Bipolar I Disorder Patients Research Articles

Dorsal attention network centrality increases during recovery from acute stress exposure

Stress is a major risk factor for the development of almost all psychiatric disorders. In addition to the acute stress response, an efficient recovery in the aftermath of stress is important for optimal resilience. Increased stress vulnerability across psychiatric disorders may therefore be related to altered trajectories during the recovery phase following stress. Such recovery trajectories can be quantified by changes in functional brain networks. This study therefore evaluated longitudinal functional network changes related to stress in healthy individuals (N = 80), individuals at risk for psychiatric disorders (healthy siblings of schizophrenia patients) (N = 39), and euthymic bipolar I disorder (BD) patients (N = 36). Network changes were evaluated before and at 20 and 90 min after onset of an experimental acute stress task (Trier Social Stress Test) or a control condition. Whole-brain functional networks were analyzed using eigenvector centrality as a proxy for network importance, centrality change over time was related to the acute stress response and recovery for each group. In healthy individuals, centrality of the dorsal attention network (DAN; p = 0.007) changed over time in relation to stress. More specifically, DAN centrality increased during the recovery phase after acute stress exposure (p = 0.020), while no DAN centrality change was observed during the initial stress response (p = 0.626). Such increasing DAN centrality during stress recovery was also found in healthy siblings (p = 0.016), but not in BD patients (p = 0.554). This study highlights that temporally complex and precise changes in network configuration are vital to understand the response to and recovery from stress.

Cognitive subgroups in first episode bipolar I disorder: Relation to clinical and brain volumetric variables.

Distinct cognitive subgroups are seen in patients with long duration bipolar I disorder (BDI), possibly reflective of underlying pathophysiological differences. It is unknown whether such cognitive heterogeneity is present at illness onset. We applied latent class analysis (LCA) to cognitive test scores in first episode BDI patients. Exploratory analysis elucidated whether impaired subgroups were characterized by 'early neurodevelopmental' (low premorbid IQ and intracranial volume) versus 'later neurodevelopmental' (decline from premorbid to current IQ, changes in relative grey (GM)/white (WM) matter volumes) pathology. Recently recovered first manic episode BDI patients (n=91) and healthy controls (HC, n=63) comprised the study sample. LCA identified subgroups based on processing speed, verbal memory, non-verbal memory, executive functioning, attention and working memory scores. Subgroups were compared amongst each other and HC on premorbid/current IQ, intracranial (ICV), total brain and regional volumes. Three cognitive subgroups emerged: (i) globally impaired (GI, n=31), scoring 0.5-1 SD below demographically corrected norms across domains, (ii) selectively impaired (SI, n=47), with predominant processing speed deficits and (iii) high performing (HP, n=13), with above-average cognitive performance. GI patients showed a 'later neurodevelopmental' pattern, with normal ICV, significant decline from premorbid to current IQ, higher total GM and lower total WM (with respect to total brain volume) versus SI and HC (p=0.003). GI patients had higher left frontal pole GM versus HC (p<0.05, FWE corrected). A globally impaired patient subgroup is identifiable in first episode BDI, possibly characterized by unique neurodevelopmental pathologic processes proximal to illness onset.

Disturbances of Dynamic Function in Patients With Bipolar Disorder I and Its Relationship With Executive-Function Deficit.

Abnormity in brain regional function and inter-regional cooperation have been linked with the dysfunction during cognitive and emotional processing in bipolar disorder (BD) patients. Recent evidences have suggested that brain function is not static but temporal dynamic. In present study, we aimed to characterize the temporal dynamics of regional function and inter-regional cooperation in BD and its relationship with executive dysfunction, an important deficit in BD. Resting-state functional MRI was performed in patients with bipolar I disorder (BDI) (n = 18) and healthy controls (HCs, n = 19). We first assessed local-function temporal variety with dynamic amplitude of low-frequency fluctuation (dALFF). Region with significant inter-groups difference in dALFF was chosen as a seed to calculate inter-regions connective temporal variety with dynamic functional connectivity (dFC). The executive function was measured by Verbal Fluency Test (VFT). The relationship between executive function and brain dynamics were examined. Compared with HC, the BDI group showed decreased dALFF (less temporal variability) in the posterior cingulate cortex (PCC) and decreased dFC between PCC and medial prefrontal cortex (mPFC). The PCC-mPFC dFC was positively associated with VFT in BDI patients, but not in HC. These findings implicated the reduced temporal variability in local region and inter-regions cooperation in BDI, which may be a neural substrate of executive-function deficit in BDI.

