Longitudinal course of inflammatory-cognitive subgroups across first treatment severe mental illness and healthy controls.

BACKGROUND: While inflammation is associated with cognitive impairment in severe mental illnesses (SMI), there is substantial heterogeneity and evidence of transdiagnostic subgroups across schizophrenia (SZ) and bipolar (BD) spectrum disorders. There is however, limited knowledge about the longitudinal course of this relationship. METHODS: Systemic inflammation (C-Reactive Protein, CRP) and cognition (nine cognitive domains) was measured from baseline to 1 year follow-up in first treatment SZ and BD (n = 221), and healthy controls (HC, n = 220). Linear mixed models were used to evaluate longitudinal changes separately in CRP and cognitive domains specific to diagnostic status (SZ, BD, HC). Hierarchical clustering was applied on the entire sample to investigate the longitudinal course of transdiagnostic inflammatory-cognitive subgroups. RESULTS: There were no case-control differences or change in CRP from baseline to follow-up. We confirm previous observations of case-control differences in cognition at both time-points and domain specific stability/improvement over time regardless of diagnostic status. We identified transdiagnostic inflammatory-cognitive subgroups at baseline with differing demographics and clinical severity. Despite improvement in cognition, symptoms and functioning, the higher inflammation - lower cognition subgroup (75% SZ; 48% BD; 38% HC) had sustained inflammation and lower cognition, more symptoms, and lower functioning (SMI only) at follow-up. This was in comparison to a lower inflammation - higher cognition subgroup (25% SZ, 52% BD, 62% HC), where SMI participants showed cognitive functioning at HC level with a positive clinical course. CONCLUSIONS: Our findings support heterogenous and transdiagnostic inflammatory-cognitive subgroups that are stable over time, and may benefit from targeted interventions.

Dosing levels of antipsychotics and mood stabilizers in bipolar disorder: A Nationwide cohort study on relapse risk and treatment safety.

BACKGROUND: Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non-psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder. METHODS: Individuals aged 15-65 with bipolar disorder were identified from Finnish national health registers in 1996-2018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time-varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non-psychiatric hospitalization (treatment safety). Stratified Cox regression in within-individual design was used. RESULTS: The cohort included 60,045 individuals (mean age 41.7 years, SD 15.8; 56.4% female). Mean follow-up was 8.3 years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57-0.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56-0.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non-psychiatric hospitalization. Lithium was associated with a decreased risk of non-psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84-0.93) and standard doses (aHR 0.81, 95% CI 0.74-0.88). CONCLUSIONS: Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non-psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose.

Characterization of Bipolar Disorder I and II: Clinical Features, Comorbidities, and Pharmacological Pattern.

Objective: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition provides precise diagnostic criteria to differentiate between bipolar disorder (BD) type I and II; nevertheless, it can be challenging to come up with the right diagnosis. The aim of this study is to evaluate the sociodemographic differences, clinical features, comorbidities, and pharmacological pattern between patients with BD type I and II. Methods: A total of 680 patients with BD type I and II were consecutively recruited to our psychiatry department. A semi-structured interview was used to collect several information. Results: Patients with BD type I were mostly males, single, with a lower current age, and unemployed compared to patients with BD type II. Furthermore, patients with BD type I showed an earlier age at onset and a significant higher prevalence of psychotic and residual symptoms, a higher number of hospitalizations, and involuntary admissions. On the other hand, patients with BD type II were associated with a significant higher prevalence of lifetime suicide attempts, psychiatric comorbidities, and use of alcohol. Finally, antidepressant drugs were prescribed more often to patients with BD type II, while antipsychotics and mood stabilizers were mostly prescribed in patients with BD type I. Conclusion: the differentiation of the 2 nosologic bipolar diagnosis is in line with the current scientific interest, confirming the existence of a markedly different profile between BD type I and II. This differentiation could reduce the heterogeneity of bipolar presentation in research, optimize clinical assessment, and increase the interest in developing more precise and individualized therapeutic strategies, also implementing psychosocial therapies.

Predicting remission after acute phase pharmacotherapy in patients with bipolar I depression: A machine learning approach with cross-trial and cross-drug replication.

