Bipolar Disorder Research Articles

Embracing complexity in psychiatry-from reductionistic to systems approaches.

The understanding and treatment of psychiatric disorders present unique challenges due to these conditions' multifaceted nature, comprising dynamic interactions between biological, psychological, social, and environmental factors. Traditional reductionistic approaches often simplify these conditions into linear cause-and-effect relationships, overlooking the complexity and interconnectedness inherent in psychiatric disorders. Advances in complex systems approaches provide a comprehensive framework to capture and quantify the non-linear and emergent properties of psychiatric disorders. This Personal View emphasises the importance of identifying rules for generative models that govern brain and behaviour over time, which might contribute to personalised assessments and interventions for psychiatric disorders. For instance, mood fluctuations in bipolar disorder can be understood through dynamical systems modelling, which identifies modifiable parameters, such as circadian disruption, that can be addressed through targeted therapies such as light therapy. Similarly, recognition of depression as an emergent property arising from complex interactions highlights the need for integrated treatment strategies that enhance adaptive reactions in the individual. A framework for quantifying multilevel interactions and network dynamics can help researchers and clinicians to understand the interplay between neural circuits, behaviours, and social contexts. Probabilistic models and self-organisation concepts contribute to building concrete dynamical systems models of mental disorders, facilitating early identification of risk states and promoting resilience through adaptive interventions delivered with optimal timing. Embracing these complex systems approaches in psychiatry could capture the true nature of psychiatric disorders as properties of a dynamic complex system and not the manifestation of any lesion or insult. This line of thinking might improve diagnosis and treatment, offering new hope for individuals affected by psychiatric conditions and paving the way for more effective, personalised mental health care.

Association between frailty and common psychiatric disorders: A bidirectional Mendelian randomization study

BackgroundThere is growing interest in exploring the relationship between frailty and common psychiatric disorders. However, there have been limited reports on the genetic variation level of frailty with psychiatric disorders. MethodWe conducted large-scale Two-sample Mendelian randomization (MR) analyses to examine whether there is an association between frailty and common psychiatric disorders (bipolar disorder [BD], major depressive disorder [MDD], schizophrenia, and suicide or other Intentional self-harm). We employed multiple MR approaches to conduct the MR analysis, including MR-Egger, weighted median, and random-effect inverse variance weighted (IVW). The IVW method served as the primary analysis. Heterogeneity testing and sensitivity analysis were also conducted in the MR study. ResultsThe MR results denoted that frailty was associated with an increased risk of BD (odds ratio (OR) =1.60, PIVW = 0.017), MDD (OR = 2.04, PIVW < 0.001), schizophrenia (OR = 1.91, PIVW = 0.005), and suicide or other Intentional self-harm (OR = 1.77, PIVW < 0.001). For reverse analysis, we observed no significant association between psychiatric disorders and the risk of frailty. These results remained consistent across sensitivity assessments. ConclusionsOur research indicates a potential unidirectional causal relationship, suggesting that frailty may serve as a risk factor for certain common psychiatric disorders. These findings carry important for implications for psychiatric disorders and frailty patient care.

The efficacy of valproate in acute mania, bipolar depression and maintenance therapy for bipolar disorder: an overview of systematic reviews with meta-analyses.

This study aims to conduct an overview on the comparative efficacy of valproate in acute mania, bipolar depression and maintenance treatment of bipolar disorder (BD). We performed an overview of systematic reviews with meta-analyses of randomised controlled trials (RCTs), registered in PROSPERO (CRD42024497749). We searched Medline and Cochrane Database of Systematic Reviews. Summary measures comparing valproate with placebo or other active drugs were described. We included 26 systematic reviews. For acute mania (31 RCTs, n=4376), valproate showed a significantly better response than placebo in two high-quality systematic reviews (RR=1.42; 95% CI: 1.19 to 1.71) (OR=2.05; 95% CI: 1.32 to 3.20). No significant differences with lithium were found in most outcomes. Valproate had similar efficacy to quetiapine and lower efficacy compared with risperidone, with conflicting results when compared with olanzapine. In bipolar depression (7 RCTs, n=399), valproate was more effective than placebo in reducing depressive symptoms (OR=2.80; 95% CI: 1.26 to 6.18) and achieving remission (OR=2.4; 95% CI: 1.09 to 5.29) (OR=2.15; 95% CI: 0.82 to 5.6), considering the results of three high-quality systematic reviews. No significant difference was observed with lithium, lurasidone, quetiapine or olanzapine plus fluoxetine, but valproate showed superior efficacy to aripiprazole, ziprasidone and agomelatine. In maintenance treatment (11 RCTs, n=1063), valproate was superior to placebo in preventing relapse of any mood episode in two high-quality systematic reviews (RR=0.63; 95% CI: 0.48 to 0.83) (RR=0.63; 95% CI: 0.47 to 0.83). No significant difference was found with lithium, olanzapine or lamotrigine. This overview highlights favourable results for valproate compared with placebo in all phases of BD, as well as presenting specific results in comparison with other active drugs. However, these results must be interpreted considering the methodological limitations of our study.

