Search Results (18)

Background: Bipolar disorder (BD) and borderline personality disorder (BPD) share common cognitive impairments. These deficits are also shared by bipolar offspring (BD-OFF). Nevertheless, little is known regarding the association between cognitive impairments and BPD features in youth with BD and BD-OFF. Objectives: This study aimed to investigate the association between BPD features and cognitive impairments in youth with BD and BD-OFF. Methods: Thirty-nine participants (7–17 years) with BD, 18 BD-OFF, and 50 healthy controls (HCs) were recruited. BPD features were assessed using the Borderline Personality Features Scale for Children (BPFS-C). Deficits in executive functions and affective processing were assessed using tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), namely, the Cambridge gambling task (CGT), the stockings of Cambridge (SOC), and the Affective Go/No-Go (AGN) and rapid visual processing (RVP) tasks. Between-group differences were analyzed through ANOVAs. Relationships between the BPFS-C and cognitive tasks were examined using multiple linear regressions in youth with BD and BD-OFF. Results: Youth with BD and BD-OFF showed higher scores on the BPFS-C. Youth with BD had increased deficits in the CGT and SOC compared to HCs. In both youth with BD and BD-OFF, BPD features were associated with increased deficits in the CGT, and a bias toward positive emotions in the AGN task. Conclusions: In youth with BD and BD-OFF, clinical and cognitive assessments for BPD features are of relevance as they have the potential to inform targeted interventions. Full article

Impulsivity is increasingly recognized as a transdiagnostic feature that spans multiple psychiatric disorders, including borderline personality disorder (BPD), bipolar disorder, and substance use disorders. In BPD, impulsive behaviors manifest as substance misuse, risky sexual activity, self-injury, and other maladaptive patterns. This review article updates the clinical and preclinical literature to explore the biological and psychological bases of impulsivity in BPD and considers whether methylphenidate (MPH) can be used as a treatment in this context. Although no medication is specifically approved for BPD, limited evidence from patients with comorbid BPD and attention-deficit/hyperactivity disorder (ADHD) indicates that MPH may reduce impulsivity and improve key symptoms. In addition, real-world data indicate that MPH may be associated with better outcomes and a lower risk of suicidal behaviors in patients with BPD. Nevertheless, such evidence remains scant, particularly among those with a primary diagnosis of BPD without a diagnosis of ADHD. Larger, methodologically rigorous studies are needed to clarify the efficacy and safety of MPH in targeting impulsivity within this population. An improved understanding of dopaminergic mechanisms may eventually shed light on MPH’s therapeutic role in BPD, although current data remain preliminary. Overall, recognizing impulsivity as a core symptom rather than focusing exclusively on diagnostic boundaries may facilitate more tailored and effective interventions for BPD. Full article

Many psychiatric disorders are associated with major cognitive deficits. However, it is uncertain whether these deficits develop as a result of psychiatric disorders and what shared risk factors might mediate this relationship. Here, we utilized the Mendelian randomization (MR) analysis to investigate the complex causal relationship between nine major psychiatric disorders and three cognitive phenotypes, while also examining the potential mediating role of oxidative stress as a shared biological underpinning. Schizophrenia (SZ), major depressive disorder (MDD), and attention deficit hyperactivity disorder (ADHD) showed a decreasing effect on cognitive performance, intelligence, and education, while bipolar disorder (BPD) increased educational attainment. MR-Clust results exhibit the shared genetic basis between SZ and other psychiatric disorders in relation to cognitive function. Furthermore, when oxidative stress was considered as a potential mediating factor, the associations between SZ and the three dimensions of cognition, as well as between MDD and intelligence and ADHD and intelligence, exhibited larger effect sizes than the overall. Mediation MR analysis also supported the causal effects between psychiatric disorders and cognition via oxidative stress traits, including carotene, vitamin E, bilirubin, and uric acid. Finally, summary-based MR identified 29 potential causal associations of oxidative stress genes with both cognitive performance and psychiatric disorders. Our findings highlight the importance of considering oxidative stress in understanding and potentially treating cognitive impairments associated with psychiatric conditions. Full article