Identifying Plasma Biomarkers with high specificity for major depressive disorder: A multi-level proteomics study

BackgroundThere are currently no objective diagnostic biomarkers for major depressive disorder (MDD) due to the biological complexity of the disorder. The existence of blood-based biomarkers with high specificity would be convenient for the clinical diagnosis of MDD. MethodsA comprehensive plasma proteomic analysis was conducted in a highly homogeneous cohort [7 drug-naïve MDD patients and 7 healthy controls (HCs)], with bioinformatics analysis combined with machine learning used to screen candidate proteins. Verification of reproducibility and specificity was conducted in independent cohorts [60 HCs and 74 MDD, 42 schizophrenia (SZ) and 39 bipolar I disorder (BD-I) drug-naïve patients]. Furthermore, verification of consistency was accomplished by proteomic analysis of postmortem brain tissue from 16 MDD patients and 16 HCs. Results: Levels of C-reactive protein (CRP), antithrombin III (ATIII), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and vitamin D-binding protein (VDB) were significantly higher in MDD patients, both in the discovery cohort and independent replication cohort. In comparison with SZ or BD-I patients, two proteins (VDB and ITIH4) were significantly elevated only in MDD patients. In addition, increased VDB and ITIH4 were observed consistently in both plasma and postmortem dorsolateral prefrontal cortex tissues of MDD patients. Furthermore, a panel consisting of all four plasma proteins was able to distinguish MDD patients from HCs or SZ or BD-I patients with the highest accuracy. ConclusionPlasma ITIH4 and VDB may be potential plasma biomarkers of MDD with high specificity. The four-protein panel is more suitable as a potential clinical diagnostic marker for MDD.

Neurocognitive Impairments (NCI) in bipolar disorder: Comparison with schizophrenia and healthy controls

BackgroundNeurocognitive impairments (NCI) are common in patients with bipolar I disorder. However, reports about the affected domains, outcomes and magnitude have been inconsistent. The aim of this study was to compare the magnitude (severity) and specificity (domains), of (NCI) in euthymic Bipolar I Disorder (BD) patients with a demographically and educationally matched sample of patients with schizophrenia in remission (SC) and healthy controls (HC). MethodsThe Screen for Cognitive Impairment in Psychiatry (SCIP) was applied in this cross-sectional study, to all consecutive and consenting euthymic outpatients with bipolar I disorder (BD) (n = 76), remitted patients with schizophrenia (n = 130) and age and gender-matched healthy controls (HC) (n = 100). The cognitive tests done included Verbal List Learning-Immediate (VLT-I), Working Memory Test (WMT), Verbal Fluency Test (VFT), Verbal Learning Test-Delayed (VLT-D) and Processing Speed Test (PST). Within the bipolar group, the association between NCI and functioning was assessed. ResultsThere was a significant difference in the proportions of participants that had cognitive impairment from the 3 groups (37% (HC) vs. 71.1% (BD) vs. 91.5%(SC) (p=<0.001). The BD group in comparison to the HCs did worse on all domains of the SCIP except WMT and PST. The BD group was not significantly different from the SC group in all neuropsychological domains of the SCIP except WMT. BD group significantly functions better than the SC group. The severity of depressive symptomatology and VLT-I were independent predictors of functioning in the BD group. ConclusionCognitive impairment affects almost all the neurocognitive domains of the BD group. The difference in NCI between euthymic BD patients and SC in remission are quantitative rather than qualitative.

