Severity Of Bipolar Disorder Research Articles

The effect of bipolar effective disorder and low socio-economic status on juvenile delinquents in Pakistan

Bipolar disorder remains a significant taboo in Pakistan, particularly among juvenile delinquents, leading to their social segregation. The prevalence of this mood disorder in Pakistani youth is concerning, largely due to limited awareness and inadequate mental health resources for children and adolescents. Economic instability, family conflict, and lack of access to care contribute to chronic stress, delaying the diagnosis and treatment of bipolar disorder. This study aimed to explore the relationship between socio-economic status and bipolar disorder in juvenile offenders, focusing on the role of social support. We included 220 children, aged 12 to 18, diagnosed with severe bipolar disorder. Most lived with both biological parents, while some were in single-parent households due to separation or loss. Our findings indicated that low socio-economic status significantly impacts mental health and personality development. Factors such as financial instability, inadequate housing, and lack of access to quality healthcare increase feelings of inferiority, leading to higher rates of bipolar disorder. Notably, 88.4% of participants exhibited extreme symptoms, with a higher prevalence in males (55%) than females (29%). The delinquency rate was significant, with 56% of boys and 32% of girls involved in criminal activities. These results suggest a strong correlation between low socio-economic status and the severity of bipolar disorder in juvenile delinquents. Many young individuals resort to crime due to unmet basic needs, reinforcing the idea that socio-economic challenges directly influence mental health outcomes. Overall, these findings underscore the urgent need for improved mental health care and support for vulnerable youth in Pakistan.

Risk of childhood trauma exposure and severity of bipolar disorder in Colombia

IntroductionBipolar disorder (BD) is higher in developing countries. Childhood trauma exposure is a common environmental risk factor in Colombia and might be associated with a more severe course of bipolar disorder in Low-Middle Income-Countries. We carried out the first case-control study (114 BD patients and 191 controls) in Colombia using a structural clinical interview and the Childhood Trauma Questionnaire-Short Form (CTQ-SF) to describe the prevalence and association between trauma exposure during childhood with a severe course of illness in a sample of BD patients.Objectivesto describe the prevalence and association between trauma exposure during childhood with a severe course of illness in a sample of BD patients.MethodsA case-control study (114 controls versus 191 controls) that assessed outpatients between 18 and 65 years old, at a teaching hospital in Barranquilla, Colombia was carried-out. All participants were assessed with the SCID-5-CV, the Young Mania Rating Scale (YMRS), and the Bipolar Depression Rating Scale (BDRS). Additionally, exposure to childhood trauma was assessed using The Childhood Trauma Questionnaire-Short Form (CTQ-SF). The CTQ-SF is a brevity 28-item Likert-type, with a five-factor structure: emotional abuse EA, physical abuse PA, sexual abuse SA, physical neglect PN, and emotional neglect EN, self-administered instrument in order to assess multiple types of trauma during childhood.We generate an outcome variable named severe bipolar disorder defined by course severe of bipolar disorder as the presence of any clinical indicator of severity, previously delimited by the research team (early-onset, rapid cycling, ideation or suicide attempt, or 3 or more hospitalizations per year). Also, we carried out bivariate and regression analyses with each clinical indicator of severity as an outcome.ResultsCases included 61.4% BD type I and 38.6% BD type II. The median age was 31.5 years (IQR, 75-24) for BD patients and 31 years old (IQR, 38-24) for healthy controls. A higher prevalence of childhood trauma was evidenced in cases compared to controls.Multivariate logistic regression model in severe bipolar disorderSevere Bipolar DisorderVariableBSEOR95% CIp valuep modelR2Emotional Abuse0.830.362.301.753.03<0.001<0.0010.10Physical Abuse1.070.432.921.545.53<0.001<0.001Sexual Abuse1.610.445.044.735.36<0.001<0.001Physical Neglect0.280.491.320.931.870.117<0.001Emotional Neglect1.240.383.452.285.23<0.001<0.001ConclusionsThis is the first association study between childhood trauma exposure as a higher risk for a severe course of illness in BD patients in Colombian. Our findings highlight the importance of screening and evaluating childhood trauma exposure during the course of BD patients.Disclosure of InterestNone Declared

