Affective Disorders Research Articles

Lithium is the first-line treatment for bipolar disorders and a first-line augmentation option for treatment-resistant unipolar depression. Due to its narrow therapeutic window and risk of toxicity, people taking lithium require regular blood testing to monitor lithium levels in the body. However, studies have reported that only half of lithium-treated patients receive adequate lithium monitoring. This protocol describes a trial that will test the feasibility and acceptability of a point-of-care (POC) lithium blood testing programme in patients with unipolar or bipolar affective disorders taking lithium as a maintenance treatment. The primary objectives are to establish whether testing the effectiveness of POC testing is feasible, by assessing recruitment, attrition, and adherence to monitoring guidelines compared to participants randomised to testing as usual; to test whether the programme is acceptable to patients; and to measure potential contamination bias. The secondary objectives are to examine changes in health-related quality of life, the use of healthcare services, and depressive and manic symptoms to inform the design of a larger multi-site randomised controlled trial (RCT). This feasibility RCT will recruit 80 participants with affective disorders who are taking lithium. Participants will be 1:1 randomised to either POC monitoring or monitoring as usual where they will be followed up at three research visits over 30 weeks. The proportion of patients meeting guidelines for lithium monitoring will be examined, alongside measures of acceptability, wellbeing, and health economic data. POC testing has the potential to significantly improve patient safety and satisfaction with lithium treatment.

Relevance. Parkinson's disease is a neurodegenerative disease of the nervous system and one of the most topical problems in neurology. Motor fluctuations are a common complication of long-term levodopa treatment in patients with Parkinson's disease. Рurpose of the study. To study the effect of motor fluctuations on the psychoemotional state and quality of life of patients with Parkinson's disease. Materials and methods of the study. The study included 120 patients with various clinical forms of Parkinson's disease. To compare the parameters during the study, the patients were divided into 2 groups: patients with motor fluctuations (55 people) and patients without motor fluctuations (65 people). All patients underwent clinical neurological and neuropsychological examinations. Research results. In the group with motor fluctuations, the comorbid form of affective disorders, that is, depression + anxiety, was significantly higher: in the group with fluctuations - 54.5% (30/55 patients), in the group without fluctuations - 24.6% (16/65 patients). When assessing the significance of this difference using the χ² test, the obtained value was p<0.01. Thus, it can be noted that motor fluctuations are strongly associated with more severe and comorbid forms of mental disorders (depression and anxiety). The results obtained based on the PDQ-39 scale domains show that psychoemotional disorders have varying degrees of negative impact on virtually all areas of life. Conclusion. When assessing quality of life using the PDQ-39 questionnaire, patients with anxiety and depression showed a significant decrease in indicators such as mobility, daily activities, emotional state, cognitive function, and social support. The greatest negative impact was observed in the group with comorbid depression and anxiety.

The widespread availability of melatonin without a prescription, combined with the lack of specific medications for certain disorders with increasing morbidity rates, is significant factors driving the rise in melatonin use over the past decade. Despite its growing popularity, uncertainties surrounding optimal dosage and duration of exposure remain critical concerns, as these factors could increase the risk of overexposure and adverse effects. This study aims to update the therapeutic indications for melatonin, as well as assess its prescription, and therapeutic strategies. An updated search was conducted utilizing the descriptors (melatonin AND (children OR child OR adolescent)). Results presents melatonin's use for sleep disorders, autism spectrum disorder, neurodevelopmental disorders, and Attention Deficit/Hyperactivity Disorder, along with a smaller number of studies exploring its therapeutic potential in conditions such as atopic dermatitis, obesity, functional abdominal pain disorders, Bipolar Affective Disorder, neurogenetic syndromes, and Bourneville disease. Pediatric-appropriate prolonged-release melatonin in correct dosages has demonstrated positive results in clinical trials and appears to be the predominant formulation. The dosage adjustment phase is crucial for successful treatment. Significant variations in dosage, adaptation time, and exposure time were observed across clinical trials, complicating the comparison of results.