Association of pro-inflammatory cytokines with clinical features in euthymic patients with Bipolar-I-Disorder

BackgroundA chronic low-grade inflammatory state appears to be a relevant mechanism in the pathophysiology of bipolar disorder. Pro-inflammatory cytokines may influence disease course and individual symptomatology; and biological markers correlating with illness features may be of utility in clinical decision making during euthymia. Methods51 euthymic outpatients with Bipolar-I-Disorder (BD-I) and 93 healthy controls (HC) were investigated. Comparisons between groups, and correlations with clinical features were performed. Serum concentrations of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and soluble interleukin-6 receptor (sIL-6R) were evaluated by ELISA under highly standardized conditions. Clinical features included duration of illness, number of previous suicide attempts and mood episodes (manic, hypomanic, depressive), scores of the Young Mania Rating Scale (YMRS), the Inventory of Depressive Symptoms (IDS-30), the Pittsburg Sleep Quality Index (PSQI), and the Global Assessment of Functioning (GAF). ResultsNo significant difference in serum concentrations of IL-1β, TNF-α, and sIL-6R between BD-I euthymic patients and HC could be identified. Among euthymic BD-I patients, a positive correlation of rs = 0.47 (p = 0.004) between levels of IL-1β and IDS-30 score was identified. LimitationsThe design was cross-sectional, most patients were receiving medication, only 3 cytokines were assessed, only euthymic BD-I patients were evaluated. ConclusionsThe findings suggest that elevated pro-inflammatory cytokine concentrations are likely state rather than trait markers of BD-I. It also seems unlikely that cytokine concentrations are clinically informative interepisode. An inflammatory component might possibly be involved in the pathophysiology of subsyndromic depression in BD-I, and conceivably of bipolar depression per se.

Predictors of Depressive Switch in Patients With Bipolar I Disorder Who Initiated or Changed Pharmacologic Treatment for Mania or Mixed-Mania: A Prospective Observational Study.

To evaluate the prevalence and the predictors of depressive switch in patients with bipolar I disorder (BD-I) requiring the initiation or change (but not a dose change) of treatment with oral antipsychotics or mood stabilizers for mania or mixed-mania. This was a 3-month, prospective, noninterventional study conducted in 34 Italian psychiatric centers from April 2012 to April 2013. The study sample comprised 234 patients aged 18 years or older presenting with a manic episode according to DSM-IV-TR criteria. Patients were assessed at baseline and at follow-up visits by a variety of measures, including the Clinical Global Impressions scale for use in bipolar illness (CGI-BP). The primary outcome measure was depressive switch, which was defined a posteriori on the basis of a Montgomery-Åsberg Depression Rating Scale total score ≥ 15 and a Young Mania Rating Scale total score < 10 at week 12. A stepwise backward logistic regression model was used to explore the effect of clinical variables on the occurrence of depressive switch. According to the definition used in this study, 26 (11.1%) of 234 patients switched to depression. The variables associated with a depressive switch were prescription of both first- and second-generation antipsychotics (P = .017), depressive-predominant polarity (P = .012), CGI-BP total score at baseline evaluation (P = .024), depressive temperament (P = .063), and age at evaluation (P = .020). Depressive switch was observed in about 1 of 10 of the BD-I patients. Our results suggest an association between the depressive switch and treatment with both first- and second-generation antipsychotics, depressive-predominant polarity, greater severity of the symptomatology, and older age at evaluation. Further randomized controlled studies are needed to confirm possible predictors of a depressive switch during mania.

Long-term impact of pharmacist intervention in patients with bipolar disorder: extended follow-up to the EMDADER-TAB study

BackgroundPharmaceutical care (PC) through the Dader method (DMet) vs. the usual care process (UCP) significantly reduced psychiatric hospitalizations and emergency service consultations during one year of follow-up of outpatients with bipolar I disorder (BD-I). To date, the effect of long-term PC on the use of health services by BD-I patients once pharmacist intervention has ended is unknown. ObjectiveTo determine whether the effect of PC measured by the decrease in psychiatric hospitalizations and emergency service consultations is maintained one year after pharmacist intervention ceases. MethodsThis was a retrospective analysis of patients who had previously participated in a randomized, controlled, prospective, single-center clinical trial to compare PC (intervention group) vs. UCP (control group) in BD-I patients. Data were collected from November 2012 to March 2014. The primary outcome was the use of health services measured by the number of psychiatric hospitalizations and emergency service consultations. Descriptive statistics, Student's t-test, Kaplan–Meier function, and Log-Rank test were used. ResultsThe study included 92 patients: 43 in the intervention group and 49 in the control group. Eleven psychiatric hospitalizations occurred for the intervention group and 19 for the control group. One year after pharmacist intervention ceased, there were no significant differences between the groups in psychiatric hospitalizations (p = 0.261). There were 14 emergency service consultations for the intervention group, and 24 for the control group without significant differences (p = 0.212). ConclusionsPC through the DMet has no long-term effects on psychiatric hospitalizations and emergency department consultations in patients with BD-I following discontinuation of pharmacist intervention; the effect dissipates when the intervention ceases. Future studies should focus efforts on identifying factors associated with PC that explain why the outcomes derived from this intervention are not maintained in the long term.