Risk of childhood trauma exposure and severity of bipolar disorder in Colombia

BackgroundBipolar disorder (BD) is higher in developing countries. Childhood trauma exposure is a common environmental risk factor in Colombia and might be associated with a more severe course of bipolar disorder in Low-Middle Income-Countries. We carried out the first case–control study in Colombia using a structural clinical interview and the Childhood Trauma Questionnaire-Short Form (CTQ-SF) to describe the prevalence and association between trauma exposure during childhood with a severe course of illness (early age onset, rapid cycling, ideation or suicide attempt, or ≥ 3 hospitalization) in a sample of BD patients.ResultsA total of 114 cases and 191 controls evaluated showed the following results. Cases included 61.4% BD type I and 38.6% BD type II. The median age was 31.5 years (IQR, 75–24) for BD patients and 31 years old (IQR, 38–24) for healthy controls. A higher prevalence of childhood trauma was evidenced in cases compared to controls. Emotional abuse, physical abuse, sexual abuse, physical neglect and emotional neglect evidenced a strong association with severe bipolar disorder (OR = 3.42, p < .001; OR = 4.68, p < .001; OR = 4.30, p = .003; OR = 5.10, p < .001; OR = 5.64, p < .001, respectively).ConclusionsThis is the first association study between childhood trauma exposure as a higher risk for a severe course of illness in BD patients in Colombian. Our findings highlight the higher prevalence of childhood trauma in bipolar patients and the strong association of childhood trauma with severe bipolar disorder. These findings are relevant for screening and evaluating childhood trauma exposure during the course of BD patients.

Association of premorbid intelligence with level of functioning and illness severity in bipolar disorder

BackgroundBipolar disorder is a severe psychiatric syndrome defined by periodic mood shifts. Patients with bipolar disorder show cognitive impairments relative to healthy controls. The risk of developing schizophrenia, and partially also bipolar disorder, has previously been shown to increase with lower premorbid intelligence. It is not known if premorbid intelligence is associated with level of functioning and illness severity of people having developed bipolar disorder. MethodsWe used multiple linear and ordinal regression to analyze how premorbid intelligence, as measured at conscription, associate with functional outcome and illness severity in Swedish male bipolar disorder patients (n = 788). ResultsWe found that lower premorbid intelligence is associated with lower percentage of time in work, after adjusting for age and bipolar subtype, and correcting for multiple comparisons. We also found a strong negative association with the total number of inpatient episodes and psychiatric comorbidity, but not with interepisodic remission, treatment with psychotherapy or lithium or the presence of any complicating socioeconomical factors. Adjusting for confounding genetic factors using polygenic risk scores for bipolar disorder and schizophrenia had no effect on the associations. LimitationsThis study lacks females and controls and may thus have lower generalizability. ConclusionIn conclusion, premorbid intelligence is associated with both level of functioning and illness severity as well as comorbidity in bipolar disorder patients. Further research is needed to develop targeted interventions for this subgroup of bipolar disorder patients.

Examining differences in brain metabolism associated with childhood maltreatment and suicidal attempt in euthymic patients with bipolar disorder: A PET and Machine Learning Study.

Childhood maltreatment (CM) is a significant risk factor for the development and severity of bipolar disorder (BD) with increased risk of suicide attempts (SA). This study evaluated whether a machine learning algorithm could be trained to predict if a patient with BD has a history of CM or previous SA based on brain metabolism measured by positron emission tomography. Thirty-six euthymic patients diagnosed with BD type I, with and without a history of CM were assessed using the Childhood Trauma Questionnaire. Suicide attempts were assessed through the Mini International Neuropsychiatric Interview (MINI-Plus) and a semi-structured interview. Resting-state positron emission tomography with 18F-fluorodeoxyglucose was conducted, electing only grey matter voxels through the Statistical Parametric Mapping toolbox. Imaging analysis was performed using a supervised machine learning approach following Gaussian Process Classification. Patients were divided into 18 participants with a history of CM and 18 participants without it, along with 18 individuals with previous SA and 18 individuals without such history. The predictions for CM and SA were not significant (accuracy = 41.67%; p = 0.879). Further investigation is needed to improve the accuracy of machine learning, as its predictive qualities could potentially be highly useful in determining histories and possible outcomes of high-risk psychiatric patients.