Depressive disorder (DD) is a common affective disorder with an unclear specific etiology. Although many previous studies have suggested that iron metabolism is involved in the development of DD, there is a lack of validated genetic evidence regarding whether iron metabolism-related indices (i.e., total iron binding capacity, transferrin saturation, ferritin, and serum iron) are causally related to DD. This study conducted a bidirectional Mendelian randomization (MR) analysis based on the largest existing genome-wide association study (GWAS) dataset. We used MR to investigate the causal relationship between iron metabolism indicators and DD by controlling for confounding factors and utilizing randomly assigned genetic instrumental variables that are not affected by any causal effects. Through coordinated analysis of 86 iron metabolism-related SNPs and 16,380,457 DD-related SNPs, 65 SNPs with genome-wide significance that were found to be related to DD iron homeostasis were screened. The IVW analysis results suggest that total iron binding capacity (TIBC) (β = 0.021; 95% Cl = -0.059 to 0.101; p value = 0.610), transferrin saturation (TSAT) (β = -0.038; 95% Cl = -0.146 to 0.070; p value = 0.489), and ferritin (FER) (β = 0.002; 95% Cl = -0.139 to 0.143; p value = 0.982) have no genetic causal relationship with DD, and serum iron (SI) (β = -0.100; 95% Cl = -0.194 to -0.006; p value = 0.040) is considered to have a genetic causal relationship with DD. The Cochran test of MR-IVW suggests that TSAT (p value = 0.125), FER (p value = 0.089), SI (p value = 0.667), and DD have no heterogeneity in the MR analysis results. The MR Egger level multieffect test results show that TIBC (p value = 0.875), TSAT (p value = 0.585), FER (p value = 0.990), and SI (p value = 0.352) all have no level multieffect. In addition, the IVW analysis results of the effect of DD on iron metabolism indicators suggest that there is no causal relationship between DD and TIBC (β = -0.009; 95% Cl = -0.024 to 0.007; p value = 0.218), TSAT (β = -0.008; 95% Cl = -0.024 to 0.008; p value = 0.277), FER (β = -0.002; 95% Cl = -0.016 to 0.012; p value = 0.761), and SI (β = -0.008; 95% Cl = -0.024 to 0.008; p value = 0.263). The results of the sensitivity analysis indicate that no heterogeneity or horizontal pleiotropy was present in the observed results (p > 0.05). The iron metabolism markers TIBC, TSAT, and FER have no genetic causal relationship with DD, while SI has a genetic causal relationship with DD. Decreased SI levels may increase the risk of DD. In addition, DD has no clear genetic association with the four indicators of iron metabolism.

Today’s research highlights the therapeutic potential of the hallucinogen psilocybin in the treatment of pathologies associated with mood, cognitive, and affective dysregulation. These domains of function are regulated by the serotonergic system, which can be influenced by sex hormones, like estrogen and testosterone, and psychedelic compounds including psilocybin. Current evidence supports a higher prevalence of affective disorders in females, and a growing awareness of sex-based differences in response to drug therapy. Estrogen’s influence on serotonin physiology is an aspect that must be accounted for when planning a treatment regimen that includes a psychoactive drug such as psilocybin. A review of the current literature was conducted, and an analysis of how the fluid hormonal states in females across their different reproductive phases may impact serotonin dynamics, synaptic plasticity, and therapeutic timing of psilocybin use is discussed. Future research should focus on the influence of sex hormones on psychedelic-assisted therapy in the effort to further personalize treatment plans for these pathologies.

High-sensitivity C-reactive protein as an early transdiagnostic biomarker for thoughts of death in mood disorders.

Structural connectomic signatures of childhood maltreatment across affective and psychotic disorders.

Transdiagnostic effectiveness and safety of clozapine in individuals with psychotic, affective, and personality disorders: nationwide and meta-analytic comparisons with other antipsychotics.