Association of self-harm and suicidality with psychiatric co-occurring conditions in autistic individuals: a systematic review and pooled analysis

Autistic individuals frequently experience psychiatric co-occurring conditions, but the association with self-harm/suicidality according to these conditions was not yet elucidated. We aimed to summarize the association between self-harm/suicidality and psychiatric co-occurring conditions in autistic people. We systematically searched PubMed, Scopus, Embase, Web of Science, and Cochrane Database of Systematic Reviews until June 4, 2024 (PROSPERO registration number: CRD42023412860). Observational studies were included that provided information to calculate the odds ratio (OR) regarding the association between self-harm/suicidality and psychiatric co-occurring conditions in autistic individuals. We summarized the identified associations by presenting OR range or meta-analyzing when 7 or more estimates are available. The systematic search found 20 eligible studies with 301,841 participants. Our findings suggested that autistic individuals with any psychiatric disorder (k=1; OR 3.55; 95% CI 1.27-9.98), ADHD (k=3; OR range: 1.07-1.65), or mood disorder (k=1; OR 1.26; 95% CI 1.05-1.51) may be associated with higher odds of self-harm than those without these conditions. We identified potential positive associations between suicidality and the following co-occurring conditions: any psychiatric disorder (k=1; OR 11.65; 95% CI 10.68-12.71), psychotic disorder (k=4; OR range: 1.95-10.97), mood disorder (k=3; OR range: 1.75-9.82), bipolar disorder (k=2; ORrange: 2.55-4.95), depressive disorder (k=10; pooled OR 2.29; 95% CI 1.39-3.77), trauma- and stress-related disorder (k=2; OR range: 1.28-10.47), and adjustment disorder (k=1; OR 3.52; 95% CI 2.89-4.28). We found psychiatric co-occurring conditions that may be associated with higher odds of self-harm/suicidality in autistic individuals. However, our findings should be interpreted with caution considering the limited number of included studies. We suggested that clinicians should remain vigilant for autistic individuals with psychiatric co-occurring conditions for their potentially higher likelihood of self-harm and suicidality. This research was supported by a grant of the R&D project, funded by the National Center for Mental Health (grant number: MHER22A01).

First bipolar episode following booster dose of COVID-19 vaccination

Introduction and importance: The interactions between the susceptibility of the host and some of the COVID-19 vaccine components happened. Viral infections, including COVID-19, are related to the pathogenesis of bipolar disorder (BD). These findings could trigger an initial bipolar episode. Case presentation: A 48-year-old Syrian married female, presented to the out-clinic of Modern Medical Centre Hospital, in July 2022 for episodes of sub-maniac/mania episodes, which began within 15 days after the booster dose of COVID-19 vaccination, preceded by depressive mood. Both family and personal past psychiatric and/or trauma history were negatives. Initiation of carbamazepine 600 mg/day showed significant improvement within 3 days; 3 months later, carbamazepine dose was decreased to 200 mg/day, as there were no clinical symptoms. Clinical discussion: mRNA vaccines of COVID-19 increase the levels of type I interferon (INF), an inflammatory cytokine that creates a signal leading to the expression of interleukins, INF, and tumor necrosis factor-alpha. The pathology of BD is also unclear. Genetic predisposition, immunological effects, and the classification of BD, itself, as an autoimmune disease play a role. Although rapid improvement following treatment, prolonged and maintenance treatment by essentially mood stabilizer should be considered in bipolar episodes initiated by COVID-19 vaccination. Rare data are available about maniac episodes after COVID-19 infection, but to our knowledge, we reported the first case of bipolar onset after the booster vaccination of COVID-19. Conclusion: Bipolar disease can present following a booster dose of COVID-19 vaccination in previously healthy people.