Correlation of Global DNA Methylation with Symptom Severity in Drug-Naïve Bipolar Disorder Patients: A Cross-sectional Study

health problem in India. Global Deoxyribonucleic Acid (DNA) methylation studies could provide a significant clues toward the early identification of high-risk individuals. Aim: To estimate the levels of global DNA methylation in drugnaïve bipolar disorder patients and healthy controls and to correlate the global DNA methylation levels with the severity of the disease. Materials and Methods: A cross-sectional study was conducted in the Department of Psychiatry at SCB Medical College, Cuttack, Odisha, India, from January 2019 to March 2020. A total of 50 bipolar disorder patients and 50 age-matched healthy adult controls were recruited from the Outpatient Departments (OPD) of the hospital, and the severity of bipolar disorder was assessed using Young's Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D). DNA methylation levels were estimated from serum samples of the subjects using a methylated DNA quantification kit. The data was analysed using Statistical Package for Social Sciences (SPSS) version 25.0. The Kruskal-Wallis test was used to compare the DNA methylation scores, and the Pearson’s correlation test was used to correlate DNA methylation levels with disease severity. A p-value &lt;0.05 was considered significant. Results: The mean age of the study participants was 34.44±12.45 years. A total of 100 subjects were included in the study, with 50 being bipolar disorder patients and the remaining 50 in the control group. Bipolar cases, particularly depression, had higher levels of DNA methylation than controls (p=0.0001). On correlation analysis, patients with Bipolar Depression (BD) had a significant correlation with DNA methylation (p-value &lt;0.001) compared to patients with mania and controls. Conclusion: Bipolar patients, especially those with BD, exhibit higher levels of global DNA methylation in genes compared to healthy control groups. Global DNA methylation can serve as an important early disease marker for bipolar patients, aiding in prevention and early detection efforts.

Functional connectivity alterations of the somatomotor network in euthymic bipolar disorder

While individuals with bipolar disorder are assumed to recover between mood episodes, some nevertheless experience lingering subsyndromal symptoms and suffer from cognitive and functional impairments. Here, we propose that these enduring impairments may be linked to aberrations in brain networks. To test this, we conducted a resting-state functional magnetic resonance imaging (fMRI) study and used network-based statistic to compare functional connectivity between euthymic individuals with bipolar disorder (N = 96) and healthy control individuals (N = 61) both within and between resting-state networks. We also investigated the association of functional connectivity with lingering psychomotor symptoms and illness severity in bipolar disorder. We found stronger functional connectivity between the somatomotor network and the frontoparietal network in individuals with bipolar disorder compared with healthy controls, but weaker functional connectivity within the somatomotor network as well as between the somatomotor and the visual network. Results remained after adjusting for antipsychotic medication. No significant association with psychomotor performance and illness severity was found. We conclude that stronger functional connectivity between the somatomotor and frontoparietal network might be associated with lingering symptoms in bipolar euthymia. Dysconnectivity within the somatomotor network might relate to psychomotor symptoms beyond the impact of medication. Our findings contribute to the sparse field of somatomotor network aberrancies in bipolar disorder and may present a potential target for brain stimulation treatment.

The Mediation Effect of Peripheral Biomarkers of Calcium Metabolism and Chronotypes in Bipolar Disorder Psychopathology.