Background:Nonadherence jeopardizes treatment outcomes in the psychiatric care continuum. However, there was a paucity of data in the resource-limited life trajectories.Objectives:This study sought to uncover the psychotropic medications adherence behavior of older adults with severe mental disorders and its modeling predictors.Design:A hospital-based cross-sectional study was conducted in selected hospitals of the South Gondar Zone from March 1 to August 30, 2024.Methods:A multistage sampling technique followed by stratified and systematic random sampling methods was employed. Data were collected via interviewer-administered semistructured questionnaire and medical record review. A medication adherence rating scale, medication regimen complexity index instrument, Oslo social support scale, drug attitude inventory scale, and internal stigma monitoring index scale were utilized to assess adherence, treatment regimen complexity, social/family support, attitudes toward treatment, and internal stigma, respectively. Ordinal logistic regression deciphered key predictors using adjusted odds ratios (AORs) with a 95% confidence interval at p < 0.05.Results:The study sample comprised 423 patients with severe psychiatric disorder (mean (SD) age, 67.3 (±11.9) years; 56.03%, 237 male). Among the participants 255 (60.28%, (95% CI: 58.86–62.11)) had suboptimal adherence behavior. Age, education status, adherence counseling, attitude toward treatment, memory aids, internal stigma, insight, social support, illicit drug use, comorbidity, ADRs, patient-level medication regimen complexity index, and polypharmacy were the predictors identified in the final model.Conclusion:Despite multiple methodological limitations, this study suggests that suboptimal psychotropic medications adherence behavior was a critical challenge among older adults with severe mental disorders in geriatric mental healthcare in the Ethiopian hospital settings. We urge policymakers to devise evidence-based policies and strategies focusing on the identified predictors early on and intervene accordingly. Special attention should be given to individuals with low literacy levels, negative attitudes toward treatment, high internalized stigma, poor insight into their condition, substance use, comorbidities, adverse drug reactions, high levels of medication regimen complexity score, and those on polytherapy.

To analyse the changes in psychiatric inpatient admissions following the 2022 Lismore floods, focusing on admission frequency, length and reason. We separated our dataset into two groups of equal time frame, representing the 12 months directly preceding (N = 407) and directly following (N = 500) the floods, and analysed the differences between them. A retrospective cohort study. The adult inpatient mental health service of Lismore Base Hospital. 907 patients admitted to the Lismore Base Hospital adult inpatient mental health unit between 1 March 2021 and 28 February 2023. Patient characteristics, number of admissions, admission length and admission reason were compared between the pre-flood and post-flood groups. We found a 22.9% (p = 0.002) increase in the number of admissions and an 18.2% (p = 0.001) reduction in the median admission length following the floods, culminating in no change in the total time spent in hospital when summed across all admissions. Additionally, there was a reduction in the length of Suicidality, Homicidality or Deliberate Self-Harm (DSH) admissions (p < 0.001) and Bipolar Affective Disorder admissions (p = 0.026). The increase in admission frequency and decrease in admission length following the floods demonstrate the increase in demand for hospitalisation, which strained the inpatient capacity of the hospital. Further investigation is needed involving longer-term data and individual-level exposure information, along with connecting to the community-level occurrence of mental health conditions post-flood.

Long-term dementia risk following electroconvulsive therapy: A GRADE-assessed systematic review and meta-analysis.

Background: Lithium is a first-line treatment for Bipolar Affective Disorder, but it has a narrow therapeutic range and has been shown to have cardiovascular side effects. This study aimed to compile the cases of lithium-induced cardiovascular abnormalities and the pathological mechanisms behind those effects. Objectives: To conduct a systematic review of case reports in adult patients who experienced cardiovascular side effects of lithium in the last 11 years. Methods: The PRISMA method was followed to search PubMed, Wiley Online Library, ResearchGate, Springer, Semantic Scholar, and Google Scholar databases for articles from January 2013 to June 2024 using combinations of 'lithium,' 'cardiac,' 'cardiovascular,' 'side effect,' 'patient,' and 'case.' Case reports and observational studies concerning lithium use were identified for cardiovascular side effects. Results: Reported cardiovascular side effects of lithium included ECG abnormalities (N=31), myocarditis (N=1), cardiomyopathies (N=4), cardiac tamponade (N=1), thrombosis (N=1), and pulmonary hypertension (N=1). Lithium causes cardiovascular abnormalities via sodium channel blockage, interference with cardiac pacemaker cells, increased serum catecholamines and serotonin, disruption of thyroid gland functions, and induction of nephrogenic diabetes insipidus, leading to hemodynamic imbalance. Conclusion: Lithium precipitates cardiac side effects and toxicity through direct interference with the cardiac conduction system, disruption of metabolic hormones, and multi-organ interactions. Keyword : Cardiovascular Procedure; Vascular Access; Vascular System Injury.