OBJECTIVES: Interpatient variability in bipolar I depression (BP-D) symptoms challenges the ability to predict pharmacotherapeutic outcomes. A machine learning workflow was developed to predict remission after 8 weeks of pharmacotherapy (total score of ≤8 on the Montgomery Åsberg Depression Rating Scale [MADRS]). METHODS: Supervised machine learning models were trained on data from BP-D patients treated with olanzapine (N = 168) and were externally validated on patients treated with olanzapine/fluoxetine combination (OFC; N = 131) and lamotrigine (LTG; N = 126). Top predictors were used to develop a prognosis rule informing how many symptoms should change and by how much within 4 weeks to increase the odds of achieving remission. RESULTS: An AUC of 0.76 (NIR:0.59; p = 0.17) was established to predict remission in olanzapine-treated subjects. These trained models achieved AUCs of 0.70 with OFC (NIR:0.52; p < 0.03) and 0.73 with LTG (NIR:0.52; p < 0.003), demonstrating external replication of prediction performance. Week-4 changes in four MADRS symptoms (reported sadness, reduced sleep, reduced appetite, and concentration difficulties) were top predictors of remission. Across all pharmacotherapies, three or more of these symptoms needed to improve by ≥2 points at Week-4 to have a 65% chance of achieving remission at 8 weeks (OR: 3.74, 95% CI: 2.45-5.76; p < 9.3E-11). CONCLUSION: Machine learning strategies achieved cross-trial and cross-drug replication in predicting remission after 8 weeks of pharmacotherapy for BP-D. Interpretable prognoses rules required only a limited number of depressive symptoms, providing a promising foundation for developing simple quantitative decision aids that may, in the future, serve as companions to clinical judgment at the point of care.

British contributions to the therapeutic use of John Cade's lithium.

Coinciding with the 75th anniversary of John Cade's seminal publication that first reported lithium's antimanic efficacy, we briefly recount the salient findings of the historic paper and draw attention to the important psychiatric research in Britain that reinforced its findings and the critical British opinions that likely impeded its clinical use.

Effects of cognitive training under hypoxia on cognitive proficiency and neuroplasticity in remitted patients with mood disorders and healthy individuals: ALTIBRAIN study protocol for a randomized controlled trial.

BACKGROUND: Cognitive impairment is prevalent across neuropsychiatric disorders but there is a lack of treatment strategies with robust, enduring effects. Emerging evidence indicates that altitude-like hypoxia cognition training may induce long-lasting neuroplasticity and improve cognition. We will investigate whether repeated cognition training under normobaric hypoxia can improve cognitive functions in healthy individuals and patients with affective disorders and the neurobiological underpinnings of such effects. METHODS: In sub-study 1, 120 healthy participants are randomized to one of four treatment arms in a double-blind manner, allowing for examination of separate and combined effects of three-week repeated moderate hypoxia and cognitive training, respectively. In sub-study 2, 60 remitted patients with major depressive disorder or bipolar disorder are randomized to hypoxia with cognition training or treatment as usual. Assessments of cognition, psychosocial functioning, and quality of life are performed at baseline, end-of-treatment, and at 1-month follow-up. Functional magnetic resonance imaging (fMRI) scans are conducted at baseline and 1-month follow-up, and [11C]UCB-J positron emission tomography (PET) scans are performed at end-of-treatment to quantify the synaptic vesicle glycoprotein 2A (SV2A). The primary outcome is a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference with minimum n = 26 per treatment arm. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data is analyzed with the FMRIB Software Library, while PET data is quantified using the simplified reference tissue model (SRTM) with centrum semiovale as reference region. DISCUSSION: The results will provide novel insights into whether repeated hypoxia cognition training increases cognition and brain plasticity, which can aid future treatment development strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06121206 . Registered on 31 October 2023.

Divergent pattern of functional connectivity within the dorsal attention network differentiates schizophrenia and bipolar disorder patients.