Ten-Year Risk of Cardiovascular Disease in Patients with Bipolar Disorder

Patients with bipolar disorder (BPD) are less likely to seek treatment for cardiovascular diseases (CVD) despite the two fold increased CVD-related death rate in BPD. The aim of this study was to evaluate the relationship between clinical variables, exercise characteristics and 10-year risk of CVD in patients with bipolar I disorder (BPD-I). The study was carried out with 106 euthymic BPD-I patients who were followed up at the Mood Disorders Centers of Bakırköy Hospital for Mental and Neurological Diseases and Selcuk University Faculty of Medicine. The physical activity status of the patients were evaluated with the Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the prospective 10-year risk of CVD was assessed by the QRISK®2-2017 - CVD risk algorithm. Mean age of the patients were 39.5±8.6 years. The mean QRISK2 score of the patients was 3.64±0.46 %, which did not differ with respect to the gender. Patients' mean healthy heart age (QAGE) was 8.49±6.46 years ahead of their current age. There was a weak negative correlation between GLTEQ total score and QRISK2 score (r= 0.168), but this was not statistically significant. However, statistically significant positive correlations were determined between the categorical QRISK2 score and the disease age of onset (RR:1.18; 95%CI:1.09-1.28), treatment duration (RR:1.16; 95%CI:1.05-1.29) and the inclusion of atypical antipsychotic agents in the treatment received (RR:5.99; 95%CI:1.12-31.90). A strong positive correlation was determined in this study between the QRISK2 score and the use of atypical antipsychotic drugs in the treatment of the BPD-I patients. It is important to identify patients diagnosed with bipolar disorder with a high risk of developing CVD to review the psychiatric treatment and to encourage the patients for preventive approaches.

Immunophenotypes associated with bipolar disorder and lithium treatment

Immune dysfunction is implicated in the etiology of bipolar disorder. The single-nucleotide polymorphism rs17026688 in the gene encoding glutamate decarboxylase–like protein 1 (GADL1) has been found to be associated with lithium response in Han Chinese patients with bipolar I disorder (BDI). However, whether patients with GADL1 polymorphisms have different immunophenotypes is unknown. To address this issue, differences in the immune profiles based on analysis of peripheral blood mononuclear cells (PBMCs) were compared among BDI patients and healthy controls who lack or carry the T allele of rs17026688. BDI patients had significantly higher percentages of total T cells, CD4+ T cells, activated B cells, and monocytes than healthy controls, suggesting that immunologic imbalance might be involved in BDI development or progression. Treatment of BDI patients-derived PBMCs with lithium in vitro increased the percentage of CD14+ monocytes and dendritic cells, suggesting that lithium plays an immunomodulatory role in CD14+ monocytes and dendritic cells. Among BDI patients, non-T carriers had a significantly higher percentage of CD11b+/CD33lo/HLA-DR− myeloid-derived suppressor cells than T carriers. Moreover, only T carriers exhibited differential sensitivity to lithium therapeutic use with respect to the percentage of myeloid cells. These findings suggest that rs17026688 polymorphisms in GADL1 are associated with immune dysfunction in BDI patients.

Asenapine for the treatment of bipolar disorder

ABSTRACTIntroduction: Bipolar I disorder (BDI) is amongst the most debilitating psychiatric conditions with a great impact on both patients and their families. A class of drugs commonly used in this condition is second-generation antipsychotics (SGAs) including asenapine, one of the latest to be introduced into the clinical practice worldwide to treat manic episodes in BDI.Areas covered: The aim of this paper is to critically review the literature on the pharmacological characteristics, tolerability, and safety data of asenapine, as well as on its short- and long-term clinical trials in manic episodes as both a monotherapy and as an add-on treatment.Expert opinion: The available data indicate that asenapine is an effective antimanic agent in both adult and pediatric patients and that it might also improve depressive symptoms and recurrences in BDI patients. Its tolerability profile is good, and its most common side effects are somnolence, light extrapyramidal symptoms, dizziness, weight gain, and oral (but reversible) hypoesthesia. Taken together, the published studies indicate that asenapine might be an effective therapeutic agent in BDI with a broad spectrum of clinical activities. Further double-blind, short- and long-term studies are, however, necessary to clarify its precise role in the treatment of BD.