Moyamoya angiopathy is a cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries. There is limited literature addressing epilepsy in this condition, especially in Western countries. This was a retrospective study conducted in the public hospitals of Aragón, analyzing data from all patients diagnosed with moyamoya angiopathy between 1981 and 2024. Epidemiological aspects of the disease were studied, as well as the presence of epilepsy and its management in this group of patients. A total of 26 patients were included, with an estimated prevalence in Aragón of 1.71 cases per 100,000 inhabitants. The mean age at diagnosis was 36.64 years, with an equal sex distribution. Half of the patients presented with moyamoya syndrome. Fifty percent of the patients experienced a seizure and 42.31% of the total met diagnostic criteria for epilepsy. Most seizures were focal (81.8%), with a predominance of frontal lobe semiology. Levetiracetam was the most commonly used treatment. Up to four of the twelve patients with epilepsy met diagnostic criteria for drug-resistant epilepsy. Although the prevalence of moyamoya in our series was lower than in Asian populations, the prevalence of epilepsy was significantly higher (50% of patients with seizures vs 0.9-18.9% in Asian series). In our cohort, epilepsy in moyamoya angiopathy was associated with the occurrence of syncope, cognitive impairment, affective disorders, and an earlier age at diagnosis. There are no other studies available addressing the percentage of drug-resistant epilepsy in these patients.

Subtle behavioral and cognitive symptoms precede schizophrenia (SCZ) and appear in individuals with elevated risk based on polygenic risk scores (SCZ-PRS) and family history of psychosis (SCZ-FH). However, most SCZ-PRS studies focus on European ancestry youth, limiting generalizability. Furthermore, it remains unclear whether SCZ-FH reflects common-variant polygenic risk or broader SCZ liability. Using baseline data from the Adolescent Brain Cognitive Development (ABCD) study, we investigated associations of SCZ-FH and SCZ-PRS with cognitive, behavioral, and emotional measures from NIH-Toolbox, Child Behavior Checklist (CBCL), and Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) for 9,636 children (mean age=9.92yrs, 47.4% female), specifically, 5,636 European, 2,093 African, and 1,477 Admixed American ancestry individuals. SCZ-FH was associated with SCZ-PRS (b=0.05, FDR-p=0.02) and subthreshold psychotic symptoms (b=0.46, FDR-p=0.01) in European youth, higher CBCL scores (b range=0.36-0.6, FDR-p<0.001), and higher odds of multiple internalizing and externalizing disorders (OR=1.10-1.22, FDR-p<0.001) across ancestries. SCZ-PRS was associated with lower cognition across ancestries (b=-0.43, FDR-p=0.02), higher CBCL total problems, anxious/depressed, rule-breaking and aggressive behaviors in European youth (b range=0.16-0.33, FDR-p<0.04), and depressive disorders in Admixed American youth (OR=1.37, FDR-p=0.02). Results remained consistent when SCZ-PRS and SCZ-FH were jointly modeled. Some SCZ-FH associations weakened when income-to-needs was accounted for, suggesting that SCZ-FH may capture both genetic and environmental influences. SCZ-FH showed associations with broad psychopathology, while SCZ-PRS was associated with cognition and specific symptoms in European youth. Findings highlight their complementary role in SCZ risk assessment and the need to improve PRS utility across ancestries.

Hydantion indolinones as AANAT inhibitors.