Plasma neurofilament light outperforms glial fibrillary acidic protein in differentiating behavioural variant frontotemporal dementia from primary psychiatric disorders

ObjectiveTimely, accurate distinction between behavioural variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) is a clinical challenge. Blood biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have shown promise. Prior work has shown NfL helps distinguish FTD from PPD. Few studies have assessed NfL together with GFAP. MethodsWe investigated plasma GFAP and NfL levels in participants with bvFTD, bipolar affective disorder (BPAD), major depressive disorder (MDD), treatment-resistant schizophrenia (TRS), healthy controls (HC), adjusting for age and sex. We compared ability of GFAP and NfL to distinguish bvFTD from PPD. ResultsPlasma GFAP levels were significantly (all p < 0.001) elevated in bvFTD (n = 22, mean (M) = 273 pg/mL) compared to BPAD (n = 121, M = 96 pg/mL), MDD (n = 42, M = 105 pg/mL), TRS (n = 82, M = 67.9 pg/mL), and HC (n = 120, M = 76.8 pg/mL). GFAP distinguished bvFTD from all PPD with an area under the curve (AUC) of 0.85, 95 % confidence interval [0.76, 0.95]. The optimal cut-off of 105 pg/mL was associated with 73 % specificity and 86 % sensitivity. NfL had AUC 0.95 [0.91, 0.99], 13.3 pg/mL cut-off, 88 % specificity, 86 % sensitivity, and was superior to GFAP (p = 0.02863) and combination of GFAP and NfL (p = 0.04726). ConclusionsThis study found elevated GFAP levels in bvFTD compared to a large cohort of PPD, but NfL levels exhibited better performance in this distinction. These findings extend the literature on GFAP in bvFTD and build evidence for plasma NfL as a useful biomarker to assist with distinguishing bvFTD from PPD. Utilisation of NfL may improve timely and accurate diagnosis of bvFTD.

MIR218 polygenic risk score is associated with cognitive function and neurochemical metabolites among patients with depressed bipolar disorders

MIR218 polygenic risk score is associated with cognitive function and neurochemical metabolites among patients with depressed bipolar disorders

Alterations of subcortical structure volume in pediatric bipolar disorder patients with manic or depressive first-episode

BackgroundBipolar disorder may begin as depression or mania, which can affect the treatment and prognosis. The physiological and pathological differences among pediatric bipolar disorder (PBD) patients with different onset symptoms are not clear. The aims of the present study were to investigate subcortical structural alterations in PBD patients with first-episode depressive (PBD-FED) and first-episode manic (PBD-FEM).MethodsA total of 59 individuals including 28 PBD-FED, 13 PBD-FEM, and 18 healthy controls (HCs) underwent high-resolution structural magnetic resonance scans. FreeSurfer 7.2 was used to detect changes in subcortical volumes. Simultaneously, thalamic, hippocampal, and amygdala subregion volumes were compared between the three groups.ResultsAnalysis of covariance controlling for age, sex, education, and estimated intracranial volume shows third and fourth ventricle enlargement in patients with PBD. Compared with the PBD-FED and HCs, the PBD-FEM group had reduced gray matter volume in the left thalamus, bilateral hippocampus, and right amygdala. Subsequent subregion analyses showed right cortico-amygdaloid transient, bilateral accessory-basal nucleus, left hippocampal tail, right hippocampal head, and body volume reduction in the PBD-FEM group.ConclusionsThe present findings provided evidence of decreased subcortical structure in PBD-FEM patients, which might present its trait feature.