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia.

Bipolar disorder I (BD-I) is defined by episodes of mania, depression and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood. We first assessed the severity of NS in 25 euthymic BD-I patients compared with 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral (VS) and dorsal striatal (DS) activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS. In BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant VS and DS activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole-brain analyses revealed reduced extra-striatal activation in BD-I patients compared with HC and an association between reduced activation of the inferior frontal gyrus and apathy. This study found that in BD-I patients apathy is present to an extent comparable to SZ, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

Cognitive variability in bipolar I disorder: A cluster-analytic approach informed by resting-state data

BackgroundWhile the presence of cognitive performance deficits in bipolar disorder I (BD-I) is well established, there is no consensus about which cognitive abilities are affected. Heterogeneous phenotypes displayed in BD-I further suggest the existence of subgroups among the disorder. The present study sought to identify different cognitive profiles among BD-I patients as well as potentially underlying neuronal network changes. Methods54 euthymic BD-I patients underwent cognitive testing and resting state neuroimaging. Hierarchical cluster-analysis was performed on executive function scores of bipolar patients. The derived clusters were compared against 54 age-, gender- and IQ-matched healthy controls (HC) to facilitate the interpretation of results. Further, resting state network properties were compared to identify differences probably underlying cognitive profiles. ResultsA three-cluster solution emerged. Cluster 1 (n = 22) was characterized by deficits in cognitive flexibility and motor inhibition, cluster 2 (n = 12) displayed impulsive decision-making, while cluster 3 (n = 20) showed good visuospatial planning. Weaker connections in cluster 1 compared to cluster 2 were found between regions activated during tasks cluster 1 showed deficits on. Cluster 3 had a higher modularity than cluster 2, which correlated positively with problem solving performance and risk-taking in this cluster. ConclusionObtained clusters showed distinct cognitive profiles, characterized by deficits and strengths, most of which remained precluded in a general comparison. Weaker interregional connections and separated subnetworks might underly behavioral deficits and strengths, respectively. The findings help explain the phenotypic heterogeneity observed in BD-I.This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’.

Brain-derived neurotrophic factor (BDNF) and bipolar disorder

Brain-derived neurotrophic factor (BDNF) is deemed to be associated with the psychopathology of bipolar I disorder (BD). However, studies focusing on accuracy of BDNF levels to differentiate these patients from healthy controls (HCs) are scarce. Over a discrete twelve-year period, we investigated serum BDNF levels in patients with BD and compared them to age-, sex- and body mass index (BMI)-matched HCs. There were lower serum BDNF levels in 83 samples with BD than in 222 HCs samples (5.7 ± 4.2 ng/ml vs. 12.2 ± 7.5 ng/ml, F = 46.784). Pearson's correlation test showed significant positive correlations between Young Mania Rating Scale scores and the BDNF levels among 61 manic patients (γ = 0.339). The receiver operating characteristic curve analysis showed BDNF levels demonstrated a moderate accuracy of being able to differentiate BD patients from HCs (AUC = 0.801). The most adequate cut-off points of the BDNF level were 6.74 ng/ml (sensitivity = 82.0%, specificity = 63.9%). Our results support that BDNF demonstrated moderate accuracy to distinguish BD patients from HCs. In the future, greater samples would be required to prove these results.

Weight gain as a predictor of frontal and temporal lobe volume loss in bipolar disorder: A prospectiveMRIstudy