Introduction: Schizophrenia (SZ) and bipolar disorder (BD) share common clinical features, symptoms, and neurocognitive deficits, which results in common misdiagnosis. Recently, it has been suggested that alterations within brain networks associated with perceptual organization yield potential to distinguish SZ and BD individuals. The aim of our study was to evaluate whether functional connectivity (FC) of the dorsal attention network (DAN) may differentiate both conditions. Methods: The study involved 90 participants: 30 remitted SZ patients, 30 euthymic BD patients, and 30 healthy controls (HC). Resting state functional magnetic resonance imaging was used to compare the groups in terms of the FC within the core nodes of the DAN involving frontal eye fields (FEF) and intraparietal sulcus (IPS). Results: BD patients presented weaker inter-hemispheric FC between right and left FEF than HC. While SZ did not differ from HC in terms of inter-FEF connectivity, they presented increased inter- and intra-hemispheric FC between FEF and IPS. When compared with BD, SZ patients showed increased FC between right FEF and other nodes of the network (bilateral IPS and left FEF). Conclusion: We have shown that altered resting state FC within DAN differentiates BD, SZ, and HC groups. Divergent pattern of FC within DAN, consisting of hypoconnectivity in BD and hyperconnectivity in SZ, might yield a candidate biomarker for differential diagnosis between both conditions. More highly powered studies are needed to confirm these possibilities.

Exploring the efficacy and tolerability of two-injection start regimen of long-acting aripiprazole: A descriptive case series analysis.

Bipolar disorder is the fourth most debilitating psychiatric illness in the world regarding Disability Adjusted Life Years and manic episodes frequently lead to lengthy hospitalizations which restricts the freedom of patients. Therefore, decreasing the length of hospitalization with safer agents is of utmost importance in the treatment of manic episodes. Aripiprazole is a medication known for its efficacy in managing mania associated with bipolar disorder. Aripiprazole long-acting injection is approved for the treatment of mania associated with bipolar disorder in adults and found efficacious as a maintenance treatment. In the treatment of schizophrenia, European Medicines Agency has approved a simplified starting strategy of aripiprazole once a month, with two 400 mg injections and a single oral 20 mg dose of aripiprazole. To the best of our knowledge, no previous study has reported the safety, tolerability, and efficacy of this regimen in adult bipolar disorder patients. We present a case series of eight patients who were admitted to the hospital in a manic episode with psychotic features. We observed that the double injection start regimen was effective in treating manic symptoms with no specific severe adverse events. We conclude from a small sample of manic patients that a double injection start regimen has good efficacy and tolerability.

Refining criteria for a neurodevelopmental sub-phenotype of bipolar disorders: a FondaMental Advanced Centers of Expertise for Bipolar Disorders study.

BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. Neurodevelopmental factors were suggested to contribute to the etiology of BD, yet a specific neurodevelopmental phenotype of the disorder remains unidentified. Our objective was to define and characterize a neurodevelopmental phenotype (NDP) in BD and validate its associations with clinical outcomes, polygenic risk scores (PGS), and treatment responses. METHOD: We analyzed the FACE-BD cohort of 4,468 BD patients, a validation cohort of 101 BD patients, and two independent replication datasets of 274 and 89 BD patients. Using factor analyses, we identified a set of criteria for defining NDP. We next developed a scoring system for NDP-load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and sex with bootstrap replications. RESULTS: Our study established a NDP in BD consisting of nine clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention deficit hyperactivity disorder (ADHD), early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, specific learning disorders. Patients with higher NDP-load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between the NDP-load and PGS for ADHD suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and ADHD. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.

Relationships between emotional states, bipolar disorder, and gastrointestinal disorders: A two-sample Mendelian randomization study.