Bipolar disorder (BPD) is a serious psychiatric condition that is characterized by the frequent shifting of mood patterns, ranging from manic to depressive episodes. Although there are already treatment strategies that aim at regulating the manifestations of this disorder, its etiology remains unclear and continues to be a question of interest within the scientific community. The development of RNA sequencing techniques has provided newer and better approaches to studying disorders at the transcriptomic level. Hence, using RNA-seq data, we employed intramodular connectivity analysis and network pharmacology assessment of disease-associated variants to elucidate the biological pathways underlying the complex nature of BPD. This study was intended to characterize the expression profiles obtained from three regions in the brain, which are the nucleus accumbens (nAcc), the anterior cingulate cortex (AnCg), and the dorsolateral prefrontal cortex (DLPFC), provide insights into the specific roles of these regions in the onset of the disorder, and present potential targets for drug design and development. The nAcc was found to be highly associated with genes responsible for the deregulated transcription of neurotransmitters, while the DLPFC was greatly correlated with genes involved in the impairment of components crucial in neurotransmission. The AnCg did show association with some of the expressions, but the relationship was not as strong as the other two regions. Furthermore, disease-associated variants or single nucleotide polymorphisms (SNPs) were identified among the significant genes in BPD, which suggests the genetic interrelatedness of such a disorder and other mental illnesses. DRD2, GFRA2, and DCBLD1 were the genes with disease-associated variants expressed in the nAcc; ST8SIA2 and ADAMTS16 were the genes with disease-associated variants expressed in the AnCg; and FOXO3, ITGA9, CUBN, PLCB4, and RORB were the genes with disease-associated variants expressed in the DLPFC. Aside from unraveling the molecular and cellular mechanisms behind the expression of BPD, this investigation was envisioned to propose a new research pipeline in studying the transcriptome of psychiatric disorders to support and improve existing studies. Full article

Previous research has focused on understanding the occurrence of intense and fluctuating emotions and the ability to manage these emotions and affective states. These phenomena have been, respectively, labeled as affective instability and emotion regulation and have been studied among individuals diagnosed with borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BD), and post-traumatic stress disorder (PTSD). Previous findings suggest that affective instability may be associated with poorer psychological well-being. The present study aims to investigate the general tendency of affective instability and capacity for emotional regulation among college students, regardless of a previous psychological diagnosis, and to understand the relationship between these processes and psychological well-being. Three questionnaires were administered to measure levels of affective instability, the ability to manage fluctuating affective states, and overall psychological well-being. The findings suggest that (1) individuals with diagnoses experience affective lability and difficulty regulating emotions at a greater rate than those without, (2) higher affective lability scores are consistent with more significant emotion dysregulation and lower overall psychological well-being, and (3) scores on the Affective lability Scale (ALS) and the Difficulties in Emotional Regulation Scale (DERS) are reliable predictors of one’s estimated Global Assessment of Functioning (GAF) scores. Although causation has not been established, the evidence suggests that individuals with diagnoses experience greater difficulty in regulating their emotions, have greater affective lability, and experience diminished psychological well-being and day-to-day functionality. Certain anecdotal evidence suggests that emotional lability can be endogenous and affect multiple aspects of an individual’s social, occupational, and personal life. By revising the existing literature and the present findings, the authors provide insights into the significance of endogenous factors in the context of affective lability and offer suggestions for future research. Full article

Neuropsychiatric disorders (NDs) are a diverse group of pathologies, including schizophrenia or bipolar disorders, that directly affect the mental and physical health of those who suffer from them, with an incidence that is increasing worldwide. Most NDs result from a complex interaction of multiple genes and environmental factors such as stress or traumatic events, including the recent Coronavirus Disease (COVID-19) pandemic. In addition to diverse clinical presentations, these diseases are heterogeneous in their pathogenesis, brain regions affected, and clinical symptoms, making diagnosis difficult. Therefore, finding new biomarkers is essential for the detection, prognosis, response prediction, and development of new treatments for NDs. Among the most promising candidates is the apolipoprotein D (Apo D), a component of lipoproteins implicated in lipid metabolism. Evidence suggests an increase in Apo D expression in association with aging and in the presence of neuropathological processes. As a part of the cellular neuroprotective defense machinery against oxidative stress and inflammation, changes in Apo D levels have been demonstrated in neuropsychiatric conditions like schizophrenia (SZ) or bipolar disorders (BPD), not only in some brain areas but in corporal fluids, i.e., blood or serum of patients. What is not clear is whether variation in Apo D quantity could be used as an indicator to detect NDs and their progression. This review aims to provide an updated view of the clinical potential of Apo D as a possible biomarker for NDs. Full article