Calcium (Ca++) metabolism may be impaired in several psychiatric diseases. We hypothesize that calcium imbalance might also correlate with a specific chronotype and could be recognized as a marker of illness severity in bipolar disorder (BD). We aimed to (1) identify the association between calcium imbalance and a specific chronotype in a cohort of BD patients, and (2) test the mediation role of high parathyroid hormone (PTH) levels towards a specific chronotype and illness severity in BD patients. Patients’ socio-demographic and clinical characteristics were collected with an ad-hoc schedule. We administered the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Young Mania Rating Scale (YMRS), and the Morningness Eveningness Questionnaire (MEQ). 100 patients affected by BD were recruited. The Kruskal-Wallis test showed a significant difference between the three MEQ groups in PTH levels (p < 0.001) and vitamin D levels (p = 0.048) but not in Ca++ levels (p = 0.426). Dwass-Steel-Critchlow-Fligner Pairwise analyses performed concerning three MEQ groups revealed significantly higher scores on PTH levels in MEQ-E subjects compared to MEQ-M and MEQ-I (in both cases, p < 0.001). No differences emerged between calcium levels among the three chronotypes. The mediation analysis has shown that elevated PTH levels are directly influenced by more severe HAM-A, HAM-D, and YMRS scores. MEQ-E could be a marker related to BD and predispose to various factors influencing mood symptoms. The combination of vitamin D therapy in MEQ-E may help to improve prognosis in this subtype of patients affected by BD.

Personality traits as mediators of the relationship between childhood trauma and depression severity in bipolar disorder: A structural equation model.

Childhood trauma is negatively associated with depression severity in bipolar disorder; however, the underlying mechanisms remain unclear. We investigated whether personality traits (neuroticism, extraversion, openness, agreeableness, conscientiousness) mediate the relationship between childhood trauma and the severity of bipolar depression. Data from 209 individuals with bipolar disorder recruited for the Prechter Longitudinal Study of Bipolar Disorder were analysed. Using structural equation modelling, we examined the direct and indirect associations between childhood trauma (Childhood Trauma Questionnaire) and depression severity (Hamilton Depression Rating Scale) - with the personality traits (NEO Personality Inventory-Revised) as mediators. The direct effect of childhood trauma on depression severity (standardised β = 0.32, 95% bootstrap confidence interval [CI] = 0.20-0.45, p < 0.001) and the indirect effect via neuroticism (standardised β = 0.03, 95% bootstrap CI [0.002, 0.07], p = 0.039) were significant; supporting a partial mediation model. The indirect effect accounted for 9% of the total effect of childhood trauma on depression severity (standardised β = 0.09, 95% bootstrap CI [0.002, 0.19], p = 0.046). The final model had a good fit with the data (comparative fit index = 0.96; root mean square error of approximation = 0.05, 90% CI = [0.02, 0.07]). Personality traits may be relevant psychological mediators that link childhood trauma to a more severe clinical presentation of bipolar depression. Consequently, a person's personality structure may be a crucial operative factor to incorporate in therapeutic plans when treating individuals with bipolar disorder who report a history of childhood trauma.

Impact of childhood trauma on functioning of patients with bipolar disorder

IntroductionExposure to severe childhood trauma has been associated with the onset and the severity of bipolar disorder in adults.ObjectivesThe aim of this study was to examine the relationship between childhood trauma and functioning of patients suffering from bipolar disorder.MethodsWe conducted a cross-sectional, descriptive, and analytical study, including sixty-one remitted patients with BD. We used the Childhood Trauma Questionnaire (CTQ-SF) to measure history of traumatic childhood experiences and the Functioning Assessment Short Test (FAST) to assess functioning.ResultsThe mean age of patients was 43.4. The sex ratio was 2.4. Almost two-thirds of patients (64%) had experienced at least one type of childhood trauma. An overall functional impairment was found in 70.5% of participants. The CTQ total score was significantly associated with low educational level (p=0.001), low socio-economic status (P=0.034), a family history of psychosis (P=0.022), the number of mood episodes (P=0.001), the number of hospitalizations (P=0.04), the number of relapses with psychotic features (p=0.002) and that of depressive relapses (P&lt;0.001), rapid cycling (P=0.012), higher rates of suicide attempts (P=0.04) and poor functioning (P&lt;0.001).The logistic regression analyses showed a significant association of childhood trauma with low educational level (p=0.001), high number of depressive episodes (p=0.013) and poor functioning (p&lt;0.001).ConclusionsOur findings demonstrate that childhood abuse and neglect are risk factors associated with worsening clinical course of bipolar disorder and higher functional impairment. These findings press the urgency for preventive practices and early intervention strategies to diminish the prevalence of childhood trauma and minimize their impact.DisclosureNo significant relationships.