BACKGROUND: Functional gastrointestinal symptoms are frequently observed in patients with bipolar affective disorder, but the causal relationship between these conditions remains unclear. To establish causality, this study utilized Mendelian randomization (MR) with data from large-scale genomic research. The investigation aimed to elucidate the relationship between emotional states, bipolar disorder, and functional gastrointestinal disorders (FGIDs). METHODS: Summary statistics from GWAS were utilized for mood swings (UK biobank, N = 451,619), irritable mood (UK biobank, N = 373,733), bipolar disorder (UK biobank, N = 352,006),functional dyspepsia (FinnGen biobank, N = 194,071), and irritable bowel syndrome (UK biobank, N = 486,601). All GWAS summary statistics were derived from individuals of European ancestry. The primary analysis employed the inverse variance-weighted method for Mendelian randomization (MR). Additionally, we conducted tests for heterogeneity and pleiotropy to ensure the robustness of our results. RESULTS: A suggestive positive causal relationship was identified between mood swings-related conditions and IBS using the inverse variance-weighted (IVW) method [mood swings-IBS: OR/95%CI: 3.221(2.417,4.294), P(1.42E-15); irritable mood-IBS: OR/95%CI: 1.881(1.615,2.191), P(4.56E-16); bipolar disorder-IBS: OR/95%CI: 1.003(1.001,1.006), P(0.009)]. For functional dyspepsia, a suggestive positive causal relationship was observed with mood swings [mood swings-FD: OR/95%CI: 2.827(1.124,7.109), P(0.027)]. In the reverse analysis, causal relationship was observed between IBS and emotional states [IBS and mood swings: OR/95%CI: 1.030(1.021,1.040), P(1.10E-10); IBS and irritable mood: OR/95%CI: 1.064(1.041,1.087), P(2.58E-08)]. CONCLUSIONS: Mood swings, irritable mood, and bipolar disorder were associated with an increased risk of functional gastrointestinal disorders (FGIDs). Additionally, reverse analysis revealed a causal relationship between irritable bowel syndrome (IBS) and both mood swings and irritable mood. These findings suggest that targeted emotional interventions may be beneficial for patients with FGIDs. Further research is warranted to explore the relationship between mood instability-related disorders and FGIDs, particularly IBS.

Acute kidney injury induced lithium toxicity with concomitant neuroleptic malignant syndrome.

Lithium, despite being an indispensable agent in the treatment of psychiatric disorders, has a narrow therapeutic index and needs to be carefully administered. Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal complication due to central dopaminergic blockade. This case report illustrates the challenges in lithium therapy particularly related to the development of NMS when further risk factors such as polypharmacy and dehydration are present. We report a case of a 50-year-old man with underlying bipolar affective disorder who was previously able to tolerate olanzapine and lithium well, however developed chronic lithium toxicity due to diminished lithium elimination in acute kidney injury following a two-week history of viral acute gastroenteritis. He also developed NMS which could either be triggered independently by olanzapine; lithium toxicity; or attributed by a synergistic combination from lithium and olanzapine which led to an enhanced neurotoxicity in an already unstable dopaminergic pathway. Fluid therapy and supportive care allowed the patient to recover, and he was discharged well with a lower potency neuroleptic with slow dose titration.

The association of pain screening and pain level with suicide among US veterans with comorbid musculoskeletal and bipolar disorder diagnoses.

BACKGROUND: High suicide rates are documented among persons with bipolar disorder diagnoses and pain diagnoses, but few studies have examined the association of pain with suicide mortality in individuals with comorbid pain and bipolar disorders. This study assessed the association of pain screening and pain severity with suicide mortality among veterans with comorbid bipolar and musculoskeletal disorder (MSD) diagnoses. METHODS: A retrospective cohort study was conducted on 168,021 patients within the Veterans Health Administration (VHA) who received an MSD diagnosis from 2000 to 2015 and had a bipolar disorder diagnosis. Pain severity, comorbidities, demographics, and suicide mortality were extracted from VHA databases. Poisson regression examined relative risk of suicide by the presence pain screening and pain severity ratings. RESULTS: Pain was assessed in 72.73 % of veterans. Suicide risk was greater in those not assessed (0.98 % versus 0.77 % in assessed group). However, this result did not persist after adjusting for covariates (RR = 1.06). Among those assessed, higher suicide risk was associated with moderate (RR = 1.10), severe pain (RR = 1.06), and no pain (reference) relative to mild pain (RR = 0.99). Major depression, substance use disorders, and prescribed opioids and benzodiazepines increased risk. LIMITATIONS: Data were obtained from medical records; diagnoses were not confirmed via formal assessment, and no information was available on actual medication use or purpose. Over 25 % of the sample were missing pain severity ratings, which could have affected results. CONCLUSIONS: Suicide risk factors among persons with bipolar disorder are complex and multifactorial. Providers should prioritize suicide prevention efforts following new onset or worsening pain.