Are circadian rhythms more favorable with lithium than with other mood stabilizers? An exploratory actigraphy study in euthymic bipolar disorder type 1

BackgroundBipolar Disorder (BD) is associated with alterations of circadian rhythms of activity (CRA). Experimental research suggests that lithium (Li) modifies CRA, but this has been rarely explored in BD using actigraphy. MethodsThe sample comprised 88 euthymic BD-I cases with 3 weeks of actigraphy. We used a Principal Component Analysis (PCA) to generate CRA dimensions. We then used linear regression analyses to compare these dimensions between groups of individuals defined according to prescribed mood stabilizers: Li monotherapy (“Li” group, n = 28), anticonvulsant or atypical antipsychotic monotherapy (“AC or AAP” group, n = 27) or combined treatments (“Li+AC or Li+AAP” group, n = 33). Analyses were adjusted for potential confounders (gender, age, body mass index, depressive symptoms, co-prescribed benzodiazepines and antidepressants, smoking status and past alcohol use disorder). ResultsThe PCA identified two dimensions: “robust CRA” (high amplitude and interdaily stability, with low intradaily variability) and “late chronotype”. Univariate analyses showed higher scores for “robust CRA” in the “Li” versus the “AC or AAP” (p = 0.021) or “Li+AC or Li+AAP” groups (p = 0.047). These findings remained significant after adjustments (respectively p = 0.010 and p = 0.019). Post-hoc analyses suggested lower variability, higher stability and higher amplitude of CRA in the “Li” group. Medication groups were similar for the “late chronotype” dimension (p = 0.92). ConclusionsThis actigraphy study is the first to show more favorable CRA in BD-I individuals receiving a Li monotherapy when compared with those receiving other classes or combinations of mood stabilizers. Replications in larger samples are required. Prospective studies are also warranted to elucidate whether the introduction of Li or other mood stabilizers might influence CRA in BD-I.

Hybrid logistic regression support vector model to enhance prediction of bipolar disorder

Hybrid logistic regression support vector model to enhance prediction of bipolar disorder

Psychopharmacological Treatment of Depression and Anxiety and their Different Drug Delivery Targets

Abstract: General practitioners observe a high prevalence of anxiety and depression symptoms. Depressed or anxious patients frequently develop both conditions. The symptoms of both diseases may be present at the same time. There has been numerous studies on higher levels of depression, bipolar disorder II, and mixed depression. So, we ended up reviewing different drug delivery targets. Even at low dosages, antidepressants were better absorbed and were more effective when given by the nose. In this review, we focused on cutting-edge methods for intranasal antidepressant delivery vehicles. Consequently, it seems that drugs that are sufficiently effective, have fewer side effects, and are less expensive. The researchers in this metaanalysis set out to determine whether or not they have been used successfully in traditional medicine to treat depression in human or animal studies.

Mendelian randomisation analysis to explore the association between cathepsins and bipolar disorder

IntroductionBipolar disorder is a psychiatric condition characterized by the coexistence of depression and mania. Diagnosis of this disorder can be challenging due to limited pathologic and experimental tools. Treatment compliance is often poor due to medication side effects. Although cathepsin is known to play a significant role in diseases such as tumors and osteoporosis, its role in psychiatric disorders is not yet fully understood.ObjectiveThe aim of this study was to investigate the relationship between cathepsin in the blood circulation and bipolar disorder.MethodsThe causal relationship between cathepsin and different subtypes of bipolar affective disorder was explored using bidirectional Mendelian randomization analysis and multivariate analysis.ResultsIt was found that cathepsin H level was a protective factor for type II bipolar disorder. No potential causal relationship was found between cathepsin H and type I bipolar disorder, but cathepsin B changes with the development of type I bipolar disorder. A causal relationship was found between cathepsin H and cerebral dopamine neurotrophic factor.ConclusionsIn conclusion, cathepsin H may be a diagnostic target for bipolar II disorder and may play a guiding role in clinical diagnosis. Cathepsin H may have an effect on BD through cerebral dopamine neurotrophic factor.

Cariprazine in Bipolar Disorder and Substance Use: A Dual Approach to Treatment?