This narrative review examines two of the common comorbidities of attention-deficit/hyperactivity disorder, bipolar disorder (BD), and borderline personality disorder (BPD), which each share several common features with ADHD that can make assessment and diagnosis challenging. The review highlights some of the key symptomatic differences between adult ADHD and these disorders, allowing for more careful consideration before establishing a formal diagnosis. When the disorders are found to be comorbid, further complications may arise; thus, the review will also help to provide evidence-based treatment recommendations as well as suggestions on how to minimize adverse events. Incorporating evidence from systematic reviews, journal articles, randomized controlled trials, and case reports, this review highlights that the diagnosis of ADHD and some of its common comorbidities is challenging and requires full, in-depth assessment and management. The management strategies of these comorbidities will also be addressed, with emphasis on achieving mood stabilization for BD prior to initiating appropriate ADHD pharmacotherapy. Medications, specifically mood stabilizers, antipsychotics, and antidepressants, are fundamental in treating symptoms seen in BD and some cases of BPD, alongside psychotherapy and lifestyle modifications when appropriate. The review highlights the effectiveness of specific medications, including psychostimulants, atomoxetine, and bupropion, as add-on therapies to mood-stabilizing treatments for addressing ADHD symptoms in patients with these comorbidities. Despite limited research, the review will address various pharmacological and psychotherapeutic approaches for managing comorbid ADHD and BPD, emphasizing the need for further investigations to better understand the unique needs of this patient population. Full article

Background: This study aimed to compare brain asymmetry in patients with schizophrenia (SCZ), bipolar disorder (BPD), and healthy controls to test whether asymmetry patterns could discriminate and set boundaries between two partially overlapping severe mental disorders. Methods: We applied a fully automated voxel-based morphometry (VBM) approach to assess structural brain hemispheric asymmetry in magnetic resonance imaging (MRI) anatomical scans in 60 participants (SCZ = 20; BP = 20; healthy controls = 20), all right-handed and matched for gender, age, and education. Results: Significant differences in gray matter asymmetry were found between patients with SCZ and BPD, between SCZ patients and healthy controls (HC), and between BPD patients and HC. We found a higher asymmetry index (AI) in BPD patients when compared to SCZ in Brodmann areas 6, 11, and 37 and anterior cingulate cortex and an AI higher in SCZ patients when compared to BPD in the cerebellum. Conclusion: Our study found significant differences in brain asymmetry between patients with SCZ and BPD. These promising results could be translated to clinical practice, given that structural brain changes detected by MRI are good candidates for exploration as biological markers for differential diagnosis, besides helping to understand disease-specific abnormalities. Full article

Mental illness has recently become a global health issue, causing significant suffering in people’s lives and having a negative impact on productivity. In this study, we analyzed the generalization capacity of machine learning to classify various mental illnesses across multiple social media platforms (Twitter and Reddit). Language samples were gathered from Reddit and Twitter postings in discussion forums devoted to various forms of mental illness (anxiety, autism, schizophrenia, depression, bipolar disorder, and BPD). Following this process, information from 606,208 posts (Reddit) created by a total of 248,537 people and from 23,102,773 tweets was used for the analysis. We initially trained and tested machine learning models (CNN and Word2vec) using labeled Twitter datasets, and then we utilized the dataset from Reddit to assess the effectiveness of our trained models and vice versa. According to the experimental findings, the suggested method successfully classified mental illness in social media texts even when training datasets did not include keywords or when unrelated datasets were utilized for testing. Full article