Hospital admissions and clinical implications in schizophrenia and bipolar patients

This study aims to understand the long-term outcomes of schizophrenia and bipolar disorder, with a specific focus on hospital admissions and criteria for involuntary hospitalization. Conducted at the “Prof. Dr. Alexandru Obregia” Clinical Psychiatry Hospital, Bucharest, between September 2022 and January 2023, our research analyzed data from 93 patients diagnosed with either schizophrenia or bipolar disorder. We employed descriptive and inferential statistical methods, including Analysis of Variance (ANOVA), to examine differences in age, income, disease duration, hospital admissions, involuntary hospitalization days, and Clinical Global Impressions (CGI) scores. Descriptive statistics revealed that patients with bipolar disorder were older and had slightly higher education levels than those with schizophrenia. Schizophrenia patients reported higher incomes. Both groups exhibited similar disease durations, indicative of chronic disease courses. ANOVA results showed significant differences in the number of hospital admissions between the two groups (p = 0.028 when equal variances were not assumed), with schizophrenia patients experiencing more frequent hospitalizations. However, there were no significant differences in involuntary hospitalization days. Interestingly, CGI scores suggested higher perceived illness severity in bipolar disorder, although the results did not reach conventional statistical significance (p = 0.056 when variances were not assumed).

Attachment insecurity partially mediates the relationship between childhood trauma and depression severity in bipolar disorder.

BackgroundChildhood trauma is associated with greater depression severity among individuals with bipolar disorder. However, the mechanisms that explain the link between childhood trauma and depression severity in bipolar disorder remain poorly understood. The mediational role of attachment insecurity in childhood and adulthood was assessed in the current study.MethodsParticipants with bipolar disorder (N = 143) completed measures of childhood trauma (Childhood Trauma Questionnaire), attachment insecurity (Experiences in Close Relationships Scale) and depression severity (Hamilton Depression Rating Scale) as part of the Prechter Longitudinal Study of Bipolar Disorder. A sequential mediation model was tested using path analysis: the direct and indirect effects of childhood trauma on depression severity with attachment insecurity (attachment anxiety and avoidance) in childhood (mother and father) and adulthood (partner) as mediators were estimated.ResultsThe final path model demonstrated an excellent fit to the data (comparative fit index = 0.996; root mean square error of approximation = 0.021 [90% confidence interval = 0.000–0.073]). Supporting the hypothesised sequential mediation model, maternal attachment anxiety in childhood and romantic attachment avoidance in adulthood partially mediated the relationship between childhood trauma and depression severity; this effect accounted for 12% of the total effect of childhood trauma on depression severity.ConclusionAttachment insecurity in childhood and adulthood form part of the complex mechanism informing why people with bipolar disorder who have a history of childhood trauma experience greater depression severity. Addressing attachment insecurity represents a valuable psychotherapeutic treatment target for bipolar disorder.

Reduced Plasma Dopamine-β-Hydroxylase Activity Is Associated With the Severity of Bipolar Disorder: A Pilot Study.