Bipolar disorder (BD) is characterized by recurrent episodes of mania, hypomania, and depression and is often complicated by comorbid substance use disorders (SUDs). Up to 60% of individuals with BD experience SUDs, which exacerbate mood instability and increase the risk of rapid cycling, suicide, and poor clinical outcomes. Current treatment strategies, including lithium and valproate, show limited efficacy in treating both BD and SUD. Psychotherapeutic approaches such as cognitive behavioral therapy (CBT) offer benefits but lack a specific focus on substances such as cannabis and cocaine. Since there is still debate on how to treat this comorbidity, there is a need to find new therapeutic options; this mini-review examines the pharmacological properties of cariprazine and its emerging role in the treatment of comorbid BD and SUD. Cariprazine, an atypical antipsychotic with partial agonism at dopamine D2 and D3 receptors, has shown promise in treating both mood symptoms and cognitive dysfunction in BD. Its unique affinity for D3 receptors, which are involved in motivation and reward processing, may offer advantages in reducing drug craving. Clinical trials indicate that cariprazine effectively treats manic, depressive, and mixed episodes in BD with a favorable side effect profile, particularly at lower doses. Preliminary results suggest its potential to reduce craving and substance use in individuals with co-occurring BD and SUD. Therefore, cariprazine, with its unique pharmacodynamic mechanism, could be further studied for the treatment of BD in comorbidity with SUD. However, evidence on the role of cariprazine in the treatment of SUDs remains limited, based primarily on case reports and animal studies. Further research, including large-scale clinical trials, is needed to determine its full efficacy in this dual diagnosis.

Comparative Study of Inflammatory Markers in Schizophrenia, FirstEpisode Psychosis, and Bipolar Disorder

Objective: An elevated level of NLR level is defined as an indicator of systemic inflammation, and it is stated that it can be used as an effective tool in navigating psychosis. The aim of the present study is to explore the blood parameters such as neutrophil, lymphocyte, and monocyte and their ratios (NLR, MLR, PLR) in both affective and non-affective psychosis. Materials and Methods: This is a retrospective case-control study conducted on schizophrenia(Sch), first-episode psychosis(FEP), and bipolar disorder(BD). Digital medical records were retrospectively analyzed between 2016 to 2021. The total number of patients recruited for this study is 437. Patients were divided into 3 groups which are schizophrenia (n:199), FEP (n:127), and Bipolar Disorder (n:111). The healthy control (HC) group (n:200) was selected who had never been diagnosed with any psychiatric disorders. Results: In this study, no difference was found between the patient groups in terms of substance use (Chi-square= 5.008; p= 0.082), platelet count was lower in SCH patients and no difference was found between the other groups in terms of platelet count. There was no statistical difference between the study groups in terms of lymphocyte, neutrophil, and monocyte counts and their ratios (NLR, MLR, PLR) (p&amp;gt;0.05 for each). Conclusion: In contrast to the previous findings, we did not show any significant differences in NLR, MLR, and PLR levels in both affective and non-affective psychosis. To better understand the pathophysiology of psychosis, it might be more suitable to conduct a clinical trial with drug-naive FEP patients in a prospective manner.

Delirium risk and mortality in people with pre-existing severe mental illness: a retrospective cohort study using linked datasets in England.

Delirium is a severe neuropsychiatric syndrome caused by physical illness, associated with high mortality. Understanding risk factors for delirium is key to targeting prevention and screening. Whether severe mental illness (SMI) predisposes people to delirium is not known. We aimed to establish whether pre-existing SMI diagnosis is associated with higher risk of delirium diagnosis and mortality following delirium diagnosis. A retrospective cohort and nested case-control study using linked primary and secondary healthcare databases from 2000-2017. We identified people diagnosed with SMI, matched to non-SMI comparators. We compared incidence of delirium diagnoses between people with SMI diagnoses and comparators, and between SMI subtypes; schizophrenia, bipolar disorder and 'other psychosis'. We compared 30-day mortality following a hospitalisation involving delirium between people with SMI diagnoses and comparators, and between SMI subtypes. We identified 20 566 people with SMI diagnoses, matched to 71 374 comparators. Risk of delirium diagnosis was higher for all SMI subtypes, with a higher risk conferred by SMI in the under 65-year group, (aHR:7.65, 95% CI 5.45-10.7, ⩾65-year group: aHR:3.35, 95% CI 2.77-4.05). Compared to people without SMI, people with an SMI diagnosis overall had no difference in 30-day mortality following a hospitalisation involving delirium (OR:0.66, 95% CI 0.38-1.14). We found an association between SMI and delirium diagnoses. People with SMI may be more vulnerable to delirium when in hospital than people without SMI. There are limitations to using electronic healthcare records and further prospective study is needed to confirm these findings.