Delays in bipolar depression treatment in primary care vs. integrated behavioral health and specialty care.

INTRODUCTION: While bipolar disorder is not uncommon in primary care, collaborative care models for bipolar depression treatment are underdeveloped. Our aim was to compare initial pharmacological treatment patterns for an episode of bipolar depression in different care models, namely primary care (PC), integrated behavioral health (IBH), and mood specialty clinic (SC). METHODS: A retrospective study of adults diagnosed with bipolar disorder who received outpatient care in 2020 was completed. Depressive episodes were captured based on DSM-5 criteria, ICD codes, or de novo emergent symptom burden (PHQ-9 ≥ 10). Pharmacological strategies were classified as 1) continuation of current regimen, 2) dose increase or 3) augmentation 4) switch to monotherapy or 5) a combination of more than two different strategies. Logistic regression was applied. RESULTS: A total of 217 encounters (PC = 32, IBH = 53, SC = 132) representing 186 unique patients were identified. PC was significantly more likely to continue the current regimen, while combination strategies were significantly more likely recommended in IBH and SC. Mood stabilizers were significantly more utilized in IBH and SC. There were no significant group differences in antidepressant use. LIMITATIONS: Retrospective study design at a single site. CONCLUSIONS: This study provides evidence of delays in depression care in bipolar disorder. This is the first study to compare treatment recommendations for bipolar depression in different clinical settings. Future studies are encouraged to better understand this gap and to guide future clinical practice, regardless of care model, emphasizing the potential benefits of decision support tools and collaborative care models tailored for bipolar depression.

Efficacy of racemic ketamine or esketamine monotherapy for reducing suicidal ideation in uni- or bipolar depression: a systematic review and meta-analysis.

The current systematic review and meta-analysis examined the effect of racemic ketamine or esketamine on suicidal ideation in individuals with uni- or bipolar depression. We searched the MEDLINE, Embase, Central, PsycINFO, and Web of Science databases to identify randomized controlled trials that examined the effect of racemic ketamine or esketamine monotherapy on suicidal ideation (SI) in individuals with uni- or bipolar depression. The two monotherapies were compared; the primary outcome was the rate of remission of SI, and the secondary outcome was the SI score. The risk ratio was used as an effect size measure for binary variables, while the standardized mean difference was used as an effect size measure for continuous variables. Our meta-analysis included 13 randomized controlled trials involving 1,1109 individuals with uni- or bipolar depression. Patients receiving racemic ketamine monotherapy had a significantly higher acute SI remission rate than those receiving placebo or midazolam (RR = 2.06, 95% CI 1.47 to 2.91, P < 0.0001). Racemic ketamine also led to significantly lower SI scores than placebo or midazolam (SMD = -0.36, 95% CI -0.71 to -0.01, P = 0.04). The evidence for the treatment of SI with esketamine was inconsistent. The pooled effect sizes for long-term anti-SI effects did not reveal significant differences between therapies. Our study indicated the efficacy of racemic ketamine monotherapy for rapidly and transiently reducing SI in individuals with uni- or bipolar depression, but the efficacy of racemic ketamine monotherapy against long-term suicidal ideation remains unclear. There is not -sufficient evidence to support the anti-suicidal effects of esketamine monotherapy.Protocol registration: Prospero registration number: CRD42023434380.

Obsessive-compulsive symptoms relating to psychosocial functioning for people with schizophrenia, schizoaffective disorder, or bipolar disorder.