A sizable fraction of people with bipolar I disorder (BDI) experience a deteriorating clinical course with increasingly frequent mood episodes and chronic disability. This is believed to result from neurobiological illness progression, or neuroprogression. Excessive weight gain predicts neuroprogression across multiple brain illnesses, but no prospective studies have investigated this in BDI. The objective of this study was to determine whether BDI patients who experienced clinically significant weight gain (CSWG; gaining ≥7% of baseline weight) over 12months had greater 12-month brain volume loss in frontal and temporal regions important to BDI. In 55 early-stage BDI patients we measured (i) rates of CSWG, (ii) the number of days with mood symptoms, using NIMH LifeCharts, and (iii) baseline and 12-month brain volumes, using 3T MRI. We quantified brain volumes using the longitudinal processing stream in FreeSurfer v6.0. We used general linear models for repeated measures to investigate whether CSWG predicted volume loss, adjusting for potentially confounding clinical and treatment variables. After correction for multiple comparisons, CSWG in patients predicted greater volume loss in the left orbitofrontal cortex (effect size [ES; Cohen's d]=-1.01, P=0.002), left cingulate gyrus (ES=-1.31, P<0.001), and left middle temporal gyrus (ES=-0.96, P=0.004). Middle temporal volume loss predicted more days with depression (β=-0.406, P=0.010). These are the first prospective data on weight gain and neuroprogression in BDI. CSWG predicted neuroprogression, and neuroprogression predicted a worse clinical illness course. Trials of weight loss interventions are needed to confirm the causal direction of the weight gain-neuroprogression relationship, and to determine whether weight loss is a disease-modifying treatment.

Inflammatory cytokines and cognitive functioning in early-stage bipolar I disorder

BackgroundIncreased circulating inflammatory cytokines is a replicated finding in bipolar I disorder (BDI). Pro-inflammatory cytokines such as TNFα, IL-6 and IL-1 have also been associated with poorer cognitive functioning in patients with longer illness duration. However, the effect of inflammatory cytokines on cognition in early stage patients is not yet known. Here, we investigate the relationship between cytokines and cognition in BDI patients within three years of diagnosis. MethodsSerum pro-inflammatory (TNFα, IL-6 and IL-1α) and anti-inflammatory (IL-4 and IL-10) cytokine levels were compared between 51 early stage BDI patients and 20 healthy controls. 46 patients completed neuropsychological testing, and multiple regression analysis was used to assess the association between cytokine levels and cognition after accounting for relevant clinical and demographic variables. ResultsTNFα was elevated at trend level significance in BDI patients compared to healthy controls, and was negatively associated with global cognition, processing speed, and working memory in patients. IL-6, IL-1α, IL-4 and IL-10 levels were comparable between groups and were not significantly associated with cognition. LimitationsDirect causation cannot be established in this cross-sectional study; in addition, cytokine levels were not taken on the same day as neuropsychological testing for all patients. ConclusionsTNFα may negatively impact cognition in early BDI. While replication is required in larger samples, these results suggest that inhibition of TNFα activity might be a strategy to preserve cognition in newly diagnosed BDI patients.

Effect of mood stabilizer on gray matter volume in patients with bipolar disorder I

Objective To investigate the abnormal change of gray matter volume in patients with euthymic bipolar disorder I (BD-I), and to elucidate the relationship between the use of different mood stabilizers and brain structure variations. Methods Voxel-based morphometry (VBM) was used to analyze the volume of local gray matter in 35 patients with BD-I and 30 healthy controls(HC). The patients were divided into BD-I with lithium group and BD-I with valproate group according to different mood stabilizers.The volume differences of gray matter of the three groups were compared by one-way ANOVA. Results Compared with HC, BD-I patients showed significantly reduced gray matter volume in the medial frontal cortex (MNI(x, y, z): 2, 34, -18), orbital frontal cortex (MNI(x, y, z): -32, 22, -4), frontal operculum (MNI(x, y, z): 38, 18, 4) and insula cortex (MNI(x, y, z): -32, 22, -4)(P 0.05). Conclusion Emotional disturbance in patients with BD-I may be associated with reduced gray matter volume in the medial frontal cortex, orbital frontal cortex, frontal operculum and insula cortex.There are not significant difference about the effects of lithium carbonate and valproate on cerebral gray matter volume in patients with BD-I. Key words: Bipolar disorder; Voxel-based morphology; Mood stabilizer

Aggression among 216 patients with a first-psychotic episode of bipolar I disorder