Affective disorders: eliminate WArning signs And REstore functioning: AWARE. Results from a randomized controlled multimodular intervention study targeting functioning in patients with affective disorders.

There is a compelling need for innovative intervention strategies for patients with affective disorders, given their increasing global prevalence and significant associated disability and impaired functioning. This study aimed to investigate whether a comprehensive multimodule individualized intervention (AWARE), targeting known mediators of functioning, improves functioning in affective disorders. AWARE was a randomized, controlled, rater-blind clinical trial conducted at two centers in the Capital Region of Denmark (Clinicaltrials.gov, NCT04701827). Participants were adults with bipolar disorder or major depressive disorder and impaired functioning. Participants were randomized to the six-month AWARE intervention or treatment as usual (TAU). The AWARE intervention is based on the International Classification of Functioning, Disability and Health (ICF) Brief Core Set for Bipolar and Unipolar Disorder.The primary outcome was observation-based functioning using the Assessment of Motor and Process Skills (AMPS). Secondary outcomes were functioning, QoL, stress, and cognition. Between February 2021 and January 2023, 103 patients were enrolled; 50 allocated to AWARE treatment and 53 to TAU (96 included in the full analysis set). There was no statistically significant differential change over time between groups in the primary outcome (AMPS), however, both groups showed a statistically significant improvement at endpoint. The AWARE intervention had a statistically significant effect compared with TAU on secondary outcomes of patient-reported functioning, stress and cognition. Compared with TAU, the AWARE intervention was ineffective at improving overall functioning on the primary outcome, presumably due to the short duration of the intervention. Further development of effective treatments targeting functioning is needed.

Recurrence of mental disorders: Evidence from surveillance analysis

Psychosis is a psychiatric disorder characterized by hallucinations and delusions and include schizophrenia spectrum disorders and mood disorders such as depression and bipolar disorders. Treatment for psychosis lasts a long time with increased likelihood of hospitalization. Surveillance is used to monitor trends in mental disorders to predict and prevent recurrence. The objective of this paper was to the benefits of surveillance to prevent recurrence of mental disorders. The method consisted of a search for Google scholar, PubMed, NIHR and Research Gate. Ten articles obtained, while six were suitable for analysis based on suitability of purpose of the study. The results showed that surveillance variables consisted of risk factors, protective factors, triggers factors, and mental health indicators. The impact included socio-economic, disability, and the risk of suicide/self-harm. It is recommended to include surveillance activities in community-based psychosocial rehabilitation programs, so that recording signs or symptoms of relapse can be carried out routinely.

The role of immunomodulators in severe mental disorders: future perspectives.

The immune system is of pivotal importance with regard to the development and maintenance of mental illness. Aberrant cytokine levels are significant immune markers, and research is increasingly focusing on the complement system and the gut-brain axis. The efficacy and safety of immunomodulatory interventions are currently the subject of clinical studies. Hence, this review is timeline and relevant to evaluate the latest evidence on the clinical value of immunomodulatory treatments from studies over the past 18 months in schizophrenia, bipolar disorder and unipolar depression. While conventional psychotropic drugs (antidepressants, antipsychotics, lithium) appear to have immunomodulatory adverse effects, antibiotics (minocycline), nonsteroid anti-inflammatory drugs (celecoxib) and anti-inflammatory therapeutics in particular are the subject of ongoing clinical trials. Integrative medical interventions such as nutritional supplements (e.g., N-acetyl-l-cysteine, polyunsaturated fatty acids) and exercise interventions (e.g., running, yoga) are being evaluated for their immunomodulatory effects and clinical value. No evidence-based recommendation can be made for the immunomodulatory treatment of depression, although celecoxib appears to be more effective than minocycline and omega-3 fatty acid. N-acetylcysteine (NAC) may be beneficial for the treatment of bipolar and schizophrenia disorders. However, further translational research is required to confirm these findings.