To assess the psychosocial functioning concerning obsessive-compulsive symptoms (OCS) and/or obsessive-compulsive disorder (OCD) comorbidity in people with schizophrenia, schizoaffective disorder, or bipolar disorder diagnosed in a large case register database in Southeast London. Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) register using Clinical Record Interactive Search (CRIS) system, a platform allowing research on full but de-identified electronic health records for secondary and tertiary mental healthcare services. Information of schizophrenia, schizoaffective disorder, bipolar disorder diagnosis and OCS/OCD status was ascertained from structural or free-text fields through natural language processing (NLP) algorithms based on artificial intelligence techniques during the observation window of January 2007 to December 2016. Associations between comorbid OCS/OCD and recorded Health of the Nation Outcome Scales (HoNOS) for problems with activities of daily living (ADLs), living conditions, occupational and recreational activities, and relationships were estimated by logistic regression with socio-demographic confounders controlled. Of 15,412 subjects diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder, 2,358 (15.3%) experienced OCS without OCD, and 2,586 (16.8%) had OCD recorded. The presence of OCS/OCD was associated with more problems with relationships (adj.OR = 1.34, 95% CI: 1.25-1.44), ADLs (adj.OR = 1.31, 95%CI: 1.22-1.41), and living conditions (adj.OR = 1.31, 95% CI: 1.22-1.41). Sensitivity analysis revealed similar outcomes. Comorbid OCS/OCD was associated with poorer psychosocial functioning in people with schizophrenia, schizoaffective disorder, or bipolar disorder. This finding highlights the importance of identification and treatment of comorbid OCS among this vulnerable patient group.

The belief that being high is a natural part of your personality predicts an increase in manic symptoms over time in bipolar disorder.

BACKGROUND: Several psychological models of bipolar disorder propose that certain types of appraisals can lead to increases in manic symptoms. AIMS: We tested whether the belief that being 'high' is a natural part of one's personality and correlates with manic symptoms 4 months later when controlling for manic symptoms at baseline. METHOD: This was a prospective 4-month follow-up design using self-report measures. Forty people with a diagnosis of bipolar disorder completed a measure of manic symptoms, a measure of appraisals associated with bipolar disorder, and a single-item measure, 'To what extent do you feel like being "high" is a natural part of your personality?', at baseline and follow-up. RESULTS: The single-item measure showed modest stability over time and construct validity in its correlation with a standardised measure of appraisals in bipolar disorder. As predicted, the single-item measure correlated with manic symptoms at follow-up when controlling for manic symptoms at baseline. CONCLUSIONS: The belief that being 'high' is a natural part of one's personality is a potential predictor of manic symptoms. Further research needs to study the potential mediating mechanisms such as activating behaviours, and control for indicators of the bipolar endophenotype.

Assessing the Trajectory of Bipolar Disorder Effectively in Order to Treat Effectively.

Accurate diagnosis of mood disorders, particularly depression and bipolar disorder, is essential for effective treatment planning and patient management. This article emphasizes the need for systematic symptom assessment and longitudinal analysis in facilitating the precise diagnosis and planning appropriate treatment interventions. By meticulously evaluating the symptomatology and delineating the longitudinal trajectory of the illness, clinicians can distinguish between unipolar depression and bipolar disorder, and therefore optimise patient outcomes. The article describes the inherent complexities in diagnosing mood disorders. It describes the overlapping symptomatology and diagnostic challenges. Through a comprehensive review of literature and clinical insights, it argues for a structured approach to symptom assessment, focusing on both the current presentation and also retrospective evaluation of illness progression. By elucidating the longitudinal trajectory of the illness, including the presence of episodes of high mood suggestive of bipolar disorder, clinicians can differentiate between mood disorders accurately. The article discusses the implications of accurate diagnosis on treatment planning and patient prognosis. A precise diagnosis enables clinicians to plan treatment strategies to the specific needs of the individual, including pharmacotherapy, psychotherapy, or both. By addressing the underlying mechanisms and trajectory of the illness, clinicians can implement targeted interventions which reduce the risk of misdiagnosis and which optimize therapeutic outcomes.

Linking hearts and minds: understanding the cardiovascular impact of bipolar disorder.

Bipolar disorder is a severe and recurring condition that has become a significant public health issue globally. Studies indicate a heightened risk and earlier onset of cardiovascular diseases among individuals with bipolar disorder, potentially increasing mortality rates. The chronic nature of bipolar disorder leads to disturbances across multiple systems, including autonomic dysfunction, over-activation of the hypothalamic-pituitary-adrenal axis and increased levels of peripheral inflammatory markers. These disruptions cause endothelial damage, the formation of plaques and blood clots, in addition to the medications used to treat bipolar disorder and genetic associations contributing to cardiovascular disease development. Understanding the complex interplay between bipolar disorder and cardiovascular events is essential for the prevention and effective management of cardiovascular conditions in individuals with bipolar disorder.