Dopamine-β-hydroxylase (DβH) is an enzyme converting dopamine to norepinephrine, a key neurotransmitter in mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD). Due to overlapping symptomology of unipolar and bipolar depression, the present study attempted to explorer if the plasma DβH activity could discriminate the depressive episodes of BD from MDD. The aim of this study was to compare the plasma DβH activity among MDD patients (n = 104), BD patients (n = 101), and healthy controls (n = 160). Clinical characteristics and cognitive function were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Patient Health Questionnaire-9 (PHQ-9), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Our data showed a lower plasma DβH activity in patients with BD, not MDD, than that in controls. For the BD patients, the plasma DβH activities were negatively correlated with HAM-D scores and HAM-A scores. However, there was no significant correlation between plasma DβH activity and severity of depressive symptoms in MDD patients. No significant correlation between DβH activities and cognitive assessments neither in BD nor in MDD patients. The present study provides evidence that BD is associated with decreased circulating DβH activity.

The role of affective temperaments in predicting symptom severity in bipolar disorder

IntroductionBipolar disorder (BD) is one of the most burdensome psychiatric illnesses, being associated with a negative long-term outcome and high suicide rate. Although affective temperaments are considered possible mediators of outcome, their role on the course and outcome of BD remains poorly studied.ObjectivesThe aims of the present study are to describe the clinical characteristics of patients with BD more frequently associated with the different affective temperaments and to verify which affective temperaments are associated with a more severe clinical picture in a sample of patients with BD.MethodsAll patients with BD referring to the outpatient units of two Italian university sites have been recruited. Patients’ psychiatric symptoms, affective temperaments, and quality of life were investigated through validated assessment instruments.Results199 patients were recruited. 54.8% of patients had a diagnosis of bipolar I disorder. 56.8% of the sample reported at least one episode of aggressive behaviours and 30.2% of suicidal attempt. Predominant cyclothymic and irritable temperaments predicted more frequent relapses, a poorer quality of life (p&lt;;0.05), more aggressive behaviours and suicide attempts (p&lt;;0.01). The predominant hyperthymic disposition was a protective factor for several outcome measures, including relapses and suicidality (p&lt;;0.01), and was correlated with a less severity of psychiatric symptoms and later age at onset (p&lt;;0.05).ConclusionsEarly identification of affective temperaments in BD patients can help clinicians to identify those who could show a worse prognosis. A screening of affective temperaments can be useful to develop early targeted integrated pharmacological and psychosocial interventions.DisclosureNo significant relationships.

Clinical features related to rapid cycling and one-year euthymia in bipolar disorder patients: A multicenter treatment survey for bipolar disorder in psychiatric clinics (MUSUBI)

ObjectiveRapid cycling (RC) presents a risk of greater severity in bipolar disorder (BD), whereas patients with one-year euthymia (OYE) have better prognosis. The purpose of this study was to identify the clinical background and prescription characteristics of patients in the two opposing states of current RC and OYE from a large sample (N = 2609) in a multicenter treatment survey on BD in psychiatric clinics (MUSUBI). MethodsMUSIBI was a cross-sectional study wherein questionnaires, based on a retrospective medical record survey of consecutive cases of BD, were distributed to 176 outpatient clinics. The questionnaire collected information on patient background, current episode, and clinical and prescription characteristics. OYE was defined as the presence of a euthymic state for at least 12 months. ResultsIn this study, current RC (9.7% frequency) was significantly higher in females, had a younger age of onset, functional impairments, and a higher rate of neurodevelopmental disorder and physical comorbidity compared to non-RC patients. OYE (19.4% frequency) was associated with a lower proportion of females, older age, higher occupational status, and lower rate of suicide ideation, psychotic symptoms, personality disorder, and alcohol or substance abuse. Mood stabilizers were prescribed in ≥80% of cases, while antipsychotics were prescribed in half of the cases (more in RC and less in OYE). Antidepressant prescription rates were lower in OYE than in RC. ConclusionsRC and OYE generally show opposing characteristics, but the details of the opposite parameters are distinctive. Clinicians can help predict the progression of BD by understanding the clinical background and characteristics of these opposing clinical features.