Sexual Trauma, Polygenic Scores, and Mental Health Diagnoses and Outcomes

Leveraging real-world clinical biobanks to investigate the associations between genetic and environmental risk factors for mental illness may help direct clinical screening efforts and evaluate the portability of polygenic scores across environmental contexts. To examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder in a clinical biobank setting. This genetic association study was conducted using clinical and genotyping data from 96 002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee (including 58 262 individuals with high genetic similarity to the 1000 Genomes Project [1KG] Northern European from Utah reference population [1KG-EU-clustered] and 11 047 with high genetic similarity to the 1KG African-ancestry reference population of Yoruba in Ibadan, Nigeria [1KG-YRI-clustered]), and Mass General Brigham (MGB), Boston, Massachusetts (26 693 individuals with high genetic similarity to the combined European-ancestry superpopulation [1KG-EU-clustered]). Clinical data analyzed included diagnostic billing codes and clinical notes spanning from 1976 to 2023. Data analysis was performed from 2022 to 2024. Clinically documented sexual trauma disclosures and polygenic scores for schizophrenia, bipolar disorder, and major depressive disorder. Diagnoses of schizophrenia, bipolar disorder, and major depressive disorder, determined by aggregating related diagnostic billing codes, were the dependent variables in logistic regression models including sexual trauma disclosure status, polygenic scores, and their interactions as the independent variables. Across the VUMC and MGB biobanks, 96 002 individuals were included in analyses (VUMC 1KG-EU-clustered: 33 011 [56.7%] female; median [range] age, 56.8 [10.0 to >89] years; MGB 1KG-EU-clustered: 14 647 [54.9%] female; median [range] age, 58.0 [10.0 to >89] years; VUMC 1KG-YRI-clustered: 6961 [63.0%] female; median [range] age, 44.6 [10.1 to >89] years). Sexual trauma history was associated with all mental health conditions across institutions (ORs ranged from 8.83 [95% CI, 5.50-14.18] for schizophrenia in the VUMC 1KG-YRI-clustered cohort to 17.65 [95% CI, 12.77-24.40] for schizophrenia in the VUMC 1KG-EU-clustered cohort). Sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of mental health phenotypic variance. Schizophrenia and bipolar disorder polygenic scores had greater associations with mental health outcomes in individuals with no documented disclosures of sexual trauma (schizophrenia interaction: OR, 0.70 [95% CI, 0.56-0.88]; bipolar disorder interaction: OR, 0.83 [95% CI, 0.74-0.94]). Sexual trauma and mental health polygenic scores, while correlated with one another, were independent and joint risk factors for severe mental illness in a large, diverse hospital biobank population. Furthermore, associations of schizophrenia and bipolar disorder polygenic scores with respective diagnoses were greater in those without disclosures, suggesting that genetic predisposition to mental illness as measured by polygenic scores may be less impactful in the presence of this severe environmental risk factor.

A cluster analysis of attachment styles in patients with borderline personality disorder, bipolar disorder and ADHD

BackgroundInsecure adult attachment has been associated with psychiatric disorders characterized by emotional dysregulation, such as borderline personality disorder (BPD), bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD). However, little is known about the differences in attachment patterns between these diagnostic groups. The aim of this study was to identify clusters of adult attachment style in a cross-diagnostic group of patients with BDP and/or BD and/or ADHD and explore the characteristics of these clusters based on temperament profile, childhood trauma and psychiatric diagnoses.MethodsK-means cluster analysis was used to identify subgroups, based on the Attachment Style Questionnaire Short Form dimensions, in a clinical cohort of 150 young adults (113 women and 37 men, mean age ± SD = 23.3 ± 2.1) diagnosed with BPD, and/or BD, and/or ADHD.ResultsThree distinct clusters were identified: a secure, an insecure/avoidant-anxious and an insecure/avoidant cluster. These three clusters differed in temperament profile and related psychiatric diagnoses.ConclusionsThe three clusters of attachment in individuals with BPD, BD and/or ADHD could support differentiation between the disorders as well provide information usable for planning of treatment.