Bipolar disorder is a mental health condition that affects mood and behavior, significantly impacting the lives of many people around the world. People with this disorder are also at a higher risk for heart diseases, including heart attacks and strokes. Certain lifestyle factors, common among people with bipolar disorder, such as smoking, poor diet and lack of exercise, can cause inflammation and stress, which damage blood vessels and increase the likelihood of heart conditions. The relationship between bipolar disorder and heart disease is complex. The condition affects how the body handles stress and can disrupt normal heart functions. For instance, stress from bipolar disorder can lead to high blood pressure and irregular heartbeats and certain medications taken by those with bipolar disorder can further damage the heart. To better manage these risks, it's important to understand the connection between bipolar disorder and heart disease. Future research should focus on creating guidelines for regular heart health check-ups for people with bipolar disorder and improving overall care to help prevent unfavorable outcomes.

Case report: IORT as an alternative treatment option for breast cancer patients with difficulty staying still.

Background: Administering radiation therapy to individuals with intellectual disabilities (ID) and psychiatric patients taking antipsychotics poses challenges, especially with whole breast irradiation (WBI) due to difficulty staying still (DSS). In such scenarios, intraoperative radiotherapy (TARGIT-IORT) provides an alternative. Although prior studies have shown its applicability in special cases where WBI may be contraindicated, there is a paucity of literature emphasizing its role in patients with ID and psychiatric conditions who have DSS. Therefore, our case series aims to highlight the applicability of administering TARGIT-IORT in such patients. Case reports: Four breast cancer patients underwent lumpectomy and TARGIT-IORT. Among them, two patients had ID, with one experiencing a decreased range of motion. The other two had psychiatric disorders, including schizophrenia and bipolar disorder, both manifesting involuntary movements and DSS. Three patients had invasive ductal carcinoma (IDC), and one had invasive lobular carcinoma (ILC). All patients undergoing TARGIT-IORT tolerated the procedure well. Notably, none of the patients exhibited evidence of disease on follow-up. Conclusion: Our study underscores the potential use of TARGIT-IORT as a viable treatment option for breast cancer patients with intellectual and psychiatric disabilities. Unlike traditional EBRT, TARGIT-IORT offers a single radiation dose, addressing challenges associated with compliance or DSS. Our findings demonstrate positive outcomes and tolerance, especially in patients where standard oncologic procedures are difficult to achieve. TARGIT-IORT could also benefit breast cancer patients with concurrent movement disorders like Parkinson's disease and other movement disorders. Nonetheless, future studies are needed to reinforce its applicability for patients with DSS.

GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.

The microcircuitry within superficial layers of the dorsolateral prefrontal cortex (DLPFC), composed of excitatory pyramidal neurons and inhibitory GABAergic interneurons, has been suggested as the neural substrate of working memory performance. In schizophrenia, working memory impairments are thought to result from alterations of microcircuitry within the DLPFC. GABAergic interneurons, in particular, are crucially involved in synchronizing neural activity at gamma frequency, the power of which increases with working memory load. Alterations of GABAergic interneurons, particularly parvalbumin (PV) and somatostatin (SST) subtypes, are frequently observed in schizophrenia. Abnormalities of GABAergic neurotransmission, such as deficiencies in the 67 kDA isoform of GABA synthesis enzyme (GAD67), vesicular GABA transporter (vGAT), and GABA reuptake transporter 1 (GAT1) in presynaptic boutons, as well as postsynaptic alterations in GABA A receptor subunits further contribute to impaired inhibition. This review explores GABAergic abnormalities of the postmortem DLPFC in schizophrenia, with a focus on the roles of interneuron subtypes involved in cognition, and GABAergic neurotransmission within presynaptic boutons and postsynaptic alterations. Where available, comparisons between schizophrenia and affective disorders that share cognitive pathology such as bipolar disorder and major depressive disorder will be made. Challenges in directly measuring GABA levels are addressed, emphasizing the need for innovative techniques. Understanding GABAergic abnormalities and their implications for neural circuit dysfunction in schizophrenia is crucial for developing targeted therapies.