BackgroundAggression by patients with bipolar I disorder (BD-I) is not uncommon. Identifying potential risk factors early in the illness-course should inform clinical management and reduce risk.MethodsIn a study sample of 216 initially hospitalized, first-psychotic episode subjects diagnosed with DSM-IV-TR BD-I, we identified recent (within 1 month before hospitalization) aggression by ratings on the Brief Psychiatric Rating Scale-Expanded and review of detailed clinical research records. We compared subjects with versus without aggressive behavior for associations with selected demographic and clinical factors.ResultsAggression was identified in 23/216 subjects (10.6%). It was associated significantly with recent suicide attempt (OR = 4.86), alcohol abuse (OR = 3.63), learning disability (OR = 3.14), and initial manic episode (OR = 2.59), but not with age, sex, onset-type, personality disorder, time to recovery, or functional status.ConclusionsAmong first-major episode BD-I patients with psychotic features, recent serious aggression towards others was identified in 10.6%. The odds of aggression increased by 4.9-times in association with a recent suicide attempt, more than 3-times with alcohol-abuse or learning disability, and by 2.6-times if the episode polarity was manic. The findings encourage closer management of alcohol misuse, suicide risk, and manic symptoms, and early detection of learning problems in BD-I patients.

Comparing the Effects of Continuous Care Model and Psychological Support Training Package on Self-Care in Patients with Bipolar I Disorder

Background: Despite the growing prevalence of bipolar I disorder (BD-I), implementation of continuous care after hospital discharge in these patients is limited. Aim: To compare the effects of continuous care model (CCM) and psychological support training package (PSTP) on self-care in patients with BD-I. Method: This clinical trial was conducted during 2017-2018 on 90 BD-I patients admitted to Ibn-Sina Psychiatric Hospital in Mashhad, Iran. CCM and PSTP designed in the form of a CD and a manual were implemented (within 12 weeks) to intervention groups. A control group received the routine care. The research instrument was Roldan-Merino Self-Care Requisites Scale completed before and two months following the intervention. To analyze the data, one-way analysis of variance (ANOVA) was run in SPSS, version 16. Results: The two study groups were homogeneous in terms of demographic characteristics. The results of one-way ANOVA before the intervention revealed no significant difference among the three groups considering self-care mean scores (P=0.52); however, this variable was significantly different among the groups following the intervention (P<0.001). According to the post-hoc Dunnett’s test results, a significant difference was observed in self-care mean scores between the CCM and control groups (P<0.001) and between the CCM and PSTP groups (P=0.04). Nonetheless, there was no significant difference between the CCM and control groups in this regard (P=0.13). Implications for Practice: CCM can improve self-care in patients with BD-I. Therefore, it could be used to empower these patients and their families.

The effects of psychoeducational family intervention on coping strategies of relatives of patients with bipolar I disorder: results from a controlled, real-world, multicentric study.

BackgroundPsychoeducational family intervention (PFI) has been proven to be effective in improving the levels of family burden and patients’ personal functioning in schizophrenia and bipolar disorders (BDs). Less is known about the impact of PFI on relatives’ coping strategies in BD.MethodsA multicenter, controlled, outpatient trial funded by the Italian Ministry of Health and coordinated by the Department of Psychiatry of the University of Campania “Luigi Vanvitelli” has been conducted in patients with bipolar I disorder (BD-I) and their key relatives consecutively recruited in 11 randomly selected Italian community mental health centers. We aim to test the hypothesis that PFI improves problem-oriented coping strategies in relatives of BD-I patients compared to the Treatment As Usual (TAU) group.ResultsThe final sample was constituted of 123 patients and 139 relatives. At baseline assessment (T0), the vast majority of relatives already adopted problem-oriented coping strategies more frequently than the emotion-focused ones. At the end of the intervention, relatives receiving PFI reported a higher endorsement of adaptive coping strategies, such as “maintenance of social interests” (odds ratio [OR]=0.309, CI=0.04–0.57; p=0.023), “positive communication with the patient” (OR=0.295, CI=0.13–0.46; p=0.001), and “searching for information” (OR=0.443, CI=0.12–0.76; p=0.007), compared to TAU relatives, after controlling for several confounders. As regards the emotion-focused coping strategies, relatives receiving the experimental intervention less frequently reported to adopt “resignation” (OR=−0.380, CI=−0.68 to −0.08; p=0.014) and “coercion” (OR=−0.268, CI=−0.46 to −0.08; p=0.006) strategies, compared to TAU relatives.ConclusionPFI is effective in improving the adaptive coping strategies of relatives of BD-I patients, but further studies are needed for evaluating the long-term benefits of this intervention.