Schizophrenia is characterized by relational memory impairments that disrupt the ability to form novel inferences based on prior knowledge. The current study examined three aspects of relational memory impairments in psychosis. First, do relational memory deficits reflect specific difficulties in learning across repeated exposures? Second, can associative inference deficits be explained by a more general deficit in paired associate learning? Third, are relational memory deficits specific to schizophrenia or do they extend to affective psychosis? We studied persons with schizophrenia spectrum disorders (n = 244), persons with affective psychosis (n = 77), and healthy control participants (n = 186) with the Associative Inference Paradigm. Participants learned overlapping (A-B, B-C) and non-overlapping (D-E) pairs across multiple training blocks and were later tested on both directly studied (e.g., D-E) and inferred (i.e., A-C) associations. Persons with psychosis exhibited slower learning, a lower learning ceiling, and increased forgetting when compared to healthy control participants. Critically, associative inference impairments were disproportionally greater in schizophrenia and persisted even after accounting for paired-associate learning deficits. Our results reveal that relational memory impairments in psychosis reflect difficulties in learning and retaining associations and that their integration, necessary to form novel inferences, is especially impaired.

Lithium is an effective treatment for recurrent affective disorders, but it has a narrow therapeutic window and requires regular serum concentration monitoring, especially during periods of dose titration. Numerous attempts have been made to develop dose prediction methods to facilitate initiation and swift achievement of effective levels, but these typically lack sufficient accuracy and can be challenging to implement in practice. Develop a pharmacokinetic model of lithium to enable accurate dose prediction which is adaptable for clinical practice. The calculator was developed from a one-compartment model, which assumes that lithium distributes into total body water and requires only simple body measurements (age, sex, height and weight) as input variables. Its performance was compared to six commonly cited dose prediction methods in patients with bipolar disorder taking lithium, using two independent research samples from the United Kingdom (n = 40) and Germany (n = 18). Our one-compartment model performed better than the previous models, accurately predicting the required lithium dose within one 200 mg lithium carbonate tablet. The mean prediction error was 10 mg (SD = 148 mg) in this sample of euthymic subjects taking stable doses of lithium sampled at steady state. This model sets a new benchmark for lithium dose prediction accuracy and requires only simple body measurements. Further validation work in larger, diverse samples and future developments, such as the ability of the model to back-calculate levels from samples taken outside the recommended 12-hour window, may support its translation and use in practice.

This review considers the available research testing the efficacy of self-guided psychotherapeutic interventions in the management of affective premenstrual disorder (PMD) symptoms. Recent research confirms that clinician-guided internet-delivered cognitive behavior therapy is effective for the management of PMD symptoms. There is also mounting research suggesting that self-guided psychotherapy interventions are effective for a range of mental health conditions when featuring specific design elements aimed at enhancing engagement and learning. Self-guided psychotherapeutic interventions hold promise for the treatment of PMD symptoms. Integrating such interventions within existing menstrual cycle tracking mobile applications may increase access to affordable and effective mental healthcare. Further research in this area is warranted.

Abstract Background Some observational studies have reported that sodium–glucose cotransporter 2 (SGLT2) inhibitors may have an impact on psychiatric disorders. This Mendelian randomization (MR) study aims to explore the causal relationship between SGLT2 inhibition and five types of psychiatric disorders. Methods Genetic variants associated with the SLC5A2 gene and glycated hemoglobin were selected from the eQTLGen Consortium and Genotype-Tissue Expression datasets. Type 2 diabetes served as a positive control in the application of MR and colocalization analyses to investigate potential causal relationships between SGLT2 inhibition and depression, anxiety disorder, schizophrenia, obsessive-compulsive disorder, and bipolar affective disorder. The impact of glycated hemoglobin on psychiatric disorders was additionally analyzed. Results SGLT2 inhibition was associated with an increased risk of anxiety disorder, obsessive-compulsive disorder, and bipolar affective disorder. The effect of SGLT2 inhibition on depression did not reach Bonferroni-corrected significance levels. No association was found between SGLT2 inhibition and schizophrenia. Conclusions This study provides genetic evidence supporting that SGLT2 inhibitors increase the risk of obsessive-compulsive disorder, anxiety disorder, and bipolar affective disorder.

Characterization of a novel small chemical entity with anxiolytic- and antidepressant-like effects targeting multiple receptors.