subtype (OCD-Order), generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder (PD), and major depressive disorder (MDD) and were asked to identify each condition, perceived disorder causes, and provide treatment referrals. Descriptive analyses were used to characterize disorder recognition rates, perceived disorder causes, and treatment referrals. Binary logistic regression analyses were conducted to examine the degree to which demographic characteristics, mental health stigma, and exposure to mental health conditions predict accurate disorder recognition.

Results: Identification rates for each vignette were: OCD-Aggression (27.9%), OCD-Order (75.5%), SAD (34.1%), GAD (76.0%), PD (78.8%), and MDD (91.3%). First-choice treatment referrals were a psychiatrist for OCD-Aggression (63.0%), OCD-Order (53.8%), and MDD (46.6%), a psychologist/therapist for SAD (58.7%) and GAD (48.6%), and a PCP for PD (39.9%). Mislabeling conditions was significantly associated with older age (for GAD, OCD-Aggression, PD and MDD), male gender (for GAD), greater mental health stigma (for OCD-Order), and lack of exposure to mental health conditions (for SAD).

Conclusions: Findings highlight strengths (e.g., depression recognition) and limitations in knowledge of mental health conditions among PCPs in Hungary and identifies targets to address to improve mental health literacy.

Background: Atypical antipsychotics are a common treatment for serious mental illness, but many are associated with adverse effects, including weight gain and cardiovascular issues, and real-world experience may differ from clinical trial data. Cariprazine has previously demonstrated a favorable safety and tolerability profile in clinical trials. Here, we evaluated the effects of cariprazine on body weight and blood pressure for bipolar I disorder (BP-I), schizophrenia, or as adjunctive treatment for major depressive disorder (MDD) using real-world data.

Methods: Symphony Health's Integrated Dataverse® with electronic medical record access (3/1/2015-10/31/2018) was used to identify adults (≥ 18 years) diagnosed with BP-I depression, BP-I mania/mixed, schizophrenia, or MDD, with ≥ 2 cariprazine dispensings (first dispensing = index) and continuous clinical activity for ≥ 12 months pre-index (baseline) and ≥ 3 months post-index. The on-treatment period spanned from index to cariprazine discontinuation, exposure to another atypical or long-acting injectable antipsychotic, or end of clinical activity/data availability. Outcomes included estimated annual linear trajectories for weight, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) during baseline and on treatment. Changes were estimated using linear mixed-effects models fitted over measurements pre-index and on treatment; 95% CIs were derived from nonparametric bootstrap procedures.

Results: The body weight analysis included 612 patients (BP-I, n = 331 [BP-I depression, n = 172; BP-I mania/mixed, n = 159]; schizophrenia, n = 75; MDD, n = 206). The mean patient age was 43.4 years, 75.2% were female, and the mean (SD) on-treatment period was 219 (185) days. Among patients with measurements before and during cariprazine treatment, estimated annual weight trajectories were + 3.55 (95% CI 2.38, 4.59) kg/year before cariprazine initiation and + 0.91 (- 1.17, 2.82) kg/year during cariprazine treatment. Additionally, annual linear trajectories evaluated across the on-treatment period were + 0.31 (- 0.42, 1.01) kg/m²/year for BMI, - 2.38 (- 4.27, - 0.76) mmHg/year for SBP, and - 0.57 (- 1.75, 0.61) mmHg/year for DBP.

Conclusion: In this real-world analysis, cariprazine was associated with an estimated weight gain of + 0.91 kg/year and had minimal impact on BMI and blood pressure when evaluated up to 12 months.

Schizophrenia is one of the most debilitating mental illnesses affecting any age group. The mechanism and etiology of schizophrenia are extremely complex and multiple signaling pathways recruit genes implicated in the etiology of this disease. While the role of Wnt/β-catenin signaling in this disorder has been verified, the impact of long noncoding RNAs (lncRNAs) associated with this pathway has not been studied in schizophrenia. The objective of this study was to examine the expression levels of Wnt/β-catenin-related lncRNAs, namely CCAT2, SNHG5, PTCSC3, and DANCR, as well as the CTNNB1 gene encoding beta-catenin protein in two groups of schizophrenia patients (drug-naïve and medicated) compared with healthy individuals. This study included 50 medicated patients in the remission phase of the disease, 25 drug-naive patients in the acute phase, and 50 control subjects. There was no significant difference in CTNNB1 gene expression in the medicated patients compared to controls (P value = 0.9754). However, the expression of this gene was significantly decreased in drug-naïve first-episode patients compared with controls (P value < 0.001). In contrast, expression of DANCR, PTCSC3, SNHG5, and CCAT2 genes was significantly higher in medicated (P values < 0.001, < 0.001, = 0.01, < 0.001, respectively) and drug-naive first-episode patients (P value < 0.001) compared to control subjects. ROC curve analysis revealed that DANCR, PTCSC3, SNHG5, and CCAT2 genes had diagnostic power with specificity and sensitivity of 80% and above in separation between study subgroups. In brief, our data demonstrated dysregulation of Wnt/β pathway related genes and lncRNAs in the peripheral blood of patients with schizophrenia and their potential as biomarkers for this disorder.