Sortilin-related vacuolar protein sorting 10 (VPS10) domain containing receptor 3 (SORCS3) is a neuron-specific transmembrane protein involved in the trafficking of proteins between intracellular vesicles and the plasma membrane. Genetic variation at SORCS3 is associated with multiple neuropsychiatric disorders and behavioural phenotypes. Here, we undertake a systematic search of published genome-wide association studies to identify and catalogue associations between SORCS3 and brain-related disorders and traits. We also generate a SORCS3 gene-set based on protein–protein interactions and investigate the contribution of this gene-set to the heritability of these phenotypes and its overlap with synaptic biology. Analysis of association signals at SORSC3 showed individual SNPs to be associated with multiple neuropsychiatric and neurodevelopmental brain-related disorders and traits that have an impact on the experience of feeling, emotion or mood or cognitive function, while multiple LD-independent SNPs were associated with the same phenotypes. Across these SNPs, alleles associated with the more favourable outcomes for each phenotype (e.g., decreased risk of neuropsychiatric illness) were associated with increased expression of the SORCS3 gene. The SORCS3 gene-set was enriched for heritability contributing to schizophrenia (SCZ), bipolar disorder (BPD), intelligence (IQ) and education attainment (EA). Eleven genes from the SORCS3 gene-set were associated with more than one of these phenotypes at the genome-wide level, with RBFOX1 associated with SCZ, IQ and EA. Functional annotation revealed that the SORCS3 gene-set is enriched for multiple ontologies related to the structure and function of synapses. Overall, we find many independent association signals at SORCS3 with brain-related disorders and traits, with the effect possibly mediated by reduced gene expression, resulting in a negative impact on synaptic function. Full article

Introduction: Investigations on predictors of real-world functioning were mainly performed in patients with schizophrenia, while fewer studies have been conducted in other psychiatric disorders. Objective: Our objective was to identify clinical, socio-demographic, and illness-related predictors of real-world functioning during 12 months of standard treatments in outpatients with different diagnoses. Methods: Outpatients (n = 1019) with schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder (BD), and borderline personality disorder (BPD) were evaluated with the following tools: SCID-5-CV and SCID-5-PD, CGI-S, SAT-P, DAI-10, and PSP. Change of PSP (ΔPSP) between baseline and 12 months was used as the dependent variable in multiple regression analysis. Results: Higher PSP score at baseline and the achievement of main milestones predicted better functioning after follow-up in all subgroups of patients, with the exception of BD. In the total sample, ΔPSP was related to age of onset, treatments, and quality of life, and inversely related to psychiatric anamnesis, antidepressants, and global symptoms. In SZ, ΔPSP was related to adherence and quality of life. In MDD, ΔPSP was related to psychotherapy and quality of life, and inversely related to antidepressants and global symptoms. In BD, ΔPSP was related to age of onset, antipsychotics, and quality of life, while it was inversely related to psychiatric anamnesis. In BPD, antipsychotics, mood stabilizers, psychotherapy, and quality of life were directly related to ΔPSP, while suicidal attempts and global symptoms had an inverse relation. Conclusions: Several socio-demographic and illness-related variables predicted improvement of real-world functioning, besides psychopathology and severity of the disease. Full article

Mitochondrial function is at the nexus of pathways regulating synaptic-plasticity and cellular resilience. The involvement of brain mitochondrial dysfunction along with increased reactive oxygen species (ROS) levels, accumulating mtDNA mutations, and attenuated autophagy is implicated in psychiatric and neurodegenerative diseases. We have previously modeled mild mitochondrial dysfunction assumed to occur in bipolar disorder (BPD) using exposure of human neuronal cells (SH-SY5Y) to rotenone (an inhibitor of mitochondrial-respiration complex-I) for 72 and 96 h, which exhibited up- and down-regulation of mitochondrial respiration, respectively. In this study, we aimed to find out whether autophagy enhancers (lithium, trehalose, rapamycin, and resveratrol) and/or ROS scavengers [resveratrol, N-acetylcysteine (NAC), and Mn-Tbap) can ameliorate neuronal mild mitochondrial dysfunction. Only lithium (added for the last 24/48 h of the exposure to rotenone for 72/96 h, respectively) counteracted the effect of rotenone on most of the mitochondrial respiration parameters (measured as oxygen consumption rate (OCR)). Rapamycin, resveratrol, NAC, and Mn-Tbap counteracted most of rotenone’s effects on OCR parameters after 72 h, possibly via different mechanisms, which are not necessarily related to their ROS scavenging and/or autophagy enhancement effects. The effect of lithium reversing rotenone’s effect on OCR parameters is compatible with lithium’s known positive effects on mitochondrial function and is possibly mediated via its effect on autophagy. By-and-large it may be summarized that some autophagy enhancers/ROS scavengers alleviate some rotenone-induced mild mitochondrial changes in SH-SY5Y cells. Full article