Decreased motor impulsivity following chronic lithium treatment in male rats is associated with reduced levels of pro-inflammatory cytokines in the orbitofrontal cortex

Lithium’s efficacy in reducing both symptom severity in bipolar disorder (BD) and suicide risk across clinical populations may reflect its ability to reduce impulsivity. Changes in immune markers are associated with BD and suicidality yet their exact role in symptom expression remains unknown. Evidence also suggests that lithium may decrease levels of pro-inflammatory cytokines in the periphery and central nervous system, and that such changes are related to its therapeutic efficacy. However, issues of cause and effect are hard to infer from clinical data alone. Here, we investigated the effects of chronic dietary lithium treatment on rats’ performance of the 5-Choice Serial Reaction Time Task (5CSRTT), a well-validated operant behavioural task measuring aspects of impulsivity, attention and motivation. Male Long-Evans rats received a diet supplemented with 0.3% LiCl (n = 13), or the equivalent control diet (n = 16), during behavioural testing. Blood and brain tissue samples were assayed for a wide range of cytokines once any changes in impulsivity became significant. After 12 weeks, chronic lithium treatment reduced levels of motor impulsivity, as indexed by premature responses in the 5CSRTT; measures of sustained attention and motivation were unaffected. Plasma levels of IL-1β, IL-10 and RANTES (CCL-5) were reduced in lithium-treated rats at this time point. IL-1β, IL-6 and RANTES were also reduced selectively within the orbitofrontal cortex of lithium-treated rats, whereas cytokine levels in the medial prefrontal cortex and nucleus accumbens were comparable with control subjects. These results are consistent with the hypothesis that lithium may improve impulse control deficits in clinical populations by minimising the effects of pro-inflammatory signalling on neuronal activity, particularly within the orbitofrontal cortex.

Differences in Kynurenine Metabolism During Depressive, Manic, and Euthymic Phases of Bipolar Affective Disorder.

The kynurenine pathway is involved in inflammatory diseases. Alterations of this pathway were shown in psychiatric entities as well. The aim of this study was to determine whether specific changes in kynurenine metabolism are associated with current mood symptoms in bipolar disorder. Sum scores of the Hamilton Depression Scale, Beck Depression Inventory, and Young Mania Rating Scale were collected from 156 bipolar individuals to build groups of depressive, manic and euthymic subjects according to predefined cut-off scores. Severity of current mood symptoms was correlated with activities of the enzymes kynurenine 3-monooxygenase (ratio of 3-hydroxykynurenine/ kynurenine), kynurenine aminotransferase (ratio of kynurenic acid/ kynurenine) and kynureninase (ratio of 3-hydroxyanthranilic acid/ 3-hydroxykynurenine), proxied by ratios of serum concentrations. Individuals with manic symptoms showed a shift towards higher kynurenine 3-monooxygenase activity (χ2 = 7.14, Df = 2, p = .028), compared to euthymic as well as depressed individuals. There were no differences between groups regarding activity of kynurenine aminotransferase and kynureninase. Within the group of depressed patients, Hamilton Depression Scale and kynurenine aminotransferase showed a significant negative correlation (r = -0.41, p = .036), displaying lower metabolism in the direction of kynurenic acid. Depression severity in bipolar disorder seems to be associated with a decreased synthesis of putative neuroprotective kynurenic acid. Furthermore, higher kynurenine 3-monooxygenase activity in currently manic individuals indicates an increased inflammatory state within bipolar disorder with more severe inflammation during manic episodes. The underlying pathophysiological mechanisms of the different affective episodes could represent parallel mechanisms rather than opposed processes.

Relationship of elevated neural cell adhesion molecule 1 with interleukin-10 and disease severity in bipolar disorder.