Background: Increased levels of emotion dysregulation and impulsive behavior are overlapping symptoms in adult Attention-Deficit/Hyperactivity Disorder (aADHD) and Borderline Personality Disorder (BPD), both symptom domains reflecting on inhibitory control, although from different angles. Our aims were to describe their differences in the above conditions, investigate their associations with childhood traumatization, and to explore the potential mediation of emotion dysregulation and impulsivity between childhood traumas and personality functioning.

Methods: Young adults between 18 and 36 years diagnosed with aADHD (n = 100) and BPD (n = 63) were investigated with structured clinical interviews, while age-matched healthy controls (n = 100) were screened for psychiatric disorders. Patients with aADHD-BPD comorbidity were excluded from further analyses. The Difficulties in Emotion Regulation Scale, the Barratt Impulsiveness Scale, the Level of Personality Functioning Scale, and the Childhood Trauma Questionnaire-Short Form were administered to investigate trait measures and childhood traumatization, respectively. Behavioral impulsivity and delay aversion were assessed using selected tests of the Cambridge Neuropsychological Test Automated Battery, and a computerized decision-making paradigm based on the Rogers decision-making task, respectively.

Results: Significantly higher levels of emotion dysregulation and impulsivity were present both in the aADHD and BPD groups, however with different profiles. Waiting and stopping impulsivity was selectively higher among aADHD patients compared to healthy controls. The BPD group reported higher levels of emotion dysregulation in all domains, and demonstrated increased delay aversion among uncertain conditions in decision-making. Higher levels of childhood trauma were associated with emotion dysregulation, trait impulsivity, and delay aversion across groups. Emotion regulatory capacity played a significant mediating role between childhood traumatization and the level of personality functioning.

Conclusions: Inhibitory control profiles of the aADHD and BPD groups were divergent. Childhood traumatization was associated with lower levels of personality functioning in adulthood, independently of diagnosis, an effect mediated more by emotion dysregulation, rather than impulsivity. These findings have various clinical implications for the treatment of aADHD and BPD, including psychoeducation, pharmacological interventions, and psychotherapy targeting specific symptom domains.

Background: Seizure threshold increases with age and the frequency of electroconvulsive therapy (ECT). Therefore, therapeutic seizures can be difficult to induce, even at maximum stimulus charge with available ECT devices. Such cases are known as difficult-to-induce-seizures electroconvulsive therapy cases (DECs). However, no clinical guidelines exist for DECs; thus, clinicians often face difficulties determining treatment strategies. This study aimed to obtain a consensus among clinical experts regarding the treatment of DECs.

Methods: We asked Japanese ECT experts to rate 14 approaches under six conditions of DECs on a 9-point Likert scale (1 = "disagree" to 9 = "agree"). Based on responses from 195 experts, the approaches were classified as first-line (95% confidence interval mean ≥ 6.5), second-line (mean, 3.5-6.5), or third-line strategies (mean < 3.5). Approaches rated 9 points by at least 50% of the respondents were considered "treatments of choice."

Results: To avoid difficult seizure induction, dose reduction of benzodiazepine receptor agonist (BZRA) (8.33 ± 1.25), dose reduction or discontinuation of antiepileptic drugs (AEDs) or other drugs that may make seizure induction difficult (8.16 ± 1.18), and ensure hyperventilation (7.95 ± 1.47) were classified as treatments of choice. First-line treatment strategies were BRZA discontinuation (7.89 ± 1.45), stimulation timing adjustment (7.00 ± 2.00), and anesthetic dose reduction (6.93 ± 1.94). Dose reduction or discontinuation of AEDs or other drugs that might make seizure induction difficult and ensure hyperventilation were the treatments of choice across all patient conditions. The results of rating approaches for patients with mood disorders and schizophrenia were similar, with differences observed among the approaches for patients with catatonia, high risk of cognitive impairment, and cardiovascular events.

Conclusions: ECT expert recommendations are useful and can assist in clinical decision-making. Our results suggest that while some strategies are applicable across all conditions, others should be tailored to meet the specific needs of patients. These recommendations should be further evaluated in future clinical studies.

Background: Foreign language syndrome is a rare neuropsychiatric phenomenon typically following general anesthesia. To date, foreign language syndrome has not been associated with neuroleptic malignant syndrome (NMS) in the literature. This case aims to broaden the clinical understanding of NMS by presenting an atypical manifestation of foreign language syndrome and emphasizing the need for prompt recognition of such presentations for accurate diagnosis and management.

Case presentation: A 34-year-old Caucasian male with a history of schizoaffective disorder and recurrent psychiatric hospitalizations was admitted for a depressive episode. His condition worsened hours after the administration of intramuscular chlorpromazine, leading to NMS characterized by agitation, muscle rigidity, hyperthermia, autonomic instability, abnormal laboratory findings, and altered mental status, including foreign language syndrome. Management included the discontinuation of the prior psychopharmacotherapy, intravenous hydration, and medications (biperiden, lorazepam). The patient showed significant improvement, with resolution of NMS symptoms and normalized sleep patterns by the time of discharge.

Conclusion: Foreign language syndrome is an exceptionally rare occurrence, with only nine documented cases to date, all involving male patients. This case presents a novel instance of foreign language syndrome in the context of NMS in a male patient, providing insight into the potential sex-specific mechanisms underlying this rare phenomenon. This case adds valuable evidence to the understanding of the clinical spectrum of NMS and highlights the importance of recognizing atypical presentations in managing patients with neuropsychiatric conditions.