(1) Background: Previous literature reported in both subjects with Borderline personality disorder (BPD) and Bipolar disorder (BD) higher levels of autistic traits, linked to a greater suicidality risk. The aim of this study was to evaluate and compare the presence of autistic traits in a sample of individuals with BD or BPD, with a specific focus on suicidality. (2) Methods: We recruited two clinical samples of subjects (BPD and BD) and a control group without a diagnosis according to DSM-5 (CTL). Subjects were assessed with the AdAS Spectrum, the RRS and, for evaluating suicidality, the MOODS-SR. (3) Results: The CTL group showed significantly lower scores of both BD and BPD on AdAS Spectrum, RRS, and suicidality scores. BPD subjects showed significantly lower scores than BD ones in most of AdAS Spectrum domain scores. Correlation and regression analyses highlighted specific patterns of association among AdAS Spectrum domains, RRS, and suicidality in each clinical group. (4) Conclusions: Both BPD and BD individuals show greater levels of autistic traits, which seem to be distributed in a continuum featuring the highest levels among BD subjects. In both disorders, higher autistic traits were linked to suicidal tendencies, although with different patterns of association between BD and BPD subjects. Full article

G protein coupled receptors (GPCRs) are the main mediators of signal transduction in the central nervous system. Therefore, it is not surprising that many GPCRs have long been investigated for their role in the development of anxiety and mood disorders, as well as in the mechanism of action of antidepressant therapies. Importantly, the endogenous ligands for a large group of GPCRs have not yet been identified and are therefore known as orphan GPCRs (oGPCRs). Nonetheless, growing evidence from animal studies, together with genome wide association studies (GWAS) and post-mortem transcriptomic analysis in patients, pointed at many oGPCRs as potential pharmacological targets. Among these discoveries, we summarize in this review how emotional behaviors are modulated by the following oGPCRs: ADGRB2 (BAI2), ADGRG1 (GPR56), GPR3, GPR26, GPR37, GPR50, GPR52, GPR61, GPR62, GPR88, GPR135, GPR158, and GPRC5B. Full article

The molecular mechanisms underlying bipolar disorder (BPD) have remained largely unknown. Postmortem brain tissue studies comparing BPD patients with healthy controls have produced a heterogeneous array of potentially implicated protein-coding RNAs. We hypothesized that dysregulation of not only coding, but multiple classes of RNA (coding RNA, long non-coding (lnc) RNA, circular (circ) RNA, and/or alternative splicing) underlie the pathogenesis of BPD. Using non-polyadenylated libraries we performed RNA sequencing in postmortem human medial frontal gyrus tissue from BPD patients and healthy controls. Twenty genes, some of which not previously implicated in BPD, were differentially expressed (DE). PCR validation and replication confirmed the implication of these DE genes. Functional in silico analyses identified enrichment of angiogenesis, vascular system development and histone H3-K4 demethylation. In addition, ten lncRNA transcripts were differentially expressed. Furthermore, an overall increased number of alternative splicing events in BPD was detected, as well as an increase in the number of genes carrying alternative splicing events. Finally, a large reservoir of circRNAs populating brain tissue not affected by BPD is described, while in BPD altered levels of two circular transcripts, cNEBL and cEPHA3, are reported. cEPHA3, hitherto unlinked to BPD, is implicated in developmental processes in the central nervous system. Although we did not perform replication analyses of non-coding RNA findings, our findings hint that RNA dysregulation in BPD is not limited to coding regions, opening avenues for future pharmacological investigations and biomarker research. Full article