Neural plasticity and inflammation are known to play a role in the pathogenesis of Bipolar disorder. The data related to markers of neural plasticity in bipolar disorder are limited. The objective of the study was to assess the levels of neural cell adhesion molecule 1 (NCAM 1) and interleukin-10 and their association with disease severity in bipolar disorder. 40 bipolar disorder I patients with acute manic symptoms and 40 age matched controls were enrolled in the study. Neural cell adhesion molecule 1 and interleukin-10 (IL-10) levels were assessed in both the groups. NCAM 1 and interleukin-10 levels were significantly increased in bipolar disorder when compared with controls. There was significant positive correlation of Young Mania Rating score with NCAM 1 (r = 0.538, p = < 0.001) in patients with BD. Multi variate analysis revealed that IL-10 (p = 0.021) was lower in controls by 0.012 ng/L and NCAM 1(p = 0.048) was lower in controls by 0.002 ng/L compared to BD cases and this difference was statistically significant. Based on the findings we conclude that neural cell adhesion molecule 1 is increased and associated with disease severity in bipolar disorder.

Comparisons of the clinical outcomes between early- and adult-onset bipolar disorders: A prospective cohort analysis

BackgroundThis study aimed to explore the impact of age-at-onset on clinical outcomes in bipolar-spectrum disorders, including the development of alcohol or substance use disorder, suicidality, and psychiatric hospitalization. MethodsThis population-based study enrolled newly-diagnosed bipolar-spectrum patients, including 4,367 patients with early-onset bipolar disorder (EOBD), 64,787 patients with adult-onset bipolar disorder (AOBD), and the same number of age-controlled comparison subjects without bipolar disorder, from Taiwan's National Health Insurance Research Database. Time-dependent covariate Cox regression models were used to estimate the effect of age-at-onset on clinical outcomes with adjustment for pre-existing psychiatric comorbid conditions and pharmacological treatment patterns. Sensitivity analyses using different definitions of study sample and age cutoffs were conducted. ResultsThe average follow-up duration was 5.7 years. After adjustment with time-dependent covariates and chronological age, there were no significant differences in the risks for developing new-onset alcohol or substance use disorders and psychiatric hospitalization between EOBD and AOBD patients. Although EOBD patients had a higher risk of hospitalization for suicide and self-harm than did AOBD patients in primary analysis, this finding did not replicated in the sensitivity analyses. LimitationsThe symptom profile and severity of bipolar disorder was not available in the NHIRD; therefore, surrogate indicators of clinical outcome might not be sensitive enough to detect the subtle differences. ConclusionsEOBD and AOBD patients had similar risks for developing alcohol or substance use disorders. Their risk of psychiatric hospitalization was similar. Whether EOBD patients might have a higher risk of hospitalization for suicide and self-harm warrants further investigations.

Adverse childhood experiences and clinical severity in bipolar disorder and schizophrenia: A transdiagnostic two-step cluster analysis

BackgroundAdverse childhood experiences (ACEs) are risk factors for psychiatric disorders, but evidence about their relationship with clinical severity is limited. We aimed to classify patients according to ACEs and to compare these clusters with regards to the clinical severity. MethodsSeventy-four patients with Bipolar Disorder (BD) and 91 patients with a diagnosis within the Schizophrenia Spectrum Disorders (SSDs) were interviewed. The Childhood Experience of Care and Abuse scale (CECA) and the Positive and Negative Symptoms Scale (PANSS) were administered. A two-step cluster analysis was run to identify clusters according to ACEs. PANSS average scores were compared between clusters. ResultsThree clusters emerged; significant differences in ACEs distribution were evident. Cluster 1 was characterized by very low frequency of ACEs. ACEs related to lack of support/isolation were more frequent within Cluster 2, instead ACEs related to abuse/neglect were over represented in Cluster 3. The comparison of PANSS through ANOVA demonstrated that Cluster 3 not only had significantly higher scores in all dimensions than Cluster 1 and 2 but also a higher average number of ACEs. LimitationsCECA is a self-report scale and is subject to recall bias. ConclusionsSpecific ACEs are related to clinical severity among BD and SSD patients. Early life adversities related to abuse and neglect are associated to greater symptomatic severity than those related to lack of support/isolation. Our findings suggest that a history of ACEs could be used to identify patients at higher risk of unfavorable clinical features.